Science.gov

Sample records for borderline melanocytic tumor

  1. Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous melanocytic tumors with malignant potential and normal cytogenetics.

    PubMed

    Magro, Cynthia M; Abraham, Ronnie M; Guo, Ruifeng; Li, Shibo; Wang, Xuan; Proper, Steven; Crowson, A Neil; Mihm, Martin

    2014-01-01

    Deep penetrating nevi (DPN) are a relatively uncommon subtype of melanocytic nevi. A small subset of these lesions exhibit atypical features (cytologic and architectural atypia, mitotic activity) seen in melanoma. These lesions we term the deep penetrating nevus-like borderline tumor. Unequivocal melanomas can show overlapping morphologic features of DPN, which have been termed plexiform melanomas. 40 cases of DPN-like borderline tumor were identified along with 6 cases of plexiform melanoma. Clinical follow up was obtained, along with cytogenetic analysis in the form of fluorescent in situ hybridization (FISH) and/or comparative genomic hybridization (CGH). The DPN-like borderline tumor cases included 24 females and 16 males. Of sentinel lymph node biopsies performed, 1/3 of cases showed lymph node involvement. All patients where an aggressive clinical approach was adopted remain free of disease. All 6 DPN-like borderline tumor cases tested by CGH showed normal cytogenetics, as did 7 of 9 cases tested by FISH. Of the plexiform melanomas, 4/6 patients died of disease. In 3 cases there was morphologic progression from a DPN-like borderline tumor to overt melanoma. In one case of progression, cytogenetics was normal in the DPN-like borderline tumor and then abnormal in the progressed melanoma. DPN-like borderline tumors are melanocytic tumors associated with a high incidence of regional lymph node disease and exhibiting the potential for melanoma progression despite a normal cytogenetic profile. Patients with these lesions should be aggressively managed, with at least complete re-excision and consideration of sentinel node biopsy, regardless of cytogenetic data.

  2. Therapy of melanocytic conjunctival tumors.

    PubMed

    Halas, Jr M; Svetlosakova, Z; Babal, P

    2013-01-01

    Clinical experience of our single center in dealing with pigmented epibulbar lesions - melanocytic conjunctival tumors is presented. Since 2008 we use the topical treatment with mitomycin C (MMC) as an alternative or adjunctive method for excision in the treatment of melanocytic neoplasia of the conjunctiva. The retrospective case series of 85 patients with pigmented lesions of the conjunctiva - melanocytic conjunctival tumors, histopathologically examined in the period 2001-2010 is presented. Since 2008 we started to apply MMC in the treatment of primary acquired melanosis (PAM) and dysplastic nevi. We apply MMC topically directly after an excision as 2-times five minutes application. In 85 patients with pigmented lesions of the conjunctiva histopathological findings after excision of the lesion showed in 68 (80 %) cases melanocytic nevocelullar nevus, out of which 55 cases were combined and 13 cases were junctional nevi. In 60 (80 %) cases of melanocytic nevi atypia was found in 25 patients (42 %), nevus without atypia was present in 35 cases (58 %). PAM with atypia was found in 16 patients (classified since 2000). During the period of application of MMC we diagnosed only one patient with primary conjunctival melanoma. There was no presence of relapse of the pigmented lesion either after primary excision or after excision with MMC. Resection of more than one quadrant of bulbar conjunctiva in patients with pigmented lesions of the conjunctiva in cases of conjunctival nevus with atypia and PAM with atypia combined with topical MMC chemotherapy is an alternative therapy for residual pigmented lesions. There was no presence of relapse of pigmentation in area of excision with or without using MMC during the surgery in patients with PAM. The number of our patients is not sufficient yet to draw a conclusion (Fig. 6, Ref. 21).

  3. [Molecular diagnosis of melanocytic tumors].

    PubMed

    Bauer, J

    2016-01-01

    Melanoma therapy has undergone a paradigm shift. Classic chemotherapies with poor treatment responses have been replaced by modern immune checkpoint blockades and targeted therapies with excellent responses. The latter require precise diagnosis of mutations in the melanoma genome as molecular targets for the small molecules. The diagnosis of melanomas has also been supplemented by molecular techniques. Differential diagnosis of melanoma and melanoma simulators such as atypical Spitz nevi can be supported by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Here we review the indications and methods for molecular diagnosis of melanocytic tumors.

  4. GI tract tumors with melanocytic differentiation.

    PubMed

    Karamchandani, Dipti M; Patil, Deepa T; Goldblum, John R

    2013-11-01

    Gastrointestinal (GI) tract tumors with melanocytic differentiation may present significant diagnostic challenges both for the pathologist and the clinician. This comprehensive review discusses the relatively common as well as rare entities that have melanocytic differentiation in the GI tract. Clinical, histologic, immunohistochemical and molecular features are discussed along with prognosis and differential diagnosis.

  5. [Ovarian tumors of low malignant potential (borderline ovarian tumors)].

    PubMed

    Luchian, Alina-Mihaela; Pricop, M

    2011-01-01

    Ovarian borderline tumors are rare, their good prognosis depending on their stage at the time of diagnosis, and the presence of invasive implants. There is little information on tumor type identified intra-surgically, as well as on the most favorable treatment in borderline ovarian tumors. To determine the criteria of identification and presurgery and intra-surgery differentiation of the ovarian borderline tumors from the invasive carcinoma and benign ovarian tumors. This study included 54 patients with TPMS (ovarian borderline tumors) surgically treated in the past 22 years (January 1988-December 2009) at the 4th Gynecological Clinic of the lasi "Gr. T. Popa" University of Medicine and Pharmacy. In this interval 1,107 ovarian tumors: 575 benign, 478 malignant, and 54 TPMS (4.87%) were recorded. The age of the patients with borderline tumors ranged between 20 and 78 years, mean age 46 years, and the histological types were: mucinous (27 cases), serous (18 cases), mixed (8 cases), and Brenner tumor (1 case). We have analyzed the distribution of these cases according to the time when surgical treatment was performed. The frequency of borderline ovarian tumors in our study is 4.87%, lower than in the literature. We believe that this low percentage in our study is due to missing the microscopic data in some macroscopic benign tumors. By this research we aimed at elaborating a therapeutic strategy for each case using with discernment the modern treatment (surgery, chemotherapy, radiotherapy), as well as new chemical drugs with the goal of obtaining better results and longer survival. There are no tumor markers which could predict the progression of a borderline ovarian tumor to invasive tumors, but the invasive course is only 0.7%.

  6. Needleoscopic Conservative Staging of Borderline Ovarian Tumor.

    PubMed

    Gueli Alletti, Salvatore; Rossitto, Cristiano; Perrone, Emanuele; Cianci, Stefano; De Blasis, Ilaria; Fagotti, Anna; Scambia, Giovanni

    To investigate the safety and technical feasibility of needleoscopic fertility-sparing staging of borderline ovarian tumors. Video article and review of the literature (Canadian Task Force classification Level III). This 29-year-old woman had a right ovarian cyst suspicious for borderline ovarian tumor on preoperative magnetic resonance imaging and ultrasound showing the presence of a right unilocular ovarian cyst with a papillary projection. Informed consent for abdominal or laparoscopic approach was obtained from the patient in accordance with the local legislation. The patient also provided informed consent to use images and videos of the procedure. Institutional Review Board approval was not required for this kind of procedure. Treatment involved conservative staging with right ovarian cystectomy, peritoneal biopsies, infracolic omental biopsy, and peritoneal cytology. Instrumentation included two 2.4-mm needleoscopic instruments. The total operative time was 62 minutes, and estimated blood loss was <10 mL. No intraoperative complications were recorded. At the end of the surgical procedure, the outer diameter of the incision was increased by only up to 3 mm. The patient was discharged the day after the procedure. Histopathological analysis confirmed a serous borderline ovarian tumor. A 30 days postoperative follow-up, a satisfactory cosmetic result was reported by both the patient (score of 10 of out of a possible 10) and the surgeon (10 of 10). To the best of our knowledge, there are no previously published reports of needleoscopic treatment of borderline ovarian tumor, which represents a great challenge for ultra-minimally invasive approaches [1-3]. Based on our initial experience, the needleoscopic instruments could prove to be a beneficial tool in adnexal benign or borderline disease. At present, only a hybrid operative setting should be considered to overcome the lack of bipolar energy [4-6]. Further studies are needed to define the benefits

  7. The ultrastructure of conjunctival melanocytic tumors.

    PubMed Central

    Jakobiec, F A

    1984-01-01

    The ultrastructure of conjunctival melanocytic lesions in 49 patients was evaluated to find significant differences between benign and malignant cells. The patients studied included 9 with benign epithelial (racial) melanosis, 2 with pigmented squamous cell papillomas, 16 with conjunctival nevi, 18 with primary acquired melanosis, and 11 with invasive nodules of malignant melanoma. In benign epithelial melanosis, dendritic melanocytes were situated along the basement membrane region of the conjunctival epithelium, with one basilar dendritic melanocyte lodged among every five or six basilar keratinocytes. The dendritic melanocytes extended arborizing cellular processes between the basilar and among the suprabasilar keratinocytes, which manifested considerable uptake of melanin granules into their cytoplasm. The benign dendritic melanocytes possessed nuclei with clumped heterochromatin at the nuclear membrane, small, tightly wound nucleoli, and large, elongated, fully melaninized melanin granules. In two patients with benign hyperplasia of the dendritic melanocytes, occasional dendritic melanocytes were located in a suprabasilar position, but were always separated from each other by keratinocytes or their processes. In the two black patients with benign pigmented squamous papillomas, the benign dendritic melanocytes were located hapharzardly at all levels of the acanthotic epithelium and not just along the basement membrane region. Melanin uptake by the proliferating keratinocytes was minimal. In benign melanocytic nevi of the conjunctiva, nevus cells within the intraepithelial junctional nests displayed a more rounded cellular configuration; short villi and broader cellular processes suggestive of abortive dendrites were found. The nuclear chromatin pattern was clumped at the nuclear membrane, but the nucleoli were somewhat larger than those of benign dendritic melanocytes in epithelial melanosis. The melanosomes were smaller and rounder than those in dendritic

  8. Borderline ovarian tumors: a review of treatment.

    PubMed Central

    Chambers, J. T.

    1989-01-01

    Borderline ovarian tumors have an excellent prognosis. In stage I disease, no therapy in addition to surgery is needed, and conservation of ovarian tissue for future childbearing may be appropriate. In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported. A randomized study of no adjuvant therapy versus adjuvant treatment with long-term follow-up will be necessary to determine the efficacy of additional treatment. PMID:2556863

  9. Automatic Differential Diagnosis of Melanocytic Skin Tumors Using Ultrasound Data.

    PubMed

    Andrėkutė, Kristina; Linkevičiūtė, Gintarė; Raišutis, Renaldas; Valiukevičienė, Skaidra; Makštienė, Jurgita

    2016-12-01

    We describe a novel automatic diagnostic system based on quantitative analysis of ultrasound data for differential diagnosis of melanocytic skin tumors. The proposed method has been tested on 160 ultrasound data sets (80 of malignant melanoma and 80 of benign melanocytic nevi). Acoustical, textural and shape features have been evaluated for each segmented lesion. Using parameters selected according to Mahalanobis distance and linear support vector machine classifier, we are able to differentiate malignant melanoma from benign melanocytic skin tumors with 82.4% accuracy (sensitivity = 85.8%, specificity = 79.6%). The results indicate that high-frequency ultrasound has the potential to be used for differential diagnosis of melanocytic skin tumors and to provide supplementary information on lesion penetration depth. The proposed system can be used as an additional tool for clinical decision support to improve the early-stage detection of malignant melanoma. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Melanocytic Malignant Peripheral Nerve Sheath Tumor of the Male Breast.

    PubMed

    Wang, Haijun; Ge, Jing; Chen, Lirong; Xie, Panpan; Chen, Fangfang; Chen, Yiding

    2009-01-01

    SUMMARY: BACKGROUND: Malignant peripheral nerve sheath tumors are rare tumor entities that originate from peripheral nerve sheaths and have an unfavorable prognosis. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an absolutely rare location of this lesion, and presentation as a breast lump in the male breast is even rarer. CASE REPORT: A 65-year-old man presented with a 6-month history of a painless mass of the left breast. Tissue biopsy was performed. Histopathology revealed a malignant spindle cell tumor which was confirmed to be a melanocytic malignant peripheral nerve sheath tumor on the basis of immunopositivity for HMB45 and S-100. CONCLUSION: There are no generally accepted guidelines for the treatment of malignant peripheral nerve sheath tumors in the male breast. The patient was referred for radiation therapy after simple mastectomy.

  11. Epithelial borderline ovarian tumor: Diagnosis and treatment strategy.

    PubMed

    Ushijima, Kimio; Kawano, Kouichiro; Tsuda, Naotake; Nishio, Shin; Terada, Atsumu; Kato, Hiroyuki; Tasaki, Kazuto; Matsukuma, Ken

    2015-05-01

    Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

  12. Diagnosis, Treatment, and Follow-Up of Borderline Ovarian Tumors

    PubMed Central

    Zikan, Michal; Dundr, Pavel; Cibula, David

    2012-01-01

    Borderline ovarian tumors represent a heterogeneous group of noninvasive tumors of uncertain malignant potential with characteristic histology. They occur in younger women, are present at an early stage, and have a favorable prognosis, but symptomatic recurrence and death may be found as long as 20 years after therapy in some patients. The molecular changes in borderline ovarian tumors indicate linkage of this disease to type I ovarian tumors (low-grade ovarian carcinomas). The pathological stage of disease and subclassification of extraovarian disease into invasive and noninvasive implants, together with the presence of postoperative macroscopic residual disease, appear to be the major predictor of recurrence and survival. However, it should be emphasized that the most important negative prognostic factor for recurrence is just the use of conservative surgery, but without any impact on patient survival because most recurrent diseases are of the borderline type—easily curable and with an excellent prognosis. Borderline tumors are difficult masses to correctly preoperatively diagnose using imaging methods because their macroscopic features may overlap with invasive and benign ovarian tumors. Over the past several decades, surgical therapy has shifted from a radical approach to more conservative treatment; however, oncologic safety must always be balanced. Follow-up is essential using routine ultrasound imaging, with special attention paid to the remaining ovary in conservatively treated patients. Current literature on this topic leads to a number of controversies that will be discussed thoroughly in this article, with the aim to provide recommendations for the clinical management of these patients. PMID:23024155

  13. Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors.

    PubMed

    Skalet, Alison H; Li, Yan; Lu, Chen D; Jia, Yali; Lee, ByungKun; Husvogt, Lennart; Maier, Andreas; Fujimoto, James G; Thomas, Charles R; Huang, David

    2017-02-01

    , including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  14. Borderline and malignant phyllodes tumors display similar promoter methylation profiles.

    PubMed

    Kim, Jo-Heon; Choi, Yoo Duk; Lee, Ji Shin; Lee, Jae Hyuk; Nam, Jong Hee; Choi, Chan; Park, Min Ho; Yoon, Jung Han

    2009-12-01

    Mammary phyllodes tumors (PTs) are uncommon fibroepithelial neoplasms. On the basis of histologic criteria, PTs can be divided into benign, borderline, and malignant groups; however, the histologic distinction of PTs is often difficult and arbitrary. In breast cancer, promoter hypermethylation is a common phenomenon, but there are no data available concerning methylation status in PTs. The aim of this study was to assess whether the methylation profiles support the classification of PTs into three subgroups. A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of five genes (GSTP1, HIN-1, RAR-beta, RASSF1A, and Twist) in 87 PTs (54 benign, 23 borderline, and 10 malignant). Immunohistochemical staining for GSTP1 was performed using tissue microarray blocks to determine whether GSTP1 promoter hypermethylation correlated with loss of GSTP1 expression. There was a trend of increasing methylation frequency with increasing grade of PTs. The methylation frequency of all genes and the mean number of methylated genes in borderline and malignant PTs were higher than those in benign PTs; however, there were no statistically significant differences between borderline and malignant PTs. GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.001). These results suggest that PTs segregate into only two groups on the basis of their methylation profiles: the benign group and the combined borderline/malignant group.

  15. Extremely rare borderline phyllodes tumor in the male breast: a case report.

    PubMed

    Kim, Jung Gyu; Kim, Shin Young; Jung, Hae Yoen; Lee, Deuk Young; Lee, Jong Eun

    2015-01-01

    Phyllodes tumor of the male breast is an extremely rare disease, and far fewer cases of borderline phyllodes tumors than benign or malignant tumors in the male breast have been reported. We report a case of borderline phyllodes tumor in the male breast with imaging findings of the tumor and pathologic correlation.

  16. Long-term survival in women with borderline ovarian tumors: a population-based survey of borderline ovarian tumors in Sweden 1960-2007.

    PubMed

    Kalapotharakos, Grigorios; Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer

    2016-04-01

    We conducted an evaluation of incidence and survival of women with borderline ovarian tumors in Sweden. All women diagnosed with borderline ovarian tumor in the Swedish Cancer Register 1960-2007 (n = 6252) combined with follow up in the Swedish Death Registry to 1 July 2009 were included. Estimation of age-standardized relative survival rate according to time periods for diagnosis. The incidence of borderline ovarian tumors increased during the study period, with a steep increase during the 1980s. The age standardized 5-year relative survival including all borderline tumors diagnosed 2000-07 was 97% (95% CI 92-99%). In women aged ≤64 years, the 10-year relative survival related to age at diagnosis of borderline tumors ranged from 95 to 98% and was 89% in women aged 65-74 years. In a multivariable analysis including age and decade of diagnosis relative survival for every decade increased. The 10-year relative survival in women with mucinous and serous borderline tumors did not differ significantly (p = 0.121). Results of the present study are reassuring about long-term survival in women with borderline ovarian tumors. The age-standardized relative survival rate increased across time periods for diagnosis. There was no difference in long-term survival between mucinous and serous borderline ovarian tumors. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  17. An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.

    PubMed

    Cruz-Galarza, Daniel; Pérez-Rodríguez, Omar; Laboy-Torres, Joaquín; Gutiérrez-Rivera, Silvia

    2014-01-01

    Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

  18. Morphological features of melanocytic tumors with depigmented halo: review of the literature and personal results.

    PubMed

    Nedelcu, Roxana Ioana; Zurac, Sabina Andrada; Brînzea, Alice; Cioplea, Mirela Daniela; Turcu, Gabriela; Popescu, Raluca; Popescu, Cătălin Mihai; Ion, Daniela Adriana

    2015-01-01

    Halo (Sutton's) phenomenon has been described as a depigmented halo that is associated most commonly with acquired melanocytic nevi; but it may be associated with various types of melanocytic skin tumors, melanoma being the most concerning. Different authors have been preoccupied with elucidating morphological features of melanocytic tumors associated with a depigmented halo. We reviewed the literature and discussed the main features of melanocytic halo tumors regarding histopathological, immune microenvironment profile and dermatoscopic appearance. We highlighted similarities and differences between Sutton's nevus and halo melanoma, also presenting relevant aspects of our results. Depigmented halo must be regarded as a phenomenon that may be associated with different types of melanocytic tumors and with a broad spectrum of histopathological atypia degree. Certain correlations between the shape, diameter, symmetry observed in clinical examination, histopathological appearance, dermatoscopic aspect of peritumoral halo and central tumor type could not be established due to insufficient data and contrasting results. Further studies are expected to add valuable information regarding the depigmented halo tumors features.

  19. Incidentally Discovered Extensive Squamous Metaplasia within Borderline Phyllodes Tumor: Presentation of a Rare Tumor.

    PubMed

    Uğraş, Nesrin; Tolunay, Şahsine; Öz Atalay, Fatma; Gökgöz, Şehsuvar

    2016-01-01

    Phyllodes tumors are uncommon biphasic fibroepithelial neoplasms of breast, comprising less than 1% of all breast neoplasms. We therefore aimed to present the case with its microscopic findings. In this article, we report a 59-year-old female admitted to the general surgery department with a rapidly, enlarging, palpable mass in right breast. After histopathological examination, it was diagnosed as borderline phyllodes tumor with extensive squamous metaplasia. Metaplastic changes are infrequent in the stromal and epithelial component of these tumors. Extensive squamous metaplasia within phyllodes tumor is rare and may occur in benign, borderline and malign subtypes.

  20. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  1. Mucinous Cystic Borderline Tumor of the Mesentery: A Case Report.

    PubMed

    Poudel, R; Acharya, A; Pokhrel, S; Adhikari, S K

    2015-01-01

    Mucinous cystic neoplasms are rare tumors of uncertain histogenesis. They arise from the ovaries, pancreas, and other intra-abdominal sites but more unusually from the mesentery. They can present with abdominal pain, distension, or a palpable mass but are commonly an incidental finding. We present a case of a 33-year-old female who presented with complain of pain abdomen for one-year duration. On Physical examination there was a palpable lump in right lumbar region extending to right iliac fossa. CT scan of abdomen and pelvis suggested the mass to be a Mesenteric Cyst. Enucleation of the cyst was done and histopathology report revealed Mucinous Cystic borderline tumor of the Mesentery.

  2. Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

    PubMed

    Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

    2017-09-01

    Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Primary melanocytic tumors of the central nervous system: a review with focus on molecular aspects.

    PubMed

    Küsters-Vandevelde, Heidi V N; Küsters, Benno; van Engen-van Grunsven, Adriana C H; Groenen, Patricia J T A; Wesseling, Pieter; Blokx, Willeke A M

    2015-03-01

    Primary melanocytic tumors of the central nervous system (CNS) represent a spectrum of rare tumors. They can be benign or malignant and occur in adults as well as in children, the latter often in the context of neurocutaneous melanosis. Until recently, the genetic alterations in these tumors were largely unknown. This is in contrast with cutaneous and uveal melanomas, which are known to harbor distinct oncogenic mutations that can be used as targets for treatment with small-molecule inhibitors in the advanced setting. Recently, novel insights in the molecular alterations underlying primary melanocytic tumors of the CNS were obtained, including different oncogenic mutations in tumors in adult patients (especially GNAQ, GNA11) vs. children (especially NRAS). In this review, the focus is on molecular characteristics of primary melanocytic tumors of the CNS. We summarize what is known about their genetic alterations and discuss implications for pathogenesis and differential diagnosis with other pigmented tumors in or around the CNS. Finally, new therapeutic options with targeted therapy are discussed. © 2014 International Society of Neuropathology.

  4. Serous borderline tumor of the fallopian tube presented as hematosalpinx: a case report

    PubMed Central

    Krasevic, Maja; Stankovic, Teodora; Petrovic, Oleg; Smiljan-Severinski, Neda

    2005-01-01

    Background Compared with their ovarian counterparts, serous borderline tumors of the fallopian tube are uncommon, with limited experience about their clinical behaviour. We present a case of serous borderline tumor of the fallopian tube with unusual presentation and summarise all the published cases to date. Case presentation A case of serous borderline tumor of the fallopian tube in a 34-year old patient is presented, incidentally found during routine gynecologic examination. At laparoscopy the tumor was unusualy presented as hematosalpinx and was treated by salpingectomy. Cell-cycle analysis of the tumor tissue revealed a diploid DNA content and a low S-phase fraction. There was no evidence of the disease during the follow-up period of 4.6 years. Conclusion The current case and review of the literature suggest salpingectomy as the optimal treatment for patients with serous borderline tumor of the fallopian tube. PMID:16212662

  5. Pregnancy after fertility-sparing surgery for borderline ovarian tumors.

    PubMed

    Lian, Chengying; Chen, Xiujuan; Ni, Yihua; Huang, Xiaochen; Lin, Yuan

    2016-09-01

    To investigate the ability to conceive and the factors affecting chances of pregnancy among patients with borderline ovarian tumors (BOTs) treated with fertility-sparing surgery. A retrospective study included nulliparous patients aged 40years or younger who had undergone fertility-sparing surgery for BOTs between January 2005 and June 2012 at a center in Fuzhou, China. Identified patients were followed up by telephone or mail between March 15 and June 30, 2013. Patients who had already been pregnant and those who had not but had discontinued contraception for more than 1year were included in final analyses. Among 23 included patients, 17 (74%) had become pregnant within the mean follow-up period of 48.2months. The frequencies of previous infertility, sequelae of pelvic inflammatory disease, and endometriosis were all higher in the nonpregnant group than in the pregnant group (P≤0.021 for all). More women in the nonpregnant group that in the pregnant group had BOTs of stage II or worse, but the difference was nonsignificant (P=0.059). Fertility-sparing surgery in young patients with BOTs is associated with a good pregnancy rate. However, the tumor stage and coexisting infertility factors are important considerations in selecting the optimal surgical approach. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Mucinous borderline ovarian tumor: a case report with diagnostic insights on ultrasound findings

    PubMed Central

    Śniadecki, Marcin; Bianek-Bodzak, Agnieszka; Liro, Marcin; Szurowska, Edyta

    2016-01-01

    Borderline ovarian tumors represent about 10% of all epithelial ovarian cancers, but in contrast to epithelial ovarian cancers, they constitute a group of tumors with a much better prognosis. An assessment of clinical presentation, physical examination, radiological and biochemical findings is necessary to tailor management strategies for patients with ovarian tumors. The article, which is based on a case report, describes different approaches for preoperative diagnosis as well as discusses approaches that might bring some insights on tumor histology. Furthermore, it raises a question about which imaging techniques should be proposed for a reliable diagnosis of borderline ovarian tumors to ensure safe surgery planning. PMID:28138412

  7. The molecular pathology of ovarian serous borderline tumors.

    PubMed

    Malpica, A; Wong, K-K

    2016-04-01

    Molecular studies in ovarian serous borderline tumors (OSBTs) have been used to understand different aspects of this neoplasm. (i) Pathogenesis, Kras and Braf mutations represent very early events in the tumorigenesis of OSBT as both are detected in serous cystadenomas associated with OSBTs. In contrast, serous cystadenomas without OSBTs do not show Kras or Braf mutations. In OSBTs, Kras mutations range from 17% to 39.5%, while Braf mutations range from 23% to 48%. The former is comparable with the range of Kras mutations in ovarian low-grade serous carcinomas (OLGSCa), 19%-54.5%. In contrast, Braf mutations in OLGSCa range from 0% to 33%. Serous cystadenomas appear to progress to OSBT due to a Braf mutation, but this mutation is rarely involved in the progression to OLGSCa. OSBTs with Braf mutation are associated with cellular senescence and up-regulation of tumor suppressor genes. In contrast, OSBTs without a Braf mutation may progress to OLGSCa due to Kras mutation or some other genetic alterations. (ii) The relationship between OSBTs and the extraovarian disease, a monoclonal versus mutifocal origin? This is still matter of debate as studies using different techniques have failed to settle this controversy. (iii) Biological behavior, Braf mutations appear to have a protective role against the progression of OSBT to OLGSCa, while Kras mutations are commonly seen in cases of OSBT that recurred as LGSCa. Nevertheless, LGSCa as a recurrence of an OSBT can originate from OSBTs with or without detectable Kras mutations. Also, it appears to be an association between Kras G12v mutation and a more aggressive phenotype of OSBT that recurred as LGSCa. (iv) Actionable targets, currently there are limited data. It has been reported that cancer cell lines with Kras G12v mutation are more sensitive to selumetinib than cell lines with wild-type Kras.

  8. p14 expression differences in ovarian benign, borderline and malignant epithelial tumors.

    PubMed

    Cabral, Vinicius Duarte; Cerski, Marcelle Reesink; Sa Brito, Ivana Trindade; Kliemann, Lucia Maria

    2016-10-22

    Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian epithelial carcinogenesis, p16 and p53 show higher immunohistochemical staining frequencies in malignant tumors and are associated with poor prognoses. p14 was only analyzed in carcinomas, with conflicting results. There are no reports on its expression in benign and borderline tumors. This study aims to determine p14, p16 and p53 expression frequencies in ovarian benign, borderline and malignant tumors and their associations with clinical parameters. A cross-sectional study utilizing immunohistochemistry was performed on paraffin-embedded ovarian epithelial tumor samples. Clinical data were collected from medical records. Fisher's exact test and the Bonferroni correction were performed for frequency associations. Survival comparisons utilized Kaplan-Meier and log rank testing. Associations were considered significant when p < 0.05. p14 absent expression was associated with malignant tumors (60 % positive) (p = 0.000), while 93 % and 94 % of benign and borderline tumors, respectively, were positive. p16 was positive in 94.6 % of carcinomas, 75 % of borderline and 45.7 % of benign tumors (p = 0.000). p53 negative staining was associated with benign tumors (2.9 % positive) (p = 0.016) but no difference was observed between borderline (16.7 %) and malignant tumors (29.7 %) (p = 0.560). No associations were found between expression rates, disease-free survival times or clinical variables. Carcinoma subtypes showed no difference in expression. This is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate that p14 abnormalities occur later in carcinogenesis. p16 and p53 frequencies increase from benign to borderline and malignant tumors, similarly to previous reports, possibly reflecting the

  9. Assessment of tumor thickness in melanocytic skin lesions: comparison of optical coherence tomography, 20-MHz ultrasound and histopathology.

    PubMed

    Hinz, Torsten; Ehler, Lin-Kristin; Voth, Harald; Fortmeier, Ines; Hoeller, Tobias; Hornung, Thorsten; Schmid-Wendtner, Monika-Hildegard

    2011-01-01

    Accurate assessment of vertical tumor size is important for surgical treatment planning of melanocytic skin lesions. High-frequency ultrasound (HFUS) is frequently used for this purpose, but overestimation of tumor thickness is known as a problem especially in thin melanocytic lesions. Optical coherence tomography (OCT) as a new imaging technique might be a promising alternative. To evaluate the ability of OCT to accurately determine the vertical tumor thickness of melanocytic skin lesions and to compare it with HFUS and histopathology in order to improve surgical planning. In this single-center study, 26 melanocytic lesions were imaged by OCT and HFUS. Vertical lesion dimensions of both methods were compared with histopathological measurements. Bland-Altman plots for OCT and histopathology as well as for HFUS and histopathology revealed better agreement for OCT and histopathology concerning tumor thickness measurements. Tumor thickness values for the melanocytic lesions measured by OCT presented a median tumor thickness of 0.31 mm (range 0.10-0.77) compared to a median tumor thickness of 0.25 mm (range 0.06-1.5) measured by histopathology. The median tumor thickness of HFUS was 0.44 mm (range 0.23-1.1). A Spearman correlation procedure including the correlation coefficient (r) showed a stronger relationship between OCT and histopathology (r = 0.734) compared to HFUS and histopathology (r = 0.390). On the basis of this smaller study cohort, OCT seems to be more exact than HFUS as far as thickness determination of thin melanocytic skin lesions is concerned. Copyright © 2011 S. Karger AG, Basel.

  10. [Borderline ovarian tumors and global radiation in relation with climate change impact].

    PubMed

    Luchian, Alina-Mihaela; Pricop, M

    2011-01-01

    There is limited information on borderline ovarian tumor detected intra-surgically and its most favorable treatment in relation with global radiation and climate changes. To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iaşi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors.

  11. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.

  12. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report.

    PubMed

    Takemoto, Shuji; Kawano, Ryosuke; Honda, Kazumi; Nakazono, Aki; Shimamatsu, Kazuhide

    2012-05-14

    Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery.

  13. Benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor: a case report

    PubMed Central

    2012-01-01

    Introduction Benign multicystic peritoneal mesothelioma is an extremely rare tumor that occurs mainly in women in their reproductive age. Its preoperative diagnosis and adequate treatment are quite difficult to attain. Case presentation Our patient was a 23-year-old Japanese woman who had a history of right oophorectomy and left ovarian cystectomy for an ovarian tumor at 20 years of age. The left ovarian tumor had been diagnosed on histology as a mucinous borderline tumor. Two years and nine months after the initial operation, multiple cysts were found in our patient. A laparotomy was performed and her uterus, left ovary, omentum and pelvic lymph nodes were removed due to suspicion of recurrence of the borderline tumor. A histological examination, however, revealed that the cysts were not a recurrence of the borderline tumor but rather benign multicystic peritoneal mesothelioma. There were no residual lesions and our patient was followed up with ultrasonography. She remains free from recurrence nine months after treatment. Conclusion We report a case of benign multicystic peritoneal mesothelioma mimicking recurrence of an ovarian borderline tumor. Benign multicystic peritoneal mesothelioma should be suspected when a multicystic lesion is present in the pelvis as in the case presented here, especially in patients with previous abdominal surgery. PMID:22583977

  14. Paraganglioma-like dermal melanocytic tumor: a unique entity distinct from cellular blue nevus, clear cell sarcoma, and cutaneous melanoma.

    PubMed

    Deyrup, Andrea T; Althof, Pamela; Zhou, Ming; Morgan, Michael; Solomon, Alvin R; Bridge, Julia A; Weiss, Sharon W

    2004-12-01

    We are reporting a previously undescribed primary dermal melanocytic tumor identified by reviewing all dermal melanocytic tumors referred in consultation that did not qualify histologically as a previously described entity. From these cases, 8 were remarkably similar. We termed them "paraganglioma-like dermal melanocytic tumor" (PDMT) based on their nested growth pattern. This term is used descriptively and does not imply any histogenetic or biologic similarity to true paraganglioma. PDMT is primarily a tumor of the extremities of adult females (18-53 years, mean 35 years; males 2; females 6) which present as a dermal nodule (range, 0.5-4.2 cm; mean, 1.4 cm) composed of nests of clear to amphophilic oval cells separated by delicate fibrous strands. Nuclear atypia was mild and mitotic activity low (1-4 mitoses/10 HPF). Melanin was not obvious on light microscopy. Tumors expressed S-100 protein (8 of 8), Melan-A (4 of 8), HMB-45 (8 of 8), and microphthalmia transcription factor (8 of 8) and lacked pancytokeratin (8 of 8) and smooth muscle actin (8 of 8). FISH analysis of 5 cases revealed an intact EWS gene locus, supporting absence of the clear cell sarcoma 12;22 translocation. Follow-up information in 8 patients (range, 35-92 months; mean, 54 months) indicated that all were alive without disease. PDMT comprises a clinically and pathologically unique subtype of dermal melanocytic tumors. Our study suggests a benign course, although a lesion of low malignant potential cannot be excluded.

  15. Isolated subcutaneous implantation of a borderline ovarian tumor: A case report and review of the literature

    PubMed Central

    Banys-Paluchowski, Malgorzata; Yeganeh, Borsu; Luettges, Jutta; Maibach, Achim; Langenberg, Ruediger; Krawczyk, Natalia; Paluchowski, Peter; Maul, Holger; Gebauer, Gerhard

    2016-01-01

    Laparoscopy-related tumor implantations of gynecological malignancies into the subcutaneous tissue are rarely diagnosed. We report an interesting case of a 46-year-old female who presented with an abdominal subcutaneous metastasis of a borderline ovarian tumor. The patient received a laparoscopic unilateral adnexectomy for a solid-cystic tumor of the right ovary. Histopathological workup showed a papillary borderline tumor of mucinous type. Nine days later she underwent a hysterectomy, left adnexectomy, appendectomy and omentectomy. Exploration of the peritoneum revealed no intraperitoneal implants. Further exploration showed a non-invasive implant of a borderline tumor in the subcutaneous tissue above the fascia that had no contact to the peritoneum. It is hypothesized that tumor cells may have been implanted during a previous laparoscopy, the most recent of which had been fourteen years prior to her current presentation. Various risk factors for port-site malignancies have been identified. Tumor manipulation and extraction of tumor tissue without a protective bag may contribute to development of trocar-site metastasis. PMID:27081651

  16. Comparison of clinical characteristics between benign borderline and malignant phyllodes tumors of the breast.

    PubMed

    Wang, Hui; Wang, Xiang; Wang, Cheng-Feng

    2014-01-01

    Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known about this disease entity. The present study was designed to identify differences in clinical features between benign borderline and malignant phyllodes tumors. Data from 246 women with phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012 were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor, location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenoma history, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant tumors. In univariate analysis, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number of mitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003, <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statistically significant variation (p=0.400, 0.286 and 0.413, respectively). Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize.

  17. CD44 and melanocytic tumors: a possible role for standard CD44 in the epidermotropic spread of melanoma.

    PubMed

    Fernández-Figueras, M T; Ariza, A; Calatrava, A; Puig, L; Fernández-Vasalo, A; Ferrándiz, C

    1996-04-01

    CD44 is a polymorphic family of cell membrane glycoproteins that mediate cell-matrix and cell-cell interactions involved in the mechanisms of tumor invasion and metastasis, and are subject to differential regulation during normal and malignant cell growth. We have investigated immunohistochemically the expression of CD44S and the variant isoforms CD44v3 and CD44v6 in paraffin-embedded tissue from 5 Spitz nevi, 3 compound melanocytic nevi, 2 blue nevi, 6 primary melanomas, 15 cutaneous metastases (three epidermotropic, nine dermal and three ulcerated) and 10 lymph node metastases of melanoma. Melanocytes were extensively positive for CD44S in primary melanomas and benign melanocytic proliferations. Among 15 cases of cutaneous metastases of melanoma, the three epidermotropic metastases, as well as one of the three ulcerated ones were positive for CD44S. CD44S expression was diminished or totally absent in six of the nine dermal metastases, in two of the ulcerated metastases and in seven of the ten lymph node metastases. CD44v3 and CD44v6 melanocytic expression was absent in all the lesions studied. According to our results, selective retention of CD44S expression by melanocytes in epidermotropic metastases of melanoma seems to indicate that preservation of CD44S may contribute to the intraepidermal spread of melanoma.

  18. In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells

    PubMed Central

    Leikam, C; Hufnagel, A L; Otto, C; Murphy, D J; Mühling, B; Kneitz, S; Nanda, I; Schmid, M; Wagner, T U; Haferkamp, S; Bröcker, E-B; Schartl, M; Meierjohann, S

    2015-01-01

    Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS61K in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation. PMID:25837487

  19. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria.

    PubMed

    Hauptmann, Steffen; Friedrich, Katrin; Redline, Raymond; Avril, Stefanie

    2017-02-01

    Borderline ovarian tumors (BOT) are uncommon but not rare epithelial ovarian neoplasms, intermediate between benign and malignant categories. Since BOT were first identified >40 years ago, they have inspired controversies disproportionate to their incidence. This review discusses diagnostic criteria for the histologic subtypes of BOT, highlighting areas of diagnostic challenges, ongoing controversies, and changes in terminology implemented by the recent 2014 WHO Classification of Tumours of the Female Genital Organs. Emerging knowledge supports the notion that subtypes of borderline ovarian tumors comprise distinct biologic, pathogenetic, and molecular entities, precluding a single unifying concept for BOT. Serous borderline tumors (SBT) share molecular and genetic alterations with low-grade serous carcinomas and can present at higher stages with peritoneal implants and/or lymph node involvement, which validates their borderline malignant potential. All other (non-serous) subtypes of BOT commonly present at stage I confined to the ovary(ies) and are associated with overall survival approaching that of the general population. An important change in the WHO 2014 classification is the new terminology of non-invasive implants associated with SBT, as any invasive foci (previously called "invasive implants") are now in line with their biological behavior considered peritoneal low-grade serous carcinoma (LGSC). The controversy regarding the terminology of non-serous borderline tumors, called by some pathologists "atypical proliferative tumor" in view of their largely benign behavior, has not been resolved. The concepts of intraepithelial carcinoma and microinvasion may evolve in further studies, as their presence appears to have no prognostic impact and is subject to considerable inter-observer variability.

  20. Interaction between omega 3 PUFA and UVB radiation: Photoprotective effect in normal and tumoral murine melanocytes?

    PubMed

    Vasconcelos, Renata Ottes; Bustos, Silvina Odete; Gonzalez, Juliana Ramos; Soares, Camila Wink; Barbosa, Makely Daiane; Chammas, Roger; Votto, Ana Paula de Souza; Trindade, Gilma Santos

    2016-11-01

    Omega 3 polyunsaturated fatty acids (omega 3 PUFA) are attracting a growing interest as potential adjuvants for cancer prevention and treatment. There is evidence about photoprotection in normal cells, but few previous studies have evaluated it in tumoral cells. Therefore, this study investigated the effect of α-linolenic acid (ALA) in normal murine melanocytic cells (Melan-a) and in tumoral murine melanocytic cells (B16F10) exposed to UVB radiation. Our results showed that ALA exhibited an antiproliferative effect in B16F10 cells, and had minimal effect in Melan-a cells, as demonstrated by MTT assay. On the other hand, the combination of ALA (7.5μM) and UVB (0.01J/cm(2)) showed a protective effect for both cell lines, Melan-a and B16F10. ALA and UVB combined or UVB alone induced an accumulation of cell lines at the S/G2/M phase. In addition, the combination of ALA and UVB, and UVB alone, both induced cell death in 24h; and in 48h, ALA attenuated this effect in both cells. Further to these findings, it was demonstrated that ALA did not alter ROS levels in both cells exposed to UVB radiation. The effect of an omega 6 PUFA, linoleic acid, under the same conditions of ALA were tested. It was not protective in either cell line. Therefore, our results can be very important since it was shown another role to an omega 3 PUFA as a photoprotective agent in a melanoma cell.

  1. Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

    PubMed

    Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

    2017-01-01

    Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

  2. Ovarian serous borderline tumors with noninvasive and invasive peritoneal implants: A case report each.

    PubMed

    Srinivasamurthy, Banushree C; Kulandai Velu, Ambedkar Raj; Krishnan, Nagarajan; Patil, Anand Shankar Rao

    2015-01-01

    Serous borderline tumors (SBT) are defined by the World Health Organization (WHO) as serous neoplasms that show epithelial proliferation greater than that seen in serous cystadenomas, as evidenced by cellular stratification, cytologic atypicality, and epithelial tufting, but which exhibit no evidence of "destructive stromal" invasion and can show extra-ovarian implants. Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications. Peritoneal implants have been classified as either noninvasive or invasive based on their histopathologic appearance. Three criteria were applied for the diagnosis of "invasive" implants: Invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. We encountered two cases of unilateral ovarian serous borderline tumors with non-invasive peritoneal implants in a 43-year-old female, and invasive peritoneal implants in 76-year-old female.

  3. A case-control study of borderline ovarian tumors: the influence of perineal exposure to talc.

    PubMed

    Harlow, B L; Weiss, N S

    1989-08-01

    The authors interviewed 116 female residents of western Washington State with serous and mucinous borderline ovarian tumors diagnosed between 1980 and 1985 and questioned them on their use of hygienic powders. A sample of 158 control women from the same counties were identified through random digit dialing and were interviewed as well. Neither the perineal application of baby powder nor the perineal application of cornstarch was associated with an appreciably altered risk of borderline ovarian tumors. However, women who used deodorizing powders alone or in combination with other talc-containing powders had 2.8 times the risk (95% confidence interval 1.1-11.7) of women who had not had perineal exposure to powder. These results suggest that future studies of ovarian tumors in relation to the application of talc-containing powders should consider ascertaining the specific type(s) of powder used.

  4. Differentiation between borderline and benign ovarian tumors: combined analysis of MRI with tumor markers for large cystic masses (≥5 cm).

    PubMed

    Park, Sung Yoon; Oh, Young Taik; Jung, Dae Chul

    2016-05-01

    There is overlap in imaging features between borderline and benign ovarian tumors. To analyze diagnostic performance of magnetic resonance imaging (MRI) combined with tumor markers for differentiating borderline from benign ovarian tumor. Ninety-nine patient with MRI and surgically confirmed ovarian tumors 5 cm or larger (borderline, n = 37; benign, n = 62) were included. On MRI, tumor size, septal number (0; 1-4; 5 or more), and presence of solid portion such as papillary projection or septal thickening 0.5 cm or larger were investigated. Serum tumor markers (carbohydrate antigen 125 [CA 125] and CA 19-9) were recorded. Multivariate analysis was conducted for assessing whether combined MRI with tumor markers could differentiate borderline from benign tumor. The diagnostic performance was also analyzed. Incidence of solid portion was 67.6% (25/37) in borderline and 3.2% (2/62) in benign tumors (P < 0.05). In all patients, without combined analysis of MRI with tumor markers, multivariate analysis revealed solid portion (P < 0.001) and CA 125 (P = 0.039) were significant for predicting borderline tumors. When combined analysis of MRI with CA 125 ((i) the presence of solid portion or (ii) CA 125 > 44.1 U/mL with septal number ≥5 for borderline tumor) is incorporated to multivariate analysis, it was only significant (P = 0.001). The sensitivity, specificity, PPV, NPV, and accuracy of combined analysis of MRI with CA 125 were 89.1%, 91.9%, 86.8%, 93.4, and 90.9%, respectively. Combined analysis of MRI with CA 125 may allow better differentiation between borderline and benign ovarian tumor compared with MRI alone. © The Foundation Acta Radiologica 2015.

  5. Endometrioid Paraovarian Borderline Cystic Tumor in an Infant with Proteus Syndrome

    PubMed Central

    Tello, Mariela; Oscanoa, Monica; Dueñas, Milagros; Castro, Haydee; Latorre, Alan

    2015-01-01

    Ovarian and paraovarian neoplasms are uncommon in children, mainly originating from germ cell tumors and, least frequently, epithelial tumors. There is an association between genital tract tumors and Proteus syndrome, a rare, sporadic, and progressive entity, characterized by a postnatal overgrowth in several tissues caused by a mosaic mutation in the AKT1 gene. We describe a 20-month-old asymptomatic infant with Proteus syndrome who developed an endometrioid paraovarian borderline cystic tumor. This is the youngest patient so far reported in the literature with this rare syndrome and an adnexal tumor of borderline malignancy. A total of nine patients have been described with female tract tumors and associated Proteus syndrome, which includes bilateral ovarian cystadenomas and other benign masses. A paraovarian neoplasm is extremely rare in children and could be considered a criterion for Proteus syndrome. Standardized staging and treatment of these tumors are not well established; however, most authors conclude that these neoplasms must be treated as their ovarian counterparts. PMID:26558123

  6. Serous borderline tumor of the fallopian tube in a patient with Klippel-Trenaunay syndrome.

    PubMed

    Stephens, Daniel; Pillai, Srikumar; Cham, Elaine; Arensman, Robert; Chou, Pauline

    2010-11-01

    We describe a case of a 3-year-old girl with Klippel-Trenaunay syndrome who presented with an enlarging abdominal mass caused by a serous borderline tumor of the fallopian tube. This case is notable for the rarity of this neoplasm in a premenarchal patient as well as the association with this syndrome. We briefly review these entities and the significance of malignancy in Klippel-Trenaunay syndrome. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Borderline ovarian tumors: a study of 100 cases from a Tertiary Care Hospital

    PubMed Central

    Mun, Semih; Uysal, Fatma; Öztekin, Murat; Büyüktosun, Cem; Şehirali1, Salim; Başoğul, Ömer; Taner, Cüneyt E.

    2013-01-01

    Aim of the study The purpose of the study was to evaluate patients with borderline ovarian tumors. Material and methods Clinical features, treatment and survival status of 100 patients with borderline ovarian tumors were retrospectively evaluated between 1998 and 2007. Results Patients’ mean age was 37.75 years (range: 15–72); 22 of them were postmenopausal. Histopathological diagnoses were serous, mucinous, endometrioid and clear cell in 54%, 41%, 2% and 3% of the patients, respectively; 70 patients had stage IA disease, 8 were at stage IB, 16 at stage IC, 2 at stage IIIA, 3 at stage IIIB and 1 at stage IIIC. Restaging laparotomies were performed on 19 patients; fertility-sparing surgery was performed on 52 patients; 2 patients received chemotherapy because of advanced-stage disease. All patients are currently alive. The 5-year disease-free survival rate for 71 cases was 100%. Conclusions Borderline ovarian tumors have excellent prognoses, and fertility-conserving surgery can be performed in young patients with early-stage disease. PMID:24596520

  8. Decision making in borderline ovarian tumors: report of a rare case of mesosigma psammocarcinoma.

    PubMed

    Grimaldi, Luciano; Danzi, Michele; Reggio, Stefano; Pannullo, Mario; Danzi, Roberta; Lauria, Rossella

    2013-09-03

    Psammocarcinoma is a rare variant of serous carcinoma arising either from ovary or peritoneum, characterized by massive psammoma body formation, low-grade of cytologic differentiation and invasiveness. Its clinical behavior is similar to the serous borderline tumors, whose prognosis is significantly better compared to invasive forms, with a 5-year survival in stage I greater than 95%. A typical feature of borderline ovary tumors is the presence, in more than 30% of cases, of borderline peritoneal implants similar to primary ovarian cancer or of invasive forms. We report a case of a 44-years-old woman who referred to our clinic for mesosigmoid mass , accidentally discovered by ultrasonography. Sigmoidectomy with fertility sparing surgery was performed in september 2010. The mass was hystologically characterized by many psammoma bodies and low grade cytological features with diagnosis of psammocarcinoma of mesosigma. One year after the primary surgery, the patient showed with left adnexial mass; optimal debulking surgery was performed including omentectomy, total abdominal hysterectomy, bilateral adnexectomy and appendicectomy. The patient did not receive any adjuvant chemotherapy and to date she is alive and with no evidence of disease. The conclusion is that psammocarcinoma is a very rare tumor that behaves less aggressively than typical serous carcinoma, the mainstay of treatment is surgical debulking , with fertility sparing surgery as possible option in young patients with ovaries macroscopically free of disease.

  9. Intramedullary and retroperitoneal melanocytic tumor associated with congenital blue nevus and nevus flammeus: an uncommon combination of neurocutaneous melanosis and phacomatosis pigmentovascularis--case report.

    PubMed

    Kurokawa, Ryu; Kim, Phyo; Kawamoto, Toshiki; Matsuda, Hadzki; Hayashi, Shujiro; Yamazaki, Soji; Hatamochi, Atsushi; Mori, Shozo; Shimoda, Mitsugi; Kubota, Keiichi

    2013-01-01

    Neurocutaneous melanosis (NCM) is a rare condition characterized by central nervous system melanocytic tumors associated with congenital melanocytic nevi. Phacomatosis pigmentovascularis (PPV) is an association of vascular nevus with pigmentary nevus. Aberrant maturation of neural crest-derived cells is considered to be related to pathogenesis in both conditions. However, association of NCM and PPV has not been reported to the best of our knowledge. Melanocytoma, which usually involves the leptomeninges or spinal cord, is extremely rare in the retroperitoneum. We present here a case of a patient with NCM, PPV, and melanocytic tumors in the spinal cord and retroperitoneum, which were treated surgically. A 40-year-old woman had a 2-year history of dysesthesia and weakness in the left leg. History included congenital giant blue nevus-like lesion in the trunk, a port-wine stain in the sacral area, and Caesarean section performed 8 years before, when diffuse pigmentation in the peritoneum was noted. Magnetic resonance (MR) imaging of the spine revealed an intramedullary tumor at T10 level with paramagnetic signal characteristics. The spinal cord tumor was totally removed, and the histological diagnosis was melanocytoma. Three months later, a left retroperitoneal mass with histological features of melanocytic tumor was removed. Neither tumors recurred and the patient stays ambulatory 4 years after the surgery. Multiple subtypes of melanocytic tumors with distinctive features of NCM and PPV can develop simultaneously, mimicking malignant melanoma. Gross total resection of each tumor, when indicated, is beneficial.

  10. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  11. Differentiating intratumoral melanocytes from Langerhans cells in nonmelanocytic pigmented skin tumors in vivo by label-free third-harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Weng, Wei-Hung; Liao, Yi-Hua; Tsai, Ming-Rung; Wei, Ming-Liang; Huang, Hsin-Yi; Sun, Chi-Kuang

    2016-07-01

    Morphology and distribution of melanocytes are critical imaging information for the diagnosis of melanocytic lesions. However, how to image intratumoral melanocytes noninvasively in pigmented skin tumors is seldom investigated. Third-harmonic generation (THG) is shown to be enhanced by melanin, whereas high accuracy has been demonstrated using THG microscopy for in vivo differential diagnosis of nonmelanocytic pigmented skin tumors. It is thus desirable to investigate if label-free THG microscopy was capable to in vivo identify intratumoral melanocytes. In this study, histopathological correlations of label-free THG images with the immunohistochemical images stained with human melanoma black (HMB)-45 and cluster of differentiation 1a (CD1a) were made. The correlation results indicated that the intratumoral THG-bright dendritic-cell-like signals were endogenously derived from melanocytes rather than Langerhans cells (LCs). The consistency between THG-bright dendritic-cell-like signals and HMB-45 melanocyte staining showed a kappa coefficient of 0.807, 84.6% sensitivity, and 95% specificity. In contrast, a kappa coefficient of -0.37, 21.7% sensitivity, and 30% specificity were noted between the THG-bright dendritic-cell-like signals and CD1a staining for LCs. Our study indicates the capability of noninvasive label-free THG microscopy to differentiate intratumoral melanocytes from LCs, which is not feasible in previous in vivo label-free clinical-imaging modalities.

  12. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast.

    PubMed

    Moutte, Amandine; Chopin, Nicolas; Faure, Christelle; Beurrier, Frédéric; Ho Quoc, Christophe; Guinaudeau, Florence; Treilleux, Isabelle; Carrabin, Nicolas

    2016-09-01

    Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. © 2016 Wiley Periodicals, Inc.

  13. Immunofluorescence and confocal microscopy for ex-vivo diagnosis of melanocytic and non-melanocytic skin tumors: a pilot study.

    PubMed

    Hartmann, Daniela; Krammer, Sebastian; Vural, Secil; Bachmann, Mario Raphael; Ruini, Cristel; Sárdy, Miklós; Ruzicka, Thomas; Berking, Carola; von Braunmühl, Tanja

    2017-09-26

    Ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) offers rapid examination of freshly excised tissue. During the conventional examination immunohistochemistry enables to distinguish various cell types. The possibility of immunofluorescent techniques could enhance the accuracy of the diagnosis performed by ex-vivo CLSM. The tissue probes from various skin tumors were stained with FITC labelled S-100A10, Melan-A and anti-Ber-EP4 antibodies before examination with ex-vivo CLSM in the fluorescence (FM) and reflectance modes (RM). Results were compared to negative controls and conventional histopathology. The staining protocols were evaluated by establishing a scoring system according to the signal intensity found in ex-vivo CLSM. S100 immunostaining was successful in 55.6%. Dilution of 1:200 resulted in the best possible evaluation of the tumor. The best suitable protocol was protocol B (phosphate buffered saline /PBS/, without blocking agent). Melan A immunostaining was positive in 66.7%; 1:500 was the best dilution and protocol B (PBS, without blocking agent) the most suitable. Ber-EP4 immunostaining presented a signal in 85.7%, the best dilutions were 1:200 and 1:500 and protocol A (PBS, with blocking agent) showed most optimal results. The use of fluorescent-labeled antibodies in ex-vivo CLSM is possible and could improve intraoperative diagnostics of skin tumors. This article is protected by copyright. All rights reserved.

  14. Mucinous borderline ovarian tumors: Analysis of 75 patients from a single center

    PubMed Central

    Cömert, Duygu Kavak; Üreyen, Işın; Karalok, Alper; Taşçı, Tolga; Türkmen, Osman; Öcalan, Reyhan; Turan, Taner; Tulunay, Gökhan

    2016-01-01

    Objective To analyze the clinicopathologic features, recurrence and survival rates, reproductive history, and treatment of patients with mucinous borderline ovarian tumors (mBOTs). Material and Methods Patients with a diagnosis of mBOT were evaluated retrospectively. Patients with borderline ovarian tumors other than mucinous type and concomitant invasive cancer were excluded. Results A total of 75 patients were identified. Median age was 38 years. The most common symptom was pain (42.7%). Median CA-125 level was 23.5 IU/mL (range, 1–809 IU/mL). Median tumor size was 200 mm (range, 40–400 mm), and 6.7% of mBOTs were bilateral. Thirty-six (48%) patients underwent staging surgery. Two patients (5.9%) had nodal involvement. One patient received platinum-based adjuvant chemotherapy. One (1.3%) patient had recurrence. None of the patients died because of the ovarian tumor. A total of 43 patients had conservative surgery. Conclusion Prognosis of mBOTs is excellent, and fertility-sparing surgery should be considered in the reproductive age group. Furthermore, the necessity of staging surgery is controversial. PMID:27403076

  15. Ultrasonographic diagnosis and longitudinal follow-up of recurrences after conservative surgery for borderline ovarian tumors.

    PubMed

    Franchi, Dorella; Boveri, Sara; Radice, Davide; Portuesi, Rosalba; Zanagnolo, Vanna; Colombo, Nicoletta; Testa, Antonia Carla

    2016-12-01

    Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline

  16. Comparison of stromal CD10 expression in benign, borderline, and malignant phyllodes tumors among Egyptian female patients.

    PubMed

    Ibrahim, Wael S

    2011-01-01

    Phyllodes tumors are group of biphasic fibroepithelial tumors of the breast of varying malignant potential, ranging from benign tumors to fully malignant sarcomas. According to the Egyptian National Cancer Institute, female malignant cases showed appreciable increase in the recent time period for breast cancer with the malignant phyllodes tumors representing 0.41% of cases in the year 2003-2004. This is an immunohistochemical study to compare CD10 expression in benign, borderline, and malignant phyllodes tumors, in order to highlight its diagnostic and prognostic values. This study conducted 34 Egyptian female cases of phyllodes tumors of different grades to be studied histologically and immunohistochemically using antibodies against CD10. The Chi-square test was used to determine differences in CD10 expression between benign, borderline, and malignant tumors. One-way ANOVA test was used to determine whether the difference was significant. Significance was established at P<0.05. In the 24 cases of benign phyllodes tumors, only four cases (16.7%) showed positive CD10 reactivity. Three cases (60%) out of five borderline phyllodes tumors showed positive CD10 reactivity, while four (80%) out of five cases of malignant phyllodes tumors showed positive CD10 staining. From these highly significant results, we believe that there is a strong correlation between CD10 expression and tumor grade, which could be an important observation that may have both diagnostic and prognostic implications as well as promising potential target for development of novel therapies.

  17. Sox10 – A marker for not only Schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue. A systematic analysis of 5134 tumors

    PubMed Central

    Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; Wang, Zengfeng; Fetsch, John F.

    2015-01-01

    Sox10 transcription factor is expressed in Schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. Additionally, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 express-ion in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30–70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the GI-tract and metastatic melanoma, and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, PEComa, and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell type breast cancers, were only rarely positive but included rare squamous carcinomas of head and neck and pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors. PMID:25724000

  18. Differential expression of basic fibroblast growth factor (bFGF) in melanocytic lesions demonstrated by in situ hybridization. Implications for tumor progression.

    PubMed Central

    Reed, J. A.; McNutt, N. S.; Albino, A. P.

    1994-01-01

    Basic fibroblast growth factor (bFGF) is an angiogenic and mitogenic polypeptide produced by diverse cell types including cell lines derived from malignant melanomas but not from normal melanocytes. However, there is no consensus concerning in vivo expression of bFGF in melanocytic lesions due in part to the small numbers of cases studied to date. To evaluate further the possible differential expression of bFGF in melanocytic lesions, we examined 110 formalin-fixed, paraffin-embedded metastatic and primary invasive melanomas, melanomas in situ, nevi with architectural disorder and cytological atypia, and ordinary benign melanocyte nevi by nucleic acid in situ hybridization. All metastatic and primary invasive melanomas studied expressed bFGF mRNA, whereas melanomas in situ and benign melanocyte nevi were negative. Melanomas in situ with features of tumor regression and a majority of nevi with architectural disorder and cytological atypia also contained bFGF mrNA. The results suggest that in vivo bFGF expression is not requisite for malignant transformation per se, but appears to correlate more with invasion or fibroblastic reactions adjacent to the melanocyte lesions. Images Figure 1 Figure 2 PMID:8311116

  19. Ovarian high-grade serous carcinoma with a noninvasive growth pattern simulating a serous borderline tumor.

    PubMed

    Imamura, Hiroko; Ohishi, Yoshihiro; Aman, Murasaki; Shida, Kaai; Shinozaki, Tomoko; Yasutake, Nobuko; Sonoda, Kenzo; Kato, Kiyoko; Oda, Yoshinao

    2015-10-01

    Ovarian serous borderline tumors (SBTs) being a precursor of low-grade serous carcinomas are morphologically characterized by noninvasive growth and low-grade cytology. On the other hand, many pathologists regard cytologically high-grade, noninvasive (HG-noninv) ovarian serous tumors resembling SBTs in low magnification as conventional high-grade serous carcinomas (HGSCs) by personal experiences. Nonetheless, there are no established molecular characteristic of such tumors. In this study, therefore, we attempted to provide the molecular evidence. We selected 37 ovarian serous tumors that exhibited a cytologically HG-noninv growth pattern, including 36 tumors that coexisted with conventional invasive HGSC components (HG-inv) and a single tumor exclusively composed of pure HG-noninv. Histologically, all HG-noninv showed many mitotic figures, and serous tubal intraepithelial carcinomas were identified in 3 tumors with HG-noninv. Immunohistochemically, most HG-noninv showed aberrant p53 expression, frequent IMP3 positivity, p16 overexpression, a high MIB-1 labeling index, and infrequent PAX2. By molecular analysis, the pure HG-noninv and 13 HGSCs with HG-noninv showed TP53 mutations, but KRAS/BRAF mutations were not detected in any of them. In 1 tumor, we detected an identical TP53 mutation in both HG-noninv and HG-inv components by using laser capture microdissection. These immunohistochemical and molecular features of HG-noninv were similar to those of conventional invasive HGSCs but different from those of SBTs. In conclusion, our results showed that a cytologically HG-noninv growth pattern simulating an SBT is a morphological spectrum of HGSC, but not a true SBT.

  20. Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system

    PubMed Central

    van de Nes, Johannes; Gessi, Marco; Sucker, Antje; Moller, Inga; Stiller, Mathias; Horn, Susanne; Scholz, Simone L.; Pischler, Carina; Stadtler, Nadine; Schilling, Bastian; Zimmer, Lisa; Hillen, Uwe; Scolyer, Richard A.; Buckland, Michael E.; Lauriola, Libero; Pietsch, Torsten; Waha, Andreas; Schadendorf, Dirk; Murali, Rajmohan; Griewank, Klaus G.

    2017-01-01

    Melanocytic tumors originating in the central nervous system (MT-CNS) are rare tumors that generally have a favorable prognosis, however malignant tumors do occur. Pathogenetically MT-CNS are not well characterized. Similar to uveal melanoma and blue nevi, they frequently harbor activating GNAQ or GNA11 mutations. Rare NRAS mutations have also been reported. Other mutations have not yet been described. We analyzed 19 MT-CNS, 7 uveal melanomas and 19 cutaneous melanomas using a targeted next generation sequencing approach analyzing 29 genes known to be frequently mutated in other melanocytic tumors (in particular uveal and cutaneous melanomas). In concordance with previous studies, cutaneous melanoma samples showed frequent NRAS or BRAF mutations, as well as mutations in other genes (e.g. NF1, RAC1, PIK3CA, ARID1A). Metastasized uveal melanomas exhibited mutations in GNAQ, GNA11 and BAP1. In contrast, MT-CNS almost exclusively demonstrated mutations in GNAQ (71 %) or GNA11 (12 %). Interestingly both GNA11 mutations identified were detected in MT-CNS diagnosed as intermediate grade melanocytomas which also recurred. One of these recurrent cases also harbored an inactivating BAP1 mutation and was found to have lost one copy of chromosome 3. Our findings show that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas. Considering chromosome 3 and BAP1 loss are robust markers of poor prognosis in uveal melanoma, it will prove interesting to determine whether these genomic alterations are also of prognostic significance in MT-CNS. PMID:26744134

  1. Targeted next generation sequencing reveals unique mutation profile of primary melanocytic tumors of the central nervous system.

    PubMed

    van de Nes, Johannes; Gessi, Marco; Sucker, Antje; Möller, Inga; Stiller, Mathias; Horn, Susanne; Scholz, Simone L; Pischler, Carina; Stadtler, Nadine; Schilling, Bastian; Zimmer, Lisa; Hillen, Uwe; Scolyer, Richard A; Buckland, Michael E; Lauriola, Libero; Pietsch, Torsten; Waha, Andreas; Schadendorf, Dirk; Murali, Rajmohan; Griewank, Klaus G

    2016-05-01

    Melanocytic tumors originating in the central nervous system (MT-CNS) are rare tumors that generally have a favorable prognosis, however malignant tumors do occur. Pathogenetically MT-CNS are not well characterized. Similar to uveal melanoma and blue nevi, they frequently harbor activating GNAQ or GNA11 mutations. Rare NRAS mutations have also been reported. Other mutations have not yet been described. We analyzed 19 MT-CNS, 7 uveal melanomas and 19 cutaneous melanomas using a targeted next generation sequencing approach analyzing 29 genes known to be frequently mutated in other melanocytic tumors (in particular uveal and cutaneous melanomas). In concordance with previous studies, cutaneous melanoma samples showed frequent NRAS or BRAF mutations, as well as mutations in other genes (e.g. NF1, RAC1, PIK3CA, ARID1A). Metastasized uveal melanomas exhibited mutations in GNAQ, GNA11 and BAP1. In contrast, MT-CNS almost exclusively demonstrated mutations in GNAQ (71 %) or GNA11 (12 %). Interestingly both GNA11 mutations identified were detected in MT-CNS diagnosed as intermediate grade melanocytomas which also recurred. One of these recurrent cases also harbored an inactivating BAP1 mutation and was found to have lost one copy of chromosome 3. Our findings show that while MT-CNS do have GNAQ or GNA11 mutations, they rarely harbor other recurrent mutations found in uveal or cutaneous melanomas. Considering chromosome 3 and BAP1 loss are robust markers of poor prognosis in uveal melanoma, it will prove interesting to determine whether these genomic alterations are also of prognostic significance in MT-CNS.

  2. [Prognostic analysis of benign, borderline and malignant phyllodes tumors of the breast].

    PubMed

    Wang, Hui; Wang, Xiang; Wang, Chengfeng

    2015-12-01

    To explore the prognosis of benign, borderline and malignant phyllodes tumors of the breast. Data from 246 women with phyllodes tumors of the breast treated in the Cancer Hospital, Chinese Academy of Medical Sciences between January 2002 and December 2012, were collected and analyzed retrospectively. The patients were followed-up for a median of 48 months (range 1-138 months). Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the factors affecting the disease-free survival. Among the 246 patients, 65 were dropped out from the follow-up. 56 patients had local recurrence, 5 patients had distant metastasis, while one case had both local recurrence and distant metastasis. The median disease-free survival time was 39 months. Kaplan-Meier survival analysis revealed that fibroadenoma history and type of primary surgery were associated to the disease-free survival of phyllodes tumors of the breast (P<0.001, P=0.043), while histological type and primary tumor size had no significant relationship with the disease-free survival (P=0.083, P=0.974). The multivariate Cox proportional hazard model showed that type of primary surgery, fibroadenoma history and histological types are all independent factors affecting the disease-free survival (P=0.009, P=0.001 and P<0.001). Phyllodes tumors of the breast have a relatively good prognosis on the whole. Type of primary surgery, fibroadenoma history and histological type are independent factors predicting the disease-free survival of patients with phyllodes tumors of the breast.

  3. Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.

    PubMed

    Emmanuel, Catherine; Chiew, Yoke-Eng; George, Joshy; Etemadmoghadam, Dariush; Anglesio, Michael S; Sharma, Raghwa; Russell, Peter; Kennedy, Catherine; Fereday, Sian; Hung, Jillian; Galletta, Laura; Hogg, Russell; Wain, Gerard V; Brand, Alison; Balleine, Rosemary; MacConaill, Laura; Palescandolo, Emanuele; Hunter, Sally M; Campbell, Ian; Dobrovic, Alexander; Wong, Stephen Q; Do, Hongdo; Clarke, Christine L; Harnett, Paul R; Bowtell, David D L; deFazio, Anna

    2014-12-15

    Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. ©2014 American Association for Cancer Research.

  4. Phyllodes tumor of borderline malignancy: seven year follow up with immunohistochemical study.

    PubMed

    Tomita, Tatsuo; Ren, Yafei; Davis, Marilyn; Tawfik, Ossama

    2005-09-01

    The patient was 80 years old when she initially presented with a left breast mass. Originally, a needle biopsy showed benign stromal and ductal cells. Five years later, the breast mass increased in size and a core needle biopsy showed a biphasic intraductal papillomatous tumor with cellular stroma. Eighteen months later, another biopsy was taken from the breast mass, revealing a well-developed phyllodes tumor (PT) of borderline malignancy. One month later, a simple mastectomy was performed for this 87-year-old woman. Histolopathologic and immunohistochemical studies, including estrogen and progesterone receptors, Ki-67 and p53, performed on tissues from the different biopsy specimens confirmed the progressive transition of the tumor in a 7 year period. An increase in mitotic activity was noted in the later samples. Similarly, percentages of p53- and Ki-67-positive cells were much higher in the stromal and ductal cells of the later samples compared to the original specimen. These findings support the notion that Ki-67 and p53 immunohistochemical staining may be used as simple and practical markers for the evaluation of the malignant potential of PT.

  5. Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: A nationwide population-based cohort study.

    PubMed

    Rasmussen, Christina B; Jensen, Allan; Albieri, Vanna; Andersen, Klaus K; Kjaer, Susanne K

    2016-11-01

    Some studies suggest that pelvic inflammatory disease (PID) is a potential risk factor for ovarian cancer. However, only few studies have investigated the association between PID and risk of borderline ovarian tumors. We conducted a population-based cohort study to investigate the association between PID and risk of borderline ovarian tumors. Using various nationwide Danish registries we identified all women in Denmark during 1978-2012, who were born during 1940-1970 (n=1,318,925). Of these, 81,263 women were diagnosed with PID in the study period, and 2736 women had a borderline ovarian tumor (1290 serous and 1344 mucinous). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PID and risk of borderline tumors were estimated using Cox regression models with adjustment for potential confounders. A history of PID was associated with an increased risk of borderline ovarian tumors (HR=1.39; 95% CI: 1.19-1.61). However, histotype-specific analyses revealed significant variation in risk as PID was only associated with an increased risk of serous borderline tumors (HR=1.85; 95% CI: 1.52-2.24), but not with mucinous borderline tumors (HR=1.06; 95% CI: 0.83-1.35). PID is associated with an increased risk of serous borderline tumors. Further research on the potential underlying biological mechanisms and on the identification of the subset of women with PID who are at increased risk of serous borderline tumors is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Cytoskeleton alterations in melanoma: aberrant expression of cortactin, an actin-binding adapter protein, correlates with melanocytic tumor progression

    PubMed Central

    Xu, Xu-Zhi; Garcia, Marileila Varella; Li, Tian-yu; Khor, Li-Yan; Gajapathy, R Sujatha; Spittle, Cindy; Weed, Scott; Lessin, Stuart R; Wu, Hong

    2010-01-01

    Cortactin is a multidomain actin-binding protein important for the functions of cytoskeleton by regulating cortical actin dynamics. It is involved in a diverse array of basic cellular functions. Tumorigenesis and tumor progression involves alterations in actin cytoskeleton proteins. We sought to study the role of cortactin in melanocytic tumor progression using immunohistochemistry on human tissues. The results reveal quantitative differences between benign and malignant lesions. Significantly higher cortactin expression is found in melanomas than in nevi (P<0.0001), with levels greater in metastatic than in invasive melanomas (P<0.05). Qualitatively, tumor tissues often show aberrant cortactin localization at the cell periphery, corresponding to its colocalization with filamentous actin in cell cortex of cultured melanoma cells. This suggests an additional level of protein dysregulation. Furthermore, in patients with metastatic disease, high-level cortactin expression correlates with poor disease-specific survival. Our data, in conjunction with outcome data on several other types of human cancers and experimental data from melanoma cell lines, supports a potential role of aberrant cortactin expression in melanoma tumor progression and a rational for targeting key elements of actin-signaling pathway for developmental therapeutics in melanomas. PMID:19898426

  7. Epidemiologic features of borderline ovarian tumors in California: a population-based study.

    PubMed

    Morris, Cyllene R; Liu, Lihua; Rodriguez, Anne O; Cress, Rosemary D; Snipes, Kurt

    2013-04-01

    Borderline ovarian tumors (BOT) became no longer reportable in 2001, and few registries still collect information on these still poorly understood tumors. This study's objective was to describe epidemiologic features, trends, and survival of BOTs compared with those of low-grade (LG) and high-grade (HG) epithelial ovarian cancer (EOC) in the large and diverse population of California. Data from the California Cancer Registry were used to examine demographic and tumor characteristics among women diagnosed with BOT (n = 9,786), LG-EOC (n = 3,656), and HG-EOC (n = 40,611) from 1988 to 2010. Annual percent changes in BOT and LG-EOC incidence rates were estimated using Joinpoint regression; 5-year relative survival was calculated for both BOTs and LG-EOCs by age, race/ethnicity, and histology. Age-adjusted incidence rates of BOT in 2009 were 3.1, 2.3, 2.2, and 1.4 per 100,000 among whites, Latinas, African Americans, and Asian/Pacific Islanders, respectively. Incidence rates for LG-EOC decreased by 2.2 % per year; rates for BOT increased by 7.3 % per year until 1993, remained unchanged until 2006, and seemed to decline thereafter. Compared with LG-EOCs, BOTs were diagnosed in higher frequency among Latinas, at younger age, and were more likely to affect only one ovary. Overall, 5-year relative survival for BOT was 98.9 %; among women diagnosed with stage IV BOT, survival was 77.1 %. In this study, differences between BOTs and LG-EOCs were marked but varied substantially by histologic subtype and were far less dramatic than differences between BOTs and HG-EOCs. Findings underscore the importance of understanding these enigmatic tumors.

  8. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas.

    PubMed

    Halperin, R; Zehavi, S; Dar, P; Habler, L; Hadas, E; Bukovsky, I; Schneider, D

    2001-01-01

    The aim of this study was to characterize the clinical and molecular markers of borderline serous ovarian tumors (BSOT), and to study their expression in the progression from benign lesions to advanced serous papillary ovarian carcinomas (SPOC). The clinical records of 20 patients with BSOT and 22 patients with SPOC were reviewed. Specimens from all these cases and from six benign ovarian serous cystadenomas were evaluated for expression of estrogen receptors (ER), progesterone receptors (PR), p53. HER-2/neu and Ki-67 by immunohistochemical techniques. The mean patient age and the age at menarche differed significantly between the compared groups of BSOT and SPOC (p=0.0006 and p=0.0014, respectively). No difference was observed comparing the other clinical parameters. The immunohistochemical analysis demonstrated a significant increase in the expression of ER (100% vs 72.7%), and a significant decrease in the immunoreactivity for p53 (0% vs 45.4%) and Ki-67 (2% vs 26.8%) in cases of BSOT compared with those of SPOC (p=0.007, p=0.0003 and p=0.012, respectively). No significant difference was demonstrated comparing the expression of PR and HER-2/neu. The immunostaining of benign ovarian serous cystadenoma specimens did not differ significantly from immunoreactivity observed in cases of BSOT. According to immunohistochemical analysis, BSOT had much more in common with benign serous tumors than with SPOC. The main difference between BSOT and SPOC was regarding the overexpression of p53 and Ki-67.

  9. Genetics of Melanocytic Nevi

    PubMed Central

    Roh, Mi Ryung; Eliades, Philip; Gupta, Sameer; Tsao, Hensin

    2015-01-01

    Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial “driver” mutations are thought to trigger the establishment of benign nevi. After this initial phase of cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene-induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy. PMID:26300491

  10. A Case of a Giant Borderline Phyllodes Tumor Early in Pregnancy Treated with Mastectomy and Immediate Breast Reconstruction.

    PubMed

    Gentile, Lori F; Gaillard, William Foster; Wallace, Jodi-Ann; Spiguel, Lisa R P; Alizadeh, Layla; Lentz, Ashley; Shaw, Christiana

    2016-11-01

    Breast tumors in pregnancy are often times diagnosed at advanced stages secondary to difficulty distinguishing between pathologic from normal physiologic changes. Often benign, phyllodes tumors are rare fibroepithelial stromal tumors of the breast, most commonly diagnosed in the 4th and 5th decades of life. However, these tumors may be characterized by malignancy with metastases in 10% of cases. In this paper, we report a novel case of a young woman presenting at 8 weeks gestation with a large borderline phyllodes tumor. An exceedingly rare condition, with only nine previously reported cases, phyllodes tumors in pregnancy frequently display more aggressive characteristics with larger median tumor size, more malignant potential, and more rapid growth rate. Here, we describe our experience safely and effectively treating this rare condition in a young gravid women with mastectomy and immediate breast reconstruction in the second trimester.

  11. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors.

    PubMed

    El Din, Amina A Gamal; Badawi, Manal A; Aal, Shereen E Abdel; Ibrahim, Nihad A; Morsy, Fatma A; Shaffie, Nermeen M

    2015-12-15

    Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours.

  12. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  13. Expression of p16, p53, CD24, EpCAM and calretinin in serous borderline tumors of the ovary.

    PubMed

    Aktaş, Işıl Yildiz; Buğdayci, Meral; Usubütün, Alp

    2012-01-01

    According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core. For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tumors while expression of EpCAM was lost in the same areas. Strong cytoplasmic CD24 expression was detected in cases with peritoneal implants, favoring the theory that change of expression localization of cell adhesion molecules is in accordance with phenotypical changes and tumor progresssion. Furthermore, circumfrential membranous and cytoplasmic expression of CD24 and EpCAM was detected in neoplastic cells in lymph nodes and microinvasion areas. Our results show that different levels of serous ovarian tumor progression are accompanied by changes in the immunohistochemical expression pattern of EpCAM, CD24, and calretinin.

  14. The effect of hysterectomy on survival of patients with borderline ovarian tumors.

    PubMed

    Menczer, Joseph; Chetrit, Angela; Sadetzki, Siegal

    2012-05-01

    The classically recommended surgical treatment of borderline ovarian tumors (BOTs) includes hysterectomy in addition to bilateral adnexectomy. Possible reasons for hysterectomy might be a high frequency of uterine involvement and its favorable effect on survival. The purpose of the present study was to assess the frequency of uterine involvement in patients with BOTs and the effect of hysterectomy on survival. All incident cases of histological confirmed BOTs diagnosed in Israeli Jewish women between March 1 1994 and June 30 1999, were identified. Clinical and pathological characteristics were abstracted from medical records. Patients with tumors grossly confined to the ovaries (apparently stage I) were considered to have had surgical staging when at least hysterectomy, bilateral salpingooophorectomy, omentectomy and pelvic lymph node sampling were done. The study group comprised 225 patients. Hysterectomy was performed in 147 (65.31%) patients and uterine involvement was present in only 3 (2.0%) of them. The 13 year survival of the total group of patients was 85.8% and of those in apparent stage I, 88.5%. Among patients with tumors apparently confined to the ovaries, no significant survival difference was observed between unstaged and surgically staged patients. There was also no survival difference between the overall staged and unstaged patients and between patients in stages II-III who did and did not undergo hysterectomy. Our data indicate that the rate of uterine involvement in BOT is low and that hysterectomy does not favorably affect survival. The necessity of hysterectomy in BOT patients is questioned. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

    PubMed Central

    Chuong, Michael D.; Frakes, Jessica M.; Figura, Nicholas; Hoffe, Sarah E.; Shridhar, Ravi; Mellon, Eric A.; Hodul, Pamela J.; Malafa, Mokenge P.; Springett, Gregory M.

    2016-01-01

    Background While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. Methods This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. Results We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. Conclusions These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients. PMID:27034789

  16. Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer.

    PubMed

    Chuong, Michael D; Frakes, Jessica M; Figura, Nicholas; Hoffe, Sarah E; Shridhar, Ravi; Mellon, Eric A; Hodul, Pamela J; Malafa, Mokenge P; Springett, Gregory M; Centeno, Barbara A

    2016-04-01

    While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described. This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score. We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS. These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.

  17. Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

    PubMed

    Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

    2013-07-09

    Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

  18. May increased CA125 in borderline ovarian tumor be indicative of a poor prognosis? A case report.

    PubMed

    Anastasi, Emanuela; Porpora, Maria Grazia; Pecorella, Irene; Bernardo, Silvia; Frati, Luigi; Benedetti Panici, Pierluigi; Manganaro, Lucia

    2014-07-01

    We present a case of a 58-year-old menopausal woman referred to our hospital for the presence of large pelvic masses diagnosed by clinical examination and pelvic ultrasound. MRI examination showed voluminous bilateral capsulated multilocular ovarian cysts slightly hyperintense on T1-weighted images with thick septa and small papillary projections. CT scan confirmed the MRI findings. Among the ovarian tumor markers analyzed (CA125, HE4, and CA72.4), only Ca125 was slightly increased (48 U/ml). These data were suggestive of mucinous ovarian tumor. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, appendectomy, and multiple peritoneal biopsies. Pathological examination revealed bilateral borderline mucinous ovarian tumor with superficial atypical implants. Nine months later, the patient complained of left coxofemoral pain and underwent a PET/TC total body that suggested pubic bone metastases. Ovarian tumor markers were analyzed, and a second PET/TC was performed. CA125 was 252 U/ml, HE4 62 pM/L, and CA72.4 > 100 U/Ml. PET/TC was suggestive of peritoneal carcinosis. The patient was readmitted to the hospital. Clinical examination revealed small vaginal nodules. All nodules were excised. Microscopic analysis of all specimens revealed metastatic mucinous adenocarcinoma of intestinal type.The case shows that even a slight CA125 increase in the presence of a borderline ovarian tumor should not be overlooked since it can be indicative of a progressive disease. This case also highlights its additional diagnostic value when serum CA125 analysis is used in conjunction with MRI and CT imaging for the prognosis of mucinous borderline ovarian tumors (mBOTs).

  19. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  20. Genetic vaccination against the melanocyte lineage-specific antigen gp100 induces cytotoxic T lymphocyte-mediated tumor protection.

    PubMed

    Schreurs, M W; de Boer, A J; Figdor, C G; Adema, G J

    1998-06-15

    Melanocyte lineage-specific antigens, such as gp100, have been shown to induce both cellular and humoral immune responses against melanoma. Therefore, these antigens are potential targets for specific antimelanoma immunotherapy. A novel approach to induce both cellular and humoral immunity is genetic vaccination, the injection of antigen-encoding naked plasmid DNA. In a mouse model, we investigated whether genetic vaccination against the human gp100 antigen results in specific antitumor immunity. The results demonstrate that vaccinated mice were protected against a lethal challenge with syngeneic B16 melanoma-expressing human gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific for human gp100 could be detected in human gp100-vaccinated mice. However, only adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from protected mice was able to transfer antitumor immunity to nonvaccinated recipients, indicating that CTLs are the predominant effector cells. CTI, lines generated from human gp100-vaccinated mice specifically recognized human gp100. Interestingly, one of the CTL lines cross-reacted between human and mouse gp100, indicating the recognition of a conserved epitope. However, these CTLs did not appear to be involved in the observed tumor protection. Collectively, our results indicate that genetic vaccination can result in a potent antitumor response in vivo and constitutes a potential immunotherapeutic strategy to fight cancer.

  1. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

  2. Coexistence of borderline ovarian epithelial tumor, primary pelvic hydatid cyst, and lymphoepithelioma-like gastric carcinoma.

    PubMed

    Gungor, Tayfun; Altinkaya, Sunduz Ozlem; Sirvan, Levent; Lafuente, Roberto Alvarez; Ceylaner, Serdar

    2011-06-01

    Borderline ovarian tumors (BOTs) represent a heterogeneous group of ovarian epithelial neoplasms. Despite a favorable prognosis, 10-20% of BOTs exhibit progressively worsening clinic. Primary involvement of pelvic organs with echinococcus is very rare. Lymphoepithelioma-like gastric carcinoma is a rare neoplasm of the stomach. A 58-year-old woman referred with abdominal swelling and gastric complaints. Imaging studies revealed a huge cystic mass with multiple septations and solid component, another cystic mass with an appearance of cyst hydatid in the pelvis, and thickening of the small curvature of stomach. Gastroscopy revealed an ulcer with a suspicious malignant appearance, and histology of the endoscopic specimen showed severe chronic inflammation and lymphocytic infiltration. No other involvement of hydatid cyst was detected. In the exploration, there was a 25cm cystic lesion with solid components arising from right ovary, another 6cm cyst over the former, 7cm cystic lesion arising from left ovary, and 10cm mass near the small curvature of the stomach. Excision of the masses; total gastrectomy with esophagojejunal anastomosis; total abdominal hysterectomy; bilateral salpingo-oophorectomy; omentectomy; appendectomy; splenectomy; and pelvic, paraaortic, and coeliac lympadenectomy were performed. Final pathology revealed lymphoepithelioma-like gastric carcinoma, bilateral serous BOT, and hydatid cyst. Hydatid cyst should always be considered in the differential diagnosis of abdominopelvic masses in endemic regions of the world. Preoperative diagnosis of primary pelvic hydatid disease is difficult and awareness of its possibility is very important especially in patients residing in or coming from endemic areas. Copyright © 2011. Published by Elsevier B.V.

  3. A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

    PubMed

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

    2016-06-01

    To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

  4. Exploiting tyrosinase expression and activity in melanocytic tumors: quercetin and the central role of p53.

    PubMed

    Vargas, Ashley J; Sittadjody, Sivanandane; Thangasamy, Thilakavathy; Mendoza, Erin E; Limesand, Kirsten H; Burd, Randy

    2011-12-01

    Melanoma is an aggressive tumor that expresses the pigmentation enzyme tyrosinase. Tyrosinase expression increases during tumorigenesis, which could allow for selective treatment of this tumor type by strategies that use tyrosinase activity. Approaches targeting tyrosinase would involve gene transcription or signal transduction pathways mediated by p53 in a direct or indirect manner. Two pathways are proposed for exploiting tyrosinase expression: (a) a p53-dependent pathway leading to apoptosis or arrest and (b) a reactive oxygen species-mediated induction of endoplasmic reticulum stress in p53 mutant tumors. Both strategies could use tyrosinase-mediated activation of quercetin, a dietary polyphenol that induces the expression of p53 and modulates reactive oxygen species. In addition to antitumor signaling properties, activation of quercetin could complement conventional cancer therapy by the induction of phase II detoxification enzymes resulting in p53 stabilization and transduction of its downstream targets. In conclusion, recent advances in tyrosinase enzymology, prodrug chemistry, and modern chemotherapeutics present an intriguing and selective multitherapy targeting system where dietary bioflavonoids could be used to complement conventional cancer treatments.

  5. Melanocytic nevi and non-neoplastic hyperpigmentations.

    PubMed

    Clemente, C

    2017-06-01

    This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the

  6. Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status.

    PubMed

    Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia; Derchain, Sophie

    2013-04-01

    To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression.

  7. Survival of women with ovarian carcinomas and borderline tumors is not affected by estrogen and progesterone receptor status

    PubMed Central

    Sallum, Luis Felipe; Sarian, Luis Otavio; Lucci De Angelo Andrade, Liliana; Vassallo, José; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Ferreira, Patrícia Andréia

    2013-01-01

    Objective To examine the patterns of estrogen receptor (ER) and progesterone receptor (PR) expression in borderline ovarian tumors (BOTs) and ovarian carcinomas. We also assessed the disease-free survival (DFS) and overall survival (OS) in women with ovarian carcinoma, in relation to ER and/or PR expression. Methods We examined ER/PR expression in 38 BOTs and 172 ovarian carcinomas removed from patients treated at the State University of Campinas-UNICAMP (Brazil), from 1993 to 2008 and followed for up to 60 months using tissue microarray-based immunohistochemistry. Results Twenty-eight (73.7%) mucinous and 10 (26.3%) serous BOTs were included. Ovarian carcinomas consisted mainly of 79 (46.0%) serous, 44 (25.5%) mucinous, 17 (9.8%) endometrioid, 10 (5.8%) clear-cell types. There was no significant difference of the ER/PR expression between BOT and ovarian carcinoma (p=0.55 for ER alone, 0.90 for PR alone, and 0.12 for combined expression). The level of ER/PR expression in BOTs was significantly higher in serous than in mucinous tumors (p<0.01). In carcinomas, ER/PR was higher in serous tumors than in mucinous (p<0.01) and clear cell tumors (p=0.02), and higher in endometrioid tumors than in mucinous tumors (p<0.01). DFS was affected neither by the clinical characteristics nor by combined steroid receptor status. OS was found to be significantly worse (p<0.01) only in women with stages II-IV tumors and those with residual disease after surgery (p<0.01). Conclusion Overall, serous and endometrioid tumors were predominantly ER/PR positive, whereas mucinous and clear-cell tumors were preponderantly ER/PR negative. DFS and OS were not affected by ER/PR expression. PMID:23653835

  8. Five-Year Disease-Free Follow-Up of a Borderline Breast Phyllodes Tumor in a 15-year-old Patient

    PubMed Central

    Güler, Sertaç Ata; Uğurlu, M. Ümit; Güllüoğlu, Bahadır M.

    2015-01-01

    Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.

  9. Assessment of the argyrophilic nucleolar organizer region area/nucleus ratio in ovarian serous epithelial adenomas, borderline tumors and cancers

    PubMed Central

    Danilewicz, Marian; Suzin, Jacek; Wagrowska-Danilewicz, Malgorzata; Spych, Michal; Tylinski, Wieslaw; Topczewska-Tylinska, Katarzyna; Piekarski, Janusz; Kazmierczak-Lukaszewicz, Sylwia; Cialkowska-Rysz, Aleksandra

    2013-01-01

    Introduction There is a need to assess the value of the novel potentially useful biomarkers in ovarian tumors. The aim of study was to assess the value of sAgNOR analysis in ovarian serous epithelial tumors. Material and methods The analysis was performed in ovaries from 113 patients treated operatively due to serous ovarian tumors (30 adenomas, 14 borderline tumors and 69 cancers). After silver staining of paraffin specimens from surgery, sAgNOR in tumor cells was analyzed. Additionally, the value of the argyrophilic nucleolar organizer region area/nucleus ratio (sAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in 52 patients with serous ovarian cancer with complete follow-ups in November 2009 was evaluated. Age, grading, radicality of surgery and FIGO staging were analyzed as additional factors. Results sAgNOR in adenomas, borderline tumors and cancers was in the following ranges: (0.73 ±0.23) × 106, (0.81 ±0.18) × 106 and (0.96 ±0.33) × 106 [AgNOR/cm2] respectively. In cancers from G1 to G3 sAgNOR was (1.02 ±0.32) × 106 (G1), (0.98 ±0.37) × 106 (G2) and (0.82 ±0.24) × 106 (G3) [AgNOR/cm2] respectively. In univariate analysis, but not in multivariate analysis, staging negatively correlated with better DFS and OS. sAgNOR, age of patients, grading and radicality of surgery were not associated with DFS or OS in either univariate or multivariate analysis. Conclusions sAgNOR analysis is not sufficient to precisely characterize cellular kinetics in serous ovarian tumors, and the analysis of sAgNOR, mAgNOR and pAgNOR should be performed commonly. The prognostic significance of sAgNOR in patients with serous ovarian cancer was not proven. PMID:23515230

  10. Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

    PubMed

    Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

    2017-02-01

    We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p < 0.05). At the API cutoff level of 6.0, API and CA125 had equal positive rates of detecting cancers and borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p < 0.05). API is an effective new tumor marker to detect ovarian cancers and borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

  11. HER-2 and cancer antigen 125 evaluation in ovarian borderline tumors by immunohistochemistry and fluorescence in situ hybridization.

    PubMed

    Heinrich, J K R; Böttcher-Luiz, F; Andrade, L L A; Davidson, S; Bonds, L; Stephens, J; Varella-Garcia, M

    2004-01-01

    The study determined the expression of cancer antigen (CA) 125 and HER-2 in 45 borderline ovarian tumors (BOTs) and investigated the correlation of these biologic markers with histologic type, clinical stage, and outcome. The level of CA 125 protein was assessed using DAKO's M-11 clone antibody in immunohistochemistry (IHC) assays (Carpinteria, CA). The HER-2 protein expression was assessed in IHC assays using the HercepTest (DAKO), and the HER-2 gene copy number per cell was investigated through fluorescence in situ hybridization (FISH) assays using VYSIS' PathVysion DNA Probe (Downers Grove, IL). Expression of the CA 125 protein was detected in 49% of the samples (22 out of 45 tumors) and significantly associated with the serous histologic type. However, CA 125 expression did not associate with clinical stage or outcome. Protein overexpression or gene amplification of HER-2 was not found. However, abnormal FISH results were detected in 16% (seven out of 45 patients) of specimens comprising extranumerary copies of HER-2 and/or chromosome 17 per cell. Abnormal FISH results were found to be independent of CA 125 expression and histologic type whereas they positively associate with advanced clinical stage. Our data show that HER-2 is not altered in BOTs, and the presence of aneusomy for chromosome 17 and HER-2 may predict tumor progression.

  12. Classification of melanocytic skin lesions from non-melanocytic lesions.

    PubMed

    Iyatomi, Hitoshi; Norton, Kerri-Ann; Celebi, M; Schaefer, Gerald; Tanaka, Masaru; Ogawa, Koichi

    2010-01-01

    In this paper, we present a classification method of dermoscopy images between melanocytic skin lesions (MSLs) and non-melanocytic skin lesions (NoMSLs). The motivation of this research is to develop a pre-processor of an automated melanoma screening system. Since NoMSLs have a wide variety of shapes and their border is often ambiguous, we developed a new tumor area extraction algorithm to account for these difficulties. We confirmed that this algorithm is capable of handling different dermoscopy images not only those of NoMSLs but also MSLs as well. We determined the tumor area from the image using this new algorithm, calculated a total 428 features from each image, and built a linear classifier. We found only two image features, "the skewness of bright region in the tumor along its major axis" and "the difference between the average intensity in the peripheral part of the tumor and that in the normal skin area using the blue channel" were very efficient at classifying NoMSLs and MSLs. The detection accuracy of MSLs by our classifier using only the above mentioned image feature has a sensitivity of 98.0% and a specificity of 86.6% in a set of 107 non-melanocytic and 548 melanocytic dermoscopy images using a cross-validation test.

  13. Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies.

    PubMed

    Rasmussen, Christina B; Kjaer, Susanne K; Albieri, Vanna; Bandera, Elisa V; Doherty, Jennifer A; Høgdall, Estrid; Webb, Penelope M; Jordan, Susan J; Rossing, Mary Anne; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Edwards, Robert P; Schildkraut, Joellen M; Berchuck, Andrew; Olson, Sara H; Kiemeney, Lambertus A; Massuger, Leon F A G; Narod, Steven A; Phelan, Catherine M; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H; Pearce, Celeste L; Risch, Harvey A; Jensen, Allan

    2017-01-01

    Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. [A case of coexisting borderline phyllodes tumor and non-invasive ductal carcinoma].

    PubMed

    Toyoda, Yasuhiro; Hojo, Shigeyuki; Yoshioka, Setsuko; Kojima, Fumiyoshi; Matsunaga, Hiroki; Fujie, Yujiro; Fukunaga, Hiroki; Ota, Hirofumi; Endo, Wakio; Maeura, Yoshiichi

    2013-11-01

    A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

  15. "Borderline" Children.

    ERIC Educational Resources Information Center

    Gualtieri, C. Thomas C.; And Others

    1983-01-01

    The use of the diagnosis "borderline" was evaluated with 16 children (6 to 13 years old) who were referred for comprehensive evaluation. None met DSM III criteria for borderline personality disorder. The borderline label had a negative impact on some children and was not helpful for treatment planning or disposition. (Author/SEW)

  16. Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment.

    PubMed

    Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M; Hao, Hongying

    2016-07-01

    The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma.

  17. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

    PubMed

    Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

    2017-04-01

    The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

  18. A Case of Giant Borderline Phyllodes Tumor of the Breast Associated with Hypoglycemia.

    PubMed

    Saito, Yuki; Suzuki, Yasuhiro; Inomoto, Chie; Kumaki, Nobue; Yokoyama, Kozue; Ogiya, Rin; Oshitanai, Risa; Terao, Mayako; Tsuda, Banri; Morioka, Tooru; Niikura, Naoki; Okamura, Takuho; Masuda, Shinobu; Tokuda, Yutaka

    2016-09-20

    We report a patient with a giant phyllodes tumor of the right breast associated with a hypoglycemic attack. A 48-year-old woman experienced a loss of consciousness and was transferred via ambulance to our hospital emergency department. Upon arrival, her blood glucose level was 26 mg/dl, and a giant tumor (>20 cm in diameter) with skin ulceration was observed on the right breast. Core needle biopsy led to a histological diagnosis of a phyllodes tumor of the breast. Ultrasonography and computed tomography detected neither distant metastasis nor a pancreatic endocrine tumor. Her preoperative serum insulin-like growth factor (IGF)-II and insulin levels were 1,330 ng/ml (normal range, 519-1067 ng/ml) and <1.0 µU/ml, respectively. Following a simple mastectomy, the 24-h postoperative serum IGF-II and insulin levels were 496 ng/ml and 10.0 µU/ml, respectively. The IGF-II levels detected in the phyllodes tumor and normal breast tissue were 10,600 ng/Wg (wet weight in grams) and 855 ng/Wg. We conclude from these findings that the hypoglycemic attack was related to the elevated IGF-II level in the giant phyllodes tumor of the breast.

  19. Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors

    PubMed Central

    2012-01-01

    Background In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2), c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors. Methods Total of 68 ovarian tumors, 25 benign [13 (19.1%) serous and12 (17.6%) mucinous], 16 borderline [9 (13.2%) serous and 7(10.3%) mucinous], and 27 malignant ovarian tumors [24 (35.3%) serous and 3 (4.4%) mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl–2, telomerase, c-kit, and metallothionein were evaluated. Results When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p < 0.05). After evaluation of all 68 cases, the serous tumors showed significantly higher staining scores of p53, p21, c-kit, and metallothionein compared to the mucinous ones (p < 0.05). For differentiation of benign and borderline and malignant tumors combined, p53 was not used because all benign tumors has no staining, and p21, bax, and metallothionein was determined the significant predictors for borderline and malignant tumors combined (p < 0.05). For differentiation of borderline and malignant tumors, only p53 was determined the significant predictor for malignant tumors (p < 0.05). Conclusions In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and

  20. A Tete – a – tete of benign, borderline and malignant fibrohistiocytic tumor

    PubMed Central

    M.V, Rashmi.; P, Pavithra; G.M, Shivakumarappa

    2016-01-01

    Dermatofibrosarcoma protruberans is a relatively uncommon slow growing, locally aggressive fibrous tumor of the skin. It has a prospensity of progressing to fibrosarcomatous change in 5% of the cases. We present a case of a 56 yr old male with presented to the outpatient department of surgery, Sri Siddhartha Medical College, Tumkur with a chest swelling in 2013. FNAC was inconclusive and the mass was excised. On histopathology, areas of benign fibrohistiocytic tumor, dermatofibrosarcoma protruberans and fibrosarcomatous dermatofibrosarcoma were identified in the same tumor. Immunohistochemistry confirmed the diagnosis of DFSP with fibrosarcomatous change. Although, transformed DFSP is more aggressive, the prognosis is influenced by the extent of excision and with wide excision, there may be little increased risk for recurrence and metastasis over that of conventional DFSP. PMID:27799980

  1. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    SciTech Connect

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-07

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  2. Borderline osteoblastic tumors: problems in the differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma.

    PubMed

    Dorfman, H D; Weiss, S W

    1984-08-01

    A series of 102 benign osteoblastic tumors of multiple skeletal sites was reviewed, and on the basis of their clinical, radiologic, and pathologic features they were classified into three diagnostic categories: osteoid osteoma, osteoblastoma, and aggressive osteoblastoma. A historic review of the development of the nomenclature of benign osteoblastic tumors, with special emphasis on the evolving concept of aggressive and malignant behavior, is presented. Histologic criteria for the recognition of aggressive osteoblastoma are presented and illustrated in connection with the 15 cases so classified in the present series. The differential diagnosis of aggressive osteoblastoma and low-grade osteosarcoma is discussed. In defining the problem of differentiating locally aggressive osteoblastic lesions from potentially metastasizing tumors, the authors propose that four categories of these osteoblastic tumors can be defined: (1) Innocuous-appearing low-grade osteosarcomas that resemble osteoblastomas histologically. This mimicry accounts for most errors in diagnosis. (2) Rare osteoblastomas that have undergone spontaneous transformation into osteosarcomas. (3) Very rare, clinically and radiologically typical osteoblastomas that show pseudosarcomatous histologic features but pursue a benign course. (4) Locally aggressive osteoblastomas that are likely to recur, do not metastasize, and show characteristic and recognizable histologic features.

  3. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

    PubMed

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

    2015-01-01

    Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

  4. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.

    PubMed

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-07

    Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  5. Clinical application of optical coherence tomography for the imaging of non–melanocytic cutaneous tumors: a pilot multi–modal study

    PubMed Central

    Carstea, EM; Ghervase, L; Giurcaneanu, C; Pavelescu, G

    2010-01-01

    Context: Optical coherence tomography (OCT) is an emergent imaging technique, based on the interference of infrared radiation and living tissues, that allows the in vivo visualisation of the skin structures, at high resolution and up to 1.6 mm depth. As such, there is mounting evidence that OCT may be an interesting technique for the diagnossis of skin diseases, including the non–invasive early detection of cutaneous tumors. Objective: We aimed to investigate the utility of OCT for the diagnosis of non–melanocytic, non–pigmented cutaneous tumors. Methods: Preliminary results are presented from an initiated study. Fifteen consecutive patients with clinical suspicion of epithelial cancers and precancers registered over one week in an university dermatologic department were included. As control were selected 7 patients with inflammatory skin diseases (psoriasis, lichen planus, cutaneous lupus erythematosus). In all study and control patients the lesions and samples of normal, perilesional skin were documented by clinical digital photography, contact dermoscopy with digital image capture and OCT with central wavelength of 930 nm. Final diagnosis was certified by histopathological analysis. Results: We could identify morphological features in OCT examination that distinguished between normal and lesional skin, and between neoplastic vs. inflamatory lesions. In the same time, combining OCT and dermatoscopical evaluation of a lesion improved the performance of diagnosis when compared to clinical diagnosis alone and with either OCT or dermoscopy imaging used alone. Conclusions: OCT appears as a promising method of in vivo diagnosis of early neoplastic cutaneous lesions with equivocal clinical and/or dermoscopic aspect. Continuation of our study as well as other larger investigation will be able to contribute with new insights in the role of OCT in the non–invasive diagnosis of skin disease. PMID:21254735

  6. A pilot study to compartmentalize small melanocytic choroidal tumors and choroidal vessels with speckle-noise free 1050 nm swept source optical coherence tomography (OCT choroidal "tumoropsy").

    PubMed

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal Willy

    2016-06-01

    The purpose was to illustrate small melanocytic choroidal tumors with speckle-noise free swept-source optical coherence tomography (SSOCT). Twenty-five small melanocytic choroidal tumors in 24 eyes underwent 1050 nm OCT. All tumors were measured manually with the built-in caliper tool and compared to data derived from a semiautomated algorithm that removed speckle noise but preserved the structure of the tumors from the SSOCT data. The average manual measurements for the horizontal, vertical, and axial diameters were 1535.28 μm (range, 547-2807 μm), 1713.8 μm (range, 574-3921 μm), and 227.28 μm (range, 115-489 μm), respectively. The measured average volumes of the tumors were 835,248,212 μm(3) (range, 48,818,700 to 4,567,401,810 μm(3)) and 228,588,535 μm(3) (range, 22,879,641 to 787,668,886 μm(3)) for caliper measurements, respectively, for the extracted volumes. The average volume variation between the two methods was 66.16 % (range, 46.5 % to 82.75 %). The average ratio between the caliper and extracted volumes was 3.402 (range, 1.346-8.198, SD 1.681), 2.367 (range, 1.346-3.258, SD 0.618), 2.321 (range, 1.346-3.258, SD 0.611), 2.402 (range, 1.518-3.258, SD 0.591), and 1.749 (range, 1.518-1.733, SD 0.239) for all tumors, all tumors with the exclusion of extreme parameters, tumor <3 mm, tumor <2 mm, and tumor <1 mm, respectively. The average ratio (tumor index) between the tumor volume and the choroidal vessel volume was 12.539 (range, 0.489-73.701). Speckle-noise free swept-source OCT may be an illustrative OCT imaging technology. OCT may be useful for describing and monitoring small melanocytic choroidal tumors and the choroidal vessels.

  7. Postpubertal Persistent Hyperestrogenemia in McCune-Albright Syndrome: Unilateral Oophorectomy Improved Fertility but Detected an Unexpected Borderline Epithelial Ovarian Tumor.

    PubMed

    Chevalier, Nicolas; Paris, Françoise; Fontana, Sylvie; Delotte, Jérôme; Gaspari, Laura; Ferrari, Patricia; Sultan, Charles; Fénichel, Patrick

    2015-12-01

    McCune-Albright syndrome (MAS), due to a somatic mutation of the GNAS1 gene, begins usually in girls with peripheral precocious puberty. Ovarian autonomy may persist in adulthood with acyclic hyperestrogenemia, infertility, and a potential risk of estrogen-dependent cancer. A 22-year-old woman, with MAS, was referred for infertility with left macropolycystic ovary, hyperestrogenemia, and chronic anovulation unsuccessfully treated by controlled hyperstimulation. Once ovarian cyst punctures and cDNA analysis verified that GNAS1 mutation was restricted to the left ovary, unilateral ovariectomy was performed. It improved right ovarian function, allowed an in vitro fertilization-induced pregnancy, but revealed an unexpected borderline epithelial ovarian tumor. Several breast cancers have already been reported in young MAS patients but not a borderline epithelial ovarian tumor. In this context, we would recommend that persistent hyperestrogenemia in an adult be corrected and gynecological follow-up of the breasts, ovaries, and endometrium be implemented. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  8. Loss of p16 expression and copy number changes of CDKN2A in a spectrum of spitzoid melanocytic lesions.

    PubMed

    Harms, Paul W; Hocker, Thomas L; Zhao, Lili; Chan, May P; Andea, Aleodor A; Wang, Min; Harms, Kelly L; Wang, Michael L; Carskadon, Shannon; Palanisamy, Nallasivam; Fullen, Douglas R

    2016-12-01

    Spitzoid melanocytic lesions, including Spitz nevi (benign), spitzoid melanoma (malignant), and borderline atypical Spitz tumors (ASTs), frequently present challenges for accurate diagnosis and prognosis. Evaluation for loss of the tumor suppressor p16, encoded by CDKN2A gene on chromosome 9p21.3, has been proposed to be useful for evaluation of spitzoid melanocytic lesions. However, reports on the utility of p16 immunohistochemistry for spitzoid lesions have been conflicting, and few studies have directly compared p16 immunohistochemistry with fluorescence in situ hybridization (FISH) for CDKN2A genomic status. We analyzed a spectrum of benign (n=24), borderline (n=27), and malignant (n=19) spitzoid lesions for p16 protein expression by immunohistochemistry and CDKN2A copy number by FISH. Immunohistochemistry was evaluated by 2 scoring methods: H score and 2-tiered score (positive or negative for p16 loss). By immunohistochemistry, loss of p16 expression was not observed in Spitz nevi (0/24) but was seen in ASTs (7/27; 26%) and spitzoid melanomas (3/19; 16%). By H score, p16 expression was significantly higher in Spitz nevi relative to ASTs or spitzoid melanomas. Similarly, copy number aberrations of CDKN2A by FISH were absent in Spitz nevi but were found in 2 (9.5%) of 21 ASTs and 4 (33%) of 12 spitzoid melanomas. Our findings from this large cohort suggest that p16 aberrations are highly specific for borderline and malignant spitzoid neoplasms relative to Spitz nevi. Similar to ASTs, p16 loss in spitzoid melanomas may occur in the presence or absence of genomic CDKN2A loss.

  9. Endometriosis-associated serous borderline tumor and endometrial stromal sarcoma of the ovary: a report of a rare lesion in an infant.

    PubMed

    Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C

    2012-01-01

    Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.

  10. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays.

  11. Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

    PubMed

    Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

    2017-05-11

    The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinico-pathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinico-pathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We

  12. Giant congenital melanocytic nevus.

    PubMed

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.

  13. Giant congenital melanocytic nevus*

    PubMed Central

    Viana, Ana Carolina Leite; Gontijo, Bernardo; Bittencourt, Flávia Vasques

    2013-01-01

    Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion. PMID:24474093

  14. Histology-specific long-term trends in the incidence of ovarian cancer and borderline tumor in Japanese females: a population-based study from 1983 to 2007 in Niigata.

    PubMed

    Yahata, Tetsuro; Banzai, Chiaki; Tanaka, Kenichi

    2012-04-01

    The histology-specific long-term trends in the incidence of ovarian cancer and borderline tumors in Japanese women were examined, based on data from the population-based cancer registry in Niigata, Japan. Data were obtained from the Niigata Gynecological Cancer Registry, which covered the entire female population in Niigata prefecture, Japan, during the period from 1983 to 2007. A total of 3134 females with epithelial ovarian cancer, including borderline tumor cases, were diagnosed between 1983 and 2007. The age-standardized rates (ASRs) of both ovarian cancer and borderline tumors have steadily increased, with significant changes in ovarian cancer in all age groups, and borderline ovarian tumors in subjects aged <50. The ASRs of endometrioid adenocarcinoma showed a steady increasing trend, and those of clear cell and mucinous adenocarcinomas showed significant increasing trends in the total population. The ASRs of clear cell, mucinous, and endometrioid adenocarcinomas in the 50+ age group were significantly increased, especially the incidence of clear cell adenocarcinoma, which strikingly increased by approximately threefold from 1.2 (1983-1989) to 3.5 (2000-2007) per 100,000 females. This prefecture-wide study showed the practical trends in ovarian cancer and borderline tumors in Japanese females. The incidence of ovarian cancer has steadily increased, with significant increases in the incidence of clear cell and mucinous adenocarcinomas in the total population during the past two decades. Because of the poor response rate of these histological subtypes to platinum-based regimens, novel treatment approaches should be adopted to improve the prognostic outcome in patients with ovarian cancer in Japan. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  15. Population-based cohort follow-up study of all patients operated for borderline ovarian tumor in western Sweden during an 11-year period.

    PubMed

    Akeson, M; Zetterqvist, B-M; Dahllöf, K; Jakobsen, A-M; Brännström, M; Horvath, G

    2008-01-01

    Borderline ovarian tumors (BOTs) make up around 10-20% of all epithelial ovarian tumors. The aim of the present study was to investigate the outcome of a complete large population-based cohort of patients treated for BOT. All patients (n= 399) treated for BOT in the western part of Sweden (population around 1.6 million) between 1993 and 2004 were followed. The treatment consisted of primary staging surgery with addition of platinum-based adjuvant chemotherapy for the majority of aneuploid tumors. Data relating to the surgical procedure, FIGO stage, histopathology, ploidy status, adjuvant chemotherapy, and disease state (recurrence or death) at follow-up visits were continuously entered into a cancer quality registry. Data concerning cases and deaths were also controlled against the Swedish National Cancer Registry. The median age of the BOT patients was 55 years (range 16-90). The relative 5- and 10-year survivals were 99.9% (95% CI 96.3-102.4) and 103.5% (95% CI 97.2-108.2), respectively. Aneuploidy was found in 63 (17%) patients, with significantly more aneuploid tumors found among patients of older (>60 years) age. Out of the 399 patients, 8 had recurrence of the disease. Three of the eight patients died from the disease. Five patients with recurrence are alive, three of these patients with no signs of disease after additional treatment. This complete long-term follow-up of a large population-based cohort of BOT patients shows that there is a good overall survival in this patient group.

  16. Frequency of papillary tubal hyperplasia (PTH), salpingoliths and transition from adenoma to borderline ovarian tumors (BOT): A systematic analysis of 74 BOT with different histologic types.

    PubMed

    Horn, Lars-Christian; Angermann, Karolin; Hentschel, Bettina; Einenkel, Jens; Höhn, Anne Kathrin

    2017-02-06

    Borderline ovarian tumors (BOT) arise from cystadenomas and represent a transition step within the development of low-grade ovarian carcinomas (Type I tumors). That pathway mirrors the adenoma-to-carcinoma sequence known for colorectal cancer. It has been suggested that papillary tubal hyperplasia (PTH) and salpingoliths may be associated with the development of BOT. To evaluate the frequency of the presence of benign cystadenoma and its transition to BOT in a given patient as well as the presence of PTH and salpingoliths we re-valuated in 74 consecutive cases of BOT with different histologic types. The majority of cases represented serous-BOT (60.8%), followed by mucinous BOT (25.7%), other histologic types were rare. 86.5% showed an adenoma-BOT sequence, which was seen in all mucinous BOT but was missed in 15.6% of serous BOT. Two cases had salpingoliths without associated PTH. PTH was seen in four out of the 74 (5.4%) BOT and occurred only in cases with serous histology. The vast majority of BOT represent a transition from benign cystadenoma to BOT in cases with mucinous and serous histology. Salpingoliths are rarely seen in association with BOT and occurred exclusively in BOT with serous histology. PTH may represent a distinct lesion but is rarely seen in association with BOT, especially in those with non-serous histology. Further studies are needed to evaluate the frequency and pathogenetic association of PTH with BOT.

  17. [Dysplastic melanocytic nevus].

    PubMed

    Bierhoff, E

    2015-02-01

    Dysplastic nevus is still a controversial entity both clinically and histologically. The occurrence of dysplastic nevus especially in the context of dysplastic nevus cell syndrome is associated with an increased risk for melanoma. The following minimal histological criteria should be fulfilled: nests of melanocytes varying in size and shape, bridging and confluent, proliferation of single melanocytes basal and suprabasal, cytoplasmic and nuclear atypia of melanocytes and subepidermal fibroplasia. The biological behavior (common nevus variant or precursor of melanoma?) is difficult to evaluate by presently available methods. The further development of new molecular biology techniques may allow a better prognosis of dysplastic nevi in an objective and reproducible manner. Against this background complete excision followed by clinical surveillance has to be recommended for the routine practice.

  18. Melanocytes: the new Black.

    PubMed

    Goding, Colin R

    2007-01-01

    Melanocytes, pigment-producing cells residing primarily in the hair follicle, epidermis and eye, are responsible for skin hair and eye pigmentation. Pigmentation is achieved by the highly regulated manufacture of the pigment melanin in specialised organelles, melanosomes that are transported along dendritic processes before being transferred to growing hair, or keratinocytes where melanin protects from UV-induced DNA damage. Because loss of melanocytes gives a clear pigmentation phenotype yet is non-lethal, over 130 genes implicated in the development or function of this cell type have been identified to date, and in humans the loss of melanocytes or their ability to produce pigment, or transport or transfer melanosomes is associated with several diseases such as vitiligo, albinism and Hermansky-Pudlak syndrome. Importantly, the effective combination of genetics, cell and molecular biology possible with this cell type is attracting an increasing number of researchers focussed on understanding how cells coordinate survival, proliferation, differentiation and stem cell maintenance.

  19. Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) – a study of the TOC Consortium

    PubMed Central

    2014-01-01

    Background Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. Objective The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Methods Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. Results There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Conclusions Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants. PMID:24872845

  20. Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) - a study of the TOC Consortium.

    PubMed

    Braicu, Elena Ioana; Van Gorp, Toon; Nassir, Mani; Richter, Rolf; Chekerov, Radoslav; Gasimli, Khayal; Timmerman, Dirk; Vergote, Ignace; Sehouli, Jalid

    2014-01-01

    Borderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants. The aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants. Retrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease. There were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples. Both HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

  1. [Melanocyte stem cells in adults].

    PubMed

    Aubin-Houzelstein, Geneviève; Djian-Zaouche, Johanna; Panthier, Jean-Jacques

    2008-01-01

    Melanocyte stem cells have been recently localized in mice, in the outer root sheath of the lower permanent portion of the hair follicle. Specific depletion of melanocyte stem cell population is responsible for natural hair greying in aging mice and humans. Melanocyte stem cells also seem to drive the growth of malignant melanomas. A few mutations, either spontaneous or genetically engineered, accelerate the natural process of hair greying with age. These mutations allowed the identification of genes and signalling pathways controlling emergence, maintenance and/or differentiation of melanocyte stem cells. This review summarizes recent studies on the melanocyte stem cells and defines a few major unanswered questions in the field.

  2. Skin melanocytes: biology and development

    PubMed Central

    Wachulska, Małgorzata; Stasiewicz, Aneta; Tymińska, Agata

    2013-01-01

    In the human skin, melanocytes are present in the epidermis and hair follicles. The basic features of these cells are the ability to melanin production and the origin from neural crest cells. This last element is important because there are other cells able to produce melanin but of different embryonic origin (pigmented epithelium of retina, some neurons, adipocytes). The life cycle of melanocyte consists of several steps including differentiation of melanocyte lineage/s from neural crest, migration and proliferation of melanoblasts, differentiation of melanoblasts into melanocytes, proliferation and maturation of melanocytes at the target places (activity of melanogenic enzymes, melanosome formation and transport to keratinocytes) and eventual cell death (hair melanocytes). Melanocytes of the epidermis and hair are cells sharing some common features but in general they form biologically different populations living in unique niches of the skin. PMID:24278043

  3. Inverse expression of cystein-rich 61 (Cyr61/CCN1) and connective tissue growth factor (CTGF/CCN2) in borderline tumors and carcinomas of the ovary.

    PubMed

    Bartel, Frank; Balschun, Katharina; Gradhand, Elise; Strauss, Hans G; Dittmer, Jürgen; Hauptmann, Steffen

    2012-09-01

    Members of the CCN [cystein-rich 61 (Cyr61)/connective tissue growth factor (CTGF)/nephroblastoma (NOV)] protein family are involved in the regulation of cellular proliferation, apoptosis, and migration and are also assumed to play a role in carcinogenesis. Therefore, we performed a retrospective study to investigate the immunohistochemical expression of both Cyr61 and CTGF in 92 borderline tumors (BOTs) and 107 invasive carcinomas of the ovary (IOCs). To determine their diagnostic and prognostic value, we correlated protein expression with clinicopathologic factors including overall and disease-free survival. Cyr61 and CTGF were found to be inversely expressed in both BOTs and IOCs, with a stronger expression of Cyr61 in IOCs. Moreover, Cyr61 was found to be preferentially expressed in high-grade serous carcinomas, whereas CTGF was found more frequently in low-grade serous carcinomas. Weak Cyr61 levels correlated with both low estrogen receptor and p53 expression (P=0.038, P=0.04, respectively). However, no association was observed between CTGF, estrogen receptor, and p53 expression levels in IOCs. Regarding prognosis, Cyr61 was found to be of no value, but the loss of CTGF was found to be associated with a poor prognosis in multivariate analysis of overall (relative risk 2.8; P=0.050) and disease-free (relative risk 2.3; P=0.031) survival. Cyr61 and CTGF are inversely expressed in BOTs and IOCs, and loss of CTGF independently indicates poor prognosis in IOCs.

  4. State of the art, nomenclature, and points of consensus and controversy concerning benign melanocytic lesions: outcome of an international workshop.

    PubMed

    Barnhill, Raymond L; Cerroni, Lorenzo; Cook, Martin; Elder, David E; Kerl, Helmut; LeBoit, Philip E; McCarthy, Stanley W; Mihm, Martin C; Mooi, Wolter J; Piepkorn, Michael W; Prieto, Victor G; Scolyer, Richard A

    2010-03-01

    The following communication summarizes the proceedings of a one-day International Workshop focusing on the histology of benign melanocytic nevi. Areas of controversy identified in 6 focus sessions were the nomenclature and relationships among common nevi including nevi with halo reactions, traumatized nevi, "dysplastic" nevi, and nevi from particular anatomic sites; developmental biology and frequency of malignant transformation associated with congenital nevi; the characterization and biologic nature of atypical spitzoid neoplasms; the basic definition of particular melanocytic cellular phenotypes, and the nomenclature and biologic nature of many candidate blue nevi, combined nevi, and other controversial lesions such as deep penetrating nevus and pigmented epithelioid melanocytoma. Concentrated data collection and follow-up, molecular characterization, and future consensus Workshops may facilitate the resolution of some of these problems. The Group recommended the description of ambiguous or "borderline" lesions as tumors with indeterminate or uncertain biologic/malignant potential. The participants also advised that such lesions at a minimum should be managed by complete excision with clear surgical margins.

  5. MITF accurately highlights epidermal melanocytes in atypical intraepidermal melanocytic proliferations.

    PubMed

    Nybakken, Grant E; Sargen, Michael; Abraham, Ronnie; Zhang, Paul J; Ming, Michael; Xu, Xiaowei

    2013-02-01

    Atypical intraepidermal melanocytic proliferations (AIMP) have random cytologic atypia and other histologic features that are concerning for malignancy and often require immunohistochemistry to differentiate from melanoma in situ. Immunostaining with S100, Melan-A, and microphthalmia-associated transcription factor (MITF) was performed for 49 morphologically well-characterized AIMP lesions. The percentage of cells in the basal layer of the epidermis that were identified as melanocytes by immunohistochemistry was compared with the percentage observed by morphology on hematoxylin and eosin staining, which is the gold standard stain for identifying cytologic atypia within an AIMP. Melan-A estimated the highest percentage of melanocytes and S100 the fewest in 47 of the 49 lesions examined. The estimated percentage of melanocytes was 23.3% (95% confidence interval: 18.6-28.1; P < 0.001) higher for Melan-A compared with hematoxylin and eosin staining. Melanocyte estimates were similar for hematoxylin and eosin and MITF (P = 0.15) although S100 estimated 21.8% (95% confidence interval: -27.2 to -16.4; P < 0.001) fewer melanocytes than hematoxylin and eosin. Melan-A staining produces higher estimates of epidermal melanocytes than S100 and MITF, which may increase the likelihood of diagnosing melanoma in situ. In contrast, melanoma in situ may be underdiagnosed with the use of S100, which results in lower estimates of melanocytes than the other 2 immunostains. Therefore, the best immunohistochemical marker for epidermal melanocytes is MITF.

  6. A new transgenic mouse line for tetracycline inducible transgene expression in mature melanocytes and the melanocyte stem cells using the Dopachrome tautomerase promoter.

    PubMed

    Woods, Susan L; Bishop, J Michael

    2011-04-01

    We have generated a novel transgenic mouse to direct inducible and reversible transgene expression in the melanocytic compartment. The Dopachrome tautomerase (Dct) control sequences we used are active early in the development of melanocytes and so this system was designed to enable the manipulation of transgene expression during development in utero and in the melanocyte stem cells as well as mature melanocytes. We observed inducible lacZ and GFP reporter transgene activity specifically in melanocytes and melanocyte stem cells in mouse skin. This mouse model will be a useful tool for the pigment cell community to investigate the contribution of candidate genes to normal melanocyte and/or melanoma development in vivo. Deregulated expression of the proto-oncogene MYC has been observed in melanoma, however whether MYC is involved in tumorigenesis in pigment cells has yet to be directly investigated in vivo. We have used our system to over-express MYC in the melanocytic compartment and show for the first time that increased MYC expression can indeed promote melanocytic tumor formation.

  7. Pirin Inhibits Cellular Senescence in Melanocytic Cells

    PubMed Central

    Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

    2011-01-01

    Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

  8. Melanocytes and Their Diseases

    PubMed Central

    Yamaguchi, Yuji; Hearing, Vincent J.

    2014-01-01

    Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues. Melanocytes, which are derived from the neural crest, are unique in that they produce eu-/pheo-melanin pigments in unique membrane-bound organelles termed melanosomes, which can be divided into four stages depending on their degree of maturation. Pigmentation production is determined by three distinct elements: enzymes involved in melanin synthesis, proteins required for melanosome structure, and proteins required for their trafficking and distribution. Many genes are involved in regulating pigmentation at various levels, and mutations in many of them cause pigmentary disorders, which can be classified into three types: hyperpigmentation (including melasma), hypopigmentation (including oculocutaneous albinism [OCA]), and mixed hyper-/hypopigmentation (including dyschromatosis symmetrica hereditaria). We briefly review vitiligo as a representative of an acquired hypopigmentation disorder. PMID:24789876

  9. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

    PubMed

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

    2017-03-01

    Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

    PubMed

    Horn, Lars-Christian; Höhn, Anne K; Einenkel, Jens; Siebolts, Udo

    2014-11-01

    Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

  11. Congenital melanocytic nevus with features of hybrid schwannoma/perineurioma.

    PubMed

    Wang, Lei; Wang, Gang; Gao, Tianwen

    2013-05-01

    Neural differentiation by melanocytic nevi represents a well-recognized phenomenon, and melanocytic nevi with perineurial differentiation have been reported recently. We reported a case of a congenital melanocytic nevus with histopathologic features of hybrid schwannoma/perineurioma. The patient was a 36-year-old male who presented with a black tumor on his arm since birth. Histopathology showed a congenital melanocytic nevus in the superficial dermis, but more strikingly, in continuity with the melanocytic nevus, there was a well-circumscribed but unencapsulated nodule in the deep dermis. The nodule was composed of cellular and myxoid areas with storiform, laminated or whorled growth patterns. The cellular area was mainly composed of proliferation of plump spindle, oval or epithelioid cells. The myxoid area was mainly composed of proliferation of slender spindle cells with mucin deposition. Immunohistochemical stains showed that the cellular area was positive for S100 and CD34, weakly positive for EMA, negative for Glut-1 and collagen IV, the myxoid area was positive for S100, negative for CD34, strongly positive for EMA and focally positive for Glut-1 and collagen IV. Our results show that congenital melanocytic nevi may show neural differentiation with histopathologic features of hybrid schwannoma/perineurioma.

  12. IMP-3 expression in melanocytic lesions.

    PubMed

    Yu, Limin; Xu, Haodong; Wasco, Matthew J; Bourne, Patricia A; Ma, Linglei

    2010-03-01

    Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3 ), a member of the insulin-like growth factor mRNA-binding protein family, is expressed in several human malignancies, including melanomas. However, the expression of IMP-3 has not been explored in melanoma in situ, various histologic subtypes of invasive melanomas and atypical Spitz tumors. IMP-3 immunostain was performed in 157 melanocytic lesions. Nearly all benign (8/8), dysplastic (8/8) and Spitz nevi (8/9) were negative for IMP-3. Focal IMP-3 positivity was observed in 5/12 melanoma in situ and 4/15 superficial melanomas (Breslow depth 1 mm) and 25/52 metastatic melanomas demonstrated strong IMP-3 staining. IMP-3 expression differs significantly between non-desmoplastic melanomas (superficial and deep) and benign or dysplastic or Spitz nevi (p = 0.0427, respectively). Four of 23 desmoplastic melanomas expressed IMP-3 , which was significantly different from deep melanomas (p = 0.0109). IMP-3 stained 7 of 10 atypical Spitz tumors. The difference between atypical Spitz tumors and Spitz nevi was statistically significant (p = 0.0256). A malignant circumstance, such as non-desmoplastic melanoma or atypical Spitz tumor, can be inferred when IMP-3 is expressed, suggesting potential diagnostic value of IMP-3 in melanocytic lesions.

  13. VITILIGO AND THE MELANOCYTE RESERVOIR

    PubMed Central

    Falabella, Rafael

    2009-01-01

    Repigmentation of vitiligo depends on available melanocytes from three possible sources: from the hair follicle unit which is the main provider of pigment cells, from the border of vitiligo lesions, and from unaffected melanocytes within depigmented areas; pigment cells at these locations originate a perifollicular, border spreading and a diffuse repigmentation pattern. In order for repigmentation to take place under stimulation with diverse therapies, melanocytes should be present in appropriate numbers. Melanocyte tissue stem cells located in the niche at the bulge region of the hair follicle are the most important sources for providing immature pigment cells that undergo terminal differentiation and originate repigmentation, but cytokines, UVR and other molecules acting in melanogenesis with adequate regulation mechanisms contribute to successful recovery in vitiligo. The presence of keratinocyte stem cells in the interfollicular epidermis raises the question on the possibility of melanocyte stem cells in a similar location and the development of future strategies for therapeutic purposes. PMID:20101329

  14. The biology of melanocyte and melanocyte stem cell.

    PubMed

    Li, Ang

    2014-04-01

    The melanocyte stem cells of the hair follicle provide an attractive system for the study of the stem cells. Successful regeneration of a functional organ relies on the organized and timely orchestration of molecular events among distinct stem/progenitor cell populations. The stem cells are regulated by communication with their specialized microenvironment known as the niche. Despite remarkable progress in understanding stem cell-intrinsic behavior, the molecular nature of the extrinsic factors provided to the stem cells by the niche microenvironment remains poorly understood. In this regard, the bulge niche of the mammalian hair follicle offers an excellent model for study. It holds two resident populations of SCs: epidermal stem cells and melanocyte stem cells. While their behavior is tightly coordinated, very little of the crosstalk involved is known. This review summarized the recent development in trying to understand the regulation of melanocyte and melanocyte stem cells. A better understanding of the normal regulation and behaviors of the melanocytes and the melanocyte stem cells will help to improve the clinical applications in regenerative medicine, cancer therapy, and aging.

  15. Amelanotic Melanoma in the Vicinity of Acquired Melanocytic Nevi and not Arising from Agminated Melanocytic Nevi: Masquerading as Pyogenic Granuloma

    PubMed Central

    Rao, Angoori Gnaneshwar; Babu, V Ashok; Koppada, Divya; Haritha, M; Chandana, P; Swapna; Anoosha

    2016-01-01

    Amelanotic melanoma (AMM) presenting as pyogenic granuloma and occurring in the vicinity of acquired melanocytic nevi is rare. Herein, we report such a manifestation in a 68-year-old male who presented with the painful red nodule and multiple pigmented patches involving the left great toe. Histopathological examination of skin biopsy taken from the nodule with an immunohistochemical study using HMB45 and S-100 confirmed the diagnosis of AMM. Biopsy from the pigmented patch near the nodule showed features of melanocytic nevus. Investigative work up revealed metastatic deposits in the left inguinal lymph node with no evidence of systemic involvement, placing him in malignant melanoma Stage IIIC of American Joint Committee on Cancer (AJCC) tumor node metastasis system. The development of AMM in the vicinity of acquired melanocytic nevi and manifesting as granuloma pyogenicum is unique in this case. PMID:26955141

  16. Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin.

    PubMed

    Bonchak, Jonathan G; Eby, Jonathan M; Willenborg, Kristin A; Chrobak, David; Henning, Steven W; Krzywiec, Anna; Johnson, Steven L; Le Poole, I Caroline

    2014-12-01

    Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations.

  17. Signet ring cell melanocytic nevus: report of a case over trichilemmal cyst and review of the literature.

    PubMed

    Sabater Marco, Vicente; Escutia Muñoz, Begoña; Morera Faet, Arturo; Botella Estrada, Rafael

    2012-02-01

    Different melanocytic nevi have been reported as being associated with dermal cysts. Signet ring cell melanocytic nevus is a rare variant of melanocytic nevus characterized by cells with signet ring morphology within a common melanocytic nevus. This article describes an exceptional case of melanocytic nevus composed exclusively of signet ring cells over a trichilemmal cyst. Histologically, above the cyst, there was a small, symmetrical and sharply demarcated lesion showing a compound proliferation of small, round, monomorphous cells with signet ring morphology. Immunohistochemically, signet ring cells were negative for cytokeratin AE1/3, leukocyte common antigen, HMB-45, and CD34. Occasionally, isolated signet ring cells were positive for S-100 and melan A. Melanocytic nevus composed of signet ring cells should raise the differential diagnosis with other cutaneous tumors exhibiting signet ring cells. Previous cases of this entity reported in the literature are also reviewed.

  18. Borderline Space for Voice

    ERIC Educational Resources Information Center

    Batchelor, Denise

    2012-01-01

    Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…

  19. Borderline Space for Voice

    ERIC Educational Resources Information Center

    Batchelor, Denise

    2012-01-01

    Being on the borderline as a student in higher education is not always negative, to do with marginalisation, exclusion and having a voice that is vulnerable. Paradoxically, being on the edge also has positive connections with integration, inclusion and having a voice that is strong. Alternative understandings of the concept of borderline space can…

  20. Pathology of eyelid tumors

    PubMed Central

    Pe’er, Jacob

    2016-01-01

    The eyelids are composed of four layers: skin and subcutaneous tissue including its adnexa, striated muscle, tarsus with the meibomian glands, and the palpebral conjunctiva. Benign and malignant tumors can arise from each of the eyelid layers. Most eyelid tumors are of cutaneous origin, mostly epidermal, which can be divided into epithelial and melanocytic tumors. Benign epithelial lesions, cystic lesions, and benign melanocytic lesions are very common. The most common malignant eyelid tumors are basal cell carcinoma in Caucasians and sebaceous gland carcinoma in Asians. Adnexal and stromal tumors are less frequent. The present review describes the more important eyelid tumors according to the following groups: Benign and malignant epithelial tumors, benign and malignant melanocytic tumors, benign and malignant adnexal tumors, stromal eyelid tumors, lymphoproliferative and metastatic tumors, other rare eyelid tumors, and inflammatory and infections lesions that simulate neoplasms. PMID:27146927

  1. Melanocytes, melanocyte stem cells, and melanoma stem cells.

    PubMed

    Lang, Deborah; Mascarenhas, Joseph B; Shea, Christopher R

    2013-01-01

    Melanocyte stem cells differ greatly from melanoma stem cells; the former provide pigmented cells during normal tissue homeostasis and repair, and the latter play an active role in a lethal form of cancer. These 2 cell types share several features and can be studied by similar methods. Aspects held in common by both melanocyte stem cells and melanoma stem cells include their expression of shared biochemical markers, a system of similar molecular signals necessary for their maintenance, and a requirement for an ideal niche microenvironment for providing these factors. This review provides a perspective of both these cell types and discusses potential models of stem cell growth and propagation. Recent findings provide a strong foundation for the development of new therapeutics directed at isolating and manipulating melanocyte stem cells for tissue engineering or at targeting and eradicating melanoma specifically, while sparing nontumor cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Genetics Home Reference: giant congenital melanocytic nevus

    MedlinePlus

    ... noncancerous skin patch (nevus) that is composed of pigment-producing cells called melanocytes . It is present from ... called neurocutaneous melanosis, which is the presence of pigment-producing skin cells (melanocytes) in the tissue that ...

  3. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity.

    PubMed

    Kelly, J M; Moir, A J G; Carlson, K; Yang, Y; MacNeil, S; Haycock, J W

    2006-02-01

    alpha-MSH is an anti-inflammatory peptide which signals by binding to the melanocortin-1 receptor (MC1R) and elevating cyclic AMP in several different cells and tissues. The carboxyl terminal peptides of alpha-MSH (KPV/GKPV) are the smallest minimal sequences that prevent inflammation, but it is not known if they operate via MC1R or cyclic AMP. The aim of this study was to examine the intracellular signaling potential of the GKPV peptide sequence when immobilized to polystyrene beads via a polyethylene glycol moiety. Beads containing an immobilized GKPV peptide were investigated for their ability to inhibit proinflammatory tumor necrosis factor-alpha (TNF-alpha) stimulated activation of NF-kappaB in HBL cells stably transfected with an NF-kappaB-luciferase reporter construct. Peptide functionalized beads were compared with the ability of soluble peptide alone (alpha-MSH or GKPV) or non-functionalized beads to inhibit TNF-alpha stimulated activation of NF-kappaB. GKPV peptide functionalized beads significantly inhibited NF-kappaB-luciferase activity in comparison to beads containing no peptide moiety in one of two growths conditions investigated. Soluble alpha-MSH and GKPV peptides were also confirmed to inhibit NF-kappaB-luciferase. The present study suggests that the carboxyl terminal MSH peptide acts via a cell receptor-based mechanism and furthermore may support the potential use of such immobilized ligands for anti-inflammatory therapeutic use.

  4. Borderline personality disorder

    MedlinePlus

    American Psychiatric Association. Borderline personality disorder. Diagnostic and Statistical Manual of Mental Disorders . 5th ed. Arlington, VA: American Psychiatric Publishing. 2013:663-666. Blais MA, Smallwood P, Groves ...

  5. Treatment of Borderline Adolescents.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    1983-01-01

    Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)

  6. Treatment of Borderline Adolescents.

    ERIC Educational Resources Information Center

    Green, Maurice R.

    1983-01-01

    Describes characteristics of borderline adolescents and reviews diagnostic issues. Uses two case studies to illustrate general treatment strategies that could be useful to clinicians in mental health programs and family courts. (JAC)

  7. Cutaneous photobiology. The melanocyte vs. the sun: who will win the final round?

    PubMed

    Kadekaro, Ana Luisa; Kavanagh, Renny J; Wakamatsu, Kazumasa; Ito, Shosuke; Pipitone, Michelle A; Abdel-Malek, Zalfa A

    2003-10-01

    Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long-term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV-induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self-renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.

  8. Isolation and cultivation of canine uveal melanocytes.

    PubMed

    Dawson-Baglien, Ethan M; Winkler, Paige A; Bruewer, Ashlee R; Petersen-Jones, Simon M; Bartoe, Joshua T

    2015-07-01

    To establish a method for isolation and culture of canine uveal melanocytes. Uveal explants from five mixed-breed dogs. Donor globes were dissected, and the anterior uvea removed. The uveal explants were placed in trypsin solution for enzymatic digestion. Extracted cells were cultured in modified F12 media. Immunocytochemistry was performed to confirm the identity of the extracted cells. Melanocytes were successfully isolated from uveal explants. Contaminating cell types were not observed. Repeated passaging of the melanocytes resulted in a gradual decrease in intracellular pigment. Melanocyte cell lines could be cryopreserved, thawed, and cultures successfully reestablished. This extraction technique allows for generation of large populations of canine uveal melanocytes in a relatively short period of time. This technique could be a useful tool for future studies investigating both normal cellular characteristics and alterations found in melanocytes from dogs with ocular melanocytic disorders. © 2014 American College of Veterinary Ophthalmologists.

  9. Neuroendocrine activity of the melanocyte

    PubMed Central

    Slominski, Andrzej

    2009-01-01

    More than 15 years ago, we have proposed that melanocytes are sensory and regulatory cells with computing capability, which transform external and/or internal signals/energy into organized regulatory network(s) for the maintenance of the cutaneous homeostasis. This concept is substantiated by accumulating evidence that melanocytes produce classical stress neurotransmitters, neuropeptides and hormones, express corresponding receptors and these processes are modified and/or regulated by ultraviolet radiation, biological factors or stress. Examples of the above are catecholamines, serotonin, N-acetyl-serotonin, melatonin, proopiomelanocortin-derived adrenocorticotropic hormone, β-endorphin or melanocyte-stimulating hormone peptides, corticotropin releasing factor, related urocortins and corticosteroids including cortisol and corticosterone as well as their precursors. Furthermore, their production is not random, but hierarchical and follows the structures of classical neuroendocrine organizations such as hypothalamic-pituitary-adrenal axis, serotoninergic, melatoninergic and catecholaminergic systems. An example of an intrinsic but overlooked neuroendocrine activity is production and secretion of melanogenesis intermediates including L-DOPA or its derivatives that could enter circulation and act on distant sites. Such capabilities have defined melanocytes as neuroendocrine cells that not only coordinate cutaneous but also can affect a global homeostasis. PMID:19558501

  10. Pigment-Synthesizing Melanocytic Neoplasm With Protein Kinase C Alpha (PRKCA) Fusion

    PubMed Central

    Bahrami, Armita; Lee, Seungjae; Wu, Gang; Kerstetter, Justin; Rahvar, Maral; Li, Xinmin; Easton, John; Zhang, Jinghui; Barnhill, Raymond L.

    2016-01-01

    IMPORTANCE Melanocytic neoplasms with prominent pigment synthesis mimicking equine melanoma represent a rare variant of biologically indeterminate or low-grade malignant melanocytic tumors in which the molecular profile and exact histologic classification are not established. Tumors with these characteristics rarely occur as congenital lesions. We performed genomic analysis of a congenital pigment synthesizing melanocytic neoplasm with indeterminate biological potential. OBSERVATIONS The patient was a 5-month-old girl presenting with a 6-cm protuberant scalp mass, which had doubled in size since birth. Histologic examination showed heavily pigmented intradermal proliferation of large, epithelioid melanocytes with mild cytologic atypia, low mitotic activity, focal necrosis, and ulceration. RNA sequencing identified a novel ATPase, Ca2+ transporting, plasma membrane 4 (ATP2B4)–protein kinase C-alpha (PRKCA) fusion transcript. The fusion resulted in an in-frame linkage of the PRKCA catalytic domain with the N-terminal of ATP2B4 and high expression of the PRKCA kinase domain. Break-apart fluorescence in situ hybridization showed PRKCA rearrangement, and reverse transcriptase–polymerase chain reaction confirmed the presence of the fusion transcript. The patient was alive and well, with no evidence of recurrence, at the 1-year follow-up. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of PRKCA fusions in melanocytic neoplasms. Future studies need to determine the frequency of PRKCA fusions in pigment-synthesizing melanocytic neoplasms. PMID:26676968

  11. [Concerning the borderline (author's transl)].

    PubMed

    Modestin, J

    1980-03-01

    A general survey of the borderline literature is presented. The diagnostic label "borderline" has predominantly been used in North America; nevertheless, many roots of this conception originate in the classical European psychiatry and psychoanalysis. The various diagnostic (mainly descriptive) criteria and characteristics of the borderline are discussed, as well as the most important psychoanalytic hypotheses and conceptions (such as splitting, projective identification, identity diffusion). The therapeutic principles are mentioned as well. The analysis of the surveyed literature reveals on the one hand, that a well defined borderline exists neither as a generally acknowledged clinical entity nor as a circumscribed psychopathological syndrome. On the other hand, there are three various borderline concepts clearly discernible: 1) borderline conceptualized as a form of schizophrenia, 2) borderline conceptualized as synonymous with the general category of psychopathy (personality disorder) and 3) borderline conceptualized as a special form of psychopathy.

  12. Melanocytes Affect Nodal Expression and Signaling in Melanoma Cells: A Lesson from Pediatric Large Congenital Melanocytic Nevi.

    PubMed

    Margaryan, Naira V; Gilgur, Alina; Seftor, Elisabeth A; Purnell, Chad; Arva, Nicoleta C; Gosain, Arun K; Hendrix, Mary J C; Strizzi, Luigi

    2016-03-22

    Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro

  13. The melanocyte lineage in development and disease

    PubMed Central

    Mort, Richard L.; Jackson, Ian J.; Patton, E. Elizabeth

    2015-01-01

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. PMID:25670789

  14. Sox proteins in melanocyte development and melanoma

    PubMed Central

    Harris, Melissa L.; Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.

    2010-01-01

    Over ten years has passed since the first Sox gene was implicated in melanocyte development. Since then, we have discovered that SOX5, SOX9, SOX10 and SOX18 all participate as transcription factors that affect key melanocytic genes in both regulatory and modulatory fashions. Both SOX9 and SOX10 play major roles in the establishment and normal function of the melanocyte; SOX10 has been shown to heavily influence melanocyte development and SOX9 has been implicated in melanogenesis in the adult. Despite these advances, the precise cellular and molecular details of how these SOX proteins are regulated and interact during all stages of the melanocyte life cycle remain unknown. Improper regulation of SOX9 or SOX10 is also associated with cancerous transformation, and thus understanding the normal function of SOX proteins in the melanocyte will be key to revealing how these proteins contribute to melanoma. PMID:20444197

  15. The melanocyte lineage in development and disease.

    PubMed

    Mort, Richard L; Jackson, Ian J; Patton, E Elizabeth

    2015-02-15

    Melanocyte development provides an excellent model for studying more complex developmental processes. Melanocytes have an apparently simple aetiology, differentiating from the neural crest and migrating through the developing embryo to specific locations within the skin and hair follicles, and to other sites in the body. The study of pigmentation mutations in the mouse provided the initial key to identifying the genes and proteins involved in melanocyte development. In addition, work on chicken has provided important embryological and molecular insights, whereas studies in zebrafish have allowed live imaging as well as genetic and transgenic approaches. This cross-species approach is powerful and, as we review here, has resulted in a detailed understanding of melanocyte development and differentiation, melanocyte stem cells and the role of the melanocyte lineage in diseases such as melanoma. © 2015. Published by The Company of Biologists Ltd.

  16. Borderline Personality Disorder

    MedlinePlus

    ... to environmental factors — such as a history of child abuse or neglect — borderline personality disorder may be linked ... Do you use alcohol or recreational drugs or abuse prescription drugs? How ... neglected as a child? Have any of your close relatives or caregivers ...

  17. [Borderline personality disorder].

    PubMed

    Sipos, V; Schweiger, U

    2006-02-23

    Characteristics of a borderline personality disorder include emotional instability and a self-threatening lack of impulsive control. As a result, interpersonal relationships are rendered difficult. The central elements of treatment are psychoeducation, self-management, improved stress tolerance and awareness, emotion managment and training in social competence.

  18. Melanocyte expression of Survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice

    PubMed Central

    Thomas, Joshua; Liu, Tong; Cotter, Murray A.; Florell, Scott R.; Robinette, Kyle; Hanks, Adrianne N.; Grossman, Douglas

    2008-01-01

    We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma, but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared to melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of DMBA did not reveal significant differences in lesion onset (median 10 wks) or density (4 lesions/mouse after 15 wks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 wks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin−/HGF+ mice. Onset of melanocytic tumors was earlier (median 18 vs. 24 wks, p = .01, log-rank test) and overall tumor density was greater (7.7 vs. 5.2 tumors/mouse, p = .04) in Survivin+/HGF+ compared to Survivin−/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice demonstrated a greater tendency for lymph node (35% vs. 0%, p = .04) and lung (53% vs. 22%) metastasis, and lower rates of spontaneous apoptosis, than those in Survivin−/HGF+ mice. These studies demonstrate a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo. PMID:17545596

  19. Repression of genes involved in melanocyte differentiation in uveal melanoma

    PubMed Central

    Bergeron, Marjorie-Allison; Champagne, Sophie; Gaudreault, Manon; Deschambeault, Alexandre

    2012-01-01

    Purpose Uveal melanoma (UM) has been the subject of intense interest due to its distinctive metastatic pattern, which involves hematogenous dissemination of cancerous cells toward the liver in 50% of patients. To search for new UM prognostic markers, the Suppressive Subtractive Hybridization (SSH) technique was used to isolate genes that are differentially expressed between UM primary tumors and normal uveal melanocytes (UVM). Methods A subtracted cDNA library was prepared using cDNA from uncultured UM primary tumors and UVM. The expression level of selected genes was further validated by cDNA microarray, semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence analyses. Results One hundred-fifteen genes were identified using the SSH technique. Microarray analyses comparing the gene expression profiles of UM primary tumors to UVM validated a significant differential expression for 48% of these genes. The expression pattern of selected genes was then analyzed by semi-quantitative RT–PCR and was found to be consistent with the SSH and cDNA microarray findings. A down-regulation of genes associated with melanocyte differentiation was confirmed in UM primary tumors. Presence of undifferentiated cells in the UM was demonstrated by the expression of stem cell markers ATP-binding cassette sub-family G member 2 (ABCG2) and octamer-binding protein 4 (OCT4). Conclusions We demonstrated that the SSH technique is efficient to detect differentially expressed genes between UM and UVM. The genes identified in this study represent valuable candidates for further functional analysis in UM and should be informative in studying the biology of this tumor. In addition, deregulation of the melanocyte differentiation pathway revealed the presence of UM cells exhibiting a stem cell-like phenotype. PMID:22815634

  20. Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.

    PubMed

    Tseng, Diane; Kim, Julie; Warrick, Andrea; Nelson, Dylan; Pukay, Marina; Beadling, Carol; Heinrich, Michael; Selim, Maria Angelica; Corless, Christopher L; Nelson, Kelly

    2014-08-01

    The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). Our study is limited by the small sample size of this rare subset of melanomas. KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  1. Melanocytic Hyperplasia in the Epidermis Overlying Trichoblastomas in 100 Randomly Selected Cases.

    PubMed

    Al Omoush, Tahseen M M; Michal, Michael; Konstantinova, Anastasia M; Michal, Michal; Kutzner, Heinz; Kazakov, Dmitry V

    2016-04-01

    One hundred cases of trichoblastomas (large nodular, small nodular, cribriform, lymphadenoma, and columnar) were randomly selected and studied for the presence of melanocytic hyperplasia in the epidermis overlying the tumors, which was defined as foci of increased melanocytes in the basal layer of the epidermis (more than 1 per 4 basal keratinocytes). Focal melanocytic hyperplasia was detected in a total of 22 cases of trichoblastoma (22%), and this phenomenon was most frequently seen in columnar trichoblastoma (7 cases), followed by large nodular trichoblastoma (5 cases). The mechanism of epidermal melanocytic hyperplasia overlying trichoblastoma is unclear. Ultraviolet may be a contributing factor, as focal melanocytic hyperplasia was also detected in one-third of cases in the epidermis overlying uninvolved skin, usually associated with solar elastosis. This is further corroborated by the occurrence of the lesions predominantly on the face. Melanocytic hyperplasia overlying trichoblastoma appears to have no impact on the clinical appearance of the lesion and is recognized only microscopically. In an adequate biopsy specimen containing at least part of trichoblastoma, it should not cause any diagnostic problems.

  2. Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin

    PubMed Central

    Bonchak, Jonathan G.; Eby, Jonathan M.; Willenborg, Kristin A.; Chrobak, David; Henning, Steven W.; Krzywiec, Anna; Johnson, Steven L.; Le Poole, I. Caroline

    2014-01-01

    Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations. PMID:25132642

  3. Gene expression profiling of cultured human NF1 heterozygous (NF1+/-) melanocytes reveals downregulation of a transcriptional cis-regulatory network mediating activation of the melanocyte-specific dopachrome tautomerase (DCT) gene.

    PubMed

    Boucneau, Joachim; De Schepper, Sofie; Vuylsteke, Marnik; Van Hummelen, Paul; Naeyaert, Jean-Marie; Lambert, Jo

    2005-08-01

    One of the major primary features of the neurocutaneous genetic disorder Neurofibromatosis type 1 are the hyperpigmentary café-au-lait macules where disregulation of melanocyte biology is supposed to play a key etiopathogenic role. To gain better insight into the possible role of the tumor suppressor gene NF1, a transcriptomic microarray analysis was performed on human NF1 heterozygous (NF1+/-) melanocytes of a Neurofibromatosis type 1 patient and NF1 wild type (NF1+/+) melanocytes of a healthy control patient, both cultured from normally pigmented skin and hyperpigmented lesional café-au-lait skin. From the magnitude of gene effects, we found that gene expression was affected most strongly by genotype and less so by lesional type. A total of 137 genes had a significant twofold or more up- (72) or downregulated (65) expression in NF1+/- melanocytes compared with NF1+/+ melanocytes. Melanocytes cultured from hyperpigmented café-au-lait skin showed 37 upregulated genes whereas only 14 were downregulated compared with normal skin melanocytes. In addition, significant genotype xlesional type interactions were observed for 465 genes. Differentially expressed genes were mainly involved in regulating cell proliferation and cell adhesion. A high number of transcription factor genes, among which a specific subset important in melanocyte lineage development, were downregulated in the cis-regulatory network governing the activation of the melanocyte-specific dopachrome tautomerase (DCT) gene. Although the results presented have been obtained with a restricted number of patients (one NF1 patient and one control) and using cDNA microarrays that may limit their interpretation, the data nevertheless addresses for the first time the effect of a heterozygous NF1 gene on the expression of the human melanocyte transcriptome and has generated several interesting candidate genes helpful in elucidating the etiopathology of café-au-lait macules in NF1 patients.

  4. Ocular surface tumors

    PubMed Central

    Othman, Ihab Saad

    2009-01-01

    Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, mucoepidermoid, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Ocular surface tumors include a variety of neoplasms originating from squamous epithelium, melanocytic tumors and lymphocytic resident cells of the conjunctival stroma. In this review, we highlight clinical features of these lesions, important diagnostic and investigative tools and standard care of management. PMID:21234217

  5. Risk factors for growth and metastasis of small choroidal melanocytic lesions.

    PubMed Central

    Shields, C L; Shields, J A; Kiratli, H; De Potter, P; Cater, J R

    1995-01-01

    PURPOSE: To investigate the clinical features that predict growth and metastasis of an unselected group of small melanocytic choroidal tumors. METHODS: A retrospective review was performed on 1329 patients with small melanocytic choroidal tumors measuring 3 mm in thickness or less. Clinical parameters of the patient and tumor were extracted and analyzed for their relationship to eventual tumor growth and metastasis using a Cox proportional hazards regression model. RESULTS: Tumor growth was documented in 18% of patients. The factors predictive of tumor growth (multivariate analysis) included greater tumor thickness, posterior tumor margin touching optic disc, symptoms of flashes, floaters, and blurred vision, orange pigment on the tumor surface, and the presence of subretinal fluid. The relative risk (rr) was greatest for initial tumor thickness > 2.0 mm (rr 5.2) and posterior margin touching the optic disc (rr 2.6). After adjusting for significant tumor variables, the effect of interventional tumor treatment showed a decreasing risk for tumor growth as compared to continued observation without treatment. Of 1329 patients, 35 (3%) developed metastases. The factors predictive of metastases (multivariate analysis) included: posterior tumor margin touching the optic disc, documented growth, and greater tumor thickness. The relative risk for metastases was greatest for tumor thickness 1.1-3.0 mm (rr 8.8) and growth (rr 3.2). CONCLUSION: Of small choroidal melanocytic tumors measuring 3 mm or less in thickness at the time of initial examination, 18% demonstrate growth and 3% metastasize during the period of followup. Based on this analysis, the clinical features of these tumors can be used to estimate the risk for tumor growth and metastases and assist the clinician with patient management. PMID:8719682

  6. The effects of dickkopf 1 on gene expression and Wnt signaling by melanocytes: mechanisms underlying its suppression of melanocyte function and proliferation.

    PubMed

    Yamaguchi, Yuji; Passeron, Thierry; Watabe, Hidenori; Yasumoto, Ken-ichi; Rouzaud, Francois; Hoashi, Toshihiko; Hearing, Vincent J

    2007-05-01

    Dickkopf 1 (DKK1), which is expressed at high mRNA levels by fibroblasts in the dermis of human skin on the palms and soles, inhibits the function and proliferation of melanocytes in the epidermis of those areas via the suppression of beta-catenin and microphthalmia-associated transcription factor (MITF). In this study, we investigated the protein expression levels of DKK1 between palmoplantar and non-palmoplantar areas and the effects of DKK1 on melanocyte gene expression profiles and on Wnt signaling pathways using DNA microarray technology, reverse transcriptase-PCR, Western blot, 3-dimensional reconstructed skin, immunocytochemistry, and immunohistochemistry. DKK1-responsive genes included those encoding proteins involved in the regulation of melanocyte development, growth, differentiation, and apoptosis (including Kremen 1, G-coupled receptor 51, lipoprotein receptor-related protein 6, low-density lipoprotein receptor, tumor necrosis factor receptor super-family 10, growth arrest and DNA-damage-inducible gene 45beta, and MITF). Of special interest was the rapid decrease in expression of MITF in melanocytes treated with DKK1, which is concurrent with the decreased activities of beta-catenin and of glucose-synthase kinase 3beta via phosphorylation at Ser9 and with the upregulated expression of protein kinase C alpha. These results further clarify the mechanism by which DKK1 suppresses melanocyte density and differentiation, and help explain why DKK1-rich palmoplantar epidermis is paler than non-palmoplantar epidermis via mesenchymal-epithelial interactions.

  7. Biological characteristics of mouse skin melanocytes.

    PubMed

    Shi, Zhanquan; Ji, Kaiyuan; Yang, Shanshan; Zhang, Junzhen; Yao, Jianbo; Dong, Changsheng; Fan, Ruiwen

    2016-04-01

    The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with α-melanocyte stimulating hormone (α-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse.

  8. Melanocytic naevi clustered on normal background skin.

    PubMed

    Torchia, D

    2015-04-01

    Several types of maculopapular melanocytic naevi can occur in a multiple form, and be arranged in a nonrandom fashion on the skin. The most frequently reported segmentally grouped naevi are lentigines. Two types of segmentally arranged lentigines probably exist. The first is associated with neurofibromatosis (NF)1 or NF1 signs, features scattered light-brown lesions and can be considered a type of mosaic NF1. By contrast, non-NF1 associated lesions are characterized by densely packed, dark lesions, and can be defined as 'non-NF1 checkerboard-arranged lentigines'. Blue naevi, Spitz naevi and common acquired melanocytic naevi can occur, clustered in an agminated (or cannonball) shape. However, if large enough, they always follow a checkerboard pattern. Hence, such mosaic conditions should be termed 'checkerboard-arranged blue naevi', 'checkerboard-arranged Spitz naevi' and 'checkerboard-arranged common acquired melanocytic naevi'. Segmentally arranged dysplastic melanocytic naevi probably represent a mosaic form of dysplastic naevus syndrome. Dysplastic melanocytic naevi confined to a cutaneous segment could be defined as 'isolated segmental dysplastic naevus syndrome', while segmentally arranged dysplastic melanocytic naevi co-occurring with widespread, nonsegmental dysplastic melanocytic naevi might configure a 'superimposed segmental dysplastic naevus syndrome'. Small congenital melanocytic naevi are always grouped along Blaschko lines. The only other instances following Blaschko lines are the so-called 'linear lentiginous naevus' and a unique case of multiple deep penetrating naevi.

  9. Melanoma and melanocytic nevi in decorative tattoos: three case reports.

    PubMed

    Varga, Erika; Korom, Irma; Varga, János; Kohán, József; Kemény, Lajos; Oláh, Judit

    2011-12-01

    In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Copyright © 2011 John Wiley & Sons A/S.

  10. 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo.

    PubMed

    Kroll, Tara M; Bommiasamy, Hemamalini; Boissy, Raymond E; Hernandez, Claudia; Nickoloff, Brian J; Mestril, Ruben; Caroline Le Poole, I

    2005-04-01

    The trigger initiating an autoimmune response against melanocytes in vitiligo remains unclear. Patients frequently experience stress to the skin prior to depigmentation. 4-tertiary butyl phenol (4-TBP) was used as a model compound to study the effects of stress on melanocytes. Heat shock protein (HSP)70 generated and secreted in response to 4-TBP was quantified. The protective potential of stress proteins generated following 4-TBP exposure was examined. It was studied whether HSP70 favors dendritic cell (DC) effector functions as well. Melanocytes were more sensitive to 4-TBP than fibroblasts, and HSP70 generated in response to 4-TBP exposure was partially released into the medium by immortalized vitiligo melanocyte cell line PIG3V. Stress protein HSP70 in turn induced membrane tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression and activation of DC effector functions towards stressed melanocytes. Melanocytes exposed to 4-TBP demonstrated elevated TRAIL death receptor expression. DC effector functions were partially inhibited by blocking antibodies to TRAIL. TRAIL expression and infiltration by CD11c+ cells was abundant in perilesional vitiligo skin. Stressed melanocytes may mediate DC activation through release of HSP70, and DC effector functions appear to play a previously unappreciated role in progressive vitiligo.

  11. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth

    PubMed Central

    Soong, Joanne; Chen, Yulin; Shustef, Elina; Scott, Glynis

    2011-01-01

    Semaphorins are secreted and membrane bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilins receptors. We recently reported that Plexin B1, the Semaphorin 4D receptor, is a tumor suppressor protein for melanoma, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to ultraviolet irradiation, that it stimulates proliferation, and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, in part through down-regulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Semaphorin 4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly down-regulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF dependent effects on melanocytes, including melanocyte migration. PMID:22189792

  12. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth.

    PubMed

    Soong, Joanne; Chen, Yulin; Shustef, Elina M; Scott, Glynis A

    2012-04-01

    Semaphorins are secreted and membrane-bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilin receptors. We recently reported that Plexin B1, the Semaphorin 4D (Sema4D) receptor, is a tumor-suppressor protein for melanoma, which functions, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor. In this report, we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to UV irradiation, and that it stimulates proliferation and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, partly through downregulation of the cell adhesion molecule E-cadherin. Sema4D suppressed activation of c-Met in response to its ligand, hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration. These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Sema4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met-dependent effects in human melanocytes. Because our data show that Plexin B1 is profoundly downregulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF-dependent effects on melanocytes, including melanocyte migration.

  13. Maintenance of distinct melanocyte populations in the interfollicular epidermis.

    PubMed

    Glover, James D; Knolle, Stefan; Wells, Kirsty L; Liu, Dianbo; Jackson, Ian J; Mort, Richard L; Headon, Denis J

    2015-07-01

    Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not produce melanin. They serve as a source of differentiated melanocytes for the hair follicle and contribute to the interfollicular epidermis upon wounding, exposure to ultraviolet irradiation or in remission from vitiligo, where repigmentation often spreads outwards from the hair follicles. It is unknown whether these observations reflect the normal homoeostatic mechanism of melanocyte renewal or whether unperturbed interfollicular epidermis can maintain a melanocyte population that is independent of the skin's appendages. Here, we show that mouse tail skin lacking appendages does maintain a stable melanocyte number, including a low frequency of amelanotic melanocytes, into adult life. Furthermore, we show that actively cycling differentiated melanocytes are present in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied on for melanocyte homoeostasis. © 2015 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons Ltd.

  14. Isolation, culture, and transfection of melanocytes.

    PubMed

    Godwin, Lauren S; Castle, Joanna T; Kohli, Jaskaren S; Goff, Philip S; Cairney, Claire J; Keith, W Nicol; Sviderskaya, Elena V; Bennett, Dorothy C

    2014-06-03

    Located in the basal epidermis and hair follicles, melanocytes of the integument are responsible for its coloration through production of melanin pigments. Melanin is produced in lysosomal-like organelles called melanosomes. In humans, this skin pigmentation acts as an ultraviolet radiation filter. Abnormalities in the division of melanocytes are quite common, with potentially oncogenic growth usually followed by cell senescence producing benign naevi (moles), or occasionally melanoma. Therefore, melanocytes are a useful model for studying melanoma, as well as pigmentation and organelle transport and the diseases affecting these mechanisms. This chapter focuses on the isolation, culture, and transfection of human and murine melanocytes. The first basic protocol describes the primary culture of melanocytes from human skin and the maintenance of growing cultures. The second basic protocol details the subculture and preparation of mouse keratinocyte feeder cells. The primary culture of melanocytes from mouse skin is described in the third basic protocol, and, lastly, the fourth basic protocol outlines a technique for transfecting melanocytes and melanoma cells.

  15. [Whose borderline is it? Hypothesized etiologies of borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    Borderline personality is a well known concept in psychiatric literature, however, not fully understood as to its very nature. This article presents a short review of hypothesized etiologies of the borderline personality, starting with so called traditional theories, namely, borderline personality as a consolidated personality organization, in which the patient pathologically deals with his or her inner aggression, or with an enduring developmental failure. More modern hypotheses focus on possible childhood sexual abuse as the origin of the borderline, viewing the adult personality as a chronic, unresolved, post-traumatic disorder. Additionally, a neuro-epigenetic view hypothesized that a unique congenital neurological structure interacts with consequential events in early childhood to create the borderline personality.

  16. Pigmentation PAX-ways: The role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease

    PubMed Central

    Kubic, Jennifer D.; Young, Kacey P.; Plummer, Rebecca S.; Ludvik, Anton E.; Lang, Deborah

    2010-01-01

    Transcription factors initiate a program of gene expression and are catalysts in downstream molecular cascades that modulate a variety of cellular processes. Pax3 is a transcription factor that is important in the melanocyte and influences melanocytic proliferation, resistance to apoptosis, migration, lineage specificity and differentiation. In this review, we focus on Pax3 and the molecular pathways that Pax3 is a part of during melanogenesis and in the melanocyte stem cell. These roles of Pax3 are emphasized during the development of diseases and syndromes resulting from either too much or too little Pax3 function. Due to its key task in melanocyte stem cells and tumors, the Pax3 pathway may provide an ideal target for either stem cell or cancer therapies. PMID:18983540

  17. Basic fibroblast growth factor promotes melanocyte migration via increased expression of p125(FAK) on melanocytes.

    PubMed

    Wu, Ching-Shuang; Lan, Cheng-Che E; Chiou, Min-Hsi; Yu, Hsin-Su

    2006-01-01

    Vitiligo is an acquired pigmentary disorder characterized by depigmentation of skin and hair. Melanocyte migration is an important event in re-pigmentation of vitiligo. We have demonstrated that narrow-band ultraviolet B (UVB) irradiation stimulated cultured keratinocytes to release a significant amount of basic fibroblast growth factor (bFGF). Furthermore, narrow-band UVB enhanced migration of melanocytes via increased expression of phosphorylated focal adhesion kinase (p125(FAK)) on melanocytes. The aim of this study was to investigate the effect of recombinant human bFGF (rhbFGF) on melanocyte migration. The relationship between the expression of p125(FAK) and melanocyte migration induced by rhbFGF was also studied. Our results demonstrated that rhbFGF significantly enhanced migration of melanocytes and p125(FAK) expression on melanocytes. Herbimycin A, a potent p125(FAK) inhibitor, effectively abolished rhbFGF-induced melanocyte migration. The combined results indicated that p125(FAK) plays an important role in the signal transduction pathway of melanocyte migration induced by bFGF.

  18. The Long Noncoding RNA SPRIGHTLY Regulates Cell Proliferation in Primary Human Melanocytes.

    PubMed

    Zhao, Wei; Mazar, Joseph; Lee, Bongyong; Sawada, Junko; Li, Jian-Liang; Shelley, John; Govindarajan, Subramaniam; Towler, Dwight; Mattick, John S; Komatsu, Masanobu; Dinger, Marcel E; Perera, Ranjan J

    2016-04-01

    The long noncoding RNA SPRIGHTLY (formerly SPRY4-IT1), which lies within the intronic region of the SPRY4 gene, is up-regulated in human melanoma cells compared to melanocytes. SPRIGHTLY regulates a number of cancer hallmarks, including proliferation, motility, and apoptosis. To better understand its oncogenic role, SPRIGHTLY was stably transfected into human melanocytes, which resulted in increased cellular proliferation, colony formation, invasion, and development of a multinucleated dendritic-like phenotype. RNA sequencing and mass spectrometric analysis of SPRIGHTLY-expressing cells revealed changes in the expression of genes involved in cell proliferation, apoptosis, chromosome organization, regulation of DNA damage responses, and cell cycle. The proliferation marker Ki67, minichromosome maintenance genes 2-5, antiapoptotic gene X-linked inhibitor of apoptosis, and baculoviral IAP repeat-containing 7 were all up-regulated in SPRIGHTLY-expressing melanocytes, whereas the proapoptotic tumor suppressor gene DPPIV/CD26 was down-regulated, followed by an increase in extracellular signal-regulated kinase 1/2 phosphorylation, suggesting an increase in mitogen-activated protein kinase activity. Because down-regulation of DPPIV is known to be associated with malignant transformation in melanocytes, SPRIGHTLY-mediated DPPIV down-regulation may play an important role in melanoma pathobiology. Together, these findings provide important insights into how SPRIGHTLY regulates cell proliferation and anchorage-independent colony formation in primary human melanocytes.

  19. Agreement Between Cytology and Histopathology for Regional Lymph Node Metastasis in Dogs With Melanocytic Neoplasms.

    PubMed

    Grimes, Janet A; Matz, Brad M; Christopherson, Pete W; Koehler, Jey W; Cappelle, Kelsey K; Hlusko, Katelyn C; Smith, Annette

    2017-07-01

    Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κw) or kappa (κ) analysis (original cytology vs cytology review κw = 0.24; original cytology vs original histopathology κw = 0.007; original cytology vs histopathology review κw = 0.23; cytology review vs original histopathology κw = 0.008; cytology review vs histopathology review κw = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.

  20. Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma

    PubMed Central

    Byrne, Katelyn T.; Côté, Anik L.; Zhang, Peisheng; Steinberg, Shannon M.; Guo, Yanxia; Allie, Rameeza; Zhang, Weijun; Ernstoff, Marc S.; Usherwood, Edward J.; Turk, Mary Jo

    2011-01-01

    A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship between these two phenomena remains unclear. In the present study we have found that vitiligo, the autoimmune destruction of melanocytes, generates self antigen required for mounting persistent and protective memory CD8+ T cell responses to melanoma. Vitiligo developed in approximately 60% of mice that were depleted of regulatory CD4+ T cells and then subjected to surgical excision of large established B16 melanomas. Mice with vitiligo generated 10-fold larger populations of CD8+ memory T cells specific for shared melanoma/melanocyte antigens. CD8+ T cells in mice with vitiligo acquired phenotypic and functional characteristics of effector memory, suggesting that they were supported by ongoing antigen stimulation. Such responses were not generated in melanocyte-deficient mice, indicating a requirement for melanocyte destruction in maintaining CD8+ T cell immunity to melanoma. Vitiligo-associated memory CD8+ T cells provided durable tumor protection, were capable of mounting a rapid recall response to melanoma, and did not demonstrate phenotypic or functional signs of exhaustion even after many months of exposure to antigen. This work establishes melanocyte destruction as a key determinant of lasting melanoma-reactive immune responses, thus illustrating that immune-mediated destruction of normal tissues can perpetuate adaptive immune responses to cancer. PMID:21540555

  1. Killing of normal melanocytes, combined with heat shock protein 70 and CD40L expression, cures large established melanomas.

    PubMed

    Sanchez-Perez, Luis; Kottke, Timothy; Daniels, Gregory A; Diaz, Rosa Maria; Thompson, Jill; Pulido, Jose; Melcher, Alan; Vile, Richard G

    2006-09-15

    Previously, we showed that nine intradermal injections of a plasmid in which the HSVtk suicide gene is expressed from a melanocyte-specific promoter (Tyr-HSVtk), combined with a plasmid expressing heat shock protein 70 (CMV-hsp70), along with systemic ganciclovir, kills normal melanocytes and raises a CD8+ T cell response that is potent enough to eradicate small, 3-day established B16 tumors. We show in this study that, in that regimen, hsp70 acts as a potent immune adjuvant through TLR-4 signaling and local induction of TNF-alpha. hsp70 is required for migration of APC resident in the skin to the draining lymph nodes to present Ags, derived from the killing of normal melanocytes, to naive T cells. The addition of a plasmid expressing CD40L increased therapeutic efficacy, such that only six plasmid injections were now required to cure large, 9-day established tumors. Generation of potent immunological memory against rechallenge in cured mice accompanied these therapeutic gains, as did induction of aggressive autoimmune symptoms. Expression of CD40L, along with hsp70, increased both the frequency and activity of T cells activated against melanocyte-derived Ags. In this way, addition of CD40L to the hsp70-induced inflammatory killing of melanocytes can be used to cure large established tumors and to confer immunological memory against tumor cells, although a concomitant increase in autoimmune sequelae also is produced.

  2. Porcine melanotic cutaneous lesions and lymph nodes: immunohistochemical differentiation of melanocytes and melanophages.

    PubMed

    Grossi, A B; Hyttel, P; Jensen, H E; Leifsson, P S

    2015-01-01

    Porcine melanomas have proven interesting in a wider biological perspective due to a common phenomenon of spontaneous regression, which is characterized by infiltration of macrophages, among others. Separation of neoplastic melanocytes from pigment-laden macrophages may, however, be challenging as the morphology of melanocytes varies considerably and sometimes resembles macrophages. The aim of this study was correspondingly to characterize and differentiate the cells in 20 porcine melanocytomas and regional lymph nodes by histologic examination and immunohistochemistry for melan A, PNL2, S100, lysozyme, alpha-1-antitrypsin, and ionized calcium binding adaptor molecule 1 (Iba1). Grossly, the melanocytomas were divided into 2 distinct types: pigmented maculae (n = 7) and raised tumors (n = 13). In the maculae, the pigmented cells were mainly melanocytes reactive for melan A, PNL2 and S100. In contrast, the majority of the cells in the raised tumors were melanophages, which expressed Iba1, alpha-1-antitrypsin, and lysozyme. Yet, cells histomorphologically indistinguishable from the melanophages expressed melan A and PNL2. These cells were Iba1 and S100 negative, and ultrastructurally, they were devoid of lysosomal bodies and filled with stage III and IV melanosomes. In the regional lymph nodes, melanocytes were present in the trabecular sinuses. In focally or diffusely black lymph nodes, pigmentation was, however, mainly due to aggregates of melanophages, which were confined to the trabeculae, deep cortex, and peripheral lymphoreticular tissue. Normal and neoplastic porcine melanocytes express melan A and PNL2, and immunohistochemical staining for melan A, PNL2, and Iba1 was found useful to identify and distinguish melanocytes and melanophages in porcine melanotic lesions.

  3. Lineage relationship of direct-developing melanocytes and melanocyte stem cells in the zebrafish.

    PubMed

    Tryon, Robert C; Higdon, Charles W; Johnson, Stephen L

    2011-01-01

    Previous research in zebrafish has demonstrated that embryonic and larval regeneration melanocytes are derived from separate lineages. The embryonic melanocytes that establish the larval pigment pattern do not require regulative melanocyte stem cell (MSC) precursors, and are termed direct-developing melanocytes. In contrast, the larval regeneration melanocytes that restore the pigment pattern after ablation develop from MSC precursors. Here, we explore whether embryonic melanocytes and MSCs share bipotent progenitors. Furthermore, we explore when fate segregation of embryonic melanocytes and MSCs occurs in zebrafish development. In order to achieve this, we develop and apply a novel lineage tracing method. We first demonstrate that Tol2-mediated genomic integration of reporter constructs from plasmids injected at the 1-2 cell stage occurs most frequently after the midblastula transition but prior to shield stage, between 3 and 6 hours post-fertilization. This previously uncharacterized timing of Tol2-mediated genomic integration establishes Tol2-mediated transposition as a means for conducting lineage tracing in zebrafish. Combining the Tol2-mediated lineage tracing strategy with a melanocyte regeneration assay previously developed in our lab, we find that embryonic melanocytes and larval regeneration melanocytes are derived from progenitors that contribute to both lineages. We estimate 50-60 such bipotent melanogenic progenitors to be present in the shield-stage embryo. Furthermore, our examination of direct-developing and MSC-restricted lineages suggests that these are segregated from bipotent precursors after the shield stage, but prior to the end of convergence and extension. Following this early fate segregation, we estimate approximately 100 embryonic melanocyte and 90 MSC-restricted lineages are generated to establish or regenerate the zebrafish larval pigment pattern, respectively. Thus, the dual strategies of direct-development and MSC-derived development

  4. Lineage Relationship of Direct-Developing Melanocytes and Melanocyte Stem Cells in the Zebrafish

    PubMed Central

    Tryon, Robert C.; Higdon, Charles W.; Johnson, Stephen L.

    2011-01-01

    Previous research in zebrafish has demonstrated that embryonic and larval regeneration melanocytes are derived from separate lineages. The embryonic melanocytes that establish the larval pigment pattern do not require regulative melanocyte stem cell (MSC) precursors, and are termed direct-developing melanocytes. In contrast, the larval regeneration melanocytes that restore the pigment pattern after ablation develop from MSC precursors. Here, we explore whether embryonic melanocytes and MSCs share bipotent progenitors. Furthermore, we explore when fate segregation of embryonic melanocytes and MSCs occurs in zebrafish development. In order to achieve this, we develop and apply a novel lineage tracing method. We first demonstrate that Tol2-mediated genomic integration of reporter constructs from plasmids injected at the 1–2 cell stage occurs most frequently after the midblastula transition but prior to shield stage, between 3 and 6 hours post-fertilization. This previously uncharacterized timing of Tol2-mediated genomic integration establishes Tol2-mediated transposition as a means for conducting lineage tracing in zebrafish. Combining the Tol2-mediated lineage tracing strategy with a melanocyte regeneration assay previously developed in our lab, we find that embryonic melanocytes and larval regeneration melanocytes are derived from progenitors that contribute to both lineages. We estimate 50–60 such bipotent melanogenic progenitors to be present in the shield-stage embryo. Furthermore, our examination of direct-developing and MSC-restricted lineages suggests that these are segregated from bipotent precursors after the shield stage, but prior to the end of convergence and extension. Following this early fate segregation, we estimate approximately 100 embryonic melanocyte and 90 MSC-restricted lineages are generated to establish or regenerate the zebrafish larval pigment pattern, respectively. Thus, the dual strategies of direct-development and MSC

  5. "Melanocytic Nests Arising in Lichenoid Inflammation": Reappraisal of the Terminology "Melanocytic Pseudonests".

    PubMed

    Chung, Hye Jin; Simkin, A David; Bhawan, Jag; Wolpowitz, Deon

    2015-12-01

    Pseudonests or pseudomelanocytic nests represent aggregates of cells and cell fragments, including keratinocytes, macrophages, lymphocytes, and occasional melanocytes. Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Several reports documented nonspecific staining of pseudonests with melanoma antigen recognized by T cells-1/Melan-A, which can be detected in the cytoplasm of nonmelanocytic cells. In contrast, nuclear stains, such as MITF and SOX10, avoid this nonmelanocyte cytoplasmic staining. The authors have previously proposed the term melanocytic pseudonests to describe junctional nests with numerous (>2) true melanoma antigen recognized by T cells-1/Melan-A, SOX10, and MITF in a nonmelanocytic lesion with lichenoid inflammation (unilateral lichen planus pigmentosus/erythema dyschromicum perstans). In this study, the authors report another case of this phenomenon arising in a different lichenoid inflammatory dermatitis (lichen planus). The immunophenotype and number of clustered true melanocytes indicate that these dermoepidermal aggregates represent true melanocytic nests and not pseudonests of any type. Therefore, the authors propose the revised terminology of "melanocytic nests arising in lichenoid inflammation" to describe this novel pattern of benign melanocytic reorganization or proliferation in a subset of lichenoid dermatitides. Because this phenomenon can mimic atypical melanocytic proliferations, clinicopathologic correlation is essential for the correct diagnosis.

  6. Melanocytic Nests Arising in Lichenoid Inflammation”: Reappraisal of the Terminology “Melanocytic Pseudonests”

    PubMed Central

    Chung, Hye Jin; Simkin, A. David; Bhawan, Jag

    2015-01-01

    Abstract: Pseudonests or pseudomelanocytic nests represent aggregates of cells and cell fragments, including keratinocytes, macrophages, lymphocytes, and occasional melanocytes. Pseudomelanocytic nests in the setting of lichenoid inflammation can mimic atypical melanocytic proliferations. Several reports documented nonspecific staining of pseudonests with melanoma antigen recognized by T cells-1/Melan-A, which can be detected in the cytoplasm of nonmelanocytic cells. In contrast, nuclear stains, such as MITF and SOX10, avoid this nonmelanocyte cytoplasmic staining. The authors have previously proposed the term melanocytic pseudonests to describe junctional nests with numerous (>2) true melanoma antigen recognized by T cells-1/Melan-A, SOX10, and MITF in a nonmelanocytic lesion with lichenoid inflammation (unilateral lichen planus pigmentosus/erythema dyschromicum perstans). In this study, the authors report another case of this phenomenon arising in a different lichenoid inflammatory dermatitis (lichen planus). The immunophenotype and number of clustered true melanocytes indicate that these dermoepidermal aggregates represent true melanocytic nests and not pseudonests of any type. Therefore, the authors propose the revised terminology of “melanocytic nests arising in lichenoid inflammation” to describe this novel pattern of benign melanocytic reorganization or proliferation in a subset of lichenoid dermatitides. Because this phenomenon can mimic atypical melanocytic proliferations, clinicopathologic correlation is essential for the correct diagnosis. PMID:26588340

  7. Prescribing and borderline personality disorder

    PubMed Central

    Chanen, Andrew M; Thompson, Katherine N

    2016-01-01

    Summary Accurate diagnosis is fundamental to effective management of borderline personality disorder, but many patients remain undetected. The first-line management for borderline personality disorder is psychosocial treatment, not drugs. There are major prescribing hazards including polypharmacy, overdose and misuse. Drug treatment might be warranted for patients who have a co-occurring mental disorder such as major depression. If a drug is prescribed for borderline personality disorder, it should only be as an adjunct to psychosocial treatment. There should be clear and collaborative goals that are regularly reviewed with the patient. Use single drugs prescribed in limited quantities for a limited time. Stop drugs that are ineffective. PMID:27340322

  8. Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the cell migration process.

    PubMed

    Choi, Hyunjung; Jin, Sun Hee; Han, Mi Hwa; Lee, Jinyoung; Ahn, Seyeon; Seong, Minjeong; Choi, Hyun; Han, Jiyeon; Cho, Eun-Gyung; Lee, Tae Ryong; Noh, Minsoo

    2014-10-01

    The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. Adipocyte Secretome Increases Radioresistance of Malignant Melanocytes by Improving Cell Survival and Decreasing Oxidative Status.

    PubMed

    Coelho, Pedro; Silva, Liliana; Faria, Isabel; Vieria, Mónica; Monteiro, Armanda; Pinto, Gabriela; Prudêncio, Cristina; Fernandes, Rúben; Soares, Raquel

    2017-05-01

    Radiotherapy is a treatment option for the majority of malignancies. However, because melanoma is known to be radioresistant, the use of ionizing radiation as an adjuvant therapy in cutaneous melanoma patients is ineffective. Obesity has now been recognized as a risk factor for melanoma. High adiposity is generally associated with a more pro-oxidative status. Oxidative stress is a major player in radiation therapy and also a common link between obesity and cancer. Several adipocyte-released proteins are known to have a role in controlling cellular growth and pro-survival signaling. For that reason, we investigated the influence of 3T3-L1 mature adipocyte secretome in B16-F10 malignant melanocyte radiosensitivity. We evaluated B16-F10 cell survival and redox homeostasis when exposed to four daily doses of ionizing radiation (2 Gy per day) up to a total of 8 Gy in a medical linear accelerator. B16-F10 melanocytes exhibited slight alterations in survival, catalase activity, nitrative stress and total oxidant concentration after the first 2 Gy irradiation. The motility of the melanocytes was also delayed by ionizing radiation. Subsequent irradiations of the malignant melanocytes led to more prominent reductions in overall survival. Remarkably, 3T3-L1 adipocyte-secreted molecules were able to increase the viability and migration of melanocytes, as well as lessen the pro-oxidant burden induced by both the single and cumulative X-ray doses. In vitro adipocyte-released factors protected B16-F10 malignant melanocytes from both oxidative stress and loss of viability triggered by radiation, enhancing the radioresistant phenotype of these cells with a concomitant activation of the AKT signaling pathway. These results both help to elucidate how obesity influences melanoma radioresistance and support the usage of conventional medical linear accelerators as a valid model for the in vitro radiobiological study of tumor cell lines.

  10. Links between Schwann cells and melanocytes in development and disease.

    PubMed

    Van Raamsdonk, Catherine D; Deo, Mugdha

    2013-09-01

    Melanocytes are pigment-producing cells that reside in the skin, eyes, ears, heart, and central nervous system meninges of mammals. Schwann cells are glial cells, which closely associate with peripheral nerves, myelinating, and sheathing them. Melanocytes and Schwann cells both arise from the neural crest during development, and some melanocytes arise directly from Schwann cell precursors lining developing spinal nerves. In this review, we explore the connections between melanocytes and Schwann cells in development and transformation.

  11. Uveal melanocytes do not respond to or express receptors for alpha-melanocyte-stimulating hormone.

    PubMed

    Li, Li; Hu, Dan-Ning; Zhao, Huiquan; McCormick, Steven A; Nordlund, James J; Boissy, Raymond E

    2006-10-01

    Whereas cutaneous pigmentation increases after exposure to ultraviolet (UV) irradiation, ocular pigmentation does not. This study was designed to examine the evidence that alpha-melanocyte-stimulating hormone (alpha-MSH), which is thought to be the mediator of UV response in the skin, has any role to play in uveal melanocytes. Human uveal melanocytes derived from the choroid and the iris were cultivated by using eyes harvested from adult cadaveric donors and were assessed by Northern blot analysis for growth and melanogenic response to alpha-MSH and expression of the receptor for alpha-MSH (MC1-R). In addition, expression of alpha-MSH was evaluated in ocular tissue by immunocytochemistry. Uveal melanocytes, unlike cutaneous melanocytes in vitro, exhibited no stimulation of proliferation in response to alpha-MSH at dosages ranging from 0.1 to 100 muM. In addition, tyrosine hydroxylase, DOPA oxidase, and protein levels for tyrosinase, TRP-1, and TRP-2 were not influenced by alpha-MSH. Associated with the lack of alpha-MSH response in cultured uveal melanocytes was the absence of expression of the receptor for alpha-MSH (MC1-R), as assessed by Northern blot analysis. Also in contrast to the skin, pigmented ocular tissue lacked expression of the alpha-MSH ligand, as assessed by immunocytochemistry. In conclusion, ocular pigmentation does not appear to be regulated by melanocyte stimulating hormone.

  12. Congenital Melanocytic Nevus Syndrome: A Case Series.

    PubMed

    Recio, A; Sánchez-Moya, A I; Félix, V; Campos, Y

    2017-01-19

    Congenital melanocytic nevus syndrome (CMNS) is the result of an abnormal proliferation of melanocytes in the skin and central nervous system caused by progenitor-cell mutations during embryonic development. Mutations in the NRAS gene have been detected in many of these cells. We present 5 cases of giant congenital melanocytic nevus, 3 of them associated with CMNS; NRAS gene mutation was studied in these 3 patients. Until a few years ago, surgery was the treatment of choice, but the results have proved unsatisfactory because aggressive interventions do not improve cosmetic appearance and only minimally reduce the risk of malignant change. In 2013, trametinib was approved for use in advanced melanoma associated with NRAS mutations. This drug, which acts on the intracellular RAS/RAF/MEK/pERK/MAPK cascade, could be useful in pediatric patients with CMNS. A better understanding of this disease will facilitate the development of new strategies.

  13. The Relationship of Psoriasis and Melanocytic Nevi

    PubMed Central

    Cengiz, Fatma Pelin; Emiroglu, Nazan; Bahali, Anil Gulsel; Ozkaya, Dilek Biyik; Su, Ozlem; Onsun, Nahide

    2016-01-01

    Background: There is limited data about the relationship between psoriasis and melanocytic lesions and melanoma. Immunologic pathways which were implicated in psoriasis induce a reduction in the number of melanocytic nevi. Aims and Objectives: To investigate the number of melanocytic nevi in psoriatic patients compared with controls and its relationship with disease severity and type of treatment. Methods: We performed a prospective study in 100 psoriatic patients and 100 controls. Clinical data were recorded for all participants. Results: As compared with controls, patients had overall fewer nevi congenital nevi. Among psoriatic patients, biologic agents and disease severity did not correlate with the number of nevi. Conclusions: Psoriatic patients have fewer nevi than controls. Frequency of nevi in psoriatic patients is not related to treatment and disease severity. PMID:27904187

  14. UV light phototransduction depolarizes human melanocytes.

    PubMed

    Bellono, Nicholas W; Oancea, Elena

    2013-01-01

    Exposure of human skin to low doses of solar UV radiation (UVR) causes increased pigmentation, while chronic exposure is a powerful risk factor for skin cancers. The mechanisms mediating UVR detection in skin, however, remain poorly understood. Our recent studies revealed that UVR activates a retinal-dependent G protein-coupled signaling pathway in melanocytes. This phototransduction pathway leads to the activation of transient receptor potential A1 (TRPA1) ion channels, elevation of intracellular calcium (Ca( 2+)) and rapid increase in cellular melanin content. Here we report that physiological doses of solar-like UVR elicit a retinal-dependent membrane depolarization in human epidermal melanocytes. This transient depolarization correlates with delayed inactivation time of the UVR-evoked photocurrent and with sustained Ca( 2+) responses required for early melanin synthesis. Thus, the cellular depolarization induced by UVR phototransduction in melanocytes is likely to be a critical signaling mechanism necessary for the protective response represented by increased melanin content.

  15. Glial versus melanocyte cell fate choice: Schwann cell precursors as a cellular origin of melanocytes.

    PubMed

    Adameyko, Igor; Lallemend, Francois

    2010-09-01

    Melanocytes and Schwann cells are derived from the multipotent population of neural crest cells. Although both cell types were thought to be generated through completely distinct pathways and molecular processes, a recent study has revealed that these different cell types are intimately interconnected far beyond previously postulated limits in that they share a common post-neural crest progenitor, i.e. the Schwann cell precursor. This finding raises interesting questions about the lineage relationships of hitherto unrelated cell types such as melanocytes and Schwann cells, and may provide clinical insights into mechanisms of pigmentation disorders and for cancer involving Schwann cells and melanocytes.

  16. Borderline Personality Disorder

    PubMed Central

    Brüne, Martin

    2016-01-01

    The term ‘Borderline Personality Disorder’ (BPD) refers to a psychiatric syndrome that is characterized by emotion dysregulation, impulsivity, risk-taking behavior, irritability, feelings of emptiness, self-injury and fear of abandonment, as well as unstable interpersonal relationships. BPD is not only common in psychiatric populations but also more prevalent in the general community than previously thought, and thus represents an important public health issue. In contrast to most psychiatric disorders, some symptoms associated with BPD may improve over time, even without therapy, though impaired social functioning and interpersonal disturbances in close relationships often persist. Another counterintuitive and insufficiently resolved question is why depressive symptoms and risk-taking behaviors can occur simultaneously in the same individual. Moreover, there is an ongoing debate about the nosological position of BPD, which impacts on research regarding sex differences in clinical presentation and patterns of comorbidity. In this review, it is argued that many features of BPD may be conceptualized within an evolutionary framework, namely behavioral ecology. According to Life History Theory, BPD reflects a pathological extreme or distortion of a behavioral ‘strategy’ which unconsciously aims at immediate exploitation of resources, both interpersonal and material, based on predictions shaped by early developmental experiences. Such a view is consistent with standard medical conceptualizations of BPD, but goes beyond classic ‘deficit’-oriented models, which may have profound implications for therapeutic approaches. PMID:26929090

  17. Congenital agminated melanocytic nevus - case report*

    PubMed Central

    da Rocha, Camila Roos Mariano; Grazziotin, Thaís Corsetti; Rey, Maria Carolina Widholzer; Luzzatto, Laura; Bonamigo, Renan Rangel

    2013-01-01

    Agminated nevus is a cluster group of melanocytic nevi confined to a localized area of the body. There are many pigmented lesions described in the literature as agminated, such as blue nevi, multiple lentigines and Spitz nevi, but only a few cases of congenital agminated melanocytic nevi have been described. We report a case of a male child who presented with congenital agminated nevi, emphasizing the importance of physical examination, dermoscopy, histopathological evaluation, differential diagnosis and follow up to rule out the possibility of dysplastic or malignant changes. PMID:24346910

  18. [Whose borderline is it? Reconsidering diagnosing borderline personality].

    PubMed

    Gil, Tsvi E

    2008-11-01

    The present article critically discusses diagnosing borderline personality, demonstrating ideas raised with a treated case. In contrast to routine diagnoses made by psychiatrists according to common diagnosing systems (such as the American DSM or the WHO's ICD), we wonder whether this diagnosis reflects a medico-social construct, which is associated to the female status in masculine (or even patriarch) society, and probably associated even to the context of a woman diagnosed by a psychiatric system. In the context of critically viewing aetiological hypotheses to borderline personality (presented in our former article as a personality constellated around complex and prolonged trauma) in this article we suggest viewing borderline behaviours and symptoms as manifestations of coping and survival of a woman-victim in abusing surroundings.

  19. THE MOLECULAR PATHOLOGY OF MELANOMA: AN INTEGRATED TAXONOMY OF MELANOCYTIC NEOPLASIA

    PubMed Central

    Bastian, Boris C.

    2016-01-01

    Melanomas are comprised of multiple biologically distinct categories, which differ in cell of origin, age of onset, clinical and histologic presentation, pattern of metastasis, ethnic distribution, causative role of UV radiation, predisposing germ line alterations, mutational processes, and patterns of somatic mutations. Neoplasms are initiated by gain of function mutations in one of several primary oncogenes, typically leading to benign melanocytic nevi with characteristic histologic features. The progression of nevi is restrained by multiple tumor suppressive mechanisms. Secondary genetic alterations override these barriers and promote intermediate or overtly malignant tumors along distinct progression trajectories. The current knowledge about pathogenesis, clinical, histological and genetic features of primary melanocytic neoplasms is reviewed and integrated into a taxonomic framework. PMID:24460190

  20. Borderline resectable pancreatic cancer: Definitions and management

    PubMed Central

    Lopez, Nicole E; Prendergast, Cristina; Lowy, Andrew M

    2014-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. While surgical resection remains the only curative option, more than 80% of patients present with unresectable disease. Unfortunately, even among those who undergo resection, the reported median survival is 15-23 mo, with a 5-year survival of approximately 20%. Disappointingly, over the past several decades, despite improvements in diagnostic imaging, surgical technique and chemotherapeutic options, only modest improvements in survival have been realized. Nevertheless, it remains clear that surgical resection is a prerequisite for achieving long-term survival and cure. There is now emerging consensus that a subgroup of patients, previously considered poor candidates for resection because of the relationship of their primary tumor to surrounding vasculature, may benefit from resection, particularly when preceded by neoadjuvant therapy. This stage of disease, termed borderline resectable pancreatic cancer, has become of increasing interest and is now the focus of a multi-institutional clinical trial. Here we outline the history, progress, current treatment recommendations, and future directions for research in borderline resectable pancreatic cancer. PMID:25152577

  1. Hormones and Borderline Personality Features

    PubMed Central

    Evardone, Milagros; Alexander, Gerianne M.; Morey, Leslie C.

    2009-01-01

    Borderline personality is diagnosed in clinical settings three times more often in women than in men, and symptom severity in women appears sensitive to circulating sex steroid levels. In non-human mammals, prenatal hormones contribute to the development of sex-linked behavior and their responsiveness to postnatal hormones. Therefore, this study examined the hypothesis that prenatal hormones may influence the development of borderline personality traits by measuring a marker of perinatal androgen action, the 2D:4D ratio, and salivary hormone levels in 58 men and 52 women. Participants completed the Borderline Features Subscales (BOR) of the Personality Assessment Inventory, gender role questionnaires, and four sex-linked cognitive tasks. Digit ratios were a significant predictor of the affective component of borderline personality, such that in both sexes 2D:4D ratios suggestive of weaker perinatal androgen action contributed to greater borderline personality features overall and greater affective instability. In addition, women reporting greater affective instability showed larger changes in estradiol across the session, consistent with the influence of stress and emotional reactivity on hormonal function. These findings are consistent with an increasing body of research suggesting that hormonal factors associated with the expression of typical gender-linked behavior may also contribute to the expression of gender-linked maladaptive behavior. PMID:19554197

  2. Hormones and Borderline Personality Features.

    PubMed

    Evardone, Milagros; Alexander, Gerianne M; Morey, Leslie C

    2008-01-01

    Borderline personality is diagnosed in clinical settings three times more often in women than in men, and symptom severity in women appears sensitive to circulating sex steroid levels. In non-human mammals, prenatal hormones contribute to the development of sex-linked behavior and their responsiveness to postnatal hormones. Therefore, this study examined the hypothesis that prenatal hormones may influence the development of borderline personality traits by measuring a marker of perinatal androgen action, the 2D:4D ratio, and salivary hormone levels in 58 men and 52 women. Participants completed the Borderline Features Subscales (BOR) of the Personality Assessment Inventory, gender role questionnaires, and four sex-linked cognitive tasks. Digit ratios were a significant predictor of the affective component of borderline personality, such that in both sexes 2D:4D ratios suggestive of weaker perinatal androgen action contributed to greater borderline personality features overall and greater affective instability. In addition, women reporting greater affective instability showed larger changes in estradiol across the session, consistent with the influence of stress and emotional reactivity on hormonal function. These findings are consistent with an increasing body of research suggesting that hormonal factors associated with the expression of typical gender-linked behavior may also contribute to the expression of gender-linked maladaptive behavior.

  3. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation.

    PubMed

    Nishimura, Emi K

    2011-06-01

    Most mammals are coated with pigmented hair. Melanocytes in each hair follicle produce melanin pigments for the hair during each hair cycle. The key to understanding the mechanism of cyclic melanin production is the melanocyte stem cell (MelSC) population, previously known as 'amelanotic melanocytes'. The MelSCs directly adhere to hair follicle stem cells, the niche cells for MelSCs and reside in the hair follicle bulge-subbulge area, the lower permanent portion of the hair follicle, to serve as a melanocyte reservoir for skin and hair pigmentation. MelSCs form a stem cell system within individual hair follicles and provide a 'hair pigmentary unit' for each cycle of hair pigmentation. This review focuses on the identification of MelSCs and their characteristics and explains the importance of the MelSC population in the mechanisms of hair pigmentation, hair greying, and skin repigmentation. 2011 John Wiley & Sons A/S.

  4. Metastatic melanoma in association with a giant congenital melanocytic nevus in an adult: controversial CGH findings.

    PubMed

    Machan, Salma; Molina-Ruiz, Ana M; Fernández-Aceñero, Maria J; Encabo, Beatriz; LeBoit, Philip; Bastian, Boris C; Requena, Luis

    2015-06-01

    Giant congenital melanocytic nevi (GCMNs) represent a distress to patients for 2 reasons: one is disfigurement, and the other is the increased risk of developing secondary melanocytic tumors, such as benign proliferative nodules (BPNs) and malignant melanoma (MM). BPN present as a rapid growth nodule arising within a congenital melanocytic nevus (CMN) that often ulcerates, occurs in children younger than 2 years of age. BPNs arising within a CMN are exceedingly rare after childhood, and very few cases have been described in adults. Despite the worrisome clinical and histologic findings of BPN, most laboratory investigations seem to support their benignity. The distinction between MM and BPN is extremely important, but the histopathology of BPN of GCMN can be a challenge to differentiate from MM. In the recent years, molecular tests that investigate DNA copy number alterations such as fluorescence in situ hybridization and comparative genomic hybridization have shown promise to help guide the diagnosis of ambiguous melanocytic proliferations arising within CMNs. We report the case of a 22-year-old woman with a nodule arising in a GCMN and with an axillary mass suggesting a nodal metastasis of melanoma, and discuss the unusual clinical, histopathologic, and molecular findings that make this case particularly interesting.

  5. Isolating primary melanocyte-like cells from the mouse heart.

    PubMed

    Hwang, Hayoung; Liu, Fang; Levin, Mark D; Patel, Vickas V

    2014-09-29

    We identified a novel population of melanocyte-like cells (also known as cardiac melanocytes) in the hearts of mice and humans that contribute to atrial arrhythmia triggers in mice. To investigate the electrical and biological properties of cardiac melanocytes we developed a procedure to isolate them from mouse hearts that we derived from those designed to isolate neonatal murine cardiomyocytes. In order to obtain healthier cardiac melanocytes suitable for more extensive patch clamp or biochemical studies, we developed a refined procedure for isolating and plating cardiac melanocytes based on those originally designed to isolate cutaneous melanocytes. The refined procedure is demonstrated in this review and produces larger numbers of healthy melanocyte-like cells that can be plated as a pure population or with cardiomyocytes.

  6. Clear-cell melanocytic lesions with balloon-cell and sebocyte-like melanocytes: a unifying concept.

    PubMed

    Kazlouskaya, Viktoryia; Guo, Ying; Maia-Cohen, Sandra; Mones, Joan

    2014-05-01

    Melanocytes may assume unique shapes and sizes but rarely have clear cytoplasm. We studied 28 melanocytic lesions that contained clear-cell melanocytes of the balloon-cell and sebocyte-like types. Clear-cell melanocytes were found more commonly in females (64%) than in males (36%), with predominance in females younger than 50 years (79%) and predominance in males older than 50 years (67%). They were distributed evenly throughout the body but were not found on acral sites. Clear-cell melanocytes were most prevalent in congenital nevi (18 or 72%) but were also found in 5 Clark nevi, 2 Meischer nevi, 1 Unna nevus, 1 atypical intra-epidermal proliferation, and 1 melanoma. The clear cells were distributed diffusely in 86% of the lesions and focally in 14%. The overall percentage of clear-cell melanocytes was 56%. The percentage of balloon cells was 57% and sebocyte-like melanocytes 32%. Clear cells with morphologic features of both balloon cells and sebocyte-like melanocytes, that is, intermediate cells, were present in all lesions with an overall percentage of 12%. The presence of melanocytes of both the balloon-cell and sebocyte-like types and the finding of clear-cell melanocytes with intermediate features in all lesions lends support to the theory that balloon-cell and sebocyte-like melanocytes may represent morphologic expressions of the same alteration in melanogenesis.

  7. Melanocyte antigen triggers autoimmunity in human psoriasis

    PubMed Central

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus

    2015-01-01

    Psoriasis vulgaris is a common T cell–mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8+ T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02–restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8+ T cell clone of an HLA-C*06:02–positive psoriasis patient specifically recognizes HLA-C*06:02–positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02–presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8+ T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8+ T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8+ T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway. PMID:26621454

  8. Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation1

    PubMed Central

    Ricca, Tatiana I; Liang, Gangning; Suenaga, Ana Paula M; Han, Sang W; Jones, Peter A; Jasiulionis, Miriam G

    2009-01-01

    Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. In melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2′-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as a MMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. In this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation. PMID:19956395

  9. The relationship of melanocytic differentiation with prognostic markers in medullary thyroid carcinomas.

    PubMed

    Karaarslan, Serap; Nur Yurum, Fatma; Ebru Pala, Emel; Ortac, Ragip; Husnu Bugdayci, Mehmet

    2015-05-01

    Medullary thyroid carcinoma (MTC) makes up 5-10% of thyroid malignancies. Small cell, squamous, giant cell or melanocytic differentiation can rarely be seen in MTCs. It is important to determine those with the potential to act aggressively such as cases with melanocytic differentiation at the time of diagnosis. A total of 46 MTC cases diagnosed at four different centers between 2002 and 2013 were included in the study. Immunohistochemical (IHC) staining with Melan-A and HMB-45 was performed in all cases. Six of the 46 MTC cases were medullary microcarcinomas and three were multicentric medullary carcinomas. There were 34 females and 12 males with a mean age at onset of 51.4 years and mean tumor diameter of 23.2mm. Lymph node metastasis (LNM) was found in 13 of the 38 cases that had data regarding the lymph nodes. Immunohistochemically, Melan A staining was seen in four cases. HMB45 staining was seen in four cases. A statistically significant relationship was found between LNM and diameter, Melan A expression (p=0.02, p=0.03 respectively) but there was no significant relationship with HMB45 expression (p=0.07). General survival data were present for 35 of the 46 cases. All cases without lymph node metastasis survived (21/21) while 8 of 11 cases with lymph node metastasis survived among cases with survival data; one case that was diffuse-strong positive for both HMB45 and Melan A was lost due to distant organ metastasis six months after the diagnosis. Should the possibility of melanocytic differentiation be evaluated in cases where melanocytic differentiation is not reflected in the morphology (lack of pigment) in MTCs? We did not come across a study on the subject in the English literature. The effect of melanocytic differentiation on the prognosis in MTCs should be investigated in larger series. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Is it a primary or metastatic melanocytic neoplasm of the central nervous system?: A molecular based approach.

    PubMed

    Cornejo, Kristine M; Hutchinson, Lloyd; Cosar, Ediz F; Smith, Thomas; Tomaszewicz, Keith; Dresser, Karen; Deng, April

    2013-11-01

    Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon and must be distinguished from metastatic lesions as patients with metastatic disease carry a worse prognosis. Therefore, tools to aid in the diagnosis of a primary CNS melanocytic neoplasm would be of clinical utility. Primary CNS melanocytic neoplasms, including uveal melanomas have frequent mutations in GNAQ and GNA11, but are rare in cutaneous and mucosal melanomas. Additionally, primary uveal melanomas often exhibit monosomy 3 conferring an elevated risk of metastasis. We present a 63 year-old male with a melanocytic neoplasm in the thoracic spinal cord. Molecular studies revealed the tumor contained a GNAQ mutation and four-color fluorescent in situ hybridization (FISH) composed of chromosome enumeration probes for 3, 7, 17 and a locus specific probe for 9p21/CDKN2A yielded a normal result (i.e. two copies per cell), favoring a primary versus metastatic melanocytic neoplasm of the CNS. We report a case in which the combination of mutational analysis and FISH aided in identifying the origin of the neoplasm. © 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  11. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2016-10-20

    Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer

  12. Automatic evaluation of skin histopathological images for melanocytic features

    NASA Astrophysics Data System (ADS)

    Koosha, Mohaddeseh; Hoseini Alinodehi, S. Pourya; Nicolescu, Mircea; Safaei Naraghi, Zahra

    2017-03-01

    Successfully detecting melanocyte cells in the skin epidermis has great significance in skin histopathology. Because of the existence of cells with similar appearance to melanocytes in hematoxylin and eosin (HE) images of the epidermis, detecting melanocytes becomes a challenging task. This paper proposes a novel technique for the detection of melanocytes in HE images of the epidermis, based on the melanocyte color features, in the HSI color domain. Initially, an effective soft morphological filter is applied to the HE images in the HSI color domain to remove noise. Then a novel threshold-based technique is applied to distinguish the candidate melanocytes' nuclei. Similarly, the method is applied to find the candidate surrounding halos of the melanocytes. The candidate nuclei are associated with their surrounding halos using the suggested logical and statistical inferences. Finally, a fuzzy inference system is proposed, based on the HSI color information of a typical melanocyte in the epidermis, to calculate the similarity ratio of each candidate cell to a melanocyte. As our review on the literature shows, this is the first method evaluating epidermis cells for melanocyte similarity ratio. Experimental results on various images with different zooming factors show that the proposed method improves the results of previous works.

  13. Borderline Personality and Externalized Aggression

    PubMed Central

    Sansone, Lori A.

    2012-01-01

    Individuals with borderline personality disorder are diagnostically and clinically characterized by self-harm behavior, as indicated by the criterion in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, “recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior.” However, individuals with borderline personality disorder can display externalized aggressive behavior, as well. In an area characterized by considerably less research, empirical evidence indicates that individuals with borderline personality disorder may exhibit physical violence toward partners, physical violence toward known but nonintimate individuals, criminal behaviors that embody externalized violence (e.g., property damage), and, on very rare occasion, murderous behavior (either of family members or anonymous others through serial killing). Given this under-researched area, there are probably other types of externalized aggressive behaviors that have not been empirically revealed. However, externalized aggressive behaviors in individuals with borderline personality disorder clearly exist and need to be assessed in both psychiatric and primary care settings in an effort to promote safety of medical personnel and effective patient management. PMID:22567607

  14. Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

    PubMed

    Seleit, Iman; Bakry, Ola Ahmed; Abdou, Asmaa Gaber; Dawoud, Noha Mohammed

    2014-05-01

    There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.

  15. Periorbital melanocytic lesions: excision and reconstruction in 40 patients.

    PubMed

    Glat, P M; Longaker, M T; Jelks, E B; Spector, J A; Roses, D F; Shapiro, R A; Zide, B M; Jelks, G W

    1998-07-01

    The treatment of melanoma arising in the periorbital region is a difficult reconstructive problem. The abundance of vital structures in close proximity to one another makes the resection and subsequent reconstructive procedures extremely challenging. Reported here is experience with periorbital melanocytic lesions in 40 patients with the emphasis on the types of reconstruction performed. Forty patients with periorbital melanocytic lesions were treated between 1984 and 1995. The periorbital region was subdivided into five zones. These zones are the following: zone I, upper eyelid; zone II, lower eyelid; zone III, medial canthus; zone IV, lateral canthus; and zone V, contiguous structures. Ocular melanomas were not included in this study. The distribution of the lesions in our 40 patients was zone I (n = 1), zone II (n = 14), zone III (n = 1), zone IV (n = 9), and zone V (n = 31). The ages of the patients ranged from 3 to 84 years at the time of reconstruction, with an average age of 57 years. Resection and reconstruction were performed simultaneously in all patients. Thirty-six of the patients were reconstructed with one procedure, three patients required two procedures, and one patient required five procedures. The tumor type was superficial spreading melanoma in 15 patients, melanoma in situ in 17 patients, malignant spindle cell neoplasm in 2 patients, desmoplastic melanoma in 2 patients, amelanocytic melanoma in 1 patient, epithelioid melanoma in 1 patient, and atypical melanocytic nevus in 2 patients in which an early, evolving melanoma could not be excluded. Elective lymph node dissection was performed in four patients for intermediate thickness lesions (1.5 to 4.0 mm). The types of reconstructions performed included full-thickness skin grafts, upper lid myocutaneous flaps, cheek advancement flaps, cervicofacial flaps, inferiorly based nasolabial flaps, tarsoconjunctival flaps, frontalis muscle flaps, medial transposition Z-plasty, and primary closure. The

  16. Apoptosis of melanocytes in vitiligo results from antibody penetration.

    PubMed

    Ruiz-Argüelles, Alejandro; Brito, Gustavo Jiménez; Reyes-Izquierdo, Paola; Pérez-Romano, Beatriz; Sánchez-Sosa, Sergio

    2007-12-01

    Vitiligo is a rather common disease characterized by depigmentation of skin and mucosae due to the loss of melanocytes, most likely as a result of autoimmune phenomena. In this study we demonstrated apoptotic markers in residual melanocytes in skin biopsies of patients with vitiligo, as well as the presence of serum antibodies to melanocyte-specific antigens in the vast majority of patients. Moreover, we were able to prove that serum IgG antibodies from vitiligo patients, but not from healthy controls, were capable to penetrate into cultured melanocytes in vitro, and trigger them to engage in apoptosis. Our results are consonant with the theory that melanocyte-specific antibodies are responsible for the deletion of melanocytes through antibody penetration and apoptosis.

  17. Melanoma Arising in a Melanocytic Nevus.

    PubMed

    Martín-Gorgojo, A; Nagore, E

    2017-08-14

    The association of melanoma with a preexisting melanocytic nevus varies considerably between series, depending on whether the association is based on histological signs (4%-72%) or a clinically evident lesion (42%-85%). Histological association with a nevus correlates with favorable prognostic factors, whereas a clinical association correlates with unfavorable factors. In this review, we discuss the characteristics of nevus-associated melanoma from different perspectives: Whiteman's divergent pathway hypothesis for the development of cutaneous melanoma; and the factors involved in nevogenicity, including both the genetic and molecular factors involved in the development of the melanoma and its precursor lesions. Finally, a cumulative analysis of the 16 162 cases reported in the literature revealed that 29.8% of melanomas are histologically associated with a melanocytic nevus. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. A morphometric and immunohistochemical study of melanocytes in periorbital hyperpigmentation.

    PubMed

    Boruah, Dibyajyoti; Manu, V; Malik, Ajay; Chatterjee, Manas; Vasudevan, Biju; Srinivas, V

    2015-01-01

    An increase in number of melanocytes in the basal cell layer of the epidermis is an important feature in many disorders of hyperpigmentation. In this study, we attempted an objective evaluation of the linear density of melanocytes and keratinocytes, along with other epidermal characteristics, in periorbital hyperpigmentation using immunohistochemistry and morphometric techniques. Melanocytes and epidermal parameters were assessed by digital morphometry in 30 newly diagnosed cases of periorbital hyperpigmentation and 14 controls from the post-auricular region. Melanocytes were labelled with the immunohistochemical stains, Melan-A and tyrosinase. We studied the linear keratinocyte density, mean linear melanocyte density, ratio of melanocytes to keratinocytes, the ratio between inner and outer epidermal length, maximum epidermal thickness and minimum epidermal thickness. Melan-A expression of melanocytes showed strong positive correlation (r=0.883) with the tyrosinase expression. Mean linear melanocyte density was 24/mm (range: 13-30/mm) in cases and 17/mm (13-21/mm) in controls and this difference was statistically significant (P<0.001). The mean ratio of melanocyte to keratinocyte was 0.22 (0.12-0.29) in cases and 0.16 (0.12-0.21) in controls; again, this difference was statistically significant (P<0.001). There was a mild negative correlation with linear keratinocyte density (r=-0.302) and the ratio between inner and outer epidermal length (r=-0.456). However, there were no differences in epidermal thicknesses. There were fewer control biopsies than optimal, and they were not taken from the uninvolved periorbital region. Mean linear melanocyte density and the ratio of melanocytes to keratinocytes is increased in cases with periorbital hyperpigmentation. It is, therefore, likely that increased melanocyte density may be the key factor in the pathogenesis of periorbital hyperpigmentation.

  19. Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes.

    PubMed

    Aoki, Hitomi; Yamada, Yasuhiro; Hara, Akira; Kunisada, Takahiro

    2009-08-01

    Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear - the so-called non-cutaneous melanocytes - remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.

  20. The inflammatory infiltrate of melanocytic nevus.

    PubMed

    Fernandez-Flores, Angel; Saeb-Lima, Marcela

    2014-01-01

    Melanocytic nevi are frequently accompanied by inflammatory cells of different types, in varied amounts and distributed in different patterns. In the current report, we review the knowledge on inflammation seen in different types of melanocytic nevi. As an additional contribution, we studied the lymphocytic inflammatory component of Duperrat nevus, as well as the cytotoxic component of Sutton nevus, two contributions that we have not found in the literature. We conclude that: (a) Duperrat nevus has a mixed inflammatory reaction that includes histiocytes, foreign-body multinucleated giant cells, polymorphonuclears, lymphocytes (predominantly CD4+) and plasma cells (commonly abundant); (b) common melanocytic nevi with reactive inflammatory infiltrate usually show a CD4+ predominant population; (c) Meyerson nevus commonly shows an inflammatory infiltrate mainly made up of CD4+ T-cells; (d) Sutton nevus with halo phenomenon is accompanied by a dense inflammatory infiltrate with lymphocytes in a CD4:CD8 ratio varying from 1:1 to 1:3 and in which most of the CD8+ T-cells do not express cytotoxic markers; (e) Wiesner nevus commonly shows a spare lymphocytic infiltrate but the nature of the infiltrate has not yet been investigated.

  1. The discovery of the human melanocyte.

    PubMed

    Westerhof, Wiete

    2006-06-01

    Around 2200 bc the first written description of a human pigmentation disorder, most likely vitiligo, was recorded, and from that moment the history of research into human pigmentation can be traced. For the following 4000 yr, the origins of human skin colour remained an enigma that was to generate a multitude of misconceptions. Even after European physicians began to dissect and compare dark and light coloured skin to reveal its underlying anatomy, the origins of skin and hair pigmentation were a matter of frequently erroneous speculation. The true source of human pigmentation was only finally revealed with the discovery of the melanocyte in the 19th century. Once tyrosinase was identified to be the key enzyme in pigment formation, attention focused on elucidating the chemical structure of melanin, an enterprise that remains incomplete. The developmental origins of the melanocyte were described from 1940 to 1960, and the concept of the epidermal melanin unit was introduced together with a description of the ultrastructure of the melanosome and melanosome transfer. With these advances came the realization that different skin types exhibit distinct differences at the histological level that relate to varying amounts of eumelanin and pheomelanin produced by the melanocytes. The foundation established over the past 4000 yr is the basis for all current research into this fascinating cell type.

  2. Treatment histories of borderline inpatients.

    PubMed

    Zanarini, M C; Frankenburg, F R; Khera, G S; Bleichmar, J

    2001-01-01

    In this study, we describe the types and amounts of psychiatric treatment received by a well-defined sample of borderline personality disorder (BPD) inpatients, and compare these parameters with those of a group of carefully diagnosed personality-disordered controls. Finally, we assess the risk factors associated with a history of intensive, high-cost treatment, which we defined as having had two or more prior psychiatric hospitalizations. The treatment histories of 290 borderline inpatients and 72 axis II controls were assessed using a reliable semistructured interview. All nine forms of treatment studied except electroconvulsive therapy (ECT) were common among borderline patients (36% to 96%). In addition, a significantly higher percentage of borderline patients than axis II controls reported a history of individual and group therapy, day and residential treatment, psychiatric hospitalization, participating in self-help groups, and taking standing medications. They were also significantly younger when they first entered individual therapy and began to take standing medications. In addition, borderline patients spent more time than axis II controls in individual therapy and psychiatric hospitals, and were on standing medications for a significantly longer period of time. They also reported a significantly higher number of psychiatric hospitalizations, lifetime number of standing medications, and number of psychotropic medications taken at the same time. In addition, we found a highly significant multivariate predictive model for multiple prior hospitalizations. The six significant predictors were age 26 or older, a history of quasi psychotic thought, lifetime number of self-mutilative efforts and suicide attempts, a childhood history of reported sexual abuse, and an adult history of being physically and/or sexually assaulted. Taken together, these results confirm clinical impressions concerning the high rates of mental health services used by borderline patients

  3. Growth of melanocytes in human epidermal cell cultures

    SciTech Connect

    Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C. )

    1990-08-01

    Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient.

  4. Metabotropic glutamate receptor 1 mediates melanocyte transformation via transactivation of insulin-like growth factor 1 receptor.

    PubMed

    Teh, Jessica L F; Shah, Raj; Shin, Seung-Shick; Wen, Yu; Mehnert, Janice M; Goydos, James; Chen, Suzie

    2014-07-01

    Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1-mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet-R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1-melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin-like growth factor 1 receptor (IGF-1R). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer.

    PubMed

    McDonnell, Kevin J; Gallanis, Gregory T; Heller, Kathleen A; Melas, Marilena; Idos, Gregory E; Culver, Julie O; Martin, Sue-Ellen; Peng, David H; Gruber, Stephen B

    2016-03-01

    Germline mutations in the tumor suppressor gene, BRCA-1 associated protein (BAP1), underlie a tumor predisposition syndrome characterized by increased risk for numerous cancers including uveal melanoma, melanocytic tumors and mesothelioma, among others. In the present study we report the identification of a novel germline BAP1 mutation, c.1777C>T, which produces a truncated BAP1 protein product and segregates with cancer. Family members with this mutation demonstrated a primary clinical phenotype of autosomal dominant, early-onset melanocytic neoplasms with immunohistochemistry (IHC) of these tumors demonstrating lack of BAP1 protein expression. In addition, family members harboring the BAP1 c.1777C>T germline mutation developed other neoplastic disease including thyroid cancer. IHC analysis of the thyroid cancer, as well, demonstrated loss of BAP1 protein expression. Our investigation identifies a new BAP1 mutation, further highlights the relevance of BAP1 as a clinically important tumor suppressor gene, and broadens the range of cancers associated with BAP1 inactivation. Further study will be required to understand the full scope of BAP1-associated neoplastic disease.

  6. Eating disorder symptoms and borderline personality symptomatology.

    PubMed

    Sansone, R A; Chu, J W; Wiederman, M W; Lam, C

    2011-06-01

    According to the empirical literature, there are high rates of borderline personality disorder (BPD) among individuals with formal diagnoses of eating disorders, and high rates of eating disorders among individuals with BPD. In this study, we examined relationships between three eating disorder symptoms (i.e., binge eating, starving oneself, abusing laxatives) and borderline personality symptomatology according to two self-report measures (the borderline personality scale of the Personality Diagnostic Questionnaire-4 and the Self- Harm Inventory) in a sample of psychiatric inpatients (N=126) and in a sample of internal medicine outpatients (N=419). Each individual eating disorder item, as well as a composite score of all three items, demonstrated statistically significant correlations with both measures of borderline personality symptomatology in both samples. In addition, endorsement of all three symptoms was invariably associated with borderline personality symptomatology on both measures. Specific eating disorder symptoms, alone, may predict for borderline personality symptomatology.

  7. Interferon-γ induces senescence in normal human melanocytes.

    PubMed

    Wang, Suiquan; Zhou, Miaoni; Lin, Fuquan; Liu, Dongyin; Hong, Weisong; Lu, Liangjun; Zhu, Yiping; Xu, Aie

    2014-01-01

    Interferon-γ (IFN-γ) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. To investigate the effects of IFN-γ on viability and cellular functions of melanocytes. Primary human melanocytes were treated with IFN-γ. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. β-galactosidase staining was utilized to evaluate melanocyte senescence. Persistent IFN-γ treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of β-galactosidase activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes. IFN-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu.

  8. Interferon-γ Induces Senescence in Normal Human Melanocytes

    PubMed Central

    Wang, Suiquan; Zhou, Miaoni; Lin, Fuquan; Liu, Dongyin; Hong, Weisong; Lu, Liangjun; Zhu, Yiping; Xu, Aie

    2014-01-01

    Background Interferon-γ (IFN-γ) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. Objective To investigate the effects of IFN-γ on viability and cellular functions of melanocytes. Methods Primary human melanocytes were treated with IFN-γ. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. β-galactosidase staining was utilized to evaluate melanocyte senescence. Results Persistent IFN-γ treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of β-galactosidase activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes. Conclusion IFN-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu. PMID:24681574

  9. Mortality after diagnosis of small melanocytic lesions of the choroid.

    PubMed

    Lane, Anne Marie; Egan, Kathleen M; Kim, Ivana K; Gragoudas, Evangelos S

    2010-08-01

    To evaluate the risk of dying of metastatic choroidal melanoma in patients with small, indeterminate, pigmented lesions of the uveal tract. A cohort of 1063 consecutive patients were evaluated in the Ocular Oncology Clinic of the Massachusetts Eye and Ear Infirmary between January 1976 and June 1996 with definite choroidal nevus (n = 256), indeterminate lesions (n = 334), or small melanoma (n = 373). Deaths occurring up to December 1998 were identified through active follow-up or by a search of the National Death Index. Cumulative death rates were compared among diagnostic groups using the Kaplan-Meier method. Mean lesion diameter was 4.6 mm in the nevi, 7.0 mm in the indeterminate lesions, and 8.1 mm in the small melanomas. Patients ranged in age from 3 to 95 years (median, 64 years). A total of 15 deaths due to ocular melanoma were ascertained (median follow-up of survivors, 8.2 years), 13 in the melanoma group and 2 in the indeterminate lesion group; actuarial tumor-specific death rates at 10 years after evaluation were 5% (95% confidence interval, 3%-8%) and 1% (95% confidence interval 0%-3%), respectively. No deaths due to ocular melanoma occurred in the nevus group. These data document the very low malignant potential of most indeterminate melanocytic lesions of the choroid and support the current practice of monitoring these tumors, with treatment provided when growth and other signs of malignant transformation are observed.

  10. Cancer of the melanocytic system

    SciTech Connect

    Setlow, R.B.

    1994-12-31

    Within reasonably homogenous populations, skin cancer increases toward low latitudes, but this association does not indicate the wavelength regions involved in cancer induction. At present, the only animal model suitable for determining the wavelengths effective in melanoma induction are certain inter- and intraspecies hybrids of the small fish, Xiphophorus. Genetic evidence indicates that the hybrids contain only one tumor suppressor gene and, therefore, are very sensitive to cancer induction by single exposures to light. 5-Day old fish were exposed in spectrophotometer cuvettes, to different monochromatic wavelengths and fluences. The fish were kept for two months in tanks shielded with yellow plastic, so as to minimize the possibility of photoreactivation, and were scored at four months. The melanoma prevalence increased with exposure to a maximum of {approximately} 0.5. The fluence-response curves were fitted to surviving fraction = a+b(l-e{sup {minus}kE}), where a is the background prevalence with no exposure, b is the maximum induced prevalence, k is the sensitivity parameter (the cross section for melanoma induction), and E is the incident fluence. The value of k at 302 nm was 0.05 m{sup 2}/J giving a mean melanoma inducing exposure, for swimming fish, of 200 J/m{sup 2}, corresponding to 3.5 cyclobutane pyrimidine dimers per Mbp of DNA in irradiated fish skin.

  11. Recollections of family experience in borderline patients.

    PubMed

    Frank, H; Paris, J

    1981-09-01

    To test psychodynamic hypotheses about the etiology of the borderline syndrome, female borderline patients were asked whether they remembered their mothers and fathers as having responded with approval, disinterest, or criticism to dependent and independent behaviors. Comparisons were made with a group of normal controls and with a group of neurotics and patients with personality disorders. The main finding was that borderline patients remembered their fathers as neglectful. The recollections did not support an overprotection hypothesis.

  12. [A psychoanalytical approach of the borderline personality].

    PubMed

    Slucki, Daniel; Wikinski, Mariana

    A bibliographic review of the last year's psychoanalytic literature on borderline personality is presented. We expose diagnostic considerations, with special emphasis on those which refer to the boundaries between borderline personality, neurosis and psychosis on one hand, and those which distinguish between borderline personality and narcissistic disorders on the other. Vicissitudes of these patient's object relationships, their bond with other significant persons, their main psychic mechanisms, clinical traits and technical difficulties in the treatment are also described.

  13. Borderline Personality in the Medical Setting.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings-namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet's syndrome, somatic preoccupation, somatic. Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation.

  14. Emotional Hypochondriasis, Hyperbole, and the Borderline Patient

    PubMed Central

    ZANARINI, MARY C.; FRANKENBURG, FRANCES R.

    1994-01-01

    The authors define a new defense mechanism, emotional hypochondriasis, that is hypothesized to be central to borderline psychopathology. The behavioral manifestation of this defense—the hyperbolic stance of the borderline patient—is also defined and related to the complex phenomenology of borderline personality disorder. Borderline patients are seen as making an active attempt to maintain a tolerable, if tenuous, adaptation in the face of tremendous subjective emotional pain that has been shaped in large measure by traumatic childhood events that have never been validated. Twelve treatment implications and three expectable, if overlapping, stages of treatment stemming from the use of this defense and its behavioral sequelae are detailed. PMID:22700171

  15. Tumor

    MedlinePlus

    ... excessively in the body. Normally, the body controls cell growth and division. New cells are created to replace ... room for healthy replacements. If the balance of cell growth and death is disturbed, a tumor may form. ...

  16. A murine model for the development of melanocytic nevi and their progression to melanoma

    PubMed Central

    Nasti, Tahseen H.; Cochran, J. Barry; Tsuruta, Yuko; Yusuf, Nabiha; McKay, Kristopher M.; Athar, Mohammad; Elmets, Craig A.

    2015-01-01

    Acquired melanocytic nevi are commonly found in sun exposed and unexposed human skin, but the potential for their transformation into invasive melanoma is not clear. Therefore, a mouse model of nevus initiation and progression was developed in C3H/HeN mice using a modified chemical carcinogenesis protocol. Nevi develop due to DNA damage initiated by dimethylbenz(a) anthracene (DMBA) followed by chronic promotion with 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Dysplastic pigmented skin lesions appeared in 7–9 wk with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 wk, but not in age matched controls. Immunohistochemistry, real‐time PCR, and flow cytometric analyses confirmed their melanocytic origin. Transformed cells were present in a subset of nevi and dLNs, which exhibited anchorage‐independent growth, tumor development, and metastasis in nude mice. Approximately 50% of the cell lines contained H‐Ras mutations and lost tumor suppressor p16Ink4a expression. While most studies of melanoma focus on tumor progression in transgenic mouse models where the mutations are present from birth, our model permits investigation of acquired mutations at the earliest stages of nevus initiation and promotion of nevus cell transformation. This robust nevus/melanoma model may prove useful for identifying genetic loci associated with nevus formation, novel oncogenic pathways, tumor targets for immune‐prevention, screening therapeutics, and elucidating mechanisms of immune surveillance and immune evasion. © 2015 The Authors. Molecular Carcinogenesis, published by Wiley Periodicals, Inc. PMID:25788145

  17. How to Differentiate Borderline Hepatic Nodules in Hepatocarcinogenesis: Emphasis on Imaging Diagnosis.

    PubMed

    Park, Hyun Jeong; Choi, Byung Ihn; Lee, Eun Sun; Park, Sung Bin; Lee, Jong Beum

    2017-06-01

    Rapid advances in liver imaging have improved the evaluation of hepatocarcinogenesis and early diagnosis and treatment of hepatocellular carcinoma (HCC). In this situation, detection of early-stage HCC in its development is important for the improvement of patient survival and optimal treatment strategies. Because early HCCs are considered precursors of progressed HCC, precise differentiation between a dysplastic nodule (DN), especially a high-grade DN, and early HCC is important. In clinical practice, these nodules are frequently called "borderline hepatic nodules." This article discusses radiological and pathological characteristics of these borderline hepatic nodules and offers an understanding of multistep hepatocarcinogenesis by focusing on the descriptions of the imaging changes in the progression of DN and early HCC. Detection and accurate diagnosis of borderline hepatic nodules are still a challenge with contrast enhanced ultrasonography, CT, and MRI with extracellular contrast agents. However, gadoxetic acid-enhanced MRI may be useful for improving the diagnosis of these borderline nodules. Since there is a net effect of incomplete neoangiogenesis and decreased portal venous flow in the early stage of hepatocarcinogenesis, borderline hepatic nodules commonly show iso- or hypovascularity. Therefore, precise differentiation of these nodules remains a challenging issue. In MRI using hepatobiliary contrast agents, signal intensity of HCCs on hepatobiliary phase (HBP) is regarded as a potential imaging biomarker. Borderline hepatic nodules are seen as nonhypervascular and hypointense nodules on the HBP, which is important for predicting tumor behavior and determining appropriate therapeutic strategies.

  18. In Vitro Dedifferentiation of Melanocytes from Adult Epidermis

    PubMed Central

    Kormos, Bernadett; Belső, Nóra; Bebes, Attila; Szabad, Gábor; Bacsa, Sarolta; Széll, Márta; Kemény, Lajos; Bata-Csörgő, Zsuzsanna

    2011-01-01

    In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation. PMID:21383848

  19. Iris melanocyte numbers in Asian, African American, and Caucasian irides.

    PubMed

    Albert, Daniel M; Green, W Richard; Zimbric, Michele L; Lo, Cecilia; Gangnon, Ronald E; Hope, Kirsten L; Gleiser, Joel

    2003-01-01

    The anatomical basis for iris color has long been a controversial issue in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray-eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The present investigation was carried out to compare melanocyte numbers in the irides of Asian, African American, and Caucasian brown-eyed individuals. Paraffin-embedded sections from 71 brown-colored irides were incubated with rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody, and counterstained with Evans blue. Cells were counted under a fluorescence microscope and scored as melanocytes or other cells. Cell number, density, and iris area were calculated for each specimen. Caucasian and African American irides had comparable mean total melanocyte numbers. Asian irides had fewer total melanocytes than African American (P = .042) and Caucasian (P = .001) irides and smaller total number of cells (ie, melanocytes plus other cells) than African American (P = .054) or Caucasian (P = .009) irides. There is a statistically significant smaller mean total melanocyte number and mean total cellularity in Asian irides as compared to Caucasian and African American irides. This difference appears to be due to the combination of smaller iris area and lower melanocyte density in the Asian irides. The possibility exists that this may be a factor in ethnic variations in certain ocular diseases.

  20. In vitro dedifferentiation of melanocytes from adult epidermis.

    PubMed

    Kormos, Bernadett; Belso, Nóra; Bebes, Attila; Szabad, Gábor; Bacsa, Sarolta; Széll, Márta; Kemény, Lajos; Bata-Csörgo, Zsuzsanna

    2011-02-23

    In previous work we described a novel culture technique using a cholera toxin and PMA-free medium (Mel-mix) for obtaining pure melanocyte cultures from human adult epidermis. In Mel-mix medium the cultured melanocytes are bipolar, unpigmented and highly proliferative. Further characterization of the cultured melanocytes revealed the disappearance of c-Kit and TRP-1 and induction of nestin expression, indicating that melanocytes dedifferentiated in this in vitro culture. Cholera toxin and PMA were able to induce c-Kit and TRP-1 protein expressions in the cells, reversing dedifferentiation. TRP-1 mRNA expression was induced in dedifferentiated melanocytes by UV-B irradiated keratinocyte supernatants, however direct UV-B irradiation of the cells resulted in further decrease of TRP-1 mRNA expression. These dedifferentiated, easily accessible cultured melanocytes provide a good model for studying melanocyte differentiation and possibly transdifferentiation. Because melanocytes in Mel-mix medium can be cultured with human serum as the only supplement, this culture system is also suitable for autologous cell transplantation.

  1. Iris melanocyte numbers in Asian, African American, and Caucasian irides.

    PubMed Central

    Albert, Daniel M; Green, W Richard; Zimbric, Michele L; Lo, Cecilia; Gangnon, Ronald E; Hope, Kirsten L; Gleiser, Joel

    2003-01-01

    PURPOSE: The anatomical basis for iris color has long been a controversial issue in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray-eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The present investigation was carried out to compare melanocyte numbers in the irides of Asian, African American, and Caucasian brown-eyed individuals. METHODS: Paraffin-embedded sections from 71 brown-colored irides were incubated with rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody, and counterstained with Evans blue. Cells were counted under a fluorescence microscope and scored as melanocytes or other cells. Cell number, density, and iris area were calculated for each specimen. RESULTS: Caucasian and African American irides had comparable mean total melanocyte numbers. Asian irides had fewer total melanocytes than African American (P = .042) and Caucasian (P = .001) irides and smaller total number of cells (ie, melanocytes plus other cells) than African American (P = .054) or Caucasian (P = .009) irides. CONCLUSIONS: There is a statistically significant smaller mean total melanocyte number and mean total cellularity in Asian irides as compared to Caucasian and African American irides. This difference appears to be due to the combination of smaller iris area and lower melanocyte density in the Asian irides. The possibility exists that this may be a factor in ethnic variations in certain ocular diseases. PMID:14971580

  2. Meningeal Melanocytes in the Mouse: Distribution and Dependence on Mitf

    PubMed Central

    Gudjohnsen, Stefán A. H.; Atacho, Diahann A. M.; Gesbert, Franck; Raposo, Graca; Hurbain, Ilse; Larue, Lionel; Steingrimsson, Eirikur; Petersen, Petur Henry

    2015-01-01

    Summary: Melanocytes are pigment producing cells derived from the neural crest. They are primarily found in the skin and hair follicles, but can also be found in other tissues including the eye, ear and heart. Here, we describe the distribution of pigmented cells in C57BL/6J mouse meninges, the membranes that envelope the brain. These cells contain melanosomes of all four stages of development and they depend on Microphthalmia associated transcription factor (MITF), the master regulator of melanocyte development, suggesting that they are bona-fide melanocytes. The location of these pigmented cells is consistent with the location of meningeal melanomas in humans and animal models. Significance: Here, we document and define pigmented cells in the meninges of the mouse brain and confirm that they are melanocytes. This is important for understanding the role of this cell type and for understanding primary meningeal melanoma, a rare disease that likely arises from normal meningeal melanocytes. PMID:26635543

  3. Exosomes released by keratinocytes modulate melanocyte pigmentation

    PubMed Central

    Cicero, Alessandra Lo; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-01-01

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states. PMID:26103923

  4. Exosomes released by keratinocytes modulate melanocyte pigmentation.

    PubMed

    Lo Cicero, Alessandra; Delevoye, Cédric; Gilles-Marsens, Floriane; Loew, Damarys; Dingli, Florent; Guéré, Christelle; André, Nathalie; Vié, Katell; van Niel, Guillaume; Raposo, Graça

    2015-06-24

    Cells secrete extracellular vesicles (EVs), exosomes and microvesicles, which transfer proteins, lipids and RNAs to regulate recipient cell functions. Skin pigmentation relies on a tight dialogue between keratinocytes and melanocytes in the epidermis. Here we report that exosomes secreted by keratinocytes enhance melanin synthesis by increasing both the expression and activity of melanosomal proteins. Furthermore, we show that the function of keratinocyte-derived exosomes is phototype-dependent and is modulated by ultraviolet B. In sum, this study uncovers an important physiological function for exosomes in human pigmentation and opens new avenues in our understanding of how pigmentation is regulated by intercellular communication in both healthy and diseased states.

  5. Effects of hydroxybenzyl alcohols on melanogenesis in melanocyte-keratinocyte co-culture and monolayer culture of melanocytes.

    PubMed

    Liu, Szu-Hsiu; Chu, I-Ming; Pan, I-Horng

    2008-08-01

    In mammalian skin, melanocyte proliferation and melanogenesis can be stimulated by keratinocytes, fibroblasts and other regulatory factors. To determine whether hydroxybenzyl alcohols (HBAs) show more inhibitory in melanocytes cultured alone or in melanocytes co-cultured with keratinocytes, we developed a murine melanocyte-keratinocyte co-culture model to investigate the pigmentation regulators in company with other melanogenic inhibitors and stimulators. It was found that the effects of HBAs and melanogenic factors were more evident in melanocytes co-cultured with keratinocytes. Keratinocytes may play a synergistic role in melanocyte melanogenesis and influence the pigment production. The tests in the co-culture model also imply that the inhibitory effects of HBAs on melanogenesis are due to the direct inhibition of melanosomal tyrosinase activity. HBAs showed a low cytotoxicity. The eventual results proved that HBAs are promising and safe agents for skin whitening in melanocyte alone and in co-culture systems. The co-culture model provides a more physiologically realistic condition to study the interaction between melanocytes and keratinocytes, which enables a reliable screening system for depigmenting compounds.

  6. The Borderline Personality--An Adlerian Overview.

    ERIC Educational Resources Information Center

    Rattner, Leo

    The person with a borderline personality is considered to be neither neurotic nor psychotic, but to exist somewhere in between these two diagnostic categories. Psychoanalytic theorists who have researched the phenomenon of the borderline personality have shifted their emphasis away from Freud's instinct psychology and toward an ego psychology…

  7. Borderline Clients: Practice Implications of Recent Research.

    ERIC Educational Resources Information Center

    Johnson, Harriette C.

    1991-01-01

    Reviews current research on treatment of borderline clients with medication, individual counseling, and family interventions. Notes that recent studies indicate that borderline personality is heterogeneous condition in which different underlying disorders (affective, schizotypal, and neurological) may be present. Reviews effectiveness of various…

  8. Facial emotion recognition and borderline personality pathology.

    PubMed

    Meehan, Kevin B; Panfilis, Chiara De; Cain, Nicole M; Antonucci, Camilla; Soliani, Antonio; Clarkin, John F; Sambataro, Fabio

    2017-09-01

    The impact of borderline personality pathology on facial emotion recognition has been in dispute; with impaired, comparable, and enhanced accuracy found in high borderline personality groups. Discrepancies are likely driven by variations in facial emotion recognition tasks across studies (stimuli type/intensity) and heterogeneity in borderline personality pathology. This study evaluates facial emotion recognition for neutral and negative emotions (fear/sadness/disgust/anger) presented at varying intensities. Effortful control was evaluated as a moderator of facial emotion recognition in borderline personality. Non-clinical multicultural undergraduates (n = 132) completed a morphed facial emotion recognition task of neutral and negative emotional expressions across different intensities (100% Neutral; 25%/50%/75% Emotion) and self-reported borderline personality features and effortful control. Greater borderline personality features related to decreased accuracy in detecting neutral faces, but increased accuracy in detecting negative emotion faces, particularly at low-intensity thresholds. This pattern was moderated by effortful control; for individuals with low but not high effortful control, greater borderline personality features related to misattributions of emotion to neutral expressions, and enhanced detection of low-intensity emotional expressions. Individuals with high borderline personality features may therefore exhibit a bias toward detecting negative emotions that are not or barely present; however, good self-regulatory skills may protect against this potential social-cognitive vulnerability. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  9. The roles of Frizzled-3 and Wnt3a on melanocyte development: in vitro studies on neural crest cells and melanocyte precursor cell lines.

    PubMed

    Chang, Chung-Hsing; Tsai, Rong-Kung; Tsai, Ming-Hsien; Lin, Yi-Hsiung; Hirobe, Tomohisa

    2014-08-01

    Wnt3a and Frizzled-3 are both expressed in the dorsal neural tube that gives rise to the neural crest in Xenopus, zebrafish and mice. Melanocytes originate from the neural crest (NC) and postnatally, melanocyte stem cells reside in the hair follicle bulge and in the dermis. However, the roles of Wnt3a and Frizzled-3 in melanocyte development have not been clarified. The aim of this study was to delineate the expression of Frizzled-3 in murine melanocyte lineage and human melanocytes, and to study the effects of Wnt3a on melanocyte development at various stages. Murine NC explant cultures and three NC-derived melanocyte lineage cell lines, including NCCmelb4M5 (Kit(-) melanocyte precursors), NCCmelb4 (Kit(+) melanoblasts) and NCCmelan5 (differentiated melanocytes), and human epidermal melanocytes were treated with pure recombinant Wnt3a protein and their cell behaviors were analyzed including their proliferation, Kit expression, tyrosinase (Tyr) activity, melanin production, dendrite formation and migration. Frizzled-3 was expressed in Tyr-related protein (TRP)-1(+) cells in NC explant cultures, in all 3 melanocyte precursor cell lines and in human melanocytes. Wnt3a increased the population of TRP-1(+) cells, the number of L-3,4-dihydroxyphenylalanine (DOPA)(+) cells and dendrite formation in NC explant cultures. Wnt3a stimulated the proliferation of all 3 melanocyte precursor cell lines in a dose-dependent manner and also stimulated human melanocyte proliferation. Moreover, Wnt3a increased Tyr activity and melanin content of differentiated melanocytes, but did not activate Tyr activity in melanoblasts. Wnt3a stimulated dendrite formation in differentiated melanocytes, but not in melanoblasts. Wnt3a did not affect melanoblast or melanocyte migration. Wnt3a did not induce c-Kit expression in Kit(-) NCCmelb4M5 cells and did not affect c-Kit expression in any cell line tested. Frizzled-3 is constitutively expressed in murine melanocyte precursors, melanocytes and

  10. Transitional objects and borderline personality disorder.

    PubMed

    Cardasis, W; Hochman, J A; Silk, K R

    1997-02-01

    The relationship of possession of transitional objects to the borderline personality disorder diagnosis was explored in a psychiatric inpatient setting. It was hypothesized that a greater proportion of inpatients who bring objects of special meaning with them to the hospital have borderline personality disorder. Psychiatric inpatients (N = 146) were administered a semistructured interview to determine the presence of special (i.e., transitional) objects in the hospital, at home, or during childhood. Borderline personality disorder was determined by criteria on a DSM-III-R borderline personality disorder checklist and by DSM-III-R discharge diagnosis. Significantly more patients who endorsed having transitional objects in the hospital or at home had the diagnosis of borderline personality disorder. Sensitivity, specificity, positive predictive power, and negative predictive power of the possession of the transitional object for the borderline personality disorder diagnosis were calculated. Specificity was higher than sensitivity, and negative predictive power was higher than positive predictive power in each instance. While these results suggest that absence of a transitional object is more likely to be associated with absence of borderline personality disorder than the presence of a transitional object is with the presence of borderline personality disorder, the sensitivity of a transitional object during adulthood to predict a diagnosis of borderline personality disorder was 63%, and the positive predictive power was 45%. A transitional object brought to the hospital may help remind the inpatient with borderline personality disorder of home or provide soothing during separation from home. The persistence of transitional objects into adulthood may inform the therapist of possible transference paradigms that may develop in treatment.

  11. Defects in ErbB-dependent establishment of adult melanocyte stem cells reveal independent origins for embryonic and regeneration melanocytes.

    PubMed

    Hultman, Keith A; Budi, Erine H; Teasley, Daniel C; Gottlieb, Andrew Y; Parichy, David M; Johnson, Stephen L

    2009-07-01

    Adult stem cells are responsible for maintaining and repairing tissues during the life of an organism. Tissue repair in humans, however, is limited compared to the regenerative capabilities of other vertebrates, such as the zebrafish (Danio rerio). An understanding of stem cell mechanisms, such as how they are established, their self-renewal properties, and their recruitment to produce new cells is therefore important for the application of regenerative medicine. We use larval melanocyte regeneration following treatment with the melanocytotoxic drug MoTP to investigate these mechanisms in Melanocyte Stem Cell (MSC) regulation. In this paper, we show that the receptor tyrosine kinase, erbb3b, is required for establishing the adult MSC responsible for regenerating the larval melanocyte population. Both the erbb3b mutant and wild-type fish treated with the ErbB inhibitor, AG1478, develop normal embryonic melanocytes but fail to regenerate melanocytes after MoTP-induced melanocyte ablation. By administering AG1478 at different time points, we show that ErbB signaling is only required for regeneration prior to MoTP treatment and before 48 hours of development, consistent with a role in establishing MSCs. We then show that overexpression of kitla, the Kit ligand, in transgenic larvae leads to recruitment of MSCs, resulting in overproliferation of melanocytes. Furthermore, kitla overexpression can rescue AG1478-blocked regeneration, suggesting that ErbB signaling is required to promote the progression and specification of the MSC from a pre-MSC state. This study provides evidence that ErbB signaling is required for the establishment of adult MSCs during embryonic development. That this requirement is not shared with the embryonic melanocytes suggests that embryonic melanocytes develop directly, without proceeding through the ErbB-dependent MSC. Moreover, the shared requirement of larval melanocyte regeneration and metamorphic melanocytes that develops at the larval

  12. Non psammomatous melanocytic schwannoma presenting as a subcutaneous nodule: A rare presentation of a rare lesion

    PubMed Central

    Gulati, Harveen Kaur; Joshi, Avinash R.; Anand, Mani; Deshmukh, S. D.

    2016-01-01

    Melanocytic schwannoma (MS) is an extremely rare soft tissue tumor accounting for less than 1% of all primitive nerve sheath tumors, with a predilection for spinal nerve involvement. To date, only 20 cases of cutaneous/subcutaneous MS have been described in literature. Here, we describe a case of MS presenting as a subcutaneous nodule in a 22-year-old male in right thigh. On examination, the nodule measured 2.5 × 2.0 × 1.5 cm with overlying skin showing a bluish hue and an ulcer. With a preoperative diagnosis of hemangioma, the patient was taken up for wide local excision and was diagnosed as a case of non psammomatous melanocytic schwannoma based on clinical, histological, and immunohistochemical studies. Immunohistochemistry revealed positivity with S-100, HMB-45, and Melan A with pericellular Laminin positivity. Carney's syndrome was ruled out. MS needs to be differentiated from other pigmented lesions like pigmented neurofibroma, Bednar tumor, cellular blue neavus, and especially malignant melanoma, which has an obvious ominous prognosis. Since MS can show unpredictable behavior especially in absence of overt malignant features, a long term follow up with or without radiotherapy is recommended. PMID:27366278

  13. Positive and negative elements regulate a melanocyte-specific promoter.

    PubMed Central

    Lowings, P; Yavuzer, U; Goding, C R

    1992-01-01

    Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed. Images PMID:1321344

  14. Multiple roles of NF1 in the melanocyte lineage.

    PubMed

    Larribère, Lionel; Utikal, Jochen

    2016-07-01

    NF1 is a tumour suppressor gene, germline mutations of which lead to neurofibromatosis type 1 syndrome. Patients develop benign tumours from several types of cells including neural crest-derived cells. NF1 somatic mutations also occur in 15% of sporadic melanoma, a cancer originating from melanocytes. Evidence now suggests the involvement of NF1 mutations in melanoma resistance to targeted therapies. Although NF1 is ubiquitously expressed, genetic links between NF1 and genes involved in melanocyte biology have been described, implying the lineage-specific mechanisms. In this review, we summarize and discuss the latest advances related to the roles of NF1 in melanocyte biology and in cutaneous melanoma.

  15. Giant melanocytic nevi with neurocutaneous melanosis masquerading as neurofibromas

    PubMed Central

    Gowda, Vykuntaraju K.; Basude, Anita; Srinivas, Sahana M.; Bhat, Maya

    2016-01-01

    Neurocutaneous melanosis is congenital melanocytic nevus with neurological manifestations. We report a 4-year-old female child presenting with hyperpigmented and nodular skin lesion associated with developmental delay and convulsions. The child had multiple brownish-black nevi on the face and chest and giant melanocytic nevi on thoraco-abdomen, back, and gluteal region. Computed tomography scan of the brain showed calcification in the pons, right cerebellar hemisphere, and left medial temporal lobe. Skin biopsy done from nodular hyperpigmented site was suggestive of melanocytic nevi. Electroencephalogram showed multifocal epileptiform discharges. PMID:27857802

  16. Comparative Study of Efficacy of Epidermal Melanocyte Transfer Versus Hair Follicular Melanocyte Transfer in Stable Vitiligo

    PubMed Central

    Donaparthi, Navya; Chopra, Ajay

    2016-01-01

    Background: Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell suspension and latest to the extracted hair follicle outer root sheath cell suspension (EHFORSCS) transplantation. The progressive development from one technique to the other is always on a quest for the best. In the latest development, EHFORSCS, which is an enriched source of follicular inactive melanocyte (melanocyte stem cells), seems to be a good addition to the prevailing cell-based therapies for vitiligo. However, it needs to be explored further in larger, clinical trials. Methodology: A total of 11 patients with sixty stable vitiligo sites attending dermatology outpatient department were included for the open-labeled, prospective, comparative study. The sites were sequentially distributed into two groups of thirty each. Sites of one group were subjected to epidermal melanocyte transfer (EMT) and the others to hair follicular melanocyte transfer (HFMT). Response to treatment was evaluated on the basis of degree of repigmentation; final evaluation of area of involvement was done after completion of 6 months. Results: At the end of 6 months, repigmentation >90% was observed in 83.33% patches of EMT group and 43.33% in HFMT group. Repigmentation >75% was observed in 90% of patches in Group A and 43.34% of patches in Group B, respectively. There was statistically significant difference in the overall pigmentation between these two groups. Conclusion: Both noncultured autologous epidermal cell suspension transfer and noncultured EHFORSCS transfer are safe and effective surgical modalities in the management of stable vitiligo though EMT has shown a better response in the present study. Outer root sheath cell suspension transfer is a novel, minimally invasive technique in its nascent stage in the surgical management of vitiligo which requires further larger clinical trials for evaluation of its efficacy. PMID:27904182

  17. Borderline Personality in the Medical Setting

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Objective: Individuals with borderline personality disorder in mental health settings tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior. In contrast, it appears that individuals with borderline personality disorder in medical settings manifest physical symptoms that are medically difficult to substantiate. Through a review of the literature, we examine 2 symptom manifestations among patients with borderline personality in primary care and general medical settings—namely pain sensitivity and multiple somatic complaints. In addition to reviewing the research of others, we also highlight our own investigations into these 2 areas. Data Sources: We conducted a literature search of the PubMed database and a previous version of the PsycINFO search engine (no restrictions). Search terms included borderline personality, borderline personality disorder, personality disorders; chronic pain, pain, pain syndromes; and somatization disorder, Briquet’s syndrome, somatic preoccupation, somatic. Study Selection: Published articles related to borderline personality, pain and somatic symptoms (ie, somatization disorder, somatic preoccupation) were examined. Results: According to our review, the literature indicates higher-than-expected rates of borderline personality disorder among patients in primary care and general medical settings who present with chronic pain conditions and/or somatic preoccupation. Conclusions: Unlike patients with borderline personality disorder in mental health settings, who tend to present with relationship difficulties, mood instability/dysphoria, and overt self-harm behavior, patients with borderline personality disorder in primary care settings tend to present with unsubstantiated chronic pain of various types as well as somatic preoccupation. PMID:26644960

  18. Radioimmunoassay for. gamma. -melanocyte stimulating hormone

    SciTech Connect

    Shibasaki, T.; Ling, N.; Guillemin, R.

    1980-05-26

    A specific radioimmunoassay for ..gamma..-melanocyte stimulating hormone-like peptides was developed. An antiserum raised in rabbit to synthetic bovine ..gamma../sub 3/-MSH, one of the possible ..gamma..-MSH peptides, specifically recognizes the portion between His/sup 5/ and Arg/sup 14/ of ..gamma../sub 3/-MSH without significant cross-reaction with other synthetic ..gamma..-MSH-like peptides, ..cap alpha..-, ..beta..-MSH, adrenocorticotropin, and ..beta..-endorphin. The usable range of this RIA is 10 pg to 600 pg of synthetic ..gamma../sub 3/-MSH. Three immunoreactive ..gamma..-MSH peaks were thus found in gel permeation chromatography of the whole bovine pituitary extract.

  19. IMP-3 EXPRESSION IN BENIGN MELANOCYTIC NEVI, DYSPLASTIC NEVI AND MALIGNANT MELANOMA: PRELIMINARY FINDINGS IN BULGARIAN PATIENTS.

    PubMed

    Chokoeva, A A; Ananiev, J; Wollina, U; Tana, C; Lotti, T; Cardoso, J C; Tchernev, G

    2015-01-01

    IMP-3 is generally considered as an oncofetal protein, which plays a critical role in regulation of cell proliferation via an IGF-II-dependent pathway in K562 leukemia cells. IMP-3 expression has been detected in malignancies with various origins, while its appearance in adult tissue is generally considered abnormal, with some exceptions. IMP3 is also considered a prognostic biomarker in patients with renal cell carcinoma and clear-cell type ovarian carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma and in patients with poorly differentiated thyroid carcinoma and uterine cervical carcinomas, testicular cancer and malignant melanoma. To our knowledge, no more than 4 PubMed-indexed studies have investigated the expression of IMP-3 in melanocytic lesions, namely its role in the differentiation between benign and malignant neoplasms. We investigated the expression of IMP-3 in a small series of benign melanocytic lesions, dysplastic nevi and melanomas, aiming to establish its significance as a marker for their distinction, comparing the results with those from the literature. IMP- 3 immunostaining was performed in 30 melanocytic lesions: 10 malignant melanomas, 10 dysplastic nevi and 10 benign melanocytic nevi. Our results revealed expression in 20% of dysplastic lesions and 40% of melanoma cases, while none of the benign nevi showed positive expression. These data contradict some of the results from other studies and raise some questions regarding the correlation between IMP- 3 and the degree of dysplasia of melanocytic nevi, as well as its potential relationship with prognostic parameters in melanoma, including tumor thickness and mitotic rate. Our results suggest that IMP-3 expression could be only an auxiliary marker for differentiation between dysplastic nevi and benign nevi, since although it is not expressed in all dysplastic lesions, staining correlates with the degree of dysplasia/atypia. It seems that IMP-3 expression is not a useful

  20. Congenital melanocytic nevus: two clinicopathological forms.

    PubMed

    Magaña, Mario; Sánchez-Romero, Elizabeth; Magaña, Pablo; Beck-Magaña, Andrés; Magaña-Lozano, Mario

    2015-01-01

    Congenital melanocytic nevus (CMN) is a hamartomatous disease for which many attempts at classification have been proposed. This disease is relevant not only because of its functional and esthetic implications but also because it is a well-documented precursor to malignant melanoma. We performed a clinical and pathological prospective study of 200 cases of CMN and were able to identify 2 different forms of CMN, each one with biological, clinical, and histopathological features and criteria that are consistent and repeatable. We propose to name them types I and II. Type I CMN is the most common, usually, if not always, a single lesion, it consists of a plaque that involves only 1 anatomic region and does not go beyond it; type I CNM grows in proportion to the growth of the child, melanoma rarely develops from it, and when it does it usually arises at the dermoepidermal junction. Its histopathology shows cords, strands, nests, and single units of melanocytes spreading between collagen bundles only in the dermis and frequently the epidermis too, but without trespassing to the hypodermis, that is, it is superficial. Type II CMN is always made up of many lesions, one of them being very large and surrounded by many lesions; histopathologically, it involves not only the skin but also deeper structures, sometimes bone and central nervous system; therefore, it is deep; when melanoma develops, it does in the dermal component and usually from the largest plaque. This type of CMN is the one that develops neurocutaneous melanocytosis. This system is not only easy and logical but it also has biologic advantages and the clinical-pathological correlation and criteria are repeatable by clinicians and pathologists.

  1. Prevalence and implications of TERT promoter mutation in uveal and conjunctival melanoma and in benign and premalignant conjunctival melanocytic lesions.

    PubMed

    Koopmans, Anna E; Ober, Kimberley; Dubbink, Hendrikus J; Paridaens, Dion; Naus, Nicole C; Belunek, Stephan; Krist, Bart; Post, Edward; Zwarthoff, Ellen C; de Klein, Annelies; Verdijk, Robert M

    2014-08-26

    Hot-spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in cutaneous and conjunctival melanoma and are exceedingly rare in uveal melanoma. No information is available on the presence of these mutations in the conjunctival melanocytic precursor lesion primary acquired melanosis (PAM). We tested a cohort of uveal and conjunctival melanomas as well as conjunctival benign and premalignant melanocytic lesions for TERT promoter mutations in order to elucidate the role of these mutations in tumor progression. TERT promoter mutation analysis on fresh tumor DNA and DNA from formalin-fixed, paraffin-embedded specimens was performed by SNaPshot analysis in 102 uveal melanomas, 39 conjunctival melanomas, 26 PAM with atypia, 14 PAM without atypia, and 56 conjunctival nevi. Mutations of the TERT promoter were not identified in conjunctival nevi or PAM without atypia, but were detected in 2/25 (8%) of PAM with atypia and 16/39 (41%) of conjunctival melanomas. A single TERT promoter mutation was detected in 102 uveal melanomas (1%). We present the second documented case of TERT promoter mutation in uveal melanoma. In comparison with other types of melanoma, TERT promoter mutations occur at extremely low frequency in uveal melanoma. TERT promoter mutations are frequent in conjunctival melanoma and occur at lower frequency in PAM with atypia but were not detected in benign conjunctival melanocytic lesions. These findings favor a pathogenetic tumor progression role for TERT promoter mutations in conjunctival melanocytic lesions. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  2. Borderline resectable pancreatic cancer: conceptual evolution and current approach to image-based classification.

    PubMed

    Gilbert, J W; Wolpin, B; Clancy, T; Wang, J; Mamon, H; Shinagare, A B; Jagannathan, J; Rosenthal, M

    2017-09-01

    Diagnostic imaging plays a critical role in the initial diagnosis and therapeutic monitoring of pancreatic adenocarcinoma. Over the past decade, the concept of 'borderline resectable' pancreatic cancer has emerged to describe a distinct subset of patients existing along the spectrum from resectable to locally advanced disease for whom a microscopically margin-positive (R1) resection is considered relatively more likely, primarily due to the relationship of the primary tumor with surrounding vasculature. This review traces the conceptual evolution of borderline resectability from a radiological perspective, including the debates over the key imaging criteria that define the thresholds between resectable, borderline resectable, and locally advanced or metastatic disease. This review also addresses the data supporting neoadjuvant therapy in this population and discusses current imaging practices before and during treatment. A growing body of evidence suggests that the borderline resectable group of patients may particularly benefit from neoadjuvant therapy to increase the likelihood of an ultimately margin-negative (R0) resection. Unfortunately, anatomic and imaging criteria to define borderline resectability are not yet universally agreed upon, with several classification systems proposed in the literature and considerable variance in institution-by-institution practice. As a result of this lack of consensus, as well as overall small patient numbers and lack of established clinical trials dedicated to borderline resectable patients, accurate evidence-based diagnostic categorization and treatment selection for this subset of patients remains a significant challenge. Clinicians and radiologists alike should be cognizant of evolving imaging criteria for borderline resectability given their profound implications for treatment strategy, follow-up recommendations, and prognosis.

  3. Marginalization of borderline personality disorder.

    PubMed

    Kealy, David; Ogrodniczuk, John S

    2010-05-01

    Individuals with borderline personality disorder (BPD) face considerable difficulties, both in terms of their symptom and functional status, as well as in attempting to obtain professional help. Their exclusion from appropriate mental health care and opportunities for recovery can be examined using the social construct of marginalization. Pervasive attitudes among clinicians, health care administrators, and policy-makers perpetuate the marginalization of BPD within systems of mental health care. Patients with BPD may be regarded as not suffering from a legitimate disorder, comprising a minority of the clinical population, and/or being a chronic drain on health care resources. Lack of suitable mental health services may be rationalized based on these attitudes. Considerable development in the empirical understanding of BPD challenges these stigmatizing attitudes and calls for critical questioning of the marginalized status of patients with BPD.

  4. Borderline personality disorder: toward integration.

    PubMed

    Stein, Dan J

    2009-07-01

    Several psychiatric disorders, including borderline personality disorder (BPD), are characterized by emotional dysregulation and impulse dyscontrol. More specifically, symptoms in patients with BPD often occur within the context of disruptions in attachment and related distortions in cognitive-affective processing of the self and others. From a neurocircuitry perspective, findings include prefrontal hypoactivity, amygdala hyperreactivity, and alterations in prefrontal-limbic interaction. Molecular pathways relevant to these circuits include the serotonergic, noradrenergic, and dopaminergic systems, and there is some evidence that pharmacotherapy with agents that act on these systems may be useful. Given the disruptions in attachment and schemas of the self and others in BPD, establishing a therapeutic alliance is crucial while psychotherapy remains the cornerstone of an integrated approach to management.

  5. Patient With Borderline Personality Disorder

    PubMed Central

    Griffiths, Dorothy E.

    1989-01-01

    Every family practice includes people who are difficult to manage. Persons with a borderline personality disorder can be the most difficult of all. They will trust no one, and consequently few, if any, others will be able to tolerate their profoundly difficult interpersonal communication style. These patients will present to their family physician more and more often with a variety of somatic and emotional symptoms. They will demand, either verbally or silently, that these symptoms be relieved immediately. This increasing demand for immediate response may eventually cause the physician to reject the patient. An understanding of this condition and how it develops in infancy may enable the physician to help the patient. A family physician who can set appropriate limits to the patient's demands may slowly convince the patient that he can trust and not be hurt. PMID:21248944

  6. Monitoring human melanocytic cell responses to piperine using multispectral imaging

    NASA Astrophysics Data System (ADS)

    Samatham, Ravikant; Phillips, Kevin G.; Sonka, Julia; Yelma, Aznegashe; Reddy, Neha; Vanka, Meenakshi; Thuillier, Philippe; Soumyanath, Amala; Jacques, Steven

    2011-03-01

    Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.

  7. Adrenocorticotrophic and melanocyte-stimulating peptides in the human pituitary

    PubMed Central

    Scott, Alexander P.; Lowry, Philip J.

    1974-01-01

    The adrenocorticotrophic and melanocyte-stimulating peptides of the human pituitary were investigated by means of radioimmunoassay, bioassay and physicochemical procedures. Substantial amounts of adrenocorticotrophin and a peptide resembling β-lipotrophin were identified in pituitary extracts, but α-melanocyte-stimulating hormone, β-melanocyte-stimulating hormone and corticotrophin-like intermediate lobe peptide, which have been identified in the pars intermedia of pituitaries from other vertebrates, were not found. The absence of β-melanocyte-stimulating hormone appears to contradict previous chemical and radioimmunological studies. Our results suggest, however, that it is not a natural pituitary peptide but an artefact formed by enzymic degradation of β-lipotrophin during extraction. PMID:4368382

  8. Immunohistochemical diagnosis of canine oral amelanotic melanocytic neoplasms.

    PubMed

    Smedley, R C; Lamoureux, J; Sledge, D G; Kiupel, M

    2011-01-01

    Definitive diagnosis of canine oral melanocytic neoplasms is often difficult because of variability in pigmentation and cellular pleomorphism. These neoplasms can resemble carcinomas, sarcomas, and round cell neoplasms, which differ in prognosis and treatment. A variety of immunohistochemical antibodies have been used for diagnosis of melanocytic neoplasms in humans and dogs; however, sensitivity and specificity of many markers have not been determined in amelanotic melanocytic neoplasms in dogs. The authors investigated a comprehensive panel of immunohistochemical markers in 49 canine oral amelanotic melanocytic neoplasms--namely, Melan-A, PNL2, HMB-45, microphthalmia transcription factor (MiTF), S-100, tyrosine hydroxylase, tyrosinase, tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), and CD34. Ten well-differentiated cutaneous soft tissue spindle cell sarcomas were negative controls. Melan-A, PNL2, TRP-1, and TRP-2 were highly sensitive and 100% specific for the diagnosis of canine oral amelanotic melanocytic neoplasms. S-100 and MiTF showed high sensitivity but were less specific; that is, they also labeled a proportion of the soft tissue spindle cell sarcomas. HMB-45, tyrosinase, and tyrosine hydroxylase were 100% specific but had low sensitivities. CD34 did not label any of the melanocytic neoplasms but did label 80% of the soft tissue spindle cell sarcomas. A cost-effective and efficient immunodiagnostic cocktail containing antibodies against PNL2, Melan-A, TRP-1, and TRP-2 was created that had 100% specificity and 93.9% sensitivity in identifying canine oral amelanotic melanocytic neoplasms. The spindloid variant was the variant with the lowest sensitivity to the cocktail. The likelihood of correctly diagnosing canine oral amelanotic melanocytic neoplasms was dramatically higher when biopsy samples contained ample overlying and adjacent epithelium.

  9. Distinctive molecular responses to ultraviolet radiation between keratinocytes and melanocytes

    PubMed Central

    Sun, Xiaoyun; Kim, Arianna; Nakatani, Masashi; Shen, Yao; Liu, Liang

    2017-01-01

    Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm2) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin. PMID:27119462

  10. Melanocyte Stem Cells as Potential Therapeutics in Skin Disorders

    PubMed Central

    Lee, Ju Hee; Fisher, David E.

    2015-01-01

    Introduction Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSC) that are present in hair bulges or sub-bulge regions and function as melanocyte reservoirs. Quiescence, maintenance, activation, and proliferation of MelSC are controlled by specific activities in the microenvironment that can influence the differentiation and regeneration of melanocytes. Therefore, understanding MelSC and their niche may lead to use of MelSC in new treatments for various pigmentation disorders. Areas covered We describe here pathophysiological mechanisms by which melanocyte defects lead to skin pigmentation disorders such as vitiligo and hair graying. The development, migration, and proliferation of melanocytes and factors involved in the survival, maintenance, and regeneration of MelSC are reviewed with regard to the biological roles and potential therapeutic applications in skin pigmentation diseases. Expert Opinion MelSC biology and niche factors have been studied mainly in murine experimental models. Human MelSC markers or methods to isolate them are much less well understood. Identification, isolation and culturing of human MelSC would represent a major step toward new biological therapeutic options for patients with recalcitrant pigmentary disorders or hair graying. By modulating the niche factors for MelSC it may one day be possible to control skin pigmentary disorders and prevent or reverse hair graying. PMID:25104310

  11. Melanocyte stem cells as potential therapeutics in skin disorders.

    PubMed

    Lee, Ju Hee; Fisher, David E

    2014-11-01

    Melanocytes produce pigment granules that color both skin and hair. In the hair follicles melanocytes are derived from stem cells (MelSCs) that are present in hair bulges or sub-bulge regions and function as melanocyte reservoirs. Quiescence, maintenance, activation and proliferation of MelSCs are controlled by specific activities in the microenvironment that can influence the differentiation and regeneration of melanocytes. Therefore, understanding MelSCs and their niche may lead to use of MelSCs in new treatments for various pigmentation disorders. We describe here pathophysiological mechanisms by which melanocyte defects lead to skin pigmentation disorders such as vitiligo and hair graying. The development, migration and proliferation of melanocytes and factors involved in the survival, maintenance and regeneration of MelSCs are reviewed with regard to the biological roles and potential therapeutic applications in skin pigmentation diseases. MelSC biology and niche factors have been studied mainly in murine experimental models. Human MelSC markers or methods to isolate them are much less well understood. Identification, isolation and culturing of human MelSCs would represent a major step toward new biological therapeutic options for patients with recalcitrant pigmentary disorders or hair graying. By modulating the niche factors for MelSCs, it may one day be possible to control skin pigmentary disorders and prevent or reverse hair graying.

  12. Pigmented basal cell carcinoma: increased melanin or increased melanocytes?

    PubMed

    Brankov, Nikoleta; Prodanovic, Edward M; Hurley, M Yadira

    2016-12-01

    Studies on the precise cause of increased melanization in pigmented basal cell carcinomas (BCC) are limited. We aimed to determine whether the cause of melanization is from increased number of melanocytes or increased melanin pigment, and if there is a difference in the number of melanocytes on different sun-exposed locations. A retrospective review of 45 skin biopsies from January 2011 to February 2011 was performed; 30 were diagnosed as pigmented BCC and 15 as non-pigmented BCC. Immunohistochemistry for MART-1 (melanoma-associated antigen recognized by T-cell 1)/Melan-A (clone M2-7610 + M2-9E3; Leica Microsystems Inc. Buffalo Grove, IL, USA) from Biocare Medical (Concord, CA, USA) was performed on all biopsies. Associations between histopathologic features, number of melanocytes, location, and specific diagnoses were analyzed by Mann-Whitney U test. The mean melanocyte count per high powered field in pigmented BCCs from sun-exposed skin was 101.9 and from intermittently sun-exposed skin was 122.5, as compared to the controls (nodular non-pigmented BCC) of 27.4 (p = 0.002) and 34.9 (p = 0.002), respectively. Pigmented BCCs have a higher mean melanocyte count as compared to non-pigmented BCCs irrespective of location. Therefore, the pigment is not only due to increased melanin, but also due to increased melanocytes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro

    PubMed Central

    Xu, Ping; Chen, Jie; Lai, Ren-Sheng; Min, Zhong-Sheng

    2017-01-01

    Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 102 nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 102 and 103 nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 102 nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 102 nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression. PMID:28461770

  14. Pimecrolimus increases the melanogenesis and migration of melanocytes in vitro.

    PubMed

    Xu, Ping; Chen, Jie; Tan, Cheng; Lai, Ren-Sheng; Min, Zhong-Sheng

    2017-05-01

    Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, 10(2) nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, 10(2) and 10(3) nM significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to 10(2) nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at 10(2) nM. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

  15. Borderline Personality Disorder: Ontogeny of a Diagnosis

    PubMed Central

    Gunderson, John G.

    2011-01-01

    Objective The purpose of this article is to describe the development of the borderline personality disorder diagnosis, highlighting both the obstacles encountered and the associated achievements. Method On the basis of a review of the literature, the author provides a chronological account of the borderline construct in psychiatry, summarizing progress in decade-long intervals. Results Borderline personality disorder has moved from being a psychoanalytic colloquialism for untreatable neurotics to becoming a valid diagnosis with significant heritability and with specific and effective psychotherapeutic treatments. Nonetheless, patients with this disorder pose a major public health problem while they themselves remain highly stigmatized and largely neglected. Conclusions Despite remarkable changes in our knowledge about borderline personality disorder, increased awareness involving much more education and research is still needed. Psychiatric institutions, professional organizations, public policies, and reimbursement agencies need to prioritize this need. PMID:19411380

  16. Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

    PubMed

    Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

    2000-11-01

    Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

  17. BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION ASSOCIATED WITH RENAL CANCER: THE IMPORTANCE OF INDOCYANINE GREEN ANGIOGRAPHY AND EARLY DIAGNOSIS.

    PubMed

    Kniggendorf, Vinicius F; Neto, Elmar T; Maia, Elizabeth M; Grando, Joao P S; Bardal, Anne M C; Beato, Patrícia M M; Torres, Caroline C; Maia, Mauricio

    2016-11-17

    To report a case of bilateral diffuse uveal melanocytic proliferation associated with renal carcinoma and to illustrate the importance of ancillary examinations to early diagnosis and treatment. Clinical case report. A 56-year-old man reported a 3-day history of visual impairment and scotoma in the right eye. An ophthalmoscopic examination, visual field test, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and systemic evaluation were performed. Fundus examination showed multiple nevus-like uveal pigmented lesions bilaterally. Optical coherence tomography showed a subfoveal serous retinal detachment and focal loss of the retinal pigment epithelium with adjacent areas of retinal pigment epithelial thickening in the right eye, explaining the scotoma on the visual field examination. Indocyanine green angiography showed multiple round areas of hypofluorescence corresponding to the nevus-like pigmented tumors seen on funduscopy, and retinal pigment epithelium damage corresponding to hypoautofluorescence on fundus autofluorescence imaging and window defects points seen on fluorescein angiography bilaterally. After bilateral diffuse uveal melanocytic proliferation diagnosis, a systemic workup showed clear cell carcinoma in the left kidney. Owing to the tumoral size, chemotherapy was administered. Renal carcinoma associated with bilateral diffuse uveal melanocytic proliferation is rare, and the patterns observed in the ancillary examinations, including indocyanine green angiography, are useful for early-stage diagnosis and immediate referral for systemic investigation and treatment.

  18. Defense Mechanisms Associated with Borderline Personality Disorder

    PubMed Central

    Zanarini, Mary C.; Weingeroff, Jolie L.; Frankenburg, Frances R.

    2011-01-01

    This study assessed the defensive functioning of 290 criteria-defined borderline patients and compared it to that of 72 patients with other forms of axis II psychopathology. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was administered to 362 axis II inpatients diagnosed using semistructured interviews of proven reliability. Borderline patients had significantly higher scores than axis II comparison subjects on three of the four defense styles assessed by the DSQ: self-sacrificing, maladaptive action, and image-distorting defenses. They also had significantly higher scores than axis II comparison subjects on eight of the 19 defense mechanisms studied. More specifically, borderline patients had significantly higher scores on one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image- distorting/borderline defenses (projective identification and splitting). In contrast, axis II comparison subjects had a significantly higher score than borderline patients on one mature defense (suppression). When all significant defenses were considered together, three were found to be significant predictors of a borderline diagnosis: acting out, emotional hypochondriasis, and undoing. This model has both good sensitivity (.95) and positive predictive power (.86). Taken together, the results of this study suggest that the defensive profile of borderline patients is distinct from that of patients with other forms of axis II pathology. They also suggest that the defensive triad of acting out, emotional hypochondriasis, and undoing may serve as a useful clinical marker for the borderline diagnosis, particularly in settings where the base rate of the disorder is high. PMID:19379090

  19. [Concepts of the borderline personality disorders].

    PubMed

    Ogłodek, Ewa; Araszkiewicz, Aleksander

    2011-08-01

    For many years, the borderline personality disorders have mainly been researched in terms of psychoanalytical theories, such as theories on relations with the object. Nowadays, there are three kinds of concepts that are distinguishable. The first ones are those which are group models, serving attempts to made characteristic sets of qualities, represented by individuals suffering from the borderline personality disorders, more precise. The remaining concepts are models of conflict and deficit, which explain complicated mechanisms of interactions of social, psychological and biological factors, and therefore, contribute to better understanding of the genesis of the symptoms of this disorder. Upon the basis of the attempts made so far in the field of describing the borderline personality disorders, one may indicate certain criteria, representative for the entire group of individuals with this diagnosis, regardless of the assumptions applicable to the genesis of the disorder and its symptoms, even though the population of the infirm suffering from the borderline personality disorders is not internally homogenous. The interest of psychologists, attempting to describe the borderline personality disorders, is focused upon certain sets of qualities, presented as the examples of descriptive models. Among the researchers, working on the issues of the borderline personality disorders in this manner, there are: Gunderson, Kernberg, Kohut, Winnicot, Guntrip, Fairbaim, Adler and Buie.

  20. Neurochemical alterations associated with borderline personality disorder.

    PubMed

    Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi

    2015-01-01

    In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder.

  1. Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

    PubMed

    Gamo, R; Floristan, U; Pampín, A; Caro, D; Pinedo, F; López-Estebaranz, J L

    2015-10-01

    The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma.

  2. Nanostructural change of human melanocytes stimulated with α-melanocyte stimulating hormone observed by atomic force microscopy.

    PubMed

    Shin, Min Kyung; Lim, Hee Kyeong; Kang, Boo Kyoung; Lee, Gi-Ja; Uhm, Yun-Kyung; Lee, Mu-Hyoung

    2014-01-01

    It is well known that α-melanocyte stimulating hormone (α-MSH) induces melanization, but structural changes of melanocytes after α-MSH exposure are not well known. This study investigated the serial morphologic changes of human cultured melanocytes after stimulation with α-MSH using atomic force microscopy (AFM). Cultured human melanocytes were treated with α-MSH for 7 days. Contact mode AFM images were obtained using a NANOstation II and fixed melanocytes were scanned in PBS solution at a resolution of 512 × 512 pixels, at a scan speed of 0.4 line/s. The surface roughness and pore-like structures of the melanocytes were measured from topographic images using the Scanning Probe Imaging Processor. The surface roughness of cell body did not change significantly over time. All three roughness parameters (Sa, Sq, Sz) inside the pore-like structures on the dendrites increased significantly. The number of pore-like structures increased and the length and the breadth of pore-like structures also increased gradually. Pore-like structures changed statistically significantly in response to α-MSH stimulation. Further study will be needed to clarify whether the nature of pore-like structures is related to movement of melanosomes.

  3. Specific expression of Gsta4 in mouse cochlear melanocytes: a novel role for hearing and melanocyte differentiation.

    PubMed

    Uehara, Shigeyuki; Izumi, Yoshiko; Kubo, Yuko; Wang, Chi Chiu; Mineta, Katsuhiko; Ikeo, Kazuho; Gojobori, Takashi; Tachibana, Masayoshi; Kikuchi, Toshihiko; Kobayashi, Toshimitsu; Shibahara, Shigeki; Taya, Choji; Yonekawa, Hiromichi; Shiroishi, Toshihiko; Yamamoto, Hiroaki

    2009-02-01

    Mammalian pigment cells produce melanin as the main pigment. Melanocytes, one of the two types of mammalian pigment cells, differentiate from the neural crest and migrate to a variety of organs during development. Melanocytes exist not only in the skin but also in other sites such as the cochlea where they are essential for hearing. Mitf(mi-bw) is one of the known recessive alleles of the mouse microphthalmia-associated transcription factor (Mitf) locus, which is essential for the development of pigment cells. Homozygous Mitf(mi-bw)/Mitf(mi-bw) mice have a completely white coat with black eyes and are deaf due to the lack of melanocytes. By comparing gene expression profiles in cochleae of wild-type and Mitf(mi-bw)/Mitf(mi-bw) mice, we now demonstrate the specific expression of glutathione S-transferase alpha 4 (Gsta4) in the stria vascularis. Gsta4 encodes one of the cytosolic glutathione S-transferases (GSTs) which participate in detoxification processes of many tissues. This gene is specifically expressed in intermediate cells of the stria vascularis, suggesting a novel function for cochlear melanocytes. Moreover, among mammalian pigment cells, expression of Gsta4 was restricted to cochlear melanocytes, suggesting that melanocytes in various tissues differentiate from one another depending on their location.

  4. TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF

    PubMed Central

    Loftus, Stacie K.; Liu, Huan; Sompallae, Ramakrishna; Gildea, Derek E.; Santana, Juan F.; Manak, J. Robert; Pavan, William J.; Williams, Trevor; Cornell, Robert A.

    2017-01-01

    Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the “master regulator” of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of melanin in mitfa

  5. TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF.

    PubMed

    Seberg, Hannah E; Van Otterloo, Eric; Loftus, Stacie K; Liu, Huan; Bonde, Greg; Sompallae, Ramakrishna; Gildea, Derek E; Santana, Juan F; Manak, J Robert; Pavan, William J; Williams, Trevor; Cornell, Robert A

    2017-03-01

    Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the "master regulator" of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of melanin in mitfa

  6. Borderline and Psychotic Adolescents: Borderline Symptomatology from Childhood--Actual Therapeutic Approach

    ERIC Educational Resources Information Center

    Aarkrog, Tove

    1977-01-01

    The symptoms of, and possible treatments for 21 borderline and psychotic adolescents who had suffered from borderline psychoses in childhood were examined from a developmental point of view. It was concluded that therapeutic possibilities exist. Some childhood symptoms could be used directly in treatment, while others disappeared with general…

  7. Muse Cells Derived from Dermal Tissues Can Differentiate into Melanocytes.

    PubMed

    Tian, Ting; Zhang, Ru-Zhi; Yang, Yu-Hua; Liu, Qi; Li, Di; Pan, Xiao-Ru

    2017-02-07

    The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively. These Muse cells differentiated into melanocytes in differentiation medium. The SSEA-3-positive cells were scattered in the basement membrane zone and the dermis, with comparatively more in the sebaceous glands, vascular and sweat glands, as well as the outer root sheath of hair follicles, the dermal papillae, and the hair bulbs. Muse cells, which have the ability to self-renew, were obtained from scalp dermal fibroblasts by flow cytometry sorting with an anti-SSEA-3 antibody. The results of RT-PCR, Western blot, and immunofluorescence staining showed that the expression levels of Oct4, Nanog, Sox2, and Klf4 mRNAs and proteins in Muse cells were significantly different from their parental dermal fibroblasts. Muse cells differentiated into melanocytes when cultured in melanocyte differentiation medium, and the Muse cell-derived melanocytes expressed the melanocyte-specific marker HMB45. Muse cells could be obtained by flow cytometry from primary cultures of scalp dermal fibroblasts, which possessed the ability of pluripotency and self-renewal, and could differentiate into melanocytes in vitro.

  8. Attachment and borderline personality disorder.

    PubMed

    Fonagy, P

    2000-01-01

    The author outlines his concept of reflective function or mentalization, which is defined as the capacity to think about mental states in oneself and in others. He presents evidence to suggest that the capacity for reflective awareness in a child's caregiver increases the likelihood of the child's secure attachment, which in turn facilitates the development of mentalization in the child. He proposes that a secure attachment relationship offers the child a chance to explore the mind of the caregiver, and in this way to learn about minds; he formulates this model of the birth of the psychological self as a variation on the Cartesian cogito: "My caregiver thinks of me as thinking and therefore I exist as a thinker." This model is then applied to provide insight into some personality-disordered individuals who were victims of childhood abuse. The author proposes (1) that individuals who experience early trauma may defensively inhibit their capacity to mentalize to avoid having to think about their caregiver's wish to harm them; and (2) that some characteristics of severe borderline personality disorder may be rooted in developmental pathology associated with this inhibition. He offers evidence for and some qualifications of this model, and argues that the therapeutic effect of psychoanalysis depends on its capacity to activate patients' ability to evolve an awareness of mental states and thus find meaning in their own and other people's behavior.

  9. Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression.

    PubMed

    Einspahr, Janine G; Thomas, Tracy L; Saboda, Kathylynn; Nickolof, Brian J; Warneke, James; Curiel-Lewandrowski, Clara; Ranger-Moore, James; Duckett, Laura; Bangert, Jerry; Fruehauf, John P; Alberts, David S

    2007-12-01

    A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers. Markers of angiogenesis that included expression of the vascular endothelial growth factor A (VEGF-A) and microvessel density counts (MVD) were evaluated in 13 prospectively collected benign nevi (BN) and 19 DN from 16 individuals and in a comparison group of 17 primary melanomas (16 archival samples and 1 prospective melanoma). VEGF expression in melanocytic cells (mean+/-standard error [SE]) was low or absent in BN (3.4+/-1.4), increased significantly in DN (41.0+/-10.1; P=.0003 for BN vs DN), and increased further in primary melanoma (119.9+/-28.3; P = .06 for DN vs melanoma). MVD using CD31 (mean+/-SE [percentage x intensity]) followed a similar pattern with similarity between BN (2.6+/-0.7; N=13) and DN (2.2+/-0.8; N=19; P=.4 for BN vs DN), whereas primary melanomas were significantly higher (39.4+/-6.4; N=17; P=.0001 for BN or DN vs melanoma). In a prospective setting, the current data suggested that increased VEGF-A expression in DN may be a good indicator of preneoplastic change in melanocytic lesions with the potential for improving the understanding and prevention of the transformation of DN to melanoma. Copyright (c) 2007 American Cancer Society.

  10. Malevolence, splitting, and parental ratings by borderlines.

    PubMed

    Baker, L; Silk, K R; Westen, D; Nigg, J T; Lohr, N E

    1992-04-01

    Malevolent object relations as well as splitting have long been considered by psychodynamic theorists as central features of borderline personality disorder. We tested the hypotheses that borderlines would a) perceive their parents more negatively than both nonborderline major depressive patients and nonpatient normal controls, and b) split their representations of their parents into opposites more than the comparison subjects. Borderlines (N = 31), who were identified by the Diagnostic Interview for Borderlines, Research Diagnostic Criteria major depressives (N = 15), and nonpatient controls (N = 14) were asked to rate each parent on the Adjective Check List (ACL; Gough and Heilbrun, 1983). Seven ACL scales were studied: Favorable, Unfavorable, Critical Parent, Nurturing Parent, Nurturance, Aggression, and Dominance. Correlations were performed between scores for mother and father on the various scales for each of the three cohorts. Analysis of variance and one-way t-tests with Bonferroni correction were used to test group differences. Borderlines rated their parents, especially their fathers, not only as more unfavorable on negative scales than depressives or normals, but as less favorable on positive scales than the comparison groups. Analysis of covariance revealed that a significant portion of the variance in father scores, but not in mother scores, was related to age of respondent and history of sexual abuse. While borderlines did not appear to split their parents into one good and one bad parent, they did show significantly less correlation between parents on the Favorable scale when compared with either depressives or normal subjects. The results imply that borderlines have a greater tendency to view the world in negative, malevolent ways than to split their object representations.

  11. Adrenal incidentaloma, borderline elevations of urine or plasma metanephrine levels, and the "subclinical" pheochromocytoma.

    PubMed

    Lee, James A; Zarnegar, Rasa; Shen, Wen T; Kebebew, Electron; Clark, Orlo H; Duh, Quan-Yang

    2007-09-01

    To assess the risk of pheochromocytoma in patients with borderline-elevated urine or plasma metanephrine levels. Retrospective review. University tertiary care center. Forty-two consecutive patients with adrenal incidentalomas (defined as adrenal tumors identified during routine imaging for another condition) who were treated at the UCSF (University of California, San Francisco) Medical Center between January 1, 1995, and July 31, 2005. Patients with genetic syndromes were excluded. Laparoscopic adrenalectomy for adrenal incidentaloma based on size criteria and preoperative hormonal test results. Urine or plasma metanephrine and catecholamine levels, tumor size, and presence of pheochromocytoma. Of 42 patients, 14 (33%) had a pheochromocytoma (11 of whom had clear-cut elevations in urine or plasma metanephrine levels defined as greater than 2 times the upper limit of normal) and 28 did not. Ten of the 42 patients (24%) had borderline elevations in urine or plasma metanephrine levels (defined as 1-2 times the upper limit of normal), 3 of whom had a pheochromocytoma (30%). Of patients with borderline elevations, mean +/- SD tumor size was 5.4 +/- 3.1 and 4.8 +/- 1.9 cm for patients with and without pheochromocytoma, respectively (P = .37). In these 10 patients, no clinical factors (age, sex, hypertension, presence of symptoms, number of antihypertensive medications, preoperative hemodynamics, or size of tumor on computed tomographic scan) allowed differentiation between those with and without pheochromocytoma. Thirty percent of patients with adrenal incidentaloma and borderline-elevated urine or plasma metanephrine levels had a pheochromocytoma. Clinical factors cannot distinguish between those with and without pheochromocytoma. In this group of patients, we advocate either routine alpha-blockade preoperatively or further diagnostic tests to better characterize the tumor.

  12. Alpha-melanocyte-stimulating hormone suppresses oxidative stress through a p53-mediated signaling pathway in human melanocytes.

    PubMed

    Kadekaro, Ana Luisa; Chen, Juping; Yang, Jennifer; Chen, Shuna; Jameson, Joshua; Swope, Viki B; Cheng, Tan; Kadakia, Madhavi; Abdel-Malek, Zalfa

    2012-06-01

    Epidermal melanocytes are skin cells specialized in melanin production. Activation of the melanocortin 1 receptor (MC1R) on melanocytes by α-melanocyte-stimulating hormone (α-MSH) induces synthesis of the brown/black pigment eumelanin that confers photoprotection from solar UV radiation (UVR). Contrary to keratinocytes, melanocytes are slow proliferating cells that persist in the skin for decades, in an environment with high levels of UVR-induced reactive oxygen species (ROS). We previously reported that in addition to its role in pigmentation, α-MSH also reduces oxidative stress and enhances the repair of DNA photoproducts in melanocytes, independent of melanin synthesis. Given the significance of ROS in carcinogenesis, here we investigated the mechanisms by which α-MSH exerts antioxidant effects in melanocytes. We show that activation of the MC1R by α-MSH contributes to phosphorylation of p53 on serine 15, a known requirement for stabilization and activation of p53, a major sensor of DNA damage. This effect is mediated by the cAMP/PKA pathway and by the activation of phosphoinositide 3-kinase (PI3K) ATR and DNA protein kinase (DNA-PK). α-MSH increases the levels of 8-oxoguanine DNA glycosylase (OGG1) and apurinic apyrimidinic endonuclease 1 (APE-1/Ref-1), enzymes essential for base excision repair. Nutlin-3, an HDM2 inhibitor, mimicked the effects of α-MSH resulting in reduced phosphorylation of H2AX (γ-H2AX), a marker of DNA damage. Conversely, the p53 inhibitor pifithrin-α or silencing of p53 abolished the effects of α-MSH and augmented oxidative stress. These results show that p53 is an important target of the downstream MC1R signaling that reduces oxidative stress and possibly malignant transformation of melanocytes.

  13. Wnt inhibitory factor (WIF)-1 promotes melanogenesis in normal human melanocytes.

    PubMed

    Park, Tae Jun; Kim, Misun; Kim, Hyeran; Park, Sun Yi; Park, Kyoung-Chan; Ortonne, Jean-Paul; Kang, Hee Young

    2014-01-01

    Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with perilesional normal skin. In this study, the expression and functional roles of WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ-cultured human skin. These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes.

  14. Characterization of two novel small molecules targeting melanocyte development in zebrafish embryogenesis.

    PubMed

    Chen, Lu; Ren, Xi; Liang, Fang; Li, Song; Zhong, Hanbing; Lin, Shuo

    2012-07-01

    Melanocytes are pigment cells that are closely associated with many skin disorders, such as vitiligo, piebaldism, Waardenburg syndrome, and the deadliest skin cancer, melanoma. Through studies of model organisms, the genetic regulatory network of melanocyte development during embryogenesis has been well established. This network also seems to be shared with adult melanocyte regeneration and melanoma formation. To identify chemical regulators of melanocyte development and homeostasis, we screened a small-molecule library of 6000 compounds using zebrafish embryos and identified five novel compounds that inhibited pigmentation. Here we report characterization of two compounds, 12G9 and 36E9, which disrupted melanocyte development. TUNEL assay indicated that these two compounds induced apoptosis of melanocytes. Furthermore, compound 12G9 specifically inhibited the viability of mammalian melanoma cells in vitro. These two compounds should be useful as chemical biology tools to study melanocytes and could serve as drug candidates against melanocyte-related diseases. © 2012 John Wiley & Sons A/S.

  15. Effect of streptomycin on melanogenesis and antioxidant status in melanocytes.

    PubMed

    Wrześniok, Dorota; Beberok, Artur; Otręba, Michał; Buszman, Ewa

    2013-11-01

    Streptomycin is an aminoglycoside antibiotic with an antituberculosis activity commonly used in clinical practice due to its good antimicrobial characteristics. A well-known undesirable side effect of this drug is ototoxicity, which may be caused by overproduction of reactive oxygen species and loss of melanocytes in the inner ear. The aim of this study was to examine the effect of streptomycin on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMa-LP). Streptomycin induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be ~5.0 mM. It has been shown that streptomycin causes inhibition of tyrosinase activity and reduces melanin content in human melanocytes in a concentration-dependent manner. Significant changes in the activity of cellular antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase were also stated. The results obtained in vitro may explain a potential role of melanocytes and melanin in the causative mechanisms of aminoglycosides ototoxic effects in vivo.

  16. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin.

  17. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia.

    PubMed

    Pollock, Pamela M; Cohen-Solal, Karine; Sood, Raman; Namkoong, Jin; Martino, Jeffrey J; Koganti, Aruna; Zhu, Hua; Robbins, Christiane; Makalowska, Izabela; Shin, Seung-Shick; Marin, Yari; Roberts, Kathleen G; Yudt, Laura M; Chen, Amy; Cheng, Jun; Incao, Arturo; Pinkett, Heather W; Graham, Christopher L; Dunn, Karen; Crespo-Carbone, Steven M; Mackason, Kerine R; Ryan, Kevin B; Sinsimer, Daniel; Goydos, James; Reuhl, Kenneth R; Eckhaus, Michael; Meltzer, Paul S; Pavan, William J; Trent, Jeffrey M; Chen, Suzie

    2003-05-01

    To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.

  18. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation

    PubMed Central

    2014-01-01

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis. There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease. In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation. PMID:24661309

  19. Lineage specific transcriptional regulation of DICER by MITF in melanocytes

    PubMed Central

    Levy, Carmit; Khaled, Mehdi; Robinson, Kathleen C.; Veguilla, Rosa A.; Chen, Po-Hao; Yokoyama, Satoru; Makino, Eiichi; Lu, Jun; Larue, Lionel; Beermann, Friedrich; Chin, Lynda; Bosenberg, Marcus; Song, Jun. S.; Fisher, David E.

    2010-01-01

    Summary DICER is a central regulator of microRNA maturation. However little is known about mechanisms regulating its expression in development or disease. While profiling miRNA expression in differentiating melanocytes, two populations were observed: some upregulated at the pre-miRNA stage, and others upregulated as “mature” miRNAs (with stable pre-miRNA levels). Conversion of pre-miRNAs to fully processed miRNAs appeared to be dependent upon stimulation of DICER expression—an event found to occur via direct transcriptional targeting of DICER by the melanocyte master transcriptional regulator MITF. MITF binds and activates a conserved regulatory element upstream of DICER’s transcriptional start site upon melanocyte differentiation. Targeted KO of DICER is lethal to melanocytes, at least partly via DICER-dependent processing of the pre-miRNA-17~92 cluster thus targeting BIM, a known pro-apoptotic regulator of melanocyte survival. These observations highlight a central mechanism underlying miRNA regulation which could exist for other cell types during development. PMID:20550935

  20. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation.

    PubMed

    Feller, Liviu; Masilana, Aubrey; Khammissa, Razia A G; Altini, Mario; Jadwat, Yusuf; Lemmer, Johan

    2014-03-24

    The presence of melanocytes in the oral epithelium is a well-established fact, but their physiological functions are not well defined. Melanin provides protection from environmental stressors such as ultraviolet radiation and reactive oxygen species; and melanocytes function as stress-sensors having the capacity both to react to and to produce a variety of microenvironmental cytokines and growth factors, modulating immune, inflammatory and antibacterial responses. Melanocytes also act as neuroendocrine cells producing local neurotransmitters including acetylcholine, catecholamines and opioids, and hormones of the melanocortin system such as proopiomelanocortin, adrenocorticotropic hormone and α-melanocyte stimulating hormone, that participate in intracellular and in intercellular signalling pathways, thus contributing to tissue homeostasis.There is a wide range of normal variation in melanin pigmentation of the oral mucosa. In general, darker skinned persons more frequently have oral melanin pigmentation than light-skinned persons. Variations in oral physiological pigmentation are genetically determined unless associated with some underlying disease.In this article, we discuss some aspects of the biophysiology of oral melanocytes, of the functions of melanin, and of physiological oral pigmentation.

  1. Mining Gene Expression Signature for the Detection of Pre-Malignant Melanocytes and Early Melanomas with Risk for Metastasis

    PubMed Central

    de Souza, Camila Ferreira; Xander, Patrícia; Monteiro, Ana Carolina; Silva, Amanda Gonçalves dos Santos; da Silva, Débora Castanheira Pereira; Mai, Sabine; Bernardo, Viviane; Lopes, José Daniel; Jasiulionis, Miriam Galvonas

    2012-01-01

    Background Metastatic melanoma is a highly aggressive skin cancer and currently resistant to systemic therapy. Melanomas may involve genetic, epigenetic and metabolic abnormalities. Evidence is emerging that epigenetic changes might play a significant role in tumor cell plasticity and metastatic phenotype of melanoma cells. Principal findings In this study, we developed a systematic approach to identify genes implicated in melanoma progression. To do this, we used the Affymetrix GeneChip Arrays to screen 34,000 mouse transcripts in melan-a melanocytes, 4C pre-malignant melanocytes, 4C11− non-metastatic and 4C11+ metastatic melanoma cell lines. The genome-wide association studies revealed pathways commonly over-represented in the transition from immortalized to pre-malignant stage, and under-represented in the transition from non-metastatic to metastatic stage. Additionally, the treatment of cells with 10 µM 5-aza-2′-deoxycytidine (5AzaCdR) for 48 hours allowed us to identify genes differentially re-expressed at specific stages of melan-a malignant transformation. Treatment of human primary melanocytes with the demethylating agent 5AzaCdR in combination to the histone deacetylase inhibitor Trichostatin A (TSA) revealed changes on melanocyte morphology and gene expression which could be an indicator of epigenetic flexibility in normal melanocytes. Moreover, changes on gene expression recognized by affecting the melanocyte biology (NDRG2 and VDR), phenotype of metastatic melanoma cells (HSPB1 and SERPINE1) and response to cancer therapy (CTCF, NSD1 and SRC) were found when Mel-2 and/or Mel-3-derived patient metastases were exposed to 5AzaCdR plus TSA treatment. Hierarchical clustering and network analyses in a panel of five patient-derived metastatic melanoma cells showed gene interactions that have never been described in melanomas. Significance Despite the heterogeneity observed in melanomas, this study demonstrates the utility of our murine melanoma

  2. Pigmented odontogenic tumors: Adding color to diagnosis?

    PubMed Central

    Bhanu, Udhay; Kulkarni, Rasika; Boaz, Karen; Srikant, N

    2014-01-01

    Melanocytes are neural crest derivatives that exhibit a ubiquitous presence in the epidermis. They determine the complexion of an individual and most importantly, provide a barrier against ultraviolet radiations from the sun. Their presence in the oral cavity is a consistent finding, especially in the gingiva and buccal mucosa of the dark complexioned. Melanocytes occasionally form a part of the histology of a variety of odontogenic cysts and tumors. How these cells make their way into the lesional tissue and the diagnostic relevance of their presence remains elusive. This write up attempts to trace the path melanocytes take to find themselves within odontogenic tumors and also offer possible explanations for the same. PMID:25948995

  3. Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity.

    PubMed

    Bin, Bum-Ho; Kim, Dae-Kyum; Kim, Nan-Hyung; Choi, Eun-Jeong; Bhin, Jinhyuk; Kim, Sung Tae; Gho, Yong Song; Lee, Ai-Young; Lee, Tae Ryong; Cho, Eun-Gyung

    2016-05-01

    Skin melanocytes are activated by exposure to UV radiation to secrete melanin-containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin-containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf

    PubMed Central

    Taylor, Kerrie L.; Lister, James A.; Zeng, Zhiqiang; Ishizaki, Hironori; Anderson, Caroline; Kelsh, Robert N.; Jackson, Ian J.; Patton, E. Elizabeth

    2011-01-01

    Coordination of cell proliferation and differentiation is crucial for tissue formation, repair and regeneration. Some tissues, such as skin and blood, depend on differentiation of a pluripotent stem cell population, whereas others depend on the division of differentiated cells. In development and in the hair follicle, pigmented melanocytes are derived from undifferentiated precursor cells or stem cells. However, differentiated melanocytes may also have proliferative capacity in animals, and the potential for differentiated melanocyte cell division in development and regeneration remains largely unexplored. Here, we use time-lapse imaging of the developing zebrafish to show that while most melanocytes arise from undifferentiated precursor cells, an unexpected subpopulation of differentiated melanocytes arises by cell division. Depletion of the overall melanocyte population triggers a regeneration phase in which differentiated melanocyte division is significantly enhanced, particularly in young differentiated melanocytes. Additionally, we find reduced levels of Mitf activity using an mitfa temperature-sensitive line results in a dramatic increase in differentiated melanocyte cell division. This supports models that in addition to promoting differentiation, Mitf also promotes withdrawal from the cell cycle. We suggest differentiated cell division is relevant to melanoma progression because the human melanoma mutation MITF4TΔ2B promotes increased and serial differentiated melanocyte division in zebrafish. These results reveal a novel pathway of differentiated melanocyte division in vivo, and that Mitf activity is essential for maintaining cell cycle arrest in differentiated melanocytes. PMID:21771814

  5. Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf.

    PubMed

    Taylor, Kerrie L; Lister, James A; Zeng, Zhiqiang; Ishizaki, Hironori; Anderson, Caroline; Kelsh, Robert N; Jackson, Ian J; Patton, E Elizabeth

    2011-08-01

    Coordination of cell proliferation and differentiation is crucial for tissue formation, repair and regeneration. Some tissues, such as skin and blood, depend on differentiation of a pluripotent stem cell population, whereas others depend on the division of differentiated cells. In development and in the hair follicle, pigmented melanocytes are derived from undifferentiated precursor cells or stem cells. However, differentiated melanocytes may also have proliferative capacity in animals, and the potential for differentiated melanocyte cell division in development and regeneration remains largely unexplored. Here, we use time-lapse imaging of the developing zebrafish to show that while most melanocytes arise from undifferentiated precursor cells, an unexpected subpopulation of differentiated melanocytes arises by cell division. Depletion of the overall melanocyte population triggers a regeneration phase in which differentiated melanocyte division is significantly enhanced, particularly in young differentiated melanocytes. Additionally, we find reduced levels of Mitf activity using an mitfa temperature-sensitive line results in a dramatic increase in differentiated melanocyte cell division. This supports models that in addition to promoting differentiation, Mitf also promotes withdrawal from the cell cycle. We suggest differentiated cell division is relevant to melanoma progression because the human melanoma mutation MITF(4T)(Δ)(2B) promotes increased and serial differentiated melanocyte division in zebrafish. These results reveal a novel pathway of differentiated melanocyte division in vivo, and that Mitf activity is essential for maintaining cell cycle arrest in differentiated melanocytes.

  6. Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines.

    PubMed

    Yamada, Takaaki; Hasegawa, Seiji; Inoue, Yu; Date, Yasushi; Arima, Masaru; Yagami, Akiko; Iwata, Yohei; Abe, Masamichi; Takahashi, Masayuki; Yamamoto, Naoki; Mizutani, Hiroshi; Nakata, Satoru; Matsunaga, Kayoko; Akamatsu, Hirohiko

    2014-03-01

    Solar lentigines (SLs) are characterized by hyperpigmented macules, commonly seen on sun-exposed areas of the skin. Although it has been reported that an increase in the number of melanocytes and epidermal melanin content was observed in the lesions, the following questions remain to be answered: (1) Is acceleration of melanogenesis in the epidermis caused by an increased number of melanocytes or the high melanogenic potential of each melanocyte? (2) Why does the number of melanocytes increase? To elucidate the pathogenic mechanism of SLs by investigating the number, melanogenic potential and proliferation status of the melanocyte lineage in healthy skin and SL lesions. Immunostaining for melanocyte lineage markers (tyrosinase, MART-1, MITF, and Frizzled-4) and a proliferation marker, Ki67, was performed on skin sections, and the obtained images were analyzed by image analysis software. The expression level of tyrosinase to MART-1 of each melanocyte was significantly higher in SL lesions than healthy skin. The numbers of melanocytes in the epidermis, melanoblasts in the hair follicular infundibulum and melanocyte stem cells in the bulge region were increased in SL; however, no significant difference was observed in the Ki67-positive rate of these cells. The melanogenic potential of each melanocyte was elevated in SL lesions. It was suggested that the increased number of melanocytes in the SL epidermis might be attributed to the abnormal increase of melanocyte stem cells in the bulge. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Expression and activity of alcohol and aldehyde dehydrogenases in melanoma cells and in melanocytes.

    PubMed

    Amann, Philipp M; Hofmann, Claudia; Freudenberger, Muriel; Holland-Cunz, Stefan; Eichmüller, Stefan B; Bazhin, Alexandr V

    2012-03-01

    Disturbances in vitamin A metabolism are an important attribute of some cancer cells. Most evidence point that these disturbances lead to decreasing of the retinoic acid concentration in tumor cells. Up to now, in benign and malignant skin cells the features of vitamin A metabolism with its participating enzymes are not entirely understood. Alcohol and aldehyde dehydrogenases (ALDH) are involved in the retinol metabolism, oxidizing retinol, and retinal in retinoic acid or reducing retinal in retinol. In this work we investigated the expression and enzymatic activity of alcohol and ALDH in melanoma cells compared to their benign counterparts. We demonstrated that melanoma cell lines and melanocytes despite similar pattern of the enzyme expression, show different general ALDH activity. Retinal, the substrate of ALDH, could stimulate the ALDH activity through up-regulation of retinaldehyde dehydrogenase 1 and aldehyde dehydrogenase 6. Furthermore, we found that retinoids regulate alcohol dehydrogenase activity, probably via effects on alcohol dehydrogenase expression at the post-transcriptional level. We suggest that melanoma cells in contrast to melanocytes should favor the retinal reduction over its oxidation. The decreasing cellular amount of the precursor molecules of retinoic acid could result in a changed gene regulation in melanoma cells. Copyright © 2011 Wiley Periodicals, Inc.

  8. Metaplastic breast carcinoma; melanocytic variant, a very rare tumour

    PubMed Central

    Nzegwu, Martin A.; Sule, Emmanuel; Uzoigwe, Joseph; Achi, Franklyn

    2015-01-01

    Metaplastic breast carcinoma (MBC) is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Melanocytic variant was first described by Ruffolo et al. in 1997. We report a case of MBC, melanocytic variant, in a 57-year-old Nigerian female who presented with a left breast mass 8 cm in diameter in the upper outer quadrant, hard and gradually increase in size to become painful. Breast examination showed gross asymmetry. Left breast was oedematous and shiny with extensive peau d'orange. No palpable axillary nodes were seen. Chest X-ray and abdominal ultrasound scan showed no involvement. Breast biopsy revealed an invasive metaplastic ductal carcinoma with melanocytic differentiation. PMID:25666364

  9. Induction of nerve growth factor receptors on cultured human melanocytes

    SciTech Connect

    Peacocke, M.; Yaar, M.; Mansur, C.P.; Chao, M.V.; Gilchrest, B.A. )

    1988-07-01

    Normal differentiation and malignant transformation of human melanocytes involve a complex series of interactions during which both genetic and environmental factors play roles. At present, the regulation of these processes is poorly understood. The authors have induced the expression of nerve growth factor (NGF) receptors on cultured human melanocytes with phorbol 12-tetradecanoate 13-acetate and have correlated this event with the appearance of a more differentiated, dendritic morphology. Criteria for NGF receptor expression included protein accumulation and cell-surface immunofluorescent staining with a monoclonal antibody directed against the human receptor and induction of the messenger RNA species as determined by blot-hybridization studies. The presence of the receptor could also be induced by UV irradiation or growth factor deprivation. The NGF receptor is inducible in cultured human melanocytes, and they suggest that NGF may modulate the behavior of this neural crest-derived cell in the skin.

  10. N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of UV-induced melanoma in mice

    PubMed Central

    Cotter, Murray A.; Thomas, Joshua; Cassidy, Pamela; Robinette, Kyle; Jenkins, Noah; Scott, R. Florell; Leachman, Sancy; Samlowski, Wolfram E.; Grossman, Douglas

    2008-01-01

    UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In melan-a cells, a mouse melanocyte line, NAC (1–10 mM) conferred protection from several UV-induced oxidative sequelae including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine (8-OG), and depletion of free reduced thiols (primarily glutathione). Mice transgenic for hepatocyte growth factor and Survivin, previously shown to develop melanoma following a single neonatal dose of UV irradiation, were administered NAC (7 mg/ml, mother’s drinking water) transplacentally and through nursing until two weeks after birth. Delivery of NAC in this manner reduced thiol depletion and blocked formation of 8-OG in skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared to control mice (21 vs. 14 weeks, p=0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma, and suggest that NAC may be useful as a chemopreventive agent. PMID:17908992

  11. Accurately Diagnosing and Treating Borderline Personality Disorder

    PubMed Central

    Gentile, Julie P.; Correll, Terry L.

    2010-01-01

    The high prevalence of comorbid bipolar and borderline personality disorders and some diagnostic criteria similar to both conditions present both diagnostic and therapeutic challenges. This article delineates certain symptoms which, by careful history taking, may be attributed more closely to one of these two disorders. Making the correct primary diagnosis along with comorbid psychiatric conditions and choosing the appropriate type of psychotherapy and pharmacotherapy are critical steps to a patient's recovery. In this article, we will use a case example to illustrate some of the challenges the psychiatrist may face in diagnosing and treating borderline personality disorder. In addition, we will explore treatment strategies, including various types of therapy modalities and medication classes, which may prove effective in stabilizing or reducing a broad range of symptomotology associated with borderline personality disorder. PMID:20508805

  12. A quantum probability perspective on borderline vagueness.

    PubMed

    Blutner, Reinhard; Pothos, Emmanuel M; Bruza, Peter

    2013-10-01

    The term "vagueness" describes a property of natural concepts, which normally have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno's sorites paradox. We will discuss the psychology of vagueness, especially experiments investigating the judgment of borderline cases and contradictions. In the theoretical part, we will propose a probabilistic model that describes the quantitative characteristics of the experimental finding and extends Alxatib's and Pelletier's () theoretical analysis. The model is based on a Hopfield network for predicting truth values. Powerful as this classical perspective is, we show that it falls short of providing an adequate coverage of the relevant empirical results. In the final part, we will argue that a substantial modification of the analysis put forward by Alxatib and Pelletier and its probabilistic pendant is needed. The proposed modification replaces the standard notion of probabilities by quantum probabilities. The crucial phenomenon of borderline contradictions can be explained then as a quantum interference phenomenon.

  13. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  14. Presence of cytoadhesins (IIb-IIIa-like glycoproteins) on human metastatic melanomas but not on benign melanocytes.

    PubMed

    McGregor, B C; McGregor, J L; Weiss, L M; Wood, G S; Hu, C H; Boukerche, H; Warnke, R A

    1989-10-01

    Glycoproteins IIb and IIIa, a heterodimer complex, play a vital role in blood platelet aggregation and are members of a wide family of membrane receptors known as integrins or cytoadhesins. Cellular interaction to extracellular matrix (ECM) adhesive proteins is mediated by integrins. Certain tumor cells are known to interact with ECM and blood platelets in the process of metastasis. However, it is not known if tumor cells, compared with their normal counterparts, acquire IIb-IIIa-like receptors to help them in their metastatic spread. In this study, monoclonal antibodies directed against the IIb-IIIa platelet glycoprotein complex were used on frozen biopsies of normal and various tumor tissues to detect the presence of these integrins. These studies demonstrate the presence of IIb-IIIa-like glycoproteins on the cells of metastatic malignant melanoma but not on benign melanocytes and rarely on other tumors. The presence of integrins on melanomas may help explain their propensity for frequent metastasis.

  15. Unblending Borderline Personality and Bipolar Disorders.

    PubMed

    di Giacomo, Ester; Aspesi, Flora; Fotiadou, Maria; Arntz, Arnoud; Aguglia, Eugenio; Barone, Lavinia; Bellino, Silvio; Carpiniello, Bernardo; Colmegna, Fabrizia; Lazzari, Marina; Lorettu, Liliana; Pinna, Federica; Sicaro, Aldo; Signorelli, Maria Salvina; Clerici, Massimo

    2017-03-07

    Borderline Personality (BPD) and Bipolar (BP) disorders stimulate an academic debate between their distinction and the inclusion of Borderline in the Bipolar spectrum. Opponents to this inclusion attribute the important differences and possible diagnostic incomprehension to overlapping symptoms. We tested 248 Borderline and 113 Bipolar patients, consecutively admitted to the Psychiatric Unit, through DSM-IV Axis I and II Disorders (SCID-I/II), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS) and Borderline Personality Disorder Severity Index-IV (BPDSI-IV). All the tests statistically discriminated the disorders (p < 0.0001). Overlapping symptoms resulted significantly different (impulsivity = 5.32 in BPD vs 1.55 in BP, p < 0.0001; emotional instability = 7.11 in BPD vs 0.55 in BP, p < 0.0001) and the range of their scores gives the opportunity for an even more precise discrimination. Distinctive traits (e.g. irritability or sexual arousal) are also discussed in order to try to qualify the core of these disorders to a higher degree. Comorbidity proves to be extremely small (3.6%). However, Borderline patients with manic features offer a privileged point of view for a deeper analysis. This allows for the possibility of a more precise examination of the nature and load of each symptom. Borderline Personality and Bipolar Disorders can be distinguished with high precision using common and time-sparing tests. The importance of discriminating these clinical features may benefit from this evidence.

  16. Management considerations for giant congenital melanocytic nevi in adults.

    PubMed

    Green, Margaret C; Mitchum, Marsha D; Marquart, Jason D; Bingham, Jonathan L

    2014-04-01

    Giant congenital melanocytic nevi (GCMN) are a rare type of melanocytic nevus that covers a large body surface, often with satellite nevi scattered on the rest of the skin. There are several complications associated with GCMN, including malignant melanoma and neurocutaneous melanosis. The management of GCMN is very complex because of the cosmetic appearance and the associated psychological distress, the risk of severe complications, and the need for long-term follow-up. We report a case of a 43-year-old active-duty female with a GCMN reporting new and symptomatic satellite lesions with atypical features on dermoscopy.

  17. Dysfunction of melanocytes in photoleukomelanoderma following photosensitivity caused by hydrochlorothiazide.

    PubMed

    Masuoka, Eriko; Bito, Toshinori; Shimizu, Hideki; Nishigori, Chikako

    2011-12-01

    We report a 68-year-old Japanese man who developed photoleukomelanoderma following prolonged photosensitivity caused by hydrochlorothiazide. He showed complete recovery from the leukomelanoderma with the discontinuation of the responsive drug and with topical application of tacrolimus hydrate and corticosteroid. Histological and immunohistochemical examination revealed that there were no melanin-positive cells in the hypopigmented area, despite the presence of melanocytes. These results and the clinical course indicate that leukomelanoderma is postulated temporary dysfunction of melanocytes. We also conducted a review of previous case reports regarding drug-induced photoleukomelanoderma. © 2011 John Wiley & Sons A/S.

  18. The risk of cutaneous melanoma in melanocytic nevi*

    PubMed Central

    Fernandes, Nurimar Conceição

    2013-01-01

    The data on melanoma associaed with melanocytic nevus are controversial. A longitudinal prospective study of 107 cases of cutaneous melanoma revealed that 9 (8.4%) cases were presumed to be linked to a precursor lesion, but only in 1 (0.9%) out of these cases the histopathological examination showed an associated melanocytic nevus. The vague information of a preexisting lesion of cutaneous melanoma is not sufficient to consider it a tumour precursor and it requires histopathological evidence to confirm the diagnosis. PMID:23739702

  19. Neoadjuvant chemoradiation therapy for borderline pancreatic adenocarcinoma: report of two cases.

    PubMed

    Galindo, José; Gabrielli, Mauricio; Guerra, Juan Francisco; Cassina, Juan Carlos; Garrido, Marcelo; Jarufe, Nicolás; Borghero, Yerko; Madrid, Jorge; Zoroquiain, Pablo; Roa, Juan Carlos; Martínez, Jorge

    2013-02-05

    Pancreatic cancer remains as one of the most aggressive human neoplasms, with overall poor survival rates. Radical surgery of the primary lesion is the best option for treatment. Borderline resectable pancreatic tumors (BRPT), defined as partial involvement of peripancreatic vasculature, may benefit from neoadjuvant therapy. We report on the first two BRPT cases treated with neoadjuvant chemoradiation at our institution. Preoperative CT and MRI demonstrated pancreatic tumors encasing the porto-mesenteric confluence suggestive of BRPT. Patients received neoadjuvant chemotherapy (gemcitabine/cisplatin), followed by radiochemotherapy. After treatment, follow-up images demonstrated tumor downsize, allowing for the tumors to be considered then as resectable. They underwent partial pancreatoduodenectomies (Whipple procedure). In case 1, histopathology revealed a complete, margin-free resection, whereas in case 2 there was a complete pathological response, with no evidence of residual tumor. According to the literature, our initial experience using neoadjuvant chemoradiotherapy on BRPT allowed us to downsize the tumor and, subsequently, to perform a curative surgery.

  20. Immunoselection in vivo: independent loss of MHC class I and melanocyte differentiation antigen expression in metastatic melanoma.

    PubMed

    Jäger, E; Ringhoffer, M; Altmannsberger, M; Arand, M; Karbach, J; Jäger, D; Oesch, F; Knuth, A

    1997-04-10

    Peptides derived from melanocyte differentiation antigens have been identified as targets for MHC class I-restricted cytolytic T lymphocytes (CTLs) in human melanoma Regression of antigen-expressing tumors as well as selection of antigen-loss variants in the presence of antigen-specific CTLs have previously been reported. In the present study, we determined the expression of the melanocyte differentiation antigens Melan A/MART-1 and tyrosinase by mRNA analysis and by immunohistochemical staining with the monoclonal antibodies (MAbs) A103 and T311. Co-expression of Melan A/MART-1 and tyrosinase was detected by both methods in 18/20 melanomas tested. However, immunohistochemistry provided additional information on intensity and microheterogeneity of antigen expression that cannot be detected by mRNA analysis as a molecular basis for the escape from CTL recognition of antigen-negative tumor cells. Comparative analysis of repeated biopsies of metastatic lesions in 5 HLA-A2+ patients showed a gradual loss of Melan A/MART-1 expression in 4/5 and of tyrosinase in 2/5 samples in association with tumor progression. However, 3 of these patients had growing antigen-positive tumors in the presence of antigen-specific CTLs. This led us to assess the expression of MHC class I, the essential restriction element for CTL recognition, and of HLA-A2. We found an unexpectedly high frequency of MHC class I-negative tumors (9/20). Loss of MHC class I expression was detected in 3/5 progressive tumors and isolated loss of HLA-A2 in 1/5 tumors. Our results suggest that strategies enhancing the expression of MHC class I and tumor-associated antigens need to be considered in attempts at making vaccination more effective.

  1. Human fibroblasts treated with hydrogen peroxide stimulate human melanoblast proliferation and melanocyte differentiation, but inhibit melanocyte proliferation in serum-free co-culture system.

    PubMed

    Hirobe, Tomohisa; Shibata, Tatako; Sato, Kiyoshi

    2016-12-01

    Oxidative stress caused by hydrogen peroxide (H2O2) elicits harmful effects on human melanocytes such as DNA damage and cell death. On the contrary, H2O2 is known to possess beneficial effects on melanocytes. However, mechanisms of the beneficial effects of H2O2 on melanocytes have not been fully understood, especially the indirect effects on melanocyte proliferation and differentiation from cells constituting surrounding tissue environment such as fibroblasts. The aim of this study was to clarify whether H2O2-treated human fibroblasts affect the proliferation and differentiation of human melanocytes using serum-free co-culture system. Epidermal melanoblasts and melanocytes were co-cultured with H2O2-treated or control fibroblasts in serum-free culture media. The effects of H2O2-treated fibroblasts were detected by changes in the proliferation and differentiation of melanoblasts/melanocytes. H2O2-treated fibroblasts stimulated the proliferation of melanoblasts and the differentiation, melanogenesis, and dendritogenesis of melanocytes, but inhibited the proliferation of melanocytes. In the melanocytes co-cultured with H2O2-treated fibroblasts, the expression of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and KIT was increased, whereas TYRP2 and microphthalmia-associated transcription factor showed no change. These results suggest that H2O2-treated fibroblasts can produce and release some mitogenic and melanogenic factors toward melanoblasts in addition to some proliferation-inhibiting factors toward melanocytes. The stimulation of melanocyte differentiation seems to be performed through the upregulation of TYR, TYRP1, and KIT. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. The borderline diagnosis in adolescents: symptoms and developmental history.

    PubMed

    Ludolph, P S; Westen, D; Misle, B; Jackson, A; Wixom, J; Wiss, F C

    1990-04-01

    Adult criteria for borderline personality disorder distinguished a group of 27 inpatient adolescent girls from 23 nonborderline inpatient female comparison subjects. The two groups were compared on retrospectively assessed variables measuring psychological, familial, and constitutional factors. Variables most likely to predict borderline personality disorder included history of disrupted attachments, maternal neglect, maternal rejection, grossly inappropriate parental behavior, number of mother and father surrogates, physical abuse, and sexual abuse. Families of borderline adolescents were chronically disrupted, particularly during the patients' early childhoods. The traumatic childhood experiences of the borderline adolescents were similar to those of adults with borderline personality disorder in recent studies.

  3. Site-specific migration of human fetal melanocytes in volar skin.

    PubMed

    Nakamura, Motoki; Fukunaga-Kalabis, Mizuho; Yamaguchi, Yuji; Furuhashi, Takuya; Nishida, Emi; Kato, Hiroshi; Mizuno, Toshihiko; Sugiura, Mayumi; Morita, Akimichi

    2015-05-01

    Melanocytes originate from the neural crest and migrate ventrally from the dorsal neural tube during embryogenesis. How human melanocytes locate at their suitable positions during embryogenesis, however, is unclear. Although a growing body of evidence indicates that melanocytes, melanoblasts, and melanocyte stem cells are closely related to hair follicles, little is known about volar skin. The aim of this study was to observe skin development during human fetal period and clarify the site-specific migration process of human fetal sole melanocytes. We obtained 4-mm punch biopsies from the scalp, back, abdomen, and right sole of 36 aborted fetuses (gestational age 12-21 weeks). We compared the migration process between hairly areas and volar areas by immunohistochemical staining. Immunohistochemical examination revealed that gp100 (HMB-45) sensitively detects human melanocytes in embryogenesis. Melanocytes were present at the epidermal base, where hair placodes/buds form at 12-15 weeks gestation. Fetal melanocytes in hair follicles are supplied from the epidermis. In volar skin, melanocytes originally localize only in the acrosyringium, where they migrate deeper into with gland development at 16-18 weeks gestation. Palmoplantar melanocyte migration and maturation processes differ considerably from those of the other hairy skin sites. Eccrine sweat glands seem to have a central role in the palmoplantar melanocyte migration process, similar to the role of hair follicles in hairy sites. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. [Frequency of benign tumors at the Hospital General "Dr. Manuel Gea Gonzalez". Record review between 2000-2006].

    PubMed

    Káram-Orantes, Marcia; Fonte-Avalos, Verónica; Zuloaga-Salcedo, Soraya; Domínguez-Cherit, Judith

    2007-01-01

    Benign skin neoplasms are defined as autonomous growing tissue unrelated to normal growing of the skin, that persist even after the originating stimulus dissapears. Almost all human beings have a certain number of benign cutaneous neoplasms and many never seek medical attention. There is a dearth of information regarding the frequency of these tumors. The aim of this study was to record the number of benign tumors studied at the Dermatology Department of a medical facility. A retrospective study analyzed medical records between 2000 and 2006. We included year of admission, number of biopsies, sex, age, tumor location, histological and clinical diagnoses. We analyzed 9,436 biopsies of which 3,765 constituted benign neoplasms; 595 were not included and our total sample was 3,170 tumors. The most frequent tumors according to histopathological diagnoses in descending order were: melanocytic, cutaneous cysts, fibrous tumors, vascular tumors, epidermal tumors, fat tumors, tumors with hair differentiation, neural tumors, glandular tumors, tumors with sebaceous differentiation, cartilage and bone tumors, and smooth muscle tumors. The most common benign tumors were: Melanocytic nevi, epidermal cysts, seborrheic keratoses, pyogenic granulomas, lipomas and dermatofibromas. Melanocytes represented by melanocytic nevi (junctional, intradermic and compound) were the most frequent benign neoplasms, followed by epidermoid cysts. Our results illustrate the most common benign tumors observed in a dermatology department.

  5. Families of borderline patients: a psychoeducational approach.

    PubMed

    Gunderson, J G; Berkowitz, C; Ruiz-Sancho, A

    1997-01-01

    The development of the psychoeducational form of treatment described in this article has been prompted by changes in our understanding of borderline psychopathology and changes in the health care system in which these patients are treated. After reviewing these background changes, the authors describe the treatment itself, its form, its purpose, and the preliminary suggestions of its effectiveness.

  6. Relationship Enhancement Therapy with Borderline Personality.

    ERIC Educational Resources Information Center

    Waldo, Michael; Harman, Marsha J.

    1993-01-01

    Briefly describes Borderline Personality Disorder (BPD) and explains Relationship Enhancement (RE) marital and family therapy. Provides rationale for understanding BPD as manifestation of lack of differentiation in intimate relationships, followed by explanation of how RE fosters differentiation between partners. Includes case study. (Author/NB)

  7. The Relationship Between Borderline Personality and Obesity

    PubMed Central

    Sansone, Lori A.

    2013-01-01

    Obesity is a significant health problem in the United States. Therefore, it is extremely important to understand potential clinical associations with obesity, including personality pathology. From studies of personality disorders in other types of eating pathology, it appears that restrictive personality disorders (e.g., obsessive-compulsive disorder) are associated with restrictive eating pathology (e.g., anorexia nervosa, restricting type) whereas impulsive personality disorders (e.g., borderline personality disorder) are associated with impulsive eating pathology (e.g., anorexia nervosa, binge-eating/purging type; bulimia nervosa, binge eating disorder). Because binge eating disorder is oftentimes associated with an obese status, it seems likely that borderline personality disorder may also be associated with obesity. At the present time, there appear to be nine accessible studies in this area, comprising 639 obese individuals. While rates of borderline personality disorder in these studies vary from 2.2 to 94.1 percent, 10 of 19 measures detected this disorder at rates of 25 percent or higher, and the average of all percentages is 26.9 percent. Findings appear to support the association between impulsive personality pathology and impulsive eating pathology, and underscore that a significant minority of obese individuals may suffer from borderline personality disorder. PMID:23696958

  8. Borderline Intellectual Functioning: A Systematic Literature Review

    ERIC Educational Resources Information Center

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-01-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…

  9. Borderline Intellectual Functioning: A Systematic Literature Review

    ERIC Educational Resources Information Center

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-01-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health…

  10. Phyllodes tumor: a clinicopathologic and immunohistochemical study of 30 cases.

    PubMed

    Esposito, Nicole Nicosia; Mohan, Deepak; Brufsky, Adam; Lin, Yan; Kapali, Malathy; Dabbs, David J

    2006-10-01

    Phyllodes tumors (PTs) of the breast are biphasic neoplasms composed of epithelium and a spindle-cell stroma. Currently, PTs are classified as benign, borderline, or malignant based on histopathologic features. However, histologic classification does not always predict outcome. Objective.-To determine the prognostic value of a variety of clinicopathologic features and immunoreactivities in PTs. Sixteen benign, 8 borderline, and 6 malignant PTs with follow-up were examined for reactivity across a panel of immunohistochemical stains, including c-Kit, endothelin 1, p16, p21, p53, and Ki-67. Clinicopathologic features, including stromal cellularity, mitotic rate, and margin status, were also assessed. Tumor variables were compared among tumor subgroups and between tumors that did and did not recur. Of the 30 PTs, 4 recurred (1 benign, 2 borderline, 1 malignant). One patient with a malignant tumor died of metastatic disease 34 months after initial diagnosis. The overall positive rate of c-Kit immunoreactivity was 13% in benign, 63% in borderline, and 67% in malignant PTs. Endothelin 1 epithelial cytoplasmic staining was seen in 100% of benign, 50% of borderline, and 17% of malignant PTs. Additionally, p16, p21, p53, and Ki-67 were differentially expressed among benign, borderline, and malignant tumors. Positive surgical resection margins was the only variable that significantly predicted recurrent disease (P = .02). Stromal c-Kit positivity and epithelial endothelin 1 negativity are more often associated with malignant PTs; however, only positive margin status is significantly associated with tumor behavior.

  11. Differential effects of selenite and selenate on human melanocytes, keratinocytes, and melanoma cells.

    PubMed

    Bandura, Laura; Drukala, Justyna; Wolnicka-Glubisz, Agnieszka; Björnstedt, Mikael; Korohoda, Wlodzimierz

    2005-04-01

    Among the substances that attracted the attention of oncologists in recent years are selenium-containing compounds, both inorganic and organic. Several epidemiological studies have shown an inverse correlation between selenium intake and cancer incidence. In the experiments reported here, we compared the effects of 2 inorganic selenium-containing salts that differed in the level of selenium oxidation, selenite IV and selenate VI. We tested the effects of these 2 compounds on cell survival and growth, cell cycle processing, cell morphology, cytoskeleton, and lipid peroxidation in 3 human skin cell types: normal keratinocytes, melanocytes, and human melanoma cell line HTB140. The different effects of selenite and selenate on the viability, growth, and morphology of normal cells and tumor cells are reported and provide a base for future research and treatment of some neoplastic diseases. The attention is paid to cell apoptosis induced by selenite and not by selenate, and the effects of tested substances on thioredoxin reductase system are postulated.

  12. Genome-wide transcriptome analysis of human epidermal melanocytes

    PubMed Central

    Haltaufderhyde, Kirk D.; Oancea, Elena

    2015-01-01

    Because human epidermal melanocytes (HEMs) provide critical protection against skin cancer, sunburn, and photoaging, a genome-wide perspective of gene expression in these cells is vital to understanding human skin physiology. In this study we performed high throughput sequencing of HEMs to obtain a complete data set of transcript sizes, abundances, and splicing. As expected, we found that melanocyte specific genes that function in pigmentation were among the highest expressed genes. We analyzed receptor, ion channel and transcription factor gene families to get a better understanding of the cell signalling pathways used by melanocytes. We also performed a comparative transcriptomic analysis of lightly versus darkly pigmented HEMs and found 16 genes differentially expressed in the two pigmentation phenotypes; of those, only one putative melanosomal transporter (SLC45A2) has known function in pigmentation. In addition, we found 166 genes with splice isoforms expressed exclusively in one pigmentation phenotype, 17 of which are genes involved in signal transduction. Our melanocyte transcriptome study provides a comprehensive view and may help identify novel pigmentation genes and potential pharmacological targets. PMID:25451175

  13. Traumatic iridial extrusion mimicking a conjunctival melanocytic neoplasm

    PubMed Central

    Zoroquiain, Pablo; Ganimi, Maria SB; Alghamdi, Sarah; Burnier, Julia V; Aldrees, Sultan S; Burnier, Miguel N

    2016-01-01

    Conjunctival melanoma is a rare malignant tumour of the eye. Its diagnosis represents a challenge for general pathologists due to low exposure to ocular biopsies and a broad differential diagnosis. In addition, conjunctival samples are often small and are associated with a high frequency of artefacts due to their processing. Here, we present the first case to date of a traumatic iridial extrusion masquerading as a conjunctival melanocytic neoplasm. An 83-year-old Asian man presented with a conjunctival-pigmented nodule surrounded by an area of diffuse pigmentation. Histopathology revealed in the nodule a well-demarcated lesion composed of spindle shaped melanocytes with thick-walled blood vessels. At higher magnification, the blood vessels were composed of thick walls with collagen fibres in an onion-skin-like arrangement. The histological findings were consistent with extruded iridial tissue. The map biopsies of the flat, pigmented lesion showed melanocytic cell proliferation with dendritic processes restricted to the lamina propria without any epithelial involvement, consistent with ocular melanocytosis. The diagnosis of conjunctival melanocytic lesions is challenging, and non-neoplastic conditions should always be included in the differential diagnosis. Pathologists should correlate clinicopathological findings and be familiar with the normal histology in order to achieve the correct diagnosis. PMID:26913071

  14. Traumatic iridial extrusion mimicking a conjunctival melanocytic neoplasm.

    PubMed

    Zoroquiain, Pablo; Ganimi, Maria Sb; Alghamdi, Sarah; Burnier, Julia V; Aldrees, Sultan S; Burnier, Miguel N

    2016-01-01

    Conjunctival melanoma is a rare malignant tumour of the eye. Its diagnosis represents a challenge for general pathologists due to low exposure to ocular biopsies and a broad differential diagnosis. In addition, conjunctival samples are often small and are associated with a high frequency of artefacts due to their processing. Here, we present the first case to date of a traumatic iridial extrusion masquerading as a conjunctival melanocytic neoplasm. An 83-year-old Asian man presented with a conjunctival-pigmented nodule surrounded by an area of diffuse pigmentation. Histopathology revealed in the nodule a well-demarcated lesion composed of spindle shaped melanocytes with thick-walled blood vessels. At higher magnification, the blood vessels were composed of thick walls with collagen fibres in an onion-skin-like arrangement. The histological findings were consistent with extruded iridial tissue. The map biopsies of the flat, pigmented lesion showed melanocytic cell proliferation with dendritic processes restricted to the lamina propria without any epithelial involvement, consistent with ocular melanocytosis. The diagnosis of conjunctival melanocytic lesions is challenging, and non-neoplastic conditions should always be included in the differential diagnosis. Pathologists should correlate clinicopathological findings and be familiar with the normal histology in order to achieve the correct diagnosis.

  15. Molecular biology of normal melanocytes and melanoma cells.

    PubMed

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya

    2013-08-01

    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  16. Adipose-Derived Stem Cells Improve Efficacy of Melanocyte Transplantation in Animal Skin

    PubMed Central

    Lim, Won-Suk; Kim, Chang-Hyun; Kim, Ji-Young; Do, Byung-Rok; Kim, Eo Jin; Lee, Ai-Young

    2014-01-01

    Vitiligo is a pigmentary disorder induced by a loss of melanocytes. In addition to replacement of pure melanocytes, cocultures of melanocytes with keratinocytes have been used to improve the repigmentation outcome in vitiligo treatment. We previously identified by in vitro studies, that adipose-derived stem cells (ADSCs) could be a potential substitute for keratinocytes in cocultures with melanocytes. In this study, the efficacy of pigmentation including durability of grafted melanocytes and short-term safety was examined in the nude mouse and Sprague-Dawley rat after grafting of primary cultured human melanocytes, with or without different ratios of primary cultured human ADSCs. Simultaneous grafting of melanocytes and ADSCs, which were separately cultured and mixed on grafting at the ratios of 1:1, 1:2, or 1:3, showed better efficacy than that of pure melanocytes. Grafting of melanocytes cocultured with ADSCs resulted in a similar outcome as the grafting of cell mixtures. Skin pigmentation by melanocytes : ADSCs at the ratios of 1:1 and 1:2 was better than at 1:3. No significant difference was observed between the 1-week and 2-week durations in coculturing. Time-course microscopic examination showed that the grafted melanocytes remained a little longer than 6-week post-grafting. No inflammatory cell infiltration was observed in the grafted skin and no melanocytes were detectable in other organs. Collectively, grafting of melanocytes and ADSCs was equally safe and more effective than grafting of melanocytes alone. Despite the absence of significant differences in efficacy between the group of 1:1 and that of 1:2 ratio, 1:2 ratio for 1-week coculturing may be better for clinical use from the cost-benefit viewpoint. PMID:25143812

  17. [The melanocyte and the eye: a review with special emphasis on the cornea].

    PubMed

    Rohrbach, J M; Süsskind, D; Grüb, M

    2012-01-01

    Various publications especially from the field of dermatology have indicated in the recent years that the melanocyte is a "multitalent" with--besides UV-protection--(neuro-)humoral and immunological functions. Moreover, the melanocyte could play a role as a scavenger of free radicals or in pressure perception, so that it could even perhaps be part of the "intraocular pressure sensor". It is generally assumed that the cornea is devoid of melanocytes under physiological conditions. However, to the best of our knowledge a systematic investigation with a larger quantity of specimens has not been performed thus far. 103 corneal specimens (whole eyes, corneal explants with different corneal diseases, corneoscleral donor buttons) and 13 pterygia (corneal part) were studied immunohistochemically using the monoclonal antibody Melan A which is specific for melanocytes. In healthy cornea melanocytes are found in the limbal area. In the corneal periphery, up to 1 mm distant from the limbus, the melanocytes disappear so that the mid-peripheral and the central epithelium of the cornea are devoid of melanocytes. Under pathological conditions (dystrophies, scars, ulcers) there is only exceptionally an invasion of melanocytes into the mid-peripheral corneal epithelium. The central epithelium almost always remains free of melanocytes even in various corneal diseases. In more than 50% of the pterygia melanocytes can be found in the epithelium. Under certain, pathological conditions melanocytes can settle in more central regions of the corneal epithelium. Thus, the very few "corneal melanomas" described in the literature could have theoretically developed within the cornea itself (and not within the limbus). Obviously, the cornea possesses mechanisms to inhibit centripetal migration of melanocytes perhaps via a (still hypothetic) "corneal melanocyte suppression factor" ("CoMeSuF"). To identify this factor will be the task for the coming years. If this factor is really existent it

  18. Optimal management of common acquired melanocytic nevi (moles): current perspectives

    PubMed Central

    Sardana, Kabir; Chakravarty, Payal; Goel, Khushbu

    2014-01-01

    Although common acquired melanocytic nevi are largely benign, they are probably one of the most common indications for cosmetic surgery encountered by dermatologists. With recent advances, noninvasive tools can largely determine the potential for malignancy, although they cannot supplant histology. Although surgical shave excision with its myriad modifications has been in vogue for decades, the lack of an adequate histological sample, the largely blind nature of the procedure, and the possibility of recurrence are persisting issues. Pigment-specific lasers were initially used in the Q-switched mode, which was based on the thermal relaxation time of the melanocyte (size 7 μm; 1 μsec), which is not the primary target in melanocytic nevus. The cluster of nevus cells (100 μm) probably lends itself to treatment with a millisecond laser rather than a nanosecond laser. Thus, normal mode pigment-specific lasers and pulsed ablative lasers (CO2/erbium [Er]:yttrium aluminum garnet [YAG]) are more suited to treat acquired melanocytic nevi. The complexities of treating this disorder can be overcome by following a structured approach by using lasers that achieve the appropriate depth to treat the three subtypes of nevi: junctional, compound, and dermal. Thus, junctional nevi respond to Q-switched/normal mode pigment lasers, where for the compound and dermal nevi, pulsed ablative laser (CO2/Er:YAG) may be needed. If surgical excision is employed, a wide margin and proper depth must be ensured, which is skill dependent. A lifelong follow-up for recurrence and melanoma is warranted in predisposed individuals, although melanoma is decidedly uncommon in most acquired melanocytic nevi, even though histological markers may be seen on evaluation. PMID:24672253

  19. Seven-Year Course of Borderline Personality Disorder Features: Borderline Pathology Is as Unstable as Depression during Adolescence.

    PubMed

    Conway, Christopher C; Hipwell, Alison E; Stepp, Stephanie D

    2017-07-01

    Borderline personality disorder (PD) historically is construed as an unremitting condition with poor prognosis. The present study takes a new approach to examining stability and change in borderline PD by explaining symptom expression in terms of an unchanging foundation-termed borderline proneness-on one hand, and transitory influences on the other. We monitored borderline PD symptoms annually in a large sample of high-risk adolescent girls (N = 2,450) from ages 14 to 20. Trait-state-occasion modeling revealed that just over half (52-57%) of borderline PD symptom variation was attributable to fixed borderline proneness, whereas the remainder was subject to change across yearly measurement occasions. This degree of stability was no larger than the corresponding estimate for depression, a condition known for its variable course. Our results indicate that, contrary to its reputation, borderline pathology is not set in stone, and it fluctuates in response to situational influences.

  20. No. 347-Obstetric Management at Borderline Viability.

    PubMed

    Ladhani, Noor Niyar N; Chari, Radha S; Dunn, Michael S; Jones, Griffith; Shah, Prakesh; Barrett, Jon F R

    2017-09-01

    The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. Women presenting for possible birth at borderline viability. This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. A multidisciplinary approach should be used in counselling women and families at borderline

  1. Opening a Window into Living Tissue: Histopathologic Features of Confocal Microscopic Findings in Skin Tumors.

    PubMed

    Tavoloni Braga, Juliana Casagrande; de Paula Ramos Castro, Raquel; Moraes Pinto Blumetti, Tatiana Cristina; Rocha Mendes, Fernanda Berti; Arêas de Souza Lima Beltrame Ferreira, Juliana; Rezze, Gisele Gargantini

    2016-10-01

    The knowledge of histopathology and in vivo reflectance confocal microscopy correlation has several potential applications. Reflectance confocal microscopy can be performed in all skin tumors, and in this article, the most common histopathologic features of confocal microscopic findings in melanocytic skin tumors and nonmelanocytic skin tumors are described. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Ectopic differentiation of melanocyte stem cells is influenced by genetic background

    PubMed Central

    Harris, Melissa L.; Levy, Denise J.; Watkins-Chow, Dawn E.; Pavan, William J.

    2015-01-01

    Summary Hair graying in mouse is attributed to the loss of melanocyte stem cell function and the progressive depletion of the follicular melanocyte population. Single-gene, hair graying mouse models have pointed to a number of critical pathways involved in melanocyte stem cell biology; however, the broad range of phenotypic variation observed in human hair graying suggests that additional genetic variants involved in this process may yet be discovered. Using a sensitized approach, we ask here whether natural genetic variation influences a predominant cellular mechanism of hair graying in mouse, melanocyte stem cell differentiation. We developed an innovative method to quantify melanocyte stem cell differentiation by measuring ectopically pigmented melanocyte stem cells in response to the melanocyte-specific transgene Tg(Dct-Sox10). We make the novel observation that the production of ectopically pigmented melanocyte stem cells varies considerably across strains. The success of sensitizing for melanocyte stem cell differentiation by Tg(Dct-Sox10) sets the stage for future investigations into the genetic basis of strain-specific contributions to melanocyte stem cell biology. PMID:25495036

  3. Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

    PubMed

    Wagner, Roselyne Y; Luciani, Flavie; Cario-André, Muriel; Rubod, Alain; Petit, Valérie; Benzekri, Laila; Ezzedine, Khaled; Lepreux, Sébastien; Steingrimsson, Eirikur; Taieb, A; Gauthier, Yvon; Larue, Lionel; Delmas, Véronique

    2015-07-01

    Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

  4. Ectopic differentiation of melanocyte stem cells is influenced by genetic background.

    PubMed

    Harris, Melissa L; Levy, Denise J; Watkins-Chow, Dawn E; Pavan, William J

    2015-03-01

    Hair graying in mouse is attributed to the loss of melanocyte stem cell function and the progressive depletion of the follicular melanocyte population. Single-gene, hair graying mouse models have pointed to a number of critical pathways involved in melanocyte stem cell biology; however, the broad range of phenotypic variation observed in human hair graying suggests that additional genetic variants involved in this process may yet be discovered. Using a sensitized approach, we ask here whether natural genetic variation influences a predominant cellular mechanism of hair graying in mouse, melanocyte stem cell differentiation. We developed an innovative method to quantify melanocyte stem cell differentiation by measuring ectopically pigmented melanocyte stem cells in response to the melanocyte-specific transgene Tg(Dct-Sox10). We make the novel observation that the production of ectopically pigmented melanocyte stem cells varies considerably across strains. The success of sensitizing for melanocyte stem cell differentiation by Tg(Dct-Sox10) sets the stage for future investigations into the genetic basis of strain-specific contributions to melanocyte stem cell biology. Published 2014. This article is a US Government work and is in the public domain in the US.

  5. The "Umbrella Sign": A Useful Clue in the Diagnosis of Melanocytic Lesions in Sun Damaged Skin.

    PubMed

    Wood, Benjamin A; Harvey, Nathan T

    2016-07-01

    As ultraviolet radiation is an important aetiological agent in melanoma development, the presence of solar elastosis is an important factor in the assessment of any melanocytic lesion. However, melanocytic naevi are also seen in chronically sun damaged skin, particularly in regions with high levels of ultraviolet exposure and fair skinned populations. It has previously been noted that the relationship of a melanocytic proliferation to elastic fibers in the dermis can be of discriminatory value in the separation of melanoma from melanocytic naevus, in particular, it has been proposed that naevi act as a "sunscreen," which may result in a histological clue that the authors colloquially refer to in practice as "the umbrella sign." The aim of this study was to evaluate the patterns of solar elastosis within and beneath melanocytic proliferations developing in sun damaged skin and to determine the utility of the "umbrella sign" in diagnostic practice. We assessed 81 melanocytic proliferations in sun damaged skin for the presence of an umbrella sign, that was present in 49/53 melanocytic naevi (92%) compared with only 2/28 melanomas (7%, P < 0.05). In addition, entrapped elastotic fibers displaying distinct purple discolouration were identified in 16 melanocytic naevi. This finding was not identified in any of the melanomas. The umbrella sign appears to be a useful clue in the distinction of melanoma from melanocytic naevus in sun damaged skin, although as with all histological features in melanocytic pathology, it requires interpretation within a multifactorial assessment cognizant of potential diagnostic pitfalls.

  6. Endothelin-1 increases melanin synthesis in an established sheep skin melanocyte culture.

    PubMed

    Pang, Yamiao; Geng, Jianjun; Qin, Yilong; Wang, Haidong; Fan, Ruiwen; Zhang, Ying; Li, Hongquan; Jiang, Shan; Dong, Changsheng

    2016-08-01

    The aims of the study were to establish a culture system for sheep skin melanocytes and uncover the effects of endothelin-1 on melanin synthesis in cultured melanocytes in order to provide an optimal cell system and a theoretical basis for studying the regulatory mechanism of coat color in sheep. In this study, skin punch biopsies were harvested from the dorsal region of 1-3-yr-old sheep, and skin melanocytes were then obtained by the two-step digestion using dispase II and trypsin/ethylene diamine tetraacetic acid (EDTA). The primary cultures of the melanocytes were established and characterized by dopa-staining, immunocytochemical localization of melanocyte markers, and RT-polymerase chain reaction (PCR) analysis of coat color genes. To determine the effect of endothelin-1 on proliferation and melanin synthesis of melanocytes, the cultured cells were treated with different doses of endothelin-1 (10(-7), 10(-8), 10(-9), 10(-10), and 0 mol/L), and the growth rate of melanocytes, production of melanin, expression of related genes, and location of related protein in cultured cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ultraviolet spectrophotometry, qRT-PCR, and immunocytochemical localization, respectively. The results showed that the established melanocyte culture functions properly. Endothelin-1 treatment increased markedly the number of melanocytes and melanin content. In responding to this treatment, expressions of microphthalmia-associated transcription factor (MITF), melanocortin 1 receptor (MC1R), tyrosinase (TYR), and endothelin receptor B (EDNRB) in the melanocytes were significantly up regulated (P < 0.05). Immunocytochemical localization revealed that TYR was mainly localized in the cytoplasm. Positive staining of TYR in the melanocytes was significant. The findings demonstrated that the culture system of sheep skin melanocytes was established successfully in vitro, and endothelin-1 promotes the

  7. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  8. Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

    PubMed

    Mahanty, Sarmistha; Kawali, Ankush A; Dakappa, Shruthi Shirur; Mahendradas, Padmamalini; Kurian, Mathew; Kharbanda, Varun; Shetty, Rohit; Setty, Subba Rao Gangi

    2017-09-01

    Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p < 0.0001) or Tobramycin-treated eyes (p < 0.0001), which indicated that few quinolones under certain conditions are toxic to the iris melanocytes. However, the reduced TYR activity in the aqueous of Moxifloxacin-treated eyes was possibly due to the presence of a higher drug concentration, which inhibits TYR activity. Consistently

  9. Social interaction in borderline personality disorder.

    PubMed

    Lis, Stefanie; Bohus, Martin

    2013-02-01

    Studies on natural long-term course of borderline personality disorder (BPD) as well as on treatment outcome suggest that social integration remains seriously unsatisfactory in the majority of the subjects concerned. Identification of typical borderline problems in social interaction should facilitate both, treatment development and elucidation of the related neuropsychological mechanisms and underpinnings. This review focuses on the experimental investigation of three core domains of social interaction: social affiliation, cooperation and hostility. Data converge, that patients meeting criteria for BPD show a tendency to misinterpret neutral situations, feel socially rejected during normative inclusion conditions and reveal difficulties in repairing cooperation after experiencing disappointment. While from a clinical perspective, most attention has been focused on relationships of BPD patients with their significant others, the literature suggests that encounters with unknown individuals also indicate impairments in interaction behavior, and that such impairments can be linked to altered cerebral processing. Considering these findings psychosocial treatments should extend the programs and develop trainings in normative behavior.

  10. [Mentalization based treatment and borderline personality disorder].

    PubMed

    De Oliveira, C; Rahioui, H; Smadja, M; Gorsane, M A; Louppe, F

    2017-08-01

    The borderline personality disorder is a complex psychiatric disorder that represents a high number of patients in a psychiatric adult service. Even if some therapies have shown to be effective in the therapeutic care of the borderline personality disorder they only target certain symptoms (e.g. anxiety, sadness, self-mutilation). The aim of this paper is to introduce a therapeutic model little known in France: the mentalization based therapy (MBT) developed in 2004 by Bateman and Fonagy. This therapeutic model apprehends the borderline personality disorder in all its complexity and is based on two main concepts: Bowlby's attachment theory and the concept of mentalization. The MBT is based on the hypothesis that a deficit of mentalization leads to the development of borderline disorder. The capacity of mentalization, also known as reflexive function, is acquired in infancy through interpersonal relationships, in particular those of attachment, and is the ability to understand the mental state (emotions, needs, thoughts, etc.) of oneself and others which underlies explicit behaviour. This reflexive capacity is of a better quality when the person has a secure attachment style. Indeed, borderline patients have, mainly, a deficit of mentalization capacity associated with an insecure attachment style. Thus, the main objective of the Bateman and Fonagy approach is to develop and reinforce the mentalization capacity through a therapeutic relationship as a secure base, a group therapy and the concept of insight. Classically, MBT is structured over a period of 18 months divided into 3 distinct phases distributed in two therapeutic axes: group and individual therapy. The initial phase aims to engage the patient in the therapy by evaluating attachment style, mentalization's ability, interpersonal functioning; providing psychoeducation about borderline disorder and establishing a therapeutic contract. To evaluate attachment style, the authors strongly recommend the use of the

  11. Treatment of Borderline Personality Disorder in Youth

    PubMed Central

    Biskin, Robert S.

    2013-01-01

    Objectives: Borderline personality disorder (BPD) is frequently encountered in both adult and youth populations. There is a robust literature supporting psychotherapy for adults with BPD, but the literature supporting its use for BPD in youth is more limited. Methods: A literature review was conducted using the keywords “borderline personality disorders” and “adolescence.” Relevant articles were reviewed for inclusion. Results: Several specialized treatments have been studied with mixed results. Dialectical behaviour therapy has no randomized controlled trials in adolescents, emotion regulation training has not demonstrated superiority of treatment as usual, and cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up. Mentalization-based treatment has one study supporting its use in self-harming adolescents. Pharmacotherapy has no evidence supporting its use in this population. Conclusions: Structured therapy may be the most important therapeutic component in this population. PMID:23970912

  12. Developmental antecedents of borderline personality disorder.

    PubMed

    Helgeland, Margareth I; Torgersen, Svenn

    2004-01-01

    Developmental antecedents of borderline personality disorders (BPDs) were examined in 25 DSM-IV-diagnosed subjects with BPD and 107 non-borderline control subjects on the basis of medical records and 28 years follow-up. Abuse, neglect, environmental instability, paternal psychopathology, and lower score on protective factors differentiated significantly between the groups. Environmental instability and lower score on protective factors such as artistic talents, superior school performance, above average intellectual skills, and talents in other areas were found to be independent predictors of BPD diagnosis. The results of this study suggest that both abuse and neglect, unpredictable and unstable early environment, as well as deficit in protective factors may substantially contribute to the development of BPD in persons constitutionally predisposed for the disorder. The results of the study also suggest that future research should address the impact of social and cultural context, as well as the absence of protective factors, on the development of the BPD.

  13. [Screening measure for borderline personality disorder].

    PubMed

    Kröger, Christoph; Vonau, Melanie; Kliem, Sören; Kosfelder, Joachim

    2010-01-01

    Borderline personality disorder (BPD) is a life-threatening mental disorder. To date, there is no German screening tool available. To examine the psychometric properties of a German version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD). A heterogeneous outpatient sample (N=168) was used to examine discriminatory ability, diagnostic efficiency as well as indicators for internal consistency and convergent validity. The area under the curve was AUC=0.90 (CI 95%: 0.85

  14. Making psychotherapy for borderline personality disorder accessible.

    PubMed

    Paris, Joel

    2015-11-01

    Psychotherapies specifically designed for borderline personality disorder (BPD) are the most effective form of treatment for this population, but these modalities are not easily accessible. Narrative review. Although research shows that such therapies are effective, the best-known methods are lengthy, expensive, and difficult for patients to access. This review recommends that interventions for patients with BPD should be briefer, less costly, and more accessible.

  15. [Borderline personality disorders in somatic illness].

    PubMed

    Vender, Simone; Callegari, Camilla; Poloni, Nicola

    2004-06-01

    The borderline personality disorders are very frequent in modern society because of cultural and social reasons. The authors analyze the disturbed mental processes (impulsiveness and memory) because they represent risk factors for the treatment of diseases. On the base of experience of consultation-liaison psychiatry, the authors show some guidelines in the medical practice (primary care and general hospital) in order to overcome the troubles of the treatment.

  16. Maturation in patients with borderline personality disorder.

    PubMed

    Levallius, Johanna; Rydén, Göran; Norring, Claes

    2015-08-30

    Patients with borderline personality disorder have a characteristic and extreme personality associated with psychopathology. The aim was to investigate personality change in relation to suicidality following treatment. 21 patients were assessed before and after psychotherapy on personality (NEO PI-R) and suicidality (SUAS). At follow-up, Neuroticism and Conscientiousness normalized along with six lower-order facets; Depression, Impulsiveness, Competence, Achievement Striving, Self-Discipline and Deliberation. Thirteen patients showed a positive personality development paralleled by a lesser degree of suicidality.

  17. Antisocial and borderline personality disorders revisited.

    PubMed

    Paris, Joel; Chenard-Poirier, Marie-Pierre; Biskin, Robert

    2013-05-01

    Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) have an overlap in both symptoms and risk factors, suggesting that they might reflect the same form of psychopathology, shaped by gender. However other lines of evidence point to the presence of partly unique, albeit overlapping, trait dimensions, specifically affective instability which differentiates BPD from ASPD. Our conclusion is that ASPD and BPD are separate disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Clinical status of comorbid bipolar disorder and borderline personality disorder.

    PubMed

    Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

    2016-09-01

    The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

  19. Paracrine Secreted Frizzled-Related Protein 4 Inhibits Melanocytes Differentiation in Hair Follicle

    PubMed Central

    Guo, Haiying; Lei, Mingxing; Li, Yuhong; Liu, Yingxin; Tang, Yinhong; Xing, Yizhan; Deng, Fang

    2017-01-01

    Wnt signaling plays crucial role in regulating melanocyte stem cells/melanocyte differentiation in the hair follicle. However, how the Wnt signaling is balanced to be overactivated to control follicular melanocytes behavior remains unknown. Here, by using immunofluorescence staining, we showed that secreted frizzled-related protein 4 (sFRP4) is preferentially expressed in the skin epidermal cells rather than in melanocytes. By overexpression of sFRP4 in skin cells in vivo and in vitro, we found that sFRP4 attenuates activation of Wnt signaling, resulting in decrease of melanocytes differentiation in the regenerating hair follicle. Our findings unveiled a new regulator that involves modulating melanocytes differentiation through a paracrine mechanism in hair follicle, supplying a hope for potential therapeutic application to treat skin pigmentation disorders. PMID:28337220

  20. Cellular origin and developmental mechanisms during the formation of skin melanocytes

    SciTech Connect

    Ernfors, Patrik

    2010-05-01

    Melanocytes are derived from the neural crest (NC), which are transient multipotent cells arising by delamination from the developing dorsal neural tube. During recent years, signaling systems and molecular mechanisms of melanocyte development have been studied in detail, but the exact diversification of the NC into melanocytes and how they migrate, expand and disperse in the skin have not been fully understood. The recent finding that Schwann cell precursors (SCPs) of the growing nerve represents a stem cell niche from which various cell types, including Schwann cells, endoneural fibroblasts and melanocytes arise has exposed new knowledge on the cellular basis for melanocyte development. This opens for the identification of new factors and reinterpretation of old data on cell fate instructive, proliferative, survival and cell homing factors participating in melanocyte development.

  1. INTEGRATIVE BORDERLINE ADOLESCENT FAMILY THERAPY: MEETING THE CHALLENGES OF TREATING ADOLESCENTS WITH BORDERLINE PERSONALITY DISORDER

    PubMed Central

    SANTISTEBAN, DANIEL A.; MUIR, JOAN A.; MENA, MAITE P.; MITRANI, VICTORIA B.

    2014-01-01

    With the growing acceptance of the borderline personality disorder diagnosis for adolescents has come a need for specialized treatments for this challenging population. Further, because of the prominence of the family system during early and later adolescence, family treatments are particularly needed. The purpose of this article is to present the integrative borderline adolescent family therapy (I-BAFT) model that emerged from a National Institute on Drug Abuse–funded (Stage 1) treatment development and enhancement effort. I-BAFT integrates (a) key interventions from the family treatment of adolescent drug abuse (D. A. Santisteban et al., 2003; J. Szapocznik & W. Kurtines, 1989), (b) skills training shown effective with adults with borderline personality disorder (M. Linehan, 1993a) and adapted for adolescents, and (c) individual treatment interventions that promote motivation for treatment and enhance the integration of the 3 treatment components. PMID:25663719

  2. Spontaneous Involution of Congenital Melanocytic Nevus With Halo Phenomenon.

    PubMed

    Lee, Noo Ri; Chung, Hee-Chul; Hong, Hannah; Lee, Jin Wook; Ahn, Sung Ku

    2015-12-01

    Congenital melanocytic nevus (CMN) is a neural crest-derived hamartoma, which appear at or soon after birth. CMN has a dynamic course and may show variable changes over time, including spontaneous involution. Spontaneous involution of CMN is a rare phenomenon and is often reported in association with halo phenomenon or vitiligo. The mechanism of halo phenomenon is yet to be investigated but is suggested to be a destruction of melanocytes by immune responses of cytotoxic T cells or IgM autoantibodies. Here, the authors report an interesting case of spontaneously regressed medium-sized CMN with halo phenomenon and without vitiligo, which provides evidence that cytotoxic T cells account for the halo formation and pigmentary regression of CMN.

  3. Molecular pathogenesis of cutaneous melanocytic neoplasms.

    PubMed

    Ibrahim, Nageatte; Haluska, Frank G

    2009-01-01

    Melanoma is the deadliest form of skin cancer without an effective treatment. An understanding of the genetic basis of melanoma has recently shed light on some of the mechanisms of melanomagenesis. This review explores the major genes involved in familial and sporadic cutaneous melanoma with an emphasis on CDKN2A, CDK4, MC1R, and MAPK pathway targets (e.g., RAS and BRAF), apoptosis regulators (e.g., BCL-2, AKT, and APAF-1), and the tumor-suppressor genes TP53 and PTEN. New directions for therapeutics based on our current knowledge of the genes implicated in melanoma are also discussed.

  4. CD10, actin, and vimentin expression in breast phyllodes tumors correlates with tumor grades of the WHO grading system.

    PubMed

    Tsai, Wen-Chiuan; Jin, Jong-Shiao; Yu, Jyh-Cherng; Sheu, Lai-Fa

    2006-04-01

    The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.

  5. Ultraviolet radiation directly induces pigment production by cultured human melanocytes

    SciTech Connect

    Friedmann, P.S.; Gilchrest, B.A.

    1987-10-01

    In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of /sup 14/C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.

  6. Clues to the diagnosis of atypical melanocytic lesions.

    PubMed

    McKee, Phillip H

    2010-01-01

    This review, based on a lecture given at the 2009 Update in Dermatopathology meeting held at the Institute of Dermatology (London, UK), discusses the problem of misdiagnosing atypical benign melanocytic lesions as melanoma and the alternative problem of interpreting naevoid melanoma as a banal naevus. Consequences are considered. Brief consideration of a range of other melanoma variants that may be a source of diagnostic difficulty is also included.

  7. Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry.

    PubMed

    Nagarajan, P; Tetzlaff, M T; Curry, J L; Prieto, V G

    Melanoma remains one of the most aggressive forms of cutaneous malignancies. While its diagnosis based on histologic parameters is usually straight forward in most cases, distinguishing a melanoma from a melanocytic nevus can be challenging in some instances, especially when there are overlapping clinical and histopathologic features. Occasionally, melanomas can histologically mimic other tumors and even demonstration of melanocytic origin can be challenging. Thus, several ancillary tests may be employed to arrive at the correct diagnosis. The objective of this review is to summarize these tests, including the well-established and commonly used ones such as immunohistochemistry, with specific emphasis on emerging techniques such as comparative genomic hybridization, fluorescence in situ hybridization and imaging mass spectrometry. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. The optical properties and spectral features of malignant skin melanocytes in the terahertz frequency range

    NASA Astrophysics Data System (ADS)

    Goryachuk, A. A.; Begaeva, V. A.; Khodzitsky, M. K.; Truloff, A. S.

    2016-08-01

    The samples of cells of mice's melanocytes have been investigated. Their optical properties and spectral features were investigated by terahertz time-domain spectroscopy (TDS) in transmission mode. It was found that the optical properties of oncological melanocytes and normal cells are different and oncological cells have spectral features of absorption coefficient so it can be concluded that it is easy to discriminate mice's oncological skin melanocytes by using THz TDS.

  9. Expression profiling of human melanocytes in response to UV-B irradiation

    PubMed Central

    López, Saioa; Smith-Zubiaga, Isabel; Alonso, Santos

    2015-01-01

    A comprehensive gene expression analysis of human melanocytes was performed assessing the transcriptional profile of dark melanocytes (DM) and light melanocytes (LM) at basal conditions and after UV-B irradiation at different time points (6, 12 and 24 h), and in culture with different keratinocyte-conditioned media (KCM + and KCM −). The data, previously published in [1], have been deposited in NCBI's Gene Expression Omnibus (GEO accession number: GSE70280). PMID:26697372

  10. Epithelioid melanocytic nevus with tubule and pseudoacini formation.

    PubMed

    Uhlenhake, Elizabeth E; Smoller, Bruce R; Gardner, Jerad M; Shalin, Sara C

    2015-03-01

    A 26-year-old female presented with a 7 mm irritated pink-red papule on the left posterior shoulder. A shave biopsy revealed a dermal proliferation of epithelioid cells arranged in small nests with central lumen-like structures resembling glands set in a densely sclerotic stroma. S100 and Melanoma antigen recognized by T cells 1 (MART-1) immunohistochemical positivity confirmed a dermal melanocytic neoplasm. Pan-cytokeratin and cytokeratin 7 were negative within the nests ruling out an adnexal neoplasm or metastatic adenocarcinoma. A Spitz nevus variant characterized by the presence of focal tubular structures (tubular epithelioid cell nevus) has rarely been described in the literature and is of uncertain biological significance. Similar structures have also been observed in Clark/dysplastic nevi and melanoma. Glandular differentiation is seen in a wide variety of benign and malignant epithelial neoplasms; however, melanocytes are not known to be capable of forming true glands. The exact mechanism and significance of this phenomenon are currently unknown. Certain postulations include central melanocyte apoptosis, autocrine or paracrine factor secretion or retraction artifact caused by tissue fixation. This distinctive finding is important to recognize in order to avoid misdiagnosis as a glandular neoplasm.

  11. Ultrastructural changes in the melanocytes of aging human choroid.

    PubMed

    Nag, Tapas Chandra

    2015-12-01

    Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85-94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light.

  12. Diagnostic utility of 5-hydroxymethylcytosine immunohistochemistry in melanocytic proliferations

    PubMed Central

    Rodić, Nemanja; Zampella, John; Sharma, Reema; Burns, Kathleen H.; Taube, Janis M.

    2015-01-01

    Decreased hydroxymethylated cytosine (5-hydroxymethycytosine, 5-hmC) is reported to correlate with melanocyte dysplasia. The purpose of this study was to assess the diagnostic utility of this observation. 5-hmC immunohistochemistry was performed on tissue microarrays containing 171-melanocytic lesions from two different institutions. An immunohistochemical staining score representing the percentage and intensity of nuclear staining was assigned. The performance characteristics of 5-hmC immunohistochemistry for discriminating between a nevus and melanoma were determined. Additional cases of melanoma arising in a nevus (n = 8), nodal nevi (n = 5) and melanoma micrometastases to a lymph node (n = 6) were also assessed. Pronounced 5-hmC loss was observed in melanomas when compared with nevi (mean ± standard deviation = 6.71 ± 11.78 and 55.19 ± 23.66, respectively, p < 0.0001). While the mean immunohistochemical staining score values for melanocytic nevi and melanoma were distinct, there was considerable variability in immunohistochemical staining score within a single diagnostic category. The sensitivity and specificity of this assay for nevus vs. melanoma is 92.74 and 97.78%, respectively. Distinct biphasic staining patterns were observed in cases of melanoma arising in association with a nevus. Relative changes of 5-hmC expression within a single lesion may be more informative than absolute values when using 5-hmC as a diagnostic adjunct. PMID:26239102

  13. EFFECT OF PARACETAMOL ON MELANIZATION PROCESS IN HUMAN EPIDERMAL MELANOCYTES.

    PubMed

    Wrześniok, Dorota; Oprzondek, Martyna; Hechmann, Anna; Beberok, Artur; Otreba, Michał; Buszman, Ewa

    2016-01-01

    Paracetamol (acetaminophen) is commonly used as a drug of choice for treatment of pain and fever. Unlike non-steroidal anti-inflammatory drugs (NSAIDs) it does not cause gastrointestinal damage or untoward cardiorenal effects, however cutaneous adverse effects have been reported. It is known that paracetamol binds to melanin biopolymers, but the relation between the affinity of this drug to melanin and its toxicity is not documented. The aim of this work was to examine the impact of paracetamol on melanogenesis in cultured human normal epidermal melanocytes (HEMn-DP). The effect of paracetamol on cell viability was determined by WST-1 assay, melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that paracetamol induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be - 20.0 mM. The analyzed drug inhibited melanin biosynthesis in a concentration-dependent manner by decreasing the melanin content as well as the tyrosinase activity. The demonstrated inhibitory effect of paracetamol on melanization process in normal epidermal melanocytes in vitro may explain the potential role of melanin biopolymer in the mechanisms of undesirable side effects of this drug in vivo, as a result of its accumulation in pigmented tissues.

  14. Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence

    PubMed Central

    Jaworek-Korjakowska, Joanna; Kłeczek, Paweł

    2016-01-01

    Background. Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. Method. In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. Results. The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. Conclusions. A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision. PMID:26885520

  15. UVA phototransduction drives early melanin synthesis in human melanocytes.

    PubMed

    Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

    2011-11-22

    Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin.

  16. Melanocytes in the skin--comparative whole transcriptome analysis of main skin cell types.

    PubMed

    Reemann, Paula; Reimann, Ene; Ilmjärv, Sten; Porosaar, Orm; Silm, Helgi; Jaks, Viljar; Vasar, Eero; Kingo, Külli; Kõks, Sulev

    2014-01-01

    Melanocytes possess several functions besides a role in pigment synthesis, but detailed characteristics of the cells are still unclear. We used whole transcriptome sequencing (RNA-Seq) to assess differential gene expression of cultivated normal human melanocytes with respect to keratinocytes, fibroblasts and whole skin. The present results reveal cultivated melanocytes as highly proliferative cells with possible stem cell-like properties. The enhanced readiness to regenerate makes melanocytes the most vulnerable cells in the skin and explains their high risk of developing into malignant melanoma.

  17. Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo

    PubMed Central

    He, Yuanmin; Li, Shuli; Zhang, Weigang; Dai, Wei; Cui, Tingting; Wang, Gang; Gao, Tianwen; Li, Chunying

    2017-01-01

    In vitiligo, melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis and to the genetic antioxidant defects. Autophagy is a controlled self-digestion process which can protect cells against oxidative damage. However, the exact role of autophagy in vitiligo melanocytes in response to oxidative stress and the mechanism involved are still not clear. To determine the implications of autophagy for melanocyte survival in response to oxidative stress, we first detected the autophagic flux in normal melanocytes exposure to H2O2, and found that autophagy was significantly enhanced in normal melanocytes, for protecting cells against H2O2-induced oxidative damage. Nevertheless, vitiligo melanocytes exhibited dysregulated autophagy and hypersensitivity to H2O2-induced oxidative injury. In addition, we confirmed that the impairment of Nrf2-p62 pathway is responsible for the defects of autophagy in vitiligo melanocytes. Noteworthily, upregulation of the Nrf2-p62 pathway or p62 reduced H2O2-induced oxidative damage of vitiligo melanocytes. Therefore, our data demonstrated that dysregulated autophagy owing to the impairment of Nrf2-p62 pathway increase the sensitivity of vitiligo melanocytes to oxidative stress, thus promote the development of vitiligo. Upregulation of p62-dependent autophagy may be applied to vitiligo treatment in the future. PMID:28186139

  18. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    SciTech Connect

    Medic, Sandra; Rizos, Helen; Ziman, Mel

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  19. Intelligent bioengineering in vitiligo treatment: transdermal protein transduction of melanocyte-lineage-specific genes.

    PubMed

    Mou, Yi; Jiang, Xian; Du, Yu; Xue, Li

    2012-12-01

    Vitiligo is a common, incurable skin disease with a prevalence of about 1%. Although many vitiligo therapies are available in clinics, there is almost no one method that causes significant improvement in all vitiligo patients. Some have hypothesized that melanocyte dysfunction or deficiency underlies the loss of skin pigmentation observed in vitiligo. The autoimmune-mediated apoptosis of melanocytes might be an important part of the etiology of vitiligo, which prevents the formation of melanocytes in the skin. Here we propose a novel hypothesis for vitiligo treatment using in situ melanocyte regeneration induced by melanocyte-lineage-specific genes (MLSGs). This may serve as an intelligent bioengineering prototype. The hypothesis is based on the fact that MLSGs regulate melanocyte differentiation through epigenetic reprogramming, which includes microphthalmia-associated transcription factor (MITF), paired box 3 (PAX3), and Notch signaling. MITF directs the terminal differentiation of melanocytes, and PAX3 helps to establish the properties of the melanocyte stem cells. Notch signaling promotes adult stem cell proliferation and self-renewal. This process could be mimicked by Notch intracellular domain (NICD). MLSGs could also stimulate anti-apoptotic gene expression. Recent improvements in relevant biotechniques allow the transdermal delivery of MLSG proteins into the patient, where they enter cells through protein transduction. This process may promote melanocyte regeneration in situ with little impact on the hair follicular cycle or on carcinogenesis. This simple and efficient treatment may have significant impact on the treatment of vitiligo patients.

  20. Melanocytes in the Skin – Comparative Whole Transcriptome Analysis of Main Skin Cell Types

    PubMed Central

    Reemann, Paula; Reimann, Ene; Ilmjärv, Sten; Porosaar, Orm; Silm, Helgi; Jaks, Viljar; Vasar, Eero; Kingo, Külli; Kõks, Sulev

    2014-01-01

    Melanocytes possess several functions besides a role in pigment synthesis, but detailed characteristics of the cells are still unclear. We used whole transcriptome sequencing (RNA-Seq) to assess differential gene expression of cultivated normal human melanocytes with respect to keratinocytes, fibroblasts and whole skin. The present results reveal cultivated melanocytes as highly proliferative cells with possible stem cell-like properties. The enhanced readiness to regenerate makes melanocytes the most vulnerable cells in the skin and explains their high risk of developing into malignant melanoma. PMID:25545474

  1. Gene expression profiling of melanocytes following Q-Switched Ruby laser irradiation.

    PubMed

    Hafner, Christian; Stempfl, Thomas; Bäumler, Wolfgang; Hohenleutner, Ulrich; Landthaler, Michael; Vogt, Thomas

    2008-01-01

    The Q-switched Ruby laser (QSRL) is used for the treatment of pigmented lesions. The influence of QSRL treatment on gene expression of nontransformed primary melanocytes has not been addressed in vitro. We investigated the gene expression profile of melanocytes following QSRL irradiation. Primary melanocytes were irradiated with the QSRL (694 nm). Early and late transcriptional effects were analyzed using the Affymetrix gene array platform. Laser irradiation of melanocytes had minor effects on mRNA expression. We found only 31 out of 14,500 genes which were at least twofold up- or downregulated. The differential expression of heme oxygenase 1 and galanin in QSRL-treated melanocytes was additionally confirmed by real-time RT-PCR. Analysis of a selection of 36 genes which are known to be associated with malignant melanoma development and progression revealed no significantly aberrant expression in the QSRL-treated melanocytes. Our study shows that QSRL treatment of primary melanocytes in vitro does not cause major alterations of global gene expression and particularly of genes associated with malignant melanoma. However, since QSRL treatment may have different effects on gene expression of melanocytic cells in vivo, further studies are required to evaluate QSRL treatment of (nevo-) melanocytic lesions. (c) 2008 S. Karger AG, Basel.

  2. Pharmacological inhibitors of c-KIT block mutant c-KIT mediated migration of melanocytes and melanoma cells in vitro and in vivo.

    PubMed

    Posch, Christian; Moslehi, Homayoun; Sanlorenzo, Martina; Green, Gary; Vujic, Igor; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-07-19

    Mutations in the receptor tyrosine kinase c-KIT (KIT) are frequent oncogenic alterations in melanoma and are predominantly detected in tumors of acral, mucosal, and chronically sun-damaged skin. Research indicates that melanocytes with aberrant KIT signaling can be found in the distant periphery of the primary tumor; However, it is hitherto unknown whether KIT might confer a migratory advantage, thereby enabling genetically abnormal cells to populate a distal area. In this study, we investigated the role of mutant KIT in melanocyte- and melanoma cell migration using KIT mutant lines as well as genetically manipulated murine and primary human melanocytes. Our results revealed that melanocytes, stably transduced with mutant KIT closed a gap inflicted on cell monolayers faster than wild-type controls. Similarly, KIT mutant human melanoma lines were able to populate a larger area in a 3D in vitro skin model compared to KIT wild type and BRAF mutant lines. Genomic profiling revealed that genes associated with increased cell-dispersal of KIT mutant variants were linked to a statistically significant up-regulation of 60 migratory genes (z-score 1.334; p=0.0001). In addition, in vivo experiments harnessing a mouse xenograft model of early melanoma development demonstrated rapid lateral migration of KIT mutant cells compared to respective controls. The specific kinase inhibitors imatinib and nilotinib, could abrogate this migratory advantage in vitro and in vivo. Our work suggests that KIT inhibition might help to target migratory active, KIT mutant melanoma cells, thus representing a potential strategy to reduce spread and local recurrence.

  3. Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy.

    PubMed

    Faião-Flores, Fernanda; Coelho, Paulo Rogério Pinto; Arruda-Neto, João Dias Toledo; Camillo, Maria Aparecida Pires; Maria-Engler, Silvya Stuchi; Rici, Rose Eli Grassi; Sarkis, Jorge Eduardo Souza; Maria, Durvanei Augusto

    2012-08-01

    Information on (10)B distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The (10)B concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the (10)B concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of (10)B uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

  4. Pharmacological inhibitors of c-KIT block mutant c-KIT mediated migration of melanocytes and melanoma cells in vitro and in vivo

    PubMed Central

    Posch, Christian; Moslehi, Homayoun; Sanlorenzo, Martina; Green, Gary; Vujic, Igor; Panzer-Grümayer, Renate; Rappersberger, Klemens; Ortiz-Urda, Susana

    2016-01-01

    Mutations in the receptor tyrosine kinase c-KIT (KIT) are frequent oncogenic alterations in melanoma and are predominantly detected in tumors of acral, mucosal, and chronically sun-damaged skin. Research indicates that melanocytes with aberrant KIT signaling can be found in the distant periphery of the primary tumor; However, it is hitherto unknown whether KIT might confer a migratory advantage, thereby enabling genetically abnormal cells to populate a distal area. In this study, we investigated the role of mutant KIT in melanocyte- and melanoma cell migration using KIT mutant lines as well as genetically manipulated murine and primary human melanocytes. Our results revealed that melanocytes, stably transduced with mutant KIT closed a gap inflicted on cell monolayers faster than wild-type controls. Similarly, KIT mutant human melanoma lines were able to populate a larger area in a 3D in vitro skin model compared to KIT wild type and BRAF mutant lines. Genomic profiling revealed that genes associated with increased cell-dispersal of KIT mutant variants were linked to a statistically significant up-regulation of 60 migratory genes (z-score 1.334; p=0.0001). In addition, in vivo experiments harnessing a mouse xenograft model of early melanoma development demonstrated rapid lateral migration of KIT mutant cells compared to respective controls. The specific kinase inhibitors imatinib and nilotinib, could abrogate this migratory advantage in vitro and in vivo. Our work suggests that KIT inhibition might help to target migratory active, KIT mutant melanoma cells, thus representing a potential strategy to reduce spread and local recurrence. PMID:27322141

  5. Phyllodes Tumor of the Breast

    SciTech Connect

    Belkacemi, Yazid Bousquet, Guilhem; Marsiglia, Hugo; Ray-Coquard, Isabelle; Magne, Nicolas; Malard, Yann; Lacroix, Magalie; Gutierrez, Cristina; Senkus, Elzbieta; Christie, David; Drumea, Karen; Lagneau, Edouard; Kadish, Sidney P.; Scandolaro, Luciano; Azria, David; Ozsahin, Mahmut

    2008-02-01

    Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapy (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.

  6. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors.

    PubMed

    Goldstein, Nathaniel B; Koster, Maranke I; Hoaglin, Laura G; Spoelstra, Nicole S; Kechris, Katerina J; Robinson, Steven E; Robinson, William A; Roop, Dennis R; Norris, David A; Birlea, Stanca A

    2015-08-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human vitiligo skin. NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo. We identified several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities. The primary melanocyte germ was present in the untreated and treated hair follicle bulge, whereas a possible secondary melanocyte germ composed of C-KIT+ melanocytes was found in the infundibulum and interfollicular epidermis of UV-treated vitiligo. This is an exceptional model for studying the mobilization of melanocyte stem cells in human skin. Improved understanding of this process is essential for designing better treatments for vitiligo, ultimately based on melanocyte stem cell activation and mobilization.

  7. Narrow Band Ultraviolet B Treatment for Human Vitiligo Is Associated with Proliferation, Migration, and Differentiation of Melanocyte Precursors

    PubMed Central

    Goldstein, Nathaniel B.; Koster, Maranke I.; Hoaglin, Laura G.; Spoelstra, Nicole S.; Kechris, Katerina J.; Robinson, Steven E.; Robinson, William A.; Roop, Dennis R.; Norris, David A.; Birlea, Stanca A.

    2015-01-01

    In vitiligo, the autoimmune destruction of epidermal melanocytes produces white spots that can be repigmented by melanocyte precursors from the hair follicles, following stimulation with UV light. We examined by immunofluorescence the distribution of melanocyte markers (C-KIT, DCT, PAX3, and TYR) coupled with markers of proliferation (KI-67) and migration (MCAM) in precursors and mature melanocytes from the hair follicle and the epidermis of untreated and narrow band UVB (NBUVB)-treated human vitiligo skin. NBUVB was associated with a significant increase in the number of melanocytes in the infundibulum and with restoration of the normal melanocyte population in the epidermis, which was lacking in the untreated vitiligo. We identified several precursor populations (melanocyte stem cells, melanoblasts, and other immature phenotypes), and progressively differentiating melanocytes, some with putative migratory and/or proliferative abilities. The primary melanocyte germ was present in the untreated and treated hair follicle bulge, whereas a possible secondary melanocyte germ composed of C-KIT+ melanocytes was found in the infundibulum and interfollicular epidermis of UV-treated vitiligo. This is an exceptional model for studying the mobilization of melanocyte stem cells in human skin. Improved understanding of this process is essential for designing better treatments for vitiligo, ultimately based on melanocyte stem cell activation and mobilization. PMID:25822579

  8. New melanogenesis and photobiological processes in activation and proliferation of precursor melanocytes after UV-exposure: ultrastructural differentiation of precursor melanocytes from Langerhans cells

    SciTech Connect

    Jimbow, K.; Uesugi, T.

    1982-02-01

    Photobiological processes involving new melanogenesis after exposure to ultraviolet (UV) light were experimentally studied in C57 black adult mice by histochemistry, cytochemistry, and autoradiography. The trunk and the plantar region of the foot, where no functioning melanocytes were present before exposure, were exposed to UV-A for 14 consecutive days. Both regions revealed a basically similar pattern for new melanogenesis which involved an activation of precursor melanocytes. Essentially all of ''indeterminate'' cells appeared to be precursor melanocytes, the fine structure of which could be differentiated even from poorly developed Langerhans cells. New melanogenesis was manifested by 4 stages of cellular and subcellular reactions of these cells as indicated by histochemistry of dihydroxyphenylalanine (dopa) and autoradiography of thymidine incorporation: (a) an initial lag in the activation of precursor melanocytes with development of Golgi cisternae and rough endoplasmic reticulum followed by formation of unmelanized melanosomes (day 0 to 2); (b) synthesis of active tyrosinase accumulated in Golgi cisternae and vesicles with subsequent formation of melanized melanosomes in these cells (day 3 to 5); (c) mitotic proliferation of many of these activated cells, followed by an exponential increase of new melanocytes (day 6 to 7); and (d) melanosome transfer with differentiation of 10 nm filaments and arborization of dendrites, but without any significant change in the melanocyte population (day 8 to 14). The melanosome transfer was, however, not obvious until after 7 days of exposure. The size of newly synthesized melanosomes was similar to that of tail skin where native melanocytes were present before exposure.

  9. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone

    PubMed Central

    Böhm, Markus; Hill, Helene Z.

    2016-01-01

    Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA) damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation. PMID:27303631

  10. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone.

    PubMed

    Böhm, Markus; Hill, Helene Z

    2016-01-01

    Alpha-melanocyte-stimulating hormone (alpha-MSH) increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA) damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

  11. Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65.

    PubMed

    Amann, Philipp M; Luo, Chonglin; Owen, Robert W; Hofmann, Claudia; Freudenberger, Muriel; Schadendorf, Dirk; Eichmüller, Stefan B; Bazhin, Alexandr V

    2012-02-01

    Disturbance in vitamin A metabolism seems to be an important attribute of cancer cells. Retinoids, particularly retinoic acid, have critical regulatory functions and appear to modulate tumor development and progression. The key step of vitamin A metabolism is the esterification of all-trans retinol, catalyzed by lecithin/retinol acyltransferase (LRAT). In this work, we show that malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11-cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions. Besides, melanoma cell lines express lecithin/retinol acyltranseferase both at the mRNA and protein levels. In contrast, melanocytes do not express this enzyme at the protein level, but mRNA of lecithin/retinol acyltransefrase could still be present at mRNA level. RPE65 is expressed in both melanocytic counterparts, and could be involved in the subsequent isomerization of RE produced by lecithin/retinol acyltransefrase to 11-cis retinol. Cellular retinol-binding protein 2 does not appear to be involved in the regulation of all-trans retinol esterification in these cells. Expression of LRAT and RPE65 can be modulated by retinoids. We propose that the post-transcriptional regulation of lecithin/retinol acyltransefrase could be involved in the differential expression of this enzyme. Besides, activities of LRAT and RPE65 may be important for removal of all-trans retinal which is the substrate for retinoic acid production in skin cells. Consequently, the decreasing cellular amount of retinoic acid and its precursor molecules could result in a change of gene regulation.

  12. Detection of auto antibodies and transplantation of cultured autologous melanocytes for the treatment of vitiligo

    PubMed Central

    Zhu, Mei-Cai; Ma, Hong-Yu; Zhan, Zhi; Liu, Cheng-Gang; Luo, Wei; Zhao, Guang

    2017-01-01

    The aim of the present study was to establish an immunofluorescence method of antibody detection to identify melanocytes in the serum of vitiligo patients. Furthermore, we aimed to establish a method for the culture and proliferation of autologous pure melanocytes and to observe the effect of their transplantation for the treatment of vitiligo. Suspension of epidermal cells with melanocytes was performed using trypsin digestion of normal epiderm from eyelid operation and melanocytes were selectively cultured and proliferated in serum-free M2 medium. FITC-labeled rabbit anti-human antibody was used to detect the relative fluorescence intensity of the melanocytes. After identification with immunological and biological examinations, the melanocytes were transplanted to depigmented areas of vitiligo. Repigmentation was observed continuously. The results indicated that melanocytes could be selectively proliferated in the medium. Subsequently, pure melanocytes without contamination of fibroblast and keratinocyte were harvested. A total of 34 patients suffering vitiligo for between 3 months and 20 years with depigmented area (between 4 cm2 and 70% of body surface) were divided into 19 cases of developing stage and 15 cases of stable stage, according to the change of depigmentation. A total of 15 developing cases were positive for the antibody against melanocytes, with the positive rate of 79%. The titers of serum was >1:50 in 10 patients at the developing stage, and 5 developing patients were 1:10. Among the 15 stable cases, four were positive, with a positive rate of 27%. Fluorescence of antibody was localized in the cytoplasm of the melanocytes. Autologous melanocytes of vitiligo patients could be selectively proliferated in the medium. Next, pure melanocytes without contamination with fibroblasts and keratinocytes were harvested. A total of 16 vitiligo patients with 28 depigmented areas (2–200 cm2) were treated with transplantation of melanocytes. Repigmentation of

  13. Plexin B1 inhibits MET through direct association and regulates Shp2 expression in melanocytes.

    PubMed

    Soong, Joanne; Scott, Glynis

    2013-01-15

    Plexin B1, the receptor for Semaphorin 4D (Sema4D), is expressed by melanocytes in the skin. We recently showed that Sema4D suppresses activation of the hepatocyte growth factor receptor, MET, in melanocytes, and that knockdown of Plexin B1 results in activation of MET. MET signaling mediates proliferation, survival and migration in melanocytes, and its activation is associated with transformation of melanocytes to melanoma. In this report we investigated the mechanism by which Plexin B1 inhibits MET activation. Our results show that Plexin B1 and MET exist as an oligomeric receptor-receptor complex in melanocytes, and that receptor association is increased by Sema4D. MET and Plexin B1 receptor complexes were identified along the cell body of melanocytes, and Sema4D increased receptor association on dendrites, suggesting that Sema4D regulates MET-dependent processes at precise locations on the melanocyte. Despite activation of MET, Plexin B1 knockdowns proliferated slowly and showed increased apoptosis compared with controls. Shp2, a non-receptor protein tyrosine phosphatase, translates growth and survival signals from MET and other receptor tyrosine kinases. Plexin B1 knockdowns had markedly lower levels of Shp2 compared with controls, and Sema4D upregulated Shp2 expression at the protein and message level in normal melanocytes. Functional studies showed that blockade of Shp2 activity abrogated MET-dependent activation of Erk1/Erk2 and Akt in melanocytes. These results suggest a complex role for Sema4D and Plexin B1 in orchestrating signaling from the MET receptor in melanocytes. Because Shp2 is a downstream adaptor protein for multiple receptors, Sema4D may control the effects of several growth factors on melanocytes through regulation of Shp2.

  14. Adipose-derived stem cells inhibit epidermal melanocytes through an interleukin-6-mediated mechanism.

    PubMed

    Kim, Deok-Woo; Jeon, Byung-Joon; Hwang, Na-Hyun; Kim, Min-Sook; Park, Seung-Ha; Dhong, Eun-Sang; Yoon, Eul-Sik; Lee, Byung-Il

    2014-09-01

    Several investigators have postulated that human adipose-derived stem cells can be used for skin rejuvenation, but there have been few reports about their direct effects on human epidermal melanocytes. The authors studied the effects on melanocytes, and the causative agent of those effects was further investigated in this study. Human epidermal melanocytes were divided into three groups and cultured in adipose-derived stem cell-conditioned medium, human dermal fibroblast-conditioned medium, or control medium. Concentrations of melanogenic cytokines in these media were measured using enzyme-linked immunosorbent assay kits. After 3 and 7 days of incubation, cell proliferation, melanin content, tyrosinase activity, and melanogenic gene expression were measured. Interleukin-6-neutralizing antibodies were mixed with adipose-derived stem cell-conditioned medium in which human epidermal melanocytes were cultured, and melanocyte growth and melanogenesis were measured again. Interleukin-6 concentrations in adipose-derived stem cell- and human epidermal melanocyte-conditioned media were 1373 and 495 pg/ml, respectively. Both types of medium suppressed melanocyte proliferation and melanin synthesis (p < 0.05), but adipose-derived stem cell-conditioned medium was more effective than human dermal fibroblast-conditioned medium in inhibition of human epidermal melanocyte proliferation, melanin synthesis, and tyrosinase activity (p < 0.05). Interleukin-6-neutralizing antibody sufficiently reversed the antimelanogenic effects of adipose-derived stem cell-conditioned medium such that human epidermal melanocyte proliferation, melanin content, tyrosinase activity, and tyrosinase mRNA levels were restored (p < 0.05). Adipose-derived stem cell-conditioned medium inhibited melanocyte proliferation and melanin synthesis by down-regulating melanogenic enzymes. Interleukin-6 plays a pivotal role in inhibition of melanocytes.

  15. Therapeutic Self-Disclosure With Borderline Patients

    PubMed Central

    WILKINSON, SALLYE M.; GABBARD, GLEN O.

    1993-01-01

    The therapeutic use of countertransference disclosure as a means of highlighting the borderline patient’s intrapsychic and interpersonal use of the therapist is discussed. Countertransference disclosure is narrowly defined as a form of clinical honesty that focuses on the therapist’s experience of the patient in the here-and-now moment of the session. The effects of disclosure on transference exploration, neutrality, and patient revelations are explored through examination of detailed process notes of therapy sessions. Technical issues such as indirect versus direct disclosure and responses to direct questions are also addressed. PMID:22700154

  16. Mental capacity and borderline personality disorder

    PubMed Central

    Ayre, Karyn; Owen, Gareth S.; Moran, Paul

    2017-01-01

    The use of the Mental Capacity Act 2005 in assessing decision-making capacity in patients with borderline personality disorder (BPD) is inconsistent. We believe this may stem from persisting confusion regarding the nosological status of personality disorder and also a failure to recognise the fact that emotional dysregulation and characteristic psychodynamic abnormalities may cause substantial difficulties in using and weighing information. Clearer consensus on these issues is required in order to provide consistent patient care and reduce uncertainty for clinicians in what are often emergency and high-stakes clinical scenarios. PMID:28184315

  17. The Lifetime Course of Borderline Personality Disorder

    PubMed Central

    Biskin, Robert S

    2015-01-01

    Borderline personality disorder (BPD) has historically been seen as a lifelong, highly disabling disorder. Research during the past 2 decades has challenged this assumption. This paper reviews the course of BPD throughout life, including childhood, adolescence, and adulthood. BPD can be accurately identified in adolescence, and the course of the disorder, in adolescence and adulthood, is generally similar, with reductions in symptoms over time. Functional recovery is less consistent, and further research on factors or treatments that may improve the long-term functional outcome of patients with BPD is warranted. PMID:26175388

  18. Treating Obesity: Clinical Implications of Comorbid Borderline Personality Disorder.

    ERIC Educational Resources Information Center

    Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.

    1999-01-01

    Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)

  19. Borderline Personality Disorder: Too Complex for Cognitive Therapy?

    ERIC Educational Resources Information Center

    Pretzer, James L.

    Historically, the literature on psychotherapy with borderline personality disorder has been based on object-relations theory or psychoanalytical approaches, rather than cognitive and behavioral approaches. In clinical assessment, the term borderline has been used to refer to patients with both neurotic and psychotic symptoms, a particular type of…

  20. Familial Characteristics of Individuals with Borderline Personality Disorder Diagnosis.

    ERIC Educational Resources Information Center

    Bernhardt, James Lawrence

    This paper explores the findings and current state of research on the familial characteristics of persons with borderline personality disorder (BPD). A review of the borderline personality disorder emphasizes the development of the term, etiological issues, and treatment issues related to BPD. Two formal approaches for obtaining accurate diagnosis…

  1. Treating Obesity: Clinical Implications of Comorbid Borderline Personality Disorder.

    ERIC Educational Resources Information Center

    Sansone, Randy A.; Wiederman, Michael W.; Sansone, Lori A.

    1999-01-01

    Reviews possible links between obesity and borderline-personality disorder and discusses treatment approaches for those individuals demonstrating such comorbidity. Approaches include modification of current techniques for obesity treatment and incorporation of psychodynamic counseling specific to borderline-personality disorder. (Author/GCP)

  2. Parenting Children with Borderline Intellectual Functioning: A Unique Risk Population

    ERIC Educational Resources Information Center

    Fenning, Rachel M.; Baker, Jason K.; Baker, Bruce L.; Crnic, Keith A.

    2007-01-01

    Parenting was examined among families of children with borderline intelligence in comparison to families of typically developing children and children with developmental delays. Parenting data were obtained at child age 5 via naturalistic home observation. Mothers of children with borderline intelligence exhibited less positive and less sensitive…

  3. Adverse perinatal outcomes in borderline amniotic fluid index.

    PubMed

    Jamal, Ashraf; Kazemi, Maryam; Marsoosi, Vajiheh; Eslamian, Laleh

    2016-11-01

    Normal amniotic fluid predicts normal placental function, fetal growth and fetal well-being. To determine adverse pregnancy outcomes in borderline amniotic fluid index (AFI). Pregnant women (37-40 wks) with diagnosis of borderline AFI between December 2012 and August 2014 were identified. Antepartum, intrapartum and neonatal data were collected and compared with those of pregnant women with normal AFI. An AFI less than 8 and more than 5 cm was defined for borderline AFI. Pregnancy outcomes included Cesarean section for non-reassuring fetal heart rate, meconium stained amniotic fluid, 5-min Apgar score <7, low birth weight, umbilical cord blood pH at term and NICU admission. Gestational age at delivery in pregnancies with borderline AFI was significantly lower than normal AFI. Cesarean section rate for non-reassuring fetal heart rate in women of borderline AFI was significantly higher and there was an increased incidence of birth weight less than 10(th) percentile for gestation age in borderline AFI group. Incidence of low Apgar score and low umbilical artery pH in pregnancies with borderline AFI was significantly higher than women with normal AFI. There were no significant difference in the rate of NICU admission and meconium staining in both groups. There are significant differences for adverse pregnancy outcomes , such as Cesarean section due to non-reassuring fetal heart rate, birth weight less than 10(th) percentile for gestation age, low 5 min Apgar score and low umbilical artery pH between pregnancies with borderline and normal AFI.

  4. Principles in the Psychotherapy of Self-Destructive Borderline Patients

    PubMed Central

    PLAKUN, ERIC M.

    1994-01-01

    Patients with borderline personality disorder often exhibit lethal or nonlethal self-destructive behavior. The author offers seven principles for establishing and maintaining a therapeutic alliance in the insight-oriented psychodynamic psychotherapy of borderline personality disorder patients with self-destructive behavior serious enough to threaten the continuity of the therapy. PMID:22700187

  5. Sensitivity, specificity, and diagnostic accuracy of three dermoscopic algorithmic methods in the diagnosis of doubtful melanocytic lesions: the importance of light brown structureless areas in differentiating atypical melanocytic nevi from thin melanomas.

    PubMed

    Annessi, Giorgio; Bono, Riccardo; Sampogna, Francesca; Faraggiana, Tullio; Abeni, Damiano

    2007-05-01

    Over the past decade numerous epiluminescence microscopy (ELM) criteria and algorithmic methods have been developed to improve the diagnosis of cutaneous melanocytic lesions. Our purpose was to compare the sensitivity, specificity, and diagnostic accuracy of 3 algorithmic methods (pattern analysis, ABCD rule of dermoscopy, and the 7-point checklist) on a series of highly atypical melanocytic lesions. We also determined the diagnostic value of distinct ELM structures by evaluating their frequency in these lesions. A total of 198 consecutive atypical macular melanocytic lesions were studied. ELM assessment was based on the presence or absence of 23 dermoscopic features. Two ELM-experienced dermatologists classified each lesion as benign or malignant using the pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist method. After surgical excision, 102 lesions were histologically diagnosed as Clark's nevi and 96 as thin melanomas (TMs) (mean tumor thickness, 0.3 mm). ELM and histologic diagnoses were then compared to assess the sensitivity, specificity, and diagnostic accuracy as well as positive and negative predictive values (PPV and NPV, respectively) for TMs of the 3 algorithmic methods. Univariate and multivariate analyses were performed to determine which ELM criteria were most strongly associated with TM. Of the melanocytic lesions studied, 82.3% were correctly diagnosed by using pattern analysis (85.4% sensitivity, 79.4% specificity, 79.6% PPV, and 70.8% diagnostic accuracy), compared with correct diagnosis of 79.3% (84.4% sensitivity, 74.5% specificity, 75.7% PPV, and 67.8% diagnostic accuracy) and 71.2% (78.1% sensitivity, 64.7% specificity, 67.6% PPV, and 57.7% diagnostic accuracy) with the ABCD and the 7-point checklist methods, respectively. The 7-point checklist yielded the highest number of false-negative results (21.8%) with respect to the ABCD rule (15.6%) and pattern analysis (14.6%). Univariate analysis showed that an atypical

  6. Isolating RNA from precursor and mature melanocytes from human vitiligo and normal skin using laser capture microdissection.

    PubMed

    Goldstein, Nathaniel B; Koster, Maranke I; Hoaglin, Laura G; Wright, Michael J; Robinson, Steven E; Robinson, William A; Roop, Dennis R; Norris, David A; Birlea, Stanca A

    2016-10-01

    To characterize the gene expression profile of regenerated melanocytes in the narrow band UVB (NBUVB)-treated vitiligo epidermis and their precursors in the hair follicle, we present here a strategy of RNA isolation from in situ melanocytes using human frozen skin. We developed a rapid immunostaining protocol using the NKI-beteb antibody, which labels differentiated and precursor melanocytes, followed by fluorescent laser capture microdissection. This technique enabled the direct isolation, from melanocyte and adjacent keratinocyte populations, of satisfactory quality RNA that was successfully amplified and analysed by qRT-PCR. The melanocyte-specific gene transcripts TYR, DCT, TYRP1 and PMEL were significantly upregulated in our NBUVB-treated melanocyte samples as compared with the keratinocyte samples, while keratinocyte-specific genes (KRT5 and KRT14) were expressed significantly higher in the keratinocyte samples as compared with the melanocyte samples. Furthermore, in both NBUVB-treated vitiligo skin and normal skin, when bulge melanocytes were compared with epidermal melanocytes, we found significantly lower expression of melanocyte-specific genes and significantly higher expression of three melanocytic stem cell genes (SOX9, WIF1 and SFRP1), while ALCAM and ALDH1A1 transcripts did not show significant variation. We found significantly higher expression of melanocyte-specific genes in the epidermis of NBUVB-treated vitiligo, as compared to the normal skin. When comparing bulge melanocyte samples from untreated vitiligo, NBUVB-treated vitiligo and normal skin, we did not find significant differences in the expression of melanocyte-specific genes or melanocytic stem cell genes. These techniques offer valuable opportunities to study melanocytes and their precursors in vitiligo and other pigmentation disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Relationship between schizotypal and borderline traits in college students.

    PubMed

    Fonseca-Pedrero, Eduardo; Lemos-Giráldez, Serafín; Paino, Mercedes; Sierra-Baigrie, Susana; Muñiz, José

    2012-03-01

    The main objective of the present investigation was to analyze the relationship between self-reported schizotypal and borderline personality traits in a sample of 759 college students (M = 19.63 years; SD = 2.03). For this purpose, the Schizotypal Personality Questionnaire-Brief (SPQ-B; Raine and Benishay, 1995) and Borderline Personality Questionnaire (BPQ; Poreh et al., 2006) were administered. The results showed that schizotypal and borderline features are partially related at subclinical level. The exploratory factor analysis conducted on the subscales revealed a three-factor solution comprised of the following factors: Identity/Interpersonal, Lack of Control and Schizotypal. The canonical correlation analysis showed that schizotypal features and borderline personality traits shared 34.8% of the variance. The data highlight the overlap between schizotypal and borderline personality traits in nonclinical young adults. Future studies should continue to examine the relationship and the degree of overlap between these traits in community samples.

  8. The relationship between forgiveness and borderline personality symptomatology.

    PubMed

    Sansone, Randy A; Kelley, Amy R; Forbis, Jeremy S

    2013-09-01

    The relationship between forgiveness and borderline personality symptomatology has been rarely studied. Using a consecutive cross-sectional sample of 307 internal medicine outpatients and a survey methodology, we examined correlations between the Forgiveness Scale and borderline personality symptomatology as measured by the borderline personality disorder scale of the Personality Diagnostic Questionnaire-4 and the Self-Harm Inventory. Numerous forgiveness subscales as well as the composite Forgiveness Scale score demonstrated statistically significant relationships with both measures for borderline personality symptomatology, such that individuals with this personality pathology demonstrated lower scores on these forgiveness subscales. Findings indicate that among individuals with borderline personality symptomatology, there are numerous aspects of forgiveness that are significantly lower than in individuals without this symptomatology.

  9. [The mechanism of anti-tumor immune response against mouse melanoma to xenogeneic vaccination].

    PubMed

    Luo, Feng; Mao, Yong-qiu; Kan, Bing; He, Qiu-Ming; Jiang, Yu; Peng, Feng; Yang, Li; Tian, Ling

    2004-11-01

    To investigate the immunological mechanism for inhibiting melanoma growth in mouse by vaccination with xenogeneic melanocytes. Xenogeneic vaccine was prepared from pig eye melanocytes. By means of indirect ELISA the antibodies against pig melanocytes and B16 melanoma cells in immunized mice sera were detected and the immunoglobulin subclass were analyzed. Then after purification, the immunoglobulins were used for the inhibition of cell proliferation in vitro. Analyses of cross-reactive antigen in both pig melanocytes and B16 melanoma cells were performed by Western blot. Xenogeneic vaccine was used before B16 melanoma challenge in C57 BL/c mice and then the growth of tumor was monitored. Meanwhile, other mice immunized with xenogeneic vaccine were depleted of NK cells or CD4+ or CD8+ T lymphocytes. The antibodies against pig melanocytes and B16 melanoma cells in mice sera were not detected by indirect ELISA until 2 weeks after first xenogeneic vaccination, and after the first finding, the antibody titers increased with the time of immunization. The anti-tumor activity and production of autoantibodies, conspicuously those of the elevated IgG, could be abrogated by the depletion of CD4+ T lymphocytes. The cross-reactive antigen with 180 kda protein in both pig melanocytes and B16 melanoma cells was confirmed. Xenogeneic vaccination resulted in inhibition of tumor growth in 90% of the immunized mice. The protective immune response elicited in this fashion was dispelled in the mice depleted of CD4+ T lymphocytes. However this response was found in 70% of the mice depleted of CD8+ T lymphocytes, and the depletion NK cells did not influence the anti-tumor effect of the vaccine. The anti-tumor immune response is capable of inhibiting melanoma growth; both humoral immunity and cellular immunity could be induced by xenogeneic melanocytes vaccination. This immune response is mainly mediated by CD4+ T lymphocytes.

  10. Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.

    PubMed

    Koludrovic, Dana; Laurette, Patrick; Strub, Thomas; Keime, Céline; Le Coz, Madeleine; Coassolo, Sebastien; Mengus, Gabrielle; Larue, Lionel; Davidson, Irwin

    2015-10-01

    MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes.

  11. Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells

    PubMed Central

    Koludrovic, Dana; Laurette, Patrick; Strub, Thomas; Keime, Céline; Le Coz, Madeleine; Coassolo, Sebastien; Mengus, Gabrielle; Larue, Lionel; Davidson, Irwin

    2015-01-01

    MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes. PMID:26440048

  12. Relationships between melanocytes, mechanical properties and extracellular matrix composition in mouse heart valves.

    PubMed

    Carneiro, Flavia; Kruithof, Boudewijn Pt; Balani, Kanthesh; Agarwal, Arvind; Gaussin, Vinciane; Kos, Lidia

    2015-01-01

    Heart valves are complex structures composed of organized layers of extracellular matrix, and interstitial and overlying endothelial cells. In this article, we present the specific localization of a population of melanocytes within the murine heart valves at ages important for their post-natal development. In all stages analyzed in our study, melanocytes were found in high numbers populating the atrial aspect of the tricuspid and mitral leaflets. The pulmonary valve did not present melanocytes. To characterize a putative role for the valve melanocytes, the dynamic nanomechanical properties of tricuspid leaftets containing large numbers or no melanocytes were measured. The stiffness coefficient of hyperpigmented leaflets was higher (11.5 GPa) than the ones from wild-type (7.5 GPa) and hypopigmented (5.5 GPa) leaflets. These results suggest that melanocytes may contribute to the mechanical properties of the heart valves. The arrangement of extracellular matrix molecules such as Collagen I and Versican B is responsible for the mechanical characteristics of the leaflets. Melanocytes were found to reside primarily in areas of Versican B expression. The patterns of expression of Collagen I and Versican B were not, however, disrupted in hyper or hypopigmented leaflets. Melanocytes may affect other extracellular matrix molecules to alter the valves' microenvironment.

  13. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization.

    PubMed

    Birlea, Stanca A; Costin, Gertrude-E; Roop, Dennis R; Norris, David A

    2017-07-01

    Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. © 2016 Wiley Periodicals, Inc.

  14. Possible patterns of epidermal melanocyte disappearance in nonsegmental vitiligo: a clinicopathological study.

    PubMed

    Benzekri, L; Hmamouchi, I; Gauthier, Y

    2015-02-01

    The depigmentation of vitiligo results in a progressive and chronic melanocyte loss with rare melanocytes occasionally remaining in the epidermis or the hair follicle reservoirs. Destruction by immune infiltrates in close contact with melanocytes within microvesicles and/or detachment of melanocytes followed by their transepidermal elimination should be regarded as possible mechanisms of chronic loss of pigment cells. To assess the frequency of these two histological findings and to establish a direct correlation with clinical features. This was a prospective observational study that took place over 1 year. Each patient received a standardized evaluation that included daylight and Wood's lamp examinations, pictures, biopsies performed on the marginal area, and histological and immunohistological studies. A second examination to assess the activity of the lesions was performed 1 year after inclusion in the study. Clinical changes associated with microvesicles were compared with those associated with detached melanocytes from the basal layer. This study included 50 patients. The histological findings were classified as inflammatory with isolated microvesicles (29 cases), noninflammatory with only detached melanocytes from the basal layer (12 cases) and a combination of coexisting microvesicles and detached melanocytes (six cases). Correlations were obtained between the histological findings and clinical features (aspect and activity of the lesions) and E-cadherin expression. Our data suggest the existence of two patterns of melanocyte disappearance in nonsegmental vitiligo. © 2014 British Association of Dermatologists.

  15. Trends in Regenerative Medicine: Repigmentation in Vitiligo Through Melanocyte Stem Cell Mobilization

    PubMed Central

    Birlea, Stanca A.; Costin, Gertrude-E.; Roop, Dennis R.; Norris, David A.

    2017-01-01

    Vitiligo is the most frequent human pigmentary disorder, characterized by progressive autoimmune destruction of mature epidermal melanocytes. Of the current treatments offering partial and temporary relief, ultraviolet (UV) light is the most effective, coordinating an intricate network of keratinocyte and melanocyte factors that control numerous cellular and molecular signaling pathways. This UV-activated process is a classic example of regenerative medicine, inducing functional melanocyte stem cell populations in the hair follicle to divide, migrate, and differentiate into mature melanocytes that regenerate the epidermis through a complex process involving melanocytes and other cell lineages in the skin. Using an in-depth correlative analysis of multiple experimental and clinical data sets, we generated a modern molecular research platform that can be used as a working model for further research of vitiligo repigmentation. Our analysis emphasizes the active participation of defined molecular pathways that regulate the balance between stemness and differentiation states of melanocytes and keratinocytes: p53 and its downstream effectors controlling melanogenesis; Wnt/β-catenin with proliferative, migratory, and differentiation roles in different pigmentation systems; integrins, cadherins, tetraspanins, and metalloproteinases, with promigratory effects on melanocytes; TGF-β and its effector PAX3, which control differentiation. Our long-term goal is to design pharmacological compounds that can specifically activate melanocyte precursors in the hair follicle in order to obtain faster, better, and durable repigmentation. PMID:28029168

  16. Constitutive gray hair in mice induced by melanocyte-specific deletion of c-Myc

    PubMed Central

    Pshenichnaya, Irina; Schouwey, Karine; Armaro, Marzia; Larue, Lionel; Knoepfler, Paul S.; Eisenman, Robert N.; Trumpp, Andreas; Delmas, Véronique; Beermann, Friedrich

    2012-01-01

    Summary c-Myc is involved in the control of diverse cellular processes and implicated in the maintenance of different tissues including the neural crest. Here, we report that c-Myc is particularly important for pigment cell development and homeostasis. Targeting c-Myc specifically in the melanocyte lineage using the floxed allele of c-Myc and Tyr::Cre transgenic mice results in a congenital gray hair phenotype. The gray coat color is associated with a reduced number of functional melanocytes in the hair bulb and melanocyte stem cells in the hair bulge. Importantly, the gray phenotype does not progress with time, suggesting that maintenance of the melanocyte through the hair cycle does not involve c-Myc function. In embryos, at E13.5, c-Myc-deficient melanocyte precursors are affected in proliferation in concordance with a reduction in numbers, showing that c-Myc is required for the proper melanocyte development. Interestingly, melanocytes from c-Myc-deficient mice display elevated levels of the c-Myc paralog N-Myc. Double deletion of c-Myc and N-Myc results in nearly complete loss of the residual pigmentation, indicating that N-Myc is capable of compensating for c-Myc loss of function in melanocytes. PMID:22420299

  17. Giant congenital melanocytic nevus with developmental dysplasia of bilateral hip: a rare association.

    PubMed

    Imchen, Sutsungkokla; Ghosh, Sangita; Dayal, Surabhi; Marwah, Nisha; Jindal, Nidhi; Sangal, Shikha

    2013-11-01

    Giant congenital melanocytic nevi are rare congenital disfiguring benign neoplasms with a risk of transformation to malignant melanoma. They often present with various extra-cutaneous features. Here, we describe a case of giant melanocytic nevus with developmental dysplasia of bilateral hip, a novel association.

  18. Affective Disorders among Patients with Borderline Personality Disorder

    PubMed Central

    Sjåstad, Hege Nordem; Gråwe, Rolf W.; Egeland, Jens

    2012-01-01

    Background The high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders. Methods In a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice. Results More subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders. Conclusions The results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar

  19. Keratinocytes and fibroblasts in a human skin equivalent model enhance melanocyte survival and melanin synthesis after ultraviolet irradiation.

    PubMed

    Archambault, M; Yaar, M; Gilchrest, B A

    1995-05-01

    To investigate paracrine effects of fibroblasts and keratinocytes on melanocyte behavior after ultraviolet (UV) irradiation, we compared an in vitro skin equivalent model with melanocyte cultures. Human melanocytes were maintained alone in monolayer cultures or on dermal equivalents with or without keratinocytes and were irradiated daily with solar-simulated light. After seven daily UV irradiations, monolayer melanocytes displayed dose-dependent increases in cellular damage. In contrast, melanocytes on dermal equivalents survived strikingly better. Moreover, UV-irradiated skin equivalent melanocytes became highly dendritic as compared with sham-irradiated cells, closely mimicking their morphology in UV-irradiated skin. In addition, in skin equivalents melanocytes migrated from the center to the periphery of the keratinocyte layer after UV irradiation. Melanin production per culture, as measured by 14C-dihydroxyphenylalanine incorporation, was consistently higher in skin equivalent melanocytes than in monolayer melanocytes from the same donor, and it was highest in melanocytes from skin equivalents containing both keratinocytes and fibroblasts. Our data strongly suggest that fibroblasts and keratinocytes modulate melanocyte function in skin. The skin equivalent is a valuable model for investigating paracrine effects on melanocytes after UV irradiation.

  20. In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells.

    PubMed

    Allouche, Jennifer; Bellon, Nathalia; Saidani, Manoubia; Stanchina-Chatrousse, Laure; Masson, Yolande; Patwardhan, Anand; Gilles-Marsens, Floriane; Delevoye, Cédric; Domingues, Sophie; Nissan, Xavier; Martinat, Cécile; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

    2015-07-21

    "Café-au-lait" macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases.

  1. In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells

    PubMed Central

    Allouche, Jennifer; Bellon, Nathalia; Saidani, Manoubia; Stanchina-Chatrousse, Laure; Masson, Yolande; Patwardhan, Anand; Gilles-Marsens, Floriane; Delevoye, Cédric; Domingues, Sophie; Nissan, Xavier; Martinat, Cécile; Lemaitre, Gilles; Peschanski, Marc; Baldeschi, Christine

    2015-01-01

    “Café-au-lait” macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS oncogene. In contrast, the molecular mechanisms associated with alteration of skin pigmentation have remained elusive. We have reassessed this issue by differentiating human embryonic stem cells into melanocytes. In the present study, we demonstrate that NF1 melanocytes reproduce the hyperpigmentation phenotype in vitro, and further characterize the link between loss of heterozygosity and the typical CALMs that appear over the general hyperpigmentation. Molecular mechanisms associated with these pathological phenotypes correlate with an increased activity of cAMP-mediated PKA and ERK1/2 signaling pathways, leading to overexpression of the transcription factor MITF and of the melanogenic enzymes tyrosinase and dopachrome tautomerase, all major players in melanogenesis. Finally, the hyperpigmentation phenotype can be rescued using specific inhibitors of these signaling pathways. These results open avenues for deciphering the pathological mechanisms involved in pigmentation diseases, and provide a robust assay for the development of new strategies for treating these diseases. PMID:26150484

  2. Nicotinamide enhances repair of ultraviolet radiation-induced DNA damage in primary melanocytes.

    PubMed

    Thompson, Benjamin C; Surjana, Devita; Halliday, Gary M; Damian, Diona L

    2014-07-01

    Cutaneous melanoma is a significant cause of morbidity and mortality. Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. Here, we report the effect of nicotinamide on DNA damage and repair in primary human melanocytes. Nicotinamide significantly enhanced the repair of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine) and cyclobutane pyrimidine dimers induced by UV exposure. It also enhanced the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine induced by the culture conditions in unirradiated melanocytes. A significant increase in the percentage of melanocytes undergoing unscheduled but not scheduled DNA synthesis was observed, confirming that nicotinamide enhances DNA repair in human melanocytes. In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma.

  3. Oral Congenital Melanocytic Nevus: A Rare Case Report and Review of the Literature.

    PubMed

    Marangon Júnior, Helvécio; Souza, Paulo Eduardo Alencar; Soares, Rodrigo Villamarim; de Andrade, Bruno Augusto Benevenuto; de Almeida, Oslei Paes; Horta, Martinho Campolina Rebello

    2015-12-01

    Melanocytic nevi are congenital or acquired benign proliferations of cells of melanocytic origin. Oral congenital melanocytic nevi are rare, and only a few cases have been reported in the literature. The purpose of this study is to present the clinical, histological and immunohistochemical features of an oral congenital melanocytic nevus in a 16-year-old female with an 11-year follow-up and to review the pertinent literature. The reported case is the fifth well-documented case report of oral congenital melanocytic nevus in the English literature and the first with a long period of follow-up, thereby making it an important contribution to the knowledge regarding this uncommon oral mucosa lesion.

  4. The important role of interdisciplinary collaboration in the management of a melanocytic skin lesion

    PubMed Central

    Balato, Anna; Raimondo, Annunziata; Cantelli, Mariateresa; Siano, Maria; Lembo, Serena; Scalvenzi, Massimiliano; Balato, Nicola

    2011-01-01

    One of the most confounding characteristics, commonly seen in malignant, but even in benign melanocytic nevi, is represented by the regression phenomenon. The identification of regression, through dermoscopical observation, can be predictive of a tricky histopathological examination. Therefore, this feature should be an alert to a meticulous clinical, dermoscopical and histopathological correlation for correct analysis of melanocytic skin lesions. A 26-year-old man was referred to our department for a pigmented skin lesion localized on his trunk. It was clinically and dermoscopically diagnosed as atypical melanocytic nevus with central regression. After 1 year the lesion underwent considerable changes, leading to a nearly complete regression. The lesion was excised and, on the basis of clinical, dermoscopical and histopathological correlation, was interpreted as a junctional melanocytic nevus with regression. In our case the association of clinical, dermoscopical and histopathological experience, resulted an important and useful method, in order to proper interpret and correctly diagnose an atypical melanocytic skin lesion. PMID:25386254

  5. ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment.

    PubMed

    Pérez-Alea, M; McGrail, K; Sánchez-Redondo, S; Ferrer, B; Fournet, G; Cortés, J; Muñoz, E; Hernandez-Losa, J; Tenbaum, S; Martin, G; Costello, R; Ceylan, I; Garcia-Patos, V; Recio, J A

    2017-06-05

    Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. We found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. Furthermore, it is highly expressed in a large percentage of human nevi and melanomas during melanocyte transformation, which is consistent with the data from the TCGA, CCLE and protein atlas databases. Melanoma treatment with the novel irreversible isoform-specific ALDH1 inhibitor [4-dimethylamino-4-methyl-pent-2-ynthioic acid-S methylester] di-methyl-ampal-thio-ester (DIMATE) or depletion of ALDH1A1 and/or ALDH1A3, promoted the accumulation of apoptogenic aldehydes leading to apoptosis and tumor growth inhibition in immunocompetent, immunosuppressed and patient-derived xenograft mouse models. Interestingly, DIMATE also targeted the slow cycling label-retaining tumor cell population containing the tumorigenic and chemoresistant cells. Our findings suggest that aldehyde detoxification is relevant metabolic mechanism in melanoma cells, which can be used as a novel approach for melanoma treatment.Oncogene advance online publication, 5 June 2017; doi:10.1038/onc.2017.160.

  6. Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes.

    PubMed

    Chen, Tianzhi; Wang, Haidong; Liu, Yu; Zhao, Bingling; Zhao, Yuanyuan; Fan, Ruiwen; Wang, Pengchao; Dong, Changsheng

    2016-09-27

    To investigate whether ocular albinism type 1 (OA1) is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes' pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP1) and premelanosome protein (PMEL). However, the tyrosinase-related protein 2 (TRP2) level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB) was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may participate in the

  7. The most common mistakes on dermatoscopy of melanocytic lesions

    PubMed Central

    Kamińska-Winciorek, Grażyna

    2015-01-01

    Dermatoscopy is a method of in vivo evaluation of the structures within the epidermis and dermis. Currently, it may be the most precise pre-surgical method of diagnosing melanocytic lesions. Diagnostic errors may result in unnecessary removal of benign lesions or what is even worse, they can cause early and very early melanomas to be overlooked. Errors in assessment of dermatoscopy can be divided into those arising from failure to maintain proper test procedures (procedural and technical errors) and knowledge based mistakes related to the lack of sufficient familiarity and experience in dermatoscopy. The article discusses the most common mistakes made by beginner or inexperienced dermatoscopists. PMID:25821425

  8. ON THE ACTION OF COLCHICINE, THE MELANOCYTE MODEL.

    PubMed

    MALAWISTA, S E

    1965-08-01

    The effect of colchicine was studied on the rapid, reversible darkening of frog skin under the influence of melanocyte-stimulating hormone (MSH). Darkening is due to dispersion of melanin granules in melanocytes and is thought to be accompanied by a gel-to-sol cytoplasmic transformation. After subsequent washing, the skin lightens, with aggregation of melanin granules and cytoplasmic gelation. Preincubation of skin with colchicine had the following effects: 1. Darkening induced by MSH was increased in comparison to control skins, and on removal of MSH, lightening was inhibited. Inhibition was a function of both concentration (1 x 10(-5) to 9 x 10(-5)M) and exposure time (2 to 30 minutes). Once established, inhibition was maintained throughout the remainder of the experiment. 2. The same effects were noted (a) when darkening was effected by agents other than MSH (ATP) 0.9 x 10(-3)M; caffeine, 5.2 x 10(-3)M; ethyl acetate, 0.8 x 10(-2)M), and (b) when lightening was effected by addition of chemical agents (melatonin, 4.3 x 10(-10)M; hydrocortisone, 1 x 10(-3)M; norepinephrine, 1 x 10(-3)M), instead of by washing. 3. Colchicine alone produced a gradual, irreversible, dosage-dependent darkening over several hours. This darkening was inhibited by melatonin, 4.3 x 10(-10)M. The melanocyte model is used to construct a general theory of colchicine action on living cells, an action resulting in decreased protoplasmic viscosity. In this formulation colchicine lowers the potential limit of protoplasmic gelation, and does it rapidly, reversibly, in low concentration, in a dosage-dependent manner, and without killing the cell. The theory allows interpretation of "synergism" and "antagonism" to colchicine by other substances. It suggests a tentative approach to the understanding of colchicine action in acute gouty arthritis, where interference with ameboid activities of polymorphonuclear leukocytes is one possible aspect of the anti-inflammatory effect of colchicine. Finally

  9. Autologous noncultured melanocyte transplantation for stable vitiligo: can suspending autologous melanocytes in the patients' own serum improve repigmentation and patient satisfaction?

    PubMed

    Sahni, Kanika; Parsad, Davinder; Kanwar, Amrinderjit J; Mehta, Swami Dass

    2011-02-01

    Vitiligo is a cosmetically disfiguring acquired depigmenting disorder caused by the loss of functional melanocytes from the epidermis. Various approaches that have been used for the treatment of vitiligo can be classified as medical and surgical therapies. Noncultured autologous melanocyte transplantation is a new and effective surgical treatment for stable vitiligo. To compare the repigmentation results in stable vitiligo of transplantation of autologous noncultured melanocytes suspended in normal saline with that of those suspended in the patient's own serum. Twenty-five patients with 36 lesions of stable vitiligo were randomized into two groups for noncultured melanocyte transplantation. Patients in Group A received melanocytes suspended in normal saline, and those in Group B received melanocytes suspended in their own serum. Statistically significant difference in repigmentation results and reduction in Dermatology Life Quality Index (DLQI) score was observed between the two groups 16 weeks after surgery. Repigmentation results were excellent (>90%) and very good to excellent (>75%) in 44.4% and 66.7% of lesions, respectively, in Group A and 88.8% and 94.4% of lesions, respectively, in Group B. There was also a significant (p=.002) decline in DLQI score in both groups, with the mean reduction being significantly greater in Group B than Group A (p=.005). Results of noncultured melanocyte transplantation can be improved significantly more by suspending the melanocytes in the patients' autologous serum than in normal saline. This could be an important innovation in the surgical management of patients with stable vitiligo. © 2011 by the American Society for Dermatologic Surgery, Inc.

  10. PGE2 is a UVR-inducible autocrine factor for human melanocytes that stimulates tyrosinase activation

    PubMed Central

    Starner, Renny J.; McClelland, Lindy; Abdel-Malek, Zalfa; Fricke, Alex; Scott, Glynis

    2013-01-01

    Melanocyte proliferation, dendrite formation, and pigmentation are controlled by paracrine factors, particularly following exposure to ultraviolet radiation (UVR). Little is known about autocrine factors for melanocytes. Prostaglandins activate signaling pathways involved in growth, differentiation and apoptosis. Prostaglandin E2 (PGE2) is the most abundant prostaglandin released by keratinocytes following UVR, and stimulates the formation of dendrites in melanocytes. Synthesis of PGE2 is controlled by cPLA2, which releases arachidonic acid from membranes, and COX-2 and prostaglandin E2 synthases (PGES), which convert arachidonic acid to PGH2 and PGH2 to PGE2, respectively. In this report we show that multiple irradiations of human melanocytes with UVR stimulates tyrosinase activity, independent of expression of a functional melanocortin 1 receptor, suggesting the presence of a non-melanocortin autocrine factor. Irradiation of melanocytes activated cPLA2, the rate-limiting step in eicosanoid synthesis, and stimulated PGE2 secretion. PGE2 increased cAMP production, tyrosinase activity and proliferation in melanocytes. PGE2 binds to four distinct G-protein coupled receptors (EP1–4). We show that EP4 receptor signaling stimulates cAMP production in melanocytes. Conversely, stimulation of the EP3 receptor lowered basal cAMP levels. These data suggest that relative levels or activity of these receptors controls effects of PGE2 on cAMP in melanocytes. The data are the first to identify PGE2 as an UVR-inducible autocrine factor for melanocytes that stimulates tyrosinase activity and proliferation, and to show that EP3 and EP4 receptor signaling have opposing effects on cAMP production, a critical signaling pathway that regulates proliferation and melanogenesis in melanocytes. PMID:20500768

  11. Increased endogenous DNA oxidation correlates to increased iron levels in melanocytes relative to keratinocytes.

    PubMed

    Pelle, Edward; Huang, Xi; Zhang, Qi; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna

    2014-01-01

    The endogenous oxidative state of normal human epidermal melanocytes was investigated and compared to normal human epidermal keratinocytes (NHEKs) in order to gain new insight into melanocyte biology. Previously, we showed that NHEKs contain higher levels of hydrogen peroxide (H2O2) than melanocytes and that it can migrate from NHEKs to melanocytes by passive permeation. Nevertheless, despite lower concentrations of H2O2, we now report higher levels of oxidative DNA in melanocytes as indicated by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG): 4.49 (±0.55 SEM) 8-oxo-dG/10(6) dG compared to 1.49 (±0.11 SEM) 8-oxo-dG/10(6) dG for NHEKs. An antioxidant biomarker, glutathione (GSH), was also lower in melanocytes (3.14 nmoles (±0.15 SEM)/cell) in comparison to NHEKs (5.98 nmoles (±0.33 SEM)/cell). Intriguingly, cellular bioavailable iron as measured in ferritin was found to be nearly fourfold higher in melanocytes than in NHEKs. Further, ferritin levels in melanocytes were also higher than in hepatocarcinoma cells, an iron-rich cell, and it indicates that higher relative iron levels may be characteristic of melanocytes. To account for the increased oxidative DNA and lower GSH and H2O2 levels that we observe, we propose that iron may contribute to higher levels of oxidation by reacting with H2O2 through a Fenton reaction leading to the generation of DNA-reactive hydroxyl radicals. In conclusion, our data support the concept of elevated oxidation and high iron levels as normal parameters of melanocytic activity. We present new evidence that may contribute to our understanding of the melanogenic process and lead to the development of new skin care products.

  12. S100B as a potential biomarker for the detection of cytotoxicity of melanocytes.

    PubMed

    Cheong, Kyung Ah; Noh, Minsoo; Kim, Chang-Hyun; Lee, Ai-Young

    2014-03-01

    Skin irritation is one of the most common adverse reactions in hydroquinone (HQ) and retinoic acid (RA). Although melanocytes have rarely been considered to be involved in skin irritation, RA and particularly HQ could induce melanocyte toxicity, resulting in depigmentation. We chose S100B as a candidate gene for melanocytotoxicity from a genome-wide transcriptional profiling analysis after applying irritant doses of HQ, RA and sodium lauryl sulphate (SLS) to cultures of keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte viability and cytotoxicity was examined. S100B was detected in melanocytes, but not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing concentrations of HQ, RA, SLS and urushiol showed significant increases in intracellular and extracellular S100B expression with reduced viable cell number and increased release of lactate dehydrogenase. No RAGE expression and no significant function of CD166/ALCAM in melanocyte survival and cytotoxicity favoured the role of intracellular S100B in chemically irritated melanocytes. S100B knock-down increased apoptosis through inhibition of PI3K/AKT, NF-κB and ERK activation, suggesting the increased intracellular S100B expression by chemical irritation as a compensatory reaction to reduce cytotoxicity. The numerical decrease in S100B/c-kit-double-positive melanocytes was also examined in human skin epidermis irritated by HQ or RA with stronger staining intensities of S100B. Collectively, the decrease in viable cell number by reduced intracellular S100B levels in vitro and by chemical irritation in vivo suggests that S100B could be a potential biomarker for melanocytes cytotoxicity.

  13. Neuroendocrine functions of melanocytes: beyond the skin-deep melanin maker.

    PubMed

    Takeda, Kazuhisa; Takahashi, Na-Ho; Shibahara, Shigeki

    2007-03-01

    The skin is armored with "dead cells", the stratum corneum, and is continuously exposed to external stressful environments, such as atmospheric oxygen, solar radiations, and thermal and chemical insults. Melanocytes of neural crest origin are located in the skin, eye, inner ear, and leptomeninges. Melanin pigment in the skin is produced by melanocytes under the influence of various endogenous factors, derived from neighboring keratinocytes and underlying fibroblasts. The differentiation and functions of melanocytes are regulated at multiple processes, including transcription, RNA editing, melanin synthesis, and the transport of melanosomes to keratinocytes. Impairment at each step causes the pigmentary disorders in humans, with the historical example of oculocutaneous albinism. Moreover, heterozygous mutations in the gene coding for microphthalmia-associated transcription factor, a key regulator for melanocyte development, are associated with Waardenburg syndrome type 2, an auditory-pigmentary disorder. Sun tanning, melasma, aging spots (lentigo senilis), hair graying, and melanoma are well-known melanocyte-related pathologies. Melanocytes therefore have attracted much attention of many ladies, makeup artists and molecular biologists. More recently, we have shown that lipocalin-type prostaglandin D synthase (L-PGDS) is expressed in melanocytes but not in other skin cell types. L-PGDS generates prostaglandin D2 and also functions as an inter-cellular carrier protein for lipophilic ligands, such as bilirubin and thyroid hormones. Thus, melanocytes may exert hitherto unknown functions through L-PGDS and prostaglandin D2. Here we update the neuroendocrine functions of melanocytes and discuss the possible involvement of melanocytes in the control of the central chemosensor that generates respiratory rhythm.

  14. Glabrous lesional stem cells differentiated into functional melanocytes: new hope for repigmentation.

    PubMed

    Kumar, R; Parsad, D; Rani, S; Bhardwaj, S; Srivastav, N

    2016-09-01

    Vitiligo is characterized by the loss of pigment-producing cells, melanocytes and one of the important goals of treatment is replenishing the melanocytes from existing reservoirs. Reservoir for melanocyte stem cell has been reported to be present in the skin hair follicles, but glabrous skin does not have hair follicles. Therefore, repigmentation of glabrous lesional skin is very difficult and almost rare. There is no explanation for melanocyte reservoir in the glabrous lesional skin of vitiligo patients. This study is designed to check the glabrous lesional skin for the presence of stem cells as source of melanocytes for repigmentation. Skin grafts were collected from glabrous lesional skin of vitiligo patients. Immunohistochemistry of glabrous lesional skin was performed to check for the presence of stem cells. These glabrous lesional stem cells were isolated, cultured and characterized. After characterization, glabrous lesional stem cells were differentiated into melanocytes. Our results demonstrate that NGFRp75-positive stem cells are present in the glabrous lesional skin of vitiligo patients and can be differentiated into melanocytes. These dermal stem cells showed self-renewal capacity and were capable of differentiating into melanocytes which are required for the repigmentation. Presence of stem cells in the glabrous lesional skin which are capable of self-renewal and differentiating into melanocytes gives new hope for vitiligo patients having lesion on the glabrous skin. However, still repigmentation of glabrous lesional skin is very difficult and rare with current available treatments. This clearly means that treatments available till date are not effective enough to activate these dermal stem cells differentiation and their migration to the lesional epidermis. Stimulating these stem cells to differentiate into melanocytes and migrate to lesional epidermis can be ideal for repigmentation of the glabrous lesions. © 2016 European Academy of Dermatology and

  15. Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

    PubMed Central

    Blackiston, Douglas; Adams, Dany S.; Lemire, Joan M.; Lobikin, Maria; Levin, Michael

    2011-01-01

    SUMMARY Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl). Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT). These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior. PMID:20959630

  16. The E3 ligase APC/C(Cdh1) promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth.

    PubMed

    Cao, Juxiang; Dai, Xiangpeng; Wan, Lixin; Wang, Hongshen; Zhang, Jinfang; Goff, Philip S; Sviderskaya, Elena V; Xuan, Zhenyu; Xu, Zhixiang; Xu, Xiaowei; Hinds, Philip; Flaherty, Keith T; Faller, Douglas V; Goding, Colin R; Wang, Yongjun; Wei, Wenyi; Cui, Rutao

    2015-09-01

    The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/C(Cdh1)) is an E3 ubiquitin ligase involved in the control of the cell cycle. Here, we identified sporadic mutations occurring in the genes encoding APC components, including Cdh1, in human melanoma samples and found that loss of APC/C(Cdh1) may promote melanoma development and progression, but not by affecting cell cycle regulatory targets of APC/C. Most of the mutations we found in CDH1 were those associated with ultraviolet light (UV)-induced melanomagenesis. Compared with normal human skin tissue and human or mouse melanocytes, the abundance of Cdh1 was decreased and that of the transcription factor PAX3 was increased in human melanoma tissue and human or mouse melanoma cell lines, respectively; Cdh1 abundance was further decreased with advanced stages of human melanoma. PAX3 was a substrate of APC/C(Cdh1) in melanocytes, and APC/C(Cdh1)-mediated ubiquitylation marked PAX3 for proteolytic degradation in a manner dependent on the D-box motif in PAX3. Either mutating the D-box in PAX3 or knocking down Cdh1 prevented the ubiquitylation and degradation of PAX3 and increased proliferation and melanin production in melanocytes. Knocking down Cdh1 in melanoma cells in culture or before implantation in mice promoted doxorubicin resistance, whereas reexpressing wild-type Cdh1, but not E3 ligase-deficient Cdh1 or a mutant that could not interact with PAX3, restored doxorubicin sensitivity in melanoma cells both in culture and in xenografts. Thus, our findings suggest a tumor suppressor role for APC/C(Cdh1) in melanocytes and that targeting PAX3 may be a strategy for treating melanoma.

  17. Human skin model containing melanocytes: essential role of keratinocyte growth factor for constitutive pigmentation-functional response to α-melanocyte stimulating hormone and forskolin.

    PubMed

    Duval, Christine; Chagnoleau, Corinne; Pouradier, Florence; Sextius, Peggy; Condom, Elodie; Bernerd, Françoise

    2012-12-01

    To study human skin pigmentation in a physiological in vitro model, we developed a pigmented reconstructed skin reproducing the three-dimensional architecture of the melanocyte environment and the interactions of melanocyte with its cellular partners, keratinocytes, and fibroblasts. Co-seeding melanocytes and keratinocytes onto a fibroblast-populated collagen matrix led to a correct integration of melanocytes within the epidermal basal layer, but melanocytes remained amelanotic even after supplementation with promelanogenic factors. Interestingly, normalization of keratinocyte differentiation using keratinocyte growth factor instead of epidermal growth factor finally allowed an active pigmentary system to develop, as shown by the expression of key melanogenic markers, the production, and transfer of melanosome-containing melanin into keratinocytes. Various degrees of constitutive pigmentation were reproduced using melanocytes from different skin phenotypes. Furthermore, induction of pigmentation was achieved by treatment with known propigmenting molecules, αMSH and forskolin, thus demonstrating the functionality of the pigmentary system. This pigmented full-thickness skin model therefore represents a highly relevant tool to study the role of cell-cell, cell-matrix, and mesenchymal-epithelial interactions in the control of skin pigmentation.

  18. Borderline personality features in depressed or anxious patients.

    PubMed

    Distel, Marijn A; Smit, Johannes H; Spinhoven, Philip; Penninx, Brenda W J H

    2016-07-30

    Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety. Assessments included the Personality Assessment Inventory - Borderline Features Scale and several clinical characteristics of anxiety and depression. Borderline personality features were more common in depression than in anxiety. Current comorbid anxiety and depression was associated with most borderline personality features. Anxiety and depression status explained 29.7% of the variance in borderline personality features and 3.8% (self-harm) to 31% (identity problems) of the variance in the four domains. A large part of the variance was shared between anxiety and depression but both disorders also explained a significant amount of unique variance. The severity of anxiety and depression and the level of daily dysfunctioning was positively associated with borderline personality features. Individuals with a longer duration of anxiety and depression showed more affective instability and identity problems. These findings suggest that patients with anxiety and depression may benefit from an assessment of personality pathology as it may have implications for psychological and pharmacological treatment.

  19. The prevalence of borderline personality symptoms in adolescents.

    PubMed

    Mohammadi, Mohammad Reza; Shamohammadi, Morteza; Salmanian, Maryam

    2014-07-01

    This study aimed to assess the prevalence of borderline personality symptoms in 16-18 year old adolescents. In this cross sectional - descriptive study, 422 high school students (211 boys, 211 girls) aged 16-18 were selected by cluster random sampling and simple random sampling in 2011-2012. The participants were assessed using the revised diagnostic interview for borderline questionnaire (DIB-R) and demographic questionnaire. Data were analyzed using Pearson correlation coefficient and Spearman correlation coefficient. Of the participants, 0/9% (0/22 % of the 16 year olds, 0.45 % of the 17 year olds and 0/22% of the 18 year olds) were diagnosed with borderline personality symptoms. Also, the prevalence of borderline personality symptoms in boys was 0/45 % of the total sample and it was 0/45 % of the total sample in girls. With respect to the relationship between demographic variables (age, sex, location, parents' occupation, parents' kinship, parents' education and birth order) and borderline personality symptoms, only parents' kinship showed a weak correlation with borderline personality symptoms. In the view of the prevalence of 0.9% of the borderline personality symptoms in adolescents, attention should be paid to the diagnosis and treatment of this disorder. Furthermore, works need to be done to improve the mental health and quality of life of adolescents.

  20. Covariance and specificity in adolescent schizotypal and borderline trait expression.

    PubMed

    Badoud, Deborah; Billieux, Joël; Eliez, Stephan; Imhof, Anouk; Heller, Patrick; Eytan, Ariel; Debbané, Martin

    2015-10-01

    The first aim of the present study is to assess the overlap between borderline and schizotypal traits during adolescence. The second objective is to examine whether some psychological factors (i.e. cognitive coping mechanisms, impulsivity and encoding style) are differentially related to borderline and schizotypal traits and may therefore improve the efficiency of clinical assessments. One hundred nineteen community adolescents (57 male) aged from 12 to 19 years completed a set of questionnaires evaluating the expression of borderline and schizotypal traits as well as cognitive emotion regulation (CER), impulsivity and encoding style. Our data first yielded a strong correlation between borderline and schizotypal scores (r = 0.70, P < 0.001). Secondly, linear regression models indicated that the 'catastrophizing' CER strategy and the 'lack of premeditation' impulsivity facet accounted for the level of borderline traits, whereas an internal encoding style predominantly explained schizotypal traits. Our results support the abundant literature showing that borderline and schizotypal traits frequently co-occur. Moreover, we provide original data indicating that borderline and schizotypal traits during adolescence are linked to different specific psychological mechanisms. Thus, we underline the importance of considering these mechanisms in clinical assessments, in particular to help disentangle personality disorder traits in youths. © 2014 Wiley Publishing Asia Pty Ltd.

  1. Borderline Personality and the Detection of Angry Faces.

    PubMed

    Hepp, Johanna; Hilbig, Benjamin E; Kieslich, Pascal J; Herzog, Julia; Lis, Stefanie; Schmahl, Christian; Niedtfeld, Inga

    2016-01-01

    Many studies have assessed emotion recognition in patients with Borderline Personality Disorder and considerable evidence has been accumulated on patients' ability to categorize emotions. In contrast, their ability to detect emotions has been investigated sparsely. The only two studies that assessed emotion detection abilities found contradictory evidence on patients' ability to detect angry faces. To clarify whether patients with Borderline Personality Disorder show enhanced detection of angry faces, we conducted three experiments: a laboratory study (n = 53) with a clinical sample and two highly powered web studies that measured Borderline features (n1 = 342, n2 = 220). Participants in all studies completed a visual search paradigm, and the reaction times for the detection of angry vs. happy faces were measured. Consistently, data spoke against enhanced detection of angry faces in the Borderline groups, indicated by non-significant group (Borderline vs. healthy control) × target (angry vs. happy) interactions, despite highly satisfactory statistical power to detect even small effects. In contrast to emotion categorization, emotion detection appears to be intact in patients with Borderline Personality Disorder and individuals high in Borderline features. The importance of distinguishing between these two processes in future studies is discussed.

  2. Problematizing the concept of the "borderline" group in performance assessments.

    PubMed

    Homer, Matt; Pell, Godfrey; Fuller, Richard

    2017-05-01

    Many standard setting procedures focus on the performance of the "borderline" group, defined through expert judgments by assessors. In performance assessments such as Objective Structured Clinical Examinations (OSCEs), these judgments usually apply at the station level. Using largely descriptive approaches, we analyze the assessment profile of OSCE candidates at the end of a five year undergraduate medical degree program to investigate the consistency of the borderline group across stations. We look specifically at those candidates who are borderline in individual stations, and in the overall assessment. While the borderline group can be clearly defined at the individual station level, our key finding is that the membership of this group varies considerably across stations. These findings pose challenges for some standard setting methods, particularly the borderline group and objective borderline methods. They also suggest that institutions should ensure appropriate conjunctive rules to limit compensation in performance between stations to maximize "diagnostic accuracy". In addition, this work highlights a key benefit of sequential testing formats in OSCEs. In comparison with a traditional, single-test format, sequential models allow assessment of "borderline" candidates across a wider range of content areas with concomitant improvements in pass/fail decision-making.

  3. Targeted Melanoma Imaging and Therapy with Radiolabeled Alpha-Melanocyte Stimulating Hormone Peptide Analogues

    PubMed Central

    Quinn, Thomas; Zhang, Xiuli; Miao, Yubin

    2010-01-01

    Radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogues have been used to define the expression, affinity and function of the melanocortin-1 receptor (MC1-R). The MC1-R is one of a family of five G-protein linker receptors, which is primarily involved in regulation of skin pigmentation. Over-expression of the MC1-R on melanoma tumor cells has made it an attractive target for the development of α-MSH peptide based imaging and therapeutic agents. Initially, the native α-MSH peptide was radiolabeled directly, but it suffered from low specific activity and poor stability. The addition of non-natural amino acids yielded α-MSH analogues with greater MC-1R affinity and stability. Furthermore, peptide cyclization via disulfide and lactam bond formation as well as site-specific metal coordination resulted in additional gains in receptor affinity and peptide stability in vitro and in vivo. Radiochemical stability of the α-MSH analogues was improved through the conjugation of metal chelators to the peptide’s N-terminus or lysine residues for radionuclide coordination. In vitro cell binding studies demonstrated that the radiolabeled α-MSH analogues had low to subnanomolar affinities for the MC1-R. Biodistribution and imaging studies in the B16 mouse melanoma modeled showed rapid tumor uptake of the radiolabeled peptides, with the cyclic peptides demonstrating prolonged tumor retention. Cyclic α-MSH analogues labeled with beta and alpha emitting radionuclides demonstrated melanoma therapeutic efficacy in the B16 melanoma mouse model. Strong pre-clinical imaging and therapy data highlight the clinical potential use of radiolabeled α-MSH peptides for melanoma imaging and treatment of disseminated disease. PMID:20467398

  4. The actions of melanin and melanocyte stimulating hormone (MSH).

    PubMed

    Rasmussen, Natalie; Nelson, Francine; Govitrapong, Piyarat; Ebadi, Manuchair

    1999-01-01

    The skin, the largest organ of the body, plays an important role in the total metabolism of several hormones. Melanin, the major product of the melanocyte, is largely responsible for the coloring of skin. Melanin is a complex of insoluble, polyquinone, brown or red pigment and protein, formed by the oxidation of tyrosine and 3,4-dihydroxyphenylalanine in the presence of tyrosinase. There exists two main groups of melanin: the black to dark-brown insoluble eumelanins and the yellow to reddish brown, alkali-soluble pheomelanins. MSH, ACTH and beta-lipoprotein are able to influence skin pigmentation. The functions attributed to melanins are acting as a barrier against ionizing radiation; participating in developmental processes, serving as a cosmetic entity, and scavenging cytotoxic radicals and intermediates. Melanocytes express numerous receptors that allow interaction with other cells in their microenvironment, including keratinocytes and the immune component of the skin Langerhans cells. Albinism represents a group of inherited abnormalities that present with congenital hypopigmentation that can involve the skin, hair, and eyes (oculocutaneous albinism) or be limited primarily to the eyes (ocular albinism). The inherited disorders of keratin include epidermolysis bullosu simplex causing cell degeneration within the basal layer. Sunlight and ultraviolet radiation from artificial light sources could be tonic or toxic to human skin. The harmful effects of solar radiation are skin cancer, photosensitivity diseases, sunburn, photoallergy, photoimmunologic alterations, cataracts, mutations, skin aging and phototoxicity. Sunscreen chemicals protect the skin against ultraviolet radiation.

  5. Beta-catenin inhibits melanocyte migration but induces melanoma metastasis

    PubMed Central

    Gallagher, Stuart J.; Rambow, Florian; Kumasaka, Mayuko; Champeval, Delphine; Bellacosa, Alfonso; Delmas, Véronique; Larue, Lionel

    2013-01-01

    The canonical Wnt signalling pathway induces the β-catenin/LEF transcription factors. It is activated in various cancers, most characteristically carcinomas, in which it promotes metastatic spread by increasing migration and/or invasion. The Wnt/β-catenin signalling pathway is frequently activated in melanoma, but the presence of β-catenin in the nucleus does not seem to be a sign of aggressiveness in these tumours. We found that, unlike its positive role in stimulating migration and invasion of carcinoma cells, β-catenin signalling decreased the migration of melanocytes and melanoma cell lines. In vivo, β-catenin signalling in melanoblasts reduced the migration of these cells, causing a white belly-spot phenotype. The inhibition, by β-catenin of migration was dependent on MITF-M, a key transcription factor of the melanocyte lineage, and CSK, a Src-inhibitor. Despite reducing migration, β-catenin signalling promoted lung metastasis in the Nras-driven melanoma murine model. Thus, β-catenin may play conflicting roles in the metastatic spread of melanoma, repressing migration while promoting metastasis. These results highlight that metastasis formation requires a series of successful cellular processes, any one of which may not be optimally efficient. PMID:22665063

  6. Dracula. Disorders of the self and borderline personality organization.

    PubMed

    Raines, J M; Raines, L C; Singer, M

    1994-12-01

    It has been proposed that Bram Stoker's novel Dracula can best be understood as a dramatic, hyperbolic, and fantastic expression of themes consistent with contemporary psychoanalytic conceptions of borderline personality disorder organization. Such an understanding may, in turn, shed further light on the nature of the intrapsychic world and experiences of borderline patients. Excerpts from the novel can be used to support the conceptualization of recent contributions to object relations theory and the understanding of borderline personality organization. It is uncanny how consistent Dracula's characteristics are to the generally seen complaints of patients suffering from this disorder.

  7. Malevolent object representations in borderline personality disorder and major depression.

    PubMed

    Nigg, J T; Lohr, N E; Western, D; Gold, L J; Silk, K R

    1992-02-01

    To study malevolent representations, earliest memories were reliably coded on scales of affect tone. Ss were diagnosed with borderline personality disorder: 31 without and 30 with concurrent major depression. Nonborderline comparison subjects had either major depressive disorder (n = 26) or no psychiatric diagnosis (n = 30). Borderline subjects were discriminated from comparison subjects by their more malevolent representations; they more frequently produced memories involving deliberate injury; and they portrayed potential helpers as less helpful. Results suggest the diagnostic significance of malevolent representations, which need to be explained by any theory of borderline personality disorder.

  8. Beyond borderline personality disorder: the mindful brain.

    PubMed

    Chafos, Vanessa H; Economou, Peter

    2014-10-01

    Numerous studies have showed an improvement in symptoms characteristic of borderline personality disorder (BPD) when mindfulness-based interventions were integrated into the daily lives of individuals with BPD. Although these studies have examined the etiology and diagnostic prognosis of BPD, and have discussed the use of mindfulness-based treatments, few researchers have attempted to interpret the neuroscientific findings, which have showed an increase in gray matter in key areas of the brain in clients with BPD who engaged in mindfulness practice. Some clients who had originally met a minimum of five of the DSM-IV-TR diagnostic criteria for BPD no longer did so upon engaging in mindfulness-based treatment. This article highlights the efficacy of mindfulness-based interventions with an emphasis on meditation, which leads to overall better psychological functioning in clients with BPD in three key areas: impulsivity, emotional irregularity, and relationship instability.

  9. Emotional Granularity and Borderline Personality Disorder

    PubMed Central

    Suvak, Michael K.; Litz, Brett T.; Sloan, Denise M.; Zanarini, Mary C.; Barrett, Lisa Feldman; Hofmann, Stefan G.

    2011-01-01

    This study examined the affective dysregulation component of borderline personality disorder (BPD) from an emotional granularity perspective, which refers to the specificity in which one represents emotions. Forty-six female participants meeting criteria for BPD and 51 female control participants without BPD and Axis I pathology completed tasks that assessed the degree to which participants incorporated information about valence (pleasant–unpleasant) and arousal (calm–activated) in their semantic/conceptual representations of emotions and in using labels to represent emotional reactions. As hypothesized, participants with BPD emphasized valence more and arousal less than control participants did when using emotion terms to label their emotional reactions. Implications and future research directions are discussed. PMID:21171723

  10. Borderline personality disorder and depression: an update.

    PubMed

    Luca, Maria; Luca, Antonina; Calandra, Carmela

    2012-09-01

    To review the literature related to recent temperamental and biological findings on borderline personality disorder (BPD) and major depression, the close link between the two disorders, and the latest therapeutical findings on BPD, focusing on the conditions of co-morbidity between depression and BPD. The National Institutes of Health's PubMed database was used to identify indexed studies on BPD, depression and the co-morbidity between the two. Only studies published between 2000 and 2011 were assessed. Similar temperamental features have been demonstrated in BPD and depression. The strong link between the two disorders seems to be widely recognized by scientific community. Psychotherapy and new antipsychotics are the topics of current major interest of research. The therapeutic targets in the case of co-morbidity are BPD features associated with depressive symptoms, thus influencing prognosis. A global assessment is, in fact, fundamental for a successful therapy for the treatment of the several aspects of a complex psychopathological phenomenon.

  11. Attachment, borderline personality, and romantic relationship dysfunction.

    PubMed

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  12. Borderline personality and substance use in women.

    PubMed

    Feske, Ulrike; Tarter, Ralph E; Kirisci, Levent; Pilkonis, Paul A

    2006-01-01

    The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD.

  13. ATTACHMENT, BORDERLINE PERSONALITY, AND ROMANTIC RELATIONSHIP DYSFUNCTION

    PubMed Central

    Hill, Jonathan; Stepp, Stephanie D.; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q.; Steele, Miriam; Steele, Howard; Pilkonis, Paul A.

    2014-01-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25–36. Study 2 consisted of a psychiatric sample (N = 138) aged 21–60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction. PMID:22217225

  14. Borderline personality disorder and emotional intelligence.

    PubMed

    Peter, Mathell; Schuurmans, Hanneke; Vingerhoets, Ad J J M; Smeets, Guus; Verkoeijen, Peter; Arntz, Arnoud

    2013-02-01

    The present study investigated emotional intelligence (EI) in borderline personality disorder (BPD). It was hypothesized that patients with BPD (n = 61) compared with patients with other personality disorders (PDs; n = 69) and nonpatients (n = 248) would show higher scores on the ability to perceive emotions and impairments in the ability to regulate emotions. EI was assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test (Mayer, Salovey, and Caruso [New York: MHS, 2002]). As compared with the PD group and the nonpatient group, the patients with BPD displayed the anticipated deficits in their ability to understand, whereas no differences emerged with respect to their ability to perceive, use, and regulate emotions. In addition, a negative relationship was found between the severity of BPD and total EI score. However, this relationship disappeared when intelligence quotient was partialled out. These results suggest that BPD is associated with emotion understanding deficits, whereas temporary severity of BPD is associated with emotion regulation deficits.

  15. Psychopharmacologic treatment of borderline personality disorder.

    PubMed

    Ripoll, Luis H

    2013-06-01

    The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning.

  16. [Discriminative features of borderline personality disorder].

    PubMed

    Kazuko, Tamura; Inoue, Kako

    2009-02-01

    This study investigated some discriminative features of Borderline Personality Disorder (BPD) with both clinical and normal samples using a self-report questionnaire. This questionnaire was administered to 116 clinical outpatients (diagnoses: thirty two BPD; twenty four schizophrenia; twenty six depression; twenty nine neurosis; and five other mental disorders) and to 216 college students as a normal sample. Factor analysis produced six factors: emptiness; hallucination and egorrhea; distortional body image and acts of self-inflicted injury; impulsive acting-out; loss of emotional control; and grandiose omnipotence. Distortional body image and acts of self-inflicted injury discriminated BPD the most from the other samples. No significant differences were seen between the BPD and Schizophrenia samples in terms of the hallucination or egorrhea subscales. An intense loss of emotional control, particularly control of negative emotions such as rage, was apparent in the clinical samples, which was not evident in the normal sample.

  17. Psychopharmacologic treatment of borderline personality disorder

    PubMed Central

    Ripoll, Luis H.

    2013-01-01

    The best available evidence for psychopharmacologic treatment of borderline personality disorder (BPD) is outlined here. BPD is defined by disturbances in identity and interpersonal functioning, and patients report potential medication treatment targets such as impulsivity, aggression, transient psychotic and dissociative symptoms, and refractory affective instability Few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, although multiple reviews have converged on the effectiveness of specific anticonvulsants, atypical antipsychotic agents, and omega-3 fatty acid supplementation. Stronger evidence exists for medication providing significant improvements in impulsive aggression than in affective or other interpersonal symptoms. Future research strategies will focus on the potential role of neuropeptide agents and medications with greater specificity for 2A serotonin receptors, as well as optimizing concomitant implementation of evidence-based psychotherapy and psychopharmacology, in order to improve BPD patients' overall functioning. PMID:24174895

  18. Borderline intellectual functioning: a systematic literature review.

    PubMed

    Peltopuro, Minna; Ahonen, Timo; Kaartinen, Jukka; Seppälä, Heikki; Närhi, Vesa

    2014-12-01

    The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health problems. When adults with BIF were compared with the general population, they held lower-skilled jobs and earned less money. Although some risk factors (e.g., low birth weight) and preventive factors (e.g., education) were reported, they were not specific to BIF. The review finds that, despite the obvious everyday problems, BIF is almost invisible in the field of research. More research, societal discussion, and flexible support systems are needed.

  19. Computational Psychiatry in Borderline Personality Disorder.

    PubMed

    Fineberg, Sarah K; Stahl, Dylan; Corlett, Philip

    2017-03-01

    We review the literature on the use and potential use of computational psychiatry methods in Borderline Personality Disorder. Computational approaches have been used in psychiatry to increase our understanding of the molecular, circuit, and behavioral basis of mental illness. This is of particular interest in BPD, where the collection of ecologically valid data, especially in interpersonal settings, is becoming more common and more often subject to quantification. Methods that test learning and memory in social contexts, collect data from real-world settings, and relate behavior to molecular and circuit networks are yielding data of particular interest. Research in BPD should focus on collaborative efforts to design and interpret experiments with direct relevance to core BPD symptoms and potential for translation to the clinic.

  20. Molecular pharmacognosy: a new borderline discipline.

    PubMed

    Huang, Lu-Qi; Yuan, Yuan; Cui, Guang-Hong; Dai, Zhu-Bo; Xiao, Pei-Gen

    2009-11-01

    Pharmacognosy has developed rapidly in recent years and now represents a highly interdisciplinary science. At the boundary between pharmacognosy and molecular biology, molecular pharmacognosy has developed as a new borderline discipline. Using the method and technology of molecular biology, molecular pharmacognosy focuses on resolving a wide range of challenging problems, such as distinguishing herbal and animal drug populations by molecular marker assay, conserving and utilizing wild resources on the basis of knowledge of genetic diversity, investigating the mechanism of active compound accumulation and obtaining new resources with higher quality through genetic engineering. Recent research results show that molecular pharmacognosy has extended the scope of pharmacognostical science and plays an important role in the safe and efficient usage of crude drugs.

  1. Developmental trajectories to male borderline personality disorder.

    PubMed

    Goodman, Marianne; Patel, Uday; Oakes, Allison; Matho, Andrea; Triebwasser, Joseph

    2013-12-01

    Due to the higher diagnostic prevalence of borderline personality disorder (BPD) in females, there exists a dearth of literature on the manifestations of BPD in men and minimal information on male developmental trajectories to the disorder. To identify precursors of BPD in males, surveys were administered to parents about their BPD male offspring and non-BPD male siblings. Questions covered aspects of probands' lives from infancy to late adolescence. BPD offspring were identified through self-reported clinical diagnoses and standardized diagnostic criteria embedded within the survey. A total of 263 male offspring (97 meeting strict criteria for BPD and 166 non-BPD siblings) were studied. The authors found that parents describe the early emergence of a constellation of symptoms in their BPD sons that include separation anxiety starting in infancy, body image concerns in childhood, and impulsivity, emptiness, and odd thinking in adolescence. This trajectory differs from the developmental course found in females diagnosed with BPD.