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Sample records for borderline melanocytic tumor

  1. Germline mutations in BAP1 predispose to melanocytic tumors

    PubMed Central

    Wiesner, Thomas; Obenauf, Anna C.; Murali, Rajmohan; Fried, Isabella; Griewank, Klaus G.; Ulz, Peter; Windpassinger, Christian; Wackernagel, Werner; Loy, Shea; Wolf, Ingrid; Viale, Agnes; Lash, Alex E.; Pirun, Mono; Socci, Nicholas D.; Rütten, Arno; Palmedo, Gabriele; Abramson, David; Offit, Kenneth; Ott, Arthur; Becker, Jürgen C.; Cerroni, Lorenzo; Kutzner, Heinz; Bastian, Boris C.; Speicher, Michael R.

    2012-01-01

    Common acquired melanocytic nevi are benign neoplasms that are composed of small uniform melanocytes and typically present as flat or slightly elevated, pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected patients developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of the BAP1 gene. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histologic similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm. PMID:21874003

  2. Vasculogenic mimicry: lessons from melanocytic tumors.

    PubMed

    Spiliopoulos, Konstantinos; Peschos, Dimitrios; Batistatou, Anna; Ntountas, Ioannis; Agnantis, Niki; Kitsos, Georgios

    2015-01-01

    Tumor cell vasculogenic mimicry refers to the formation of tumor cell-lined vessels that contribute to tumor neovascularization and nutrient and oxygen supply. These tumor cells express many endothelial and stem cell markers, resulting in them having a unique phenotype. This phenomenon is observed in a variety of neoplasms, such as glioblastomas and sarcomas, as well as breast, ovarian, liver and lung carcinomas. It is also evident in melanocytic lesions, regardless of their benign or malignant nature. The biochemical and molecular events that regulate vasculogenic mimicry provide opportunities for development of novel forms of tumor-targeted treatments. Furthermore, the presence of this process in a tumor might have prognostic implications. PMID:25977376

  3. Mucinous borderline ovarian tumor with ascites.

    PubMed

    Batool, Tahira; Ullah, Nasreen Rehmat

    2014-11-01

    Borderline mucinous tumors are epithelial ovarian tumors with low rate of growth and low potential to invade or metastasize and associated with significantly better prognosis and excellent disease-free survival after surgical removal than other epithelial ovarian cancers. The accepted initial treatment is surgical removal of the tumor. Fertility-sparing surgery may suffice in young patients with tumors confined to the ovary. Radical surgery is recommended in patients with advanced disease and advanced age. Long-term surveillance is recommended to document and treat late recurrences. We report a case of a 59 years old postmenopausal patient with complex ovarian mucinous tumor and gross ascites; she had received three lines of chemotherapeutic agents pre-operatively, without any favorable outcome. Then, she went for staging laparotomy and histopathology showed borderline ovarian mucinous tumor required no further treatment and is fine till date. PMID:25518783

  4. 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

  5. Borderline phylloides tumor in an 11-year-old girl.

    PubMed

    Selamzade, M; Gidener, C; Koyuncuoglu, M; Mevsim, A

    1999-07-01

    Phylloides tumor is an uncommon breast tumor in children. Only a few cases have been reported in the literature. A case of borderline phylloides tumor in an 11-year-old girl is described. PMID:10415310

  6. Sonographic findings of an ovarian serous surface papillary borderline tumor.

    PubMed

    Kwon, Yohan; Park, Sung Bin; Lee, Jong Beum; Park, Hyun Jeong

    2013-01-01

    Sonographic findings of a serous surface papillary borderline tumor of the ovary have rarely been reported in the English literature. Here, we describe a case of serous surface papillary borderline tumor, which was depicted on gray-scale and Doppler ultrasonography as smoothly lobulated and polypoid heterogeneous echoic bilateral adnexal masses encased or surrounded by what was presumed to be normal-appearing ovarian follicles with increased vascular flow. PMID:23938140

  7. 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

  8. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma. PMID:23948749

  9. 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. PMID:26316459

  10. A deep penetrating facial congenital melanocytic tumor with bone involvement and ipsilateral eye blindness.

    PubMed

    Bergman, Reuven; Ben-Arush, Miriam W; Bar-Shalom, Rachel; Gilboa, Michael; Simon, Einav; Hershkovitz, Dov; Sabo, Edmond; Maly, Alexander; Gerami, Pedram; Goldsher, Dorith

    2015-01-01

    Bone involvement has been described in tumors with melanocytic differentiation such as melanotic neuroectodermal tumor of infancy, and very rarely in cellular blue nevi and neurocristic cutaneous hamartoma. We present an unusual case of facial congenital melanocytic tumor that involved the underlying bones and maxillary sinus and led to unilateral blindness. A newborn with a large red bluish patch with peripheral brown and black macules overlying marked swelling on the left side of his face was presented. The tumor was shown by magnetic resonance imaging, scintigraphy, and histopathology to invade the underlying bones and maxillary sinus and to compress the left eyeball resulting in blindness. Histopathology, immunohistochemistry, morphometric computerized microscopy, molecular genetic mutation analysis, and fluorescent in situ hybridization studies were more congruent with a melanocytic nevus. An 8.5-year follow-up was uneventful, with spontaneous partial shrinkage of the tumor. PMID:25222197

  11. 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

  12. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes.

    PubMed

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David G; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon B; Agarwal, Roshan; El-Bahrawy, Mona

    2013-04-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  13. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

    PubMed Central

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David Gonzalez; Hird, Vicky; Brown, Robert; Flanagan, James; Hani Gabra, H; Mills, Gordon B.; Agarwal, R; El-Bahrawy, Mona

    2013-01-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study we conducted an extensive analysis of mutations and single nucleotide polymorphisms in borderline ovarian tumors. Using the Sequenom MassARRAY platform we investigated 160 mutations/polymorphisms in 33 genes involved in cell signalling, apoptosis, angiogenesis, cell cycle regulation, and cellular senescence. Of 52 tumors analysed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in 8 tumors (6 serous and 2 mucinous), BRAF V600E mutations in 2 serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in VEGF, ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at 4 loci. PHLPP2 polymorphisms were more frequent in mucinous as compared to serous tumors (p=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional single nucleotide polymorphisms in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbour somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  14. S-100 protein in soft-tissue tumors derived from Schwann cells and melanocytes.

    PubMed Central

    Stefansson, K.; Wollmann, R.; Jerkovic, M.

    1982-01-01

    In soft tissues outside the central nervous system, S-100 protein is found normally only in Schwann cells. Using the peroxidase-antiperoxidase immunohistochemical method S-100 was also found in tumors derived from Schwann cells and melanocytes, including neurofibromas, neurilemomas, granular cell myoblastomas, cutaneous nevi, and malignant melanomas. S-100 was not detected in malignant Schwannomas, neuroblastomas, oat cell carcinomas, medullary carcinomas of the thyroid, paragangliomas, or meningiomas. S-100 was also absent from neoplasms of soft tissues not usually considered to arise from cells of neural crest origin. S-100 appears to be a useful marker for identifying neoplasms derived from Schwann cells and melanocytes. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:6278936

  15. Clinicopathological and prognostic relevance of Rap1-GAP expression in melanocytic tumors.

    PubMed

    Weiss, J; Biwer, B; Schliz, M; Jung, E G

    1997-09-01

    Rap1-GAP protein has been identified as an inactivator of Rap1 activity, a putative endogenous antagonist of Ras proteins. The Rap1-GA1 locus maps to 1p36.1-35, the region which may harbor a gene for familial melanoma. In the present immunohistochemical study we analyzed the clinicopathological and prognostic relevance of Rap1-GAP expression in 60 benign and 103 malignant melanocytic tumors. Cytoplasmic immunoreactivity was detected in the cells of 27/60 nevi (45%) and 59/103 melanomas (57%). In the latter group the frequency of Rap1-GAP expression increased (P < 0.05) with the thickness of primary tumors and was highest in metastatic lesions. Rap1-GAP protein was detected in 15/19 subsequently recurring primary melanomas (79%) but only in 32/67 tumors (47%) of patients who remained free of disease (P < 0.05) for at least 6 years. Five out of six recurring thin melanomas (< 2 mm) were found to be immunoreactive. Although being no indicator for malignant transformation of melanocytic lesions, Rap1-GAP overexpression may represent a useful marker for identifying thin high-risk melanomas. Cytoplasmic expression of Rap1-GAP has also been observed in the cells of skin appendages and in keratinocytes, particularly in suprabasal layers of the epidermis. Therefore, Rap1-GAP is likely to be associated with cellular growth and/or differentiation. However, the present study did not provide evidence that this gene, despite its chromosomal localization, represents an early melanoma gene. PMID:9373716

  16. A case report of a young girl with mucinous borderline tumor of the ovary

    PubMed Central

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin

    2016-01-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

  17. A case report of a young girl with mucinous borderline tumor of the ovary.

    PubMed

    Lee, Hyun-Mi; So, Kyeong A; Kim, Mi Kyung; Lee, Yoo Kyung; Lee, In-Ho; Kim, Tae-Jin; Lee, Ki Heon

    2016-07-01

    Ovarian tumors are relatively rare in children and adolescent. The incidence of malignancies in these groups is 1% to 1.5%. The common histologic type is non-epithelial type such as germ cell tumors or sex cord-stromal tumors and only 10% to 17% of those are epithelial tumors. It is important to accurately diagnose in the early these rare tumors for proper staging and treatment to save the patient's life and fertility. We present a case of a 13-year-old girl with a giant ovarian mucinous borderline tumor. PMID:27462604

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

    PubMed

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

    2016-04-10

    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

  19. 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

  20. Jejunal Metastasis Colliding With a Borderline Tumor in the Ovary: A Hitherto Unreported Eventuality.

    PubMed

    Piana, Simonetta; Giunta, Alessandro; Valli, Riccardo

    2015-10-01

    Metastatic adenocarcinomas to the ovary can show morphologically innocuous areas simulating primary benign lesions or borderline tumors. Ruling out a metastasis can be a difficult issue for pathologists, especially when facing with cystic tumors. Because of the important clinical implications of differentiating metastatic adenocarcinomas from primary ovarian tumors, the integration of clinical, pathological, and immunohistochemical features is warranted, primarily in case of mucinous adenocarcinomas. Vice versa, the synchronous presence of a metastasis and a primary in the same ovary is virtually excluded as a very unlikely eventuality. Here, we describe a case of metastatic adenocarcinoma from the jejunum colliding with a seromucinous borderline tumor in the same ovary, an unreported eventuality so far. PMID:25911566

  1. Sarcoma-like mural nodule in a borderline mucinous tumor of the ovary: A rare entity.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik; Bhowmik, Sourav

    2014-10-01

    Sarcoma-like mural nodule (SLMN) is a very uncommon and misleading benign entity which may be associated with benign, borderline or malignant mucinous neoplasm of the ovary. It should be distinguished from other malignant mural nodules with sarcoma, carcinosarcoma or anaplastic carcinoma for proper management. We report a rare case of SLMN in a borderline mucinous tumor of the ovary in a 30-year-old lady. In spite of having confusing histopathological features the final diagnosis was made depending on the younger age of the patient, well circumscription of the nodule, absence of vascular invasion and immunohistochemical profile. PMID:25540570

  2. 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. PMID:2750733

  3. 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. PMID:26974995

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

    PubMed Central

    Vasquez, Liliana; Tello, Mariela; Maza, Ivan; 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

  5. 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.

  6. 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

  7. Ultrasound diagnosis of serous surface papillary borderline ovarian tumor: A case series with a review of the literature.

    PubMed

    Ludovisi, Manuela; Foo, Xulin; Mainenti, Sara; Testa, Antonia Carla; Arora, Rupali; Jurkovic, Davor

    2015-01-01

    Serous surface papillary borderline ovarian tumors (SSPBOTs) are a rare morphologic variant of serous ovarian tumors that are typically confined to the ovarian surface, while the ovaries themselves tend to appear normal in size and shape. In this report, we describe the findings from five premenopausal women diagnosed with SSPBOTs, in whom ultrasound showed grossly normal ovaries that were partially or wholly covered with irregular solid tumors. In all five cases, histologic examination showed evidence of borderline serous tumors. These findings demonstrate that SSPBOTs can be diagnosed on a preoperative sonographic examination, which could facilitate conservative, fertility-sparing surgery in young women affected by this condition. PMID:25706035

  8. 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. PMID:27265474

  9. 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

  10. Granulosa cell tumor presenting with ovarian torsion and de novo borderline mucinous ovarian tumor in the contralateral ovary.

    PubMed

    Ates, S; Sevket, O; Sudolmus, S; Sonmez, F C; Dansuk, R

    2015-01-01

    The authors report a case of 25-year-old women with a rare acute presentation of granulosa cell tumor (GCT) as an ovarian torsion. Right salpingoo-ooferectomy was performed. The pathological diagnosis was GCT One month after the surgery there was a three-cm ovarian cyst in the contralateral ovary and the tumor size increased to six cm in diameter in the following month. Serum inhibin-B levels progressively increased. Cystectomy was performed to contralateral ovary as frozen-section examination indicated mucinous tumor. Final histopathological examination revealed borderline mucinous tumor. Regarding her request, the patient was reoperated again and unilateral oophorectomy and hysterectomy were performed. Clinicians must be aware of the possibility of an underlying malignancy associated with adnexal torsion even in young patients. Frozen section will be helpful in order to avoid incomplete surgeries. Cyst rapidly growing in the ovary in young women should raise the suspicion of a de novo malignancy. PMID:26189271

  11. 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

  12. Primary uterine müllerian mucinous borderline tumor (MMBT) associated with adenomyosis: a case report.

    PubMed

    Kawamura, Keiko; Kaneki, Eisuke; Ogawa, Shinji; Imamura, Hiroko; Ohishi, Yoshihiro; Kobayashi, Hiroaki; Kato, Kiyoko

    2014-03-01

    Müllerian mucinous borderline tumors (MMBTs) usually arise from the ovary. The present report is the first case of primary uterine MMBTs associated with adenomyosis. A 51-year-old woman was referred to our hospital for a complex cystic and solid 4×3 cm right adnexal mass. She had a history of a left ovarian endometriotic cyst and had undergone a left oophorectomy 2 yr prior. A laparotomy was performed, and the tumor was found to be originating in the posterior wall of the uterus. She underwent a total abdominal hysterectomy, right salpingo-oophorectomy, and left salpingectomy. Microscopically, the solid portion of the tumor contained papillary proliferations of glands, which were covered by a mucinous epithelium with mild to moderate nuclear atypia, accompanied by stromal infiltration of inflammatory cells. Islands of adenomyosis were also observed around the cyst. These pathologic findings were similar to the features of ovarian MMBT. We diagnosed this tumor as a uterine MMBT, probably arising from adenomyosis. PMID:24487469

  13. Fine needle aspiration cytology of cervical lymph node involvement by ovarian serous borderline tumor

    PubMed Central

    Chen, Longwen; Butler, Kristina A.; Bell, Debra A.

    2016-01-01

    Serous borderline tumor (SBT) involving a cervical lymph node is extremely rare. In addition, fine needle aspiration (FNA) cytology of the involved cervical lymph node shares tremendous morphologic similarity with other low-grade papillary carcinomas. Thus, it can be easily misdiagnosed as metastatic carcinoma. A 42-year-old female had a history of bilateral SBT and postbilateral salpingo-oophorectomy. She presented with left cervical lymphadenopathy 6 months later. FNA cytology showed a low-grade papillary neoplasm with psammoma bodies. Needle core biopsy along with immunostains was diagnostic of cervical lymph node involvement (LNI) of SBT. although extremely rare, cervical LNI can be found in patients with SBTs. FNA cytology, sometimes, is indistinguishable from metastatic papillary adenocarcinoma. Cell block or needle core biopsy is essential to make the correct diagnosis.

  14. Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

    PubMed

    McKenney, Jesse K; Gilks, C Blake; Kalloger, Steve; Longacre, Teri A

    2016-09-01

    The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further

  15. 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

  16. Immune-phenotypical markers for the differential diagnosis of melanocytic lesions

    PubMed Central

    Botti, Gerardo; Marra, Laura; Anniciello, Annamaria; Scognamiglio, Giosuè; Gigantino, Vincenzo; Cantile, Monica

    2015-01-01

    For specific subsets of melanocytic proliferations, there are morphologic limitations in the histological diagnosis, especially for borderline melanocytic tumors. In particular, Spitzoid proliferations can be difficult to diagnose. For these reasons, in the last years, clinic research has focusedattention on discovery of new diagnostic markers. Published gene expression and proteomic profiling data indicate new candidate molecules involved in melanoma pathogenesis, and useful in differential diagnosis of difficult melanocytic lesions. Recently, the diagnostic power of galectin-3 was demonstrated in series of melanocytic lesions, with a strong increasing of expression in malignant lesions compared with benign lesions. Similarly, the accumulation of Collagen XVII antibody was detected in vertical melanoma fronts and associated with invasive phenotype. Moreover, overexpression of cyclin D1 and p21 was detected in Spitz nevi compared with non-spitzoid melanomas; Ki-67 appears highly expressed in deep areas of non-spitzoid melanomas. In this review,werealizedan overviewofthe main molecular markersthat canbe a usefultoolfor the differential diagnosisofbenign, borderlineand malignant melanocytic lesions, related to their biological behavior, useful also for predicting the evolutionof the disease. PMID:26617684

  17. 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

  18. Invasive ductal carcinoma within borderline phyllodes tumor with lymph node metastases: A case report and review of the literature

    PubMed Central

    WU, DI; ZHANG, HAIPENG; GUO, LIANG; YAN, XU; FAN, ZHIMIN

    2016-01-01

    Phyllodes tumor (PT) is a rare type of biphasic fibroepithelial neoplasm that may coexist with a breast tumor in rare cases. In the current study, a 52-year-old female presented with a left breast lump. Mammography and sonographic examination results suggested a diagnosis of malignant tumor. Histological analysis revealed a borderline PT with invasive ductal carcinoma (IDC) within the tumor. Due to the presence of a single micrometastasis in three of the sentinel lymph nodes, the patient underwent modified radical mastectomy. The excised tumor contained triple negative breast cancer; therefore, postoperative treatment included six cycles of chemotherapy and 25 cycles of radiotherapy. The patient exhibited no recurrence and no metastatic disease at the 23-month follow-up examination. Thus, the present study discussed the case of a female patient that presented with IDC within borderline PT and reviewed the literature on this rare type of neoplasm. Various types of breast carcinoma have been identified to coexist with PT in different masses; however, no standard therapeutic regimen has been established for the coexistence of PT and breast cancer in the same mass. The present study indicates that determination of an appropriate treatment strategy predominantly depends on the characteristics of the individual breast tumor. PMID:27073506

  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. Epithelial, non-melanocytic and melanocytic proliferations of the ocular surface.

    PubMed

    Kheir, Wajiha J; Tetzlaff, Michael T; Pfeiffer, Margaret L; Mulay, Kaustubh; Ozgur, Omar; Morrell, Gail; Esmaeli, Bita

    2016-05-01

    Ocular surface tumors are commonly encountered by ophthalmologists and ophthalmic pathologists. These tumors have varied clinical manifestations. In this article, we discuss the most commonly encountered non-melanocytic and melanocytic ocular surface tumors, with emphasis on their common clinical features, morphologic patterns, and prognostic factors. PMID:27021909

  1. Recurrence of Brenner ovary borderline tumor in the abdominal wall postoperative scar--a case report and research of the literature.

    PubMed

    Klasa, Lukasz; Wydra, Dariusz; Biernat, Wojciech

    2014-11-01

    We report a case of a 74-year-old female, who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy due to a solid-cystic tumor of the right ovary. The histopathological diagnosis revealed a borderline Brenner tumor (BBT). After 25 disease-free months the patient was admitted to a hospital because of a tumor in the postoperative scar of the abdominal wall, later diagnosed as infiltrating Brenner tumor consistent with ovarian borderline lesion. The tumor in the postoperative scar was therefore diagnosed as BBT. The article presents results of literature search on BBT in order to find characteristic features of this very rare ovarian tumor. To the best of our knowledge, this is the first report of subcutaneous recurrence of Brenner ovary tumor of low malignant potential. PMID:25675807

  2. Microfocus of Anaplastic Carcinoma Arising in Mural Nodule of Ovarian Mucinous Borderline Tumor With Very Rapid and Fatal Outcome.

    PubMed

    Mhawech-Fauceglia, Paulette; Ramzan, Amin; Walia, Saloni; Pham, Huyen Q; Yessaian, Annie

    2016-07-01

    A 36-yr-old woman presented with abdominal discomfort. A computed tomography scan revealed a large left cystic and solid pelvic mass without evidence of metastatic disease. Total hysterectomy with bilateral salpingo-oophorectomy and tumor staging was performed. Grossly, the ovarian mass measured 20×18 cm and the cut surface was multiloculated with 1 single mural nodule measuring 2×1.5 cm. The histologic diagnosis of ovarian mucinous borderline tumor with a microfocus of anaplastic carcinoma arising in sarcoma-like mural nodule, FIGO Stage IA was rendered. After 3 mo, the patient returned with symptomatic anemia. A computed tomography scan showed enlarged retroperitoneal and pelvic lymph nodes. Image-guided biopsy of the pelvic lymph node showed a metastatic anaplastic carcinoma from her primary ovarian carcinoma. Chemotherapy was initiated, but the patient developed fulminant disseminated intravascular coagulation within <1 wk of her presentation which was fatal. PMID:26598983

  3. 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. PMID:27063098

  4. KRAS (but not BRAF) mutations in ovarian serous borderline tumor are associated with recurrent low-grade serous carcinoma

    PubMed Central

    Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok

    2014-01-01

    BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645

  5. 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.

  6. 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

    2014-03-01

    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. PMID:24548412

  7. Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

    PubMed Central

    Mallick, Supriya; Joshi, Nikhil P.; Roy, Soumyajit; Gandhi, Ajeet Kumar; Pandit, Subhash; Sharma, Dayanand; Julka, Pramod Kumar; Rath, Goura Kishore

    2016-01-01

    Background: Phyllodes tumor (PT) of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful. Materials and Methods: We have analyzed details of all patients of PT (n = 33) treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented. Results: All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank). The disease free survival (DFS) favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank). The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015). The mode of surgery did not have any impact on survival. Conclusion: Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure. PMID:27169106

  8. Recurrent intestinal mucinous borderline tumors of the ovary: a report of 5 cases causing problems in diagnosis, including distinction from mucinous carcinoma.

    PubMed

    Irving, Julie A; Clement, Philip B

    2014-03-01

    Intestinal mucinous borderline tumors (IMBTs) of the ovary are generally associated with a highly favorable outcome and rarely recur. We describe 5 cases of IMBT initially treated by cystectomy or by salpingo-oophorectomy that was likely incomplete, with subsequent recurrences. Three cases were received in consultation, and in each of these, the clinical and intraoperative findings were worrisome for mucinous carcinoma, and diagnostic difficulty was encountered by the referring pathologist. The patient age ranged from 28 to 69 (median 53) yrs. All tumors were clinically Stage I at presentation; in at least 3 cases, extensive adhesiolysis was required during their removal. A pathologic diagnosis of IMBT was made in 4 cases; the remaining tumor was inadequately sampled (3 blocks from a 7.5-cm tumor showed predominantly benign to focally borderline mucinous epithelium). A total of 8 recurrences, all as IMBT, developed at mean follow-up of 26 (range, 6-102) mo; 6 of these occurred within ≤2 yr. In 4 cases, removal of recurrent tumor required an extensive operation because of bowel and/or vaginal involvement. Residual ovarian stroma was identified in all recurrences. There was no evidence of invasive mucinous carcinoma, pseudomyxoma peritonei, or a primary tumor elsewhere (including appendix) in any of the cases. Our findings indicate that patients with IMBTs who undergo cystectomy or oophorectomy requiring adhesiolysis are at increased risk of recurrence, which may occur early, be multiple, and potentially require extensive resection if sites such as bowel or vagina are involved. Recurrences of IMBT that develop in this setting likely represent regrowth of incompletely resected IMBT, or arise within residual ovarian tissue. This is the first detailed clinicopathologic study of such cases. PMID:24487471

  9. TERT Promoter Mutations Are Predictive of Aggressive Clinical Behavior in Patients with Spitzoid Melanocytic Neoplasms

    PubMed Central

    Lee, Seungjae; Barnhill, Raymond L.; Dummer, Reinhard; Dalton, James; Wu, Jianrong; Pappo, Alberto; Bahrami, Armita

    2015-01-01

    Spitzoid neoplasms constitute a morphologically distinct category of melanocytic tumors, encompassing Spitz nevus (benign), atypical Spitz tumor (intermediate malignant potential), and spitzoid melanoma (fully malignant). Currently, no reliable histopathological criteria or molecular marker is known to distinguish borderline from overtly malignant neoplasms. Because TERT promoter (TERT-p) mutations are common in inherently aggressive cutaneous conventional melanoma, we sought to evaluate their prognostic significance in spitzoid neoplasms. We analyzed tumors labeled as atypical Spitz tumor or spitzoid melanoma from 56 patients with available follow-up data for the association of TERT-p mutations, biallelic CDKN2A deletion, biallelic PTEN deletion, kinase fusions, BRAF/NRAS mutations, nodal status, and histopathological parameters with risk of hematogenous metastasis. Four patients died of disseminated disease and 52 patients were alive and disease free without extranodal metastasis (median follow-up, 32.5 months). We found TERT-p mutations in samples from the 4 patients who developed hematogenous metastasis but in none of tumors from patients who had favorable outcomes. Presence of TERT-p mutations was the most significant predictor of haematogenous dissemination (P < 0.0001) among variables analyzed. We conclude that TERT-p mutations identify a clinically high-risk subset of patients with spitzoid tumors. Application of TERT-p mutational assays for risk stratification in the clinic requires large-scale validation. PMID:26061100

  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. PMID:27003157

  11. Protein Expression Analysis of Melanocyte Differentiation Antigen TRP-2.

    PubMed

    Avogadri, Francesca; Gnjatic, Sacha; Tassello, Jodie; Frosina, Denise; Hanson, Nicole; Laudenbach, Megan; Ritter, Erika; Merghoub, Taha; Busam, Klaus J; Jungbluth, Achim A

    2016-03-01

    Melanocyte differentiation antigens, such as gp100, tyrosinase, and Melan-A and their corresponding antibodies HMB45, T311, and A103, are major diagnostic tools in surgical pathology. Little is known about tyrosinase-related protein 2 (TRP-2, or dopachrome tautomerase/DCT) another melanocyte differentiation antigen, which is an enzymatic component of melanogenesis. We identified a commercial reagent to TRP-2, monoclonal antibody (mAb) C-9 and undertook a comprehensive analysis to assess its specificity and usefulness for surgical pathology. Subsequently, we analyzed panels of normal tissues and tumors. We show that TRP-2 is regularly expressed in melanocytes of the normal skin. In cutaneous nevi, TRP-2 is present in junctional as well as in dermal nevocytes. In malignant tumors, C-9 reactivity is restricted to melanocytic and related lesions and present in 84% and 58% of primary and metastatic melanomas, respectively. Ten primary melanomas of the anorectal mucosa were all positive. Like the other melanocyte differentiation antigens, TRP-2 was absent in 6 desmoplastic melanomas. Also, only 2 of 9 angiomyolipomas were TRP-2 positive. We conclude that mAb C-9 is a valuable reagent for the analysis of TRP-2 expression in archival surgical pathology material. The expression pattern of TRP-2 in melanocytic and related lesions appears to parallel other melanocyte differentiation antigens, although the overall incidence is lower than other antigens, such as Melan-A or gp100. PMID:26894771

  12. A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

    PubMed Central

    Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

    2015-01-01

    Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

  13. Borderline personality disorder

    MedlinePlus

    Personality disorder - borderline ... Cause of borderline personality disorder (BPD) is unknown. Genetic, family, and social factors are thought to play roles. Risk factors for BPD include: Abandonment ...

  14. Role of TRPM in melanocytes and melanoma

    PubMed Central

    Guo, Huazhang; Carlson, J. Andrew; Slominski, Andrzej

    2012-01-01

    Transient receptor potential (TRP) cation channel superfamily plays important roles in variety cellular processes including polymodal cellular sensing, cell adhesion, cell polarity, proliferation, differentiation, and apoptosis. One of its subfamilies are TRPM channels. mRNA expression of its founding member, TRPM1 (melastatin), correlates with terminal melanocytic differentiation and loss of its expression has been identified as an important diagnostic and prognostic marker for primary cutaneous melanoma. Because TRPM1 gene codes two transcripts: TRPM1 channel protein in its exons, and miR-211 in one of its introns, we propose a dual role for TRPM1 gene where the loss of TRPM1 channel protein is an excellent marker of melanoma aggressiveness, while the expression of miR-211 is linked to the tumor suppressor function of TRPM1. In addition, three other members of this subfamily, TRPM 2, 7 and 8 are implicated in regulation of melanocytic behavior. TRPM2 is capable of inducing melanoma apoptosis and necrosis. TRPM7 can be a protector and detoxifier in both melanocytes and melanoma cells. TRPM8 can mediate agonist-induced melanoma cell death. Therefore, we propose that TRPM1, TRPM2, TRPM7, and TRPM8 play crucial roles in melanocyte physiology and melanoma oncology, and are excellent diagnostic markers and theraputic targets. PMID:22897572

  15. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

    PubMed Central

    Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

  16. Borderline Personality

    PubMed Central

    Sansone, Randy A.; Sansone, Lori A.

    2004-01-01

    BORDERLINE PERSONALITY DISORDER (BPD) IS A COMPLEX AXIS II Phenomenon that is typically described in a psychological or psychiatric context. In this article, we translate the various aspects of BPD to the primary care setting. Previous work in this area has explored specific relationships between BPD and individual medical disorders or between BPD and general somatic symptoms, but the synthesis of these findings and their augmentation with cogent psychological theory is new to the field. Specifically, we highlight the prevalence rate of BPD in the primary care setting, the effects on healthcare utilization, the themes of somatic preoccupation and somatization disorder, several medical syndromes that illustrate the dynamics of the disorder in the medical setting, and the relationship of BPD to disability. We believe that the BPD concept needs to extend beyond its traditional psychological/psychiatric borders to include the subset of BPD patients with somatic symptoms who are seen in primary care settings. PMID:21197375

  17. 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

  18. 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

  19. Borderline resectable pancreatic cancer.

    PubMed

    Hackert, Thilo; Ulrich, Alexis; Büchler, Markus W

    2016-06-01

    Surgery followed by adjuvant chemotherapy remains the only treatment option for pancreatic ductal adenocarcinoma (PDAC) with the chance of long-term survival. If a radical tumor resection is possible, 5-year survival rates of 20-25% can be achieved. Pancreatic surgery has significantly changed during the past years and resection approaches have been extended beyond standard procedures, including vascular and multivisceral resections. Consequently, borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC), which has recently been defined by the International Study Group for Pancreatic Surgery (ISGPS), has become a controversial issue with regard to its management in terms of upfront resection vs. neoadjuvant treatment and sequential resection. Preoperative diagnostic accuracy to define resectability of PDAC is a keypoint in this context as well as the surgical and interdisciplinary expertise to perform advanced pancreatic surgery and manage complications. The present mini-review summarizes the current state of definition, management and outcome of BR-PDAC. Furthermore, the topic of ongoing and future studies on neoadjuvant treatment which is closely related to borderline resectability in PDAC is discussed. PMID:26970276

  20. 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

  1. 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

  2. Borderline personality disorder

    MedlinePlus

    ... Names Personality disorder - borderline References American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing. 2013. ...

  3. Pigmented median raphe cyst of the penis with consideration of the possible mechanism of melanocytic colonization: A case report.

    PubMed

    Ishida, Mitsuaki; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

    2014-02-01

    Median raphe cyst is a rare lesion located on the median raphe. The cyst wall is lined by cuboidal to columnar cells, transitional (urothelial) cells, stratified squamous cells or a mixture of these. The normal urethral mucosa and the median raphe cyst usually lack melanocytes and/or melanin pigment. However, albeit extremely rare, the presence of melanin pigment and/or melanocytes in median raphe cyst, namely pigmented median raphe cyst, has been previously reported. The current case report presents the sixth case of pigmented median raphe cyst and discusses the possible mechanism of melanocytic colonization in this tumor. A 48-year-old male presented with a nodule on the ventral surface of the penis. Histopathological study revealed that the cyst wall was covered by uniform bland cuboidal to urothelial cells. The peculiar observation was the presence of dendritic melanocytes among the epithelial cells. Therefore, a diagnosis of pigmented median raphe cyst was determined. Immunohistochemically, stem cell factor and endothelin-1 were not expressed in the epithelial cells of the cyst wall. It is well-known that melanocytes are rarely found in various non-melanocytic tumors, a phenomenon termed 'colonization'. The mechanism by which melanocytes appear in median raphe cyst remains unclear. The present report is the first to demonstrate that melanocytic proliferation and differentiation factors, such as stem cell factor and endothelin-1, are not involved in the pigmentation of median raphe cyst. In addition, aberrant melanocytic migration may contribute to the development of this type of lesion. PMID:24396444

  4. A comparative review of melanocytic neoplasms.

    PubMed

    Smith, S H; Goldschmidt, M H; McManus, P M

    2002-11-01

    Melanoma is a devastating disease frequently encountered within both veterinary and human medicine. Molecular changes linked with neoplastic transformation of melanocytes include mutations in genes that encode proteins intrinsic to the regulatory pathways of two tumor suppressor proteins (retinoblastoma protein and p53), proto-oncogene mutation to oncogenes, altered expression of epithelial cadherin and CD44 adhesion molecules, and upregulation of angiogenic factors and other growth factors. Histologic evaluation of the primary mass is the most common means of diagnosis, with cytology used more frequently to document metastasis. Melanoma's highly variable histologic and cytologic patterns can make diagnosis by either method problematic. Adherent epithelioid morphology, including signet ring forms, and nonadherent round and spindle forms are recognized, with pigmentation an inconsistent finding. The site of the tumor, the thickness of the primary tumor or depth of invasion, and the number of mitotic figures per high-power field or per millimeter are used histologically to predict biologic behavior, whereas site and degree of pleomorphism are typically used for cytologic preparations. Diagnosis of amelanotic melanoma can be aided by ancillary diagnostic techniques. Tumor cells are usually positive for vimentin, S100, neuron-specific enolase, and Melan-A, and negative for cytokeratin. Melan-A as a positive marker is not as sensitive as the others are but is likely more specific. Monoclonal antibodies to human melanosome-specific antigens 1 and 5 cross-react with canine antigens for a combined sensitivity rate of 83%. Mouse monoclonal antibody IBF9 specifically recognizes canine melanoma antigen and also has good sensitivity. Serologic markers, including cytokines, cell adhesion molecules, and melanoma-inhibitory activity, are being investigated as potential sentinels of melanoma. Currently, there is no single diagnostic technique capable of differentiating benign from

  5. 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…

  6. 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 ...

  7. Borderline Personality and Criminality

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    Borderline personality disorder is characteristically associated with a broad variety of psychiatric symptoms and aberrant behaviors. In this edition of The Interface, we discuss the infrequently examined association between borderline personality disorder and criminality. According to our review of the literature, in comparison with the rates of borderline personality disorder encountered in the general population, borderline personality disorder is over-represented in most studies of inmates. At the same time, there is considerable variation in the reported rates of this Axis II disorder in prison populations, which may be attributed to the methodologies of and populations in the various studies. Overall, female criminals appear to exhibit higher rates of borderline personality disorder, and it is oftentimes associated with a history of childhood sexual abuse, perpetration of impulsive and violent crimes, comorbid antisocial traits, and incarceration for domestic violence. PMID:20011575

  8. Sorafenib induced eruptive melanocytic lesions.

    PubMed

    Uhlenhake, Elizabeth E; Watson, Alice C; Aronson, Peter

    2013-05-01

    Sorafenib is a multikinase inhibitor FDA-approved for the treatment of advanced renal cell and hepatocellular carcinoma. Dermatologic side effects include hand-foot skin reaction, facial and scalp erythema and desquamation, splinter subungual hemorrhages, alopecia, pruritus, xerosis, keratoacanthomas, and squamous cell carcinomas. We report sudden eruption of melanocytic nevi diffusely in a patient receiving sorafenib. PMID:24011281

  9. The melanocyte differentiation program predisposes to metastasis following neoplastic transformation.

    PubMed Central

    Gupta, Piyush B.; Kuperwasser, Charlotte; Brunet, Jean-Philippe; Ramaswamy, Sridhar; Kuo, Wen-Lin; Gray, Joe W.; Naber, Stephen P.; Weinberg, Robert A.

    2006-01-01

    The aggressive clinical behavior of melanoma has led to the hypothesis that the developmental origins of melanocytes in the neural crest might be relevant for their metastatic propensity. We demonstrate that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, while human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Importantly, these melanomas exhibit a metastasis spectrum similar to that observed in human patients. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi reveals that Slug, a master regulator of neural crest cell specification and migration, correlates in its expression pattern with other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present prior to neoplastic transformation can play a pivotal role in governing melanoma's progression. PMID:16142232

  10. From Melanocyte to Metastatic Malignant Melanoma

    PubMed Central

    Bandarchi, Bizhan; Ma, Linglei; Navab, Roya; Seth, Arun; Rasty, Golnar

    2010-01-01

    Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma. 8–12% of familial melanomas occur in a familial setting related to mutation of the CDKN2A gene that encodes p16. The aim of this is to briefly review the microanatomy and physiology of the melanocytes, epidemiology, risk factors, clinical presentation, historical classification and histopathology and, more in details, the most recent discoveries in biology and genetics of malignant melanoma. At the end, the final version of 2009 AJCC malignant melanoma staging and classification is presented. PMID:20936153

  11. Pathology of eyelid tumors.

    PubMed

    Pe'er, Jacob

    2016-03-01

    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

  12. 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

  13. A Case of Melanoacanthoma: Immunohistochemical Staining Using VECTOR® NovaRED™ to Distinguish Melanocytes from the Cutaneous Pigment

    PubMed Central

    Choi, Jae Eun; Bae, Eui Jong; Kim, Ae Ree; Son, Sang Wook; Song, Hae Jun

    2008-01-01

    Melanoacanthoma is a rare benign mixed tumor of both keratinocytes and melanocytes. Although some authors said that it is a rare variant of seborrheic keratosis, it has clinical and histological features distinct from seborrheic keratosis. It has large dendritic melanin-laden melanocytes throughout all levels of epidermis showing a disruption of melanin transfer from the melanocytes to neighboring keratinocytes. However, it is difficult to distinguish melanocytes clearly from cutaneous pigment in immunohistochemical stain with usually used brown chromogen. We used chromogen with brick-red indicator product (VECTOR® NovaRED™) in S-100 and melan-A immunohistochemical staining to distinguish melanocytes from melanin laden keratinocytes. We suggest that the immunohistochemical staining using this novel chromogen may be useful in the diagnosis of melanoacanthoma.

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

    PubMed Central

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

    2016-01-01

    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

  15. 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

    2016-01-01

    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

  16. 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

  17. 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

  18. BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations.

    PubMed

    Piris, Adriano; Mihm, Martin C; Hoang, Mai P

    2015-02-01

    BAP1 (BRCA1-associated protein 1) is a tumor suppressor gene whose mutations have recently been reported to increase susceptibility for the development of uveal melanoma, cutaneous atypical and epithelioid melanocytic lesions, clear cell renal cell carcinoma, and other tumors. Screening for BAP1 mutation/loss/inactivation and BRAFV600E mutation can be done by immunohistochemistry. We investigated BAP1 and BRAFV600E expression in 193 sporadic melanocytic lesions (11 dermal nevi, 20 congenital nevi, 40 primary and nondesmoplastic melanomas, 40 desmoplastic melanomas, 23 metastatic melanomas, 17 Spitz nevi, 19 atypical Spitz nevi, 8 atypical Spitz tumors, 14 proliferative nodules arising in congenital nevi, 1 nevus during pregnancy) and 30 melanocytic lesions from 3 patients with family history of uveal melanoma and BAP1 germline mutation. Most sporadic melanocytic lesions exhibited positive BAP1 nuclear staining, except for 1 proliferative nodule arising in congenital nevus, 1 desmoplastic, 1 nevoid, and 2 metastatic melanomas. BRAFV600E positivity was demonstrated in 80% of dermal, 5% of congenital, 6% of Spitz, and 5.5% of atypical Spitz nevi; 29% of proliferative nodules arising in congenital nevi; and 24% of primary and nondesmoplastic and 35% of metastatic melanomas. Combined BAP1 loss and BRAFV600E staining was seen in 67% of BAP1 tumor syndrome-associated lesions and in none of the sporadic melanocytic proliferations including Spitz and atypical Spitz nevi and atypical Spitz tumors, with the exception of 1 primary melanoma. The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, and the designation of Spitz nevi or variants thereof appears to be inaccurate for this group of lesions. PMID:25479927

  19. 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

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

    PubMed Central

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

    2015-01-01

    Background The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. Objective 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. Methods Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Results 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%). Limitations Our study is limited by the small sample size of this rare subset of melanomas. Conclusion 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. PMID:24842760

  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. PMID:26885602

  2. 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. PMID:26905193

  3. 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. PMID:25703021

  4. Desmoplastic Melanocytic Nevus of Oral Mucosa.

    PubMed

    Damm, Douglas D; Fowler, Craig B; Schmidt, David P

    2016-09-01

    The desmoplastic melanocytic nevus is an uncommon variant that easily may be confused with a fibrohistiocytic neoplasm or a desmoplastic melanoma. It is believed that the following report describes the first known example of a desmoplastic melanocytic nevus arising in the oral mucosa. The histopathologic and immunohistochemical features that allow separation from other microscopically similar pathoses are stressed. PMID:26747459

  5. Melanocytic glaucoma in a cairn terrier.

    PubMed

    Hanselman, Beth A

    2002-04-01

    Melanocytic glaucoma, previously known as pigmentary glaucoma, is characterized by diffuse intraocular infiltration of heavily pigmented melanocytes. This unusual ocular disorder has been documented only in the cairn terrier and is considered familial. Treatment strategies are based on evidence that the condition is slowly progressive but not neoplastic. PMID:11963666

  6. Melanocytic glaucoma in a cairn terrier

    PubMed Central

    Hanselman, Beth A.

    2002-01-01

    Melanocytic glaucoma, previously known as pigmentary glaucoma, is characterized by diffuse intraocular infiltration of heavily pigmented melanocytes. This unusual ocular disorder has been documented only in the cairn terrier and is considered familial. Treatment strategies are based on evidence that the condition is slowly progressive but not neoplastic. PMID:11963666

  7. Pigmented median raphe cyst of the penis with consideration of the possible mechanism of melanocytic colonization: A case report

    PubMed Central

    ISHIDA, MITSUAKI; IWAI, MUNEO; YOSHIDA, KEIKO; KAGOTANI, AKIKO; OKABE, HIDETOSHI

    2014-01-01

    Median raphe cyst is a rare lesion located on the median raphe. The cyst wall is lined by cuboidal to columnar cells, transitional (urothelial) cells, stratified squamous cells or a mixture of these. The normal urethral mucosa and the median raphe cyst usually lack melanocytes and/or melanin pigment. However, albeit extremely rare, the presence of melanin pigment and/or melanocytes in median raphe cyst, namely pigmented median raphe cyst, has been previously reported. The current case report presents the sixth case of pigmented median raphe cyst and discusses the possible mechanism of melanocytic colonization in this tumor. A 48-year-old male presented with a nodule on the ventral surface of the penis. Histopathological study revealed that the cyst wall was covered by uniform bland cuboidal to urothelial cells. The peculiar observation was the presence of dendritic melanocytes among the epithelial cells. Therefore, a diagnosis of pigmented median raphe cyst was determined. Immunohistochemically, stem cell factor and endothelin-1 were not expressed in the epithelial cells of the cyst wall. It is well-known that melanocytes are rarely found in various non-melanocytic tumors, a phenomenon termed ‘colonization’. The mechanism by which melanocytes appear in median raphe cyst remains unclear. The present report is the first to demonstrate that melanocytic proliferation and differentiation factors, such as stem cell factor and endothelin-1, are not involved in the pigmentation of median raphe cyst. In addition, aberrant melanocytic migration may contribute to the development of this type of lesion. PMID:24396444

  8. 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. PMID:25847135

  9. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  10. Hyperspectral imaging of melanocytic lesions.

    PubMed

    Gaudi, Sudeep; Meyer, Rebecca; Ranka, Jayshree; Granahan, James C; Israel, Steven A; Yachik, Theodore R; Jukic, Drazen M

    2014-02-01

    Hyperspectral imaging (HSI) allows the identification of objects through the analysis of their unique spectral signatures. Although first developed many years ago for use in terrestrial remote sensing, this technology has more recently been studied for application in the medical field. With preliminary data favoring a role for HSI in distinguishing normal and lesional skin tissues, we sought to investigate the potential use of HSI as a diagnostic aid in the classification of atypical Spitzoid neoplasms, a group of lesions that often leave dermatopathologists bewildered. One hundred and two hematoxylin and eosin-stained tissue samples were divided into 1 of 4 diagnostic categories (Spitz nevus, Spitz nevus with unusual features, atypical Spitzoid neoplasm, and Spitzoid malignant melanoma) and 1 of 2 control groups (benign melanocytic nevus and malignant melanoma). A region of interest was selected from the dermal component of each sample, thereby maximizing the examination of melanocytes. Tissue samples were examined at ×400 magnification using a spectroscopy system interfaced with a light microscope. The absorbance patterns of wavelengths from 385 to 880 nm were measured and then analyzed within and among groups. All tissue groups demonstrated 3 common absorbance spectra at 496, 533, and 838 nm. Each sample group contained at least one absorption point that was unique to that group. The Spitzoid malignant melanoma category had the highest number of total and unique absorption points for any sample group. The data were then clustered into 12 representative spectral classes. Although each of the sample groups contained all 12 spectral vectors, they did so in differing proportions. These preliminary results reveal differences in the spectral signatures of the Spitzoid lesions examined in this study. Further investigation into a role for HSI in classifying atypical Spitzoid neoplasms is encouraged. PMID:24247577

  11. LASP1, a Newly Identified Melanocytic Protein with a Possible Role in Melanin Release, but Not in Melanoma Progression

    PubMed Central

    Houben, Roland; Grunewald, Thomas G. P.; Goebeler, Matthias; Butt, Elke

    2015-01-01

    The LIM and SH3 protein 1 (LASP1) is a focal adhesion protein. Its expression is increased in many malignant tumors. However, little is known about the physiological role of the protein. In the present study, we investigated the expression and function of LASP1 in normal skin, melanocytic nevi and malignant melanoma. In normal skin, a distinct LASP1 expression is visible only in the basal epidermal layer while in nevi LASP1 protein is detected in all melanocytes. Melanoma exhibit no increase in LASP1 mRNA compared to normal skin. In melanocytes, the protein is bound to dynamin and mainly localized at late melanosomes along the edges and at the tips of the cell. Knockdown of LASP1 results in increased melanin concentration in the cells. Collectively, we identified LASP1 as a hitherto unknown protein in melanocytes and as novel partner of dynamin in the physiological process of membrane constriction and melanosome vesicle release. PMID:26061439

  12. 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

  13. 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

  14. "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. PMID:26588340

  15. Borderline Ovarian Tumors and Diagnostic Dilemma of Intraoperative Diagnosis: Could Preoperative He4 Assay and ROMA Score Assessment Increase the Frozen Section Accuracy? A Multicenter Case-Control Study

    PubMed Central

    Gizzo, Salvatore; Berretta, Roberto; Di Gangi, Stefania; Guido, Maria; Zanni, Giuliano Carlo; Franceschetti, Ilaria; Quaranta, Michela; Plebani, Mario; Nardelli, Giovanni Battista; Patrelli, Tito Silvio

    2014-01-01

    The aim of our study was to assess the value of a preoperative He4-serum-assay and ROMA-score assessment in improving the accuracy of frozen section histology in the diagnosis of borderline ovarian tumors (BOT). 113 women presenting with a unilateral ovarian mass diagnosed as serous/mucinous BOT at frozen-section-histology (FS) and/or confirmed on final pathology were recruited. Pathologists were informed of the results of preoperative clinical/instrumental assessment of all patients. For Group_A patients, additional information regarding He4, CA125, and ROMA score was available (in Group_B only CA125 was known). The comparison between Group A and Group B in terms of FS accuracy, demonstrated a consensual diagnosis in 62.8% versus 58.6% (P: n.s.), underdiagnosis in 25.6% versus 41.4% (P < 0.05), and overdiagnosis in 11.6% versus 0% (P < 0.01). Low FS diagnostic accuracy was associated with menopausal status (OR: 2.13), laparoscopic approach (OR: 2.18), mucinous histotype (OR: 2.23), low grading (OR: 1.30), and FIGO stage I (OR: 2.53). Ultrasound detection of papillae (OR: 0.29), septa (OR: 0.39), atypical vascularization (OR: 0.34), serum He4 assay (OR: 0.39), and ROMA score assessment (OR: 0.44) decreased the probability of underdiagnosis. A combined preoperative assessment through serum markers and ultrasonographic features may potentially reduce the risk of underdiagnosis of BOTs on FS while likely increasing the concomitant incidence of false-positive events. PMID:25431767

  16. Cytolytic antibodies to melanocytes in vitiligo.

    PubMed

    Cui, J; Arita, Y; Bystryn, J C

    1993-06-01

    Patients with vitiligo have been found to have circulating antibodies to pigment cells. To evaluate the functional activity of these antibodies, a highly sensitive europium release assay was used to compare complement-mediated cytolysis of human melanocytes by sera of 56 patients with vitiligo (20 with active disease, 25 with inactive disease, 11 with unidentified disease activity) and 47 control individuals. Significant melanocyte lysis was mediated by 32 (57%) of the patients with vitiligo but by only three (6%) of the control sera (p < 0.001), and by 17 (85%) of 20 patients with active vitiligo versus 11 (44%) of 25 patients with inactive disease (p < 0.025). Mean melanocyte lysis by vitiligo sera was 24% versus 6% by control sera (p < 0.0001). A subset of 12 vitiligo sera with high titers of cytolytic antibodies to melanocytes (34% mean cytolysis) reacted minimally (< 2% mean cytolysis) to a panel of control cells that included human and murine melanomas, human fibroblasts, lung carcinoma, and rhabdomyosarcoma. These findings indicate that antibodies present in patients with vitiligo have the functional ability to selectively kill melanocytes and are more common in active disease. These observations support, but do not prove, the hypothesis that vitiligo is an autoimmune disease and that anti-pigment cell antibodies have a role in inducing the disease. PMID:8496621

  17. 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

  18. 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. PMID:23815504

  19. Giant Congenital Melanocytic Nevi and Neurocutaneous Melanosis

    PubMed Central

    Araújo, Catarina; Pardal, Francisco; Brito, Celeste

    2015-01-01

    Introduction. The major medical concern with giant congenital melanocytic nevi CMN is high risk of developing cutaneous melanoma, leptomeningeal melanoma, and neurocutaneous melanocytosis. Case Report. A 30-year-old woman with a giant congenital melanocytic nevus covering nearly the entire right thoracodorsal region and multiple disseminated melanocytic nevi presented with neurological symptoms. Cerebral magnetic resonance imaging revealed a large expansive lesion in the left frontal region. Postsurgically pathological diagnosis revealed characteristics of melanoma. Immunohistochemical examination showed S100(+), HMB45(+), MelanA(+), and MiTF(+). She received radiotherapy with temozolomide followed by two more chemotherapy cycles with temozolomide. She followed a rapidly progressive course, reflecting widespread leptomeningeal infiltration, and she died of multiorgan failure seven months after diagnosis of cerebral melanoma. Discussion. This patient was diagnosed as having a neurocutaneous melanosis with malignant widespread leptomeningeal infiltration. Diffuse spinal involvement is unusual and is described in only another patient. PMID:25722729

  20. 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; Timares, Laura; 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), and followed by chronic promotion with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Dysplastic pigmented skin lesions appeared in 7-9 weeks with 100% penetrance. Nests of melanocytic cells appeared in a subset of skin draining lymph nodes (dLN) by 25 weeks, 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. PMID:25788145

  1. Generation of Human Melanocytes from Induced Pluripotent Stem Cells

    PubMed Central

    Okada, Yohei; Akamatsu, Wado; Kuwahara, Reiko; Ohyama, Manabu; Amagai, Masayuki; Matsuzaki, Yumi; Yamanaka, Shinya; Okano, Hideyuki; Kawakami, Yutaka

    2011-01-01

    Epidermal melanocytes play an important role in protecting the skin from UV rays, and their functional impairment results in pigment disorders. Additionally, melanomas are considered to arise from mutations that accumulate in melanocyte stem cells. The mechanisms underlying melanocyte differentiation and the defining characteristics of melanocyte stem cells in humans are, however, largely unknown. In the present study, we set out to generate melanocytes from human iPS cells in vitro, leading to a preliminary investigation of the mechanisms of human melanocyte differentiation. We generated iPS cell lines from human dermal fibroblasts using the Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines were subsequently used to form embryoid bodies (EBs) and then differentiated into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven weeks after inducing differentiation, pigmented cells expressing melanocyte markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes were identified in these pigmented cells by electron microscopy, and global gene expression profiling of the pigmented cells showed a high similarity to that of human primary foreskin-derived melanocytes, suggesting the successful generation of melanocytes from iPS cells. This in vitro differentiation system should prove useful for understanding human melanocyte biology and revealing the mechanism of various pigment cell disorders, including melanoma. PMID:21249204

  2. 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

  3. Melanocytic Nevus of the Tarsal Conjunctiva

    PubMed Central

    Yazıcı, Bülent; Bilge, Ayşe Dolar; Yağcı, Ayşe; Naqadan, Faisal; Altıntepe, Filiz

    2016-01-01

    Background: Melanocytic nevus is a rare occurrence in the tarsal conjunctiva and only 7 well-described cases have been reported previously in the English literature. Case Report: The medical records of 4 patients with tarsal conjunctival melanocytic nevus were reviewed, together with the relevant literature. All patients (3 women and 1 man; age range: 17 – 40 years) had been referred with a suspicion of melanoma. There was one tarsal nevus in the lower eyelid in 3 patients and 2 nevi in the upper eyelid in 1 patient. All lesions were darkly pigmented with irregular borders and were associated with a history of a recent growth in size. An intralesional cyst was present in 1 nevus only. After surgical excision, no recurrence or complication occurred during the follow-up period (range: 7 – 48 months). Conclusion: Tarsal melanocytic nevus has been described in detail in 11 cases, including these 4 cases, in the English literature. The lesion arose from the lower eyelid in all cases except one. Tarsal melanocytic nevi may frequently display clinical features suggesting melanoma, such as advanced patient age, recent growth, dark and irregular pigmentation, nodularity, hypervascularity, and the absence of an intralesional cyst. After total excision, nevus recurrence or malignant transformation has not been reported.

  4. Acquired unilateral melanocytic nevi in otherwise normal skin.

    PubMed

    Yu, Xijun; Nagai, Hiroshi; Nishigori, Chikako; Horikawa, Tatsuya

    2008-01-01

    We describe a case with numerous melanocytic nevi in otherwise normal skin. A 5-year-old girl presented with more than 100 small pigment lesions on her left arm, shoulder and upper back without underlying light brown macule. The pigment lesions were first found on her left forearm at 3 months old and gradually increased along with her growth. Skin biopsy from a pigmented lesion shows a pathological change in compound-type melanocytic nevus without any atypical changes. Speckled lentiginous nevus is known to have multiple melanocytic lesions on the underlying brown macule from birth. Partial unilateral lentiginosis is characterized by unilateral lentigines with histopathological changes in lentigo but not melanocytic proliferation in the dermis. Agminated melanocytic nevi tend to be clustered together in a circumscribed area, whereas in the present case melanocytic nevi were segmentally arranged but not agminated. We consider that this is an unusual type of mosaicism of melanocytic disorders. PMID:18401177

  5. 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

  6. 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

  7. Melanocyte antigen triggers autoimmunity in human psoriasis.

    PubMed

    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; Prinz, Jörg C

    2015-12-14

    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. Induction of different morphologic features of malignant melanoma and pigmented lesions after transformation of murine melanocytes with bFGF-cDNA and H-ras, myc, neu, and E1a oncogenes.

    PubMed Central

    Ramon y Cajal, S.; Suster, S.; Halaban, R.; Filvaroff, E.; Dotto, G. P.

    1991-01-01

    Malignant melanomas show a remarkable degree of heterogeneity because of different morphologic features, biologic behavior, and prognosis. In this communication, the authors attempted to correlate morphologic heterogeneity of melanomas with transformation by different activated oncogenes; they studied the histologic features of melanocytic lesions induced by murine melanocytes transformed by basic fibroblast growth factor (b-FGF-cDNA) or H-ras, neu, myc, and E1a oncogenes, and the lesions were compared with those observed in human pathology. Tumors formed after grafting onto syngenic mice or subcutaneous injections in nude mice were studied. In syngenic mice, benign melanocytic lesions reminiscent of intradermal nevus were observed with melanocytes transformed with b-FGF-cDNA, and myc and E1a oncogenes. Benign lesions were also formed by neu-transformed melanocytes when they were grafted concomitantly with keratinocytes, whereas malignant tumors were formed by the same cells when grafted alone or together with fibroblasts. In contrast, H-ras melanocytes always formed malignant tumors. In nude mice, b-FGF-transformed melanocytes induced benign lesions, whereas transformed melanocytes by the other oncogenes formed malignant tumors with distinctive and homogeneous morphologic features that depended on the transforming oncogene. Melanomas with either epithelioid cell, spindle cell, small round cell, and anaplastic cell growth patterns could be distinguished after transformation with H-ras, neu, E1a, and myc oncogenes, respectively. These various histologic types are analogous to those that may be observed in human melanomas, even within the same tumor. These studies suggest a possible molecular mechanism for tumor heterogeneity in which distinct oncogenes or oncogenelike activities can be activated in different tumors or discrete parts of the same tumor. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1992762

  9. 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

  10. 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

  11. Active Notch1 Confers a Transformed Phenotype to Primary Human Melanocytes

    PubMed Central

    Pinnix, Chelsea C.; Lee, John T.; Liu, Zhao-Jun; McDaid, Ronan; Balint, Klara; Beverly, Levi J.; Brafford, Patricia A.; Xiao, Min; Himes, Benjamin; Zabierowski, Susan E.; Yashiro-Ohtani, Yumi; Nathanson, Katherine L.; Bengston, Ana; Pollock, Pamela M.; Weeraratna, Ashani T.; Nickoloff, Brian J.; Pear, Warren S.; Capobianco, Anthony J.; Herlyn, Meenhard

    2009-01-01

    The importance of MAPK signaling in melanoma is underscored by the prevalence of activating mutations in N-Ras and B-Raf; yet, clinical development of inhibitors of this pathway has been largely ineffective, suggesting that alternative oncogenes may also promote melanoma. Notch is an interesting candidate that has only been correlated with melanoma development and progression; a thorough assessment of tumor-initiating effects of activated Notch on human melanocytes would clarify the mounting correlative evidence and perhaps identify a novel target for an otherwise untreatable disease. Analysis of a substantial panel of cell lines and patient lesions demonstrated that Notch activity is significantly higher in melanomas than their non-transformed counterparts. The use of a constitutively-active, truncated Notch transgene construct (NIC) was exploited to determine if Notch activation is a ‘driving’ event in melanocytic transformation or instead a ‘passenger’ event associated with melanoma progression. NIC-infected melanocytes displayed increased proliferative capacity and biological features more reminiscent of melanoma such as dysregulated cell adhesion and migration. Gene expression analyses supported these observations and aided in the identification of MCAM, an adhesion molecule associated with acquisition of the malignant phenotype, as a direct target of Notch transactivation. NIC-positive melanocytes grew at clonal density, proliferated in limiting media conditions, and also exhibited anchorage-independent growth suggesting that Notch, alone, is a transforming oncogene in human melanocytes, a phenomenon not previously described for any melanoma oncogene; this new information yields valuable insight into the basic epidemiology of melanoma and launches a realm of possibilities for drug intervention in this deadly disease. PMID:19549918

  12. Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light

    PubMed Central

    Devi, Sulochana; Kedlaya, Rajendra; Maddodi, Nityanand; Bhat, Kumar M. R.; Weber, Craig S.; Valdivia, Hector

    2009-01-01

    Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca2+ levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role for TRPM1 in Ca2+ homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca2+ and uptake of extracellular Ca2+. These data suggest a role for TRPM1-mediated Ca2+ homeostasis, which is also regulated by ultraviolet B, in melanogenesis. PMID:19587221

  13. The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

    PubMed Central

    Pilloni, L.; Bianco, P.; Difelice, E.; Cabras, S.; Castellanos, M.E.; Atzori, L.; Ferreli, C.; Mulas, P.; Nemolato, S.; Faa, G.

    2011-01-01

    C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra-dermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing

  14. Autophagy as a melanocytic self-defense mechanism.

    PubMed

    Setaluri, Vijayasaradhi

    2015-05-01

    Defects in autophagy have implications for melanocyte survival and manifestations of skin pigmentary disorders. Zhang et al. (2015) show that mouse melanocytes lacking the autophagy protein Atg7 undergo premature senescence in vitro and accumulate products of oxidative damage, despite activation of the redox response. Interestingly, contrary to previous findings, the melanocyte-specific deficiency in autophagy did not cause major defects in melanosome biogenesis, nor did it produce visually striking changes in mouse coat color. PMID:25882462

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

    ClinicalTrials.gov

    2013-04-11

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

  16. Appearance of New Vemurafenib-associated Melanocytic Nevi on Normal-appearing Skin

    PubMed Central

    Bedikian, Agop Y.; Kim, Kevin B.

    2013-01-01

    Background: Vemurafenib, a selective BRAF inhibitor that has antineoplastic activity in patients with unresectable or metastatic malignant melanoma whose tumor harbors a BRAF V600E mutation, has multiple drug-associated cutaneous adverse effects. Purpose: To provide a detailed and comprehensive review of reported changing or new pigmented lesions in oncology patients who have been treated with vemurafenib. Methods: The new appearance of melanocytic nevi on normal-appearing skin after initiating treatment with vemurafenib is described in two men with metastatic malignant melanoma whose tumors demonstrated a BRAF V600E mutation. Using the PubMed database, an extensive literature search was performed for the following topics: vermurafenib, nevus, nevi, melanoma, pigmented lesion, cutaneous, adverse effect, side effect. The results of the search were used to secure all reports of new or changing pigmented lesions after initiating treatment with vemurafenib. Results: Vemurafenib is associated with both changes in existing pigmented lesions (including involution, alteration of color and size, and progression to melanoma) and the onset of new melanocytic lesions—nevi (in 5 patients) and primary melanomas (in 2 patients). Visual examination, dermoscopic evaluation, and reflectance confocal microscopy have been used to document the changes in existing or new melanocytic lesions subsequent to initiating treatment with vermurafenib. Histopathology analysis has shown these lesions to usually be either dysplastic nevi or new primary melanomas. Conclusion: Vemurafenib-treated patients can develop new pigmented lesions (such as nevi) and/or morphological changes in their existing melanocytic lesions (such as involution, increase in size, or alternation of color). In addition, they can develop new primary malignant melanomas that either occur de novo on normal-appearing skin or develop in pre-existing melanocytic lesions. Therefore, total body skin examination should be

  17. Melanocytes as instigators and victims of oxidative stress.

    PubMed

    Denat, Laurence; Kadekaro, Ana L; Marrot, Laurent; Leachman, Sancy A; Abdel-Malek, Zalfa A

    2014-06-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis, and to the intrinsic antioxidant defenses that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment. PMID:24573173

  18. Ancient melanocytic nevus: a simulator of malignant melanoma.

    PubMed

    Kerl, Helmut; Wolf, Ingrid H; Kerl, Katrin; Cerroni, Lorenzo; Kutzner, Heinz; Argenyi, Zsolt B

    2011-04-01

    Ancient melanocytic nevus (AN) is an unusual but distinctive melanocytic neoplasm within the spectrum of simulators of malignant melanoma. This report describes 13 patients with AN where a long follow-up information was available. Histopathology is characterized by 2 populations of melanocytes, namely, one with large pleomorphic cells and the other with small melanocytes. A few mitotic figures may be present exceptionally. MIB-1 (Ki67) proliferation marker reveals an overall low nuclear labeling index. Additional important findings are stromal degenerative changes. AN must be especially differentiated from dermal melanoma arising in a nevus. PMID:21399448

  19. 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.

  20. 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.

  1. Neurotized Congenital Melanocytic Nevus Resembling a Pigmented Neurofibroma

    PubMed Central

    Singh, Nidhi; Chandrashekar, Laxmisha; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

    2015-01-01

    Neurotized congenital melanocytic nevus and pigmented neurofibroma (PNF) are close mimics and pose a clinicopathological challenge. We present a case of pigmented hypertrichotic plaque over lumbosacral region and discuss the differential diagnosis and its clinical, histopathological and immunohistochemistry features which may aid in differentiation. We highlight the difficulties faced in differentiating neurotized congenital melanocytic nevus from pigmented neurofibroma. PMID:25657396

  2. Chronic suicidality and borderline personality.

    PubMed

    Sansone, Randy A

    2004-06-01

    Suicidal ideation is a complex clinical event. In this article, acute suicidal ideation is compared with chronic suicidal ideation, specifically their different meanings, relationships with Axis I and Axis II disorders, intrapsychic functions, approaches to assessment, and interventions. The potential risks of acute hospitalization of the chronically suicidal borderline personality disorder patient are discussed as well as a longitudinal, multidimensional treatment strategy for the chronically suicidal individual. PMID:15237042

  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

    2015-01-01

    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

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

    PubMed

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

    2016-05-01

    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 p16(Ink4a) 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

  6. 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

  7. [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. PMID:15597123

  8. What are melanocytes really doing all day long...?

    PubMed

    Plonka, P M; Passeron, T; Brenner, M; Tobin, D J; Shibahara, S; Thomas, A; Slominski, A; Kadekaro, A L; Hershkovitz, D; Peters, E; Nordlund, J J; Abdel-Malek, Z; Takeda, K; Paus, R; Ortonne, J P; Hearing, V J; Schallreuter, K U

    2009-09-01

    Everyone knows and seems to agree that melanocytes are there to generate melanin - an intriguing, but underestimated multipurpose molecule that is capable of doing far more than providing pigment and UV protection to skin (1). What about the cell that generates melanin, then? Is this dendritic, neural crest-derived cell still serving useful (or even important) functions when no-one looks at the pigmentation of our skin and its appendages and when there is essentially no UV exposure? In other words, what do epidermal and hair follicle melanocytes do in their spare time - at night, under your bedcover? How much of the full portfolio of physiological melanocyte functions in mammalian skin has really been elucidated already? Does the presence or absence of melanocytes matter for normal epidermal and/or hair follicle functions (beyond pigmentation and UV protection), and for skin immune responses? Do melanocytes even deserve as much credit for UV protection as conventional wisdom attributes to them? In which interactions do these promiscuous cells engage with their immediate epithelial environment and who is controlling whom? What lessons might be distilled from looking at lower vertebrate melanophores and at extracutaneous melanocytes in the endeavour to reveal the 'secret identity' of melanocytes? The current Controversies feature explores these far too infrequently posed, biologically and clinically important questions. Complementing a companion viewpoint essay on malignant melanocytes (2), this critical re-examination of melanocyte biology provides a cornucopia of old, but under-appreciated concepts and novel ideas on the slowly emerging complexity of physiological melanocyte functions, and delineates important, thought-provoking questions that remain to be definitively answered by future research. PMID:19659579

  9. Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation

    PubMed Central

    Jansen, Joyce C G; Van Calster, Joachim; Pulido, Jose S; Miles, Sarah L; Vile, Richard G; Van Bergen, Tine; Cassiman, Catherine; Spielberg, Leigh H; Leys, Anita M

    2015-01-01

    Background Paraneoplastic melanocytic proliferation (bilateral diffuse uveal melanocytic proliferation, BDUMP) is a rare but devastating disease that causes progressive visual loss in patients who usually have an occult malignancy. Visual loss occurs as a result of paraneoplastic changes in the uveal tissue. Methods In a masked fashion, the serum of two patients with BDUMP was evaluated for the presence of cultured melanocyte elongation and proliferation (CMEP) factor using cultured human melanocytes. We evaluated the efficacy of plasmapheresis as a treatment modality early in the disease in conjunction with radiation and chemotherapy. Results The serum of the first case patient was investigated after plasmapheresis and did not demonstrate proliferation of cultured human melanocytes. The serum of the second case was evaluated prior to treatment with plasmapheresis and did induce this proliferation. These findings are in accordance with the diminution of CMEP factor after plasmapheresis. Treatment with plasmapheresis managed to stabilise the ocular disease progression in both patients. Conclusions In the past, visual loss due to paraneoplastic melanocytic proliferation was considered progressive and irreversible. We treated two patients successfully with plasmapheresis and demonstrated a relation between CMEP factor in the serum of these patients and proliferation of cultured melanocytes. PMID:25908835

  10. [A serous cystadenoma of the ovary of borderline malignancy with a fifteen-year history. A case report].

    PubMed

    Nagata, O; Aramaki, S; Iino, H; Ishikawa, S; Yoshida, H; Azekami, M; Yamaguchi, Y; Iwasa, T; Matsukuma, K; Iwata, Y

    1990-04-01

    A case of a serous cystadenoma of a ovary of borderline malignancy is reported. Sixteen years earlier, the patient had undergone an exploratory laparotomy because of ovarian tumor, and the histologic diagnosis had been a serous cystadenocarcinoma. Postoperative chemotherapy was not effective and drainage of the tumor fluid had been performed for 15 years, with the estimated drainage volume estimated to have reached, 1,000 1. Gradual malnutrition and marked tumor growth then become apparent. A reevaluation of the initial histologic slides and her clinical course strongly suggested a serous cystadenoma of borderline malignancy. Thus a tumor resection, a bilateral salpingo-oophorectomy, and a hysterectomy was performed. A histologic diagnosis of a resected specimen confirmed a serous cystadenoma of borderline malignancy and the histologic features were quite similar to those of the initial biopsy specimens. The patient is living well postoperatively for 8 months without postoperative chemotherapy. PMID:2325270

  11. 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…

  12. 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…

  13. Giant congenital melanocytic nevus in a bulgarian newborn.

    PubMed

    Chokoeva, A A; Fioranelli, M; Roccia, M G; Lotti, T; Wollina, U; Tchernev, G

    2016-01-01

    Giant congenital melanocytic nevus (GCMN) is a rare disorder affecting 1 in 200,000–500,000 live births. Central nervous system defects such as spina bifida, meningocele, Dandy Walker malformation may accompany it and thus cause significant morbidity. Despite the related risk for malignant transformation, GCMNs may be associated with neurocutaneous melanosis, a rare syndrome in which a giant CMN or multiple smaller CMNs are accompanied by melanocytic deposition in the brain and the spinal cord. We present a case of a 5-day-old newborn with giant congenital melanocytic nevus on his back, as we discuss the diagnostic and treatment approach. PMID:27373137

  14. Melanocyte regeneration in vitiligo requires WNT beneath their wings

    PubMed Central

    Harris, John E.

    2015-01-01

    Melanocytes in patients with vitiligo possess intrinsic abnormalities that contribute to its pathogenesis. In this issue, Regazzetti, et al. report that CXCL10 expression reflects subtle inflammation in normal-appearing skin but not in stable depigmented lesions, supporting the hypothesis that melanocytes themselves initiate autoimmune inflammation prior to clinically evident disease. In addition, they find that oxidative stress in melanocytes impairs WNT signaling and that targeting this pathway induces melanoblast differentiation. Thus, activating the WNT pathway may serve as an adjunctive strategy to support repigmentation in patients with vitiligo. PMID:26569586

  15. 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

  16. Borderline personality disorder: study in adolescence.

    PubMed

    James, A; Berelowitz, M; Vereker, M

    1996-04-01

    The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile. PMID:9117533

  17. 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. PMID:25140664

  18. 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.

  19. Timeline and distribution of melanocyte precursors in the mouse heart.

    PubMed

    Brito, Flavia Carneiro; Kos, Lidia

    2008-08-01

    Apart from the well-studied melanocytes of the skin, eye and inner ear, another population has recently been described in the heart. In this study, we tracked cardiac melanoblasts using in situ hybridization with a dopachrome tautomerase (Dct) probe and Dct-LacZ transgenic mice. Large numbers of melanoblasts were found in the atrioventricular (AV) endocardial cushions at embryonic day (E) 14.5 and persisted in the AV valves into adulthood. The earliest time Dct-LacZ-positive cells were observed in the AV endocardial cushions was E12.5. Prior to that, between E10.5 and E11.5, small numbers of melanoblasts traveled between the post-otic area and third somite along the anterior and common cardinal veins and branchial arch arteries with other neural crest cells expressing CRABPI. Cardiac melanocytes were not found in the spotting mutants Ednrb s-l/s-l and Kit w-v/w-v, while large numbers were observed in transgenic mice that overexpress endothelin 3. These results indicate that cardiac melanocytes depend on the same signaling molecules known to be required for proper skin melanocyte development and may originate from the same precursor population. Cardiac melanocytes were not found in zebrafish or frog but were present in quail suggesting an association between cardiac melanocytes and four-chambered hearts. PMID:18444965

  20. 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

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

    PubMed

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

    2016-09-01

    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/cm(2) ) 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

  2. 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

  3. Functionally distinct melanocyte populations revealed by reconstitution of hair follicles in mice.

    PubMed

    Aoki, Hitomi; Hara, Akira; Motohashi, Tsutomu; Osawa, Masatake; Kunisada, Takahiro

    2011-02-01

    Hair follicle reconstitution analysis was used to test the contribution of melanocytes or their precursors to regenerated hair follicles. In this study, we first confirmed the process of chimeric hair follicle regeneration by both hair keratinocytes and follicular melanocytes. Then, as first suggested from the differential growth requirements of epidermal skin melanocytes and non-cutaneous or dermal melanocytes, we confirmed the inability of the latter to be involved as follicular melanocytes to regenerate hair follicles during the hair reconstitution assay. This clear functional discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes suggests the presence of two different melanocyte cell lineages, a finding that might be important in the pathogenesis of melanocyte-related diseases and melanomas. PMID:21054816

  4. Aggression in borderline personality disorder.

    PubMed

    Látalová, K; Prasko, J

    2010-09-01

    This review examined aggressive behavior in Borderline Personality Disorder (BPD) and its management in adults. Aggression against self or against others is a core component of BPD. Impulsiveness is a clinical hallmark (as well as a DSM-IV-TR diagnostic criterion) of BPD, and aggressive acts by BPD patients are largely of the impulsive type. BPD has high comorbidity rates with substance use disorders, Bipolar Disorder, and Antisocial Personality Disorder; these conditions further elevate the risk for violence. Treatment of BDP includes psychodynamic, cognitive behavioral, schema therapy, dialectic behavioral, group and pharmacological interventions. Recent studies indicate that many medications, particularly atypical antipsychotics and anticonvulsants, may reduce impulsivity, affective lability as well as irritability and aggressive behavior. But there is still a lack of large, double blind, placebo controlled studies in this area. PMID:20390357

  5. Phenomenology of Borderline Personality Disorder

    PubMed Central

    De Genna, Natacha M.; Feske, Ulrike

    2015-01-01

    Little is known about racial differences in borderline personality disorder (BPD) that may influence etiology, phenomenology, and treatment of women with BPD. A total of 83 women with BPD participated in this cross-sectional study: n = 41 white and n = 42 African-American women. Structured interviews were used to assess Axis I and II disorders, and a series of interviews and questionnaires captured internalizing and externalizing symptoms. The white women with BPD reported more severe internalizing symptoms, whereas the African-American women reported more severe externalizing symptoms. Except for the association between race and number of suicide attempts, the relationship between race and internalizing/externalizing symptoms was mediated by socioeconomic status. In conclusion, African-American women with BPD may present with more severe symptoms of lack of anger control and fewer suicidal behaviors than those of white women with BPD, raising the possibility that they are misdiagnosed and receive treatments that are not optimal for BPD. PMID:24284636

  6. Borderline personality disorder in adolescence.

    PubMed

    Kaess, Michael; Brunner, Romuald; Chanen, Andrew

    2014-10-01

    Borderline personality disorder (BPD) is a common and severe mental disorder that is associated with severe functional impairment and a high suicide rate. BPD is usually associated with other psychiatric and personality disorders, high burden on families and carers, continuing resource utilization, and high treatment costs. BPD has been a controversial diagnosis in adolescents, but this is no longer justified. Recent evidence demonstrates that BPD is as reliable and valid among adolescents as it is in adults and that adolescents with BPD can benefit from early intervention. Consequently, adolescent BPD is now recognized in psychiatric classification systems and in national treatment guidelines. This review aims to inform practitioners in the field of adolescent health about the nature of BPD in adolescence and the benefits of early detection and intervention. BPD diagnosis and treatment should be considered part of routine practice in adolescent mental health to improve these individuals' well-being and long-term prognosis. PMID:25246626

  7. Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer.

    PubMed

    Gram, Inger T; Braaten, Tonje; Adami, Hans-Olov; Lund, Eiliv; Weiderpass, Elisabete

    2008-02-01

    Studies regarding the association between smoking and risk of epithelial ovarian cancer (EOC) are inconsistent. The purpose of this study was to examine the association between smoking and EOC, overall and according to invasiveness and histological subtype in a cohort of women with a high proportion of smokers at enrollment. We followed 103,081 women, aged 30-50 years in 1991/1992, from the Norwegian-Swedish Women's Lifestyle and Health cohort. The women completed a questionnaire on personal characteristics and exposures at enrollment and were subsequently followed with linkages to national registers through December 31, 2004. We used Cox proportional hazard regression models to estimate hazard ratio (RR) of EOC with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 343 [241 (70%) invasive and 102(30%) borderline] incident EOC cases were identified. Former [HR = 2.2(95% CI 1.0-4.7)] and current [HR = 2.7(95% CI 1.2-5.7)] smokers had a more than doubling in risk for borderline tumors compared to never smokers. Women who had smoked for more than 20 years had 3 times [HR = 3.1(95% CI 1.5-6.7)] the risk of borderline tumors compared to never smokers. A test for trend according to smoking status was almost significant for mucinous tumors (p-trend = 0.05). A significant dose response relationship was found according to smoking intensity [pack-years; (0-9, 0-14, >or= 15)] and duration [number of years; (0-10, 11-20, >or= 20)] for borderline and serous tumors (p-trends < 0.05). In conclusion, smoking may increase the risk of borderline EOC. PMID:17918152

  8. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  9. 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. PMID:26093995

  10. Proton pump inhibitors decrease melanogenesis in melanocytes

    PubMed Central

    BAEK, SEUNG-HWA; LEE, SANG-HAN

    2015-01-01

    Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition, the melanin content and viability of melan-a cells treated with PPIs were assessed and the mRNA levels of melanogenesis-associated genes were measured by reverse transcription-polymerase chain reaction. Treatment with rabeprazole, but not the other PPIs tested, resulted in strong, dose-dependent inhibition of mushroom tyrosinase (TYR). By contrast, each of the PPIs tested exhibited copper-chelating activity. Treatment of melan-a cells with 100 µM concentrations of the PPIs resulted in significantly reduced melanin synthesis and reduced expression of several melanogenesis-associated genes, including TYR, TYR-related protein-1 (TRP-1) and TRP-2, and microphthalmia-associated transcription factor, but did not result in cytotoxic effects. These results suggest that PPIs inhibit melanin biosynthesis in melan-a cells via the downregulation of melanogenesis-associated genes. Furthermore, the findings indicate that PPIs in general could be utilized as skin-whitening agents and/or as biomaterial for treating hyperpigmentation disorders. PMID:26405553

  11. DNA microarrays and likelihood ratio bioinformatic methods: discovery of human melanocyte biomarkers.

    PubMed

    Dooley, Thomas P; Curto, Ernest V; Davis, Richard L; Grammatico, Paola; Robinson, Edward S; Wilborn, Teresa W

    2003-06-01

    In this article, some of the advantages and limitations of DNA microarray technologies for gene expression profiling are summarized. As a model experiment, DermArray DNA microarrays were utilized to identify potential biomarkers of cultured normal human melanocytes in two different experimental comparisons. In the first case, melanocyte RNA was compared with vastly dissimilar non-melanocytic RNA samples of normal skin keratinocytes and fibroblasts. In the second case, melanocyte RNA was compared with a primary cutaneous melanoma line (MS7) and a metastatic melanoma cell line (SKMel-28). The alternative approaches provide dramatically different lists of 'normal melanocyte' biomarkers. The most robust biomarkers were identified using principal component analysis bioinformatic methods related to likelihood ratios. Only three of 25 robust biomarkers in the melanocyte-proximal study (i.e. melanocytes vs. melanoma cells) were coincidentally identified in the melanocyte-distal study (i.e. melanocytes vs. non-melanocytic cells). Selected up-regulated biomarkers of melanocytes (i.e. TRP-1, melan-A/MART-1, silver/Pmel17, and nidogen-2) were validated by qRT-PCR. Some of the melanocytic biomarkers identified here may be useful in molecular diagnostics, as potential molecular targets for drug discovery, and for understanding the biochemistry of melanocytic cells. PMID:12753397

  12. [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. PMID:21936354

  13. Differential effects of UV irradiation on nuclear retinoid receptor levels in cultured keratinocytes and melanocytes.

    PubMed

    Andersson, Eva; Rosdahl, Inger; Törmä, Hans; Vahlquist, Anders

    2003-10-01

    A major risk factor for skin cancer is UV irradiation, which not only damages DNA and other photosensitive compounds like vitamin A, but may also perturb cellular signaling, e.g. via the retinoid receptor system believed to be important for cancer protection. We used cultured normal human keratinocytes and melanocytes to examine the effects of UV irradiation on the expression of the predominant retinoid receptors in the human skin (RARalpha, RARgamma and RXRalpha) and the AP-1 protein c-Jun; mRNA levels were studied by real-time PCR and protein levels by Western blot. In keratinocytes, a single dose of UVB (50 mJ/cm2) caused a rapid drop in the expression of all three receptors (mRNA levels minus 35-50% after 4 h; protein levels minus 20-45% after 8 h), which was followed over the next 40 h by a variable response, leading to full normalization for RARalpha only. In contrast, the levels of c-Jun did not change significantly after UV exposure. In melanocytes, UVB caused a similar drop of the retinoid receptor levels as in keratinocytes but this was soon followed by an increased expression leading to a complete normalization of all receptor levels within 1-3 days. The c-Jun levels in melanocytes increased 1 day after UV exposure and remained high (plus 50%) thereafter. In both cell types, a approximately 3-fold increase in apoptosis (measured by DNA fragmentation) was observed 8-48 h after UVB irradiation. In conclusion, a depletion of vitamin A and retinoid receptors by UV irradiation, together with unchanged or even increased c-Jun levels, might seriously interfere with retinoid signaling and thus promote future tumor development, especially in keratinocytes. PMID:14705796

  14. Knowledge Building Insights on Biomarkers of Arsenic Toxicity to Keratinocytes and Melanocytes

    PubMed Central

    Isokpehi, Raphael D.; Udensi, Udensi K.; Anyanwu, Matthew N.; Mbah, Andreas N.; Johnson, Matilda O.; Edusei, Kafui; Bauer, Michael A.; Hall, Roger A.; Awofolu, Omotayo R.

    2012-01-01

    Exposure to inorganic arsenic induces skin cancer and abnormal pigmentation in susceptible humans. High-throughput gene transcription assays such as DNA microarrays allow for the identification of biological pathways affected by arsenic that lead to initiation and progression of skin cancer and abnormal pigmentation. The overall purpose of the reported research was to determine knowledge building insights on biomarker genes for arsenic toxicity to human epidermal cells by integrating a collection of gene lists annotated with biological information. The information sets included toxicogenomics gene-chemical interaction; enzymes encoded in the human genome; enriched biological information associated with genes; environmentally relevant gene sequence variation; and effects of non-synonymous single nucleotide polymorphisms (SNPs) on protein function. Molecular network construction for arsenic upregulated genes TNFSF18 (tumor necrosis factor [ligand] superfamily member 18) and IL1R2 (interleukin 1 Receptor, type 2) revealed subnetwork interconnections to E2F4, an oncogenic transcription factor, predominantly expressed at the onset of keratinocyte differentiation. Visual analytics integration of gene information sources helped identify RAC1, a GTP binding protein, and TFRC, an iron uptake protein as prioritized arsenic-perturbed protein targets for biological processes leading to skin hyperpigmentation. RAC1 regulates the formation of dendrites that transfer melanin from melanocytes to neighboring keratinocytes. Increased melanocyte dendricity is correlated with hyperpigmentation. TFRC is a key determinant of the amount and location of iron in the epidermis. Aberrant TFRC expression could impair cutaneous iron metabolism leading to abnormal pigmentation seen in some humans exposed to arsenicals. The reported findings contribute to insights on how arsenic could impair the function of genes and biological pathways in epidermal cells. Finally, we developed visual analytics

  15. Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.

    PubMed

    Poorman, Kelsey; Borst, Luke; Moroff, Scott; Roy, Siddharth; Labelle, Philippe; Motsinger-Reif, Alison; Breen, Matthew

    2015-06-01

    Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways. PMID:25511566

  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. PMID:25765751

  17. 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

  18. 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. PMID:22574862

  19. 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. PMID:24131586

  20. 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.

  1. 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. PMID:27155159

  2. 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. PMID:26854492

  3. Developmental aspects of borderline personality disorder.

    PubMed

    Reich, D B; Zanarini, M C

    2001-01-01

    This study examined whether patients with borderline personality disorder and controls with other personality disorders remember their childhoods differently with respect to separation difficulties, evocative memory, temperamental factors such as frustration tolerance and mood reactivity, and onset of symptoms. Two hundred and ninety patients with borderline personality disorder and 72 with other personality disorders were assessed using an instrument to rate memories of separation difficulties, temperamental problems, and onset of symptoms before age 18. Patients with borderline personality disorder remembered more difficulties with separation between ages 6 and 17 years, more mood reactivity and poorer frustration tolerance between ages 6 and 17, and the onset of more symptoms (most prominently sadness, depression, anxiety, and suicidality) before age 18 than did patients with other personality disorders. The groups did not differ in reports of evocative memory before age 18. These results indicate that many of the features of adult patients with borderline personality disorder may initially appear during childhood and adolescence and that these features may be used to differentiate borderline from other personality disorders. PMID:11600488

  4. Characterization of the CDKN2A and ARF genes in UV-induced melanocytic hyperplasias and melanomas of an opossum (Monodelphis domestica).

    PubMed

    Chan, J; Robinson, E S; Atencio, J; Wang, Z; Kazianis, S; Coletta, L D; Nairn, R S; McCarrey, J R

    2001-05-01

    We examined the involvement of the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in the pathogenesis of ultraviolet (UV) radiation-induced melanomas in an opossum (Monodelphis domestica) melanoma model in which suckling young were exposed to UVB to produce melanocytic lesions. Monodelphis CDKN2A and alternated reading frame (ARF) cDNAs were cloned and sequenced, and the expression patterns of these genes were determined by reverse transcription-polymerase chain reaction in normal tissues, 39 primary melanocytic skin lesions, and two tumor-derived cell lines, one nonmetastatic and one metastatic. Primary melanocytic lesions, including hyperplasias, benign melanomas, melanomas metastatic to lymph nodes, and melanomas metastatic to nodes and additional visceral organs, were categorized accordingly as types I-IV. Levels of CDKN2A transcripts were most abundant in type III tumor samples and the metastatic cell line but absent in the nonmetastatic cell line. ARF transcripts were expressed in all tumors and cell lines. A UV-signature mutation was detected with the wild-type allele at the CDKN2A locus in type II and III primary tumor samples and in the nonmetastatic cell line. Interestingly, in the metastatic cell line, only the mutant allele was present and expressed. These data suggest dynamic changes in the expression and/or structure of the CDKN2A and ARF genes represent one molecular defect associated with the etiology of melanoma formation and progression in the Monodelphis model system. PMID:11398194

  5. Recognizing borderline personality disorder in the family practice setting.

    PubMed

    Hubbard, J R; Saathoff, G B; Bernardo, M J; Barnett, B L

    1995-09-01

    The first step in the management of borderline personality disorder is making the correct diagnosis. A clinical example illustrates symptoms of a patient with borderline personality disorder in a family practice setting. Major characteristics of borderline personality disorder include severe mood instability, fear of abandonment, chronic boredom, self-injury, unstable interpersonal relationships, "splitting," identity instability and borderline rage. Early diagnosis may help prevent potential management problems and possible doctor-patient conflicts. PMID:7653428

  6. 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

  7. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    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

  8. Management of borderline resectable pancreatic cancer.

    PubMed

    Lal, Alysandra; Christians, Kathleen; Evans, Douglas B

    2010-04-01

    Borderline resectable pancreatic cancer is an emerging stage of disease defined by computed tomogrpahy criteria, patient (Katz type B), or disease characteristics (Katz type C). These patients are particularly well suited to a surgery-last strategy with induction therapy consisting of chemotherapy (gemcitabine alone or in combination) followed by chemoradiation. With appropriate selection and preoperative planning, many patients with borderline resectable disease derive clinical benefit from multimodality therapy. The use of a standardized system for the staging of localized pancreatic cancer avoids indecision and allows for the optimal treatment of all patients guided by the extent of their disease. In this article, 2 case reports are presented, and the term borderline resectable pancreatic cancer is discussed. The advantages of neoadjuvant therapy and surgery are also discussed. PMID:20159519

  9. An Overview of Countertransference With Borderline Patients

    PubMed Central

    GABBARD, GLEN O.

    1993-01-01

    Successful management of countertransference is critical to the psychotherapy of borderline patients. The author discusses the most common countertransference reactions encountered in such treatments. A theoretical framework is also proposed that conceptualizes countertransference as a joint creation between therapist and patient. It follows from this conceptual framework that therapists must constantly monitor their own contributions from past relationships as well as the aspects of countertransference evoked by the patient’s behavior. Countertransference in the psychotherapy of borderline patients must be viewed as a source of valuable diagnostic and therapeutic information and not simply as interference with the therapeutic process. PMID:22700123

  10. 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. PMID:26913071

  11. 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

  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. 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

  14. 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

  15. Optimal management of common acquired melanocytic nevi (moles): current perspectives.

    PubMed

    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

  16. Digital dermoscopic follow-up of 1544 melanocytic nevi.

    PubMed

    Rotaru, Maria; Nati, Angelica-Elena; Avrămoiu, Ioan; Grosu, Florin; Mălăescu, Gheorghe Dan

    2015-01-01

    The use of dermatoscopy increases melanocytic nevi diagnostic accuracy, and is important for dermoscopic monitoring of atypical lesions, allowing to find significant changes in the earliest stage. Dermoscopic diagnosis of melanocytic nevi type in a group of patients and their follow-up with the assessment of changes occurred during dermoscopic monitoring. Dermoscopically, we followed the nevic size and pattern, the color and pigment distribution. Follow-up visits were scheduled depending on the type of the melanocytic lesions and the patient's compliance. The nevi that have shown significant dermoscopic changes were excised and histopathologically examined. The study was performed on a group of 92 patients, mostly females (56.5%), mean age of 29.1 years. Of the total of 1544 melanocytic nevi examined, 27.4% were atypical and 72.6% common nevi. The average dermoscopic examination interval was 14.1 months. During monitoring, 35.5% atypical nevi and 22.5% common nevi have modified, especially changes in pigmentation and color (31% atypical nevi and 9.9% common nevi) and the appearance of new dermoscopic structures (12.7% atypical nevi and common nevi 8.5%). Of the total nevi monitored, 3% showed significant changes and were excised and examined pathologically, without diagnose of any malignant transformation. In our study, dermoscopic changes appeared in atypical as well as in common nevi. The dermoscopic monitoring of melanocytic-pigmented lesions remains an accessible method of assessment the evolution of nevi and can reduce the risk of appearance of malignant melanoma in the general population. PMID:26743296

  17. 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…

  18. The psychotherapy of core borderline psychopathology.

    PubMed

    Adler, G

    1993-01-01

    A psychodynamic formulation of borderline psychopathology includes the understanding of the borderline patient's aloneness problems, need-fear dilemma issues, and difficulties with primitive guilt. The aloneness problems are at the core of the disorder, and involve an inability to maintain an evocative memory, and holding and soothing introjects of significant people when under stress of separation. The possible childhood origins of these difficulties are explored and related to the ways these issues emerge in psychotherapy. The psychodynamic formulation is crucial in the psychotherapeutic approach to the aloneness problems. It helps the therapist work with the aloneness difficulties and understand the options as the therapy continues. Since rapid therapeutic decisions are often necessary with borderline patients, the formulation provides the necessary framework, and helps the therapist process and utilize countertransference feelings. Projective identification is an important concept that helps explain the complex transference/countertransference experiences, and is used in defining the resolution of the aloneness problems of borderline patients. Finally, limit-setting and the use of transitional objects are explored, utilizing the psychodynamic framework that has been defined. PMID:8517469

  19. Dysphoria and aloneness in borderline personality disorder.

    PubMed

    Pazzagli, A; Monti, M R

    2000-01-01

    A close examination of dysphoria, anger and aloneness (three main characteristics of the borderline syndrome) provides a theoretical model of reference for the therapist. Dysphoria results from the cyclical emotional oscillation between hope for stability and disappointment in its inattainability; a dependent-anaclitic depression arises from the mixture of anger, aloneness and inner emptiness which is so characteristic of the borderline syndrome. The tendency to be immersed in the here-and-now, an intra-festum mentality, exacerbates the sense of isolation, causing more irritation, mute frustration and, consequently, anger. The effects and ramifications of anger, and the resultant precarious cohesion of the self, are explored in the borderline syndrome; they are especially illuminated by the application of Kernberg's pain-anger-hate-vengefulness cycle concept. Meanings of solitude, in its forms of aloneness and loneliness, are explored in their pertinence. Aloneness - the constant needy search for, but condemnation to never finding, objects to fill an inner sense of emptiness - is especially germane. Suggestions for assisting subjects with borderline personality disorder to overcome aloneness and the lack of historical progression are made. PMID:10867581

  20. 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. PMID:26909586

  1. 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. PMID:25634357

  2. 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

  3. Mitochondria are more numerous and smaller in pink-eyed dilution melanoblasts and melanocytes than in wild-type melanocytes in the neonatal mouse epidermis.

    PubMed

    Hirobe, Tomohisa; Ishizuka, Kenji; Ogawa, Shigeru; Abe, Hiroyuki

    2008-11-01

    Abstract The mouse pink-eyed dilution (p) locus is known to control the melanin content in melanocytes. However, it was not known whether the p gene is involved in regulating the proliferation and differentation of melanocytes during development, especially the biogenesis of melanosomes and other organelles. Epidermal cell suspensions of neonatal dorsal skin derived from mice wild type for the p locus (black, C57BL/10JHir-P/P) and their congenic mutant phenotype (pink-eyed dilution, C57BL/10JHir-p/p) were cultured in serum-free melanocyte-proliferation medium (MDMD). The supplement of additional L-tyrosine (Tyr) into the MDMD stimulated the differentiation of p/p melanoblasts into melanocytes. Electron microscopy revealed that in p/p melanoblasts and melanocytes treated with L-Tyr, the number of stage II and III melanosomes dramatically increased. Moreover, p/p melanoblasts possessed smaller but more numerous mitochondria than P/P melanocytes. The treatment of p/p melanoblasts and melanocytes with L-Tyr decreased the number of mitochondria. The supplement of 2, 4-dinitrophenol (DNP), an inhibitor of mitochondrial function, into the MDMD stimulated both the proliferation and differentiation of p/p melanoblasts. Simultaneous treatment of DNP and L-Tyr dramatically stimulated the differetiation of p/p melanocytes. These results suggest that L-Tyr and some unknown factors related to mitochondrial function may influence the differentiation of melanoblasts in the epidermis of p/p mice. PMID:19267617

  4. S100P is a useful marker for differentiation of ovarian mucinous tumors.

    PubMed

    Umezaki, Y; Ito, M; Nakashima, M; Mihara, Y; Naruke, Y; Kurohama, H; Yatsunami, N; Yasuhi, I

    2015-01-01

    The S100P protein stimulates cell proliferation and survival, thereby contributing to tumor progression. The purpose of this study was to evaluate S100P expression in the three subtypes of mucinous cystic tumors, cystadenomas, borderline tumors, and adenocarcinomas. The authors examined nuclear S100P expression in 60 mucinous ovarian tumor specimens, including 24 specimens of mucinous cystadenoma, 15 of borderline tumors, and 21 of adenocarcinomas. Immunohistochemistry revealed S100P expression followed one of three patterns: (1) Expressed in most nuclei of mucinous epithelial cells, (2) sporadic (spotted or patchy) expression, or (3) absent or rarely expressed in the nuclei of mucinous epithelial cells. Most adenomas showed the first expression pattern, and borderline tumors often showed a patchy expression pattern. Adenocarcinomas generally demonstrated absence of S100P expression. These data suggest that S100P is a useful histological marker to differentiate between benign, borderline, and malignant mucinous tumors of the ovary. PMID:26050349

  5. Asymmetry and irregularity border as discrimination factor between melanocytic lesions

    NASA Astrophysics Data System (ADS)

    Sbrissa, David; Pratavieira, Sebastião.; Salvio, Ana Gabriela; Kurachi, Cristina; Bagnato, Vanderlei Salvadori; Costa, Luciano Da Fontoura; Travieso, Gonzalo

    2015-06-01

    Image processing tools have been widely used in systems supporting medical diagnosis. The use of mobile devices for the diagnosis of melanoma can assist doctors and improve their diagnosis of a melanocytic lesion. This study proposes a method of image analysis for melanoma discrimination from other types of melanocytic lesions, such as regular and atypical nevi. The process is based on extracting features related with asymmetry and border irregularity. It were collected 104 images, from medical database of two years. The images were obtained with standard digital cameras without lighting and scale control. Metrics relating to the characteristics of shape, asymmetry and curvature of the contour were extracted from segmented images. Linear Discriminant Analysis was performed for dimensionality reduction and data visualization. Segmentation results showed good efficiency in the process, with approximately 88:5% accuracy. Validation results presents sensibility and specificity 85% and 70% for melanoma detection, respectively.

  6. Spontaneous Involution of Congenital Melanocytic Nevus With Halo Phenomenon

    PubMed Central

    Lee, Noo Ri; Chung, Hee-Chul; Hong, Hannah; Lee, Jin Wook

    2015-01-01

    Abstract: 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. PMID:26588343

  7. 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.

  8. Epidermal nevi with aberrant epidermal structure in keratinocytes and melanocytes.

    PubMed

    Oiso, Naoki; Sugawara, Koji; Yonamine, Ayano; Tsuruta, Daisuke; Kawada, Akira

    2015-04-01

    Epidermal nevi are congenital cutaneous hamartomas caused by embryonic somatic mutations. Ultrastructural features of adult epidermal nevi have rarely been investigated. Herein, we report a case involving a Japanese adult who had epidermal nevi with right congenital blindness and a right accessory nipple. The histopathologic and ultrastructural studies showed divergent abnormal epidermal structures in both melanocytes and keratinocytes. Our case indicates the need to further investigate histopathologic, ultrastructural, and genetic associations in adult epidermal nevi. PMID:25657059

  9. 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.

  10. UVA Phototransduction Drives Early Melanin Synthesis in Human Melanocytes

    PubMed Central

    Wicks, Nadine L.; Chan, Jason W.; Najera, Julia A.; Ciriello, Jonathan M.; Oancea, Elena

    2013-01-01

    Summary Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% UVA and ~5% 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 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 five-fold after 24 hours. 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. PMID:22055294

  11. 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

  12. 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. PMID:27476283

  13. 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

  14. UVB induces atypical melanocytic lesions and melanoma in human skin.

    PubMed Central

    Atillasoy, E. S.; Seykora, J. T.; Soballe, P. W.; Elenitsas, R.; Nesbit, M.; Elder, D. E.; Montone, K. T.; Sauter, E.; Herlyn, M.

    1998-01-01

    A direct causal relationship between ultraviolet (UV) light in the B range and melanoma development has not been demonstrated in humans; this study aims to establish causality. A total of 158 RAG-1 mice, grafted with human newborn foreskin, were separated into four groups and observed for a median of 10 months: 1) no treatment, 2) a single treatment with 7,12-dimethyl(a)benzanthracene (DMBA), 3) UVB irradiation at 500 J/m2 alone, three times weekly, and 4) a combination of DMBA and UVB. Twenty-three percent of 40 normal human skin grafts treated with UVB only and 38% of 48 grafts treated with the combination of DMBA and UVB developed solar lentigines within 5 to 10 months of treatment. Melanocytic hyperplasia was found in 73% of all UVB-treated xenografts. Histological melanocytic changes resembling lentigo and lentigo maligna were seen in several skin grafts treated with both DMBA and UVB. In one graft of an animal treated with a combination of DMBA and UVB, a human malignant melanoma, nodular type, developed. This experimental system demonstrates that chronic UVB irradiation with or without an initiating carcinogen can induce human melanocytic lesions, including melanoma. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9588887

  15. Persistence of CTL clones targeting melanocyte differentiation antigens was insufficient to mediate significant melanoma regression in humans

    PubMed Central

    Chandran, Smita S.; Paria, Biman C.; Srivastava, Abhishek K.; Rothermel, Luke D.; Stephens, Daniel J.; Dudley, Mark E.; Somerville, Robert; Wunderlich, John R.; Sherry, Richard M.; Yang, James C.; Rosenberg, Steven A.; Kammula, Udai S.

    2014-01-01

    Purpose Adoptive transfer of autologous tumor infiltrating lymphocytes (TIL) can mediate durable cancer regression in selected patients with metastatic melanoma. However, the tumor antigens associated with these favorable responses remain unclear. We hypothesized that a clinical strategy involving the iterative adoptive transfer of selected autologous antigen specific T cell clones could help systematically define immunologic targets associated with successful cancer therapy, without the interpretative ambiguity of transferring polyclonal populations. Here, we evaluated the clinical efficacy of CD8+ T cell clones specific for the melanocyte differentiation antigens (MDA), gp100 and MART-1, respectively. Experimental Design We conducted two consecutive phase II clinical trials involving the adoptive transfer of highly selected autologous antigen specific CD8+ T cell clones against gp100 and MART-1, respectively. Fifteen HLA-A2+ treatment-refractory metastatic melanoma patients received highly avid MDA specific CD8+ T cell clones specific for either gp100 (n=10) or MART-1 (n=5) with or without intravenous interleukin-2 after a lymphodepleting myeloablative preparative regimen. Results Of the fifteen treated patients, we observed immune mediated targeting of skin melanocytes in eleven patients (73%) and clonal engraftment in eight patients (53%) after cell transfer. There were only transient minor tumor regressions observed, but no objective tumor responses based upon RECIST criteria. Conclusions Despite successful clonal repopulation and evidence of in vivo antigen targeting, the poor therapeutic efficacy after the adoptive transfer of autologous MDA specific T cells raises significant concerns regarding future immunotherapy efforts targeting this class of tumor antigens. PMID:25424856

  16. Neurobehavioral study of borderline personality disorder.

    PubMed Central

    van Reekum, R; Conway, C A; Gansler, D; White, R; Bachman, D L

    1993-01-01

    The existence of an "organic" subgroup of borderline personality disorder (BPD) has been postulated. This report is of a case-controlled, chart-review study of BPD. The control sample consisted of patients with a variety of psychiatric diagnoses. The study found that 81% of the patients with BPD and 22% of the control patients had a history of brain injury, either developmental (44%), acquired (58%) or both. Furthermore, there was a positive correlation between the summed number of developmental and acquired brain injuries and the score on the retro-Diagnostic Interview for Borderline. A pilot neuropsychological study showed that seven of nine subjects with BPD had evidence of frontal system dysfunction. These results help to support the hypothesized existence of an organic BPD subgroup. PMID:8499428

  17. Borderline personality traits in hysterical neurosis.

    PubMed

    Ohshima, T

    2001-04-01

    The objective of the present study is to demonstrate the traits of the psychopathology of Borderline Personality Disorder (BPD) compared with hysterical neurosis. A total of 48 subjects with BPD and 40 subjects with hysterical neurosis both defined by DSM-III-R were assessed by Diagnostic Interview for Borderlines (DIB). Statistical analysis was done by quantification of the second type, a multivariate data analysis. The total scores of DIB were BPD group, 6.13 +/- 1.52; hysterical neurosis group, 4.9 +/- 2.12 (t = 3.05, P = 0.0016). The correlation ratio (index of to what extent the two groups are discriminated) was 0.2442. Among the four parameters of: (i) affect, (ii) cognition, (iii) impulse-action pattern, (iv), and interpersonal relationships, the partial coefficient correlations of (iii) and (iv) were significantly high (0.342, 0.287, P < 0.01). The question items with high independent coefficients were manipulation (0.4416), intolerance of aloneness (0.3797), demanding nature (0.3768), self-mutilation (0.3609), visual hallucination (0.3395). Those with low score of independent coefficients were counterdependency (0.0533), identity disturbance (0.1010), depression (0.1551), loneliness (0.1752), hypomanic episode (0.1936). Both of BPD and hysterical neurosis groups were not so fairly well discriminated. However, these results suggested that impulse-action pattern and disorder of interpersonal relationships were traits of borderline personality disorder. We could admit manipulation, intolerance of aloneness as its symptoms. In addition, counterdependency, identity disturbance were comparatively common to both. There were some borderline personality traits symptomatically in hysterical neurosis. PMID:11285092

  18. Relationship management and the borderline patient.

    PubMed Central

    Dawson, D. F.

    1993-01-01

    Treating a patient with borderline personality disorder is fraught with peril. Some psychotherapies and medications seem to make matters worse, yet these very patients are some of the most persistent in demanding help. This happens because the context of treatment, the traditional physician-patient social contract, and the personal and professional impulses of the physician can actually feed and reinforce the patient's pathological behaviour. Relationship management offers a way to understand the problem and to handle it. PMID:8495141

  19. 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.

  20. Effects of diethylstilbestrol on the proliferation and tyrosinase activity of cultured human melanocytes

    PubMed Central

    TANG, JIANBING; LI, QIN; CHENG, BIAO; HUANG, CHONG; CHEN, KUI

    2015-01-01

    The aim of the present study was to observe the effects of different exogenous estrogen diethylstilbestrol (DES) concentrations on the human melanocyte proliferation and tyrosinase activity. Skin specimens were obtained following blepharoplasty, and the melanocytes were primary cultured and passaged to the third generation. The melanocytes were seeded in 96-well plates, each well had 5×103 cells. The medium was changed after 24 h, and contained 10−4-10−8 M DES. After the melanocytes were incubated, the proliferation and tyrosinase activity were detected by the MTT assay and L-DOPA reaction. DES (10−8-10−6 M) enhanced the proliferation of cultured melanocytes. The intensity was positively correlated with the concentration of drug. DES, >10−5 M, inhibited the melanocytes proliferation or even produced the toxicity effect. Following the addition of 10−6 M DES to the medium, the tyrosinase activity of melanocytes was significantly increased, with P<0.05. In conclusion, a certain concentration of DES promoted the proliferation of melanocytes, enhanced the activity of tyrosinase and promoted pigment synthesis of melanocytes, with the optimal concentration of 10−6 M. PMID:26171155

  1. The trk family of receptors mediates nerve growth factor and neurotrophin-3 effects in melanocytes.

    PubMed Central

    Yaar, M; Eller, M S; DiBenedetto, P; Reenstra, W R; Zhai, S; McQuaid, T; Archambault, M; Gilchrest, B A

    1994-01-01

    We have recently shown that (a) human melanocytes express the p75 nerve growth factor (NGF) receptor in vitro; (b) that melanocyte dendricity and migration, among other behaviors, are regulated at least in part by NGF; and (c) that cultured human epidermal keratinocytes produce NGF. We now report that melanocyte stimulation with phorbol 12-tetra decanoate 13-acetate (TPA), previously reported to induce p75 NGF receptor, also induces trk in melanocytes, and TPA effect is further potentiated by the presence of keratinocytes in culture. Moreover, trk in melanocytes becomes phosphorylated within minutes after NGF stimulation. As well, cultures of dermal fibroblasts express neurotrophin-3 (NT-3) mRNA; NT-3 mRNA levels in cultured fibroblasts are modulated by mitogenic stimulation, UV irradiation, and exposure to melanocyte-conditioned medium. Moreover, melanocytes constitutively express low levels of trk-C, and its expression is downregulated after TPA stimulation. NT-3 supplementation to cultured melanocytes maintained in Medium 199 alone prevents cell death. These combined data suggest that melanocyte behavior in human skin may be influenced by neurotrophic factors, possibly of keratinocyte and fibroblast origin, which act through high affinity receptors. Images PMID:7929831

  2. 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

  3. [Neurocognitive functioning in borderline personality disorder].

    PubMed

    Poletti, Michele

    2009-01-01

    Neurocognitive dysfunctions in subjects with a diagnosis of borderline personality disorder (BPD) have been often reported in several recent studies, reviewed in this paper. Most marked impairments are reported for executive functions, autobiographical memory and social cognition processes. These impairments may be considered as neurocognitive correlates of some clinical symptoms of BPD: the dysexecutive impairment, particularly of those processes based on the orbitofrontal cortex, is the correlate of the increased impulsivity; the interference of negative emotions on encoding and retrieval of autobiographical memories is the correlate of the frequent dissociative symptoms; difficulties in social cognition processes (for example in emotion recognition) are the correlate of the instable interpersonal relationships. Early cognitive impairments are also detected in children and adolescents with borderline clinical symptoms, suggesting that neurocognitive functioning: (1) might be considered an indirect index of the neurobiological impact of the childhood trauma that usually BPD subjects report; (2) might be a moderator in the development of BPD. Reviewed studies suggest the utility of a neuropsychological evaluation in all those subjects, children, adolescents and adults, that present borderline clinical symptoms. PMID:20218216

  4. 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

  5. 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.

  6. 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. PMID:27303631

  7. 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. PMID:25822579

  8. 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

  9. Value of melanocytic-associated immunohistochemical markers in the diagnosis of malignant melanoma: a review and update.

    PubMed

    Ordóñez, Nelson G

    2014-02-01

    Since the identification of S100 protein as an immunohistochemical marker that could be useful in the diagnosis of melanoma in the early 1980s, a large number of other melanocytic-associated markers that could potentially be used to assist in the differential diagnosis of these tumors have also been investigated. A great variation exists, however, among these markers, not only in their expression in some subtypes of melanoma, particularly desmoplastic melanoma, but also in their specificity because some of them can also be expressed in nonmelanocytic neoplasms, including various types of soft tissue tumors and carcinomas. This article reviews the information that is currently available on the practical value of some of the markers that have more often been recommended for assisting in the diagnosis of melanomas, including those that have only recently become available. PMID:23648379

  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. PMID:26440048

  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. Ocular findings in a case of periorbital giant congenital melanocytic nevus

    PubMed Central

    Raina, Usha K.; Seth, Anisha; Gupta, Anika; Batta, Supriya

    2014-01-01

    Giant congenital melanocytic nevus (GCMN) is a large melanocytic nevus that rarely occurs in the periorbital region. Various systemic, as well as ophthalmic associations, have been reported with GCMN. However, there is only one case report describing ophthalmic findings in periorbital GCMN. We describe the ocular findings in a case of periorbital GCMN. PMID:25378884

  13. Size Functions for the Morphological Analysis of Melanocytic Lesions

    PubMed Central

    Ferri, Massimo; Stanganelli, Ignazio

    2010-01-01

    Size Functions and Support Vector Machines are used to implement a new automatic classifier of melanocytic lesions. This is mainly based on a qualitative assessment of asymmetry, performed by halving images by several lines through the center of mass, and comparing the two halves in terms of color, mass distribution, and boundary. The program is used, at clinical level, with two thresholds, so that comparison of the two outputs produces a report of low-middle-high risk. Experimental results on 977 images, with cross-validation, are reported. PMID:20300598

  14. 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

  15. Bilateral diffuse uveal melanocytic proliferation: a management dilemma

    PubMed Central

    Alrashidi, Salah; Aziz, Ayman A; Krema, Hatem

    2014-01-01

    A female patient suffered from gradual decline of vision for few months. She presented with bilateral multiple pigmented choroidal tumours, associated with overlying retinal changes. The clinical presentation suggested bilateral diffuse uveal melanocytic proliferation (BDUMP) syndrome, which is a paraneoplastic disease, although there was no evidence of any concurrent malignancy. The periodic systemic surveillance that was undertaken for the following 4 years failed to reveal any occult cancer. Nevertheless, there has been relentless progressive deterioration in vision as a consequence of BDUMP syndrome. The management of the declining vision in BDUMP syndrome is challenging and controversial. PMID:24855079

  16. 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)

  17. Positive affective and cognitive states in borderline personality disorder.

    PubMed

    Reed, Lawrence Ian; Zanarini, Mary C

    2011-12-01

    The aim of the current study was to compliment previous studies identifying negative states present in borderline personality disorder (BPD) by investigating the presence of positive affective and cognitive states. Ninety-six patients with criteria-defined borderline personality disorder and 24 axis II comparison participants completed the Positive Affect Scale, a 50-item self-report measure designed to assess positive states thought to be characteristic of and discriminating for BPD. Seventeen positive states (4 affective, 10 cognitive, and 3 mixed) were found to be significantly more common among axis II comparison participants than borderline patients. Twelve of these states were common to both borderline patients and axis II comparison participants. Furthermore, four positive states, when co-occurring together, were particularly strongly associated with borderline personality disorder (three negatively and one positively): (a) Fond of myself, (b) That things around me are real, (c) That I've forgiven others, and (d) Assertive. Finally, the overall mean score on the PAS significantly distinguished patients with borderline personality disorder from axis II comparison participants. Taken together, these results suggest that borderline patients are far less likely to report experiencing positive states of an affective, cognitive, and mixed nature than axis II comparison participants. They also suggest that being assertive is a positive state particularly discriminating for borderline personality disorder. PMID:22217230

  18. 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…

  19. 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…

  20. 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. PMID:24798949

  1. MLANA/MART1 and SILV/PMEL17/GP100 Are Transcriptionally Regulated by MITF in Melanocytes and Melanoma

    PubMed Central

    Du, Jinyan; Miller, Arlo J.; Widlund, Hans R.; Horstmann, Martin A.; Ramaswamy, Sridhar; Fisher, David E.

    2003-01-01

    The clinically important melanoma diagnostic antibodies HMB-45, melan-A, and MITF (D5) recognize gene products of the melanocyte-lineage genes SILV/PMEL17/GP100, MLANA/MART1, and MITF, respectively. MITF encodes a transcription factor that is essential for normal melanocyte development and appears to regulate expression of several pigmentation genes. In this report, the possibility was examined that MITF might additionally regulate expression of the SILV and MLANA genes. Both genes contain conserved MITF consensus DNA sequences that were bound by MITF in vitro and in vivo, based on electrophoretic mobility shift assay and chromatin-immunoprecipitation. In addition, MITF regulated their promoter/enhancer regions in reporter assays, and up- or down-regulation of MITF produced corresponding modulation of endogenous SILV and MLANA in melanoma cells. Expression patterns were compared with these factors in a series of melanoma cell lines whose mutational status of the proto-oncogene BRAF was also known. SILV and MLANA expression correlated with MITF, while no clear correlation was seen relative to BRAF mutation. Finally, mRNA expression array analysis of primary human melanomas demonstrated a tight correlation in their expression levels in clinical tumor specimens. Collectively, this study links three important melanoma antigens into a common transcriptional pathway regulated by MITF. PMID:12819038

  2. Serological analysis of Melan-A(MART-1), a melanocyte-specific protein homogeneously expressed in human melanomas.

    PubMed Central

    Chen, Y T; Stockert, E; Jungbluth, A; Tsang, S; Coplan, K A; Scanlan, M J; Old, L J

    1996-01-01

    Recent progress in the structural identification of human melanoma antigens recognized by autologous cytotoxic T cells has led to the recognition of a new melanocyte differentiation antigen, Melan-A(MART-1). To determine the properties of the Melan-A gene product, Melan-A recombinant protein was produced in Escherichia coli and used to generate mouse monoclonal antibodies (mAbs). Two prototype mAbs, A103 and A355, were selected for detailed study. Immunoblotting results with A103 showed a 20-22-kDa doublet In Melan-A mRNA positive melanoma cell lines and no reactivity with Melan-A mRNA-negative cell lines. A355, in addition to the 20-22-kDa doublet, recognized several other protein species in Melan-A mRNA-positive cell lines. Immunocytochemical assays on cultured melanoma cells showed specific and uniform cytoplasmic staining in Melan-A mRNA-positive cell lines. Immunohistochemical analysis of normal human tissues with both mAbs showed staining of adult melanocytes and no reactivity with the other normal tissues tested. Analysis of 21 melanoma specimens showed homogenous staining of tumor cell cytoplasm in 16 of 17 Melan-A mRNA-positive cases and no reactivity with the three Melan-A mRNA-negative cases. Images Fig. 1 Fig. 2 Fig. 3 PMID:8650193

  3. Parenteral and enteral nutrition: borderline substances.

    PubMed

    Hopley, P J

    1981-01-01

    The application of medicinal product legislation to products which have a possible dual function as drugs and as foods or cosmetics has been described. The approach of the Family Practitioner Services under the NHS is to allow for as much professional debate as possible over the indeterminate ground between food and drugs. The role of the Advisory Committee on Borderline Substances in this context is briefly mentioned. Finally, some practical problems which arise in hospital practise have been described and for the solution the emphasis is upon the multi-disciplinary team approach. PMID:6947663

  4. Tailoring the Psychotherapy to the Borderline Patient

    PubMed Central

    HORWITZ, LEONARD; GABBARD, GLEN O.; ALLEN, JON G.; COLSON, DONALD B.; FRIESWYK, SIEBOLT; NEWSOM, GAVIN E.; COYNE, LOLAFAYE

    1996-01-01

    Views still differ as to the optimal psychodynamic treatment of borderline patients. Recommendations range from psychoanalysis and exploratory psychotherapy to an explicitly supportive treatment aimed at strengthening adaptive defenses. The authors contend that no single approach is appropriate for all patients in this wide-ranging diagnostic category, which spans a continuum from close-to-neurotic to close-to-psychotic levels of functioning. Careful differentiations based on developmental considerations, ego structures, and relationship patterns provide the basis for the optimal treatment approach. PMID:22700301

  5. 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

  6. 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

  7. 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. PMID:24451020

  8. 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.

  9. A Primary Retroperitoneal Mucinous Tumor

    PubMed Central

    Heelan Gladden, Alicia A.; Wohlauer, Max; McManus, Martine C.; Gajdos, Csaba

    2015-01-01

    A twenty-five-year-old female presented with a large retroperitoneal mass. Workup included history and physical exam, imaging, biopsy, colonoscopy, and gynecologic exam. After surgical resection, the mass was determined to be a primary retroperitoneal mucinous tumor (PRMT). Clinically and histologically, these tumors are similar pancreatic and ovarian mucinous neoplasms. PRMTs are rare and few case reports have been published. PRMTs are divided into mucinous cystadenomas, mucinous borderline tumors of low malignant potential, and mucinous carcinoma. These tumors have malignant potential so resection is indicated and in some cases adjuvant chemotherapy and/or surveillance imaging. PMID:25874152

  10. 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. PMID:26329581

  11. Defining the mechanisms of borderline personality disorder.

    PubMed

    Clarkin, John F; Posner, Michael

    2005-01-01

    Understanding the biological connections to mental processes was one of the original goals of psychoanalysis, and the development of cognitive and affective neuroscience and its methods might contribute to actualizing this goal. Personality disorders provide an opportunity to examine the complex mental structures of individuals experiencing extreme difficulties in interacting with their social environment. We provide initial information on a collaboration exploring an approach to one of the most serious personality disorders, borderline personality disorder, based upon the study of normal attention, individual differences in temperament, self definition and attachment organization, with the potential to illuminate the psychology and psychobiology of the disorder and to contribute to psychotherapeutic intervention. This developing model of borderline personality disorder can relate the symptoms to more enduring temperamental aspects of the patients. The goal is to understand the development of neural networks that underlie the abnormalities of adults, and eventually work out the interaction between temperament, genes, and experience that produce the disorder, and potentially inform intervention. PMID:15802943

  12. Evaluations of others by borderline patients.

    PubMed

    Arntz, A; Veen, G

    2001-08-01

    This study investigated evaluations of other people in specific emotional situations by patients with borderline personality disorder (BPD). BPD patients (N = 16), control patients with cluster C personality disorder (PD; N = 12) and normal controls (N = 15) saw film clips with emotional themes centering on abandonment, rejection and abuse, hypothesized to be specific for borderline pathology. Subjects wrote down their spontaneous reactions to six film personalities, divided over three clips, including what they thought to be characteristic traits of these persons. Spontaneous reactions were coded on two dimensions, based on earlier studies by Westen and colleagues: a) affect-tone of ascribed qualities and b) complexity of evaluations of people. The number of trait dimensions constituted the third scale. The overall pattern of findings suggests that the BPD group, as well as the cluster C group, show poorly differentiated evaluations with a low number of dimensions. Thus, this seems characteristic for personality disorders in general. The BPD group shows a lower affect-tone, reflecting a stronger tendency to view others negatively, compared with both control groups. PMID:11531203

  13. 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

  14. Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates UV induced melanocyte homeostasis

    PubMed Central

    Hyter, Stephen; Coleman, Daniel J.; Ganguli-Indra, Gitali; Merrill, Gary F.; Ma, Steven; Yanagisawa, Masashi; Indra, Arup K.

    2013-01-01

    Summary Keratinocytes contribute to melanocyte activity by influencing their microenvironment, in part, through secretion of paracrine factors. Here we discovered that p53 directly regulates Edn1 expression in epidermal keratinocytes and controls UV-induced melanocyte homeostasis. Selective ablation of EDN1 in murine epidermis (EDN1ep−/−) does not alter melanocyte homeostasis in newborn skin but decreases dermal melanocytes in adult skin. Results showed that keratinocytic EDN1 in a non-cell autonomous manner controls melanocyte proliferation, migration, DNA damage and apoptosis after UVB irradiation. Expression of other keratinocyte derived paracrine factors did not compensate for the loss of EDN1. Topical treatment with EDN1 receptor (EDNRB) antagonist BQ788 abrogated UV induced melanocyte activation and recapitulated the phenotype seen in EDN1ep−/− mice. Altogether, present studies establish an essential role of EDN1 in epidermal keratinocytes to mediate UV induced melanocyte homeostasis in vivo. PMID:23279852

  15. YY1 regulates melanocyte development and function by cooperating with MITF.

    PubMed

    Li, Juying; Song, Jun S; Bell, Robert J A; Tran, Thanh-Nga T; Haq, Rizwan; Liu, Huifei; Love, Kevin T; Langer, Robert; Anderson, Daniel G; Larue, Lionel; Fisher, David E

    2012-01-01

    Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)-a general mechanism which may confer tissue-specific gene expression in multiple lineages. PMID:22570637

  16. RICTOR involvement in the PI3K/AKT pathway regulation in melanocytes and melanoma

    PubMed Central

    Laugier, Florence; Finet-Benyair, Adeline; André, Jocelyne; Rachakonda, P. Sivaramakrishna; Kumar, Rajiv; Bensussan, Armand; Dumaz, Nicolas

    2015-01-01

    Several studies have highlighted the importance of the PI3K pathway in melanocytes and its frequent over-activation in melanoma. However, little is known about regulation of the PI3K pathway in melanocytic cells. We showed that normal human melanocytes are less sensitive to selective PI3K or mTOR inhibitors than to dual PI3K/mTOR inhibitors. The resistance to PI3K inhibitor was due to a rapid AKT reactivation limiting the inhibitor effect on proliferation. Reactivation of AKT was linked to a feedback mechanism involving the mTORC2 complex and in particular its scaffold protein RICTOR. RICTOR overexpression in melanocytes disrupted the negative feedback, activated the AKT pathway and stimulated clonogenicity highlighting the importance of this feedback to restrict melanocyte proliferation. We found that the RICTOR locus is frequently amplified and overexpressed in melanoma and that RICTOR over-expression in NRAS-transformed melanocytes stimulates their clonogenicity, demonstrating that RICTOR amplification can cooperate with NRAS mutation to stimulate melanoma proliferation. These results show that RICTOR plays a central role in PI3K pathway negative feedback in melanocytes and that its deregulation could be involved in melanoma development. PMID:26356562

  17. Human melanocytes mitigate keratinocyte-dependent contraction in an in vitro collagen contraction assay.

    PubMed

    Rakar, Jonathan; Krammer, Markus P; Kratz, Gunnar

    2015-08-01

    Scarring is an extensive problem in burn care, and treatment can be especially complicated in cases of hypertrophic scarring. Contraction is an important factor in scarring but the contribution of different cell types remains unclear. We have investigated the contractile behavior of keratinocytes, melanocytes and fibroblasts by using an in vitro collagen gel assay aimed at identifying a modulating role of melanocytes in keratinocyte-mediated contraction. Cells were seeded on a collagen type I gel substrate and the change in gel dimensions were measured over time. Hematoxylin & Eosin-staining and immunohistochemistry against pan-cytokeratin and microphthalmia-associated transcription factor showed that melanocytes integrated between keratinocytes and remained there throughout the experiments. Keratinocyte- and fibroblast-seeded gels contracted significantly over time, whereas melanocyte-seeded gels did not. Co-culture assays showed that melanocytes mitigate the keratinocyte-dependent contraction (significantly slower and 18-32% less). Fibroblasts augmented the contraction in most assays (approximately 6% more). Non-contact co-cultures showed some influence on the keratinocyte-dependent contraction. Results show that mechanisms attributable to melanocytes, but not fibroblasts, can mitigate keratinocyte contractile behavior. Contact-dependent mechanisms are stronger modulators than non-contact dependent mechanisms, but both modes carry significance to the contraction modulation of keratinocytes. Further investigations are required to determine the mechanisms involved and to determine the utility of melanocytes beyond hypopigmentation in improved clinical regimes of burn wounds and wound healing. PMID:25466959

  18. Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

    PubMed Central

    Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

    2015-01-01

    Introduction Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses. Methods and Materials Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs) across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium. Results Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium. Discussion Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring. PMID:26418010

  19. 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. PMID:27183108

  20. Borderline Personality and the Detection of Angry Faces

    PubMed Central

    Hepp, Johanna; Hilbig, Benjamin E.; Kieslich, Pascal J.; Herzog, Julia; Lis, Stefanie; Schmahl, Christian; Niedtfeld, Inga

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:27031611

  1. [The phenomenology and psychodynamics of affects in borderline patients].

    PubMed

    Leichsenring, Falk

    2004-01-01

    This paper presents a review of the phenomenology and psychodynamics of affects in borderline patients. The first part demonstrates that in most current conceptions of the borderline disorder affective disturbances are regarded as to be characteristic. In this context, the strong overlap between borderline disorders and affective disorders found in many empirical studies is described and different hypotheses are presented to explain this phenomenon. The second part of this review is concerned with the psychodynamics of affects in borderline patients. The role of affects in thinking, behaviour, self perception and the regulation of object relations is discussed. Borderline and other severe personality disorders are assessed from the perspective of affective disturbances. The psychodynamic functions of particularly characteristic affects such as anger, anxiety, depression and boredom are discussed. The close connection between affective and cognitive functioning in borderline patients is described and evaluated with regard to modern theories of affect and cognition. Finally, the role of affects in the treatment of borderline patients is discussed. PMID:15510348

  2. A colonization of basal cell carcinoma by malignant melanoma in situ resembling a malignant basomelanocytic tumor.

    PubMed

    Goeser, Megan; DiMaio, Dominick J

    2014-11-01

    We report a case of colonization of basal cell carcinoma (BCC) by malignant melanoma in situ (MIS) simulating a malignant basomelanocytic tumor. A biopsy of a pigmented lesion present on an 83-year-old man's scalp displayed intimate admixing of basaloid and melanocytic cells. This seemingly inseparable combination of BCC and neoplastic melanocytes has been referred to as a malignant basomelanocytic tumor. However, our case also displays an adjacent component of MIS, thus favoring colonization of BCC by MIS as the etiology. To our knowledge, this is the third case report of colonization of BCC by MIS resembling a malignant basomelanocytic tumor. PMID:24752214

  3. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    SciTech Connect

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  4. In ovo gene manipulation of melanocytes and their adjacent keratinocytes during skin pigmentation of chicken embryos.

    PubMed

    Murai, Hidetaka; Tadokoro, Ryosuke; Sakai, Ken-Ichiro; Takahashi, Yoshiko

    2015-04-01

    During skin pigmentation in avians and mammalians, melanin is synthesized in the melanocytes, and subsequently transferred to adjacently located keratinocytes, leading to a wide coverage of the body surface by melanin-containing cells. The behavior of melanocytes is influenced by keratinocytes shown mostly by in vitro studies. However, it has poorly been investigated how such intercellular cross-talk is regulated in vivo because of a lack of suitable experimental models. Using chicken embryos, we developed a method that enables in vivo gene manipulations of melanocytes and keratinocytes, where these cells are separately labeled by different genes. Two types of gene transfer techniques were combined: one was a retrovirus-mediated gene infection into the skin/keratinocytes, and the other was the in ovo DNA electroporation into neural crest cells, the origin of melanocytes. Since the Replication-Competent Avian sarcoma-leukosis virus long terminal repeat with Splice acceptor (RCAS) infection was available only for the White leghorn strain showing little pigmentation, melanocytes prepared from the Hypeco nera (pigmented) were back-transplanted into embryos of White leghorn. Prior to the transplantation, enhanced green fluorescent protein (EGFP)(+) Neo(r+) -electroporated melanocytes from Hypeco nera were selectively grown in G418-supplemented medium. In the skin of recipient White leghorn embryos infected with RCAS-mOrange, mOrange(+) keratinocytes and transplanted EGFP(+) melanocytes were frequently juxtaposed each other. High-resolution confocal microscopy also revealed that transplanted melanocytes exhibited normal behaviors regarding distribution patterns of melanocytes, dendrite morphology, and melanosome transfer. The method described in this study will serve as a useful tool to understand the mechanisms underlying intercellular regulations during skin pigmentation in vivo. PMID:25739909

  5. Microphthalmia-associated transcription factor as the molecular target of cadmium toxicity in human melanocytes

    SciTech Connect

    Chantarawong, Wipa; Takeda, Kazuhisa; Sangartit, Weerapon; Yoshizawa, Miki; Pradermwong, Kantimanee; Shibahara, Shigeki

    2014-11-28

    Highlights: • In human melanocytes, cadmium decreases the expression of MITF-M and tyrosinase and their mRNAs. • In human melanoma cells, cadmium decreases the expression of MITF-M protein and tyrosinase mRNA. • Expression of MITF-H is less sensitive to cadmium toxicity in melanocyte-linage cells. • Cadmium does not decrease the expression of MITF-H in retinal pigment epithelial cells. • MITF-M is the molecular target of cadmium toxicity in melanocytes. - Abstract: Dietary intake of cadmium is inevitable, causing age-related increase in cadmium accumulation in many organs, including hair, choroid and retinal pigment epithelium (RPE). Cadmium has been implicated in the pathogenesis of hearing loss and macular degeneration. The functions of cochlea and retina are maintained by melanocytes and RPE, respectively, and the differentiation of these pigment cells is regulated by microphthalmia-associated transcription factor (MITF). In the present study, we explored the potential toxicity of cadmium in the cochlea and retina by using cultured human melanocytes and human RPE cell lines. MITF consists of multiple isoforms, including melanocyte-specific MITF-M and widely expressed MITF-H. Levels of MITF-M protein and its mRNA in human epidermal melanocytes and HMV-II melanoma cells were decreased significantly by cadmium. In parallel with the MITF reduction, mRNA levels of tyrosinase, the key enzyme of melanin biosynthesis that is regulated by MITF-M, were also decreased. In RPE cells, however, the levels of total MITF protein, constituting mainly MITF-H, were not decreased by cadmium. We thus identify MITF-M as the molecular target of cadmium toxicity in melanocytes, thereby accounting for the increased risk of disability from melanocyte malfunction, such as hearing and vision loss among people with elevated cadmium exposure.

  6. BAP1 deficiency causes loss of melanocytic cell identity in uveal melanoma

    PubMed Central

    2013-01-01

    Background Uveal melanoma is a highly aggressive cancer with a strong propensity for metastasis, yet little is known about the biological mechanisms underlying this metastatic potential. We recently showed that most metastasizing uveal melanomas, which exhibit a class 2 gene expression profile, contain inactivating mutations in the tumor suppressor BAP1. The aim of this study was to investigate the role of BAP1 in uveal melanoma progression. Methods Uveal melanoma cells were studied following RNAi-mediated depletion of BAP1 using proliferation, BrdU incorporation, flow cytometry, migration, invasion, differentiation and clonogenic assays, as well as in vivo tumorigenicity experiments in NOD-SCID-Gamma mice. Results Depletion of BAP1 in uveal melanoma cells resulted in a loss of differentiation and gain of stem-like properties, including expression of stem cell markers, increased capacity for self-replication, and enhanced ability to grow in stem cell conditions. BAP1 depletion did not result in increased proliferation, migration, invasion or tumorigenicity. Conclusions BAP1 appears to function in the uveal melanocyte lineage primarily as a regulator of differentiation, with cells deficient for BAP1 exhibiting stem-like qualities. It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically. PMID:23915344

  7. The nosologic status of borderline personality: clinical and polysomnographic study.

    PubMed

    Akiskal, H S; Yerevanian, B I; Davis, G C; King, D; Lemmi, H

    1985-02-01

    The REM latencies of 24 nonschizotypal borderline outpatients--who were not in the midst of a major depressive episode--were in the range of those of 30 patients with primary major depression but were significantly shorter than those of 16 patients with nonborderline personality disorders and 14 nonpsychiatric controls. Also, more of the borderline subjects had lifetime diagnoses of affective disorder, such as dysthymic, cyclothymic, and bipolar II disorder, and of a spectrum of anxiety and somatization disorders. The authors conclude that contemporary operational criteria for borderline disorder identify a wide net of temperamental disorders with strong affective coloring rather than a unitary nosologic entity. PMID:3970243

  8. 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. PMID:25409130

  9. 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. PMID:24174895

  10. 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