Evaluation of T-cell activation in the duodenum of dogs with cutaneous food hypersensitivity.

PubMed

Veenhof, Eveline Z; Rutten, Victor P; van Noort, Ronald; Knol, Edward F; Willemse, Ton

2010-04-01

To determine whether skin-related clinical signs in cutaneous food hypersensitivity (CFH) coincide with immune reactivity in the intestine in dogs. 11 dogs with CFH without intestinal clinical signs and 8 healthy control dogs. After a provocation and elimination diet, the duodenal gene expression levels of Th1-, Th2- and Treg-related cytokines and transcription factors were investigated by means of quantitative PCR assay. The presence of CD3(+), CD8(+), CD4(+), CD1c(+), gammadelta T-cell receptor(+), and major histocompatibility complex II(+) cells in duodenal epithelium and lamina propria were determined. The expression of Th1-, Th2-, and Treg-related genes in dogs with CFH and healthy control dogs was similar. Although clinical signs disappeared, there was no effect of the elimination diet on cytokines, transcription factors, or cellular phenotypes. No change in T-cell phenotypes or a distinct Th1, Th2, or Treg profile was detected in the duodenum of dogs with only cutaneous clinical signs of food hypersensitivity. This suggested that the intestinal mucosa is not the primary site of T-cell activation that eventually leads to cutaneous food hypersensitivity.

Double-hit or dual expression of MYC and BCL2 in primary cutaneous large B-cell lymphomas.

PubMed

Menguy, Sarah; Frison, Eric; Prochazkova-Carlotti, Martina; Dalle, Stephane; Dereure, Olivier; Boulinguez, Serge; Dalac, Sophie; Machet, Laurent; Ram-Wolff, Caroline; Verneuil, Laurence; Gros, Audrey; Vergier, Béatrice; Beylot-Barry, Marie; Merlio, Jean-Philippe; Pham-Ledard, Anne

2018-03-26

In nodal diffuse large B-cell lymphoma, the search for double-hit with MYC and BCL2 and/or BCL6 rearrangements or for dual expression of BCL2 and MYC defines subgroups of patients with altered prognosis that has not been evaluated in primary cutaneous large B-cell lymphoma. Our objectives were to assess the double-hit and dual expressor status in a cohort of 44 patients with primary cutaneous large B-cell lymphoma according to the histological subtype and to evaluate their prognosis relevance. The 44 cases defined by the presence of more than 80% of large B-cells in the dermis corresponded to 21 primary cutaneous follicle centre lymphoma with large cell morphology and 23 primary cutaneous diffuse large B-cell lymphoma, leg type. Thirty-one cases (70%) expressed BCL2 and 29 (66%) expressed MYC. Dual expressor profile was observed in 25 cases (57%) of either subtypes (n = 6 or n = 19, respectively). Only one primary cutaneous follicle centre lymphoma, large-cell case had a double-hit status (2%). Specific survival was significantly worse in primary cutaneous diffuse large B-cell lymphoma, leg type than in primary cutaneous follicle centre lymphoma, large cell (p = 0.021) and for the dual expressor primary cutaneous large B-cell lymphoma group (p = 0.030). Both overall survival and specific survival were worse for patients belonging to the dual expressor primary cutaneous diffuse large B-cell lymphoma, leg type subgroup (p = 0.001 and p = 0.046, respectively). Expression of either MYC and/or BCL2 negatively impacted overall survival (p = 0.017 and p = 0.018 respectively). As the differential diagnosis between primary cutaneous follicle centre lymphoma, large cell and primary cutaneous diffuse large B-cell lymphoma, leg type has a major impact on prognosis, dual-expression of BCL2 and MYC may represent a new diagnostic criterion for primary cutaneous diffuse large B-cell lymphoma, leg type subtype and further identifies patients with

Lack of relevant information for tumor staging in pathology reports of primary cutaneous melanoma.

PubMed

Busam, K J

2001-05-01

For the T classification of primary cutaneous melanoma, the current American Joint Committee on Cancer staging (AJCC) system relies on tumor thickness and level of invasion. A new T classification has been proposed based on thickness and ulceration. The slides and reports of 135 departmental pathology consultations of patients referred to a major cancer center with a diagnosis of primary cutaneous invasive malignant melanoma were examined. Whether the outside pathology reports contained information on tumor thickness, level of invasion, and ulceration was recorded. Dermatopathologists had issued 76.3% of the reports and general surgical pathologists, 24.3%. Information provided was as follows: tumor thickness, 97.8%; Clark level, 71.9%; and presence or absence of ulceration, 28.1%. Of the 97 melanomas with no comment on ulceration, 17 were indeed ulcerated. Thus, the lack of a comment on ulceration cannot be equated with the absence of ulceration. The present study documents that many pathology reports on melanomas lack sufficient information for AJCC staging. Therefore, review of outside pathology material is necessary not only to confirm or revise the tumor diagnosis but also to provide clinicians with histologic parameters required for AJCC staging.

Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-12-03

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

Brentuximab Vedotin and Lenalidomide in Treating Patients With Stage IB-IVB Relapsed or Refractory T-Cell Lymphoma

ClinicalTrials.gov

2018-03-19

Lymphomatoid Papulosis; Primary Cutaneous Anaplastic Large Cell Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage I Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage II Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma

Primary cutaneous aspergillosis from Tamilnadu diagnosed by fine needle aspiration cytology

PubMed Central

Venugopal, Taralakshmi V.; Venugopal, Pankajalakshmi V.

2012-01-01

Aspergillus are ubiquitous and more than 30 species have been reported to be involved in human infection. Most of the cases occur in immunocompromised patients and are disseminated in the blood. Primary cutaneous aspergillosis in immunocompetent hosts is rare. We report a unique case of primary cutaneous aspergillosis in an immunocompetent patient diagnosed by fine needle aspiration cytology. The characteristic ascocarp and ascospores of Aspergillus species were found in the aspirate and Aspergillus glaucus was isolated in pure culture. The case is presented to increase the awareness of the usefulness of fine needle aspiration cytology for diagnosing fungal infections. PMID:24371752

A novel splice variant of the Fas gene in patients with cutaneous T-cell lymphoma.

PubMed

van Doorn, Remco; Dijkman, Remco; Vermeer, Maarten H; Starink, Theo M; Willemze, Rein; Tensen, Cornelis P

2002-10-01

Defective apoptosis signaling has been implicated in the pathogenesis of primary cutaneous T-cell lymphomas (CTCLs), a group of malignancies derived from skin-homing T cells. An important mediator of apoptosis in T cells is the Fas receptor. We identified a novel splice variant of the Fas gene that displays retention of intron 5 and encodes a dysfunctional Fas protein in 13 of 22 patients (59%) in both early and advanced CTCL. Impairment of Fas-induced apoptosis resulting from aberrant splicing potentially contributes to the development and progression of CTCL by allowing continued clonal expansion of activated T cells and by reducing susceptibility to antitumor immune responses.

Primary cutaneous mucormycosis caused by Mucor irregularis in an elderly person.

PubMed

Yamaguchi, Sayaka; Okubo, Yuko; Katano, Azusa; Sano, Ayako; Uezato, Hiroshi; Takahashi, Kenzo

2015-02-01

Primary cutaneous mucormycosis is a rare but often lethal severe fungal infection, which usually occurs in immunocompromised patients. We report a case of primary cutaneous mucormycosis caused by Mucor irregularis in an elderly patient. Seven months after the surgical dissection of the involved skin, cutaneous mucormycosis recurred at the peripheral edge of the skin graft. Shortly subsequent to the administration of liposomal amphotericin B, the remaining skin lesion was excised again. M. irregularis is rarely but increasingly reported as a cause of mucormycosis in immunocompetent individuals, especially in Asian farmers. M. irregularis may be largely disseminated in the soils of Asia and thus the trivial trauma at the time of farm work may be a trigger for the onset. These cases tend to leave severe cosmetic damage even in healthy individuals, although the vital prognosis is not affected. © 2014 Japanese Dermatological Association.

THERAPY-RELATED T/MYELOID MIXED PHENOTYPE ACUTE LEUKEMIA IN A PATIENT TREATED WITH CHEMOTHERAPY FOR CUTANEOUS DIFFUSE LARGE B CELL LYMPHOMA.

PubMed

Roberts, Evans; Oncale, Melody; Safah, Hana; Schmieg, John

2016-01-01

Mixed-phenotype acute leukemia is a rare form of leukemia that is associated with a poor prognosis. Most cases of mixed-phenotype acute leukemia are de novo. However, therapy-related mixed-phenotype acute leukemia can occur, and are often associated with exposure to topoisomerase-II inhibitors and alkylating agents. There are no known treatment guidelines for therapy-related mixed-phenotype acute leukemia. We present a patient with T/myeloid mixed-phenotype acute leukemia secondary to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma. The patient's leukemic cells express CD34, an immaturity marker, CD3, a T-cell marker, and myeloperoxidase, a myeloid marker, and her history of chemotherapy for previous lymphoma supports the diagnosis of therapy-related T/myeloid mixed phenotype acute leukemia. Clinicians should be aware that this entity could be associated with R-CHOP chemotherapy. Given the complexity in diagnosis, and lack of treatment guidelines, a further understanding of the pathological and genetic principles of therapy-related mixed-phenotype acute leukemia will assist in future efforts to treat and categorize these patients. Mixed phenotype acute leukemia is a rare entity that accounts for two to five percent of all acute leukemias. Therapy- related mixed phenotype acute leukemia is an exceedingly rare hematological neoplasm that accounts for less than one percent of acute leukemias. We describe a case of therapy-related T/myeloid mixed phenotype acute leukemia following rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone R-CHOP chemotherapy for primary cutaneous diffuse large B-cell lymphoma DLBCL. The patient is a 63-year-old female who presented with several cutaneous nodules diagnosed as primary cutaneous DLBCL. The patient received R-CHOP chemotherapy and achieved remission. She remained in remission for four years until she presented with

Successful Cord Blood Stem Cell Transplantation for Primary Cutaneous CD8-positive Aggressive Epidermotropic Cytotoxic T-cell Lymphoma Complicated with Cerebral Infiltration.

PubMed

Ichikawa, Satoshi; Fukuhara, Noriko; Hatta, Shunsuke; Himuro, Masahito; Katsushima, Hiroki; Nasu, Kentaro; Ono, Koya; Inokura, Kyoko; Kobayashi, Masahiro; Onishi, Yasushi; Fujii, Hiroshi; Ishizawa, Kenichi; Ichinohasama, Ryo; Harigae, Hideo

2018-03-09

A 16-year-old boy, who had been initially examined for bilateral blepharedema and slight eruption, presented with rapidly deteriorating symptoms in associating with headache and consciousness disturbance. He was diagnosed to have primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) by a biopsy of the skin and brain. After whole-brain radiation and some courses of chemotherapy, cord blood transplantation was performed with myeloablative conditioning. After transplantation, the cerebral dysfunction gradually improved. Disease remission was confirmed by the disappearance of any abnormal findings on electroencephalogram and magnetic resonance imaging. PCAE-CTL is reported to be an extremely aggressive disease with a poor prognosis, but the timely performance of cord blood transplantation is considered to be a promising treatment strategy.

Adenoviral Gene Delivery to Primary Human Cutaneous Cells and Burn Wounds

PubMed Central

Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

2006-01-01

The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determined up to 30 days. Expression was quantified by FACS analysis and fluorimeter. Cytotoxicity was measured using the trypan blue exclusion method. 45 male Sprague Dawley rats received 2 × 108 pfu of Ad5-CMV-LacZ or carrier control intradermally into either superficial partial thickness scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days posttreatment. Transgene expression was assessed using immunohistochemistry and bioluminescent assays. The highest transfection rate was observed 48 h posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP expression was detectable in all groups over 30 days (P > 0.05). Cytotoxic effects of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30 days. Reporter gene expression in vivo was significantly higher in burned skin compared with unburned skin (P = 0,004). Gene expression decreases from 2 to 7 days with no significant expression after 14 days. This study demonstrates that effective adenoviral-mediated gene transfer of epidermal primary cells and cell-lines is feasible. Ex vivo gene transfer in epithelial cells might have promise for the use in severely burned patients who receive autologous keratinocyte sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors causes significant concentrations in the wound tissue for at least 1 week. Based on these findings, we hypothesize that transient cutaneous adenoviral gene delivery of wound healing promoting

Adenoviral gene delivery to primary human cutaneous cells and burn wounds.

PubMed

Hirsch, Tobias; von Peter, Sebastian; Dubin, Grzegorz; Mittler, Dominik; Jacobsen, Frank; Lehnhardt, Markus; Eriksson, Elof; Steinau, Hans-Ulrich; Steinstraesser, Lars

2006-01-01

The adenoviral transfer of therapeutic genes into epidermal and dermal cells is an interesting approach to treat skin diseases and to promote wound healing. The aim of this study was to assess the in vitro and in vivo transfection efficacy in skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC), fibroblasts (HFB), and HaCaT cells were transfected using different concentrations of an adenoviral construct (eGFP). Transfection efficiency and cytotoxicity was determined up to 30 days. Expression was quantified by FACS analysis and fluorimeter. Cytotoxicity was measured using the trypan blue exclusion method. 45 male Sprague Dawley rats received 2x10(8) pfu of Ad5-CMV-LacZ or carrier control intradermally into either superficial partial thickness scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days posttreatment. Transgene expression was assessed using immunohistochemistry and bioluminescent assays. The highest transfection rate was observed 48 h posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP expression was detectable in all groups over 30 days (P>0.05). Cytotoxic effects of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30 days. Reporter gene expression in vivo was significantly higher in burned skin compared with unburned skin (P=0,004). Gene expression decreases from 2 to 7 days with no significant expression after 14 days. This study demonstrates that effective adenoviral-mediated gene transfer of epidermal primary cells and cell-lines is feasible. Ex vivo gene transfer in epithelial cells might have promise for the use in severely burned patients who receive autologous keratinocyte sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors causes significant concentrations in the wound tissue for at least 1 week. Based on these findings, we hypothesize that transient cutaneous adenoviral gene delivery of wound healing promoting factors has

Cutaneous T-cell lymphoma in an African hedgehog (Atelerix albiventris).

PubMed

Spugnini, Enrico P; Pagotto, Annarita; Zazzera, Francesca; D'Avino, Alfredo; Caruso, Giovanni; Citro, Gennaro; Baldi, Alfonso

2008-01-01

A three-year-old male African hedgehog was presented for a non healing crusty proliferation on the left pinna. The lesion failed to respond to topical therapy and systemic antibiotic therapy. Whole body radiography and abdominal ultrasonograpy were within normal limits. The lesion was surgically removed. The patient recovered well from the procedure and remained in remission for nine months when he came back as an emergency case and died of an unrelated disease. The histopathology report enabled a diagnosis of completely excised cutaneous T-cell lymphoma. This report represents the first successful treatment of a cutanous T-cell lymphoma in this species and might help to plan future therapies.

Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

PubMed

Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

2010-12-01

This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

Familial primary cutaneous amyloidosis. Clinical, genetic, and immunofluorescent studies.

PubMed

Vasily, D B; Bhatia, S G; Uhlin, S R

1978-08-01

Familial primary cutaneous amyloidosis, a rare, autosomal dominant genodermatosis, affected 16 of 46 family members of German descent. Previous case reports involved families of Russian, Spanish, or Chinese descent. The finding of IgG, IgM, C3 in the amyloid deposits confirms recent reports of immunofluorescent dermal amyloid deposits.

[Primary cutaneous and metastasing haemangiosarcoma in an addax (Addax nasomaculatus)].

PubMed

Wohlsein, P; Schöpper, H; Kämmerling, J; Wünsch, U; Schulze, C

2008-01-01

Neoplastic diseases were described very rarely in addax (Addax nasomaculatus). In this communication clinical signs, morphological and immunohistological findings in a 15-year-old, female addax with a primary cutaneous, re-occurring and metastasing haemangiosarcoma of a forelimb are reported.

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis.

PubMed

Kuk, Deborah; Shoushtari, Alexander N; Barker, Christopher A; Panageas, Katherine S; Munhoz, Rodrigo R; Momtaz, Parisa; Ariyan, Charlotte E; Brady, Mary Sue; Coit, Daniel G; Bogatch, Kita; Callahan, Margaret K; Wolchok, Jedd D; Carvajal, Richard D; Postow, Michael A

2016-07-01

Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the

Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma From the Time of First Metastasis

PubMed Central

Kuk, Deborah; Shoushtari, Alexander N.; Barker, Christopher A.; Panageas, Katherine S.; Munhoz, Rodrigo R.; Momtaz, Parisa; Ariyan, Charlotte E.; Brady, Mary Sue; Coit, Daniel G.; Bogatch, Kita; Callahan, Margaret K.; Wolchok, Jedd D.; Carvajal, Richard D.

2016-01-01

Background. Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. Materials and Methods. We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. Results. Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006–2010 and 2011–2013 had better overall survival than patients diagnosed in 2000–2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. Conclusion. Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. Implications for Practice: Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous

Durvalumab With or Without Lenalidomide in Treating Patients With Relapsed or Refractory Cutaneous or Peripheral T Cell Lymphoma

ClinicalTrials.gov

2018-04-06

Folliculotropic Mycosis Fungoides; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Sezary Syndrome; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma

[Aggressive primary cutaneous B-cell lymphomas and novel EBV+ entities].

PubMed

Lamos, C; Dippel, E

2017-09-01

Primary cutaneous large B‑cell lymphomas (PCBLT), EBV-positive large B‑cell lymphomas, not otherwise specified (EBV+ DLBCL, NOS), and primary cutaneous intravascular large B‑cell lymphomas (PCIVLBL) are recognized as cutaneous lymphomas with intermediate to poor prognosis. Differentiation from indolent B‑cell lymphomas or other pathologies of the skin can be complex, both clinically and histologically, but vital for the outcome of the patient. The combination of immunotherapy and polychemotherapy regimens, such as R‑CHOP, has led to significant improvements in prognosis, especially in diffuse large B‑cell lymphomas. Therapeutic decisions need to be individually made for each patient, ideally within an interdisciplinary tumor conference. Immunosenescence may be an important factor in the pathogenesis of EBV+ DLBCL, NOS in elderly individuals. Their prognosis is less favorable than that of patients with EBV-negative PCBLT, whereby this has been observed particularly in elderly patients. One third of patients with PCIVLBL progress to systemic disease. The occurrence of nodal manifestation is rarely observed. Symptoms may vary depending on the organ system involved. Currently there are no evidence-based therapy recommendations due to the rarity of the disease. EBV-positive mucocutaneous ulcer is a new provisional category in the current WHO classification for lymphoid neoplasms. It has been segregated from EBV+ DLBCL, NOS due to its self-limiting course and good response to conservative therapy.

Patients' Illness Perception as a Tool to Improve Individual Disease Management in Primary Cutaneous Lymphomas.

PubMed

Porkert, Stefanie; Lehner-Baumgartner, Eva; Valencak, Julia; Knobler, Robert; Riedl, Elisabeth; Jonak, Constanze

2018-02-07

The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.

Updated evidence-based clinical practice guidelines for the diagnosis and management of melanoma: definitive excision margins for primary cutaneous melanoma.

PubMed

Sladden, Michael J; Nieweg, Omgo E; Howle, Julie; Coventry, Brendon J; Thompson, John F

2018-02-19

Definitive management of primary cutaneous melanoma consists of surgical excision of the melanoma with the aim of curing the patient. The melanoma is widely excised together with a safety margin of surrounding skin and subcutaneous tissue, after the diagnosis and Breslow thickness have been established by histological assessment of the initial excision biopsy specimen. Sentinel lymph node biopsy should be discussed for melanomas ≥ 1 mm thickness (≥ 0.8 mm if other high risk features) in which case lymphoscintigraphy must be performed before wider excision of the primary melanoma site. The 2008 evidence-based clinical practice guidelines for the management of melanoma (http://www.cancer.org.au/content/pdf/HealthProfessionals/ClinicalGuidelines/ClinicalPracticeGuidelines-ManagementofMelanoma.pdf) are currently being revised and updated in a staged process by a multidisciplinary working party established by Cancer Council Australia. The guidelines for definitive excision margins for primary melanomas have been revised as part of this process. Main recommendations: The recommendations for definitive wide local excision of primary cutaneous melanoma are: melanoma in situ: 5-10 mm margins invasive melanoma (pT1) ≤ 1.0 mm thick: 1 cm margins invasive melanoma (pT2) 1.01-2.00 mm thick: 1-2 cm margins invasive melanoma (pT3) 2.01-4.00 mm thick: 1-2 cm margins invasive melanoma (pT4) > 4.0 mm thick: 2 cm margins Changes in management as a result of the guideline: Based on currently available evidence, excision margins for invasive melanoma have been left unchanged compared with the 2008 guidelines. However, melanoma in situ should be excised with 5-10 mm margins, with the aim of achieving complete histological clearance. Minimum clearances from all margins should be assessed and stated. Consideration should be given to further excision if necessary; positive or close histological margins are unacceptable.

MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

PubMed

Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

2015-12-01

A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

Pagetoid reticulosis (epitheliotropic cutaneous T-cell lymphoma) in an adult alpaca (Vicugna pacos).

PubMed

Hasbach, Andrea E; Stern, Adam W

2016-07-01

A 9-year-old, intact female alpaca (Vicugna pacos) was presented for a second opinion with a 1-year history of nonpruritic, multifocal scaling and crusted cutaneous lesions, mainly involving skin on the face, axillae, and ventral abdomen. Clinical abnormalities were limited to the skin, and the alpaca was otherwise healthy. The initial veterinarian had examined the alpaca, found no evidence of ectoparasites with laboratory testing, and had tried several trial therapies including oral antibiotics, ivermectin, and topical use of betadine solution. At the time of presentation, the lesions had neither improved nor worsened with any attempted therapy, and multiple skin biopsies were collected. Histopathology and immunohistochemical staining findings were consistent with the pagetoid reticulosis type of cutaneous epitheliotropic T-cell lymphoma. Our report describes the clinical, histopathologic, and immunophenotypic features of pagetoid reticulosis epitheliotropic cutaneous T-cell lymphoma in an alpaca. © 2016 The Author(s).

Primary cutaneous vascular leiomyosarcoma: a rare subtype of leiomyosarcoma of the skin.

PubMed

Ortins-Pina, Ana; Soares-de-Almeida, Luís; Rütten, Arno

2018-05-08

Primary smooth muscle malignancies in the skin account for approximately 2-3% of all soft tissue sarcomas 1,2 . We read with interest a recent JCP report on a vascular leiomyosarcoma arising from vena saphena magna 3 . We report herein a case of primary cutaneous vascular leiomyosarcoma arising from a small-caliber dermal vein. This article is protected by copyright. All rights reserved.

Intertriginous mycosis fungoides: a distinct presentation of cutaneous T-cell lymphoma that may be caused by malignant follicular helper T cells.

PubMed

Gammon, Bryan; Guitart, Joan

2012-09-01

Follicular helper T cells are a subset of helper T cells that facilitate B-cell recruitment and maturation. Rare cases of cutaneous T-cell lymphoma manifesting as de novo tumor lesions in intertriginous skin contain an infiltrate rich in B cells. These cases may represent malignant counterparts of skin-homing follicular helper T cells. Two men and 1 woman (age range, 35-58 years) were seen with predominantly intertriginous tumor-stage cutaneous T-cell lymphoma lesions characterized by the absence of epidermotropism and the presence of a mixed infiltrate rich in B cells. Two of the patients died of the disease less than 3 years from the initial diagnosis. The surviving patient has aggressive disease and underwent hematopoietic stem cell transplantation. Two of the patients had a prominent CXCL13+, Bcl6/CD3+, and programmed death protein 1-positive follicular helper T-cell population. The intertriginous tumor variant of cutaneous T-cell lymphoma is heterogeneous but may be associated in some cases with a follicular helper T-cell immunophenotype. These patients may follow an aggressive clinical course. Tumor progression in sanctuary sites on patients receiving phototherapy may manifest as a similar clinical phenotype. Further characterization of the disease process is needed to confirm this observation.

Primary cutaneous anaplastic large-cell lymphoma: A case report

PubMed Central

Abed, Kamil; Stopa, Zygmunt; Siewert-Gutowska, Marta

2018-01-01

Abstract Rationale: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a rare cancer belonging to the group of primary T-cell lymphoproliferative diseases. C-ALCL is characterized by the presence of single or multiple ulcerated lesions on the skin's surface. Patient concerns: This is the case of a 73-year-old man who reported to the Clinic of Cranio-Maxillofacial and Oral Surgery and Implantology, Medical University of Warsaw, owing to a skin tumor in the right parotideomasseteric region, initially diagnosed as discoid lupus erythematosus. During treatment for discoid lupus erythematosus, biopsy was repeated because of significant disease progression and dynamic tumor growth. Histopathological examination revealed the presence of pilomatrix carcinoma (trichilemmal carcinoma). Because of the discrepancy between clinical and histopathological findings, the tumor specimen was submitted to another facility, wherein lymphoma infiltration by anaplastic large cells was found in the dermis and subcutaneous tissue. Diagnosis: C-ALCL. Interventions: The patient was transferred to the Lymphoid Tumours Clinic of the Maria Skłodowska Curie Memorial Cancer Centre and Institute of Oncology in Warsaw, where chemotherapy was initiated. Outcomes: After 4 cycles of chemotherapy, a complete remission of skin lesions was achieved. During the 5-year follow-up, no recurrence occurred. Lessons: C-ALCL is a rare type of cancer. Misdiagnosis can lead to inappropriate therapy and result in disease progression or unnecessary harm to the patient. PMID:29369180

Cutaneous epitheliotropic T-cell lymphoma with systemic dissemination in a dog.

PubMed

Mineshige, Takayuki; Kawarai, Shinpei; Yauchi, Takahiro; Segawa, Kazuhito; Neo, Sakurako; Sugahara, Go; Kamiie, Junichi; Hisasue, Masaharu; Shirota, Kinji

2016-05-01

Cutaneous epitheliotropic T-cell lymphoma (CETL) is characterized by neoplastic T-cell infiltration of the epidermis, adnexal structures, and oral mucosa. The objective of this report was to describe the pathological findings of a canine case of terminal-stage CETL. A 10-year-old, mixed-breed, neutered male dog was presented with erosion of the oral mucosa and mucocutaneous junction. The dog was diagnosed with CETL with no evidence of metastasis. Despite chemotherapy, the dog was re-presented with oral pain, vomiting, and diarrhea, and died 17 months after the first visit to the hospital. A complete autopsy was performed. Histologic examination of the primary lesion and systemic organs was performed. Gross examination revealed an advanced-stage oral lesion. Distinct tumor formation was not observed in the primary sites and systemic organs. Histologically, the primary oral lesion was characterized by massive intraepithelial infiltration of a large number of neoplastic lymphocytes. The neoplastic cells in the metastatic sites also showed exclusive epitheliotropic proliferation in organs, including the trachea, tonsils, esophagus, stomach, small intestine, colon, anal mucosa, liver, pancreas, kidneys, urinary bladder, prostate gland, ear canals, and auricular and ventral skin. Immunohistochemically, the neoplastic cells were positive for CD3 and negative for CD20 as well as CD79α, supporting a diagnosis of CETL with systemic dissemination. In canine CETL with systemic signs, systemic metastasis should be considered even without evident mass formation. Neoplastic lymphocytes of CETL showed distinct epitheliotropism even in the systemic metastatic sites. © 2016 The Author(s).

Modern radiation therapy for primary cutaneous lymphomas: field and dose guidelines from the International Lymphoma Radiation Oncology Group.

PubMed

Specht, Lena; Dabaja, Bouthaina; Illidge, Tim; Wilson, Lynn D; Hoppe, Richard T

2015-05-01

Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Allogeneic hematopoietic stem cell transplantation in Primary Cutaneous T Cell Lymphoma.

PubMed

Cudillo, Laura; Cerretti, Raffaella; Picardi, Alessandra; Mariotti, Benedetta; De Angelis, Gottardo; Cantonetti, Maria; Postorino, Massimiliano; Ceresoli, Eleonora; De Santis, Giovanna; Nasso, Daniela; Pisani, Francesco; Scala, Enrico; Di Piazza, Fabio; Lanti, Alessandro

2018-06-01

In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p < 0.04) and DFS (log-rank p < 0.05). Our results confirm on a long follow-up that CTCL appears particularly susceptible to the graft versus lymphoma (GVL) effect, so that allogeneic HSCT represents a possibility of cure for advanced CTCL. The timing of HSCT in the clinical course of disease remains an open issue.

[Posttraumatic primary cutaneous aspergillosis with Candida guilliermondii infection in a healthy host].

PubMed

Türkşen, Zeynep; Yağcı, Server; Karadağ, Ayşe Serap; Tezer, Ayla; Taner, Omer Faruk; Tekin, Fatih; Arıkan Akdağlı, Sevtap

2010-10-01

Opportunistic fungal infections are usually seen in immunocompromised patients. While Candida is the most prevalent agent in such infections, Aspergillus is at the second order. Primary cutaneous aspergillosis is most common in immunocompromised patients but can rarely be seen in healthy hosts as well. We report a case of posttraumatic primary cutaneous aspergillosis and Candida guilliermondii coinfection in a 70-years-old healthy man. The patient had an ulcerous lesion which developed in the site of a trauma on the middle finger of the right hand. Histopathological examination of the biopsy specimens revealed septate hyphae with dichotomous branching small circular blastospores. The cultures of the biopsy specimen yielded yellow-green colored, granular mold colonies and creamy white yeast colonies. Microscopic examination of the lactophenol cotton blue stained mold colonies indicated long conidiophores with vesicles surrounded by uniseriate phialides, compatible with Aspergillus flavus. Yeast colonies were identified as Candida guilliermondii by ID32C (BioMerieux, France) and by their microscopical morphology detected in corn meal-Tween 80 agar incubated at 25°C for 72 hours. The patient was treated properly with surgical debridement and itraconazole therapy. Since the immune system is compressed as a consequence of aging, cutaneous opportunistic fungal infections should be considered in the differential diagnosis of posttraumatic necrotic ulcers and black eschar in aged patients.

Brentuximab Vedotin and Lenalidomide in Treating Patients With Relapsed or Refractory T-Cell Lymphomas

ClinicalTrials.gov

2018-06-15

CD30-Positive Neoplastic Cells Present; Folliculotropic Mycosis Fungoides; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome

Primary versus secondary closure of cutaneous abscesses in the emergency department: a randomized controlled trial.

PubMed

Singer, Adam J; Taira, Breena R; Chale, Stuart; Bhat, Rahul; Kennedy, David; Schmitz, Gillian

2013-01-01

Cutaneous abscesses have traditionally been treated with incision and drainage (I&D) and left to heal by secondary closure. The objective was to compare the healing rates of cutaneous abscesses following I&D after primary or secondary closure. This was a randomized, controlled, trial, balanced by center, with blocked randomization created by a random-number generator. One urban and one suburban academic emergency department (ED) participated. Subjects were randomized to primary or secondary wound closure following I&D of the abscess. Main outcome measures were the percentage of healed wounds (wound was completely closed by visual inspection; a 40% difference in wound healing was sought) and overall failure rate (need for additional intervention including suture removal, additional drainage, antibiotics, or admission within 7 days after drainage). Fifty-six adult patients with simple localized cutaneous abscesses were included; 29 were randomized to primary closure, and 27 were randomized to secondary closure. Healing rates at 7 days were similar between the primary and secondary closure groups (69.6%, 95% confidence interval [CI] = 49.1% to 84.4% vs. 59.3%, 95% CI = 40.7% to 75.5%; difference 10.3%, 95% CI = -15.8% to 34.1%). Overall failure rates at 7 days were also similar between the primary and secondary closure groups (30.4%, 95% CI = 15.6% to 50.9% vs. 28.6%, 95% CI = 15.2% to 47.1%; difference 1.8%, 95% CI = -24.2% to 28.8%). The rates of wound healing and treatment failure following I&D of simple abscesses in the ED are similar after primary or secondary closure. The authors did not detect a difference of at least 40% in healing rates between primary and secondary closure. © 2013 by the Society for Academic Emergency Medicine.

Atrophic nodular cutaneous amyloidosis.

PubMed

Jiang, Yuan; Kong, Qingtao; Hui, Yun; Sang, Hong

2018-01-01

Primary cutaneous amyloidosis is limited to the skin without involving any other tissue. Nodular amyloidosis is rare, and atrophic nodular cutaneous amyloidosis is even rarer. We describe the fourth case of atrophic nodular cutaneous amyloidosis by searching PubMed databases. A 52-year-old female presented to our hospital with a 2-year history of orange papules and nodules without subjective symptom on her right abdomen. Review of systems was negative. Atrophic nodular amyloidosis may progress to primary systemic disease in up to 7% of cases. Because our patient had no systemic involvement, she was diagnosed with atrophic nodular cutaneous amyloidosis based on characteristic symptoms and histopathologic examination. Routine follow-up for this patient is necessary to detect any potential disease progression.

AL Amyloidoma of the Skin/Subcutis: Cutaneous Amyloidosis, Plasma Cell Dyscrasia or a Manifestation of Primary Cutaneous Marginal Zone Lymphoma?

PubMed

Walsh, Noreen M; Lano, Ian Marie; Green, Peter; Gallant, Christopher; Pasternak, Sylvia; Ly, Thai Yen; Requena, Luis; Kutzner, Heinz; Chott, Andreas; Cerroni, Lorenzo

2017-08-01

It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct entity, an indolent precursor of systemic amyloidosis, or a manifestation of cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL amyloidoma in order to better characterize the clinicopathologic features of this elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients had a solitary nodule or plaque on the lower extremity (n=7), upper extremity (n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a second lesion on the right arm showing histopathologic features of cMZL without amyloid deposits. Clinical investigations excluded relevant systemic disease in all cases. Microscopically, dermal/subcutaneous deposits of amyloid were associated with sparse to moderate perivascular infiltrates of lymphocytes and monotypic plasma cells (7 with kappa and 3 with lambda light chain restriction). The plasma cells expressed CD56 in one of 9 studied cases. One case was characterized by a t(14;18)(q32;q21)/IGH-MALT1 translocation. Follow-up was available in 8 cases. All remain systemically well after a median time of 86.5 months (range: 40 to 144 mo). Local recurrence of disease was observed in 3 patients. A fourth patient presented with a cMZL without amyloid deposits 8 years after excision of the cutaneous AL amyloidoma. Although our series is small, careful categorization and follow-up of the cases, together with updated information in the literature, show clinical and biological links between AL amyloidomas of the skin/subcutis and cMZL, suggesting that at least a subset of cutaneous AL amyloidoma may represent an unusual manifestation of cMZL (cutaneous mucosa-associated lymphoid tissue lymphomas).

Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

PubMed

Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

2015-01-01

Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

Cutaneous Collagenous Vasculopathy

PubMed Central

Ortleb, Melanie; Boyd, Alan S.; Powers, Jennifer

2015-01-01

Cutaneous collagenous vasculopathy is a rare microangiopathy of dermal blood vessels. Clinically indistinguishable from generalized essential telangiectasia, this condition is diagnosed by its unique histological appearance. In contrast to other primary telangiectatic processes, cutaneous collagenous vasculopathy has dilated vascular structures that contain deposits of eosinophilic hyaline material within the vessel walls. To date, cutaneous collagenous vasculopathy has been described in a total of 19 cases in the medical literature. The first several cases were described exclusively in middle-aged to elderly men. Though it has now been described in both men and women, cutaneous collagenous vasculopathy is still most often described in middle-aged to older adults. No particular disease or medication has been linked to the development of cutaneous collagenous vasculopathy, and the etiology remains unknown. In this case series, the authors present three additional patients diagnosed with cutaneous collagenous vasculopathy and discuss their clinical and histopathologic features. PMID:26705441

Site-Specific Expression of Polycomb-Group Genes Encoding the HPC-HPH/PRC1 Complex in Clinically Defined Primary Nodal and Cutaneous Large B-Cell Lymphomas

PubMed Central

Raaphorst, Frank M.; Vermeer, Maarten; Fieret, Elly; Blokzijl, Tjasso; Dukers, Danny; Sewalt, Richard G.A.B.; Otte, Arie P.; Willemze, Rein; Meijer, Chris J.L.M.

2004-01-01

Polycomb-group (PcG) genes preserve cell identity by gene silencing, and contribute to regulation of lymphopoiesis and malignant transformation. We show that primary nodal large B-cell lymphomas (LBCLs), and secondary cutaneous deposits from such lymphomas, abnormally express the BMI-1, RING1, and HPH1 PcG genes in cycling neoplastic cells. By contrast, tumor cells in primary cutaneous LBCLs lacked BMI-1 expression, whereas RING1 was variably detected. Lack of BMI-1 expression was characteristic for primary cutaneous LBCLs, because other primary extranodal LBCLs originating from brain, testes, and stomach were BMI-1-positive. Expression of HPH1 was rarely detected in primary cutaneous LBCLs of the head or trunk and abundant in primary cutaneous LBCLs of the legs, which fits well with its earlier recognition as a distinct clinical pathological entity with different clinical behavior. We conclude that clinically defined subclasses of primary LBCLs display site-specific abnormal expression patterns of PcG genes of the HPC-HPH/PRC1 PcG complex. Some of these patterns (such as the expression profile of BMI-1) may be diagnostically relevant. We propose that distinct expression profiles of PcG genes results in abnormal formation of HPC-HPH/PRC1 PcG complexes, and that this contributes to lymphomagenesis and different clinical behavior of clinically defined LBCLs. PMID:14742259

Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II*

PubMed Central

Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

2016-01-01

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779

Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

PubMed

Salama, S

2005-06-01

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

ClinicalTrials.gov

2018-05-25

Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

Persistent parasites and immunologic memory in cutaneous leishmaniasis: implications for vaccine designs and vaccination strategies.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2008-01-01

Despite a plethora of publications on the murine model of cutaneous leishmaniasis and their contribution to our understanding of the factors that regulate the development of CD4+ T cell immunity in vivo, there is still no effective vaccine against the human disease. While recovery from natural or experimental infection with Leishmania major, the causative agent of human cutaneous leishmaniasis, results in persistence of parasites at the primary infection site and the development of long-lasting immunity to reinfection, vaccination with killed parasites or recombinant proteins induces only short-term protection. The reasons for the difference in protective immunity following recovery from live infection and vaccination with heat-killed parasites are not known. This may in part be related to persistence of live parasites following healing of primary cutaneous lesions, because complete clearance of parasites leads to rapid loss of infection-induced immunity. Recent reports indicate that in addition to persistent parasites, IL-10-producing natural regulatory T cells may also play critical roles in the maintenance and loss of infection-induced immunity. This review focuses on current understanding of the factors that regulate the development, maintenance and loss of anti-Leishmania memory responses and highlights the role of persistent parasites and regulatory T cells in this process. Understanding these factors is crucial for designing effective vaccines and vaccination strategies against cutaneous leishmaniasis.

[Primary cutaneous aspergillosis complicated with invasive aspergillosis in an extremely preterm infant: case report and literature review].

PubMed

Stock, C; Veyrier, M; Magnin-Verschelde, S; Duband, S; Lavocat, M-P; Teyssier, G; Berthelot, P

2010-10-01

Aspergillus is a ubiquitous fungus that can cause primary cutaneous aspergillosis in extremely low-birth-weight (ELBW) neonates, then be invasive and lead to death. ELBW neonates are particularly at risk because of decreased qualitative immune defenses and defects in the skin barrier. Broad-spectrum antimicrobial therapy and corticosteroids, often used in these patients, contribute to increased risk. We present a fatal case of primary cutaneous aspergillosis complicated with invasive aspergillosis, confirmed by autopsy, in an ELBW infant. The source of contamination was probably non-sterile disposable latex gloves used for neonatal care. The early recognition of this source led to its eviction for other hospitalized ELBW infants and no outbreak was observed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

GATA3 staining in primary cutaneous apocrine cribriform carcinoma: Usefulness to differentiate it from breast cancer metastasis.

PubMed

Llamas-Velasco, Mar; Pérez-Gónzalez, Yosmar C; Daudén, Esteban; Rütten, Arno

2018-05-01

Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raises a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer. To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test its usefulness to differentiate this tumor from metastatic breast cancer. We retrieved 14 cases with PCACC (each from a different patient) from the files of the authors. Cases were dated from 1994 to 2014. We also evaluated 6 cases of cutaneous breast cancer metastasis RESULTS: No PCACCs expressed GATA3. Breast cancer metastases expressed GATA3 in 100% of our studied cases. Even though GATA3 expression has been reported in many benign and malignant adnexal tumors (mostly of sebaceous, follicular, and apocrine differentiation), as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should permit one to rule out PCACC with a high level of confidence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Treatment of Primary Cutaneous CD30+ Anaplastic Large-Cell Lymphoma With Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, James B.; McNiff, Jennifer M.; Lund, Molly W.

2008-04-01

Purpose: Primary cutaneous CD30+ anaplastic large-cell lymphoma (CALCL) is a relatively rare and indolent variant of cutaneous T-cell lymphoma (CTCL). This report examines the response of localized disease to radiation alone. Methods: The Yale Cancer Center records were examined, and all patients with CTCL from January 1, 2001, to September 1, 2006, evaluated in the Department of Therapeutic Radiology were identified. Only those patients with localized or single CALCL lesions, no clinical evidence or history of lymphomatoid papulosis, no history of other CTCLs, no history of other skin disorders, lack of lymph node involvement, unambiguous pathology reports, and treatment withmore » radiation alone were included. Results: Eight patients were identified. Median age was 67 years, and gender was split evenly. Patients received radiation ranging from 34 to 44 Gy in 2-Gy fractions. Most patients (5 of 8) received 40 Gy, using 6 to 9 MeV electrons with 0.5 to 2 cm of bolus. All patients had a complete response. All patients were without evidence of disease at the most recent follow-up (median follow-up, 12 months). Radiation therapy was well tolerated, and the only recorded toxicity was Grade I to II dermatitis. Conclusions: Radiation therapy alone for localized CALCL is very well tolerated and clinical response is excellent. A dose of 40 Gy in 2-Gy fractions seems to be well tolerated and effective in inducing a complete response. Lower doses may be effective in achieving the same result, but data are not available. Longer follow-up is necessary before conclusions regarding durable disease-free survival can be made.« less

Cutaneous bacterial colonization, modalities of chemotherapeutic infusion, and catheter-related bloodstream infection in totally implanted venous access devices.

PubMed

Laurenzi, L; Natoli, S; Benedetti, C; Marcelli, M E; Tirelli, W; DiEmidio, L; Arcuri, E

2004-11-01

Prospective clinical study to evaluate patients suffering from solid tumor using a totally implanted venous access device (TIVAD) to determine: (1) if there is a relationship between cutaneous contamination at port insertion site and catheter-related bloodstream infection (CRBI); (2) development modalities of CRBI; (3) if there is a relationship between chemotherapy administration modalities by push/ bolus versus continuous infusion and CRBI. We studied 41 consecutive patients who needed a TIVAD positioned for chemotherapy administration by bolus/ push or continuous infusion. In every patient, we performed blood cultures from blood samples from port catheters and cutaneous cultures from cutaneous tampons of the skin surrounding the implant area on the first (T0) and eight day (T1) postoperatively, after 1 month (T2), and after 3 months (T3) from insertion. The study was completed on 40 patients; in one case, the port was removed at T2 for septic complications. We obtained four positive blood cultures (two, 5%), two in the same patient, all caused by staphylococcus. Positive cutaneous tampons were 21 (13%) in 11 patients (27%); the four CRBI occurred in this group of patients with none in the remaining 30 patients (73%) for a total number of 120 tampons (p<0.01). In two cases, the same germ was isolated from both the skin and blood. None of the patients presented a local infection of the subcutaneous pocket. Positive cutaneous cultures decrease over time: T0-T2; 24-5%; T1-T3, 20-5% (p<0.04). There were no differences in CRBI incidence and positive cutaneous tampons between the two chemotherapy administration modalities. Cutaneous microbial flora has a primary role in CRBI development within TIVADs; there is a relationship between cutaneous colonization and CRBI; colonization reaches its maximum during the first days after catheterization in which the use of the system is at high risk; colonization occurs both via extraluminal and endoluminal routes; there is no

Lysosomal-associated membrane protein-2 plays an important role in the pathogenesis of primary cutaneous vasculitis.

PubMed

Takeuchi, Sora; Kimura, Satoko; Soma, Yoshinao; Waki, Masashi; Yamaguchi, Madoka; Nakazawa, Daigo; Tomaru, Utano; Ishizu, Akihiro; Kawakami, Tamihiro

2013-09-01

Recent research suggests that lysosomal-associated membrane protein-2 (LAMP-2) could be one of the target antigens in the pathogenesis of vasculitides. We established a transgenic rat model, env-pX rats, with various vasculitides including cutaneous vasculitis. Human primary cutaneous vasculitis includes cutaneous polyarteritis nodosa (CPN) and Henoch-Schönlein purpura (HSP). We measured serum anti-LAMP-2 antibody levels in morbid env-pX rats and injected anti-LAMP-2 antibody into premorbid env-pX rats. We further measured serum anti-LAMP-2 antibody levels in patients with CPN and HSP. Cutaneous vasculitis was observed in ∼30% of 6-month-old morbid env-pX rats. In contrast, these findings were rare in premorbid env-pX rats under 3 months old. We also examined 85 patients with CPN and 36 adult patients with HSP. Serum anti-LAMP-2 antibody levels were determined using ELISA. Premorbid env-pX rats under 3 months old were given an i.v. injection of anti-LAMP-2 antibody at day 0 and day 7. At day 14, these rats underwent histopathological and direct immunofluorescence examination. Cell surface LAMP-2 expression of rat neutrophils was examined by flow cytometry. Serum anti-LAMP-2 antibody levels were significantly higher in morbid env-pX rats than in wild-type normal rats. In addition, the levels in the cutaneous vasculitis group of morbid env-pX rats were significantly higher than the no cutaneous vasculitis group. Intravenous anti-LAMP-2 antibody injection into premorbid env-pX rats under 3 months old induced infiltration of neutrophils into cutaneous small vessels. Anti-LAMP-2 antibody-binding neutrophils were detected there. LAMP-2 expression on the cell surface of neutrophils in premorbid env-pX rats under PMA stimulation was higher compared with controls. Serum anti-LAMP-2 antibody levels in CPN and HSP were significantly higher than those of healthy controls. These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis.

Primary cutaneous secretory carcinoma: A previously overlooked low-grade sweat gland carcinoma.

PubMed

Llamas-Velasco, Mar; Mentzel, Thomas; Rütten, Arno

2018-03-01

Twelve cases of primary cutaneous secretory carcinoma (PCSC) have been published, 9 showing ETV6-NTRK3 translocation, a characteristic finding shared with secretory breast carcinoma and mammary analogue secretory carcinoma. A 34-year-old female presented a solitary nodule on the right groin. Biopsy revealed a secretory carcinoma staining positive with CK7, CAM5.2, mammaglobulin and S100 and negative with GATA3, CK20, podoplanin, calponin and CDX2. ETV6-NTRK3 was demonstrated by Fluorescence in situ hybridization (FISH). PCSC is a rare neoplasm, described in the skin in 2009, that affects more frequently females with a mean age of 42.3 years and it is most commonly located in axilla. Histopathologically, these tumor cells are characterized by bubbly eosinophilic secretions diastase-resistant and bland nuclei and they are arranged in various growth patterns, including microcystic, tubular, solid and papillary. S100, mammoglobin and CK7 are usually positive. We review the main histopathological features to rule out histopathologic mimics such as breast metastasis, salivary tumors, cribriform carcinoma and primary cutaneous adenoid cystic carcinoma. GATA3 negative staining, as in our case, can help to rule out breast metastasis. Moreover, long-term benign follow up (144 months) in this case as well as follow-up data on outcomes from literature review support that PCSC is a low-grade sweat gland carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutaneous metastasis of cholangiocarcinoma.

PubMed

Liu, Min; Liu, Bai-Long; Liu, Bin; Guo, Liang; Wang, Qiang; Song, Yan-Qiu; Dong, Li-Hua

2015-03-14

To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.

Total-skin electron irradiation for cutaneous T-cell lymphoma: the Northern Israel Oncology Center experience.

PubMed

Kuten, A; Stein, M; Mandelzweig, Y; Tatcher, M; Yaacov, G; Epelbaum, R; Rosenblatt, E

1991-07-01

Total-skin electron irradiation (TSEI) is effective and frequently used in the treatment of cutaneous T-cell lymphoma. A treatment technique has been developed at our center, using the Philips SL 75/10 linear accelerator. In our method, the patient is irradiated in a recumbent position by five pairs of uncollimated electron beams at a source to skin distance of 150 cm. This method provides a practical solution to clinical requirements with respect to uniformity of electron dose and low X-ray contamination. Its implementation does not require special equipment or modification of the linear accelerator, 19 of 23 patients (83%) with mycosis fungoides, treated by this method, achieved complete regression of their cutaneous lesions.

Problems in Cutaneous Communication from Psychophysics to Information Processing.

ERIC Educational Resources Information Center

Gilmer, B. VonHaller; Clark, Leslie L., Ed.

After reviewing the history of communication through the skin, this paper considers recent research into the problem of cutaneous stimulation induced both mechanically and electrically. The general demands of a cutaneous communication system are discussed, and four primary dimensions of cutaneous stimulation are summarized (locus, intensity,…

Recurrent Cutaneous Herpes Simplex in Hairless Mice

PubMed Central

Underwood, Gerald E.; Weed, Sheldon D.

1974-01-01

Passively immunized hairless mice were inoculated cutaneously with herpes simplex virus. Thirty-nine days later, when the primary cutaneous lesions had completely healed, the mice were treated subcutaneously with prednisone. Within 12 to 30 days after starting prednisone treatment, herpesvirus was recovered by skin swabs from 12 of 71 (17%) of the treated mice. This new model has potential application for understanding and treating recurrent cutaneous herpes infections. PMID:4372171

Ex vivo enrichment of circulating anti-tumor T cells from both cutaneous and ocular melanoma patients: clinical implications for adoptive cell transfer therapy.

PubMed

Mazzarella, Tonia; Cambiaghi, Valeria; Rizzo, Nathalie; Pilla, Lorenzo; Parolini, Danilo; Orsenigo, Elena; Colucci, Annalisa; Modorati, Giulio; Doglioni, Claudio; Parmiani, Giorgio; Maccalli, Cristina

2012-08-01

Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible for a limited fraction of cutaneous melanoma patients. We assessed whether an effective protocol for ex vivo T-cell expansion from peripheral blood mononuclear cells (PBMCs), suitable for ACT of both cutaneous and ocular melanoma patients, could be identified. PBMCs from both cutaneous and ocular melanoma patients were stimulated in vitro with autologous, irradiated melanoma cells (mixed lymphocyte tumor cell culture; MLTCs) in the presence of IL-2 and IL-15 followed by the rapid expansion protocol (REP). The functional activity of these T lymphocytes was characterized and compared with that of TILs. In addition, the immune infiltration in vivo of ocular melanoma lesions was analyzed. An efficient in vitro MLTC expansion of melanoma reactive T cells was achieved from all PBMC's samples obtained in 7 cutaneous and ocular metastatic melanoma patients. Large numbers of melanoma-specific T cells could be obtained when the REP protocol was applied to these MLTCs. Most MLTCs were enriched in non-terminally differentiated T(EM) cells homogeneously expressing co-stimulatory molecules (e.g., NKG2D, CD28, CD134, CD137). A similar pattern of anti-tumor activity, in association with a more variable expression of co-stimulatory molecules, was detected on short-term in vitro cultured TILs isolated from the same patients. In these ocular melanoma patients, we observed an immune infiltrate with suppressive characteristics and a low rate of ex vivo growing TILs (28.5% of our cases). Our MLTC protocol overcomes this limitation, allowing the isolation of T lymphocytes with effector functions even in these patients. Thus, anti-tumor circulating PBMC-derived T cells could be efficiently isolated from melanoma patients by our novel ex vivo enrichment protocol. This protocol appears suitable for ACT studies

Head and neck cutaneous squamous cell carcinoma metastatic to cervical sublevel IIb lymph nodes occurred from primary sites involving the auricle and adjacent neck.

PubMed

Maher, Nigel Gordon; Hoffman, Gary Russell

2014-03-01

Neck dissections that include sublevel IIb increase the risk of postoperative shoulder dysfunction. The purpose of this investigation was to document the incidence of level IIb metastatic lymphatic spread in a group of patients undergoing neck dissection as part of the surgical management of cutaneous squamous cell carcinoma of the head and neck. A retrospective review of the pathology records taken from 1 surgeon from June 2006 through June 2013 was carried out. The predictor variable was the primary tumor site. The outcome variable was the metastatic nodal involvement according to neck level and sublevel. Secondary variables included T stage, pathologist, tumor depth, and the presence of perineural, perilymphatic, and perivascular invasion. Data analyses were by descriptive statistics. Thirty-six patients with a total of 40 neck dissections met the inclusion criteria. The average primary site tumor depth was 14.7 mm, and there were 16 cases of poorly differentiated squamous cell carcinoma. Sublevel IIb was involved in 7.5% of cases, all of which occurred from lateralized primary sites of the head and neck. Cutaneous squamous cell carcinoma arising from the auricle and neck sites adjacent to sublevel IIb may have increased risk of metastatic involvement of sublevel IIb nodes. Further studies with larger numbers are required to determine the risk of metastasis to sublevel IIb from midline sites of the face. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Distinct types of primary cutaneous large B-cell lymphoma identified by gene expression profiling.

PubMed

Hoefnagel, Juliette J; Dijkman, Remco; Basso, Katia; Jansen, Patty M; Hallermann, Christian; Willemze, Rein; Tensen, Cornelis P; Vermeer, Maarten H

2005-05-01

In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma.

PubMed

Willerslev-Olsen, Andreas; Krejsgaard, Thorbjørn; Lindahl, Lise M; Litvinov, Ivan V; Fredholm, Simon; Petersen, David L; Nastasi, Claudia; Gniadecki, Robert; Mongan, Nigel P; Sasseville, Denis; Wasik, Mariusz A; Bonefeld, Charlotte M; Geisler, Carsten; Woetmann, Anders; Iversen, Lars; Kilian, Mogens; Koralov, Sergei B; Odum, Niels

2016-03-10

Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malignancy. Clinical data indicate that bacteria play a direct role in disease progression, but little is known about the mechanisms involved. Here, we demonstrate that bacterial isolates containing staphylococcal enterotoxin A (SEA) from the affected skin of CTCL patients, as well as recombinant SEA, stimulate activation of signal transducer and activator of transcription 3 (STAT3) and upregulation of interleukin (IL)-17 in immortalized and primary patient-derived malignant and nonmalignant T cells. Importantly, SEA induces STAT3 activation and IL-17 expression in malignant T cells when cocultured with nonmalignant T cells, indicating an indirect mode of action. In accordance, malignant T cells expressing an SEA-nonresponsive T-cell receptor variable region β chain are nonresponsive to SEA in monoculture but display strong STAT3 activation and IL-17 expression in cocultures with SEA-responsive nonmalignant T cells. The response is induced via IL-2 receptor common γ chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk-dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis. © 2016 by The American Society of Hematology.

Locoregional spread of cutaneous melanoma: sonography findings.

PubMed

Catalano, Orlando; Caracò, Corrado; Mozzillo, Nicola; Siani, Alfredo

2010-03-01

This article reviews various aspects of locoregional spread of malignant cutaneous melanoma, as imaged with gray-scale sonography and Doppler techniques. The scenarios illustrated include disease staging (primary melanoma, satellite metastasis, in-transit metastasis, and lymphadenopathies), sentinel lymph node biopsy procedure, patient follow-up, recurrence detection, cutaneous metastasis, and sonographically guided intervention. High-resolution sonography allows recognition of small, clinically-occult melanomatous foci. It plays a major role in locoregional staging and follow-up of patients with cutaneous melanoma.

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis.

PubMed

Duvic, Madeleine; Tetzlaff, Michael T; Gangar, Pamela; Clos, Audra L; Sui, Dawen; Talpur, Rakhshandra

2015-11-10

Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30(+) receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30(+) cutaneous T-cell lymphomas. Forty-eight patients with CD30(+) lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1

Results of a Phase II Trial of Brentuximab Vedotin for CD30+ Cutaneous T-Cell Lymphoma and Lymphomatoid Papulosis

PubMed Central

Duvic, Madeleine; Tetzlaff, Michael T.; Gangar, Pamela; Clos, Audra L.; Sui, Dawen; Talpur, Rakhshandra

2015-01-01

Purpose Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30+ receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30+ cutaneous T-cell lymphomas. Patients and Methods Forty-eight patients with CD30+ lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. Results Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy

European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas.

PubMed

Senff, Nancy J; Noordijk, Evert M; Kim, Youn H; Bagot, Martine; Berti, Emilio; Cerroni, Lorenzo; Dummer, Reinhard; Duvic, Madeleine; Hoppe, Richard T; Pimpinelli, Nicola; Rosen, Steven T; Vermeer, Maarten H; Whittaker, Sean; Willemze, Rein

2008-09-01

Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

CD20-Positive nodal natural killer/T-cell lymphoma with cutaneous involvement.

PubMed

Tsai, Yi-Chiun; Chen, Chi-Kuan; Wu, Yu-Hung

2015-09-01

CD20-positive natural killer (NK)/T-cell lymphoma is extremely rare. We describe a case of a CD20-positive nodal NK/T-cell lymphoma with cutaneous involvement in a 32-year-old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA-1 and CD20 but negative staining for other B-cell markers, including CD79a and PAX-5 and T-cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein-Barr virus-encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T- and B-cells. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutaneous EBV-related lymphoproliferative disorders.

PubMed

Gru, Alejandro A; Jaffe, Elaine S

2017-01-01

This article will focus on the cutaneous lymphoproliferative disorders associated with EBV, with an emphasis on the upcoming changes in the revised 4th Edition of the WHO classification of tumors of the hematopoietic system, many of which deal with cutaneous disorders derived from NK-cells or T-cells. Extranodal NK/T-cell lymphoma usually presents in the upper aerodigestive tract, but can involve the skin secondarily. EBV-associated T- and NK-cell lymphoproliferative disorders (LPD) in the pediatric age group include the systemic diseases, chronic active EBV infection (CAEBV) and systemic EBV+ T-cell lymphoma of childhood. Hydroa vacciniforme (HV)-like LPD is a primarily cutaneous form of CAEBV and encompasses the lesions previously referred to as HV and HV-like lymphoma (HVLL). All the T/NK-cell-EBV-associated diseases occur with higher frequency in Asians, and indigenous populations from Central and South America and Mexico. Among the B-cell EBV-associated LPD two major changes have been introduced in the WHO. The previously designated EBV-positive diffuse large B-cell lymphoma (EBV-DLBCL) of the elderly, has been changed to EBV-DLBCL with 'not otherwise specified' as a modifier (NOS). A new addition to the WHO system is the more recently identified EBV+ mucocutaneous ulcer, which involves skin and mucosal-associated sites. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vβ chain restriction.

PubMed

Gibson, Juliet F; Huang, Jing; Liu, Kristina J; Carlson, Kacie R; Foss, Francine; Choi, Jaehyuk; Edelson, Richard; Hussong, Jerry W; Mohl, Ramsey; Hill, Sally; Girardi, Michael

2016-05-01

Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vβ analysis by flow cytometry. We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vβ testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vβ testing should be considered in future diagnostic and staging algorithms. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Two Different Cell Populations Is an Important Clue for Diagnosis of Primary Cutaneous Adenoid Cystic Carcinoma: Immunohistochemical Study

PubMed Central

Alkan, Banu Ince; Karadeniz, Müjde; Bozdoğan, Nazan

2017-01-01

Primary cutaneous adenoid cystic carcinoma (PCACC) is a very rare malignancy. The differential diagnosis of PCACCs in pathology practice can be difficult and a group of primary and metastatic lesions, including adenoid basal cell carcinoma of the skin, should be considered in the differential diagnosis. Besides histomorphological clues, immunohistochemistry studies are very helpful in the differential diagnosis of PCACC. We report herein a case of PCACC with extensive immunohistochemical studies and review the literature from an immunohistochemistry perspective. PMID:28243477

Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heumann, Thatcher R.; Esiashvili, Natia; Winship Cancer Institute

2015-05-01

Purpose: To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. Methods and Materials: We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log–rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. Results: Median age at diagnosis and at time of radiation was 52 and 56 years, respectively.more » Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. Conclusions: These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.« less

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PubMed

Stuart, Lauren N; Tipton, Russell G; DeWall, Michael R; Parker, Douglas C; Stelton, Christina D; Morrison, Annie O; Coleman, Landon W; Fosko, Scott W; Vidal, Claudia I; Yadira Hurley, Maria; Deeken, Amy H; Gardner, Jerad M

2017-08-01

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Guidelines of the Brazilian Dermatology Society for diagnosis, treatment and follow up of primary cutaneous melanoma - Part I*

PubMed Central

Castro, Luiz Guilherme Martins; Messina, Maria Cristina; Loureiro, Walter; Macarenco, Ricardo Silvestre; Duprat Neto, João Pedreira; Giacomo, Thais Helena Bello Di; Bittencourt, Flávia Vasques; Bakos, Renato Marchiori; Serpa, Sérgio Schrader; Stolf, Hamilton Ometto; Gontijo, Gabriel

2015-01-01

The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In the first part, the following clinical questions were answered: 1) The use of dermoscopy for diagnosis of primary cutaneous melanoma brings benefits for patients when compared with clinical examination? 2) Does dermoscopy favor diagnosis of nail apparatus melanoma? 3) Is there a prognostic difference when incisional or excisional biopsies are used? 4) Does revision by a pathologist trained in melanoma contribute to diagnosis and treatment of primary cutaneous melanoma? What margins should be used to treat lentigo maligna melanoma and melanoma in situ? PMID:26734867

Multiple cutaneous melanomas associated with gastric and brain metastases*

PubMed Central

Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

2016-01-01

The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909

IgG4 Expression in Primary Cutaneous Marginal Zone Lymphoma: A Multicenter Study.

PubMed

De Souza, Aieska; Ferry, Judith A; Burghart, Daniel R; Tinguely, Marianne; Goyal, Amrita; Duncan, Lyn M; Kutzner, Heinz; Kempf, Werner

2017-02-01

Primary cutaneous marginal zone lymphoma (PCMZL) is the second most common B-cell lymphoma of the skin. A recent study has demonstrated a strikingly high prevalence of immunoglobulin (Ig)G4 expression in PCMZL with plasmacytic differentiation. The objective was to investigate the incidence of IgG4 expression in PCMZL, and its correlation with clinical and immunophenotypic features. Multicenter study that utilized immunohistochemistry and in-situ hybridization to evaluate the expression of IgG4, Ig light (κ and λ), and heavy chains (IgM, IgG), and the ratio of T (CD3+) and B (CD20+) cells in biopsy specimens from 30 patients with PCMZL and to correlate these findings with the clinical features. IgG4 expression was observed in 4 out of 30 patients (13%) with PCMZL. Patients with IgG4-positive lymphomas were 57 to 77 years of age (mean, 69) at biopsy. The lesions were solitary in 2 patients with IgG4-positive lymphomas, and were most commonly located on the trunk. Patients with IgG4-negative lymphomas experienced earlier disease onset at an average age of 53 years. The majority of the IgG4-negative cases presented with localized disease, on the trunk and upper extremities. There was no significant difference in the IgG4-positive versus negative cases for the following parameters: Ig κ or λ restriction, B-cell or T-cell predominance, and site of the lesions. IgG4 expression was observed in a minority of PCMZL patients. We did not identify significant clinical or immunophenotypic differences between IgG4 positive and negative cases.

Visualization of T Cell-Regulated Monocyte Clusters Mediating Keratinocyte Death in Acquired Cutaneous Immunity.

PubMed

Liu, Zheng; Yang, Fei; Zheng, Hao; Fan, Zhan; Qiao, Sha; Liu, Lei; Tao, Juan; Luo, Qingming; Zhang, Zhihong

2018-06-01

It remains unclear how monocytes are mobilized to amplify inflammatory reactions in T cell-mediated adaptive immunity. Here, we investigate dynamic cellular events in the cascade of inflammatory responses through intravital imaging of a multicolor-labeled murine contact hypersensitivity model. We found that monocytes formed clusters around hair follicles in the contact hypersensitivity model. In this process, effector T cells encountered dendritic cells under regions of monocyte clusters and secreted IFN-γ, which mobilizes CCR2-dependent monocyte interstitial migration and CXCR2-dependent monocyte cluster formation. We showed that hair follicles shaped the inflammatory microenvironment for communication among the monocytes, keratinocytes, and effector T cells. After disrupting the T cell-mobilized monocyte clusters through CXCR2 antagonization, monocyte activation and keratinocyte apoptosis were significantly inhibited. Our study provides a new perspective on effector T cell-regulated monocyte behavior, which amplifies the inflammatory reaction in acquired cutaneous immunity. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations

PubMed Central

Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

2016-01-01

Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression. PMID:27095580

Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations.

PubMed

Montagnani, Valentina; Benelli, Matteo; Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

2016-05-24

Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.

Gamma-delta t-cell lymphomas.

PubMed

Foppoli, Marco; Ferreri, Andrés J M

2015-03-01

Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, which naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease.

PubMed

Kim, Juyang; Kim, Hye J; Park, Keunhee; Kim, Jiyoung; Choi, Hye-Jeong; Yagita, Hideo; Nam, Seok H; Cho, Hong R; Kwon, Byungsuk

2007-07-15

Chronic graft-versus-host disease (cGVHD) is an increasingly frequent complication of allogeneic stem cell transplantation. Current therapies for cGVHD reduce symptoms but are not cures. The B10.D2-->Balb/c (H-2(d)) minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD, was used in this study. We demonstrated that a single injection of an agonistic monoclonal antibody (mAb) against CD137, a member of the tumor necrosis factor receptor superfamily, reverses skin fibrosis, ulceration, and alopecia, a dominant feature of cGVHD (cutaneous GVHD), ultimately improving general health conditions. The reversal is associated with markedly reduced CD4(+) T-cell cytokines and increased apoptosis of donor CD4(+) T cells. The Fas pathway is required for ameliorating cutaneous GVHD by anti-CD137 mAb. Taken together, these data indicate that the anti-CD137 mAb has a therapeutic effect on cutaneous GVHD by removing donor CD4(+) T cells that cause cutaneous GVHD. Thus, our study demonstrates an agonistic mAb, specific for a costimulatory molecule, as a possible target for therapeutic intervention in cutaneous GVHD.

Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread.

PubMed

Warren, Timothy A; Whiteman, David C; Porceddu, Sandro V; Panizza, Benedict J

2016-09-01

Perineural spread (PNS) of cutaneous squamous cell carcinoma of the head and neck (SCCHN) can be associated with poor outcomes. Disease understanding and awareness is limited leading to delayed diagnosis and treatment. The purpose of this study was to identify epidemiological features of patients with PNS of cutaneous SCCHN. Tumor characteristics and demographics of patients with PNS of cutaneous SCCHN managed through a single institution were collected between 1998 and 2013. One hundred twenty patients were included in this study. The majority had a history of skin cancer (85.8%). The median time from primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months). A total of 34.2% had no perineural invasion (PNI) detected in the primary, and 22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement at presentation. Patients can present with PNS from cutaneous SCCHN with no known primary tumor or with primary tumors without PNI. The majority of patients presented without regional nodal involvement. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1416-1420, 2016. © 2016 Wiley Periodicals, Inc.

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Sentinel lymph node biopsy in cutaneous melanoma of the head and neck using the indocyanine green SPY Elite system.

PubMed

Vahabzadeh-Hagh, Andrew M; Blackwell, Keith E; Abemayor, Elliot; St John, Maie A

2018-05-17

Lymph node status is the single most important prognostic factor for patients with early-stage cutaneous melanoma. Sentinel lymph node biopsy (SLNB) has become the standard of care for intermediate depth melanomas. Modern SLNB implementation includes technetium-99 lymphoscintigraphy combined with local administration of a vital blue dye. However, sentinel lymph nodes may fail to localize in some cases and false-negative rates range from 0 to 34%. Here we demonstrate the feasibility of a new sentinel lymph node biopsy technique using indocyanine green (ICG) and the SPY Elite near-infrared imaging system. Cases of primary cutaneous melanoma of the head and neck without locoregional metastasis, underwent SLNB at a single quaternary care institution between May 2016 and June 2017. Intraoperatively, 0.25 mL of ICG was injected intradermal in 4 quadrants around the primary lesion. 10-15 minute circulation time was permitted. SPY Elite identified the sentinel lymph node within the nodal basin marked by lymphoscintigraphy. Target first echelon lymph nodes were confirmed with a gamma probe and ICG fluorescence. 14 patients were included with T1a to T4b cutaneous melanomas. Success rates for sentinel lymph node identification using lymphoscintigraphy and the SPY Elite system were both 86%. Zero false negatives occurred. Median length of follow-up was 323 days. In this pilot study, Indocyanine green near-infrared fluorescence demonstrates a safe, and facile method of sentinel lymph node biopsy for cutaneous melanoma of the head and neck compared with lymphoscintigraphy and vital blue dyes. Copyright © 2018 Elsevier Inc. All rights reserved.

Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.

PubMed

García-Sepúlveda, Ricardo; Navarrete-Solís, Josefina; Villanueva-Lozano, Hiram; de J Treviño-Rangel, Rogelio; González, Gloria M; Enríquez-Rojas, Jorge; Molina-Durazo, Javier; Arenas-Guzmán, Roberto

2017-12-01

Mucormycosis of the scalp is a rare cutaneous presentation of the disease. It is also an unusual infection in children. We present the case of a 4-year-old girl with acute lymphoblastic leukemia, who presented with atypical cutaneous mucormycosis simulating an ecthyma gangrenosum lesion. Risk factors for the infection are diabetes, neoplastic diseases, immunosuppression in organ transplant recipients, and neutropenia. The cutaneos forms have been associated with trauma, burns and surgical wounds. First line treatment is amphotericin B. Posaconazole was recently approved to treat invasive mucormycosis. Surgical removal of the infected tissue is indicated.

Availability of sentinel lymph node biopsy for cutaneous squamous cell carcinoma.

PubMed

Maruyama, Hiroshi; Tanaka, Ryota; Fujisawa, Yasuhiro; Nakamura, Yasuhiro; Ito, Shusaku; Fujimoto, Manabu

2017-04-01

Cutaneous squamous cell carcinoma is the second common cutaneous cancer, especially in the elderly. Sentinel lymph node biopsy is generally performed in breast cancers and cutaneous melanomas to detect occult nodal metastases. The benefit of sentinel lymph node biopsy in improving cutaneous squamous cell carcinoma prognosis is doubtful. One hundred and sixty-nine patients who underwent treatment for cutaneous squamous cell carcinoma between 2004 and 2015, and who were followed up for at least 6 months or developed metastases within the follow-up period were included. Forty-nine patients underwent sentinel lymph node biopsy, whereas 120 patients did not, including 13 who exhibited clinical lymph node metastases before treatment. Of these 49 patients, nine (18.4%) presented with sentinel lymph node metastasis, which occurred after treatment in three (6.1%) of them (false-negative). Among the 107 patients who did not undergo lymph node biopsy, 12 (11.2%) developed post-treatment metastases. The metastasis-free and disease-specific survival rates were not significantly different in those who did or did not undergo sentinel lymph node biopsy. Patients with clinical lymph node metastases had a higher risk compared with those without. Patients with T2-T4 tumors had a higher risk compared with those with T1 tumors. When selecting for those with T2 tumors or greater, the same lack of relationship was observed. In conclusion, in this small retrospective cohort, in patients with cutaneous squamous cell carcinoma, there were no significant differences in metastasis-free and disease-specific survival rates between those who did or did not undergo sentinel lymph node biopsy, regardless of T staging. © 2016 Japanese Dermatological Association.

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients

PubMed Central

Bagdonaite, Ieva; Wandall, Hans H.; Litvinov, Ivan V.; Nastasi, Claudia; Becker, Jürgen C.; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M.; Zhang, Qian; Wasik, Mariusz A.; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-01-01

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22ΔN), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22ΔN mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22ΔN (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22ΔN and CD22wt in these cells. In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients. PMID:25957418

Ectopic expression of a novel CD22 splice-variant regulates survival and proliferation in malignant T cells from cutaneous T cell lymphoma (CTCL) patients.

PubMed

Bagdonaite, Ieva; Wandall, Hans H; Litvinov, Ivan V; Nastasi, Claudia; Becker, Jürgen C; Dabelsteen, Sally; Geisler, Carsten; Bonefeld, Charlotte M; Zhang, Qian; Wasik, Mariusz A; Zhou, Youwen; Sasseville, Denis; Ødum, Niels; Woetmann, Anders

2015-06-10

CD22 is a member of the Sialic acid-binding Ig-like lectin (Siglec) family of lectins described to be exclusively present in B lymphocytes and B cell-derived neoplasms. Here, we describe a novel splice form of CD22 (designated CD22∆N), which lacks the N-terminal domain as demonstrated by exon-specific RT-PCR and differential recognition by anti-CD22 antibodies. Importantly, CD22∆N mRNA is expressed in skin lesions from 39 out of 60 patients with cutaneous T cell lymphoma (CTCL), whereas few patients (6 out of 60) expresses full-length, wild type CD22 (CD22wt). In addition, IHC staining of tumor biopsies confirmed the expression of CD22 in CD4+ T cells. Moreover, four out of four malignant T cell lines express CD22: Two cell lines express CD22∆N (MyLa2059 and PB2B) and two express CD22wt (MAC-1 and MAC-2A). siRNA-mediated silencing of CD22 impairs proliferation and survival of malignant T cells, demonstrating a functional role for both CD22∆N and CD22wt in these cells.In conclusion, we provide the first evidence for an ectopic expression of CD22 and a novel splice variant regulating malignant proliferation and survival in CTCL. Analysis of expression and function of CD22 in cutaneous lymphomas may form the basis for development of novel targeted therapies for our patients.

Lack of T-cell receptor-induced signaling is crucial for CD95 ligand up-regulation and protects cutaneous T-cell lymphoma cells from activation-induced cell death.

PubMed

Klemke, Claus-Detlev; Brenner, Dirk; Weiss, Eva-Maria; Schmidt, Marc; Leverkus, Martin; Gülow, Karsten; Krammer, Peter H

2009-05-15

Restimulation of previously activated T cells via the T-cell receptor (TCR) leads to activation-induced cell death (AICD), which is, at least in part, dependent on the death receptor CD95 (APO-1, FAS) and its natural ligand (CD95L). Here, we characterize cutaneous T-cell lymphoma (CTCL) cells (CTCL tumor cell lines and primary CTCL tumor cells from CTCL patients) as AICD resistant. We show that CTCL cells have elevated levels of the CD95-inhibitory protein cFLIP. However, cFLIP is not responsible for CTCL AICD resistance. Instead, our data suggest that reduced TCR-proximal signaling in CTCL cells is responsible for the observed AICD resistance. CTCL cells exhibit no PLC-gamma1 activity, resulting in an impaired Ca(2+)release and reduced generation of reactive oxygen species upon TCR stimulation. Ca(2+) and ROS production are crucial for up-regulation of CD95L and reconstitution of both signals resulted in AICD sensitivity of CTCL cells. In accordance with these data, CTCL tumor cells from patients with Sézary syndrome do not up-regulate CD95L upon TCR-stimulation and are therefore resistant to AICD. These results show a novel mechanism of AICD resistance in CTCL that could have future therapeutic implications to overcome apoptosis resistance in CTCL patients.

Primary Subcutaneous Synovial Sarcoma: First Reported Subcutaneous Case Showing TLE1 Immunoreactivity.

PubMed

Alegría-Landa, Victoria; Nájera, Laura; Massa, Dolores Suárez; Roustan, Gastón; Río, María Del; Kutzner, Heinz; Requena, Luis

2018-05-08

Synovial sarcoma (SS) accounts for 5%-10% of all soft tissue sarcomas. It is a well-defined soft tissue neoplasm with biphasic and monophasic histologic subtypes and unknown histogenesis. It usually occurs in the extremities, especially the thigh-knee region of young adults. Recurrences are frequent and distant metastasis developed in approximately half of the patients. SSs are characterized by a recurrent nonrandom chromosomal translocation, t(X; 18) (p11; q11), which is considered the primary genetic event in more than 90% of cases. Only 4 cases of cutaneous and subcutaneous SSs have been published in the literature so far. We report a case of primary subcutaneous SS in the forearm of a young woman and discuss the histopathologic differential diagnosis with other similar neoplasms. This is the first reported case of primary cutaneous SS showing immunoreactivity for TLE1 in the nuclei of neoplastic cells, supporting the use of this marker for diagnosis of this rare cutaneous neoplasm.

Extranodal NK÷T-cell lymphoma, nasal type with cutaneous involvement - a rare case associated with chronic C hepatitis and occupational metal dust exposure.

PubMed

Ştefănescu, Eugen Horaţiu; Balica, Nicolae Constantin; Horhat, Ioana Delia; Baderca, Flavia; Pricop, Marius Octavian; Urechescu, Horaţiu Constantin; Lighezan, Daniel Florin; Sarău, Cristian Andrei

2017-01-01

Extranodal natural killer (NK)÷T-cell lymphomas, nasal type are rare and aggressive non-Hodgkin's lymphomas (NHLs), with unknown etiology, rapid evolution and poor prognosis, due to midline tissue destruction and rapid spreading of the tumor. These lymphomas occur commonly in the nasal cavity and upper aerodigestive tract, but can also present involvement of the skin, salivary gland, and testis. We describe a case of nasal type T-cell NHL involving the nasal cavity and determining right thigh cutaneous metastases in a 47-year-old female associated with liver comorbidities and occupational dust exposure. The patient was suffering from chronic type C hepatitis and cirrhosis and she has been occupationally exposed to metal dust for 10 years. Clinical and laboratory investigations were performed. Essential for diagnosis and treatment protocol was nasal endoscopy and biopsy of nasal and cutaneous lesions. The histopathological exam was consistent with NK÷T-cell lymphoma. Patient was diagnosed in Ann Arbor stage IVA. Chemotherapy was initiated with Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine and Prednisone, but it was stopped after two cycles because of the liver condition. The treatment plan also included radiotherapy, but soon after initiation, the patient died because of a liver complication. We present a rare case of extranodal NK÷T-cell lymphoma, nasal type, with cutaneous involvement to which the treatment could not be properly applied because of the late diagnosis and liver comorbidities.

Phenytoin Induced Cutaneous B Cell Pseudolymphoma

PubMed Central

Riyaz, Najeeba; Sasidharanpillai, Sarita; Aravindan, Karumathil P; Nobin, Babu K; Raghavan, Nisha T; Nikhila, Pappinissery K

2015-01-01

Cutaneous pseudolymphomas are benign lymphoproliferative processes mimicking lymphomas clinically and histologically. One of the precipitating factors for pseudolymphoma is drugs like anticonvulsants, antidepressants and angiotensin-converting enzyme inhibitors. According to existing literature phenytoin-induced cutaneous pseudolymphomas are usually T-cell predominant. Most often withdrawal of the drug with or without short-course systemic steroids can attain a cure. Rarely malignant transformation has been reported years later despite withdrawal of the offending drug, which necessitates a long-term follow up of the affected. We report an 80-year-old male patient who was receiving phenytoin sodium and who presented with diffuse erythema and infiltrated skin lesions which histologically resembled cutaneous B-cell lymphoma. Substituting phenytoin with levetiracetam achieved resolution of symptoms. Further evaluation was suggestive of a reactive process. A detailed drug history is of paramount importance in differentiating drug-induced pseudolymphoma from lymphoma. Searching literature we could not find any previous reports of phenytoin-induced cutaneous B-cell pseudolymphoma. PMID:26538730

Topical resiquimod can induce disease regression and enhance T-cell effector functions in cutaneous T-cell lymphoma.

PubMed

Rook, Alain H; Gelfand, Joel M; Gelfand, Joel C; Wysocka, Maria; Troxel, Andrea B; Benoit, Bernice; Surber, Christian; Elenitsas, Rosalie; Buchanan, Marie A; Leahy, Deborah S; Watanabe, Rei; Kirsch, Ilan R; Kim, Ellen J; Clark, Rachael A

2015-09-17

Early-stage cutaneous T-cell lymphoma (CTCL) is a skin-limited lymphoma with no cure aside from stem cell transplantation. Twelve patients with stage IA-IIA CTCL were treated in a phase 1 trial of 0.03% and 0.06% topical resiquimod gel, a Toll-like receptor 7/8 agonist. Treated lesions significantly improved in 75% of patients and 30% had clearing of all treated lesions. Resiquimod also induced regression of untreated lesions. Ninety-two percent of patients had more than a 50% improvement in body surface area involvement by the modified Severity-Weighted Assessment Tool analysis and 2 patients experienced complete clearing of disease. Four of 5 patients with folliculotropic disease also improved significantly. Adverse effects were minor and largely skin limited. T-cell receptor sequencing and flow cytometry studies of T cells from treated lesions demonstrated decreased clonal malignant T cells in 90% of patients and complete eradication of malignant T cells in 30%. High responses were associated with recruitment and expansion of benign T-cell clones in treated skin, increased skin T-cell effector functions, and a trend toward increased natural killer cell functions. In patients with complete or near eradication of malignant T cells, residual clinical inflammation was associated with cytokine production by benign T cells. Fifty percent of patients had increased activation of circulating dendritic cells, consistent with a systemic response to therapy. In summary, topical resiquimod is safe and effective in early-stage CTCL and the first topical therapy to our knowledge that can induce clearance of untreated lesions and complete remissions in some patients. This trial was registered at www.clinicaltrials.gov as #NCT813320. © 2015 by The American Society of Hematology.

Cutaneous Infections in Wrestlers

PubMed Central

Wilson, Eugene K.; deWeber, Kevin; Berry, James W.; Wilckens, John H.

2013-01-01

Context: Cutaneous infections are common in wrestlers. Although many are simply a nuisance in the everyday population, they can be problematic to wrestlers because such infections may result in disqualification from practice or competition. Prompt diagnosis and treatment are therefore important. Evidence Acquisition: Medline and PubMed databases, the Cochrane Database of Systematic Reviews, and UpToDate were searched through 2012 with the following keywords in various combinations: skin infections, cutaneous infections, wrestlers, athletes, methicillin-resistant Staphylococcus aureus, skin and soft tissue infections, tinea corporis, tinea capitis, herpes simplex, varicella zoster, molluscum contagiosum, verruca vulgaris, warts, scabies, and pediculosis. Relevant articles found in the primary search, and selected references from those articles were reviewed for pertinent clinical information. Results: The most commonly reported cutaneous infections in wrestlers are herpes simplex virus infections (herpes gladiatorum), bacterial skin and soft tissue infections, and dermatophyte infections (tinea gladiatorum). The clinical appearance of these infections can be different in wrestlers than in the community at large. Conclusion: For most cutaneous infections, diagnosis and management options in wrestlers are similar to those in the community at large. With atypical presentations, testing methods are recommended to confirm the diagnosis of herpes gladiatorum and tinea gladiatorum. There is evidence to support the use of prophylactic medications to prevent recurrence of herpes simplex virus and reduce the incidence of dermatophyte infections in wrestlers. PMID:24427413

Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.

PubMed

Roggero, E; Zucca, E; Mainetti, C; Bertoni, F; Valsangiacomo, C; Pedrinis, E; Borisch, B; Piffaretti, J C; Cavalli, F; Isaacson, P G

2000-02-01

Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.

Optical perception for detection of cutaneous T-cell lymphoma by multi-spectral imaging

NASA Astrophysics Data System (ADS)

Hsiao, Yu-Ping; Wang, Hsiang-Chen; Chen, Shih-Hua; Tsai, Chung-Hung; Yang, Jen-Hung

2014-12-01

In this study, the spectrum of each picture element of the patient’s skin image was obtained by multi-spectral imaging technology. Spectra of normal or pathological skin were collected from 15 patients. Principal component analysis and principal component scores of skin spectra were employed to distinguish the spectral characteristics with different diseases. Finally, skin regions with suspected cutaneous T-cell lymphoma (CTCL) lesions were successfully predicted by evaluation and classification of the spectra of pathological skin. The sensitivity and specificity of this technique were 89.65% and 95.18% after the analysis of about 109 patients. The probability of atopic dermatitis and psoriasis patients misinterpreted as CTCL were 5.56% and 4.54%, respectively.

Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial.

PubMed

Bruggink, Sjoerd C; Gussekloo, Jacobijn; Berger, Marjolein Y; Zaaijer, Krista; Assendelft, Willem J J; de Waal, Margot W M; Bavinck, Jan Nico Bouwes; Koes, Bart W; Eekhof, Just A H

2010-10-19

Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach. Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks. Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%-51%) in the cryotherapy group, 24% (95% CI 16%-35%) in the salicylic acid group and 16% (95% CI 9.5%-25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%-64%) in the cryotherapy group, 15% (95% CI 7%-30%) in the salicylic acid group and 8% (95% CI 3%-21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups. For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629).

Cutaneous sarcoidosis.

PubMed

Noe, Megan H; Rosenbach, Misha

2017-09-01

Cutaneous sarcoidosis occurs in up to 30% of patients with sarcoidosis and skin findings are often the initial presenting symptom. Cutaneous sarcoidosis is a rare skin disease and many aspects of the disease presentation and treatment are not well understood. This review will highlight developments in the epidemiology, clinical presentation, diagnosis and treatment of cutaneous sarcoidosis over the past several years. Epidemiological studies from several different populations reaffirm that cutaneous sarcoidosis is more common in women and is often the presenting symptom of systemic sarcoidosis. Recently, more cases are being reported in association with oncologic immune modulators, which will be of great interest as use of those agents increases. Also, ultrasound has shown promise for the imaging of cutaneous granulomas for disease assessment and measuring response to treatment. Finally, the treatment of cutaneous sarcoidosis remains difficult and is based largely on retrospective data with a paucity of large, prospective trials. There have been recently introduced and validated cutaneous scoring tools which show promise and may lead to more high-quality studies going forward. The recent developments in cutaneous sarcoidosis have identified many new pharmacologic and physical triggers of disease, but the evidence for effective treatment is still lacking. Further research is necessary to improve the care of patients with cutaneous sarcoidosis.

[Survival after cutaneous metastasis: a study of 200 cases].

PubMed

Schoenlaub, P; Sarraux, A; Grosshans, E; Heid, E; Cribier, B

2001-12-01

Cutaneous metastatic disease is uncommon and the outcome after cutaneous metastasis has rarely been thoroughly studied. The objective of this work was to study the survival after diagnosis of cutaneous metastasis in a large series of patients and to evaluate survival according to the type of cancer. This retrospective study was conducted out in the Laboratoire d'Histo-pathologie Cutanée of Strasbourg. Between 1950 to 1996, 228 patients with cutaneous metastasis were diagnosed on the basis of typical histopathology, confirmed by two dermatopathologists. We excluded lymphoma or leukaemia with secondary skin involvement. Medical and demographic data were collected from hospital data, and the "Registre du Cancer du Bas-Rhin". The type of neoplasm, the time of diagnosis of primary cancer and the time of death (or survival at 12/31/1996) was established in 200 patients, 99 men and 101 women with a mean age 62.4 +/- 13 years. We found 64 cases of breast carcinoma, 36 cases of lung carcinoma, 31 cases of melanoma and 69 cases of other cancers. Long term actuarial survival after cutaneous metastasis was calculated using by the Kaplan-Meier method. The median survival after cutaneous metastasis was 6.5 months (mean 22.8 +/- 43.8 months). The mortality rate was 13 p. 100 at 1 month, 48 p. 100 at 6 months and 64.5 p. 100 at 12 months. Median survival was calculated according to the primary neoplasm: breast carcinoma: 13.8 months, melanoma: 13.5 months, lung carcinoma: 2.9 months (36 cases). The outcome of patients with cutaneous metastasis of lung carcinoma was worse than those with melanoma (p < 10(-4)) and breast cancer (p < 10(-4)). Survival after cutaneous metastasis of other cancers could not be compared because of the small size of the subgroups: median survival after cutaneous metastasis of non cutaneous squamous cell carcinoma of the head and neck: 8.8 months (5 cases), cutaneous squamous cell carcinoma: 6.5 months (12 cases), carcinoma of oesophagus: 4.7 months (2

Review of epidemiology, clinical presentation, diagnosis, and treatment of common primary psychiatric causes of cutaneous disease.

PubMed

Krooks, J A; Weatherall, A G; Holland, P J

2018-06-01

Approximately half of all patients presenting to dermatologists exhibit signs and symptoms of psychiatric conditions that are either primary or secondary to cutaneous disease. Because patients typically resist psychiatric consult, dermatologists often are on the front line in evaluating and treating these patients. Accordingly, distinguishing the specific underlying or resulting psychiatric condition is essential for effective treatment. The etiology, epidemiology, clinical presentation, diagnosis, and first-line treatment of specific primary psychiatric causes of dermatologic conditions, including delusional infestation, Morgellons syndrome, olfactory reference syndrome, body dysmorphic disorder, excoriation disorder, trichotillomania, and dermatitis artefacta are discussed here, followed by a discussion of the recommended treatment approach with an overview of the different first-line therapies discussed in this review, specifically cognitive behavioral therapy, atypical antipsychotics, selective serotonin reuptake inhibitors, and tricyclic antidepressants. Included is a guide for dermatologists to use while prescribing these medications.

Primary Cutaneous Mucormycosis Caused by Rhizopus oryzae: A Case Report and Review of Literature.

PubMed

Rodríguez-Lobato, Erika; Ramírez-Hobak, Lourdes; Aquino-Matus, Jorge E; Ramírez-Hinojosa, Juan P; Lozano-Fernández, Víctor H; Xicohtencatl-Cortes, Juan; Hernández-Castro, Rigoberto; Arenas, Roberto

2017-04-01

Mucormycosis is an invasive infection caused by opportunistic fungi. Rhizopus, Lichtheimia, Mucor and Rhizomucor are the most common isolated genera. Primary cutaneous mucormycosis is usually related to traumatic injuries, but immunocompromised cases are associated with underlying conditions such as diabetes mellitus and malignancies. The treatment of choice is surgical debridement and liposomal amphotericin B. We present a 40-year-old male with fever and a painful necrotic lesion on the middle back and history of poorly controlled diabetes mellitus. Rhizopus oryzae was isolated and identified using an internal transcribed spacer regions ITS1 and ITS2. An initial good response to treatment was observed; however, 7 days later a diabetic ketoacidosis due to poor adherence to treatment caused a lethal outcome.

Cutaneous sarcoidosis masquerading as chronic cutaneous lupus erythematosus - case report.

PubMed

Vatanchi, Marjon; Sobhani, Kaivon; Fisher, Valerie T; Meffert, Jeffrey J

2016-09-20

Sarcoidosis is a multisystemic granulomatous disease of unknown origin. Chronic cutaneous lupus erythematosus (CCLE) is an autoimmune disease that is associated with autoantibody production and T-cell dysfunction. Cutaneous manifestations of sarcoidosis may mimic CCLE and vice versa making it difficult to reach a diagnosis clinically. We present a case of a 57-year-old woman with long-standing sarcoidosis who presented to clinic with diffuse painful plaques that were very distinct and suggestive of CCLE. She had a family history of both sarcoidosis and CCLE. The patient was immediately started on topical corticosteroids and oral hydroxychloroquine. Skin biopsy and the absence of direct immunofluorescence confirmed a skin manifestation of her previously diagnosed sarcoidosis, despite the clinical morphology favoring classic CCLE. Sarcoidosis may have diverse manifestations and may mimic other disease processes. A detailed history along with a low threshold for biopsy is important for determining a diagnosis.

Primary Uterine Peripheral T-cell Lymphoma

PubMed Central

Gong, Jing; Dong, Aisheng; Wang, Yang; Zhang, Xuefeng; Yang, Panpan; Wang, Li; Jing, Wei

2016-01-01

Abstract Primary uterine non-Hodgkin's lymphoma is extremely rare accounting for <1% of all extranodal non-Hodgkin's lymphomas. Imaging findings of primary uterine lymphoma have rarely been reported before. We present magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a patient with primary uterine peripheral T-cell lymphoma. A 27-year-old female presented with intermittent fever with neutropenia for 7 months. MRI showed an ill-defined mass involved both the uterine corpus and cervix, resulting in diffuse enlargement of the uterus. This mass showed inhomogeneous hypointensity on unenhanced T1-weighted images, hyperintensity on diffusion-weighted imaging, relative hypointensity compared to the surrounding myometrium on T2-weighted images and lower enhancement than the surrounding myometrium on enhanced T1-weighted images. FDG PET/CT showed intense FDG uptake in the thickened wall of the uterine corpus and cervix with SUVmax of 26.9. There were multiple hypermetabolic lymph nodes in the pelvis and retroperitoneum. Uterine curettage and CT-guided biopsy of the uterine mass revealed peripheral T-cell lymphoma. Bone marrow biopsy revealed no evidence of lymphomatous involvement. The imaging and pathologic findings were consistent with primary uterine lymphoma. After 3 circles of chemotherapy, follow-up enhanced MRI showed decreased thickness of the uterine wall. Despite its rarity, primary uterine non-Hodgkin's lymphoma should be taken into consideration when a uterine tumor shows large size, relative hypointesity on both T2-weighted images and enhanced T1-weighted images compared to the surrounding myometrium, and intense FDG uptake on PET/CT. MRI may be helpful for describing the relationship between the tumor and adjacent structures. FDG PET/CT may be useful for tumor detection and staging. PMID:27124063

Vaccines and vaccination strategies against human cutaneous leishmaniasis.

PubMed

Okwor, Ifeoma; Uzonna, Jude

2009-05-01

One might think that the development of a vaccine against cutaneous leishmaniasis would be relatively straightforward because the type of immune response required for protection is known and natural immunity occurs following recovery from primary infection. However, there is as yet no effective vaccine against the disease in humans. Although vaccination in murine studies has yielded promising results, these vaccines have failed miserably when tested in primates or humans. The reasons behind these failures are unknown and remain a major hurdle for vaccine design and development against cutaneous leishmaniasis. In contrast, recovery from natural, deliberate or experimental infections results in development of long-lasting immunity to re-infection. This so called infection-induced resistance is the strongest anti-Leishmania immunity known. Here, we briefly review the different approaches to vaccination against cutaneous leishmaniasis and argue that vaccines composed of genetically modified (attenuated) parasites, which induce immunity akin to infection-induced resistance, may provide best protection against cutaneous leishmaniasis in humans.

Cutaneous plasmacytosis: A rare entity with unique presentation.

PubMed

Dhar, Subhra; Liani, Lalthleng; Patole, Kamlakar; Dhar, Sandipan

2017-01-01

Primary cutaneous plasmacytosis is a rare cutaneous disorder with extensive cutaneous plaques/papules mainly on the trunk and face. Cases have mostly been documented from Japan. We present here a rare case of cutaneous plasmacytosis from India of Mongolian descent. This 50-year-old female from Mizoram had extensive maculo-papular violaceous plaques distributed on the face, axillae, trunk and lower extremities. Initial and repeat skin biopsy revealed dense perivascular and periadnexal mature plasma cells. She also had lymphadenopathy. Serum protein electrophoresis did not reveal any M band and the Bence Jones protein was negative in urine. The patient had multiple superficial lymph nodes and a biopsy from the cervical lymph node showed effacement of normal nodal architecture by sheets of plasma cells. Immuno histochemistry was done from both skin and lymph node biopsies. The kappa and lambda tight chains were not restricted; there by proving the polyclonal nature of the plasma cells. The novelty of the case lies in its classical clinical presentation with histopathological documentation.

Review of immunomodulation by photopheresis: treatment of cutaneous T-cell lymphoma, autoimmune disease, and allograft rejection.

PubMed

Wolfe, J T; Lessin, S R; Singh, A H; Rook, A H

1994-12-01

Photopheresis is an apheresis-based therapy that is currently available at approximately 70 medical centers worldwide. Recent evidence indicates that extracorporeal photopheresis can significantly prolong life as well as induce a 60-75% response rate among individuals with advanced cutaneous T-cell lymphoma (CTCL). Moreover, a 10-15% cure rate, in response to photopheresis alone, or in combination with interferon-alpha, has been obtained at our institution. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. Southern blot analysis of peripheral blood specimens has also confirmed the indefinite disappearance of the malignant T-cell clone from the blood of patients with complete responses. Current immunological data obtained from in vitro human studies and from animal models suggest that the basis for the responses of CTCL patients are related to activation of treated macrophages resulting in release of cytokines, including substantial levels of tumor necrosis factor alpha (TNF-alpha), and perhaps, to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. In addition to the treatment of CTCL, a potential role for photopheresis in the therapy of autoimmune disease has been suggested by recent pilot studies of pemphigus vulgaris, rheumatoid arthritis, and systemic lupus erythematosus. Furthermore, a randomized, single-blinded trial involving 79 patients with early onset, aggressive systemic sclerosis suggested that photopheresis could benefically affect the course of the cutaneous thickening in this form of the disease. Lastly, two independent pilot studies of cardiac transplantation have indicated that photopheresis can reverse acute cardiac allograft rejection and potentially suppress ongoing chronic rejection. Randomized, controlled trials for these new indications for photopheresis therapy are currently in the early stages of implementation.

ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project.

PubMed

Savage, Kerry J; Harris, Nancy Lee; Vose, Julie M; Ullrich, Fred; Jaffe, Elaine S; Connors, Joseph M; Rimsza, Lisa; Pileri, Stefano A; Chhanabhai, Mukesh; Gascoyne, Randy D; Armitage, James O; Weisenburger, Dennis D

2008-06-15

The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-) ALCL (5-year failure-free survival [FFS], 60% vs 36%; P = .015; 5-year overall survival [OS], 70% vs 49%; P = .016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P = .012) and OS (49% vs 32%; P = .032) were superior for ALK(-) ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-) ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course.

Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.

PubMed

Prince, H Miles; Kim, Youn H; Horwitz, Steven M; Dummer, Reinhard; Scarisbrick, Julia; Quaglino, Pietro; Zinzani, Pier Luigi; Wolter, Pascal; Sanches, Jose A; Ortiz-Romero, Pablo L; Akilov, Oleg E; Geskin, Larisa; Trotman, Judith; Taylor, Kerry; Dalle, Stephane; Weichenthal, Michael; Walewski, Jan; Fisher, David; Dréno, Brigitte; Stadler, Rudolf; Feldman, Tatyana; Kuzel, Timothy M; Wang, Yinghui; Palanca-Wessels, Maria Corinna; Zagadailov, Erin; Trepicchio, William L; Zhang, Wenwen; Lin, Hui-Min; Liu, Yi; Huebner, Dirk; Little, Meredith; Whittaker, Sean; Duvic, Madeleine

2017-08-05

Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m 2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499. Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62

[Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

PubMed

Stranzenbach, R; Theurich, S; Schlaak, M

2017-09-01

Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

Cutaneous Adverse Effects of Neurologic Medications.

PubMed

Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

2016-03-01

Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy.

PubMed

Fox, Lucy C; Yannakou, Costas K; Ryland, Georgina; Lade, Stephen; Dickinson, Michael; Campbell, Belinda A; Prince, Henry Miles

2018-06-13

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11 -activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB) negative regulator, NFKBIE . In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus), representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

Cryotherapy with liquid nitrogen versus topical salicylic acid application for cutaneous warts in primary care: randomized controlled trial

PubMed Central

Bruggink, Sjoerd C.; Gussekloo, Jacobijn; Berger, Marjolein Y.; Zaaijer, Krista; Assendelft, Willem J.J.; de Waal, Margot W.M.; Bavinck, Jan Nico Bouwes; Koes, Bart W.; Eekhof, Just A.H.

2010-01-01

Background Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach. Methods Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks. Results Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%–51%) in the cryotherapy group, 24% (95% CI 16%–35%) in the salicylic acid group and 16% (95% CI 9.5%–25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%–64%) in the cryotherapy group, 15% (95% CI 7%–30%) in the salicylic acid group and 8% (95% CI 3%–21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups. Interpretation For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629) PMID:20837684

Primary cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome and Sjögren syndrome

PubMed Central

Yan, Xin; Jin, Jinglan

2018-01-01

Abstract Rationale: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. Patient concerns: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department. Diagnoses: Due to the patient's symptoms, laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS. Interventions: She was subsequently treated with a combination of ursodeoxycholic acid (UDCA), prednisone, and azathioprine. Outcomes: While this treatment can achieve therapeutic success, it cannot prevent complications from cirrhosis. This patient remains alive but experienced an emergent gastrointestinal hemorrhage. Lessons: While we acknowledge that this is a single case, these findings extend our knowledge of immunological diseases associated with PCA and suggest a common, immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS. After 12 years of follow up, clinical manifestations have developed, and these autoimmune diseases have progressed. The combination of UDCA, prednisone, and azathioprine can achieve therapeutic success but cannot prevent disease progression. Routine follow up for this patient is necessary to document disease progression. PMID:29465536

Cutaneous Sensibility Changes in Bell's Palsy Patients.

PubMed

Cárdenas Palacio, Carlos Andrés; Múnera Galarza, Francisco Alejandro

2017-05-01

Objective Bell's palsy is a cranial nerve VII dysfunction that renders the patient unable to control facial muscles from the affected side. Nevertheless, some patients have reported cutaneous changes in the paretic area. Therefore, cutaneous sensibility changes might be possible additional symptoms within the clinical presentation of this disorder. Accordingly, the aim of this research was to investigate the relationship between cutaneous sensibility and facial paralysis severity in these patients. Study Design Prospective longitudinal cohort study. Settings Tertiary care medical center. Subjects and Methods Twelve acute-onset Bell's palsy patients were enrolled from March to September 2009. In addition, 12 sex- and age-matched healthy volunteers were tested. Cutaneous sensibility was evaluated with pressure threshold and 2-point discrimination at 6 areas of the face. Facial paralysis severity was evaluated with the House-Brackmann scale. Results Statistically significant correlations based on the Spearman's test were found between facial paralysis severity and cutaneous sensitivity on forehead, eyelid, cheek, nose, and lip ( P < .05). Additionally, significant differences based on the Student's t test were observed between both sides of the face in 2-point discrimination on eyelid, cheek, and lip ( P < .05) in Bell's palsy patients but not in healthy subjects. Conclusion Such results suggest a possible relationship between the loss of motor control of the face and changes in facial sensory information processing. Such findings are worth further research about the neurophysiologic changes associated with the cutaneous sensibility disturbances of these patients.

Primary Cutaneous Adenoid Cystic Carcinoma with MYB aberrations, report of three cases and comprehensive review of the literature

PubMed Central

Prieto-Granada, Carlos N.; Zhang, Lei; Antonescu, Cristina; Henneberry, Jean; Messina, Jane

2017-01-01

Adenoid cystic carcinoma (ACC) is a relatively rare slow growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22–23;p23–24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report 3 additional cases of PCACC harboring MYB aberrations. The tumors presented in 3 males aged 43, 81 and 55 years old and affected the extremities in the first 2 patients and the scalp in the third one. None of the patients had history of prior or concurrent ACC elsewhere. Lesions exhibited the classic ACC morphology of nests of basaloid cells arranged in cribriform and adenoid patterns. Sentinel lymph node biopsy was performed in two cases with one case showing lymph node positivity. Fluorescence in situ hybridization with break-apart probes for MYB and NFIB loci revealed that 2 cases showed MYB rearrangements while one case showed loss of one MYB signal. None of the cases showed NFIB rearrangements. We contribute with 3 additional cases of PCACC exhibiting MYB aberrations, the apparent driving genetic abnormality in these tumors. PMID:27859477

Cellular requirements for cutaneous sensitivity elicitation.

PubMed

Aoki, I

1985-01-01

The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

Deep tissue afferents, but not cutaneous afferents, mediate transcutaneous electrical nerve stimulation-Induced antihyperalgesia.

PubMed

Radhakrishnan, Rajan; Sluka, Kathleen A

2005-10-01

In this study we investigated the involvement of cutaneous versus knee joint afferents in the antihyperalgesia produced by transcutaneous electrical nerve stimulation (TENS) by differentially blocking primary afferents with local anesthetics. Hyperalgesia was induced in rats by inflaming one knee joint with 3% kaolin-carrageenan and assessed by measuring paw withdrawal latency to heat before and 4 hours after injection. Skin surrounding the inflamed knee joint was anesthetized using an anesthetic cream (EMLA). Low (4 Hz) or high (100 Hz) frequency TENS was then applied to the anesthetized skin. In another group, 2% lidocaine gel was injected into the inflamed knee joint, and low or high frequency TENS was applied. Control experiments were done using vehicles. In control and EMLA groups, both low and high frequency TENS completely reversed hyperalgesia. However, injection of lidocaine into the knee joint prevented antihyperalgesia produced by both low and high frequency TENS. Recordings of cord dorsum potentials showed that both low and high frequency TENS at sensory intensity activates only large diameter afferent fibers. Increasing intensity to twice the motor threshold recruits Adelta afferent fibers. Furthermore, application of EMLA cream to the skin reduces the amplitude of the cord dorsum potential by 40% to 70% for both high and low frequency TENS, confirming a loss of large diameter primary afferent input after EMLA is applied to the skin. Thus, inactivation of joint afferents, but not cutaneous afferents, prevents the antihyperalgesia effects of TENS. We conclude that large diameter primary afferent fibers from deep tissue are required and that activation of cutaneous afferents is not sufficient for TENS-induced antihyperalgesia. Transcutaneous electrical nerve stimulation (TENS) is an accepted clinical modality used for pain relief. It is generally believed that TENS analgesia is caused mainly by cutaneous afferent activation. In this study by

Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

PubMed

Doherty, Sarah M; Jackman, Louise M; Kirwan, John F; Dunne, Deirdre; O'Connor, Kieran G; Rouse, John M

2016-12-01

The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma].

PubMed

Delaplace, M; Mélard, P; Perrinaud, A; Goré, C; Vergier, B; Machet, L

2011-05-01

Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

[Prognostic influence of cutaneous involvement in malignant tumors of the oral cavity].

PubMed

Tankéré, F; Camproux, A; Barry, B; Guedon, C; Depondt, J; Gehanno, P

2000-03-01

The aim of this study was to assess the prognostic influence of cutaneous involvement in T4 squamous cell carcinoma of the oral cavity. The population was a homogeneous group of 137 patients. Cutaneous tumor localizations were observed in 20 of them. Surgery and radiotherapy were given in 103 cases and salvage surgery was performed in 34. Local control at 5 years was achieved in 68.5 % of the patients. Carcinologic failure rate was 55 % and 27.3 % in patients with and without cutaneous involvement respectively (p =0. 013). 5-year survivor rate was also correlated with cutaneous involvement: 10 % versus 32.2 % (p <0.0001).

Role for Lyt-2+ T cells in resistance to cutaneous leishmaniasis in immunized mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrell, J.P.; Muller, I.; Louis, J.A.

1989-03-15

The role of Lyt-2+ T cells in immunologic resistance to cutaneous leishmaniasis was analyzed by comparing infection patterns in resistant C57BL/6 mice and susceptible BALB/c mice induced to heal their infections after sub-lethal irradiation or i.v. immunization, with similar mice treated in vivo with anti-Lyt-2 antibodies. Administration of anti-Lyt-2 mAb resulted in a dramatic reduction in the number of lymphoid cells expressing the Lyt-2+ phenotype. Such treatment led to enhanced disease in both resistant C57BL/6 and irradiated BALB/c mice, as assessed by lesion size, but did not affect the capacity of these mice to ultimately resolve their infections. In contrast,more » anti-Lyt-2 treatment totally blocked the induction of resistance in i.v. immunized mice. These results suggest, that Lyt-2+ T cells may play a role in immunity to a Leishmania major infection and that their relative importance to resistance may depend on how resistance is induced.« less

A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.

PubMed

Ikebuchi, Ryoyo; Teraguchi, Shunsuke; Vandenbon, Alexis; Honda, Tetsuya; Shand, Francis H W; Nakanishi, Yasutaka; Watanabe, Takeshi; Tomura, Michio

2016-10-19

Foxp3 + regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43 + CCR5 + Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43 + CCR5 + CXCR3 - Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.

Metastatic pathways in patients with cutaneous melanoma.

PubMed

Adler, Nikki R; Haydon, Andrew; McLean, Catriona A; Kelly, John W; Mar, Victoria J

2017-01-01

Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Familial cases of cutaneous myxomas and spotty pigmentation (Carney's complex)].

PubMed

Koyano, T; Satoh, T; Ohtaki, N

1990-09-01

In 1985, Carney et al reported a complex of myxomas, spotty pigmentation, and endocrine overactivity and subsequently demonstrated dominant inheritance of the condition. The criteria for diagnosis of the complex is the presence of two or more of the following conditions: (1) cardiac myxoma, (2) cutaneous myxoma, (3) mammary myxoma, (4) spotty mucocutaneous pigmentation, (5) primary pigmented nodular adrenocortical disease (Cushing's syndrome), (6) testicular tumors (sexual precocity), (7) pituitary adenoma secreting growth hormone (acromegaly or gigantism). We encountered a family with an affected mother and daughter. Case 1 was a 43-year-old woman with multiple cutaneous myxomas, mammary myxomas and spotty mucocutaneous pigmentation. Case 2, the 19-year-old daughter of case 1 had multiple cutaneous myxomas and spotty cutaneous pigmentation. These two cases both met the criteria for the diagnosis of the complex. Our report is believed to be the first report on the complex in Japan.

Intravascular NK/T-cell lymphoma: a report of five cases with cutaneous manifestation from China.

PubMed

Wang, Lei; Chen, Siyuan; Ma, Han; Shi, Dongmei; Huang, Changzheng; Lu, Chun; Gao, Tianwen; Wang, Gang

2015-09-01

Intravascular lymphoma is a rare type of lymphoma that frequently affects the skin and is usually of B-cell origin. This lymphoma type is very rare and not recognized as a separate entity in the 2008 World Health Organization classification of hematopoietic and lymphoid tissue tumors. We reported five cases of intravascular NK/T cell lymphoma with cutaneous manifestation and reviewed 12 published cases involving Chinese patients with similar characteristics. All five patients were adults who exhibited red or brown patches or plaques on the lower extremities or trunk; four cases were associated with B symptoms; one case developed subsequent to a lymphoma on the face (possibly extranodal NK/T cell lymphoma, nasal type). Histopathologically, all patients exhibited abnormal, medium-sized intravascular lymphocytes in the dermis and subcutaneous tissues. All patients were positive for CD2, CD3ϵ, CD56 and cytotoxic proteins. All cases were Epstein-Barr virus (EBV) positive. Four of FIVE patients died of lymphoma within a few months of diagnosis. Intravascular NK/T-cell lymphoma is a rare highly aggressive and EBV-associated lymphoma that is prone to develop in Chinese patients. The relationship between intravascular NK/T-cell lymphoma and extranodal NK/T-cell lymphoma, nasal type, requires clarification. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutaneous perivascular epithelioid cell tumors: A review on an infrequent neoplasm

PubMed Central

Llamas-Velasco, Mar; Requena, Luis; Mentzel, Thomas

2016-01-01

“Perivascular epithelioid cutaneous” cell tumors (PEComa) are a family of mesenchymal tumors with shared microscopic and immunohistochemical properties: They exhibit both smooth muscle cell and melanocytic differentiation. Non-neoplastic counterpart of PEComa’s cells are unknown, as well as the relationship between extracutaneous PEComa and primary cutaneous ones. We will review the clinical setting, histopathologic features, chromosomal abnormalities, differential diagnosis and treatment options for cutaneous PEComa. PMID:27019799

Oral and Cutaneous Lymphomas other than Mycosis Fungoides and Sézary Syndrome in a Mexican Cohort: Recategorization and Evaluation of International Geographical Disparities

PubMed Central

Hernández-Salazar, Amparo; García-Vera, Jorge Andrés; Charli-Joseph, Yann; Ortiz-Pedroza, Guadalupe; Méndez-Flores, Silvia; Orozco-Topete, Rocío; Morales-Leyte, Ana Lilia; Domínguez-Cherit, Judith; Lome-Maldonado, Carmen

2017-01-01

Background: Nonmycosis fungoides/Sézary syndrome (non-MF/SS) primary cutaneous lymphomas (PCL) are currently categorized under the 2005-World Health Organization/European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for PCL. These differ in behavior from secondary cutaneous lymphomas (SCL) and to lymphomas limited to the oral cavity (primary oral lymphomas [POL]) both categorized under the 2016-WHO classification for lymphoid neoplasms. Aims: This study aims to report the first series of non-MF/SS PCL, SCL, and POL in a Mexican cohort, examine the applicability of current classification systems and compare our findings with those from foreign cohorts. Materials and Methods: Eighteen non-MF/SS PCL, four SCL, and two POL with available tissue for morphology and immunophenotypic assessment were reclassified according to the 2005-WHO/EORTC and 2016-WHO classifications. Results: Non-MF/SS PCLs were primarily of T-cell origin (61%) where CD30+ lymphoproliferative disorders predominated, followed by Epstein–Barr virus-induced lymphomas, and peripheral T-cell lymphomas, not otherwise specified. Primary cutaneous B-cell lymphomas (BCL) were primarily of follicle center cell origin followed by postgerminal lymphomas of the diffuse large BCL variety. Conclusions: Most non-MF/SS PCL, SCL, and POL can be adequately categorized according to the 2005-WHO/EORTC and 2016-WHO classification systems, even when dealing with clinically atypical cases. The relative frequencies in our cohort hold closer similarities to Asian registries than from those of Europe/USA, supporting the concept of individual and/or racial susceptibility, and the notion of geographical variances in the rate of lymphomas. In particular, such disparity may arise from viral-induced lymphomas which might show partial geographical restriction. PMID:28400635

Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.

PubMed

van Doorn, Remco; Zoutman, Willem H; Dijkman, Remco; de Menezes, Renee X; Commandeur, Suzan; Mulder, Aat A; van der Velden, Pieter A; Vermeer, Maarten H; Willemze, Rein; Yan, Pearlly S; Huang, Tim H; Tensen, Cornelis P

2005-06-10

To analyze the occurrence of promoter hypermethylation in primary cutaneous T-cell lymphoma (CTCL) on a genome-wide scale, focusing on epigenetic alterations with pathogenetic significance. DNA isolated from biopsy specimens of 28 patients with CTCL, including aggressive CTCL entities (transformed mycosis fungoides and CD30-negative large T-cell lymphoma) and an indolent entity (CD30-positive large T-cell lymphoma), were investigated. For genome-wide DNA methylation screening, differential methylation hybridization using CpG island microarrays was applied, which allows simultaneous detection of the methylation status of 8640 CpG islands. Bisulfite sequence analysis was applied for confirmation and detection of hypermethylation of eight selected tumor suppressor genes. The DNA methylation patterns of CTCLs emerging from differential methylation hybridization analysis included 35 CpG islands hypermethylated in at least four of the 28 studied CTCL samples when compared with benign T-cell samples. Hypermethylation of the putative tumor suppressor genes BCL7a (in 48% of CTCL samples), PTPRG (27%), and thrombospondin 4 (52%) was confirmed and demonstrated to be associated with transcriptional downregulation. BCL7a was hypermethylated at a higher frequency in aggressive (64%) than in indolent (14%) CTCL entities. In addition, the promoters of the selected tumor suppressor genes p73 (48%), p16 (33%), CHFR (19%), p15 (10%), and TMS1 (10%) were hypermethylated in CTCL. Malignant T cells of patients with CTCL display widespread promoter hypermethylation associated with inactivation of several tumor suppressor genes involved in DNA repair, cell cycle, and apoptosis signaling pathways. In view of this, CTCL may be amenable to treatment with demethylating agents.

Staging studies for cutaneous melanoma in the United States: a population-based analysis.

PubMed

Wasif, Nabil; Etzioni, David; Haddad, Dana; Gray, Richard J; Bagaria, Sanjay P; Pockaj, Barbara A

2015-04-01

Routine cross-sectional imaging for staging of early-stage cutaneous melanoma is not recommended. This study sought to investigate the use of imaging for staging of cutaneous melanoma in the United States. Patients with nonmetastatic cutaneous melanoma newly diagnosed between 2000 and 2007 were identified from the Surveillance Epidemiology End Results-Medicare registry. Any imaging study performed within 90 days after diagnosis was considered a staging study. The study identified 25,643 patients, 3,116 (12.2 %) of whom underwent cross-sectional imaging: positron emission tomography (PET) (7.2 %), computed tomography (CT) (5.9 %), and magnetic resonance imaging (MRI) (0.6 %). From 2000 to 2007, the use of cross-sectional imaging increased from 8.7 to 16.1 % (p < 0.001), driven predominantly by increased usage of PET (4.2-12.1 %). Stratification by T and N classification showed that cross-sectional imaging was used for 8.6 % of T1, 14.3 % of T2, 18.6 % of T3, and 26.7 % of T4 tumors (p < 0.001) and for 33.3 % of node-positive patients versus 11.1 % of node-negative patients (p < 0.001). Factors predictive of cross-sectional imaging included T classification [odds ratio (OR) for T4 vs T1, 2.66; 95 % confidence interval (CI) 2.33-3.03], node positivity (OR 2.70; 95 % CI 2.36-3.10), more recent year of diagnosis (OR 2.05 for 2007 vs 2000; 95 % CI 1.74-2.42), atypical histology, and non-Caucasian race (OR 1.32; 95 % CI 1.02-1.73). The use of cross-sectional imaging for staging of early-stage cutaneous melanoma is increasing in the Medicare population. Better dissemination of guidelines and judicious use of imaging should be encouraged.

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

PubMed

Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

2018-01-01

While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and

Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

PubMed

Toberer, Ferdinand; Enk, Alexander; Hartschuh, Wolfgang; Grüllich, Carsten

2018-07-01

A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea; the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of cutaneous scalp tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutaneous applications of lasers.

PubMed

Ries, W R; Speyer, M T

1996-12-01

The cutaneous application of lasers today includes more selective and less damaging devices. Carbon dioxide, neodymium:yttrium-aluminum-garnet, potassium titanyl phosphate, argon, and yellow lasers are most prevalent in treating cutaneous lesions. Specific techniques in skin resurfacing, keloid excision, rhinophyma, actinic cheilitis ablation, and excision of superficial cutaneous tumors are discussed. Proper management of cutaneous vascular lesions is also presented.

Role of Synchrotron infra red microspectroscopy in studying epidermotropism of cutaneous T-cell lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

El Bedewi, A.; El Anany, G; El Mofty, M

2010-01-01

The molecular mechanisms of epidermotropism in mycosis fungoides (MF) are not well understood to date. The aim of this study was to differentiate between epidermal and dermal lymphocytes within the skin of MF patients. This study was done on 10 MF patients with a mean age of 50 years diagnosed clinically in the Department of Dermatology, Cairo University, Egypt. A 6 mm biopsy was taken from each patient in order to confirm the diagnosis. Skin biopsies were cut, put on low e-slides and then stained with H&E. Further examination with Synchrotron infrared (IR) microspectroscopy was done in National Synchrotron Lightmore » Source - Brookhaven National Laboratory, New York, USA. Immunophenotyping using antibodies CD3, CD4, CD8, CD20 and CD30 was also done. Statistical analysis was done by Student's t-test and cluster analysis. Both epidermal and dermal lymphocytes were clustered separately. Also, Amide I and RNA and DNA within the lymphocytes were significantly different between the epidermis and the dermis. The biochemical analysis of protein, RNA and DNA with Synchrotron IR microspectroscopy is a promising tool for studying epidermotropism in cutaneous T-cell lymphoma.« less

Cutaneous metastasis: clinicopathological study of 72 patients from a tertiary care center in Lebanon.

PubMed

El Khoury, Jinane; Khalifeh, Ibrahim; Kibbi, Abdul-Ghani; Abbas, Ossama

2014-02-01

Cutaneous metastasis is the result of malignant cell spread from primary malignancy to the skin. This is not uncommon, and rates reported in the literature are as high as 10.4%. To the best of our knowledge, there are no studies assessing the epidemiologic, clinical, and histopathological features of cutaneous metastasis in our region. To assess the clinical and histopathological findings of all patients diagnosed with cutaneous metastasis at the American University of Beirut - Medical Center (AUB-MC) and to compare our findings with those published in the literature. Retrospective clinical and histopathologic evaluation of all cases diagnosed as cutaneous metastasis at AUB-MC between 1992 and 2010. A total of 72 patients (50 females and 22 males) were identified. The mean age at diagnosis was 55.2 years. The most common primary cancer was breast cancer in women and laryngeal cancer in men. The most common clinical presentation was a single nodule in 27% of cases followed by multiple nodules in 23%. Cutaneous metastasis lesions were asymptomatic in the majority. The chest was the most commonly affected site. On microscopy, the majority of metastatic cases were adenocarcinomas (74%). This is, to our knowledge, the first study characterizing the epidemiological, clinical, and histopathological features of cutaneous metastasis in the Lebanese population. The clinical and histopathological features observed were in concordance with the published literature, with minor differences. © 2013 The International Society of Dermatology.

Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen.

PubMed Central

Abernathy-Carver, K J; Sampson, H A; Picker, L J; Leung, D Y

1995-01-01

The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding. Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively. This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen. Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk. All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk. 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls. Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans. After in vitro stimulation with casein, but not C. albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 0.01) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls. In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups. These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement. We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses. Images PMID:7532192

Milk-induced eczema is associated with the expansion of T cells expressing cutaneous lymphocyte antigen.

PubMed

Abernathy-Carver, K J; Sampson, H A; Picker, L J; Leung, D Y

1995-02-01

The extravasation of T cells at sites of inflammation is critically dependent on the activity of homing receptors (HR) involved in endothelial cell recognition and binding. Two such HR (the cutaneous lymphocyte antigen [CLA] and L-selectin) have been shown to be selectively involved in T cell migration to skin and peripheral lymph nodes, respectively. This study was designed to assess the relationship between the organ specificity of an allergic reaction to food and the expression of HR on T cells activated in vitro by the relevant food allergen. Peripheral blood mononuclear cells were isolated from seven milk allergic children with a history of eczema when exposed to milk. All patients had a positive prick skin test and double-blind placebo-controlled food challenge to milk. 10 children with either allergic eosinophilic gastroenteritis or milk-induced enterocolitis and 8 nonatopic adults served as controls. Five-parameter flow cytometry using monoclonal antibodies was used for detection of the specific HR on freshly isolated T cells versus T cell blasts induced by a 6-d incubation with casein, as compared with Candida albicans. After in vitro stimulation with casein, but not C. albicans, patients with milk allergy and atopic dermatitis had a significantly greater percentage of CLA+ T cells (P < 0.01) than controls with milk-induced enterocolitis, allergic eosinophilic gastroenteritis, or nonatopic healthy controls. In contrast, the percentage of L-selectin-expressing T cells did not differ significantly between these groups. These data suggest that after casein stimulation allergic patients with milk-induced skin disease have an expanded population of CLA+ T cells, as compared with nonatopics or allergic patients without skin involvement. We postulate that heterogeneity in the regulation of HR expression on antigen-specific T cells may play a role in determining sites of involvement in tissue-directed allergic responses.

Tripartite differentiation (squamous, glandular, and melanocytic) of a primary cutaneous neuroendocrine carcinoma. An immunocytochemical and ultrastructural study.

PubMed

Isimbaldi, G; Sironi, M; Taccagni, G; Declich, P; Dell'Antonio, A; Galli, C

1993-06-01

We report a case of primary cutaneous neuroendocrine carcinoma (PCNEC) with squamous, glandular, and melanocytic differentiation and associated Bowen disease. The paranuclear globular positivity of low-molecular-weight cytokeratins agrees with the ultrastructural observations of paranuclear fibrous bodies in the small neuroendocrine cells, while the diffuse cytoplasmic positivity corresponds to the sparse intermediate filaments in large cells with squamous differentiation. "Transitional forms" are characterized by both diffuse and globular cytoplasmic positivity for cytokeratins and by the ultrastructural evidence of neuroendocrine and squamous features. Therefore the ultrastructural demonstration of intracytoplasmic tonofibrils and tonofilaments, intercellular glandular lumina, lined by well-formed microvilli, and immature premelanosomes in the neurosecretory cells supports the proposed tripartite differentiation of neuroendocrine cells of this case of PCNEC.

Cutaneous Pseudolymphomas.

PubMed

Romero-Pérez, D; Blanes Martínez, M; Encabo-Durán, B

2016-10-01

The term cutaneous pseudolymphoma refers to benign reactive lymphoid proliferations in the skin that simulate cutaneous lymphomas. It is a purely descriptive term that encompasses various reactive conditions with a varied etiology, pathogenesis, clinical presentation, histology, and behavior. We present a review of the different types of cutaneous pseudolymphoma. To reach a correct diagnosis, it is necessary to contrast clinical, histologic, immunophenotypic, and molecular findings. Even with these data, in some cases only the clinical course will confirm the diagnosis, making follow-up essential. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease.

PubMed

Brüggen, Marie-Charlotte; Klein, Irene; Greinix, Hildegard; Bauer, Wolfgang; Kuzmina, Zoya; Rabitsch, Werner; Kalhs, Peter; Petzelbauer, Peter; Knobler, Robert; Stingl, Georg; Stary, Georg

2014-01-09

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HCT) and can present in an acute (aGVHD), a chronic lichenoid (clGVHD), and a chronic sclerotic form (csGVHD). It is unclear whether similar or different pathomechanisms lead to these distinct clinical presentations. To address this issue, we collected lesional skin biopsies from aGVHD (n = 25), clGVHD (n = 17), and csGVHD (n = 7) patients as well as serial nonlesional biopsies from HCT recipients (prior to or post-HCT) (n = 14) and subjected them to phenotypic and functional analyses. Our results revealed striking differences between aGVHD and clGVHD. In aGVHD, we found a clear predominance of T helper (Th)2 cytokines/chemokines and, surprisingly, of interleukin (IL)-22 messenger RNA as well as an increase of IL-22-producing CD4(+) T cells. Thymic stromal lymphopoietin, a cytokine skewing the immune response toward a Th2 direction, was elevated at day 20 to 30 post-HCT in the skin of patients who later developed aGVHD. In sharp contrast to aGVHD, the immune response occurring in clGVHD showed a mixed Th1/Th17 signature with upregulated Th1/Th17 cytokine/chemokine transcripts and elevated numbers of interferon-γ- and IL-17-producing CD8(+) T cells. Our findings shed new light on the T-cell responses involved in the different manifestations of cutaneous GVHD and identify molecular signatures indicating the development of the disease.

Cutaneous Cryptococcus laurentii infection in an immunocompetent child.

PubMed

Molina-Leyva, Alejandro; Ruiz-Carrascosa, Jose C; Leyva-Garcia, Ana; Husein-Elahmed, Husein

2013-12-01

Cryptococcus laurentii is an extremely rare human pathogen. We report a case of primary cutaneous cryptococcosis caused by Cryptococcus laurentii in an immunocompetent patient, an 8-year-old child with a solitary lesion on the forearm. It was impossible to determine the source of infection and no predisposing factors were found. Oral treatment with fluconazole was totally successful. A review of the literature showed only three cases of cutaneous infection by Cryptococcus laurentii. All of the cases occurred in immunocompromised patients. To the best of our knowledge, this is the first case of Cryptococcus laurentii in an immunocompetent host. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Utilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.

PubMed

Tavera, René J; Forget, Marie-Andrée; Kim, Young Uk; Sakellariou-Thompson, Donastas; Creasy, Caitlin A; Bhatta, Ankit; Fulbright, Orenthial J; Ramachandran, Renjith; Thorsen, Shawne T; Flores, Esteban; Wahl, Arely; Gonzalez, Audrey M; Toth, Christopher; Wardell, Seth; Mansaray, Rahmatu; Radvanyi, Laszlo G; Gombos, Dan S; Patel, Sapna P; Hwu, Patrick; Amaria, Rodabe N; Bernatchez, Chantale; Haymaker, Cara

2018-05-11

In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks. Finally, providing the 3 signals attributed to optimal T-cell activation led to expansion of TIL capable of recognizing their tumor counterpart in cutaneous and uveal melanoma. This new methodology for the initial phase of TIL expansion brings a new opportunity for translation of TIL therapy in challenging malignancies such as uveal melanoma.

Cutaneous anthrax in Southeast Anatolia of Turkey.

PubMed

Tekin, Recep; Sula, Bilal; Devecı, Ozcan; Tekin, Alicem; Bozkurt, Fatma; Ucmak, Derya; Kaya, Şafak; Bekcibasi, Muhammed; Erkan, Mehmet Emin; Ayaz, Celal; Hosoglu, Salih

2015-03-01

Anthrax is a rare disease cause by Bacillus anthracis, a Gram-positive, rod-shaped endospore-forming capsuled bacterium. Anthrax is manifest in three primary forms: cutaneous, respiratory, and gastrointestinal. Cutaneous anthrax accounts for approximately 95% of all cases of anthrax in humans. In the present study, we evaluated the clinical diagnosis and treatment of cutaneous anthrax, a rare disease that nonetheless remains a serious healthcare problem in developing countries. The complete medical records of patients diagnosed with cutaneous anthrax between January 2001 and December 2012 were examined in a retrospective manner. Cutaneous anthrax was diagnosed by the identification of typical anthrax lesions and/or the presence of Gram-positive-capsuled bacillus after staining with Gram stain and methylen blue in pathology samples obtained from these lesions and the presence of characteristic scarring with a history of severe swelling, black eschar, and positive response to treatment form the basis of diagnosis in cases where cultures were negative for the presence of bacillus. A total of 58 patients were admitted to the hospital with cutaneous anthrax between January 2001 and December 2012. This included 32 (55.2%) males and 26 (44.8%) females, with an age range of 15-82 years and a mean age of 38 ± 13.8 years. The incubation period for the infection ranged between 1 and 20 d (mean 3.7 ± 1.4 d). The most common symptoms at the time of hospital referral were swelling, redness, and black eschar of the skin. The most common lesion site was the hand and fingers (41.3%). Isolated of bacteria was used to diagnose the disease in six cases (23.8%), detection of Gram-positive bacillus in samples of characteristic lesion material was used in seven (28.5%) cases, and the presence of a characteristic lesion was the sole diagnostic criteria in 45 (77.6%) cases. Treatment consisted of penicillin G (12 cases), ampicillin-sulbactam (30 cases), Cefazolin (12 cases), or

Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-01-05

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

IgV(H) and bcl6 somatic mutation analysis reveals the heterogeneity of cutaneous B-cell lymphoma, and indicates the presence of undisclosed local antigens.

PubMed

Franco, Renato; Camacho, Francisca I; Fernández-Vázquez, Amalia; Algara, Patrocinio; Rodríguez-Peralto, José L; De Rosa, Gaetano; Piris, Miguel A

2004-06-01

Our understanding of the ontology of B-cell lymphomas (BCL) has been improved by the study of mutational status of IgV(H) and bcl6 genes, but only a few cases of cutaneous BCL have been examined for this status. We analyzed IgV(H) and bcl6 somatic mutations in 10 cutaneous BCL, classified as follicular (three primary and one secondary), primary marginal zone (two cases), and diffuse large BCL (three primary and one secondary). We observed a lower rate (<2%) of IgV(H) mutation in all marginal zone lymphomas, and a preferential usage of V(H)2-70 (one primary follicular and two primary diffuse large BCL). Fewer than expected replacement mutations in framework regions (FR) were observed in three primary follicular lymphomas (FLs) and in all diffuse large BCL, indicating a negative antigen selection pressure. Ongoing mutations were observed in eight of 10 cases. Only two primary FLs and two diffuse large BCL showed bcl6 somatic mutation. These data support the heterogeneous nature of the different cutaneous BCL, and specifically the distinction between cutaneous follicular and marginal zone lymphomas. The biased usage of V(H)2-70, the low rate of replacement mutation in the FR, and the presence of ongoing mutation imply that local antigens could modulate the growth of primary cutaneous BCL.

Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.

PubMed

Channappanavar, Rudragouda; Twardy, Brandon S; Suvas, Susmit

2012-01-01

The blocking of programmed death ligand-1 (PDL-1) has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1) infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection.

Cutaneous Tuberculosis

PubMed Central

Frankel, Amylynne; Penrose, Carolin

2009-01-01

Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis. PMID:20725570

A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

PubMed Central

Patel, Atiyah; Mudenda, Victor; Lakhi, Shabir; Ngalamika, Owen

2016-01-01

Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi's sarcoma. PMID:26881148

Cutaneous manifestations of lupus erythematosus.

PubMed

Parodi, A; Cozzani, E

2014-10-01

Cutaneous involvement in case of lupus erythematosus (LE) is very frequent and can present both specific or non-specific manifestations. LE specific lesions can be classified in acute, subacute and chronic cutaneous LE lesions. All of them can be localized and generalized. The LE non specific lesions are not exclusive to LE disease but are often seen in patients with active systemic LE. All the cutaneous lesions are often induced or aggravated by ultraviolet light, in fact they are usually localized in sun-exposed areas. Acute cutaneous LE is associated with systemic disease, subacute cutaneous LE has been considered a subset of its own since 1979 when it was first described, chronic cutaneous LE is the most common subtype of LE. Although less frequently also the chronic cutaneous lesions can be an aspect of systemic LE (25%).

Characterisation of T cell phenotypes, cytokines and transcription factors in the skin of dogs with cutaneous adverse food reactions.

PubMed

Veenhof, Eveline Z; Knol, Edward F; Schlotter, Yvette M; Vernooij, Johannes C; Rutten, Victor P; Willemse, Ton

2011-03-01

The immunopathogenesis of cutaneous adverse food reactions (CAFRs) in dogs is unknown. Since the clinical manifestations in the skin are like those found in canine atopic dermatitis (AD), this study investigated the similarity in T cell phenotypes and gene expression of cytokines and transcription factors in CAFRs. In addition, the influence of an elimination diet on these parameters was tested. In the skin of canine CAFRs, a predominant presence of CD8(+) T cells and increased expression of the IL-4, IL-13, Foxp3 and SOCS-3 genes were observed. IFN-γ gene expression was increased in lesional compared to non-lesional skin. The predominance of CD8(+) T cells indicates that the immunopathogenesis of CAFRs is different from that of canine AD. The elimination diet relieved clinical signs, but did not influence T cell phenotypes or expression of the cytokine and transcription factor genes in the skin of dogs with CAFRs, indicating a continuously pre-activated immune status in dogs sensitised to food constituents. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cigarette smoking and cutaneous damage in systemic lupus erythematosus.

PubMed

Turchin, Irina; Bernatsky, Sasha; Clarke, Ann E; St-Pierre, Yvan; Pineau, Christian A

2009-12-01

To evaluate the association between cigarette smoking and cutaneous damage in systemic lupus erythematosus (SLE). Our study was performed in SLE clinic registry cohort patients, all of whom fulfilled revised American College of Rheumatology criteria for SLE; patients are followed prospectively with annual assessments that include collection of demographic variables, smoking history, disease activity (SLE Disease Activity Index version 2000, SLEDAI-2K), medications, and damage scores (Systemic Lupus International Collaborating Clinics/ACR Damage Index). Cumulative cutaneous damage scores were used for the primary analyses. Logistic and logit regression models were performed to examine potential associations between current smoking and cutaneous damage, controlling for age, sex, race, lupus disease duration, antimalarial or immunosuppressant use, and anti-DNA and anti-SSA antibody status. Of our sample (N = 276), 92% were women and 73.7% were Caucasian; the mean age was 45.1 years, mean disease duration 13.5 years, and 17.5% were current smokers. In the regression analyses, current cigarette smoking was associated with total cutaneous damage (OR 2.73, 95% CI 1.10, 6.81) and with scarring (OR 4.70, 95 CI 1.04, 21.2). In additional analyses, current smoking was also associated with active lupus rash (OR 6.18, 95% CI 1.63, 23.3). Current cigarette smoking may be associated with cutaneous damage and active lupus rash in SLE, suggesting another reason to emphasize smoking cessation in patients with SLE.

Helical irradiation of the total skin with dose painting to replace total skin electron beam therapy for therapy-refractory cutaneous CD4+ T-cell lymphoma.

PubMed

Hsieh, Chen-Hsi; Shueng, Pei-Wei; Lin, Shih-Chiang; Tien, Hui-Ju; Shiau, An-Cheng; Chou, Yueh-Hung; Wu, Meng-Hao; Wang, Jen-Yu; Chen, Chi-Kuan; Chen, Yu-Jen

2013-01-01

A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

Disseminated cutaneous sporotrichosis presenting as a necrotic facial mass: Case and review.

PubMed

He, Yong; Ma, Chelsea; Fung, Maxwell; Fitzmaurice, Sarah

2017-07-15

Sporotrichosis is a subcutaneous mycotic infection caused by Sporothrix schenckii, a group of common saprophytes of soil, plants, and organic debris. Disseminated forms may be seen in the setting of immunosuppression and are typically treated initially with intravenous lipidized amphotericin B. We report an unusual case of a 65-year-old woman who developed disseminated cutaneous sporotrichosis with extensive facial involvement in the absence of a known primary inoculation. Her cutaneous lesions completely resolved after treatment with intravenous posaconazole without amphotericin B.

Cutaneous and systematic metastasis of testicular choriocarcinoma: Case report and literature review.

PubMed

Weijin, Fu; Jinjin, Zeng; Jiwen, Cheng

2018-06-01

Cutaneous metastasis of testicular choriocarcinoma is exceptionally uncommon. To our knowledge, only 14 cases have been reported in the past 10 years in the pubmed. We have an uncommon case of testicular choriocarcinoma who has metastasized to the adjacent skin and organ systems. An 18-year-old male was diagnosed with initial presentation of cutaneous mass at the left back. Followly,biopsy was performed under local anesthesia.Histopathological examination was consistent with the diagnosis of metastatic choriocarcinoma. The histopathological assessment of the biopsied tissue, in combination with elevated serum β-HCG levels and presentation of testicular mass, indicated primary testicular choriocarcinoma with cutaneous and systemic metastasis. Subsequently radical orchiectomy was performed. Despite the case completed one cycle of cisplatin-based regimen chemotherapy, he died of multiple organ dysfunction syndrome 2 months after surgery. In this report, cutaneous metastasis with testicular choriocarcinoma is extremely rare. It is important to recognize that this unusual variant of testicular choriocarcinoma has the potential to behave aggressively and to metastasize.

Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip.

PubMed

Wang, David M; Kraft, Stefan; Rohani, Pooyan; Murphy, George F; Besaw, Robert J; Karia, Pritesh S; Morgan, Frederick C; Schmults, Chrysalyne D

2018-06-01

Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.

Cutaneous metastases from different internal malignancies: a clinical and prognostic appraisal.

PubMed

Hu, S C-S; Chen, G-S; Lu, Y-W; Wu, C-S; Lan, C-C E

2008-06-01

Cutaneous metastases are perceived as a sign of advanced disease and are regarded as a grave prognostic indicator. In addition, few reports have focused on the cutaneous metastasis profiles of Asian patients. We seek to analyse the clinical and prognostic characteristics of cutaneous tumour metastases in a Taiwanese medical centre. Clinical records from Kaohsiung Medical University Hospital over the last 20 years (1986-2006) were reviewed, and cases of biopsy-proven cutaneous metastases from internal malignancies identified. Survival rates were evaluated using the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used for univariate analysis to determine the risk of mortality among different groups. A total of 141 cases of cutaneous metastases were identified. The clinical profiles were similar to those from western countries, although the frequencies of primary tumours were different. The duration of survival was usually short following diagnosis of cutaneous metastases, but prognosis is significantly better in breast cancer patients with metastases. Moreover, the survival was even longer for breast cancer patients when the metastasis was confined to the skin. The risk of skin metastases depends largely on the characteristics of tumour cells, which is similar among different ethnic groups. In terms of prognosis, a subset of breast cancer patients has superior prognosis, even among breast cancer patients with stage IV disease. Physicians should consider this finding in clinical situations to avoid possible misinformation about the prognosis of the disease.

Disseminated cutaneous sporotrichosis.

PubMed

Chang, Shurong; Hersh, Andrew M; Naughton, Greg; Mullins, Kevin; Fung, Maxwell A; Sharon, Victoria R

2013-11-15

The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients. We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208. The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.

Emerging Skin T-Cell Functions in Response to Environmental Insults

PubMed Central

Suwanpradid, Jutamas; Holcomb, Zachary E.; MacLeod, Amanda S.

2017-01-01

Skin is the primary barrier between the body and the outside world, functioning not only as a physical barrier, but also as an immunologic first line of defense. A large number of T cells populate the skin. This review highlights the ability of these cutaneous T cells to regulate skin-specific environmental threats, including microbes, injuries, solar UV radiation, and allergens. Since much of this knowledge has been advanced from murine studies, we focus our review on how the mouse state has informed the human state, emphasizing the key parallels and differences. PMID:27784595

Cutaneous and systemic mastocytosis in children: a risk factor for anaphylaxis?

PubMed

Matito, A; Carter, M

2015-05-01

Childhood mastocytosis is usually a clonal mast cell disease related to activating mutations in KIT. The symptoms in childhood mastocytosis are typically cutaneous in nature although systemic symptoms including anaphylaxis due to the release of mast cells (MC) mediators can also manifest. The prevalence of anaphylaxis reported in childhood mastocytosis is higher than the rates reported in the pediatric general population, but lower than the prevalence of anaphylaxis described in adult mastocytosis. An extensive cutaneous involvement was reported as a risk factor for anaphylaxis, and patients with diffuse cutaneous mastocytosis have been documented to have more severe anaphylaxis symptoms. Anaphylaxis due to unknown causes or idiopathic anaphylaxis was the primary etiology in pediatric mastocytosis, followed by foods as the most relevant identified trigger; however, hymenoptera stings are not a frequent trigger of anaphylaxis in children with mastocytosis in contrast to the adult patients.

Histone deacetylase inhibitors potentiate photochemotherapy in cutaneous T-cell lymphoma MyLa cells.

PubMed

Sung, Jane J; Ververis, Katherine; Karagiannis, Tom C

2014-02-05

Cutaneous T cell lymphomas (CTCL) represent rare extranodal non-Hodgkin's lymphomas, which are characterised by pleomorphic skin lesions and distinct T-cell markers. CTCL is a relatively benign disease in its early stages, but survival rates decrease significantly with progression. Histone deacetylase inhibitors (HDACi) have recently emerged as a new class of targeted anticancer therapies for CTCL, which have been shown to induce growth inhibition, terminal differentiation and apoptosis in various cancers in vitro and in vivo. In addition to the intrinsic anticancer properties of HDACi, recent studies have demonstrated its ability to synergise with phototherapy. In particular, we examine the therapeutic potential of HDACi in combination with ultraviolet A (UV-A) phototherapy, employing a halogenated DNA minor groove binding ligand called UVASens as a photosensitiser. In vitro studies have demonstrated that UVASens is approximately 1000-fold more potent than current psoralens. The extreme photopotency of UVASens allows the use of lower radiation doses minimising the carcinogenic risks associated with the long-term use of phototherapy. Considering, previous findings using the photosensitiser UVASens and potential synergy of HDACi with phototherapy, it was hypothesised that HDACi will augment photochemotherapy-induced cytotoxicity in CTCL MyLa cells. The findings indicated that combinations of UVASens/UV-A photochemotherapy and HDACi significantly decreased cell viability and increased apoptosis and DNA double-strand breaks in MyLa cells. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways

PubMed Central

Ni, Xiao; Zhang, Xiang; Hu, Cheng-Hui; Langridge, Timothy; Tarapore, Rohinton S.; Allen, Joshua E.; Oster, Wolfgang; Duvic, Madeleine

2017-01-01

Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4+ malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1.25-10.0 μM. ONC201 also induced apoptosis in tested cells with a narrow concentration range of 2.5-10.0 μM, evidenced by increased Annexin V+ cells, accompanied by accumulated sub-G1 portions. ONC201 only induced apoptosis in CD4+ malignant T cells, not in normal CD4+ T cells. The activating transcription factor 4 (ATF4), a hallmark of integrated stress response, was upregulated in response to ONC201 whereas Akt was downregulated. In addition, molecules in JAK/STAT and NF-κB pathways, as well as IL-32β, were downregulated following ONC201 treatment. Thus, ONC201 exerts a potent and selective anti-tumor effect on CTCL cells. Its efficacy may involve activating integrated stress response through ATF4 and inactivating JAK/STAT and NF-κB pathways. PMID:28977902

ONC201 selectively induces apoptosis in cutaneous T-cell lymphoma cells via activating pro-apoptotic integrated stress response and inactivating JAK/STAT and NF-κB pathways.

PubMed

Ni, Xiao; Zhang, Xiang; Hu, Cheng-Hui; Langridge, Timothy; Tarapore, Rohinton S; Allen, Joshua E; Oster, Wolfgang; Duvic, Madeleine

2017-09-22

Cutaneous T-cell lymphomas (CTCLs) are extremely symptomatic and still incurable, and more effective and less toxic therapies are urgently needed. ONC201, an imipridone compound, has shown efficacy in pre-clinical studies in multiple advanced cancers. This study was to evaluate the anti-tumor activity of ONC201 on CTCL cells. The effect of ONC201 on the cell growth and apoptosis were evaluated in CTCL cell lines (n=8) and primary CD4 + malignant T cells isolated from CTCL patients (n=5). ONC201 showed a time-dependent cell growth inhibition in all treated cell lines with a concentration range of 1.25-10.0 μM. ONC201 also induced apoptosis in tested cells with a narrow concentration range of 2.5-10.0 μM, evidenced by increased Annexin V + cells, accompanied by accumulated sub-G1 portions. ONC201 only induced apoptosis in CD4 + malignant T cells, not in normal CD4 + T cells. The activating transcription factor 4 (ATF4), a hallmark of integrated stress response, was upregulated in response to ONC201 whereas Akt was downregulated. In addition, molecules in JAK/STAT and NF-κB pathways, as well as IL-32β, were downregulated following ONC201 treatment. Thus, ONC201 exerts a potent and selective anti-tumor effect on CTCL cells. Its efficacy may involve activating integrated stress response through ATF4 and inactivating JAK/STAT and NF-κB pathways.

CD4(+) T-cell help amplifies innate signals for primary CD8(+) T-cell immunity.

PubMed

Bedoui, Sammy; Heath, William R; Mueller, Scott N

2016-07-01

CD8(+) T cells provide an important component of protection against intracellular infections and cancer. Immune responses by these T cells involve a primary phase of effector expansion and differentiation, followed by a contraction phase leading to memory formation and, if antigen is re-encountered, a secondary expansion phase with more rapid differentiation. Both primary and secondary phases of CD8(+) T-cell immunity have been shown to depend on CD4(+) T-cell help, although during certain infections the primary phase is variable in this requirement. One explanation for such variability relates to the strength of associated inflammatory signals, with weak signals requiring help. Here, we focus on our studies that have dissected the requirements for help in the primary phase of the CTL response to herpes simplex virus, elucidating intricate interactions and communications between CD4(+) T cells, various dendritic cell subsets, and CD8(+) T cells. We place our studies in the context of others and describe a simple model of help where CD40 signaling amplifies innate signals to enable efficient CD8(+) T-cell expansion and differentiation. This model facilitates CTL induction to various different agents, without altering the qualitative innate signals that direct other important arms of immunity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cutaneous Lupus Erythematosus: Diagnosis and treatment

PubMed Central

Okon, Lauren G.; Werth, Victoria P.

2013-01-01

Cutaneous lupus erythematosus encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several subtypes, including acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus. Chronic cutaneous lupus erythematosus includes discoid lupus erythematosus, lupus erythematosus profundus, chilblain cutaneous lupus, and lupus tumidus. Diagnosis of these diseases requires proper classification of the subtype, through a combination of physical exam, laboratory studies, histology, antibody serology, and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. Treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring, or treatment-refractory disease. In this review, we discuss issues in classification and diagnosis of the various subtypes of CLE, as well as provide an update on therapeutic management. PMID:24238695

Aggressive Rare T-cell Lymphomas with Manifestation in the Skin: A Monocentric Cross-sectional Case Study.

PubMed

Brüggen, Marie-Charlotte; Kerl, Katrin; Haralambieva, Eugenia; Schanz, Urs; Chang, Yun-Tsan; Ignatova, Desislava; Dummer, Reinhard; Cozzio, Antonio; Hoetzenecker, Wolfram; French, Lars E; Guenova, Emmanuella

2018-04-24

Rare T- or NK-cell lymphomas with cutaneous manifestation may display a highly aggressive clinical course and major diagnostic/therapeutic challenges. This report describes our experiences with different lymphomas of this rare category and the therapeutic options used. This retrospective, descriptive, monocentric, cross-sectional case study, identified 4 rare aggressive T-/NK-cell lymphomas with manifestation in the skin, which were diagnosed in a tertiary care centre over a period of 4 years. Two patients had an Epstein-Barr virus-associated extranodal NK/T-cell lymphoma and 2 patients had a primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. Concomitant extracutaneous involvement was observed in 2 of all 4 patients. Two patients had fulminant disease progression and resistance to chemotherapy. Two patients underwent allogeneic haematopoietic stem cell transplantation, which resulted in one complete remission and one partial remission. This report emphasizes the importance of an early diagnostic work-up and a prompt aggressive therapeutic approach.

Primary cutaneous perivascular epithelioid cell tumor: a clinicopathological and molecular reappraisal.

PubMed

Charli-Joseph, Yann; Saggini, Andrea; Vemula, Swapna; Weier, Jingly; Mirza, Sonia; LeBoit, Philip E

2014-12-01

Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm of uncertain histogenesis with a mixed myomelanocytic immunophenotype, rarely arising in the skin (primary cutaneous PEComa [pcPEComa]). We analyzed the clinicopathological features of 8 pcPEComas, assayed for DNA copy number changes and for initiating mutations common in melanocytic neoplasms. pcPEComas were evaluated using immunohistochemistry, comparative genomic hybridization, and DNA sequencing. pcPEComas were erythematous nodules, mostly in the lower extremities of women (5/8), composed of large pale-staining epithelioid cells. The patient's age range was 26 to 67 (mean 46) years. The percentages of tumors staining positively were as follows: micro-ophthalmia-associated transcription factor, NKI/C3, bcl-1, E-cadherin, and cathepsin K (100%); HMB-45, 4E-binding protein 1, and CD68 (88%); smooth muscle actin and muscle-specific actin (40%); S100 (38%); calponin (20%); desmin (13%); and melan-A, SOX10, and keratin (0%). No chromosomal copy number changes or initiating mutations were identified. Small sample size is a limitation. pcPEComas have a different molecular signature than extracutaneous tumors and are unrelated to tuberous sclerosis. However, the common expression of 4E-binding protein 1 points to a role of the mTOR pathway in their pathogenesis. Because pcPEComas are diagnostically challenging, we propose that micro-ophthalmia-associated transcription factor, NKIC3, smooth muscle actin, desmin, bcl-1, cathepsin K, and 4E-binding protein 1 can be used when evaluating a possible pcPEComa. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Primary cutaneous neuroendocrine carcinoma, Merkel cell carcinoma. Case series 1991-2012.

PubMed

Campillo, Ramón; Gil-Carcedo, Elisa; Alonso, David; Vallejo, Luis A; Oñate, Juan M; Gil-Carcedo, Luis M

2013-01-01

Merkel cell carcinoma was first described by Toker in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears in the dermoepidermic area, grows fast, is very aggressive and has a poor prognosis. The aim of this work is to highlight the importance of this tumour, which develops mainly in the skin of the head and neck area, and whose prevalence has increased in recent years. We gathered data on 16 patients suffering cutaneous neuroendocrine carcinoma treated at our hospital between September 12, 1991 and July 13, 2012. We indicated the age and gender of patients. We described the area where the tumour was located, indicating the size in millimetres, according to the major axis of the lesion. Most of the patients studied were over 70 years old, except for one who was 55. The highest frequency of cases appeared among patients aged over 80 years. In the cases studied, when the tumour appeared in the head and neck region (10/16), its location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or mandibular. The major axis of the lesion ranged between 7 and 35 mm. Unlike with epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were common. Immunohistochemical (CK20) tests are essential for a correct diagnosis. Treatment is usually surgical and occasionally followed by radiotherapy and chemotherapy. This carcinoma is not a very common skin tumour. It appears in old age, in the head and neck region in 50% of cases and often leads to exitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Cutaneous xanthomas with concurrent demodicosis and dermatophytosis in a cat.

PubMed

Vogelnest, L J

2001-07-01

Multiple cutaneous xanthomas, associated with fasting hyperlipidaemia, are described in a 9-month-old domestic long-haired cat. A severely pruritic, papular, and crusting dermatitis affecting the head and neck, initially diagnosed as lesions of the eosinophilic granuloma complex, progressively developed on the head and pinnae. Pruritus was controlled with administration of prednisolone and chlorambucil. Repeat histological examination confirmed the diagnosis of cutaneous xanthoma and concurrent mild demodicosis. Marked fasting hypercholesterolaemia, hypertriglyceridaemia and transient hyperglycaemia were subsequently confirmed. Treatment for hyperlipidaemia and xanthomas with a low-fat diet (Hill's Feline r/d) and the previously unreported treatment for feline demodicosis of daily oral milbemycin were commenced. Multiple pink, alopecic plaques and papules gradually regressed, however pruritus recurred if immunosuppressive treatment was reduced, and well-demarcated areas of alopecia developed on the head, limbs and trunk, despite negative skin scrapings for demodex mites. Fungal culture of hair samples yielded Microsporum canis. All cutaneous lesions resolved with the addition of griseofulvin to the treatment regimen. Concurrent corneal ulceration and keratoconjunctivitis sicca ultimately resolved with treatment, including topical cyclosporin. Diabetes mellitus developed 6 months after resolution of skin lesions. No cutaneous or ocular abnormalities were present 6 months later with continued low-fat diet and insulin administration, although transient recurrence of papules and pruritus occurred after inadvertent access to a fatty meal. An underlying primary hyperlipidaemia was suspected, causing pruritic xanthomas. This may represent the first report of concurrent cutaneous xanthomas, demodicosis and dermatophytosis in a cat.

TERT promoter mutation status as an independent prognostic factor in cutaneous melanoma.

PubMed

Griewank, Klaus G; Murali, Rajmohan; Puig-Butille, Joan Anton; Schilling, Bastian; Livingstone, Elisabeth; Potrony, Miriam; Carrera, Cristina; Schimming, Tobias; Möller, Inga; Schwamborn, Marion; Sucker, Antje; Hillen, Uwe; Badenas, Celia; Malvehy, Josep; Zimmer, Lisa; Scherag, André; Puig, Susana; Schadendorf, Dirk

2014-09-01

Recently, TERT promoter mutations were identified at high frequencies in cutaneous melanoma tumor samples and cell lines. The mutations were found to have a UV-signature and to lead to increased TERT gene expression. We analyzed a large cohort of melanoma patients for the presence and distribution of TERT promoter mutations and their association with clinico-pathological characteristics. 410 melanoma tumor samples were analyzed by Sanger sequencing for the presence of TERT promoter mutations. An analysis of associations between mutation status and various clinical and pathologic variables was performed. TERT promoter mutations were identified in 154 (43%) of 362 successfully sequenced melanomas. Mutation frequencies varied between melanoma subtype, being most frequent in melanomas arising in nonacral skin (48%) and melanomas with occult primary (50%), and less frequent in mucosal (23%), and acral (19%) melanomas. Mutations carried a UV signature (C>T or CC>TT). The presence of TERT promoter mutations was associated with factors such as BRAF or NRAS mutation (P < .001), histologic type (P = .002), and Breslow thickness (P < .001). TERT promoter mutation was independently associated with poorer overall survival in patients with nonacral cutaneous melanomas (median survival 80 months vs 291 months for wild-type; hazard ratio corrected for other covariates 2.47; 95% confidence interval [CI] = 1.29 to 4.74; P = .006). UV-induced TERT promoter mutations are one of the most frequent genetic alterations in melanoma, with frequencies varying depending on melanoma subtype. In nonacral cutaneous melanomas, presence of TERT promoter mutations is independently associated with poor prognosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mouse papillomavirus infections spread to cutaneous sites with progression to malignancy

PubMed Central

Cladel, Nancy M.; Budgeon, Lynn R.; Cooper, Timothy K.; Balogh, Karla K.; Christensen, Neil D.; Myers, Roland; Majerciak, Vladimir; Gotte, Deanna; Zheng, Zhi-Ming; Hu, Jiafen

2017-01-01

We report secondary cutaneous infections in the mouse papillomavirus (MmuPV1)/mouse model. Our previous study demonstrated that cutaneous MmuPV1 infection could spread to mucosal sites. Recently, we observed that mucosal infections could also spread to various cutaneous sites including the back, tail, muzzle and mammary tissues. The secondary site lesions were positive for viral DNA, viral capsid protein and viral particles as determined by in situ hybridization, immunohistochemistry and transmission electron microscopy analyses, respectively. We also demonstrated differential viral production and tumour growth at different secondarily infected skin sites. For example, fewer viral particles were detected in the least susceptible back tissues when compared with those in the infected muzzle and tail, although similar amounts of viral DNA were detected. Follow-up studies demonstrated that significantly lower amounts of viral DNA were packaged in the back lesions. Lavages harvested from the oral cavity and lower genital tracts were equally infectious at both cutaneous and mucosal sites, supporting the broad tissue tropism of this papillomavirus. Importantly, two secondary skin lesions on the forearms of two mice displayed a malignant phenotype at about 9.5 months post-primary infection. Therefore, MmuPV1 induces not only dysplasia at mucosal sites such as the vagina, anus and oral cavity but also skin carcinoma at cutaneous sites. These findings demonstrate that MmuPV1 mucosal infection can be spread to cutaneous sites and suggest that the model could serve a useful role in the study of the viral life cycle and pathogenesis of papillomavirus. PMID:28942760

Mouse papillomavirus infections spread to cutaneous sites with progression to malignancy.

PubMed

Cladel, Nancy M; Budgeon, Lynn R; Cooper, Timothy K; Balogh, Karla K; Christensen, Neil D; Myers, Roland; Majerciak, Vladimir; Gotte, Deanna; Zheng, Zhi-Ming; Hu, Jiafen

2017-09-25

We report secondary cutaneous infections in the mouse papillomavirus (MmuPV1)/mouse model. Our previous study demonstrated that cutaneous MmuPV1 infection could spread to mucosal sites. Recently, we observed that mucosal infections could also spread to various cutaneous sites including the back, tail, muzzle and mammary tissues. The secondary site lesions were positive for viral DNA, viral capsid protein and viral particles as determined by in situ hybridization, immunohistochemistry and transmission electron microscopy analyses, respectively. We also demonstrated differential viral production and tumour growth at different secondarily infected skin sites. For example, fewer viral particles were detected in the least susceptible back tissues when compared with those in the infected muzzle and tail, although similar amounts of viral DNA were detected. Follow-up studies demonstrated that significantly lower amounts of viral DNA were packaged in the back lesions. Lavages harvested from the oral cavity and lower genital tracts were equally infectious at both cutaneous and mucosal sites, supporting the broad tissue tropism of this papillomavirus. Importantly, two secondary skin lesions on the forearms of two mice displayed a malignant phenotype at about 9.5 months post-primary infection. Therefore, MmuPV1 induces not only dysplasia at mucosal sites such as the vagina, anus and oral cavity but also skin carcinoma at cutaneous sites. These findings demonstrate that MmuPV1 mucosal infection can be spread to cutaneous sites and suggest that the model could serve a useful role in the study of the viral life cycle and pathogenesis of papillomavirus.

Herpes folliculitis masquerading as cutaneous lymphoma.

PubMed

Bae-Harboe, Yoon-Soo C; Bhawan, Jag; Demierre, Marie-France; Goldberg, Lynne J

2013-08-01

Herpes virus infections presenting as folliculitis are uncommon. We describe a 48-year-old white man with a distant history of a childhood gastric lymphoma and renal cell carcinoma presenting with an itchy eruption. He was concerned about recurrence. A punch biopsy revealed interface dermatitis with a dense atypical superficial and deep perivascular and periadnexal lymphohistiocytic infiltrate with occasional eosinophils extending to the subcutis, with destruction of vessel walls. It was composed of predominantly CD3-positive lymphocytes with scattered CD56-positive cells and CD20-positive cells, concerning for lymphoma. A T-cell gene rearrangement study was negative. Deeper sections uncovered multinucleated giant keratinocytes in the follicular epithelium of 1 hair follicle, consistent with herpes folliculitis. Cutaneous herpes infections can exhibit several variable clinical and histopathological features. Knowledge of alternative presentations of herpes infections, histological clues to the presence of herpes infections, and careful clinicopathological correlation are necessary to differentiate herpes infections from cutaneous lymphomas and other inflammatory dermatoses.

"Occult cutaneous lymphangiectasis": an unusual case of cutaneous lymphangioma.

PubMed

Kakinuma, Hiroshi

2002-01-01

An unusual case of cutaneous lymphatic abnormality is described and named as "occult cutaneous lymphangietasis". A 26-year-old man had noticed pigmented maculae in the left inguinofemoral region and waist, which had gradually increased in number for as long as he could remember. The peculiar distribution of the eruptions and their transient saccular dilatation due to infection suggested that they were of lymphatic origin. Lymphangiography showed the presence of dilated lymphatics in the left inguinofemoral area and correspondence of the distribution of dermal backflow with the locations of the pigmented maculae. The histology is consistent with a diagnosis of lymphangioma. We could find no other reports of cases of cutaneous lymphangioma featuring pigmented maculae as the sole manifestation, although whether the pigmentation is an original clinical feature of this type of lymphatic abnormality is still an open question.

Radiation Port Cutaneous Metastases: Reports of Two Patients Whose Recurrent Visceral Cancers Presented as Skin Lesions at the Site of Previous Radiation and Literature Review

PubMed Central

Hoyt, Brian Spencer; Cohen, Philip Randolph

2014-01-01

Radiation therapy is associated with a variety of complications, including the development of primary skin cancers in the radiated region. However, it is rare for patients with visceral cancers who are treated with radiation therapy to subsequently develop cutaneous metastasis within the radiation port. We describe two patients with internal malignancies who developed cutaneous metastases within their radiation ports following radiotherapy. In addition, we used PubMed to perform an extensive literature review and identify additional reports of cutaneous metastasis within a radiation port. We excluded patients who developed melanoma or primary skin cancers in the radiation port. We also excluded patients with non-solid organ malignancies. Herein, we summarize the characteristics of 23 additional patients who experienced radiation port cutaneous metastases and explore possible mechanisms for the occurrence of radiation port cutaneous metastases. PMID:24700938

A new protoparvovirus in human fecal samples and cutaneous T cell lymphomas (mycosis fungoides).

PubMed

Phan, Tung G; Dreno, Brigitte; da Costa, Antonio Charlys; Li, Linlin; Orlandi, Patricia; Deng, Xutao; Kapusinszky, Beatrix; Siqueira, Juliana; Knol, Anne-Chantal; Halary, Franck; Dantal, Jacques; Alexander, Kathleen A; Pesavento, Patricia A; Delwart, Eric

2016-09-01

We genetically characterized seven nearly complete genomes in the protoparvovirus genus from the feces of children with diarrhea. The viruses, provisionally named cutaviruses (CutaV), varied by 1-6% nucleotides and shared ~76% and ~82% amino acid identity with the NS1 and VP1 of human bufaviruses, their closest relatives. Using PCR, cutavirus DNA was found in 1.6% (4/245) and 1% (1/100) of diarrhea samples from Brazil and Botswana respectively. In silico analysis of pre-existing metagenomics datasets then revealed closely related parvovirus genomes in skin biopsies from patients with epidermotropic cutaneous T-cell lymphoma (CTCL or mycosis fungoides). PCR of skin biopsies yielded cutavirus DNA in 4/17 CTCL, 0/10 skin carcinoma, and 0/21 normal or noncancerous skin biopsies. In situ hybridization of CTCL skin biopsies detected viral genome within rare individual cells in regions of neoplastic infiltrations. The influence of cutavirus infection on human enteric functions and possible oncolytic role in CTCL progression remain to be determined. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

PubMed

Joyce, K M; McInerney, N M; Piggott, R P; Martin, F; Jones, D M; Hussey, A J; Kerin, M J; Kelly, J L; Regan, P J

2017-11-01

Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

Primary colorectal T-cell lymphoma.

PubMed

Okada, Mitsuo; Maeda, Kazuhiro; Suzumiya, Junji; Hagimoto, Tatsunobu; Wakamatsu, Sinichi; Ohshima, Koichi; Kanda, Motonobu; Sonoda, Taizou; Sakamoto, Atsuo; Tamura, Kazuo

2003-01-01

We report here a case of primary colorectal T-cell lymphoma in a 49-year-old man. Eighteen years previously, he was diagnosed as having ulcerative colitis based on the findings of colonoscopy and a barium enema. Since then, he had been treated with salicylazosulfapyridine until the most recent episode. He was refered to our clinic with the chief complaint of abdominal pain and excretion of mucus, and for a workup of bowel lesions. Physical examination results were not remarkable, except for the presence of low-grade fever. Total colonoscopy showed multiple shallow ulcers and aphthoid erosions through the entire colon and rectum, except for the descending colon. Endoscopic findings of the descending colon were normal, which was different from the findings of the active stage of ulcerative colitis. Biopsy specimens from the colon and rectum with ulcerations and aphthoid erosions showed a diffuse proliferation of medium-sized to large atypical lymphoid cells with irregular and indistinct nucleoli, thus revealing malignant lymphoma, diffuse pleomorphic type. The lymphoma cells were positive for CD2, CD3, CD5, CD8, and T-cell receptor (TCR) beta F1, but negative for CD4, CD19, CD20, CD103, and CD56. Southern blotting revealed rearrangement of TCR. Based on these findings, the patient was diagnosed as having high-grade T-cell lymphoma. The findings of computerized tomography of the chest and abdomen, gallium scintigraphy, and abdominal ultrasonography were all normal. There were no abdominal lesions throughout the esophagus, stomach, duodenum, and small intestine. As the patient refused total proctocolectomy, he was treated with one course of CHOP (cyclophosphamide, vincristine, adriamycin, and prednisolone) and subsequently with three courses of ProMACE-CytaBOM (consisting of cyclophosphamide, adriamycin, etoposide, cytarabine, bleomycin, vincristine, methotrexate, and prednisolone). After the therapy, improvement of the colorectal lesions was observed, though lesions

Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent

PubMed Central

Yuan, Jing; Guo, Sheng; Hall, David; Cammett, Anna M.; Jayadev, Supriya; Distel, Manuel; Storfer, Stephen; Huang, Zimei; Mootsikapun, Piroon; Ruxrungtham, Kiat; Podzamczer, Daniel; Haas, David W.

2012-01-01

Objective Nevirapine is widely prescribed for HIV-1 infection. We characterized relationships between nevirapine-associated cutaneous and hepatic adverse events and genetic variants among HIV-infected adults. Design We retrospectively identified cases and controls. Cases experienced symptomatic nevirapine-associated severe (grade III/IV) cutaneous and/or hepatic adverse events within 8 weeks of initiating nevirapine. Controls did not experience adverse events during more than 18 weeks of nevirapine therapy. Methods Cases and controls were matched 1 : 2 on baseline CD4 T-cell count, sex, and race. Individuals with 150 or less CD4 T cells/μl at baseline were excluded. We characterized 123 human leukocyte antigen (HLA) alleles and 2744 single-nucleotide polymorphisms in major histocompatibility complex (MHC) and drug metabolism and transport genes. Results We studied 276 evaluable cases (175 cutaneous adverse events, 101 hepatic adverse events) and 587 controls. Cutaneous adverse events were associated with CYP2B6 516G→T (OR 1.66, all), HLA-Cw*04 (OR 2.51, all), and HLA-B*35 (OR 3.47, Asians; 5.65, Thais). Risk for cutaneous adverse events was particularly high among Blacks with CYP2B6 516TT and HLA-Cw*04 (OR 18.90) and Asians with HLA-B*35 and HLA-Cw*04 (OR 18.34). Hepatic adverse events were associated with HLA-DRB*01 (OR 3.02, Whites), but not CYP2B6 genotypes. Associations differed by population, at least in part reflecting allele frequencies. Conclusion Among patients with at least 150 CD4 T cells/μl, polymorphisms in drug metabolism and immune response pathways were associated with greater likelihood of risk for nevirapine-related adverse events. Results suggest fundamentally different mechanisms of adverse events: cutaneous, most likely MHC class I-mediated, influenced by nevirapine CYP2B6 metabolism; hepatic, most likely MHC class II-mediated and unaffected by such metabolism. These risk variants are insensitive for routine clinical screening. PMID

Imported Cutaneous Diphtheria, United Kingdom

PubMed Central

de Benoist, Anne-Claire; White, Joanne Margaret; Efstratiou, Androulla; Kelly, Carole; Mann, Ginder; Nazareth, Bernadette; Irish, Charles James; Kumar, Deepti

2004-01-01

Cutaneous diphtheria is endemic in tropical countries but unusual in the United Kingdom. Four cases occurred in the United Kingdom within 2 months in 2002. Because cutaneous diphtheria causes outbreaks of both cutaneous and pharyngeal forms, early diagnosis is essential for implementing control measures; high diphtheria vaccination coverage must also be maintained. PMID:15109425

Hydroa vacciniforme-like lymphoma with primarily periorbital swelling: 7 cases of an atypical clinical manifestation of this rare cutaneous T-cell lymphoma.

PubMed

Plaza, Jose A; Sangueza, Martin

2015-01-01

Hydroa vacciniforme-like lymphoma (HVL) is a rare cutaneous T-cell lymphoma that is usually seen in children of Hispanic or Asian origin. Association between chronic latent Epstein-Barr virus infection in both hydroa vacciniforme (HV) and HVL has been demonstrated and has recently been categorized by the World Health Organization as one of the Epstein Barr virus-positive lymphoproliferative disorders of childhood. Patients with HVL present with a cutaneous rash characterized by edema, blisters, ulcers, and scars mainly seen on the face and extremities that mimic HV; however, unlike in HV, the lesions tend to be extensive and deeper and are associated with severe scarring, necrosis, and systemic manifestations. We are reporting 7 cases of an unusual clinical variant of HVL with primarily periorbital edema. All of our patients in this series presented with progressive periorbital edema that was accompanied with systemic symptoms including fever, malaise, and lymphadenopathy. Most cases were initially misinterpreted as inflammatory processes including cellulitis, arthropod bite reactions, and periorbital lupus erythematosus. The biopsy of these lesions revealed an atypical lymphocytic infiltrate predominantly distributed in the deep dermis and in subcutaneous fat. Immunohistochemistry studies revealed a cytotoxic T-cell (CD8) profile. All cases were associated with Epstein-Barr virus infection. Our study presents a rare clinical variant of HVL with predominant periorbital edema. This variant could potentially be overlooked and misdiagnosed as an inflammatory condition; thus, it needs to be included in the differential diagnosis of periorbital edema in young patients.

Cutaneous metastasis of signet-ring gastric adenocarcinoma to the breast with unusual clinicopathological features.

PubMed

Avgerinou, Georgia; Flessas, Ioannis; Hatziolou, Eftychia; Zografos, Georgios; Nitsios, Ilias; Zagouri, Flora; Katsambas, Andreas; Kanitakis, Jean

2011-06-01

Cutaneous metastasis of gastric adenocarcinoma is rare and usually presents in men, as nodules over the abdomen. We present the case of a woman with cutaneous metastasis of gastric adenocarcinoma showing unusual clinicopathological features. A 37-year-old woman developed florid cutaneous metastasis over the skin of the left breast two years after total gastrectomy for a signet-ring adenocarcinoma of the diffuse type. The metastasis presented as a multinodular growth developing over erythematous skin of the left hemithorax. Microscopically, the skin tumor was predominantly made up of spindle-shaped cells, mimicking a mesenchymal/fibrohistiocytic neoplasm. A comparative immunohistochemical study of the gastric primary and the skin tumor showed an almost identical profile (keratin 7/20+; epithelial membrane antigen+, MUC-5AC+), highlighting the gastric adenocarcinoma as the origin of the skin metastasis. Although rare, cutaneous metastases of gastric adenocarcinomas can develop in women and may mimic inflammatory metastasis of breast adenocarcinoma. Immunohistochemistry is invaluable in establishing the correct diagnosis.

A comparative review of cutaneous pH.

PubMed

Matousek, Jennifer L; Campbell, Karen L

2002-12-01

This review describes the role of pH in cutaneous structure and function. We first describe the molecules that contribute to the acidity or alkalinity of the skin. Next, differences in cutaneous pH among species, among individuals of the same species and within individuals are described. The potential functions of cutaneous pH in normal and diseased skin are analysed. For example, cutaneous pH has a role in the selection and maintenance of the normal cutaneous microbiota. In addition, cutaneous acidity may protect the skin against infection by microbes. Finally, there is evidence that a cutaneous pH gradient activates pH-dependent enzymes involved in the process of keratinization.

Cutaneous mucormycosis secondary to penetrative trauma.

PubMed

Zahoor, Bilal; Kent, Stephen; Wall, Daryl

2016-07-01

Mucormycosis is a rare but serious sequelae of penetrating trauma [1-5]. In spite of aggressive management, mortality remains high due to dissemination of infection. We completed a review of literature to determine the most optimal treatment of cutaneous mucormycosis which occurs secondary to penetrating trauma. We completed a review regarding the management of mucormycosis in trauma patients. We selected a total of 36 reports, of which 18 were case-based, for review. Surgical debridement is a primary predictor of improved outcomes in the treatment of mucormycosis [3,6,7]. Anti-fungal therapy, especially lipid soluble formulation of Amphotericin B, is helpful as an adjunct or when surgical debridement has been maximally achieved. Further research is needed to fully evaluate the impact of topical dressings; negative pressure wound therapy is helpful. An aggressive and early surgical approach, even at the expense of disfigurement, is necessary to reduce mortality in the setting of cutaneous mucormycosis that results from penetrating trauma [4,8,9]. Anti-fungal therapy and negative pressure wound therapy are formidable adjuncts. Copyright © 2016 Elsevier Ltd. All rights reserved.

Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases.

PubMed

Gehl, Julie; Sersa, Gregor; Matthiessen, Louise Wichmann; Muir, Tobian; Soden, Declan; Occhini, Antonio; Quaglino, Pietro; Curatolo, Pietro; Campana, Luca G; Kunte, Christian; Clover, A James P; Bertino, Giulia; Farricha, Victor; Odili, Joy; Dahlstrom, Karin; Benazzo, Marco; Mir, Lluis M

2018-03-25

Electrochemotherapy is now in routine clinical use to treat cutaneous metastases of any histology, and is listed in national and international guidelines for cutaneous metastases and primary skin cancer. Electrochemotherapy is used by dermatologists, surgeons, and oncologists, and for different degrees and manifestations of metastases to skin and primary skin tumours not amenable to surgery. This treatment utilises electric pulses to permeabilize cell membranes in tumours, thus allowing a dramatic increase of the cytotoxicity of anti-cancer agents. Response rates, often after only one treatment, are very high across all tumour types. The most frequent indications are cutaneous metastases from malignant melanoma and breast cancer. In 2006, standard operating procedures (SOPs) were written for this novel technology, greatly facilitating introduction and dissemination of the therapy. Since then considerable experience has been obtained treating a wider range of tumour histologies and increasing size of tumours which was not originally thought possible. A pan-European expert panel drawn from a range of disciplines from dermatology, general surgery, head and neck surgery, plastic surgery, and oncology met to form a consensus opinion to update the SOPs based on the experience obtained. This paper contains these updated recommendations for indications for electrochemotherapy, pre-treatment information and evaluation, treatment choices, as well as follow-up.

Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in resting heated humans.

PubMed

Fujii, Naoto; Honda, Yasushi; Delliaux, Stephane; Tsuji, Bun; Watanabe, Kazuhito; Sugihara, Akira; Kondo, Narihiko; Nishiyasu, Takeshi

2012-11-01

Hypocapnia attenuates the sweat response normally seen in hyperthermic resting subjects, but its effect on the blood flow response in their nonglabrous skin under the same hyperthermic conditions remains unclear. In the present study, we investigated whether hypocapnia induced by voluntary hyperventilation affects the blood flow response to heat stress in the nonglabrous skin of resting humans. Nine healthy male subjects were passively heated using legs-only hot water immersion and a water-perfused suit, which caused esophageal temperature (T(es)) to increase by as much as 1.0°C. During normothermia and at +0.6°C T(es) and +1.0°C T(es), the subjects performed two voluntary 7-min hyperventilation (minute ventilation = 40 l/min) trials (hypocapnic and eucapnic) in random order. End-tidal CO(2) pressure was reduced by 23-25 torr during hypocapnic hyperventilation, but it was maintained at the spontaneous breathing level during eucapnic hyperventilation. Cutaneous blood flow was evaluated as the cutaneous red blood cell flux in the forearm (CBF(forearm)) or forehead (CBF(forehead)) and was normalized to the normothermic spontaneous breathing value. Hypocapnic hyperventilation at +0.6°C T(es) was associated with significantly reduced CBF(forearm), compared with eucapnic hyperventilation, after 5-7 min of hyperventilation (395 to 429 vs. 487 to 525% baseline, P < 0.05). No significant difference in CBF(forehead) was seen during hypocapnic hyperventilation compared with eucapnic hyperventilation at +0.6°C T(es) or +1.0°C T(es). These results suggest that in resting humans, hypocapnia achieved through voluntary hyperventilation attenuates the increase in cutaneous blood flow elicited by moderate heat stress in the nonglabrous skin of the forearm, but not the forehead.

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.

PubMed

Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

2015-05-01

Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT. Copyright © 2015 Elsevier Inc. All rights reserved.

Cutaneous protothecosis.

PubMed

Hillesheim, Paul B; Bahrami, Soon

2011-07-01

Prototheca species are an achlorophyllic algae that cause infections primarily in immunocompromised individuals. At least one-half of infectious cases are cutaneous. Because protothecosis is seldom suspected clinically, patients may be subjected to various treatment modalities for extended periods without satisfactory results. Cutaneous protothecosis shares similar clinical and pathologic findings with deep tissue fungal mycoses. The typical presentation occurs most commonly on the face and extremities as erythematous plaques, nodules, or superficial ulcers. Prototheca spp are spherical, unicellular, nonbudding organisms that are sometimes noted on routine hematoxylin-eosin staining but are best visualized with periodic acid-Schiff and Gomori methenamine-silver histochemical stains. Although protothecosis can be diagnosed on biopsy, culture of the organism on a medium such as Sabouraud dextrose agar is required for definitive diagnosis. Treatment may require a combination of surgical excision and antifungal agents. Therefore, cutaneous protothecosis should be considered in a lesion that appears suspicious for the more-common fungal infections.

New epidemiological aspects of visceral and cutaneous leishmaniasis in Taza, Morocco.

PubMed

Hakkour, Maryam; Hmamouch, Asmae; El Alem, Mohamed Mahmoud; Rhalem, Abdelkbir; Amarir, Fatima; Touzani, Mohamed; Sadak, Abderrahim; Fellah, Hajiba; Sebti, Faiza

2016-11-29

Leishmaniasis is considered among the main endemic diseases in Morocco. However, further knowledge about epidemiological aspects of this disease is needed in several provinces to plan control and preventive strategies to tackle the disease. The present study aims to determine the epidemiological aspect of cutaneous and visceral leishmaniasis in Taza Province from 2007-2014 and to identify the circulating species in this province. The temporal study from 2007 to 2014 showed that the number of cutaneous leishmaniasis cases increased since 2010. During the period of study, most leishmaniasis cases were detected in both urban and rural areas with 34% of cases detected in two urban localities, Bab Zitouna and Bab tété with 297 and 106 cases, respectively. The molecular study of cutaneous leishmaniasis showed the presence of non-sporadic Leishmania infantum and Leishmania tropica in this province. Regarding visceral leishmaniasis, Leishmania infantum is the species that has been identified. The epidemio-molecular study of leishmaniasis in Taza Province showed the coexistence of two species of Leishmania in the same foci. They also indicated that CL due to Leishmania infantum is more prevalent than reported in the literature. These results will be helpful for the implementation of control strategies by targeting dogs that constitute a reservoir of Leishmania infantum.

Common Child and Adolescent Cutaneous Infestations and Fungal Infections.

PubMed

Alter, Sherman J; McDonald, Megan B; Schloemer, Julie; Simon, Ryan; Trevino, Julian

2018-01-01

Cutaneous infections and infestations are common among children and adolescents. Ectoparasitic infestations affect individuals across the globe. Head lice, body lice, scabies, and infestations with bed bugs are seen in individuals who reside in both resource poor areas and in developed countries. Superficial cutaneous and mucosal candida infections occur throughout the life cycle. Dermatophyte infections of keratin-containing skin and skin structures result in tinea capitis (scalp), tinea corporis (body), tinea pedis (foot), and tinea unguium (nails). Less frequent endemic fungal infections such as blastomycosis, coccidiodomycosis, and histoplasmosis may present with skin findings. This article will describe the epidemiology and transmission of these conditions as well as their clinical manifestations. The approach to diagnosis will be addressed as well as primary prevention and current therapies. Copyright © 2018 Mosby, Inc. All rights reserved.

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

PubMed

Bartralot, R; García-Patos, V; Sitjas, D; Rodríguez-Cano, L; Mollet, J; Martín-Casabona, N; Coll, P; Castells, A; Pujol, R M

2005-04-01

Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.

Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

NASA Astrophysics Data System (ADS)

Williams, Ifor R.; Kupper, Thomas S.

1994-10-01

Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

Cutaneous metastases of prostatic adenocarcinoma

PubMed Central

Patne, Shashikant C.U.; Naik, Bitan; Patnaik, Pranab; Trivedi, Sameer

2015-01-01

Prostatic adenocarcinoma (PA) is a common visceral malignancy of elderly men. Cutaneous metastasis of PA is rare. The incidence is <1%. A 55-year-old man presented with urinary symptoms and multiple cutaneous nodules around suprapubic region, inner aspect of both thighs and scrotum. Fine-needle aspiration cytology (FNAC) of cutaneous nodules was suggestive of metastatic adenocarcinoma. Skin and prostatic biopsies confirmed the cytological diagnosis. Serum level of prostate specific antigen was raised. Total prostatectomy revealed adenocarcinoma of Gleason's score 7 (3 + 4). Though rare, cutaneous metastases of PA must be known to cytopathologists. Meticulously performed FNAC in such cases may help in early diagnosis. PMID:26229250

Cryptococcal meningitis with secondary cutaneous involvement in an immunocompetent host.

PubMed

Tabassum, Saadia; Rahman, Atiya; Herekar, Fivzia; Masood, Sadia

2013-09-16

Cryptococcosis is a potentially fatal fungal disease caused by variants of Cryptococcus neoformans species.  The respiratory tract is the usual portal of entry, with a peculiar predilection to invade the central nervous system.  The skin can be secondarily involved in disseminated infection or be exceptionally involved as primary cutaneous infection by inoculation.  The disease is mostly seen in immunodeficiency states.  The diagnosis is frequently unsuspected in immunocompetent patients. We report a case of disseminated cryptococcal meningitis in an immunocompetent young adult. The cutaneous eruption prompted the accurate diagnosis.  The patient, a 20-year-old female, had fever, cough, headache and intractable vomiting for the past two months and was being managed as a case of tuberculous meningitis. Two weeks after starting antituberculous treatment she developed umbilicated papules on the head and neck region. Necessary laboratory workup identified C. neoformans in cerebrospinal fluid (CSF) and skin specimens.  The titers of cryptococcal antigen were measured in CSF and serum for diagnostic and prognostic purposes.  Anti-fungal treatment resulted in regression of the cutaneous lesions and resolution of systemic complaints. The case highlights the need for high degree of suspicion, especially in healthy young adults, in the diagnosis of cryptococcosis. The cutaneous eruptions can be the first manifestation or a diagnostic clue of enormous significance.

Skeletal Muscle Satellite Cell Activation Following Cutaneous Burn in Rats

DTIC Science & Technology

2013-12-01

satellite cell activation and survival during oxidative stress. J Muscle Res Cell Motil 2011;32(2):99–109. [33] Rathbone CR, Booth FW, Lees SJ. Sirt1 ...Skeletal muscle satellite cell activation following cutaneous burn in rats Xiaowu Wu*, Thomas J. Walters, Christopher R. Rathbone Extremity Trauma...f o Article history: Accepted 15 October 2012 Keywords: Muscle precursor cell Thermal injury Atrophy Skeletal muscle Activation a b s t r a c t

Continent cutaneous diversion.

PubMed

Skinner, Eila C

2015-11-01

This article updates the recently reported intermediate to long-term results with the most commonly used forms of continent cutaneous urinary diversion, and to discuss approaches to early and late complications. Many variations on construction of a continent cutaneous diversion have been described. Results with large series of patients demonstrate acceptable results with all of them, but with a significant revision rate. Long-term complication rates and adaptation to robotic approaches have recently been described. Continent cutaneous diversion is rarely offered in the USA to patients undergoing cystectomy except in a few centers. Most studies have found a high complication rate and need for revision surgery in 10-20% of patients. However, functional results are acceptable and many patients are willing to accept the complications in exchange for avoiding an external appliance.

Responses to romidepsin in patients with cutaneous T-cell lymphoma and prior treatment with systemic chemotherapy.

PubMed

Duvic, Madeleine; Bates, Susan E; Piekarz, Richard; Eisch, Robin; Kim, Youn H; Lerner, Adam; Robak, Tadeusz; Samtsov, Alexey; Becker, Jürgen C; McCulloch, William; Waksman, Joel; Whittaker, Sean

2018-04-01

Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy. Patients with prior chemotherapy were able to achieve durable responses to romidepsin, and response rates were similar to those in patients who were chemotherapy naïve. Overall, no new safety signals emerged in patients who had received prior chemotherapy. The data presented here suggest that romidepsin is safe and effective in patients with CTCL who received prior systemic chemotherapy.

Immunocompromised patients with metastatic cutaneous nodal squamous cell carcinoma of the head and neck: Poor outcome unrelated to the index lesion.

PubMed

Lam, Johnson K S; Sundaresan, Puma; Gebski, Val; Veness, Michael J

2018-05-01

Immunocompromised patients with metastatic cutaneous nodal head and neck squamous cell carcinoma (HNSCC) have worse outcomes compared to the immunocompetent. The purpose of this study was to investigate the characteristics of the primary cutaneous squamous cell carcinoma (SCC), nodal pathology, and outcome between these 2 groups. Analysis of a prospective database was performed. A 2:1 pooled analysis selected 46 immunocompetent patients matched with 23 immunocompromised patients. Overall survival (OS) and relapse-free survival (RFS) were calculated using the Kaplan-Meier method. No significant difference was found in the primary tumor characteristics between the 2 groups. In the immunocompromised group, RFS (hazard ratio [HR] 2.70; P = .01) and OS (HR 2.32; P = .04) were significantly worse. Extracapsular spread was present in 100% of the immunocompromised patients. No significant difference was identified in the primary cutaneous SCC between the immunocompetent and immunocompromised patients. Immunosuppression predicted worse outcome. © 2018 Wiley Periodicals, Inc.

T-Cell-Mediated Immune Responses in Patients with Cutaneous or Mucosal Leishmaniasis: Long-Term Evaluation after Therapy

PubMed Central

Da-Cruz, Alda Maria; Bittar, Rita; Mattos, Marise; Oliveira-Neto, Manuel P.; Nogueira, Ricardo; Pinho-Ribeiro, Vanessa; Azeredo-Coutinho, Rilza Beatriz; Coutinho, Sergio G.

2002-01-01

T-cell immune responses in patients with cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) were studied during the active disease, at the end of therapy, and 1 to 17 years posttherapy (long-term follow-up). Lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+ Leishmania-reactive T cells, and cytokine production were assayed. Patients with active ML and CL showed higher proportions of CD4+ than CD8+ T cells. In CL, the healing process was associated with a decrease of CD4+ and an increase of CD8+, leading to similar CD4+ and CD8+ proportions. This pattern was only seen in ML after long-term therapy. Long-term follow-up of patients with CL showed a positive CD4+/CD8+ ratio as observed during the active disease, although the percentages of these T cell subsets were significantly lower. Patients with CL did not show significant differences between gamma interferon (IFN-γ) and interleukin-5 (IL-5) production during the period of study. Patients with active ML presented higher IFN-γ and IL-5 levels compared to patients with active CL. IL-4 was only detected during active disease. Patients long term after cure from ML showed increasing production of IFN-γ, significant decrease of IL-5, and no IL-4 production. Two apparently beneficial immunological parameters were detected in tegumentary leishmaniasis: (i) decreasing proportions of CD4+ Leishmania-reactive T cells in the absence of IL-4 production associated with cure of CL and ML and (ii) decreasing levels of IL-5 long after cure, better detected in patients with ML. The observed T-cell responses maintained for a long period in healed patients could be relevant for immunoprotection against reinfection and used as a parameter for determining the prognosis of patients and selecting future vaccine preparations. PMID:11874860

Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk; Gniadecki, Robert; Iversen, Lars

2015-05-01

Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gymore » in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.« less

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

PubMed

Seibel, W; Sundberg, J P; Lesko, L J; Sauk, J J; McCleary, L B; Hassell, T M

1989-08-01

All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

Choledochorraphy (primary repair) versus t-tube drainage after open choledochotomy.

PubMed

Saeed, Nadia; Nasir, Muhammad Tauqeer; Khan, Muhammad Iqbal; Channa, Ghulam Asghar

2012-01-01

T-tube drainage used to be standard practice after surgical choledochotomy, but there is now a tendency in some canters to close the common bile duct primarily. This study was designed to compare the clinical results of primary closure with T-tube drainage after open choledocotomy and assess the safety of primary closure for future application. This study was conducted at surgical Unit-3, ward 26 Jinnah Postgraduate Medical Centre Karachi, from January 2007 to January 2008. Forty patients were included in this study out of which 20 underwent primary closure and 20 T-tube placements. It was Quasi-experimental, non-probability, purposive sampling. Main outcome measures were operating time, duration of hospital stay, and postoperative complications. SPSS-10 was used for data analysis. The age of patients in the study ranged from 29-83 years. There were 3 male while 37 female patients. Group-1 consisted of 20 patients underwent primary closure after choledocotomy, while Group-2 also consisted of 20 patients underwent T-tube drainage after duct exploration. Mean hospital stay in Group-1 patients was 7.63 days while in group 2 it was 13.6 days. Overall complication rate in group 1 was 15%, biliary leakage in 1 (5%), jaundice in 1 (5%), wound infection in 1 (5%). No re-exploration was required in Group-1. In Group-2 overall complication rate was 30%, biliary leakage in 2 (2%), jaundice in 1 (5%), dislodgement of T-tube in 1 (5%), wound infection in 1 (5%), and sepsis in 1 (5%) patients. Re-exploration was done in one patient. Primary closure of Common Bile Duct (CBD) is a safe and cost-effective alternative procedure to routine T-tube drainage after open choledocotomy.

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.

PubMed

Stephen, Sasha; Morrissey, Kelly A; Benoit, Bernice M; Kim, Ellen J; Vittorio, Carmela C; Nasta, Sunita D; Showe, Louise C; Wysocka, Maria; Rook, Alain H

2012-02-01

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

Array-based comparative genomic hybridization analysis reveals recurrent chromosomal alterations and prognostic parameters in primary cutaneous large B-cell lymphoma.

PubMed

Dijkman, Remco; Tensen, Cornelis P; Jordanova, Ekaterina S; Knijnenburg, Jeroen; Hoefnagel, Juliette J; Mulder, Aat A; Rosenberg, Carla; Raap, Anton K; Willemze, Rein; Szuhai, Károly; Vermeer, Maarten H

2006-01-10

To evaluate the clinical relevance of genomic aberrations in primary cutaneous large B-cell lymphoma (PCLBCL). Skin biopsy samples of 31 patients with a PCLBCL classified as either primary cutaneous follicle center lymphoma (PCFCL; n = 19) or PCLBCL, leg type (n = 12), according to the WHO-European Organisation for Research and Treatment of Cancer (EORTC) classification, were investigated using array-based comparative genomic hybridization, fluorescence in situ hybridization (FISH), and examination of promoter hypermethylation. The most recurrent alterations in PCFCL were high-level DNA amplifications at 2p16.1 (63%) and deletion of chromosome 14q32.33 (68%). FISH analysis confirmed c-REL amplification in patients with gains at 2p16.1. In PCLBCL, leg type, most prominent aberrations were a high-level DNA amplification of 18q21.31-q21.33 (67%), including the BCL-2 and MALT1 genes as confirmed by FISH, and deletions of a small region within 9p21.3 containing the CDKN2A, CDKN2B, and NSG-x genes. Homozygous deletion of 9p21.3 was detected in five of 12 patients with PCLBCL, leg type, but in zero of 19 patients with PCFCL. Complete methylation of the promoter region of the CDKN2A gene was demonstrated in one PCLBCL, leg type, patient with hemizygous deletion, in one patient without deletion, but in zero of 19 patients with PCFCL. Seven of seven PCLBCL, leg type, patients with deletion of 9p21.3 and/or complete methylation of CDKN2A died as a result of their lymphoma. Our results demonstrate prominent differences in chromosomal alterations between PCFCL and PCLBCL, leg type, that support their classification as separate entities within the WHO-EORTC scheme. Inactivation of CDKN2A by either deletion or methylation of its promoter could be an important prognostic parameter for the group of PCLBCL, leg type.

Characterization of systemic disease in primary Sjögren's syndrome: EULAR-SS Task Force recommendations for articular, cutaneous, pulmonary and renal involvements.

PubMed

Ramos-Casals, Manuel; Brito-Zerón, Pilar; Seror, Raphaèle; Bootsma, Hendrika; Bowman, Simon J; Dörner, Thomas; Gottenberg, Jacques-Eric; Mariette, Xavier; Theander, Elke; Bombardieri, Stefano; De Vita, Salvatore; Mandl, Thomas; Ng, Wan-Fai; Kruize, Aike; Tzioufas, Athanasios; Vitali, Claudio

2015-12-01

To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS. The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features. The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ. The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights

Treatment of Cutaneous Lupus Erythematosus

PubMed Central

Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

Changing presentation of cutaneous malignant melanoma.

PubMed

Klit, Anders; Lassen, Cecilie Brandt; Olsen, Caroline Holkmann; Lock-Andersen, Jørgen

2015-10-01

The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. none. The study has been approved by the Danish National Data Protection Agency.

T cell-B cell interactions in primary immunodeficiencies.

PubMed

Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

2012-02-01

Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

Cytomegalovirus-associated cutaneous vasculopathy and scleroderma sans inclusion body change.

PubMed

Magro, Cynthia M; Crowson, A Neil; Ferri, Clodoveo

2007-01-01

Viruses have long been held to be of pathogenetic importance in the evolution of autoimmune connective tissue disease. We describe 7 adults who developed cutaneous connective tissue disease stigmata in temporal association with recent cytomegalovirus (CMV) infection but without the classic cytopathic changes of CMV infection. We examined 7 adults with clinical presentations encompassing cutaneous vasculitis in 4 and scleroderma in 3. In all 7 patients, there was either IgM seropositivity for CMV and/or CMV DNA isolation from peripheral blood. Although no CMV inclusions were seen, in situ hybridization studies revealed very focal CMV RNA transcript expression with localization mainly to the endothelium. The patients with vasculitis treated with ganciclovir had improvement or resolution of symptoms, whereas only 1 patient with scleroderma received antiviral therapy, without benefit. Another scleroderma patient responded to infliximab therapy. Abortive/partial CMV reactivation can be associated with a syndrome complex mimicking and/or triggering a primary immune-based cutaneous microvascular injury syndrome. Antiviral therapy appears to be of therapeutic value in those cases associated with active necrotizing vasculitic changes. The role of tumor necrosis factor alpha blockers in scleroderma cases temporally associated with CMV infection requires further evaluation.

Genomic analysis and clinical management of adolescent cutaneous melanoma.

PubMed

Rabbie, Roy; Rashid, Mamunur; Arance, Ana M; Sánchez, Marcelo; Tell-Marti, Gemma; Potrony, Miriam; Conill, Carles; van Doorn, Remco; Dentro, Stefan; Gruis, Nelleke A; Corrie, Pippa; Iyer, Vivek; Robles-Espinoza, Carla Daniela; Puig-Butille, Joan A; Puig, Susana; Adams, David J

2017-05-01

Melanoma in young children is rare; however, its incidence in adolescents and young adults is rising. We describe the clinical course of a 15-year-old female diagnosed with AJCC stage IB non-ulcerated primary melanoma, who died from metastatic disease 4 years after diagnosis despite three lines of modern systemic therapy. We also present the complete genomic profile of her tumour and compare this to a further series of 13 adolescent melanomas and 275 adult cutaneous melanomas. A somatic BRAF V 600E mutation and a high mutational load equivalent to that found in adult melanoma and composed primarily of C>T mutations were observed. A germline genomic analysis alongside a series of 23 children and adolescents with melanoma revealed no mutations in known germline melanoma-predisposing genes. Adolescent melanomas appear to have genomes that are as complex as those arising in adulthood and their clinical course can, as with adults, be unpredictable. © 2017 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

Metastatic breast disease from cutaneous malignant melanoma.

PubMed

Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

2014-01-01

Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD4+Foxp3+CD25- T-cells in patients with leukemic cutaneous T-cell lymphoma

PubMed Central

Shiue, Lisa H.; Couturier, Jacob; Lewis, Dorothy E.; Wei, Caimiao; Ni, Xiao; Duvic, Madeleine

2015-01-01

Purpose Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T-cell and CD8+ T-cells in L-CTCL patients. Experimental Design Peripheral blood from 18 L-CTCL patients at baseline, Day 2, 1-month, 3-month, and 6-month post-ECP therapy were analyzed by flow cytometry for CD4+CD25+/high, CD4+Foxp3+CD25+/-, CD3+CD8+, CD3+CD8+CD69+, and CD3+CD8+IFN-γ+ T-cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. Results Twelve of 18 patients achieved clinical responses. The average baseline number of CD4+CD25+/high T-cells of PBMCs in L-CTCL patients was normal (2.2%), but increased at 6-month post-therapy (4.3%, p<0.01). The average baseline number of CD4+Foxp3+ T-cells out of CD4+ T-cells in 9 evaluable patients was high (66.8±13.7%), mostly CD25 negative. The levels of CD4+Foxp3+ T cells in responders were higher (n=6, 93.1±5.7%) than non-responders (n=3, 14.2±16.0%, p<0.01), and they declined in parallel with malignant T-cells. The numbers of CD3+CD8+CD69+ and CD3+CD8+ IFN-γ+ T-cells increased at 3-month post-therapy in 5 of 6 patients studied. Conclusions ECP alone or in combination therapy might be effective in L-CTCL patients whose malignant T-cells have a CD4+Foxp3+CD25- phenotype. PMID:25772268

Quality of Life in Cutaneous Lupus Erythematosus

PubMed Central

Klein, Rachel; Moghadam-Kia, Siamak; Taylor, Lynne; Coley, Christopher; Okawa, Joyce; LoMonico, Jonathan; Chren, Mary-Margaret; Werth, Victoria P.

2010-01-01

Background Little is known about quality of life in patients with cutaneous lupus erythematosus. Objective We sought to determine how cutaneous lupus affects quality of life and which independent variables are associated with poor quality of life. Methods 157 patients with cutaneous lupus completed surveys related to quality of life, including the Skindex-29 and the SF-36. Results Quality of life in cutaneous lupus is severely impaired, particularly with respect to emotional well-being. Patients with cutaneous lupus have worse quality of life than those with other common dermatologic conditions, such as acne, non-melanoma skin cancer, and alopecia. With respect to mental health status, patients with cutaneous lupus have similar or worse scores than patients with hypertension, type 2 diabetes mellitus, recent myocardial infarction, and congestive heart failure. Factors related to poor quality of life include female gender, generalized disease, severe disease, distribution of lesions, and younger age. Limitations The study was done at a single referral-only center. Conclusion Patients with cutaneous lupus have very impaired quality of life, particularly from an emotional perspective. PMID:21397983

A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania Major Infection

DTIC Science & Technology

2010-01-01

A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania major...United States of America Abstract Background: Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan...with other species of Leishmania , or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two

Cutaneous Manifestation of Food Allergy.

PubMed

Tam, Jonathan S

2017-02-01

Hypersensitivity reactions to foods can have diverse and highly variable manifestations. Cutaneous reactions, such as acute urticaria and angioedema, are among the most common manifestations of food allergy. However, cutaneous manifestations of food allergy encompass more than just IgE-mediated processes and include atopic dermatitis, contact dermatitis, and even dermatitis herpetiformis. These cutaneous manifestations provide an opportunity to better understand the diversity of adverse immunologic responses to food and the interconnected pathways that produce them. Copyright © 2016 Elsevier Inc. All rights reserved.

Primary T-cell Lymphoma of the Colon

PubMed Central

Son, Hee Jung; Rhee, Poong Lyul; Kim, Jae-Jun; Koh, Kwang Choel; Paik, Seong Woon; Rhee, Jong Chul; Koh, Young Hae

1997-01-01

A 40-year-old woman had been diagnosed with Crohns disease in September 1994, but later examinations revealed a primary T-cell lymphoma of the colon. Colonoscopic and histological examination showed ulcerative lesions simulating Crohns disease involving the entire colon and the terminal ileum, and she was first diagnosed as having Crohns disease. Differential therapeutic strategies, including corticosteroid, had improved the symptoms which were dominated by abdominal pain. When she visited our institute in April 1995, she presented with bloody stool twice a day, 7kg weight loss in a period of six months and a slightly painful abdomen. Colonoscopic finding showed geographic ulceration on the entire colon, especially rectum and terminal ileum. The histologic examination of specimens from colonoscopic biopsy showed primary peripheral T-cell lymphoma of the colon. Any dense lymphocyte infiltrates seen in the biopsy specimens obtained from lesions simulating ulcerative colitis or Crohns disease should be assessed to exclude intestinal lymphoma PMID:9439161

T-tube drainage versus primary closure after laparoscopic common bile duct exploration.

PubMed

Gurusamy, Kurinchi Selvan; Koti, Rahul; Davidson, Brian R

2013-06-21

T-tube drainage may prevent bile leak from the biliary tract following bile duct exploration and it offers post-operative access to the bile ducts for visualisation and exploration. Use of T-tube drainage after laparoscopic common bile duct (CBD) exploration is controversial. To assess the benefits and harms of T-tube drainage versus primary closure after laparoscopic common bile duct exploration. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until April 2013. We included all randomised clinical trials comparing T-tube drainage versus primary closure after laparoscopic common bile duct exploration. Two of four authors independently identified the studies for inclusion and extracted data. We analysed the data with both the fixed-effect and the random-effects model meta-analyses using Review Manager (RevMan) Analysis. For each outcome we calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis. We included three trials randomising 295 participants: 147 to T-tube drainage versus 148 to primary closure. All trials had a high risk of bias. No one died during the follow-up period. There was no significant difference in the proportion of patients with serious morbidity (17/147 (weighted percentage 11.3%) in the T-tube drainage versus 9/148 (6.1%) in the primary closure group; RR 1.86; 95% CI 0.87 to 3.96; three trials), and no significant difference was found in the serious morbidity rates (weighted serious morbidity rate = 97 events per 1000 patients) in participants randomised to T-tube drainage versus serious morbidity rate = 61 events per 1000 patients in the primary closure group; RR 1.59; 95% CI 0.66 to 3.83; three trials). Quality of life was not reported in any of the trials. The operating time was significantly longer in the T-tube drainage group compared with the primary

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma.

PubMed

Tejera-Vaquerizo, Antonio; Nagore, Eduardo; Puig, Susana; Robert, Caroline; Saiag, Philippe; Martín-Cuevas, Paula; Gallego, Elena; Herrera-Acosta, Enrique; Aguilera, José; Malvehy, Josep; Carrera, Cristina; Cavalcanti, Andrea; Rull, Ramón; Vilalta-Solsona, Antonio; Lannoy, Emilie; Boutros, Celine; Benannoune, Naima; Tomasic, Gorana; Aegerte, Philippe; Vidal-Sicart, Sergi; Palou, Josep; Alos, L Lúcia; Requena, Celia; Traves, Víctor; Pla, Ángel; Bolumar, Isidro; Soriano, Virtudes; Guillén, Carlos; Herrera-Ceballos, Enrique

2015-09-01

In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Progression of undiagnosed cutaneous lymphoma after anti-tumor necrosis factor-alpha therapy.

PubMed

Martinez-Escala, Maria Estela; Posligua, Alba L; Wickless, Heather; Rutherford, Audrey; Sable, Kimberly A; Rubio-Gonzalez, Belen; Zhou, Xiaolong A; Kaplan, Jason B; Pro, Barbara; Choi, Jaehyuk; Querfeld, Christiane; Rosen, Steven T; Guitart, Joan

2018-06-01

Cutaneous lymphoma diagnosed after anti-tumor necrosis factor-α therapy (anti-TNF-α) has been reported in the literature, yet a clear link between both events remains elusive. To review our experience with cutaneous lymphoma diagnosed during or after the use of anti-TNF-α therapies. This is a multicenter retrospective study and a literature review. A total of 22 cases, including 20 cutaneous T-cell lymphomas (CTCLs) and 2 cutaneous B-cell lymphomas, were identified. In the CTCL group, 75% of the patients received an anti-TNF-α agent for a presumed inflammatory skin condition. Mycosis fungoides and Sézary syndrome were the most common subtypes of CTCL diagnosed. Advanced disease (stage IIB to IVA) was commonly seen at time of diagnosis and required aggressive therapy, including stem cell transplant in 3 patients; 2 patients in whom cutaneous B-cell lymphomas was diagnosed had an indolent course. A total of 31 cases were gathered from a literature search. This is a retrospective study. Our findings suggest that the disease of most of the identified patients was misdiagnosed as psoriasis or eczema; therefore, a comprehensive morphologic and molecular review of skin biopsy specimens and peripheral blood samples should be considered before initiation of anti-TNF-α therapy in patients with poorly defined dermatitis or atypical presentations of psoriasis. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cutaneous acquired toxoplasmosis in a child: a case report and review of the literature.

PubMed

Rand, Andrew J; Buck, Andrew B; Love, Porcia B; Prose, Neil S; Selim, M Angelica

2015-04-01

Cutaneous toxoplasmosis is a rare and diagnostically challenging entity. Today, the acquired form occurs predominantly in immunocompromised patients with human immunodeficiency virus or after hematopoietic stem cell transplantation. We report a case of cutaneous toxoplasmosis in a 6-year-old girl after allogeneic stem cell transplantation for immune-mediated encephalopathy, first manifesting at 16 months of age. In the post-transplant setting, she developed a rash consisting of approximately 8 scattered 3–4-mm round, erythematous macules and papules on her back, abdomen, and right shoulder. Sections from a biopsy of a lesion on the back revealed numerous spherules tightly packed within small cystic structures in the epidermis. The diagnosis of cutaneous toxoplasmosis was confirmed by an immunohistochemical stain for Toxoplasma gondii and polymerase chain reaction on the peripheral blood for the T. gondii genome. This case should raise awareness that acquired toxoplasmosis with cutaneous involvement can occur in the pediatric population, particularly in immunocompromised patients after stem cell transplantation. Early diagnosis and treatment of this life-threatening opportunistic infection may improve patient outcomes.

Immune responses in dogs with cutaneous adverse food reactions.

PubMed

Veenhof, E Z; Knol, E F; Willemse, T; Rutten, V P M G

2012-06-01

Adverse food reactions (AFR) in dogs are reactions due to apparently harmless food antigens, with an unknown aetiology, i.e. immunopathogenesis. Despite the entry of food allergens via the intestinal tract, in the majority of dogs with AFR, clinical symptoms are only associated with the skin (CAFR). In the present review, factors are presented of relevance in triggering the differentiation of naive T cells into effector T cell types and the role of these T cell types in allergy. More specifically, the allergic immune responses in intestine and skin are discussed in this article as well as the potential pathways, e.g. homing of antigen presenting cells or allergen-induced T cells to the skin, of induction of cutaneous symptoms.

Rate of regional nodal metastases of cutaneous squamous cell carcinoma in the immunosuppressed patient.

PubMed

McLaughlin, Eamon J; Miller, Lauren; Shin, Thuzar M; Sobanko, Joseph F; Cannady, Steven B; Miller, Christopher J; Newman, Jason G

Immunosuppressed solid organ transplant recipients (SOTRs) have an increased risk of developing cutaneous squamous cell carcinomas (cSCCs) with metastatic potential. This study sought to determine the rate of regional lymph node involvement in a large cohort of solid organ transplant patients with cutaneous head and neck squamous cell carcinoma. A retrospective chart review was performed on solid organ transplant patients with head and neck cutaneous squamous cell carcinoma treated at a tertiary academic medical center from 2005 to 2015. 130 solid organ transplant patients underwent resection of 383 head and neck cutaneous squamous cell carcinomas. The average age of the patient was 63. Seven patients (5%) developed regional lymph node metastases (3 parotid, 4 cervical lymph nodes). The mean time from primary tumor resection to diagnosis of regional lymphatic disease was 6.7months. Six of these patients underwent definitive surgical resection followed by adjuvant radiation; one patient underwent definitive chemoradiation. 6 of the 7 patients died of disease progression with a mean survival of 15months. The average follow up time was 3years (minimum 6months). Solid organ transplant recipients with cutaneous squamous cell carcinoma of the head and neck develop regional lymph node metastasis at a rate of 5%. Regional lymph node metastasis in this population has a poor prognosis and requires aggressive management and surveillance. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of kinesthetic and cutaneous stimulation during the learning of a viscous force field.

PubMed

Rosati, Giulio; Oscari, Fabio; Pacchierotti, Claudio; Prattichizzo, Domenico

2014-01-01

Haptic stimulation can help humans learn perceptual motor skills, but the precise way in which it influences the learning process has not yet been clarified. This study investigates the role of the kinesthetic and cutaneous components of haptic feedback during the learning of a viscous curl field, taking also into account the influence of visual feedback. We present the results of an experiment in which 17 subjects were asked to make reaching movements while grasping a joystick and wearing a pair of cutaneous devices. Each device was able to provide cutaneous contact forces through a moving platform. The subjects received visual feedback about joystick's position. During the experiment, the system delivered a perturbation through (1) full haptic stimulation, (2) kinesthetic stimulation alone, (3) cutaneous stimulation alone, (4) altered visual feedback, or (5) altered visual feedback plus cutaneous stimulation. Conditions 1, 2, and 3 were also tested with the cancellation of the visual feedback of position error. Results indicate that kinesthetic stimuli played a primary role during motor adaptation to the viscous field, which is a fundamental premise to motor learning and rehabilitation. On the other hand, cutaneous stimulation alone appeared not to bring significant direct or adaptation effects, although it helped in reducing direct effects when used in addition to kinesthetic stimulation. The experimental conditions with visual cancellation of position error showed slower adaptation rates, indicating that visual feedback actively contributes to the formation of internal models. However, modest learning effects were detected when the visual information was used to render the viscous field.

Recurrent cutaneous leishmaniasis*

PubMed Central

Gomes, Ciro Martins; Damasco, Fabiana dos Santos; de Morais, Orlando Oliveira; de Paula, Carmen Déa Ribeiro; Sampaio, Raimunda Nonata Ribeiro

2013-01-01

We present a case of an 18-year-old male patient who, after two years of inappropriate treatment for cutaneous leishmaniasis, began to show nodules arising at the edges of the former healing scar. He was immune competent and denied any trauma. The diagnosis of recurrent cutaneous leishmaniasis was made following positive culture of aspirate samples. The patient was treated with N-methylglucamine associated with pentoxifylline for 30 days. Similar cases require special attention mainly because of the challenges imposed by treatment. PMID:23793208

Painful cutaneous metastases from esophageal carcinoma.

PubMed

Stein, Ronnit Hamuy; Spencer, James M

2002-10-01

Cutaneous metastases, which are not included among the painful dermal tumors, are primarily asymptomatic and of variable clinical appearance. Although, to our knowledge, this case report of painful cutaneous metastases is only the fifth in the literature, physicians who discover a painful tumor perhaps now should consider cutaneous metastasis. In this report, we describe painful nodular scalp lesions related to esophageal adenocarcinoma, which rarely metastasizes to the skin.

Cutaneous T cell lymphoma: Current practices in blood assessment and the utility of T-cell receptor Vβ chain restriction

PubMed Central

Gibson, Juliet F; Huang, Jing; Liu, Kristina J; Carlson, Kacie R; Foss, Francine; Choi, Jaehyuk; Edelson, Richard; Hussong, Jerry W.; Mohl, Ramsey; Hill, Sally; Girardi, Sally

2016-01-01

Background Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T cell lymphoma (CTCL) is important for early detection, prognosis, and monitoring disease burden. Objective Determine the spectrum of current clinical practices; critically evaluate elements of current ISCL B1 and B2 staging criteria; and assess the potential role of TCR-Vβ analysis by flow cytometry. Methods We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, PPV, and NPV of parameters for ISCL B2 staging. Results There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture five Yale cohort patients with immunophenotypic abnormalities who later progressed. TCR-Vβ testing was more specific than PCR and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. Limitations Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. Conclusion We propose further study of “modified B1 criteria”: CD4/CD8 ratio ≥5, %CD4+/CD26- ≥ 20%, %CD4+/CD7- ≥ 20%, with evidence of clonality. TCR-Vβ testing should be considered in future diagnostic and staging algorithms. PMID:26874819

Cutaneous sarcoidosis successfully treated with alefacept.

PubMed

Garcia-Zuazaga, Jorge; Korman, Neil J

2006-01-01

Sarcoidosis is a systemic granulomatous disease of unknown etiology that affects multiple organ systems, including the pulmonary, lymphatic, skeletal, and integumentary systems. Improved understanding of the intrinsic immunology and molecular biology in sarcoidosis can be applied to the treatment of this disease. Alefacept is a human fusion protein consisting of the extracellular domain of leukocyte function-associated antigen 3 fused with the Fc portion of human immunoglobulin G1. It works by blocking the interaction between antigen-presenting cells and T cells to inhibit activation and by inducing apoptosis of CD4+ T cells. In this case report, we describe a 46-year-old patient with recalcitrant lupus pernio who was successfully treated with alefacept. To determine whether T-cell inhibition, specifically the use of alefacept, may be used to treat a patient with recalcitrant cutaneous sarcoidosis. Case report. There was a modest clinical improvement after 8 weeks of intramuscular injections of alefacept. This case report provides further evidence of successful treatment of sarcoidosis with biologic agents directed against T-lymphocyte activation.

Efficacy of skin-directed therapy for cutaneous metastases from advanced cancer: a meta-analysis.

PubMed

Spratt, Daniel E; Gordon Spratt, Elizabeth A; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y; Lacouture, Mario E; Barker, Christopher A

2014-10-01

To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I(2) tests. After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. © 2014 by American Society of Clinical Oncology.

Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

PubMed Central

Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

2014-01-01

Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Epidemiology, management and survival outcomes of primary cutaneous melanoma: a ten-year overview.

PubMed

Aubuchon, M M F; Bolt, L J J; Janssen-Heijnen, M L G; Verleisdonk-Bolhaar, S T H P; van Marion, A; van Berlo, C L H

2017-02-01

Malignant melanoma (MM) is the most aggressive type of skin cancer, accounting for 90% of all the skin cancer mortality. The objective of this study was providing an overview of current patient- and tumour characteristics, treatment strategies, complications and survival in patients with MM over the past ten years. Hereby, an up-to-date view of every day clinical practice is obtained. Files of patients treated for primary cutaneous melanoma (n = 686) in the VieCuri Medical Centre in the Netherlands between January 2002 and December 2013 were retrospectively reviewed. Relevant patient features, tumour characteristics, and (surgical) outcomes were evaluated. The majority of all the patients presented thin tumours (59.1% stage 1A/in situ melanoma). Men showed more ulceration (17.7% vs. 8.4%, p < .01) and a significantly higher Breslow thickness than women (1.2 mm vs. 0.9 mm, p < .01). 14.6% (40/273) underwent sentinel lymph node biopsy (SLNB); 10/40 (25%) showed nodal metastasis, 50 patients (7.3%) developed distant metastases (M: 10.6%, F: 5%, p < .01). One-, 5- and 10- year disease specific survival rates were 96%, 86% and 84%, respectively. Median survival for stage 4 MM was 3 months. Extensive surgery was uncommon (n = 3). Patients generally presented with thin melanomas. Lymph node disease and distant metastases remained infrequently observed during following years, and general 1- and 5-year overall disease-specific survival rates exceeded 85%. Small numbers of rescue surgery and palliative medical treatment warrant further centralisation and investigation.

T-tube drainage versus primary closure after open common bile duct exploration.

PubMed

Gurusamy, Kurinchi Selvan; Koti, Rahul; Davidson, Brian R

2013-06-21

Between 5% and 11% of people undergoing cholecystectomy have common bile duct stones. Stones may be removed at the time of cholecystectomy by opening and clearing the common bile duct. The optimal technique is unclear. The aim is to assess the benefits and harms of T-tube drainage versus primary closure without biliary stent after open common bile duct exploration for common bile duct stones. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until April 2013. We included all randomised clinical trials comparing T-tube drainage versus primary closure after open common bile duct exploration. Two of four authors independently identified the studies for inclusion and extracted data. We analysed the data with both the fixed-effect and the random-effects model using Review Manager (RevMan) analyses. For each outcome we calculated the risk ratio (RR), rate ratio (RaR), or mean difference (MD) with 95% confidence interval (CI) based on intention-to-treat analysis. We included six trials randomising 359 participants, 178 to T-tube drainage and 181 to primary closure. All trials were at high risk of bias. There was no significant difference in mortality between the two groups (4/178 (weighted percentage 1.2%) in the T-tube group versus 1/181 (0.6%) in the primary closure group; RR 2.25; 95% CI 0.55 to 9.25; six trials). There was no significant difference in the serious morbidity rate between the two groups (24/136 (weighted serious morbidity rate, 145 events per 1000 patients) in the T-tube group versus 9/136 (weighted serious morbidity rate, 66 events per 1000 patients) in the primary closure group; RaR 2.19; 95% CI 0.98 to 4.91; four trials). Quality of life and return to work were not reported in any of the trials. The operating time was significantly longer in the T-tube drainage group compared with the primary

Tuberculose cutanée à Bamako, Mali

PubMed Central

Dicko, Adama; Faye, Ousmane; Fofana, Youssouf; Soumoutera, Moussa; Berthé, Siritio; Touré, Saidou; Traoré, Bekaye; Guindo, Binta; Tall, Koureissi; Keita, Alimata; Kéita, Lassine; Coulibaly, Karim; Keita, Somita

2017-01-01

Introduction La tuberculose est la mycobactériose la plus fréquente en Afrique subsaharienne. La localisation cutanée est rare et sous diagnostiquée à cause de son polymorphisme clinique et la faiblesse du plateau technique. Le but de cette étude était de décrire les aspects épidémiologiques, cliniques, histopathologiques de la tuberculose cutanée à Bamako (Mali). Méthodes De janvier 1991 à décembre 2008 nous avons réalisé une étude transversale descriptive. L’étude s’est déroulée dans le service de Dermatologie du Centre National d’Appui à la lutte contre la Maladie et le service de Pneumo-phtisiologie au l’hôpital du Point G. Ont été inclus dans l’étude les cas de tuberculose confirmés par l’histologie et ou la biologie. Résultats Sur 4269 dossiers, 61 cas de tuberculose cutanée étaient recensées (1,43%). Les hommes représentaient 59% des cas (36 malades) et les femmes 41 % soit (25 cas); soit un sex-ratio de 1,44. L’âge des malades variait de 3 mois à 61 ans pour une moyenne de 27,56 ± 36 ans. La durée d’évolution était en moyenne de 10,9 ± 10 mois. Les formes cliniques recensées étaient le scrofuloderme (41 cas), la forme ulcéreuse (13 cas), la forme verruqueuse (4 cas), et le lupus tuberculeux (3 cas). La tuberculose était associée au VIH dans 7 cas, à la lèpre dans 3 cas. Conclusion La tuberculose cutanée est sous diagnostiquée au Mali. Des efforts sont nécessaires pour améliorer l’accessibilité et le plateau technique des services spécialisés, pour mener une étude approfondie interdisciplinaire sur cette pathologie. PMID:28819523

Cutaneous anthrax: an overview.

PubMed

Celia, Frank

2002-04-01

The recent acts of bioterrorism have raised new questions about this uncommon disease. Clinicians are puzzled as to why some of the victims exposed to Bacillus anthracis spores developed the cutaneous form of the disease and others the inhalational form. Despite these questions, cutaneous anthrax remains relatively simple to treat effectively. The real clinical challenge lies in the diagnosis, especially being able to distinguish it from a spider bite.

[Cutaneous pigmentation related to intravenous iron extravasation: Analysis from the French pharmacovigilance database].

PubMed

Hermitte-Gandoliere, Alexia; Petitpain, Nadine; Lepelley, Marion; Thomas, Laure; Le Beller, Christine; Astoul, Jacqueline Ponte; Gillet, Pierre

Intravenous iron infusion may be complicated by extravasation and lead to cutaneous pigmentation. We queried the French pharmacovigilance database to assess the spontaneously reported cases over the 2000-2016 period. Fifty-one cases of cutaneous pigmentation related to intravenous iron extravasation were retrieved, none was associated to necrosis. Most of patients were women aged 20 to 49 years old. The pigmentation was mostly a brown coloration, persisting over one month in 19 cases (37.2%) and over 6 months in 9 cases (17.6%). The management of extravasation and pigmentation was heterogeneous and was rarely followed by a decrease of the coloration. Cutaneous pigmentation after intravenous iron extravasation can persist over time and create an aesthetic prejudice, particularly in young women. Standardized extravasation and iron-induced pigmentation management procedures appear necessary. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

ClinicalTrials.gov

2018-06-25

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

Disseminated cutaneous sporotrichosis in patient with alcoholism.

PubMed

Benvegnú, Ana Maria; Stramari, Juliana; Dallazem, Lia Natália Diehl; Chemello, Raíssa Massaia Londero; Beber, André Avelino Costa

2017-01-01

Sporotrichosis is the most prevalent subcutaneous mycosis and is characterized by a subacute or chronic development of a cutaneous or subcutaneous nodular lesion. It is caused by the dimorphic fungus Sporothrix spp, which may manifest in different clinical forms. The disseminated cutaneous form is uncommon and is more likely to occur in immunocompromised patients. We report a 47-year-old male patient with multiple cutaneous and subcutaneous nodules. The patient was diagnosed with disseminated cutaneous sporotrichosis based on the isolation and identification of Sporothrix spp. The patient was treated with potassium iodide, which resulted in clinical improvement of the lesions.

[Clinicopathologic features of primary mucosal CD30-positive T-cell lymphoproliferative disorders in head and neck region].

PubMed

Liu, F; Li, M; Zhang, L Y; Guo, L; Hu, W W; Rao, H L

2018-06-08

Objective: To study clinicopathologic features, prognosis and differential diagnoses of primary mucosal CD30-positive T-cell lymphoproliferative disorders of the head and neck(mCD30(+) TLPD-head and neck). Methods: Three cases of mCD30(+) TLPD-head and neck were collected from January 2014 to April 2017 at Sun Yat-Sen University Foshan Hospital. A literature review of mCD30(+) TLPD of head and neck was provided. Results: All three cases presented with either bulging/exophytic nodule or mucosal ulcer/erosion. Morphologically, the tumor consisted of diffuse proliferation of uniform, large atypical mononuclear lymphoid cells that showed irregular or polymorphic nuclei with small nucleoli, and abundant pale or amphophilic cytoplasm. Hallmark cells with eccentric, horseshoe, kidney-like, or doughnut-shaped nuclei were present. While mitotic figures were present, no tumor necrosis was found. Eosinophilc infiltration was obvious in the background. The atypical large lymphoid cells had a immunophenotype of CD30(+) /CD3(+) /CD4(+) /CD56(-) along with positive cytotoxic molecule. While being negative for EBER/ALK/CD20/CD8, TCR rearrangement was found in 2 out of 3 cases. Three patients were cured after excision without relapse and metastasis.The two patients with TCR rearrangement didn't show aggressive clinical course. Conclusions: mCD30(+) TLPD-head and neck is a rare benign lymphoproliferative disorder with spontaneous regression. It should be differentiated from cutaneous CD30(+) anaplstic large cell lymphoma, lymphomatoid papulosis, and EBV-related mucocutaneous ulcer. Correct recognition of mCD30(+) TLPD of head and neck is important to avoid overtreatment.

Primary Malignant Melanoma of Pleura: A Case Report and Literature Review.

PubMed

Agarwal, Poojan; Nambiyar, Kaniyyapan; Manju Kaushal; Bhardwaj, Minakshi

2016-07-01

Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648-652. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

ClinicalTrials.gov

2018-03-28

Breast Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Nodal Marginal Zone Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Breast Cancer AJCC v6 and v7

Incidence and Clinical Features of Rare Cutaneous Malignancies in Olmsted County, Minnesota, 2000 to 2010.

PubMed

Tolkachjov, Stanislav N; Schmitt, Adam R; Muzic, John G; Weaver, Amy L; Baum, Christian L

2017-01-01

The incidence of rare cutaneous malignancies is unknown. Current estimates of rare cutaneous malignancy incidences are based on broad epidemiologic data or single institution experiences, not population-based data. To determine the incidence of several rare nonmelanoma skin cancers. The authors conducted a retrospective chart review of a population-based cohort between the years 2000 and 2010. Residents of Olmsted County, Minnesota, who were diagnosed with a biopsy-proven nonmelanoma skin cancer-excluding basal cell carcinoma and squamous cell carcinoma-were included in this study. The primary outcome was tumor incidence. Additionally, the authors extracted patient demographics, tumor characteristics, treatment modalities, and outcomes. The age-adjusted and sex-adjusted incidences per 100,000 persons of multiple rare cutaneous malignancies were: atypical fibroxanthoma (1.8), sebaceous carcinoma (0.8), dermatofibrosarcoma protuberans (0.4), microcystic adnexal carcinoma (0.7), eccrine carcinoma (0.4), eccrine porocarcinoma (0.2), and leiomyosarcoma (0.2). The authors report population-based incidences and clinical characteristics for these rare cutaneous malignancies. The immune status and smoking status of patients and the treatment and outcomes of these tumors are reported. Additional studies in a broader population are needed to further define the epidemiology and outcomes of these malignancies.

The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins.

PubMed

Mocellin, Simone; Pasquali, Sandro; Nitti, Donato

2011-02-01

To quantify the impact of excision margins on disease-specific survival of patients with primary cutaneous melanoma. Current guidelines recommend narrow margins for the treatment of primary melanoma, although available evidence on this subject is not unequivocal and not always appropriately analyzed. A systematic review of randomized controlled trials (RCT) addressing the issue of wide versus narrow excision margins was performed. Meta-analysis methods for time-to-event data were used to extract hazard ratios(HR) and their 95% confidence intervals (CI) from eligible studies, and ultimately to estimate the summary effect of excision margins on patients' survival. The 5 eligible RCT enrolled a total of 3295 patients who were allocated to wide (3-5 cm) or narrow (1-2 cm) excision of their primary tumor. The data of locoregional disease-free (LDFS), disease-free (DFS),disease-specific (DSS), and overall (OS) survival were available for 3, 5, 3, and 5 RCT, respectively. The meta-analysis suggested that narrow margins might be associated with an increased risk of both locoregional disease recurrence (HR: 1.30, CI: 1.07-1.57; P = 0.01) and death by disease (HR: 1.28, CI:1.07-1.53, P = 0.01). As regards DFS, the borderline disadvantage (HR:1.13, CI: 0.995-1.28; P = 0.06) becomes significant when considering RCT that enrolled patients with thicker melanoma (HR: 1.19, CI: 1.02-1.39, P =0.03). When death by any cause (OS) was analyzed, no risk difference was found. The lack of DSS data from all the available RCT does not allow to draw definitive conclusions. However, current evidence appears sufficient to question the common belief that narrow excision margins are as safe as wide margins in the management of primary melanoma, that calls for further investigation in this field.

Highly Efficient and Versatile Plasmid-Based Gene Editing in Primary T Cells

PubMed Central

Kornete, Mara

2018-01-01

Adoptive cell transfer is an important approach for basic research and emerges as an effective treatment for various diseases, including infections and blood cancers. Direct genetic manipulation of primary immune cells opens up unprecedented research opportunities and could be applied to enhance cellular therapeutic products. In this article, we report highly efficient genome engineering in primary murine T cells using a plasmid-based RNA-guided CRISPR system. We developed a straightforward approach to ablate genes in up to 90% of cells and to introduce precisely targeted single nucleotide polymorphisms in up to 25% of the transfected primary T cells. We used gene editing–mediated allele switching to quantify homology-directed repair, systematically optimize experimental parameters, and map a native B cell epitope in primary T cells. Allele switching of a surrogate cell surface marker can be used to enrich cells, with successful simultaneous editing of a second gene of interest. Finally, we applied the approach to correct two disease-causing mutations in the Foxp3 gene. Repairing the cause of the scurfy syndrome, a 2-bp insertion in Foxp3, and repairing the clinically relevant Foxp3K276X mutation restored Foxp3 expression in primary T cells. PMID:29445007

Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-10

Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

Cutaneous hidradenocarcinoma: a clinicopathological, immunohistochemical, and molecular biologic study of 14 cases, including Her2/neu gene expression/amplification, TP53 gene mutation analysis, and t(11;19) translocation.

PubMed

Kazakov, Dmitry V; Ivan, Doina; Kutzner, Heinz; Spagnolo, Dominic V; Grossmann, Petr; Vanecek, Tomas; Sima, Radek; Kacerovska, Denisa; Shelekhova, Ksenia V; Denisjuk, Natalja; Hillen, Uwe; Kuroda, Naoto; Mukensnabl, Petr; Danis, Dusan; Michal, Michal

2009-05-01

We present a series of 14 cases of cutaneous hidradenocarcinomas. The patients included 6 women and 8 men ranging in age at diagnosis from 34 to 93 years. All but 1 patient presented with a solitary nodule. There was no predilection site. One patient presented with multiple lesions representing metastatic nodules. Of 12 patients with available follow-up, 2 died of disease, whereas the remaining 10 patients were alive but 3 of them experienced a local recurrence in the course of the disease. Grossly, the tumors ranged in size from 1.2 to 6 cm. Microscopically, of the 14 primary tumors, 9 showed low-grade cytomorphology, whereas the remaining 5 neoplasms were high-grade lesions. The residuum of a hidradenoma was present in 5 of the 14 primaries. The mitotic rate was highly variable, ranging from 2 to 64 mitoses per 10 high-power field. The cellular composition of the tumors varied slightly, with clear cells, epidermoid cells, and transitional forms being present in each case. In 1 case, there was metaplastic transformation into sarcomatoid carcinoma. Glandular differentiation varied from case to case and appeared most commonly as simple round glands or as cells with intracytoplasmic lumens. Necrosis en masse was detected in 8 specimens. One specimen represented a reexcision and was unusual as it showed a well-demarcated intradermal proliferation of relatively bland clear cells accompanied by an overlying intraepidermal growth of clear cells resembling hidradenoacanthoma simplex. Despite the bland appearance, the tumor metastasized to a lymph node. Immunohistochemically, 5 of the 8 specimens studied for Her2/neu expression were negative, whereas 3 specimens from 2 cases yielded score +2, but all the 3 specimens with score 2+ subsequently proved negative for Her2/neu gene amplification by fluorescence in situ hybridization. Of 10 primaries studied, 4 tumors showed positive p53 immunoreaction in more than 25% of the cells comprising the malignant portion of the lesions

Alkylphosphocholines and curcumin induce programmed cell death in cutaneous T-cell lymphoma cell lines.

PubMed

Yosifov, Deyan Y; Kaloyanov, Kaloyan A; Guenova, Margarita L; Prisadashka, Kamelia; Balabanova, Maria B; Berger, Martin R; Konstantinov, Spiro M

2014-01-01

While most patients with early-stage cutaneous T-cell lymphomas (CTCL) have a very good prognosis, the survival of patients with extensive tumour stage and visceral involvement remains extremely poor and necessitates the development of more effective treatment modalities. In this study, we evaluated the in vitro effects of two alkylphosphocholines (APCs, miltefosine and erufosine) and the polyphenolic compound curcumin on 5 human CTCL cell lines (Hut-78, HH, MJ, My-La CD4+ and My-La CD8+). All tested drugs showed considerable cytotoxic activity, as determined by the MTT dye reduction assay. The IC50 values of both APCs ranged from the low micromolar level (Hut-78 cells) to 60-80μM (HH cells). The IC50 values of curcumin ranged from 12 to 24μM. All tested drugs induced apoptosis, as ascertained by morphological changes, DNA fragmentation and activation of caspase cascades. Miltefosine and erufosine induced dephosphorylation of Akt in My-La CD8+ cells and phosphorylation of JNK in Hut-78 and My-La CD8+ cells. APCs increased the level of the autophagic marker LC3B in Hut-78 and MJ cells. Results from co-treatment with autophagy modulators suggested that the cytotoxicity of APCs in CTCL cells is mediated, at least in part, by induction of autophagy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Tumor attributes predicting cutaneous metastatic destiny: a report of two interesting cases.

PubMed

Gurumurthi, Ravichandran; Thirumalai, Raja; Easow, Jose M; Mohan, Subhashini

2014-07-01

Cutaneous metastases are the result of complex interaction between the tumor cells ("seed") and the host environment ("soil"). Metastases to the skin can be an early sign of internal malignancy or represent recurrence of the primary tumor and portends a poorer prognosis. Invasion and metastasis are the hallmarks of on cogenesis. Skin is the largest organ in the body, but the incidence of metastases is low. With advances in molecular biology, factors responsible for the initiation and perpetuation of metastatic tumor cells at distant sites are being elucidated. The concept of "pre-metastatic niche" and interaction between various chemokines has given a new outlook in understanding the organ specificity of metastatic tumor cells. We present two cases of cutaneous metastases with interesting clinical findings correlating with its biologic subtypes.

Annular erythema in primary Sjogren's syndrome: description of 43 non-Asian cases.

PubMed

Brito-Zerón, P; Retamozo, S; Akasbi, M; Gandía, M; Perez-De-Lis, M; Soto-Cardenas, M-J; Diaz-Lagares, C; Kostov, B; Bove, A; Bosch, X; Perez-Alvarez, R; Siso, A; Ramos-Casals, M

2014-02-01

The objective of this paper is to evaluate the prevalence and characterize the main epidemiological, clinical and immunological features of annular erythema (AE) in non-Asian patients with primary Sjögren's syndrome (SS). We carried out a retrospective study searching for AE in 377 Spanish patients with primary SS fulfilling the 2002 American-European criteria. In addition, we searched PubMed (1994-2012) using the MeSH terms "annular erythema" and "primary Sjögren's syndrome" for additional cases. All cases with AE reported in patients with SS associated with systemic lupus erythematosus were excluded. In our Spanish cohort, we found 35 (9%) patients diagnosed with AE. All were white females, with a mean age of 47 years at diagnosis of AE. AE preceded diagnosis of SS in 27 (77%) patients. Cutaneous AE lesions involved principally the face and upper extremities. All patients reported photosensitivity, with cutaneous flares being reported during the warmest months in 93% of patients. Immunological markers consisted of anti-Ro/La antibodies in 31 (89%) patients. In the literature search, we identified eight additional non-Asian patients with primary SS diagnosed with AE. In comparison with 52 Asian patients, the 43 non-Asian patients with AE related to primary SS were more frequently women (100% vs 78%, p=0.008), and cutaneous lesions were less frequently reported in the face (55% vs 81%, p=0.045) and more frequently in the neck (40% vs 14%, p=0.041). Immunologically, non-Asian patients had a lower frequency of anti-Ro antibodies and a higher frequency of negative Ro/La antibodies, although the differences were not statistically significant. AE is not an exclusive cutaneous feature of Asian patients with primary SS. In addition to the characteristic cutaneous expression, AE has a very specific clinical and immunological profile: often presenting before the fulfillment of SS criteria, overwhelmingly associated with anti-Ro antibodies but weakly associated with other

[Dermoscopy in cutaneous melanoma].

PubMed

Gallegos-Hernández, José Francisco; Ortiz-Maldonado, Alma Lilia; Minauro-Muñoz, Gerardo Gabriel; Arias-Ceballos, Héctor; Hernández-Sanjuan, Martín

2015-01-01

The mortality of cutaneous melanoma has not declined over the past 50 years. The only interventions that can reduce mortality are primary prevention and early diagnosis, and the dermoscopic evaluation is essential to achieve this. Dermoscopy identifies characteristics of melanoma that would go unnoticed to the naked eye. The aim of this paper is to report the most frequent dermoscopic findings in patients diagnosed with in situ and invasive melanoma. An observational and retrospective study of contact dermoscopy was performed using LED DermliteTM and camera DermliteTM dermoscope. The findings evaluated were: asymmetry in two axes, association of colours, lack of pigment, irregular points, atypical network, pseudopods, blue veil, ulceration, and peri-lesional pink ring. These dermoscopic findings were compared with the histological diagnosis. The study included 65 patients with cutaneous melanoma; 10 in situ, and 55 invasive. The mean Breslow in invasive melanoma was 3 mm. Most patients (35) had localization in extremities. In all patients, the most frequent dermoscopic finding was asymmetry in two axes, followed by association of two or more colours; in melanoma in situ, asymmetry was the most frequent, followed by atypical-irregular points. In invasive melanoma asymmetry in two axes, the association of two or more colours, and pseudopods, were the most frequent findings. Asymmetry in two axes is the most common dermoscopic finding in in situ and invasive melanoma. The presence of two or more colours in a pigmented lesion should be suspected in an invasive melanoma. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Cutaneous Side Effects of Antiosteoporosis Treatments

PubMed Central

Musette, Philippe; Kaufman, Jean-Marc; Rizzoli, René; Cacoub, Patrice; Brandi, Maria Louisa; Reginster, Jean-Yves

2011-01-01

Cutaneous adverse reactions are reported for many therapeutic agents and, in general, are observed in between 0% and 8% of treated patients depending on the drug. Antiosteoporotic agents are considered to be safe in terms of cutaneous effects, however there have been a number of case reports of cutaneous adverse reactions which warrant consideration. This was the subject of a working group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, which focused on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. This position paper was drafted following these discussions and includes a flowchart for their recognition. Cutaneous adverse reactions observed with antiosteoporotic agents were reviewed and included information from case reports, regulatory documents and pharmacovigilance. These reactions ranged from benign effects including exanthematous or maculopapular eruption (drug rash), photosensitivity and urticaria, to the severe and potentially life-threatening reactions of angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome and toxic epidermal necrolysis. A review of the available evidence demonstrates that cutaneous adverse reactions occur with all commonly used antiosteoporotic treatments. Notably, there are reports of Stevens Johnson syndrome and toxic epidermal necrolysis for bisphosphonates, and of DRESS and toxic epidermal necrolysis for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases). In general, with proper management and early recognition, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration and systemic corticosteroids if necessary, the prognosis is positive. PMID:22870464

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma.

PubMed

Vasan, Kartik; Low, Tsu-Hui Hubert; Gupta, Ruta; Ashford, Bruce; Asher, Rebecca; Gao, Kan; Ch'ng, Sydney; Palme, Carsten E; Clark, Jonathan R

2018-05-01

The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The minimal-P approach was used to investigate the optimal lymph node ratio threshold. Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis. The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio >6% is a significant threshold to categorize patients into low and high risk. © 2018 Wiley Periodicals, Inc.

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

PubMed Central

Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

1992-01-01

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

American cutaneous leishmaniasis triggered by electrocoagulation.

PubMed

Martins, Sofia Sales; Santos, Adriana de Oliveira; Lima, Beatriz Dolabela; Gomes, Ciro Martins; Sampaio, Raimunda Nonata Ribeiro

2018-01-01

Cutaneous leishmaniasis is usually transmitted by infected phlebotomine sand fly bites that initiate local cutaneous lesions. Few reports in the literature describe other modes of transmission. We report a case of a previously healthy 59-year-old woman who underwent electrocoagulation to remove seborrheic keratosis confirmed by dermatoscopy. Three months later, a skin fragment tested positive for Leishmania culture; the parasite was identified as L. (V.) braziliensis. Trauma may generate inflammatory cascades that favor Leishmania growth and lesion formation in previously infected patients. American cutaneous leishmaniasis is a dynamic disease with unclear pathophysiology because of continually changing environments, demographics, and human behaviors.

Cutaneous lichen planus: A systematic review of treatments.

PubMed

Fazel, Nasim

2015-06-01

Various treatment modalities are available for cutaneous lichen planus. Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database were searched for all the systematic reviews and randomized controlled trials related to cutaneous lichen planus. Two systematic reviews and nine relevant randomized controlled trials were identified. Acitretin, griseofulvin, hydroxychloroquine and narrow band ultraviolet B are demonstrated to be effective in the treatment of cutaneous lichen planus. Sulfasalazine is effective, but has an unfavorable safety profile. KH1060, a vitamin D analogue, is not beneficial in the management of cutaneous lichen planus. Evidence from large scale randomized trials demonstrating the safety and efficacy for many other treatment modalities used to treat cutaneous lichen planus is simply not available.

Advances in the treatment of cutaneous lupus erythematosus.

PubMed

Kuhn, A; Landmann, A; Wenzel, J

2016-07-01

Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE. © The Author(s) 2016.

Cutaneous HPV and skin cancer.

PubMed

Accardi, Rosita; Gheit, Tarik

2014-12-01

Papillomaviruses (HPVs) are small non-enveloped icosahedral viruses that infect the keratinocytes of skin and mucosa. The cutaneous HPV types are represented mainly by the beta and gamma genera, which are widely present in the skin of normal individuals. More than 40 beta-HPV types and 50 gamma-HPV types have been isolated, and these numbers are continuously growing. The main cause of non-melanoma skin cancer is exposure to ultraviolet radiation (UVR). However, cutaneous HPVs that belong to the beta genus may act as a co-carcinogen with UVR. The association between beta-HPVs and skin cancer was first reported in patients with epidermodysplasia verruciformis (EV), who frequently develop cutaneous squamous cell carcinoma (SCC) on sun-exposed areas. Isolation of HPVs from the lesions suggested that HPVs might act as a co-carcinogen with UVR in EV patients. Beta-HPVs may also play a role in cutaneous SCC in immunocompromised non-EV and in immunocompetent individuals. Several studies have reported an association of viral DNA and/or antibodies to beta HPV types with SCC. Interestingly, HPV prevalence and viral load decrease during skin carcinogenesis, being significantly higher in actinic keratosis than in SCC, suggesting that the virus may play a role in the early stages of tumour development (the "hit-and-run" hypothesis). Concordantly, in vivo and in vitro studies have shown that E6 and E7 from certain cutaneous HPV types display transforming activities, further confirming their potential role in carcinogenesis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Cutaneous leishmaniasis: an emerging infectious disease in travelers.

PubMed

Ergen, Elizabeth Noble; King, Allison Hutsell; Tuli, Malika

2015-10-01

Leishmaniasis describes any of 3 diseases caused by protozoan parasites of the genus Leishmania, the most common of which is cutaneous leishmaniasis. The majority of cutaneous cases occur in Central and South America, the Mediterranean basin, the Middle East, and Central Asia. Most cases diagnosed among nonmilitary personnel in the United States are acquired in Mexico and Central America. Here, we present the case of an American tourist who developed localized cutaneous leishmaniasis 2 weeks after returning from Costa Rica. After undergoing several unsuccessful rounds of empiric antibiotic treatment for a presumed Staphylococcus aureus skin infection, the patient was referred to our dermatology clinic where cutaneous leishmaniasis was diagnosed by tissue biopsy. This case highlights the importance of cutaneous leishmaniasis as an emerging infectious disease that may be misdiagnosed due to its rarity and varied clinical presentation as well as the limited use of tissue biopsy in general practice. We also provide relevant background information on cutaneous leishmaniasis, a rhyming poem, and an illustration in order to promote greater awareness of this disease and assist clinicians with its diagnosis.

21 CFR 882.1320 - Cutaneous electrode.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous electrode. 882.1320 Section 882.1320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1320 Cutaneous electrode. (a...

21 CFR 882.1320 - Cutaneous electrode.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cutaneous electrode. 882.1320 Section 882.1320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1320 Cutaneous electrode. (a...

Cutaneous consequences of accelerated thyroid function.

PubMed

Mullin, G E; Eastern, J S

1986-02-01

General and specific cutaneous findings associated with hyperthyroidism are reviewed. Familiarity with these findings may aid the practitioner in the early diagnosis of thyroid diseases. Several normally idiopathic cutaneous diseases can occasionally be controlled if underlying thyroid disease is considered as a cause, and appropriate testing performed.

Cutaneous lymphoproliferative disorder complicating infectious mononucleosis in an immunosuppressed patient.

PubMed

Owen, Cindy England; Callen, Jeffrey P; Bahrami, Soon

2011-01-01

Infectious mononucleosis is the syndrome produced by primary infection with Epstein-Barr virus during adolescence or early adulthood. In immunosuppressed individuals, depressed T-cell function allows the Epstein-Barr virus-driven B-cell proliferation to continue unabated, potentially leading to a lymphoproliferative disorder. A 15-year-old girl with a history of ulcerative colitis treated with 6-mercaptopurine and mesalamine presented with the acute onset of a rapidly enlarging, ulcerative nodule on her left lower eyelid 4 weeks following recovery from infectious mononucleosis. The biopsy revealed an Epstein-Barr virus-positive lymphoproliferative disorder. Systemic disease was absent. Following discontinuation of 6-mercaptopurine, the patient was treated with two courses of intravenous cyclophosphamide. The lesion resolved completely and she remains disease free at 14 months following diagnosis. We report a solitary cutaneous lesion of an immunosuppression-related lymphoproliferative disorder (IR-LPD) occurring as a complication of infectious mononucleosis, and review the pathogenesis and reported cases of Epstein-Barr virus-related immunosuppression-related lymphoproliferative disorder arising in the setting of inflammatory bowel disease. It is important for dermatologists and dermatopathologists to be aware of the occurrence of IR-LPD in patients being treated for inflammatory conditions, including inflammatory bowel disease. Given the role of primary infection with Epstein-Barr virus in the development of IR-LPD, consideration may be given to assessing Epstein-Barr virus status prior to initiating immunosuppressive therapy in young patients. © 2010 Wiley Periodicals, Inc.

Influence of cutaneous and muscular circulation on spatially resolved versus standard Beer-Lambert near-infrared spectroscopy.

PubMed

Messere, Alessandro; Roatta, Silvestro

2013-12-01

The potential interference of cutaneous circulation on muscle blood volume and oxygenation monitoring by near-infrared spectroscopy (NIRS) remains an important limitation of this technique. Spatially resolved spectroscopy (SRS) was reported to minimize the contribution of superficial tissue layers in cerebral monitoring but this characteristic has never been documented in muscle tissue monitoring. This study aims to compare SRS with the standard Beer-Lambert (BL) technique in detecting blood volume changes selectively induced in muscle and skin. In 16 healthy subjects, the biceps brachii was investigated during isometric elbow flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed before and after exposure of the upper arm to warm air flow. From probes applied over the muscle belly the following variables were recorded: total hemoglobin index (THI, SRS-based), total hemoglobin concentration (tHb, BL-based), tissue oxygenation index (TOI, SRS-based), and skin blood flow (SBF), using laser Doppler flowmetry. Blood volume indices exhibited similar changes during muscle contraction but only tHb significantly increased during warming (+5.2 ± 0.7 μmol/L·cm, an effect comparable to the increase occurring in postcontraction hyperemia), accompanying a 10-fold increase in SBF. Contraction-induced changes in tHb and THI were not substantially affected by warming, although the tHb tracing was shifted upward by (5.2 ± 3.5 μmol/L·cm, P < 0.01). TOI was not affected by cutaneous warming. In conclusion, SRS appears to effectively reject interference by SBF in both muscle blood volume and oxygenation monitoring. Instead, BL-based parameters should be interpreted with caution, whenever changes in cutaneous perfusion cannot be excluded.

Influence of cutaneous and muscular circulation on spatially resolved versus standard Beer–Lambert near‐infrared spectroscopy

PubMed Central

Messere, Alessandro; Roatta, Silvestro

2013-01-01

Abstract The potential interference of cutaneous circulation on muscle blood volume and oxygenation monitoring by near‐infrared spectroscopy (NIRS) remains an important limitation of this technique. Spatially resolved spectroscopy (SRS) was reported to minimize the contribution of superficial tissue layers in cerebral monitoring but this characteristic has never been documented in muscle tissue monitoring. This study aims to compare SRS with the standard Beer–Lambert (BL) technique in detecting blood volume changes selectively induced in muscle and skin. In 16 healthy subjects, the biceps brachii was investigated during isometric elbow flexion at 70% of the maximum voluntary contractions lasting 10 sec, performed before and after exposure of the upper arm to warm air flow. From probes applied over the muscle belly the following variables were recorded: total hemoglobin index (THI, SRS‐based), total hemoglobin concentration (tHb, BL‐based), tissue oxygenation index (TOI, SRS‐based), and skin blood flow (SBF), using laser Doppler flowmetry. Blood volume indices exhibited similar changes during muscle contraction but only tHb significantly increased during warming (+5.2 ± 0.7 μmol/L·cm, an effect comparable to the increase occurring in postcontraction hyperemia), accompanying a 10‐fold increase in SBF. Contraction‐induced changes in tHb and THI were not substantially affected by warming, although the tHb tracing was shifted upward by (5.2 ± 3.5 μmol/L·cm, P < 0.01). TOI was not affected by cutaneous warming. In conclusion, SRS appears to effectively reject interference by SBF in both muscle blood volume and oxygenation monitoring. Instead, BL‐based parameters should be interpreted with caution, whenever changes in cutaneous perfusion cannot be excluded. PMID:24744858

Cutaneous protothecosis following a tape-stripping injury.

PubMed

Humphrey, Shannon; Martinka, Magdalena; Lui, Harvey

2009-01-01

Prototheca species are ubiquitous achlorophyllic algae that can, in rare instances, manifest as cutaneous infection in humans at sites of traumatic inoculation into the skin. We report a 77-year-old man who developed cutaneous protothecosis at the site of an iatrogenic tape-stripping type injury. The diagnosis was confirmed by histologic examination and tissue culture. The patient responded completely to a 17-week course of oral fluconazole. Cutaneous protothecosis can present clinically as nonspecific indolent inflammatory plaques that require skin biopsy for definitive diagnosis.

Ulcerative Lesions: A Rare Cutaneous Manifestation of Brucellosis.

PubMed

Azadi, Abbas; Jafarpour Fard, Payman; Almasian, Mohammad

2018-01-01

Brucellosis is a disease that is transmitted from animals to humans mainly via the consumption of unpasteurized dairy products, and it can involve any organ all over the body. Here, we report a significant rare case of brucellosis with cutaneous manifestations in a 52-year-old male patient whose disease was diagnosed via a serology test. The patient received standard antibiotic treatment, and his cutaneous lesions healed quickly. Although the cutaneous manifestations of brucellosis are exceedingly rare, in case of encountering ulcerative lesions and other cutaneous findings, particularly in endemic areas, infection with brucellosis should be kept in mind as an important differential diagnosis.

A new concept of skin-associated lymphoid tissue (SALT): UVB light impaired cutaneous immunity reveals a prominent role for cutaneous nerves.

PubMed

Streilein, J W; Alard, P; Niizeki, H

1999-03-01

More than 20 years have passed since the concept that the skin has its own associated immune system was first proposed by Streilein. This proposal was advanced in part on evidence that cutaneous contact hypersensitivity (CH) reactions are closely correlated with Langerhans cells (LC). Recent reports have demonstrated that LC have neural connectivity with cutaneous nerve termini containing calcitonin gene-related peptide (CGRP), suggesting that a link exists between innervation and immune responses in the skin. Here we discuss the neural components which have recently been found to be participants in skin-associated lymphoid tissue (SALT). In part, discovery of a functional link between the nervous system and SALT is based on studies in which cutaneous immunity was impaired by ultraviolet-B radiation (UVR). The deleterious effects of UVR on cutaneous immunity include failed CH induction and promotion of hapten-specific tolerance, effects that are mediated by tumor necrosis factor-alpha and interleukin-10, respectively. The source of these cytokines after UVR appears to be dermal mast cells. Evidence indicates that mast cells are triggered to release these cytokines in response to CGRP, which is released from UVR-damaged cutaneous nerve endings. Moreover, a substance P agonist was able to reverse the deleterious effects of UVR on CH induction, rendering the mice able to develop intense CH. These observations indicate that two cell types not originally included in the SALT concept are critical to the functional integrity of cutaneous immunity: mast cells and cutaneous nerves. We propose that cutaneous nerves dictate whether antigen applied to or arising within skin will lead to sensitivity or tolerance.

The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms.

PubMed

Matutes, E

2018-05-01

Over the last decade, there has been a significant body of information regarding the biology of the lymphoid neoplasms. This clearly supports the need for updating the 2008 WHO (World Health Organization) classification of haematopoietic and lymphoid tumours. The 2017 WHO classification is not a new edition but an update and revision of the 4th edition. New provisional entities but not new definitive entities are included, and novel molecular data in most of the entities and changes in the nomenclature in few of them have been incorporated. In the context of the mature T- and NK-cell neoplasms, the most relevant updates concern to: 1-dysregulation of the JAK/STAT pathway due to gene mutations which are common to various aggressive and indolent neoplasms; 2-incorporation of new molecular players that are relevant to the pathogenesis of these neoplasms and/or have prognostic implications; 3-inclusion of new provisional entities within the subgroups of anaplastic, primarily intestinal and cutaneous lymphomas such as breast implant-associated anaplastic large cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and primary cutaneous acral CD8 + T-cell lymphoma; 4-identification of poor prognostic subtypes of peripheral T-cell lymphomas not otherwise specified (PTCL, NOS) characterized by overexpression of certain genes and of a subgroup PTCL, NOS with a T follicular phenotype that now is included together with angioimmunoblastic T-cell lymphoma under the umbrella of lymphomas with a T follicular helper phenotype; and 5-refinement on the designation and definition of already established entities. A review of the major changes will be outlined. © 2018 John Wiley & Sons Ltd.

Acitretin for the management of generalized cutaneous lichen planus.

PubMed

Vazirnia, Aria; Cohen, Philip R

2014-09-16

Lichen planus is an inflammatory disease that affects the skin, the oral mucosa, or both. Generalized cutaneous lichen planus may pose a therapeutic challenge for clinicians if the condition persists or flares after topical or systemic corticosteroid therapy. Acitretin, a systemic retinoid, can be considered a potential second-line treatment for patients with generalized cutaneous lichen planus. Herein, we describe a postmenopausal woman with generalized cutaneous lichen planus who was successfully treated with acitretin. A 58-year-old woman presented with generalized cutaneous lichen planus involving her upper and lower extremities as well as her lower back. After failing corticosteroid therapy, she was started on acitretin 20 mg/day, which was later increased to 30 mg/day. To review the literature on the use of acitretin in cutaneous lichen planus, we used the PubMed search engine and searched for the terms "acitretin" and "cutaneous lichen planus." Our patient had complete resolution of pruritus within one week of initiating acitretin 20 mg/day. After an increase in dose to 30 mg/day, the cutaneous lesions completely resolved over a 3-month period. There was no recurrence of disease as acitretin was tapered and discontinued. Generalized cutaneous lichen planus may pose a therapeutic challenge for the symptomatic relief of skin lesions. Topical and systemic corticosteroids are first-line treatments. In patients who fail corticosteroids, relapse after corticosteroid therapy, or have contraindications to corticosteroids, acitretin may be considered a potential second-line therapy.

Exogenous melatonin administration modifies cutaneous vasoconstrictor response to whole body skin cooling in humans.

PubMed

Aoki, Ken; Zhao, Kun; Yamazaki, Fumio; Sone, Ryoko; Alvarez, Guy E; Kosiba, Wojciech A; Johnson, John M

2008-03-01

Humans and other diurnal species experience a fall in internal temperature (T(int)) at night, accompanied by increased melatonin and altered thermoregulatory control of skin blood flow (SkBF). Also, exogenous melatonin induces a fall in T(int), an increase in distal skin temperatures and altered control of the cutaneous active vasodilator system, suggesting an effect of melatonin on the control of SkBF. To test whether exogenous melatonin also affects the more tonically active vasoconstrictor system in glabrous and nonglabrous skin during cooling, healthy males (n = 9) underwent afternoon sessions of whole body skin temperature (T(sk)) cooling (water-perfused suits) after oral melatonin (Mel; 3 mg) or placebo (Cont). Cutaneous vascular conductance (CVC) was calculated from SkBF (laser Doppler flowmetry) and non-invasive blood pressure. Baseline T(int) was lower in Mel than in Cont (P < 0.01). During progressive reduction of T(sk) from 35 degrees C to 32 degrees C, forearm CVC was first significantly reduced at T(sk) of 34.33 +/- 0.01 degrees C (P < 0.05) in Cont. In contrast, CVC in Mel was not significantly reduced until T(sk) reached 33.33 +/- 0.01 degrees C (P < 0.01). The decrease in forearm CVC in Mel was significantly less than in Cont at T(sk) of 32.66 +/- 0.01 degrees C and lower (P < 0.05). In Mel, palmar CVC was significantly higher than in Cont above T(sk) of 33.33 +/- 0.01 degrees C, but not below. Thus exogenous melatonin blunts reflex vasoconstriction in nonglabrous skin and shifts vasoconstrictor system control to lower T(int). It provokes vasodilation in glabrous skin but does not suppress the sensitivity to falling T(sk). These findings suggest that by affecting the vasoconstrictor system, melatonin has a causal role in the nocturnal changes in body temperature and its control.

Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

PubMed Central

Piekarz, Richard L.; Frye, Robin; Turner, Maria; Wright, John J.; Allen, Steven L.; Kirschbaum, Mark H.; Zain, Jasmine; Prince, H. Miles; Leonard, John P.; Geskin, Larisa J.; Reeder, Craig; Joske, David; Figg, William D.; Gardner, Erin R.; Steinberg, Seth M.; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Lade, Stephen; Fojo, A. Tito; Bates, Susan E.

2009-01-01

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL. PMID:19826128

T2 relaxation times of the glenohumeral joint at 3.0 T MRI in patients with and without primary and secondary osteoarthritis.

PubMed

Lee, So-Yeon; Park, Hee-Jin; Kwon, Heon-Ju; Kim, Mi Sung; Choi, Seon Hyeong; Choi, Yoon Jung; Kim, Eugene

2015-11-01

Quantitative magnetic resonance imaging (MRI) of cartilage has recently been applied to patients with osteoarthritis (OA). T2 mapping is a sensitive method of detecting changes in the chemical composition and structure of cartilage. To establish baseline T2 values of glenohumeral joint cartilage at 3.0 T and compare T2 values among subjects with and without OA. The study involved 30 patients (18 women, 12 men; median age, 67 years; age range, 51-78 years) with primary (n = 7) and secondary OA (n = 23) in the glenohumeral joint and 34 subjects without OA (19 women, 15 men; median age, 49 years; age range, 23-63 years). All subjects were evaluated by radiography and 3.0 T MRI including a multi-echo T2-weighted spin echo pulse sequence. The T2 value of the cartilage was measured by manually drawing the region of interest on the T2 map. Per-zone comparison of T2 values was performed using Mann-Whitney U test. Median T2 values differed significantly between subjects without OA (36.00 ms [interquartile range, 33.89-37.31 ms]) and those with primary (37.52 ms [36.84-39.11], P = 0.028), but not secondary (36.87 ms [34.70-41.10], P = 0.160) OA. Glenohumeral cartilage T2 values were higher in different zones between patients with primary and secondary OA than in subjects without OA. These T2 values can be used for comparison to assess cartilage degeneration in patients with shoulder OA. Significant differences in T2 were observed among subjects without OA and those with primary and secondary OA. © The Foundation Acta Radiologica 2014.

Lymphoscintigraphy defines new lymphatic pathways from cutaneous melanoma site: clinical implications and surgical management.

PubMed

Marone, Ugo; Aloj, Luigi; Di Monta, Gianluca; Caracò, Corrado

2011-01-01

Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called "uncommon/interval" nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement.

Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

DOE PAGES

Schumann, Kathrin; Lin, Steven; Boyer, Eric; ...

2015-07-27

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4 + T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs).more » Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 ( PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schumann, Kathrin; Lin, Steven; Boyer, Eric

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4 + T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs).more » Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 ( PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis.

PubMed

Nilforoushzadeh, Mohammad Ali; Jaffary, Fariba; Moradi, Shahram; Derakhshan, Roya; Haftbaradaran, Elaheh

2007-04-27

Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar. In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan-Mayer tests. In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime. Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04). Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.

Cutaneous mucormycosis in advanced HIV disease.

PubMed

Moreira, José; Ridolfi, Felipe; Almeida-Paes, Rodrigo; Varon, Andrea; Lamas, Cristiane C

Angionvasive mucormycosis is an emerging fungal disease known to affect mainly diabetics or subjects with profound neutropenia. Infection usually occurs through the inhalation route, but cutaneous inoculation may occur after trauma or burns. However, mucormycosis remains unusual in HIV infection. We report a fatal case of cutaneous mucormycosis due to Rhizopus arrhizus involving the scalp following herpes zoster infection. The patient was a 42-year-old man with advanced AIDS failing on salvage antiretroviral therapy. The fungus was diagnosed on the basis of histopathology and culture. Our case emphasizes the need to consider mucormycosis in the differential diagnosis of necrotic cutaneous lesions in patients with late-stage HIV disease. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

2017-06-01

Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

Necrotizing Fasciitis: How Reliable are the Cutaneous Signs?

PubMed Central

Kiat, Ho Jun; En Natalie, Yap Hui; Fatimah, Lateef

2017-01-01

Necrotizing fasciitis (NF) is a surgical emergency. It is often aggressive and characterized by the rapidly progressive inflammatory infection of the fascia that causes extensive necrosis of the subcutaneous tissue and fascia, relatively sparing the muscle and skin tissue. As the disease progresses, thrombosis of the affected cutaneous perforators subsequently devascularizes the overlying skin. The course indeed can be a fulminant one. The diagnosis of NF, especially in the early stages, is extremely challenging, and it can be very close in presentation to other skin and subcutaneous tissue infections. The primary site of the pathology is the deep fascia. Necrosis of the tissues and fascia may manifest as erythema without sharp margins, swelling, warmth, shiny, and exquisitely tender areas. Pain out of proportion to physical examination findings may be observed. The subcutaneous tissue may be firm and indurated such that the underlying muscle groups cannot be distinctly palpated. Eventually, as the overlying skin is stripped of its blood supply, skin necrosis ensues and hemorrhagic bullae form. Bacteremia and sepsis invariably develop when the infection is well established. This paper discusses some of issues related to the cutaneous signs found in NF and also provides a review the current, available literature on the subject matter. PMID:29097860

Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial.

PubMed

Hayes, Andrew J; Maynard, Lauren; Coombes, Gillian; Newton-Bishop, Julia; Timmons, Michael; Cook, Martin; Theaker, Jeffrey; Bliss, Judith M; Thomas, J Meirion

2016-02-01

The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. We did a randomised, open-label multicentre trial in 59 hospitals--57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76-135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01-1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96-1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin

Lésions bulleuses et purpuriques unilatérales: pathomimie cutanée

PubMed Central

Zinoun, Mouna; Chiheb, Soumia; Marnissi, Farida; Kadiri, Nadia; Benchikhi, Hakima

2015-01-01

La pathomimie cutanée est une forme particulière de troubles factices relativement rare, et constitue l'un des problèmes les plus complexes pour le dermatologue. Nous rapportons un cas de pathomimie révélée par des lésions cutanées unilatérales, mimant une brûlure. Une jeune femme de 27 ans, était suivie depuis 4 ans pour une dépression. Elle a présenté 15j avant sa 1ère hospitalisation un placard inflammatoire du sein gauche compliqué de lésions bulleuses et d’érosions superficielles. La biopsie cutanée avait montré une dermite non spécifique. Une cicatrisation rapide sous traitement local a été notée. Elle a présenté 10 jours plus tard de nouvelles lésions similaires étagées au membre inférieur gauche, évoluant vers le décollement bulleux spontané. La biopsie cutanée avait montré un décollement bulleux jonctionnel et des foyers de nécrose ischémique. L'IFD était négative. Devant les données anamnestiques, cliniques, la négativité du bilan paraclinique, et la guérison des lésions sous pansements occlusifs seuls, le diagnostic de pathomimie a été évoqué et retenu. La patiente a été adressée en psychiatrie où une thérapie cognitivo-comportementale a été préconisée. Notre observation correspond à un tableau de pathomimie de présentation clinique particulière par sa localisation unilatérale et son caractère bulleux. Chez notre patiente qui est droitière, la localisation unilatérale gauche sur des zones accessibles, l'absence de lésions spécifiques à l'examen histologique, la cicatrisation rapide des lésions sous traitement local occlusif seul et leur récurrence malgré des soins adaptés étaient en faveur d'une pathologie factice. Néanmoins, la localisation au niveau des seins peut être très déroutante. Le caractère bulleux des lésions dans le cadre d'une pathomimie a été rarement rapporté. Dans notre cas, la pathomimie s'associe à des troubles anxieux et dépressifs très importants

Selected Cutaneous Disorders in Athletes

PubMed Central

Walker, James D.

1988-01-01

The author discusses selected cutaneous diseases seen in the athlete. These diseases may be caused by interaction with the elements, the playing surface, other athletes, or the clothing or equipment worn during sport. All of these dermatological conditions are relatively common, but the physically active individual can suffer from these maladies and their complications more often than the inactive person. The emphasis in caring for the participant is on prevention, early recognition and practical aspects of management of cutaneous diseases. PMID:21264034

LYMPHOBLASTOMAS IN CHILDHOOD—Cutaneous Manifestations

PubMed Central

Nelson, Lawrence M.

1953-01-01

The lymphoblastomas occurring in childhood are divided for purposes of discussion into lymphocytoma cutis, mycosis fungoides, lymphosarcoma, Hodgkin's disease, and leukemia. The cutaneous lesions may be either specific (as a result of the infiltration of the skin with specific cells of the conditions) or toxic (non-specific). With the possible exception of mycosis fungoides, the cutaneous manifestations are not diagnostic. The final diagnosis depends upon microscopic examination of the specific tissue involved and the coordination of the clinical and microscopic findings. PMID:13032796

Diet phytochemicals and cutaneous carcinoma chemoprevention: A review.

PubMed

Wang, Siliang; Shen, Peiliang; Zhou, Jinrong; Lu, Yin

2017-05-01

Cutaneous carcinoma, which has occupied a peculiar place among worldwide populations, is commonly responsible for the considerably increasing morbidity and mortality rates. Currently available medical procedures fail to completely avoid cutaneous carcinoma development or to prevent mortality. Cancer chemoprevention, as an alternative strategy, is being considered to reduce the incidence and burden of cancers through chemical agents. Derived from dietary foods, phytochemicals have become safe and reliable compounds for the chemoprevention of cutaneous carcinoma by relieving multiple pathological processes, including oxidative damage, epigenetic alteration, chronic inflammation, angiogenesis, etc. In this review, we presented comprehensive knowledges, main molecular mechanisms for the initiation and development of cutaneous carcinoma as well as effects of various diet phytochemicals on chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vaginal type-II mucosa is an inductive site for primary CD8+ T-cell mucosal immunity

PubMed Central

Wang, Yichuan; Sui, Yongjun; Kato, Shingo; Hogg, Alison E.; Steel, Jason C.; Morris, John C.; Berzofsky, Jay A.

2014-01-01

The structured lymphoid tissues are considered the only inductive sites where primary T cell immune responses occur. The naïve T cells in structured lymphoid tissues, once being primed by antigen -bearing dendritic cells, differentiate into memory T cells and traffic back to the mucosal sites through the bloodstream. Contrary to this belief, here we show that the vaginal type-II mucosa itself, despite lack of structured lymphoid tissues, can act as an inductive site during primary CD8+ T cell immune responses. We provide evidence that the vaginal mucosa supports both the local immune priming of naïve CD8+ T cells and the local expansion of antigen-specific CD8+ T cells, thereby demonstrating a different paradigm for primary mucosal T cell immune induction. PMID:25600442

Cutaneous body image dissatisfaction and suicidal ideation: mediation by interpersonal sensitivity.

PubMed

Gupta, Madhulika A; Gupta, Aditya K

2013-07-01

Cutaneous body image (CBI) dissatisfaction, feelings of social exclusion and stigmatization have been associated with increased suicidality in dermatology patients. We examined the relation between CBI dissatisfaction and suicidal ideation in a non-clinical sample, and examined the possible mediating effect of interpersonal sensitivity (IS), a symptom dimension related to self-consciousness, feelings of inferiority and social exclusion. As part of a larger study, 312 community-based participants from London, Ontario, Canada (241 women, 71 men; mean±SD age: 38.4±14.9years) rated their CBI satisfaction, measured with the Cutaneous Body Image Scale (Gupta MA et al., 2004). The Brief Symptom Inventory (BSI) (Derogatis L et al.,1982) was used to measure the constructs of suicidal ideation (4 suicide-related items from the BSI) and IS (Interpersonal Sensitivity subscale of BSI). Assessing mediation using the Baron & Kenny (1986) model, CBI satisfaction had a significant negative effect on suicidal ideation [c=-0.316, t(296)=-5.73, p<0.001] and IS [a=-0.365, t(297)=-6.76, p<0.001]; when CBI satisfaction and IS were considered together, IS had a significant positive effect on suicidal ideation (b=.690, t(295)=15.80, p<.001) while the effect of CBI satisfaction on suicidal ideation was no longer significant [c*=-.063, t(295)=-1.44, ns]. Our findings suggest an inverse relationship between CBI satisfaction and suicidal ideation, which is mediated by IS. This relationship likely falls in a continuum between non-clinical and clinical situations, with suicide risk being greater when individuals experience greater CBI dissatisfaction and social alienation. Copyright © 2013 Elsevier Inc. All rights reserved.

Lack of muco-cutaneous signs of toxic shock syndrome when T cells are absent: S.aureus shock in immunodeficient adults with multiple myeloma

PubMed Central

KAMEL, N S; BANKS, M C; DOSIK, A; URSEA, D; YARILINA, A A; POSNETT, D N

2002-01-01

Staphylococcal toxic shock syndrome (TSS) is an acute life threatening disease. The diagnosis can be made clinically based on diagnostic criteria. The clinical manifestations are caused in large part by the release of high levels of T-cell-derived cytokines as a result of potent toxins, also called superantigens (SAg), produced by Staphylococcus aureus, but it is not clear which clinical symptoms/signs are strictly T-cell dependent. Here, we report on three adults with multiple myeloma (MM) presenting with S. aureus sepsis/shock, and two patients with typical TSS. The MM patients had compromised humoral immunity because of depression of normal immunoglobulin (Ig) levels at the expense of the M protein. In addition, their T cells were absent due to high dose chemotherapy initiated for bone marrow transplantation. The MM cases lacked mucosal hyperemia, erythroderma and desquamation, but were otherwise indistinguishable from the TSS cases. All patients grew S. aureus and in each case, SAg genes were detected by PCR. In several cases, the plasma contained biological SAg activity resulting in Vβ specific proliferation of indicator T cells in vitro. The same specific activity was observed with the supernatant fluids of S. aureus broth cultures from the respective bacterial isolates. This confirms the presence of bio-active toxins in the plasma but did not lead to full blown TSS when T cells were lacking. Thus, S.aureus sepsis/shock can be clinically distinguished from typical TSS, and we suggest that muco-cutaneous manifestations of TSS are the most telling signs of massive T-cell-dependent cytokine release. PMID:12033193

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma

ClinicalTrials.gov

2018-03-12

Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Plasma Cell Myeloma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified; Refractory Plasma Cell Myeloma; Refractory T-Cell Non-Hodgkin Lymphoma

The First Korean Case of Cutaneous Lung Tissue Heterotopia

PubMed Central

Jeon, Ga Won; Han, Seong Woo; Jung, Ji Mi; Kang, Mi Seon

2010-01-01

Cutaneous lung tissue heterotopia is a very rare disorder where mature lung tissues develop in the skin. This is only the second known report of cutaneous lung tissue heterotopia, with the first by Singer et al. in 1998. A newborn infant had a hemangioma-like, freely movable mass connected to the anterior aspect of the sternal manubrium. Pathologic findings showed mature lung tissues with bronchi, bronchioles, and alveoli through the dermis and subcutis, and it was diagnosed as cutaneous lung tissue heterotopia. Cutaneous lung tissue heterotopia is hypervascular, so grossly it looks like a hemangioma. It can be differentiated from pulmonary sequestration, teratoma, bronchogenic cyst, and branchial cleft cyst by histology and the location of the mass. We describe the clinical, radiologic, and pathologic findings of a cutaneous lung tissue heterotopia, the first reported in Korea. PMID:20808688

GATA3 Expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms

PubMed Central

de Peralta-Venturina, Mariza N.; Balzer, Bonnie L.; Frishberg, David P.

2015-01-01

Abstract: Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin. PMID:26595821

GATA3 Expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms.

PubMed

Mertens, Richard B; de Peralta-Venturina, Mariza N; Balzer, Bonnie L; Frishberg, David P

2015-12-01

Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin.

Separate Primary Melanomas of the Bulbar Conjunctiva and Eyelid Skin: Clinical Implications of Multiple Primary Melanomas.

PubMed

Jacinto, Frances A; Fisher, George H; Espana, Edgar M; Leyngold, Ilya M; Margo, Curtis E

2016-10-01

We report a patient with previous in situ melanoma of the forehead skin who was referred for treatment of a bulbar conjunctival melanoma and a separate superficially invasive melanoma of the eyelid skin, and we offer a review of the biological and clinical implications of patients who have multiple primary melanomas. This article offers a clinicopathological correlation with a review of the relevant literature. An 80-year-old white man was referred for evaluation of a suspicious conjunctival tumor and a lower-eyelid lesion. Excisional biopsies revealed that both were primary melanomas arising within in situ disease. Over the span of 25 years, the patient had three separate foci of in situ melanoma, two of which spawned invasive melanoma. Separate melanomas arising from the bulbar conjunctiva and eyelid skin have rarely been reported. Multiple primary melanomas of the skin, however, are not uncommon. Based on studies of persons with multiple cutaneous melanomas, the prognosis is best predicted by the tumor with the greatest depth of invasion. Patients with multiple melanomas should be examined for dysplastic nevi, additional cutaneous melanomas, and screened periodically for future lesions. Ongoing studies enrolling patients with multiple primary melanomas are attempting to generate insights into low-penetrance susceptibility genes.

Ethnic differences in the epidemiology of cutaneous lupus erythematosus in New Zealand.

PubMed

Jarrett, P; Thornley, S; Scragg, R

2016-11-01

Background The prevalence and variation by ethnicity of cutaneous lupus in New Zealand is not known. Therefore, a cross-sectional study to determine the prevalence and variation by ethnicity of cutaneous lupus in the ethnically diverse community of South Auckland, New Zealand, was undertaken. Methods Multiple sources were examined to determine the prevalence of acute cutaneous lupus erythematosus, subacute cutaneous erythematosus and discoid lupus erythematosus. Ethnicities examined were European, Māori/Pacific and Indian/Asian. Capture-recapture was used to determine the overall population prevalence of cutaneous lupus. Results A total of 145 cases of cutaneous lupus were identified. There were 22 men and 123 women, with an average age (standard deviation), respectively, of 46.4 (±21.5) and 43.1 (±14.8) years. There were 53 cases of acute cutaneous lupus erythematosus, 19 cases of subacute cutaneous erythematosus and 66 cases of discoid lupus erythematosus. The age and sex adjusted relative risk (95% confidence interval; CI) of Māori/Pacific compared to the European population was 2.47 (95% CI 1.67-3.67) for all types of cutaneous lupus, 1.60 (95% CI 0.84-3.18) for acute cutaneous lupus erythematosus, 0.09 (95% CI 0.01-1.1) for subacute cutaneous erythematosus and 5.96 (95% CI 3.06-11.6) for discoid lupus erythematosus. The overall prevalence of cutaneous lupus was 30.1 (95% CI 25.5-35.4) per 100,000. However, capture-recapture estimated the unadjusted prevalence of cutaneous lupus to be 86.0 (95% CI 78.1-94.7) per 100,000. Conclusion Māori and Pacific people in Auckland, New Zealand, have a greater relative risk of all types of cutaneous lupus compared to the European population and a particularly high risk of discoid lupus erythematosus.

Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells.

PubMed

Seki, Akiko; Rutz, Sascha

2018-03-05

CRISPR (clustered, regularly interspaced, short palindromic repeats)/Cas9 (CRISPR-associated protein 9) has become the tool of choice for generating gene knockouts across a variety of species. The ability for efficient gene editing in primary T cells not only represents a valuable research tool to study gene function but also holds great promise for T cell-based immunotherapies, such as next-generation chimeric antigen receptor (CAR) T cells. Previous attempts to apply CRIPSR/Cas9 for gene editing in primary T cells have resulted in highly variable knockout efficiency and required T cell receptor (TCR) stimulation, thus largely precluding the study of genes involved in T cell activation or differentiation. Here, we describe an optimized approach for Cas9/RNP transfection of primary mouse and human T cells without TCR stimulation that results in near complete loss of target gene expression at the population level, mitigating the need for selection. We believe that this method will greatly extend the feasibly of target gene discovery and validation in primary T cells and simplify the gene editing process for next-generation immunotherapies. © 2018 Genentech.

Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Sarah N., E-mail: shamilton7@bccancer.bc.ca; Radiation Therapy Program, BC Cancer Agency, Vancouver; Wai, Elaine S.

2013-11-15

Purpose: To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Methods and Materials: Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Results: Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects withmore » indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age >60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). Conclusions: This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the

Treatment and outcomes in patients with primary cutaneous B-cell lymphoma: the BC Cancer Agency experience.

PubMed

Hamilton, Sarah N; Wai, Elaine S; Tan, King; Alexander, Cheryl; Gascoyne, Randy D; Connors, Joseph M

2013-11-15

To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL

La tuberculose cutanée: observation de six cas confirmés au CHU Souro SANOU (CHUSS) de Bobo-Dioulasso (Burkina Faso)

PubMed Central

Andonaba, Jean Baptiste; Barro-Traoré, Fatou; Yaméogo, Téné; Diallo, Boukary; Korsaga-Somé, Nina; Traoré, Adama

2013-01-01

La localisation cutanée de la maladie tuberculeuse demeure une forme rare et représente seulement 2,1% des localisations. L'objet de cette étude est de rapporter le profil épidémiologique, anatomoclinique et évolutif des cas de tuberculose ganglio-cutanée diagnostiqués dans un CHU au Burkina Faso. La fréquence de la tuberculose cutanée est très faible au CHUSS. Six cas ont été diagnostiqués entre 2004 et 2010, soit une fréquence de un cas par an. La durée d’évolution des cas allait de deux jusqu’à dix ans avant leur diagnostic. Les lésions observées étaient: trois scrofulodermes, trois gommes, une tuberculose testiculaire associée à un mal de Pott, un cas de polyadénopathies et des cicatrices atropho-rétractiles dans la plupart des cas. Sur le plan anatomopathologique, des granulomes tuberculoïdes ont été mis en évidence dans tous les cas avec une forte réaction tuberculinique à l'IDR. Sous antituberculeux pendant six mois, l’évolution a été bonne dans tous les cas mais au prix de séquelles cutanées cicatricielles inesthétiques. Son ampleur reste peut-être encore méconnue. Le renforcement du plateau technique du CHU et une bonne collaboration interdisciplinaire contribuerait à un meilleur diagnostic et prise en charge de cette affection. PMID:24648863

[Cutaneous tuberculosis in Bamako, Mali].

PubMed

Dicko, Adama; Faye, Ousmane; Fofana, Youssouf; Soumoutera, Moussa; Berthé, Siritio; Touré, Saidou; Traoré, Bekaye; Guindo, Binta; Tall, Koureissi; Keita, Alimata; Kéita, Lassine; Coulibaly, Karim; Keita, Somita

2017-01-01

Tuberculosis is the most common mycobacteriosis in sub-Saharan Africa. Cutaneous tuberculosis is rare and underdiagnosed due to its clinical polymorphism and to the smallness of technical equipment. This study aims to describe the epidemiological, clinical, histopathological aspects of cutaneous tuberculosis in Bamako (Mali). We conducted a cross-sectional descriptive study from January 1991 to December 2008. The study was performed in the Department of Dermatology at the National Center for Disease Control and in the Department of Pneumophtisiology at the Hospital of Point G. The patients with tuberculosis confirmed by histological and/or biological examination were included in the study. Out of 4269 patients? medical records, 61 cases of cutaneous tuberculosis were identified (1.43%). Men accounted for 59% of the cases (36 patients) and women 41% (25 cases); sex-ratio was 1.44. The age of the patients ranged from 3 months to 61 years, with an average age of 27.56 ± 36 years. The average length of follow-up was 10.9 ± 10 months. The identified clinical forms were scrofuloderma (41 cases), ulcerative form (13 cases), verrucous form (4 cases), and tuberculous Lupus (3 cases). Tuberculosis was associated with HIV in 7 cases, with leprosy in 3 cases. Cutaneous tuberculosis is underdiagnosed in Mali. Efforts are needed to improve the accessibility and the technical equipment available in the Departments, in order to conduct an extensive interdisciplinary study on this pathology.

New Clinicoepidemiologic Profile of Cutaneous Leishmaniasis, Morocco

PubMed Central

Rhajaoui, Mohamed; Fellah, Hajiba; Azmi, Kifaya; Amarir, Fatima; Al-Jawabreh, Amer; Ereqat, Suheir; Planer, Joseph; Abdeen, Ziad

2007-01-01

During the past 20 years, cutaneous leishmaniasis has emerged as a major public health threat in Morocco. We describe distribution of Leishmania major and L. tropica in Morocco and a new focus of cutaneous leishmaniasis due to L. infantum. We recommend using molecular techniques to diagnose suspected leishmaniasis cases. PMID:18252108

Self-healing juvenile cutaneous mucinosis: cases highlighting subcutaneous/fascial involvement.

PubMed

Nagaraj, Lavanya V; Fangman, William; White, Wain L; Woosley, John T; Prose, Neil; Selim, M Angelica; Morrell, Dean S

2006-12-01

Self-healing juvenile cutaneous mucinosis is a rare disease affecting young people characterized by transient cutaneous lesions and sometimes mild inflammatory symptoms. The deep dermal and subcutaneous features of this disorder have not yet been well described. The purpose of our study was to present 3 cases of self-healing juvenile cutaneous mucinosis in which the histopathologic features caused diagnostic confusion between this disorder and proliferative fasciitis. The study includes clinical and histologic findings of 3 patients, complemented by a literature review. The histologic descriptions of nodular lesions in self-healing juvenile cutaneous mucinosis reveal features of proliferative fasciitis, including a myxoid stroma and gangliocyte-like giant cells. Self-healing juvenile cutaneous mucinosis is a rare condition and has not been frequently reported in medical literature. Our findings are based on the pathologic features of 3 patients. Our findings further elucidate the histologic features of self-healing juvenile cutaneous mucinosis and expand the differential diagnosis for entities in which gangliocyte-like giant cells are noted.

A Cutaneous Lupus Erythematosus-Like Eruption Induced by Hydroxyurea.

PubMed

Yanes, Daniel A; Mosser-Goldfarb, Joy L

2017-01-01

Hydroxyurea is a medication with many well-described cutaneous side effects, notably the dermatomyositis-like eruption known as hydroxyurea dermopathy. Although systemic lupus erythematosus has been reported with hydroxyurea use, cutaneous lupus has not. We report a novel case of chronic cutaneous lupus induced by hydroxyurea and propose that this is a side effect that is distinct from hydroxyurea dermopathy. © 2016 Wiley Periodicals, Inc.

Disruption of TNFα/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection

PubMed Central

Tian, Tian; Dubin, Krista; Jin, Qiushuang; Qureshi, Ali; King, Sandra L.; Liu, Luzheng; Jiang, Xiaodong; Murphy, George F.; Kupper, Thomas S.; Fuhlbrigge, Robert C.

2012-01-01

One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFR) that block TNFα function. The response to VV skin infection under conditions of TNFα deficiency, however, has not been reported. We found that TNFR1−/− mice developed larger primary lesions, numerous satellite lesions and higher skin virus levels after VV scarification. Following their recovery, these TNFR1−/− mice were fully protected against challenge with a lethal intranasal dose of VV, suggesting these mice developed an effective memory immune response. A functional systemic immune response of TNFR1−/− mice was further demonstrated by enhanced production of VV-specific IFNγ and VV-specific CD8+ T cells in spleens and draining lymph nodes. Interestingly, bone marrow (BM) reconstitution studies using WT BM in TNFR1−/− host mice, but not TNFR1−/− BM in WT host mice, reproduced the original results seen in TNFR1−/− mice, indicating that TNFR1 deficiency in resident skin cells, rather than hematopoietic cells, accounts for the impaired cutaneous immune response. Our data suggest that lack of TNFR1 leads to a skin-specific immune deficiency and that resident skin cells play a crucial role in mediating an optimal immune defense to VV cutaneous infection via TNFα/TNFR1 signaling. PMID:22318381

Mast cells have no impact on cutaneous leishmaniasis severity and related Th2 differentiation in resistant and susceptible mice.

PubMed

Paul, Christoph; Wolff, Svenja; Zapf, Thea; Raifer, Hartmann; Feyerabend, Thorsten B; Bollig, Nadine; Camara, Bärbel; Trier, Claudia; Schleicher, Ulrike; Rodewald, Hans-Reimer; Lohoff, Michael

2016-01-01

The genus leishmania comprises different protozoan parasites which are causative agents of muco-cutaneous and systemic, potentially lethal diseases. After infection with the species Leishmania major, resistant mice expand Th1 cells which stimulate macrophages for Leishmania destruction. In contrast, susceptible mice generate Th2 cells which deactivate macrophages, leading to systemic spread of the pathogens. Th-cell differentiation is determined within the first days, and Th2 cell differentiation requires IL-4, whereby the initial IL-4 source is often unknown. Mast cells are potential sources of IL-4, and hence their role in murine leishmaniasis has previously been studied in mast cell-deficient Kit mutant mice, although these mice display immunological phenotypes beyond mast cell deficiency. We therefore readdressed this question by infecting Kit-independent mast cell-deficient mice that are Th1 (C57BL/6 Cpa(Cre) ) or Th2 (BALB/c Cpa(Cre) ) prone with L. major. Using different parasite doses and intra- or subcutaneous infection routes, the results demonstrate no role of mast cells on lesion size development, parasite load, immune cell phenotypes expanding in draining lymph nodes, and cytokine production during murine cutaneous leishmaniasis. Thus, other cell types such as ILCs or T cells have to be considered as primary source of Th2-driving IL-4. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increased Soluble CD226 in Sera of Patients with Cutaneous T-Cell Lymphoma Mediates Cytotoxic Activity against Tumor Cells via CD155.

PubMed

Takahashi, Naomi; Sugaya, Makoto; Suga, Hiraku; Oka, Tomonori; Kawaguchi, Makiko; Miyagaki, Tomomitsu; Fujita, Hideki; Inozume, Takashi; Sato, Shinichi

2017-08-01

Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances. CD155 is expressed in various types of cancer, and this surface molecule on tumor cells functions either as a co-stimulatory molecule or a co-inhibitory molecule, depending on its receptor. CD226, a CD155 ligand, is mainly expressed on natural killer cells and CD8 + T cells, playing important roles in natural killer cell-mediated cytotoxicity. In this study, we investigated the expression and function of CD155 and CD226 in cutaneous T-cell lymphoma (CTCL). CD155 was strongly expressed on tumor cells and CD155 mRNA expression levels were increased in CTCL lesional skin. CD226 expression on natural killer cells and CD8 + cells in peripheral blood of CTCL patients was decreased. On the other hand, serum CD226 levels were significantly elevated in CTCL patients, strongly reflecting disease activity, suggesting that soluble CD226 in sera was generated by shedding of its membrane form. Recombinant CD226 itself showed cytotoxic activity against CD155-expressing CTCL cells in vitro. These data suggest that soluble CD226 elevated in sera of CTCL patients would be important for tumor immunity by interacting with CD155 on tumor cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cutaneous manifestations of Prototheca infections.

PubMed

Boyd, A S; Langley, M; King, L E

1995-05-01

The genus Prototheca comprises several species, the most prevalent of which is Prototheca wickerhamii. These achlorophyllic algae are found in the slime flux of trees and in freshwater environs. Cutaneous infection with these microbes was first reported 30 years ago. Subsequent case reports have described other manifestations including systemic disease. Asymptomatic and stationary cutaneous plaques may be seen in otherwise healthy patients. Susceptibility to infection is ill defined but may involve an inability of neutrophils to effectively eradicate phagocytosed organisms. Characteristic morula are seen histologically. Antifungal medications are the most effective therapy.

Lymphoscintigraphy Defines New Lymphatic Pathways from Cutaneous Melanoma Site: Clinical Implications and Surgical Management

PubMed Central

Marone, Ugo; Aloj, Luigi; Di Monta, Gianluca; Caracò, Corrado

2011-01-01

Sentinel lymph node biopsy is commonly applied as staging procedure of regional lymph nodes in patients with cutaneous melanoma. Dynamic lymphoscintigraphy defines the lymphatic pathways from a primary melanoma site and allows to identify the node receiving lymphatic drainage from the primary tumor, which is the sentinel lymph node. In rare cases, lymphoscintigraphy shows sites of lymphatic drainage in nonclassical basins never described in the past when lymphatic drainage was considered only according to the anatomical proximity of the tumor primary site. These peculiar sentinel nodes, so-called “uncommon/interval” nodes, must be surgically removed because they may contain micrometastatic disease and may be the only site of nodal involvement. PMID:22242203

Update on cutaneous tuberculosis*

PubMed Central

Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victória; do Nascimento, Leninha Valério; Nery, José Augusto da Costa; Azulay, David Rubem

2014-01-01

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

Cutaneous Squamous Cell Carcinoma.

PubMed

Parekh, Vishwas; Seykora, John T

2017-09-01

Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

[Update on cutaneous dirofilariasis].

PubMed

Benzaquen, M; Marmottant, E; Parola, P; Berbis, P

2017-10-01

Dirofilariasis is a worldwide zoonotic infection that rarely affects humans and is caused by filarial nematodes of the genus Diroflaria transmitted by mosquitoes. Cutaneous dirofilariasis, due to D. repens, presents as inflammatory lesions that develop into subcutaneous nodules. These clinical symptoms may be consistent with Wells' cellulitis. Diagnosis of dirofilariasis involves demonstration of the presence of the nematode during skin biopsy and identification of the worm through macroscopic, histological and PCR analysis. Surgical resection of the nodule remains the gold standard treatment. The number of cases of human cutaneous dirofilariasis has increased in the recent years and the disease must not be misdiagnosed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin

Reduction of CD147 surface expression on primary T cells leads to enhanced cell proliferation.

PubMed

Biegler, Brian; Kasinrerk, Watchara

2012-12-01

CD147 is a ubiquitously expressed membrane glycoprotein that has numerous functional associations in health and disease. However, the molecular mechanisms by which CD147 participates in these processes are unclear. Establishing physiologically relevant silencing of CD147 in primary T cells could provide clues essential for elucidating some aspects of CD147 biology. To date, achieving the knockdown of CD147 in primary T cells has remained elusive. Utilizing RNA interference and the Nucleofector transfection system, we were able to reduce the expression of CD147 in primary T cells. Comparison of basic functions, such as proliferation and CD25 expression, were then made between control populations and populations with reduced expression. Up-regulation of CD147 was found upon T-cell activation, indicating a role in T-cell responses. To better understand the possible importance of this up-regulation, we knocked down the expression of CD147 using RNA interference. When compared to control populations the CD147 knockdown populations exhibited increased proliferation. This alteration of cell proliferation, however, was not linked to a change in CD25 expression. We achieved reduction of CD147 surface expression in primary T cells by siRNA-mediated gene silencing. Our results point to CD147 having a possible negative regulatory role in T cell-mediated immune responses.

Cutaneous reactions to proton pump inhibitors: a case-control study.

PubMed

Chularojanamontri, Leena; Jiamton, Sukhum; Manapajon, Araya; Suvanasuthi, Saroj; Kulthanan, Kanokvalai; Dhana, Naruemon; Jongjarearnprasert, Kowit

2012-10-01

Even though proton pump inhibitors (PPIs) are commonly used in clinical practice, a limited number of studies are available about cutaneous adverse reactions from PPIs, and most of these are case reports. To demonstrate the pattern of cutaneous reactions related to PPI usage and to evaluate the risk of developing PPI drug eruptions among adult patients. We reviewed the spontaneous reports of any adverse events associated with PPI use, as reported from January 2005 through May 2010 to the Adverse Drug Reaction Center at Siriraj Hospital in Thailand. Each control was sampled from 15 patients who had consecutive hospital numbers from each study case. The prevalence of cutaneous reactions to PPIs varied, ranging from three to 20 per 100,000 of the treated population. Sixty-four patients with a history of reaction to PPIs, and 65 controls were enrolled. Most cutaneous reactions were attributed to omeprazole (n=50; 78.1%), and the most frequently observed cutaneous reaction was maculopapular rash (43.8%). None of the patients experienced a cross-reaction between individual PPIs. Cutaneous adverse reactions to PPIs range from minor drug rashes to a severe, life-threatening reaction. Individuals with a history of adverse drug reaction have an increased risk of cutaneous reaction to PPIs.

Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas.

PubMed

Martín-Sánchez, Esperanza; Rodríguez-Pinilla, Socorro M; Sánchez-Beato, Margarita; Lombardía, Luis; Domínguez-González, Beatriz; Romero, Diana; Odqvist, Lina; García-Sanz, Pablo; Wozniak, Magdalena B; Kurz, Guido; Blanco-Aparicio, Carmen; Mollejo, Manuela; Alves, F Javier; Menárguez, Javier; González-Palacios, Fernando; Rodríguez-Peralto, José Luis; Ortiz-Romero, Pablo L; García, Juan F; Bischoff, James R; Piris, Miguel A

2013-01-01

Peripheral T-cell lymphomas are very aggressive hematologic malignancies for which there is no targeted therapy. New, rational approaches are necessary to improve the very poor outcome in these patients. Phosphatidylinositol-3-kinase is one of the most important pathways in cell survival and proliferation. We hypothesized that phosphatidylinositol-3-kinase inhibitors could be rationally selected drugs for treating peripheral T-cell lymphomas. Several phosphatidylinositol-3-kinase isoforms were inhibited genetically (using small interfering RNA) and pharmacologically (with CAL-101 and GDC-0941 compounds) in a panel of six peripheral and cutaneous T-cell lymphoma cell lines. Cell viability was measured by intracellular ATP content; apoptosis and cell cycle changes were checked by flow cytometry. Pharmacodynamic biomarkers were assessed by western blot. The PIK3CD gene, which encodes the δ isoform of phosphatidylinositol-3-kinase, was overexpressed in cell lines and primary samples, and correlated with survival pathways. However, neither genetic nor specific pharmacological inhibition of phosphatidylinositol-3-kinase δ affected cell survival. In contrast, the pan-phosphatidylinositol-3-kinase inhibitor GDC-0941 arrested all T-cell lymphoma cell lines in the G1 phase and induced apoptosis in a subset of them. We identified phospho-GSK3β and phospho-p70S6K as potential biomarkers of phosphatidylinositol-3-kinase inhibitors. Interestingly, an increase in ERK phosphorylation was observed in some GDC -0941-treated T-cell lymphoma cell lines, suggesting the presence of a combination of phosphatidylinositol-3-kinase and MEK inhibitors. A highly synergistic effect was found between the two inhibitors, with the combination enhancing cell cycle arrest at G0/G1 in all T-cell lymphoma cell lines, and reducing cell viability in primary tumor T cells ex vivo. These results suggest that the combined treatment of pan-phosphatidylinositol-3-kinase + MEK inhibitors could be more

BCL11B-Mediated Epigenetic Repression Is a Crucial Target for Histone Deacetylase Inhibitors in Cutaneous T-Cell Lymphoma.

PubMed

Fu, Wenjing; Yi, Shengguo; Qiu, Lei; Sun, Jingru; Tu, Ping; Wang, Yang

2017-07-01

The treatment options for advanced cutaneous T-cell lymphoma (CTCL) are limited because of its unclear pathogenesis. Histone deacetylase (HDAC) inhibitors (HDACis) are recently developed therapeutics approved for refractory CTCL. However, the response rate is relatively low and unpredictable. Previously, we discovered that BCL11B, a key T-cell development regulator, was aberrantly overexpressed in mycosis fungoides, the most common CTCL, as compared with benign inflammatory skin. In this study, we identified a positive correlation between BCL11B expression and sensitivity to HDACi in CTCL lines. BCL11B suppression in BCL11B-high cells induced cell apoptosis by de-repressing apoptotic pathways and showed synergistic effects with suberoylanilide hydroxamic acid (SAHA), a pan-HDACi. Next, we identified the physical interaction and shared downstream genes between BCL11B and HDAC1/2 in CTCL lines. This interaction was essential in the anti-apoptosis effect of BCL11B, and the synergism between BCL11B suppression and HDACi treatment. Further, in clinical samples from 46 mycosis fungoides patients, BCL11B showed increased but varied expression in advanced tumor stage. Analysis of four patients receiving SAHA treatment suggested a positive correlation between BCL11B expression and favorable response to SAHA treatment. In conclusion, BCL11B may serve as a therapeutic target and a useful marker for improving HDACi efficacy in advanced CTCL. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cutaneous vasoregulation during short- and long-term aerial acclimation in the amphibious mangrove rivulus, Kryptolebias marmoratus.

PubMed

Cooper, C A; Litwiller, S L; Murrant, C L; Wright, P A

2012-03-01

The mangrove rivulus (Kryptolebias marmoratus) is an amphibious fish and evidence suggests that the cutaneous surface is the primary site of gas exchange during emersion. The aim of this study was to determine whether cutaneous blood vessels were regulated in the caudal fin during the initial transition from water to aerial exposure, and after 10 days of aerial acclimation. Acute changes (first 3 min following emersion) in the cutaneous vessels diameter were measured in real-time on live fish using light microscopy. The data show that under control conditions, only arterioles in the caudal fin were vasoactive. During the first 20s of aerial acclimation the arterioles significantly constricted (-2.1 ± 0.4 μm), which was followed immediately by a relaxation (from 40 to 180 s). This vasoconstriction was eliminated with the addition of phentolamine (50 μmoll(-1)), which indicates that the vasoconstriction was mediated by α-adrenoreceptors. Longer-term changes in the cutaneous surface vasculature were determined using fluorescent immunohistochemistry and antibodies for the endothelial marker, CD31. Fish aerially acclimated for 10 days exhibited significantly higher levels of endothelial fluorescence in the caudal fin when compared to control fish in water, indicating endothelial cell production (i.e. angiogenesis). These data combined show that for every emersion episode, there is an initial α-adrenergic mediated vasoconstriction, which is most likely, a stress response. This is then followed by a long-term acclimation involving an upregulation in endothelial cell production, which would subsequently enhance blood perfusion to the cutaneous surface and potentially increase the capacity for gas exchange with the external environment. Copyright © 2011 Elsevier Inc. All rights reserved.

Sentinel lymph node biopsy in cutaneous head and neck melanoma.

PubMed

Evrard, D; Routier, E; Mateus, C; Tomasic, G; Lombroso, J; Kolb, F; Robert, C; Moya-Plana, A

2018-05-01

Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO 2) monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cutaneous oxygen (PcO 2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO 2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO 2) monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cutaneous oxygen (PcO 2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO 2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

21 CFR 868.2500 - Cutaneous oxygen (PcO2) monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cutaneous oxygen (PcO2) monitor. 868.2500 Section... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2500 Cutaneous oxygen (PcO2) monitor. (a) Identification. A cutaneous oxygen (PcO2) monitor is a noninvasive, heated sensor (e.g., a...

Romidepsin for the treatment of relapsed/refractory cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome): Use in a community setting.

PubMed

Reddy, Sunil A

2016-10-01

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of rare non-Hodgkin lymphomas that arise in the skin. In advanced stages, CTCL becomes systemic and is associated with poor prognosis. Diagnosis of CTCL and treatment of early-stage disease with topical therapies often occurs under the care of a dermatologist. Community oncologists see few patients with CTCL due to direct referrals from dermatologists to academic or lymphoma specialty centers. However, some patients will continue to be managed in a community setting. Currently there is no evidence-based stepwise algorithm for treatment of patients with CTCL, and guidelines suggest a wide range of systemic therapies, including biologics, targeted agents, and more traditional chemotherapies. To provide optimal care in a community setting, oncologists must become familiar with newer nonchemotherapeutic treatment options. This review highlights romidepsin, a histone deacetylase inhibitor approved for the treatment of patients with CTCL who have received ≥1 prior systemic therapy. Copyright © 2016 The Author. Published by Elsevier Ireland Ltd.. All rights reserved.

Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon.

PubMed

Ishak, Rim; Kurban, Mazen; Kibbi, Abdul-Ghani; Abbas, Ossama

2015-01-01

Sarcoidosis is a multi-system granulomatous disease of unknown etiology. The skin is involved in 25% of cases. Studies on cutaneous sarcoidosis from our region are lacking. This study was conducted to describe clinical and histopathologic findings in all patients diagnosed with cutaneous sarcoidosis at the American University of Beirut Medical Center between 1992 and 2010 and to compare findings with those published in the literature. Clinical charts of patients with cutaneous sarcoidosis were retrospectively reviewed. Extracutaneous lesions were classified by organ involvement. Treatment was documented. Pathology specimens were reviewed. Cutaneous sarcoidosis was diagnosed in 76 Lebanese patients, 79% of whom were women. Mean age at diagnosis was 48 years. A total of 29% of patients had systemic disease that was commonly associated with lupus pernio lesions and subcutaneous sarcoidosis. The most common cutaneous lesions were sarcoidal plaques. The histopathologic features in our series did not differ from those described in the literature, except for the documented presence of a grenz zone. Interestingly, 23% of biopsy specimens contained perineural granulomas, raising the possibility of tuberculoid or borderline tuberculoid leprosy. Foreign bodies were detected in 10% of cases (all had systemic involvement), supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. The clinical and histopathologic features of cutaneous sarcoidosis patients in the present series are generally comparable with those published in the literature, with minor differences. Clinically, the most commonly seen lesion was plaque. Microscopically, cutaneous sarcoidosis may exhibit a grenz zone and may show perineural inflammation and foreign bodies. © 2014 The International Society of Dermatology.

The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.

PubMed

Hernández-Ruiz, Eugenia; Toll, Agustí; García-Diez, Irene; Andrades, Evelyn; Ferrandiz-Pulido, Carla; Masferrer, Emili; Yébenes, Mireia; Jaka, Ane; Gimeno, Javier; Gimeno, Ramón; García-Patos, Vicenç; Pujol, Ramón M; Hernández-Muñoz, Inmaculada

2018-03-08

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCCs) when compared with non-metastasizing cSCCs (non-MSCCs). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NF-κB signaling pathway. Accordingly, non-MSCCs display higher levels of membranous pS176-inhibitor of NF-kB kinase, and their stroma is enriched in neutrophils and eosinophils when compared with MSCCs. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb-depleted cSCC cells. Altogether, these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high-risk cSCCs could benefit from clinical therapies addressed to harness the immune response.

Retrospective study of canine cutaneous tumors in Korea

PubMed Central

Pakhrin, Bidur; Kang, Min-Soo; Bae, Il-Hong; Park, Mi-Sun; Jee, Hyang; You, Mi-Hyeon; Kim, Jae-Hoon; Yoon, Byung-Il; Choi, Yang-Kyu

2007-01-01

Over the 42 month period from January 2003 to June 2006, a total of 2,952 canine biopsy specimens were received from the Veterinary Medical Teaching Hospital of Seoul National University and from veterinary practitioners across the nation. Out of these, 748 (25.34%) cases were diagnosed as canine cutaneous tumors in the Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Korea. Thirty-eight different types of cutaneous tumors were identified and categorized into epithelial and melanocytic tumors (56.95%), mesenchymal tumors (38.90%), and hematopoietic tumors (4.14%) located in the skin. Among these, 69.25% were benign and 30.74% were malignant. The top ten most frequently diagnosed cutaneous tumors were epidermal and follicular cysts (12.70%), lipoma (11.36%), mast cell tumors (8.82%), cutaneous histiocytoma (7.49%), basal cell tumors (6.82%), sebaceous gland adenoma (6.68%), sebaceous gland hyperplasia (5.08%), hepatoid gland adenoma (3.61%), apocrine adenocarcinoma (3.07%), and fibroma (2.81%), in order of prevalence. They comprised 68.45% of all cutaneous tumors. These top ten cutaneous tumors were distributed on the trunk (30.08%), head and neck (20.9%), extremities (19.14%), anal and perianal area (8.59%), and tail (3.91%). The age of the dogs with the ten most frequent tumors had a mean age of 8.3 years, with a range of 2 months to 19 years. When all types of tumors were considered together in the entire population, there was no difference in incidence according to sex. PMID:17679768

Cryosurgery for the treatment of cutaneous sporotrichosis in four pregnant women.

PubMed

Fichman, Vivian; Valle, Antonio Carlos Francesconi do; de Macedo, Priscila Marques; Freitas, Dayvison Francis Saraiva; Oliveira, Manoel Marques Evangelista de; Almeida-Paes, Rodrigo; Gutierrez-Galhardo, Maria Clara

2018-04-01

Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended. Thermotherapy is the most reported treatment described in this group of patients. It entails weeks of daily self-application of heat to the lesions, requires that the patient faithfully apply it, and it could cause skin burns. Cryosurgery is a useful therapeutic tool for many cutaneous infectious diseases, safe for pregnant women, but not well evaluated for sporotrichosis treatment in this group. The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to four pregnant patients with sporotrichosis treated with cryosurgery. The authors reviewed the clinical records of four pregnant patients diagnosed with cutaneous sporotrichosis and treated with cryosurgery. The sessions were carried out monthly up to clinical cure. Molecular identification of the Sporothrix species was performed in two cases using T3B PCR fingerprinting assays. All patients were in the second trimester of pregnancy and their age ranged from 18 to 34 years. With regard to clinical presentation, two patients had lymphocutaneous and two had the fixed form. S. brasiliensis was identified in two cases as the causative agent. Cryosurgery was well tolerated and the number of sessions ranged from 1 to 3. All the patients reached a complete clinical cure. Cryosurgery was a safe, easy to perform and well tolerated method, and therefore it is suggested to be a suitable option for the treatment of cutaneous sporotrichosis in pregnant women.

Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle

Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%).more » Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.« less

Incidental finding of cutaneous meningeal heterotopia in aplasia cutis congenita.

PubMed

Kenyon, Katharine; Zedek, Daniel; Sayed, Christopher

2016-07-01

Aplasia cutis congenita and cutaneous meningeal heterotopia are both rare congenital conditions that most commonly occur on the scalp and may appear clinically and histologically similar. A subtype of aplasia cutis congenita, membranous aplasia cutis congenita, and cutaneous meningeal heterotopia are both proposed to result from neural tube closure errors. However, neither non-membranous nor membranous aplasia cutis congenita are known to occur together with cutaneous meningeal heterotopia in the same lesion. We report the incidental finding of cutaneous meningeal heterotopia within a lesion of aplasia cutis congenita. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes.

PubMed

Tsai, Wei-Jern; Chang, Chu-Ting; Wang, Guei-Jane; Lee, Tzong-Huei; Chang, Shwu-Fen; Lu, Shao-Chun; Kuo, Yuh-Chi

2011-03-25

Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT.

Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features.

PubMed

Beaty, M W; Toro, J; Sorbara, L; Stern, J B; Pittaluga, S; Raffeld, M; Wilson, W H; Jaffe, E S

2001-09-01

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-BLPD), varying widely from an indolent process to an aggressive large cell lymphoma. The skin is the extrapulmonary organ most commonly involved in LYG. We studied 32 skin lesions from 20 patients with known pulmonary LYG, using immunohistochemistry, in situ hybridization for EBV, and polymerase chain reaction for the presence of antigen receptor gene rearrangements (IgH and TCR) to better define both the clinicopathologic spectrum and pathogenesis of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodules, with or without ulceration, were present in 17 patients (85%). These lesions demonstrate a marked angiocentric lymphohistiocytic infiltrate, composed predominantly of CD4-positive T-cells, with a high propensity for involving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, and cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients; clonal immunoglobulin heavy chain gene (IgH) rearrangements were detected by polymerase chain reaction in two patients. Multiple indurated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resolution with chemo/immunomodulatory therapy (8 of 13; 62%), and progression (4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG are extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less frequently identified. This subset of cases shows the histopathologic triad of angiodestruction with associated necrosis

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Delayed seroconversion and rapid onset of lymphoproliferative disease after transmission of human T-cell lymphotropic virus type 1 from a multiorgan donor.

PubMed

Glowacka, Ilona; Korn, Klaus; Potthoff, Sebastian A; Lehmann, Ulrich; Kreipe, Hans H; Ivens, Katrin; Barg-Hock, Hannelore; Schulz, Thomas F; Heim, Albert

2013-11-01

Human T-cell lymphotropic virus type 1 (HTLV-1) screening of blood and organ donors is not mandatory in Germany because of its low prevalence (about 7/100 000). An HTLV-1 transmission event caused by a multiple organ donor was investigated. Validity of diagnostic procedures and HTLV-1 disease association in immunosuppressed organ recipients were analyzed. Two screening immunoassays and an immunoblot (confirmatory assay) were used for detection of HLTV-1/2 antibodies. Proviral DNA was quantified in blood and biopsies of organ recipients by HTLV-1 real-time polymerase chain reaction (PCR). Proviral HTLV-1-DNA was detected in all blood samples of 3 organ recipients (1-100 copies/10(2) cells), but seroconversion was delayed for up to 2 years in screening assays and >6 years in the confirmatory assay. In 2 of 3 organ recipients, a cutaneous T-cell lymphoma was diagnosed 2 and 3 years after infection, respectively. Proviral HTLV-1 DNA concentration was almost 100 copies/10(2) cells in cutaneous lymphoma biopsies whereas in biopsies of other tissues ≤3.0 copies/10(2) cells were found. The third organ recipient did not suffer from lymphoma, but detailed clinical data on this patient were not available to us. Biopsy results support an etiological role for HTLV-1 in these cases of primary cutaneous T-cell lymphoma after solid organ transplant. HTLV-1-associated lymphoma can arise quickly in immunocompromised transplant recipients. The diagnosis of potentially HTLV-1-associated disease in organ recipients may require PCR because of delayed seroconversion.

[Comparative description and retrospective analisis of modern methods of surgical wounds closure for intraoperative prophylaxis of development of pathologic cutaneous cicatrices].

PubMed

Stavyts'kyĭ, S O; Avetikov, D S; Lokes, K P; Rozkolupa, O O; Boĭko, I V

2014-05-01

The experience of application of various methods of closure was presented for the head and neck cutaneous wound surfaces after elective operative interventions. The variant of the postoperative results estimation and optimization of the wounds healing by primary closure was proposed.

Noninferiority of Miltefosine Versus Meglumine Antimoniate for Cutaneous Leishmaniasis in Children

PubMed Central

Rubiano, Luisa Consuelo; Miranda, María Consuelo; Muvdi Arenas, Sandra; Montero, Luz Mery; Rodríguez-Barraquer, Isabel; Garcerant, Daniel; Prager, Martín; Osorio, Lyda; Rojas, Maria Ximena; Pérez, Mauricio; Nicholls, Ruben Santiago

2012-01-01

Background. Children have a lower response rate to antimonial drugs and higher elimination rate of antimony (Sb) than adults. Oral miltefosine has not been evaluated for pediatric cutaneous leishmaniasis. Methods. A randomized, noninferiority clinical trial with masked evaluation was conducted at 3 locations in Colombia where Leishmania panamensis and Leishmania guyanensis predominated. One hundred sixteen children aged 2–12 years with parasitologically confirmed cutaneous leishmaniasis were randomized to directly observed treatment with meglumine antimoniate (20 mg Sb/kg/d for 20 days; intramuscular) (n = 58) or miltefosine (1.8–2.5 mg/kg/d for 28 days; by mouth) (n = 58). Primary outcome was treatment failure at or before week 26 after initiation of treatment. Miltefosine was noninferior if the proportion of treatment failures was ≤15% higher than achieved with meglumine antimoniate (1-sided test, α = .05). Results. Ninety-five percent of children (111/116) completed follow-up evaluation. By intention-to-treat analysis, failure rate was 17.2% (98% confidence interval [CI], 5.7%–28.7%) for miltefosine and 31% (98% CI, 16.9%–45.2%) for meglumine antimoniate. The difference between treatment groups was 13.8%, (98% CI, −4.5% to 32%) (P = .04). Adverse events were mild for both treatments. Conclusions. Miltefosine is noninferior to meglumine antimoniate for treatment of pediatric cutaneous leishmaniasis caused by Leishmania (Viannia) species. Advantages of oral administration and low toxicity favor use of miltefosine in children. Clinical Trial Registration. NCT00487253. PMID:22238470

[Cerebellar, pulmonary and cutaneous localizations of juvenile xanthogranuloma].

PubMed

Cauro, F; Houtteville, J P; Mesnil, J L; Guarnieri, J

2002-03-01

Juvenile xanthogranuloma is one of the most common non-langerhan cell histiocytoses in children. Usually cutaneous, there are disseminated forms. However, neurological localizations remain exceptional. We report the case of a cerebellar localization, associated with cutaneous and pulmonary lesions in a 13-month old child. Surgical treatment of the cerebellar lesion was associated with vinblastin chemotherapy, that led to total regression of the cutaneous and pulmonary lesions, neurological stabilization, without recurrence on the control IRM, after a period of 7 years. This is the second reported case of histologically documented cerebellar juvenile xanthogranuloma. In the event of cutaneous juvenile xanthogranuloma, the neurological examination must be attentive and supplemented, in case of any suspicion, by medical imaging. We believe that surgical treatment of neurological juvenile xanthogranuloma is necessary, in the event of symptomatic lesions and accessible to surgery. No consensus has been reached on subsequent treatments (radiotherapy, chemotherapy) and must be discussed according to the clinical profile and data in the literature.

Cutaneous wound healing: recruiting developmental pathways for regeneration.

PubMed

Bielefeld, Kirsten A; Amini-Nik, Saeid; Alman, Benjamin A

2013-06-01

Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments.

Flexible ammonia handling strategies using both cutaneous and branchial epithelia in the highly ammonia-tolerant Pacific hagfish.

PubMed

Clifford, Alexander M; Weinrauch, Alyssa M; Edwards, Susan L; Wilkie, Michael P; Goss, Greg G

2017-08-01

Hagfish consume carrion, potentially exposing them to hypoxia, hypercapnia, and high environmental ammonia (HEA). We investigated branchial and cutaneous ammonia handling strategies by which Pacific hagfish ( Eptatretus stoutii ) tolerate and recover from high ammonia loading. Hagfish were exposed to HEA (20 mmol/l) for 48 h to elevate plasma total ammonia (T Amm ) levels before placement into divided chambers for a 4-h recovery period in ammonia-free seawater where ammonia excretion ( J Amm ) was measured independently in the anterior and posterior compartments. Localized HEA exposures were also conducted by subjecting hagfish to HEA in either the anterior or posterior compartments. During recovery, HEA-exposed animals increased J Amm in both compartments, with the posterior compartment comprising ~20% of the total J Amm compared with ~11% in non-HEA-exposed fish. Plasma T Amm increased substantially when whole hagfish and the posterior regions were exposed to HEA. Alternatively, plasma T Amm did not elevate after anterior localized HEA exposure. J Amm was concentration dependent (0.05-5 mmol/l) across excised skin patches at up to eightfold greater rates than in skin sections that were excised from HEA-exposed hagfish. Skin excised from more posterior regions displayed greater J Amm than those from more anterior regions. Immunohistochemistry with hagfish-specific anti-rhesus glycoprotein type c (α-hRhcg; ammonia transporter) antibody was characterized by staining on the basal aspect of hagfish epidermis while Western blotting demonstrated greater expression of Rhcg in more posterior skin sections. We conclude that cutaneous Rhcg proteins are involved in cutaneous ammonia excretion by Pacific hagfish and that this mechanism could be particularly important during feeding. Copyright © 2017 the American Physiological Society.

Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

PubMed

Silverberg, J I; Ratner, D

2015-07-01

Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P < 0.0001). Smokers with a history of NMSC or melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P < 0.0001). History of NMSC was associated with higher odds of malignancies of the bladder, brain, breast, colon, oesophagus, kidney, lung, lymphoma, melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P < 0.0001), with even higher rates of increase in those with history of NMSC or melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

New clinico-epidemiologic profile of cutaneous leishmaniasis, Morocco.

PubMed

Rhajaoui, Mohamed; Nasereddin, Abedelmajeed; Fellah, Hajiba; Azmi, Kifaya; Amarir, Fatima; Al-Jawabreh, Amer; Ereqat, Suheir; Planer, Joseph; Abdeen, Ziad

2007-09-01

During the past 20 years, cutaneous leishmaniasis has emerged as a major public health threat in Morocco. We describe distribution of Leishmania major and L. tropica in Morocco and a new focus of cutaneous leishmaniasis due to L. infantum. We recommend using molecular techniques to diagnose suspected leishmaniasis cases.

Cutaneous Manifestations of Systemic Lupus Erythematosus

PubMed Central

Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Freitas, João Pedro; Marques Gomes, Manuel; Filipe, Paulo

2012-01-01

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease of unknown etiology with many clinical manifestations. The skin is one of the target organs most variably affected by the disease. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalise the definition of SLE in clinical trials. They were not intended to be used to diagnose individuals and do not do well in that capacity. Cutaneous lesions account for four of these 11 revised criteria of SLE. Skin lesions in patients with lupus may be specific or nonspecific. This paper covers the SLE-specific cutaneous changes: malar rash, discoid rash, photosensitivity, and oral mucosal lesions as well as SLE nonspecific skin manifestations, their pathophysiology, and management. A deeper thorough understanding of the cutaneous manifestations of SLE is essential for diagnosis, prognosis, and efficient management. Thus, dermatologists should cooperate with other specialties to provide optimal care of SLE patient. PMID:22888407

Acute uriticaria-like lesions in allergen-unexposed cutaneous tissues in a mouse model of late allergic rhinitis

PubMed Central

Hayashi, Toshiharu; Fujii, Taeko

2008-01-01

The mechanisms of distant manifestation after a local allergic reaction are largely unknown. This study examined the development of cutaneous lesions in a mouse model of late allergic rhinitis (LAR). BALB/c mice were sensitized by ovalbumin (OVA) intraperitoneally two times (on days 0 and 10) and challenged by OVA intranasally on day 14. Four days after OVA challenge, nasal and cutaneous lesions including helper T (Th) responses, expression of adhesion molecules and presence of OVA and IgE were examined, and compared with unsensitized and unchallenged (control) mice. Compared with the control group, the LAR group developed LAR characterized by infiltration of lymphocytes and eosinophils, increased IgE values and increased productions of IL-4 and IL-5, but not IFN-γ. A dominant infiltration of eosinophils and increase in mast cells, attachment of eosinophils to endothelium, intense expression of VCAM-1 on endothelium in venules and VLA-4 expression on eosinophils and mast cells were recognized in the cutaneous tissues. There were no differences in the expression of ICAM-1 on vascular endothelium and LFA-1 on infiltrated leucocytes between the two groups. CLA expression on lymphocytes was not detected, and the binding of OVA and IgE on mast cells and eosinophils was found in the cutaneous lesions in the LAR group, but not in the control group. This study suggests that acute uriticaria-like lesions in OVA-unexposed cutaneous tissues may be induced by immediate allergic reaction due to the systemic development of Th2-type response in a mouse model of LAR. PMID:18460071

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors.

PubMed

Osio, A; Mateus, C; Soria, J-C; Massard, C; Malka, D; Boige, V; Besse, B; Robert, C

2009-09-01

Acute and subacute cutaneous side-effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. Much less is known about the chronic cutaneous effects of these drugs and about their potential psychosocial impact on patients. We performed a retrospective study of patients treated with EGFRIs for more than 6 months. All patients had a detailed dermatological examination. The primary cancer, associated chemotherapies, skin treatment, evolution of skin symptoms and their impact on quality of life (QoL) as evaluated by the Dermatology Life Quality Index (DLQI) were noted. Seven men and nine women were identified. The mean length of EGFRI treatment was 10 months (range 6-27). At the time of examination, all patients (100%) had cutaneous side-effects. Grade I or II folliculitis was found in 37.5% of the patients. Additional skin manifestations were xerosis (100%), mucositis (69%), hair abnormalities (87.5%), eyelash trichomegaly (62.5%), facial hypertrichosis (56%), painful paronychia (56%) and onycholysis (44%). Dose reduction or EGFRI discontinuation for skin toxicity were needed in six patients (37.5%). DLQI evaluation showed a moderate to strong impact on QoL in four patients (25%). Cutaneous side-effects are found in 100% of patients treated with EGFRIs for more than 6 months and have a significant effect on patients' QoL. The clinical spectrum of skin manifestation varies over time. As the use of EGFRIs rapidly increases, it is critical for us to improve our knowledge in the understanding and managment of these skin manifestations.

Three eyelid localized cutaneous anthrax cases.

PubMed

Esmer, Oktay; Karadag, Remzi; Bilgili, Serap Gunes; Gultepe, Bilge; Bayramlar, Huseyin; Karadag, Ayse Serap

2014-12-01

Anthrax is primarily seen in the developing countries, but it can be a worldwide medical concern due to bioterrorism threats. Palpebral anthrax is a rare form of cutaneous anthrax. Untreated cutaneous anthrax can be lethal. Patients with palpebral anthrax can develop complications including cicatrisation and ectropion. Thus, anthrax should be considered in differential diagnosis for patients presenting with preseptal cellulitis in high-risk regions. Herein, we report three anthrax cases (with different age) involving eyelids that were cured without any complications due to early diagnosis and treatment.

Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

PubMed

Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Aloj, Luigi; Caracò, Corradina; Anniciello, Annamaria; Lastoria, Secondo; Botti, Gerardo; Mozzillo, Nicola

2014-01-01

To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management. This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes. Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites. The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

[Visceral and cutaneous larva migrans].

PubMed

Petithory, Jean-Claude

2007-11-30

The syndrome of visceral larva migrans was described for the first time in 1952 by Beaver. He demonstrated that the presence of nematodes larvae, particularly in the liver, were those of Toxocara canis and T. cati. Baylisascaris procyonis, the common racoon ascarid in the U.S.A. can also cause serious diseases in human. Digestive and respiratory clinical symptoms are usually moderate, however severe disease resulting from invasion of the myocardium or the brain has been reported. A blood hypereosinophilia is usually present the first few years after infection. Diagnosis uses serological methods, among them the ELISA test. Ocular larva is also possible with in that case, immunological modifications of the aqueous. Cutaneous larva migrans characterized by a linear, progressing, serpigenous eruption and intense itching is easy to diagnose. Larva migrans is due to dogs, cats and horses helminths. Dogs and cats (referred here as pets) now receive antihelmintitic treatments and parasites are now in decrease.

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.

Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

PubMed Central

2011-01-01

Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

[Topical treatment of persistent cutaneous leishmaniasis with paromomycin].

PubMed

Flaig, M J; Rupec, J; Ruzicka, T; Rupec, R A

2007-08-01

Cutaneous leishmaniasis is an infectious disease with increasing prevalence in Germany. Diagnosis and therapy may be difficult due to the variability of the clinical and histomorphological picture and resistance to therapy. In this case study we report on a female patient with a persistent cutaneous leishmaniasis successfully treated with topical administration of paromomycin.

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

PubMed

Hung, Ching-Hsia; Shieh, Ja-Ping; Chiu, Chong-Chi; Wang, Jhi-Joung; Chen, Yu-Wen

2018-06-01

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED 50 )), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED 25 , ED 50 and ED 75 ), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double-blind randomized clinical trial.

PubMed

Baughman, Robert P; Judson, Marc A; Lower, Elyse E; Drent, Marjolein; Costabel, Ulrich; Flavin, Susan; Lo, Kim Hung; Barnathan, Elliot S

2016-01-15

Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. To determine infliximab's effectiveness in sarcoidosis. We conducted a subset analysis from a randomized, double-blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration.

A Case Report of Cutaneous Larva Migrans

PubMed Central

Yavuzer, Kemal; Ak, Muharrem; Karadag, Ayse Serap

2010-01-01

Cutaneous larva migrans (CLM) is a helminthic infection most commonly found in tropical and subtropical geographic areas. However, with the ease and increase of foreign travel by many around the world, CLM is no longer confined to these areas. CLM is an erythematous, serpiginous, cutaneous eruption caused by accidental percutaneous penetration and subsequent migration of larvae. Here, we present a case diagnosed as CLM and treated with Albendazole. PMID:25610118

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO2) monitor.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cutaneous carbon dioxide (PcCO2) monitor. 868.2480... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2480 Cutaneous carbon dioxide (PcCO2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive heated...

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO 2) monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cutaneous carbon dioxide (PcCO 2) monitor. 868... dioxide (PcCO 2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive... relative changes in a hemodynamically stable patient's cutaneous carbon dioxide tension as an adjunct to...

21 CFR 868.2480 - Cutaneous carbon dioxide (PcCO 2) monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cutaneous carbon dioxide (PcCO 2) monitor. 868... dioxide (PcCO 2) monitor. (a) Identification. A cutaneous carbon dioxide (PcCO2) monitor is a noninvasive... relative changes in a hemodynamically stable patient's cutaneous carbon dioxide tension as an adjunct to...

Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in scotland.

PubMed Central

MacKie, R. M.; Aitchison, T.

1982-01-01

A case-control study of occupational and recreational sun exposure, Mediterranean and other sun-exposed holidays, tanning history and history of isolated episodes of severe sunburn has been carried out on 113 patients with cutaneous malignant melanoma and 113 age- and sex-matched controls. Social class and skin type were also considered in the analysis of the data which involved the use of conditional multiple logistic regression. A highly significant increase in the history of severe sunburn was recorded in melanoma patients of both sexes in the 5-year period preceding presentation with their tumour. Higher social class and negative history of recreational sun exposure were also significantly increased in patients by comparison with controls. In the male group severe sunburn, lack of occupational sun exposure and higher social class were significant factors while in the female group only severe sunburn was significantly increased in the melanoma patients. This study thus provides evidence to suggest that short intense episodes of UV exposure resulting in burning may be one of the aetiological factors involved in subsequent development of melanoma. PMID:7150488

Recent insights into cutaneous immunization: How to vaccinate via the skin.

PubMed

Engelke, Laura; Winter, Gerhard; Hook, Sarah; Engert, Julia

2015-09-08

Technologies and strategies for cutaneous vaccination have been evolving significantly during the past decades. Today, there is evidence for increased efficacy of cutaneously delivered vaccines allowing for dose reduction and providing a minimally invasive alternative to traditional vaccination. Considerable progress has been made within the field of well-established cutaneous vaccination strategies: Jet and powder injection technologies, microneedles, microporation technologies, electroporation, sonoporation, and also transdermal and transfollicular vaccine delivery. Due to recent advances, the use of cutaneous vaccination can be expanded from prophylactic vaccination for infectious diseases into therapeutic vaccination for both infectious and non-infectious chronic conditions. This review will provide an insight into immunological processes occurring in the skin and introduce the key innovations of cutaneous vaccination technologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

A clinical study of cutaneous changes in pregnancy.

PubMed

Panicker, Vinitha V; Riyaz, Najeeba; Balachandran, P K

2017-03-01

Pregnant women experience a myriad of physiological and metabolic changes that affect different organ systems in the body. Cutaneous and appendageal alterations that manifest during pregnancy are largely modulated by hormonal, immunologic, and metabolic factors. Detailed reports encompassing physiological changes and specific dermatoses of pregnancy and effects of various dermatoses on pregnant women are scanty in literature. This study was conducted to examine in detail both physiological changes and specific dermatoses. The cutaneous changes are divided into physiological changes, skin diseases aggravated by pregnancy, and specific dermatoses of pregnancy. The objectives were to study the various cutaneous changes of pregnancy and to know the proportion of these cutaneous manifestations in pregnant women. This study included 600 pregnant women attending the Obstetrics and Gynecology Department of a tertiary teaching hospital in Northern Kerala, India. Detailed history elicitation and complete physical and dermatological examination were performed. Skin biopsy was performed in relevant cases. Cutaneous changes were seen in a majority of patients, of which physiological changes were the most common (99%). The most common cutaneous manifestation was hyperpigmentation (526; 87.6%), followed by striae gravidarum (72.8%). Other changes were vascular, including pedal edema (10%), pregnancy gingivitis (1.8%), and varicose veins (1%). Infections were the common dermatological problem in this study group. The most common infections were vulvovaginal candidiasis (21%), Tinea versicolor (6%), scabies (2.8%), dermatophytosis (1.5%), and sexually transmitted infection (0.5%). Specific dermatoses were seen in 12 cases (2%), with the most common being pruritic urticarial papules and plaques of pregnancy (1.3%). Pregnant women are prone to suffer from a wide range of dermatological problems apart from specific dermatoses of pregnancy. The study emphasizes the need for a detailed

WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

PubMed

Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

2018-02-07

Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

PubMed

Grundmann-Kollmann, Marcella; Martin, Hans; Ludwig, Ralf; Klein, Stefan; Boehncke, Wolf-Henning; Hoelzer, Dieter; Kaufmann, Roland; Podda, Maurizio

2002-12-15

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.

Cryosurgery for the treatment of cutaneous sporotrichosis in four pregnant women

PubMed Central

2018-01-01

Background Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended. Thermotherapy is the most reported treatment described in this group of patients. It entails weeks of daily self-application of heat to the lesions, requires that the patient faithfully apply it, and it could cause skin burns. Cryosurgery is a useful therapeutic tool for many cutaneous infectious diseases, safe for pregnant women, but not well evaluated for sporotrichosis treatment in this group. Methodology The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to four pregnant patients with sporotrichosis treated with cryosurgery. The authors reviewed the clinical records of four pregnant patients diagnosed with cutaneous sporotrichosis and treated with cryosurgery. The sessions were carried out monthly up to clinical cure. Molecular identification of the Sporothrix species was performed in two cases using T3B PCR fingerprinting assays. Principal findings All patients were in the second trimester of pregnancy and their age ranged from 18 to 34 years. With regard to clinical presentation, two patients had lymphocutaneous and two had the fixed form. S. brasiliensis was identified in two cases as the causative agent. Cryosurgery was well tolerated and the number of sessions ranged from 1 to 3. All the patients reached a complete clinical cure. Conclusions Cryosurgery was a safe, easy to perform and well tolerated method, and therefore it is suggested to be a suitable option for the treatment of cutaneous sporotrichosis in pregnant women. PMID:29684015

Les tumeurs annexielles cutanées: étude anatomopathologique à propos de 96 cas

PubMed Central

El Ochi, Mohamed Réda; Boudhas, Adil; Allaoui, Mohammed; Rharrassi, Issam; Chahdi, Hafsa; Bouzidi, Abderrahman Al; Oukabli, Mohammed

2015-01-01

Les tumeurs annexielles cutanées sont des tumeurs primitives cutanées à la fois rares et hétérogènes. Elles sont le plus souvent bénignes et rarement malignes. Elles sont dominées du point de vu morphologique par leur polymorphisme lésionnel. Le but de cette étude est de relever le profil épidémiologique et les différents aspects anatomopathologiques de ce groupe de tumeurs dans une cohorte de population marocaine et de les comparer avec les données de la littérature. Il s'agit d'une étude rétrospective de 96 cas de tumeurs annexielles cutanées colligées au service d'anatomie et de cytologie pathologique de l'Hôpital Militaire d'Instruction Mohammed V de rabat durant une période de 6 ans, de Janvier 2009 à Décembre 2014. Le pic de fréquence est situé entre 31 et 40 ans. L’âge moyen est de 36 ans avec une prédominance masculine (63,5%). Le siège de prédilection est la région de la tête et cou (47,9%). Les tumeurs bénignes (97,9%) sont plus fréquentes que les tumeurs malignes. La différenciation est folliculaire dans 51% des cas, eccrine/apocrine dans 44,8% des cas et sébacée dans 4,2% des cas. Le type histologique le plus fréquent est le pilomatrixome (33,4%) suivi par l'hidradénome (12,5%) et le spiradénome eccrine (11,5%). Les tumeurs annexielles cutanées sont rares et très variées. Le profil épidémiologique et les aspects anatomopathologiques qui ressortent sont globalement superposables à ceux rapportés dans la littérature. Elles sont majoritairement bénignes, à prédominance masculine et dominées par le pilomatrixome et l'hidradénome nodulaire. Les tumeurs malignes sont rares, agressives et surviennent à un âge plus avancé. PMID:26185579

Creation of a virtual cutaneous tissue bank

NASA Astrophysics Data System (ADS)

LaFramboise, William A.; Shah, Sujal; Hoy, R. W.; Letbetter, D.; Petrosko, P.; Vennare, R.; Johnson, Peter C.

2000-04-01

Cellular and non-cellular constituents of skin contain fundamental morphometric features and structural patterns that correlate with tissue function. High resolution digital image acquisitions performed using an automated system and proprietary software to assemble adjacent images and create a contiguous, lossless, digital representation of individual microscope slide specimens. Serial extraction, evaluation and statistical analysis of cutaneous feature is performed utilizing an automated analysis system, to derive normal cutaneous parameters comprising essential structural skin components. Automated digital cutaneous analysis allows for fast extraction of microanatomic dat with accuracy approximating manual measurement. The process provides rapid assessment of feature both within individual specimens and across sample populations. The images, component data, and statistical analysis comprise a bioinformatics database to serve as an architectural blueprint for skin tissue engineering and as a diagnostic standard of comparison for pathologic specimens.

Primary cutaneous B-cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1-69 and VH4-59 segments.

PubMed

Perez, M; Pacchiarotti, A; Frontani, M; Pescarmona, E; Caprini, E; Lombardo, G A; Russo, G; Faraggiana, T

2010-03-01

Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B-cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B-cell malignancies. This work investigates the cellular origin and antigenic selection in primary cutaneous B-cell lymphoma (PCBCL). We analysed the nucleotide sequence of clonal IgV heavy-chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B-cell lymphoma, leg-type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1.6% to 21%, with a median rate of 9.8% and was independent of PCBCL histotype. Calculation of antigen-selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1-69 (12%) and VH4-59 (14%), were preferentially used in our case series. Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.

Cutaneous myeloid dendritic cell dyscrasia: A cutaneous clonal monocytosis associated with chronic myeloproliferative disorders and peripheral blood monocytosis.

PubMed

Magro, Cynthia M; Momtahen, Shabnam; Verma, Shalini; Abraham, Ronnie M; Friedman, Constantin; Nuovo, Gerard J; Tam, Wayne

2016-12-01

Monocytes are critical components of the innate immune system and they can differentiate into dendritic cells (DCs). Cutaneous neoplasms of dendritic cell origin are uncommon and mostly represented by histiocytic lesions derived primarily from Langerhans cells. The myeloid DC (mDC) while recognized in the immunology literature does not have a well-defined neoplastic cutaneous counterpart. Eleven patients with a diagnosis of cutaneous mDC dyscrasia were evaluated. Routine hematoxylin and eosin stain were performed followed by selective phenotypic studies. The patients were older without a gender predilection and exhibited an asymptomatic papular skin rash with a waxing and waning course. The biopsies demonstrated a dermal based monomorphic small mononuclear cell infiltrate. The cells expressed CD14, CD11c, HLA-DR, as well as granzyme and lysozyme that defines terminally differentiated monocyte/dendritic cells. Expression of BDCA-3 (CD141) by the tumor cells indicated that they were myeloid dendritic cells (mDC2). Each patient had a prior or subsequent diagnosis of an abnormal bone marrow biopsy that included myelodysplastic syndrome, myelofibrosis, chronic myelomonocytic leukemia, and acute myelogenous leukemia. We propose the term cutaneous mDC cell dyscrasia for distinctive infiltrates of differentiated mDCs reflective of underlying myeloproliferative disease. The clinical course is variable and can be indolent although it is strongly correlated with myelodysplastic syndrome that included leukemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Cutaneous metastases of internal tumors.

PubMed

Fernández-Antón Martínez, M C; Parra-Blanco, V; Avilés Izquierdo, J A; Suárez Fernández, R M

2013-12-01

Cutaneous metastases are relatively rare in clinical practice and their diagnosis requires a high index of suspicion because clinical findings can be subtle. These metastases reveal the presence of disseminated malignant disease and can lead to the diagnosis of unsuspected internal tumors or the spread or recurrence of an already diagnosed tumor. Early recognition of cutaneous metastases can facilitate prompt and accurate diagnosis resulting in early treatment; however, they are generally indicative of a poor prognosis. Some tumors have a predilection to metastasize to specific areas. Recognition of these patterns provides essential information that can guide the search for the underlying tumor. Copyright © 2011 Elsevier España, S.L. y AEDV. All rights reserved.

Clinicopathological characteristics of primary gastric T-cell lymphoma.

PubMed

Kawamoto, Kenichiro; Nakamura, Shotaro; Iwashita, Akinori; Watanabe, Jiro; Oshiro, Yumi; Nakayama, Yoshifuku; Nimura, Satoshi; Kimura, Nobuhiro; Aoyagi, Kunihiko; Yao, Takashi; Kuramochi, Shigeru; Matsuyama, Atsuji; Kurihara, Kenji; Ohshima, Koichi; Takeshita, Morishige

2009-12-01

To investigate the clinicopathological characteristics of 20 primary gastric T-cell lymphoma (GTCL) cases without human T-lymphotropic virus type I infection in Japan, a non-endemic area for coeliac disease. Fifteen cases had no history of persistent diarrhoea or severe hypoproteinaemia. Histologically, 13 cases (65%) consisted of large cell lymphoma and seven (35%) were of medium-sized cells. Intraepithelial lymphoma cell invasion was found in three cases (15%). Two of 10 surgical cases (20%) showed intramucosal tumour cell spreading with enteropathy-like features. Helicobacter pylori CagA gene was detected in three of 10 cases (30%). The lymphoma cells of all 20 cases were positive for CD3 and/or TCRbetaF1 and negative for CD56. CD4- and CD8- lymphoma was found in 11 cases (55%), CD4+ lymphoma in seven (35%) and CD8+ lymphoma in two (10%). CD30+, CD5+ and CD25+ lymphomas were detected in nine (45%), 10 (50%) and 11 (55%) cases, respectively. Five-year survival of the 16 available cases was 54%. Early clinical stage and medium-sized cell lymphoma were significantly (P < 0.05) better prognostic factors. Patients with GTCL exhibit distinct clinicopathological findings and prognoses from those with enteropathy-associated T-cell lymphomas. GTCL may be mainly derived from lamina propria and parafollicular T cells.

Sandfly Lutzomyia longipalpis in a Cutaneous leishmaniasis focus in central Colombia.

PubMed

López, Y; Osorio, L; Alvarez, G; Rojas, J; Jiménez, F; Gómez, C; Ferro, C

1996-01-01

Lutzomyia longipalpis, 15 other species of the genus Lutzomyia, and one species of Brumptomyia were collected in an endemic focus of cutaneous leishmaniasis in a river canyon 450 m above sea-level, in Rio Claro, Antioquia, Colombia. The presence of Lu. longipalpis is associated with the destruction of the primary forest and the development of new farmland and rural settlement in this region. The composition of species identified a different habitat for Lu. longipalpis in Colombia. Lu. yuilli and Lu. longipalpis were predominant (68.26%) followed by Lu. trapidoi, Lu. hartmani, Lu. triramula, Lu. panamensis, Lu. gomezi.

Toll-like receptors 2, 4, and 9 expressions over the entire clinical and immunopathological spectrum of American cutaneous leishmaniasis due to Leishmania (V.) braziliensis and Leishmania (L.) amazonensis

PubMed Central

Campos, Marliane Batista; Lima, Luciana Vieira do Rêgo; de Lima, Ana Carolina Stocco; Vasconcelos dos Santos, Thiago; Ramos, Patrícia Karla Santos; Gomes, Claudia Maria de Castro

2018-01-01

Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L. (L.) amazonensis drives the infection in the opposite direction to ADCL (the lowest T-cell hypersensitivity pole). This study evaluated by immunohistochemistry the expression of Toll-like receptors (TLRs) 2, 4, and 9 and their relationships with CD4 and CD8 T-cells, and TNF-α, IL-10, and TGF-β cytokines in that disease spectrum. Biopsies of skin and mucosal lesions from 43 patients were examined: 6 cases of ADCL, 5 of BDCL, and 11 of LCL caused byL. (L.) amazonensis; as well as 10 cases of LCL, 4 of BDCL, and 6 of ML caused byL. (V.) braziliensis. CD4+ T-cells demonstrated their highest expression in ML and, in contrast, their lowest in ADCL. CD8+ T-cells also showed their lowest expression in ADCL as compared to the other forms of the disease. TNF-α+showed increased expression from ADCL to ML, while IL-10+and TGF-β+ showed increased expression in the opposite direction, from ML to ADCL. With regards to TLR2, 4, and 9 expressions, strong interactions of TLR2 and 4 with clinical forms associated with L. (V.) braziliensis were observed, while TLR9, in contrast, showed a strong interaction with clinical forms linked to L. (L.) amazonensis. These findings strongly suggest the ability of L. (V.) braziliensis and L. (L.) amazonensis to interact with those TLRs to promote a dichotomous T-cell immune response in ACL

Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma.

PubMed

Warren, Timothy A; Panizza, Benedict; Porceddu, Sandro V; Gandhi, Mitesh; Patel, Parag; Wood, Martin; Nagle, Christina M; Redmond, Michael

2016-06-01

Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT. © 2015 Wiley Periodicals, Inc. Head Neck 38: 824-831, 2016. © 2015 Wiley Periodicals, Inc.

Etiology of cutaneous vasculitis: utility of a systemic approach

PubMed

Chanussot-Deprez, Caroline; Vega-Memije, María Elisa; Flores-Suárez, Luis; Ríos-Romero, Celia; Cabiedes-Contreras, Javier; Reyes, Edgardo; Rangel-Gamboa, Lucia

2018-01-01

Cutaneous vasculities (CV) represents a diagnostic challenge, occurs as primary cutaneous disorder or as a manifestation of other entities. To search the cause of CV. Methods: Patients with CV were prospectively evaluated. In all patients, skin biopsies were drawn, and direct immunofluorescence was done in most of the patients. American College of Rheumatology (ACR) and Chapel Hill Consensus Conference Criteria (CHCC) were used for classification. 32 patients were studied. There was female predominance (71.8%). Children presented drug-associated CV or Schönlein-Henoch púrpura (SHP). Adults presented more frequently SHP, systemic lupus erythematosus or paraneoplastic vasculitis, other diagnosis as polyarteritis nodosa, microscopic polyangiitis, thrombotic vasculitis (post-puerperal), antiphospholipid syndrome, Churg-Strauss syndrome, and drug-associated CV were presented. Using the ACR and CHCC criteria, 50% of cases were classified. In our institution, during this work the etiologic diagnostic of CV increased more than twice. However, in the case of HSV or LA and SHP none of the proposed criteria had high specificity; other parameters were used to discern between both. Six patients remained as not classified. In our view, cryoglobulins and hepatitis serology do not seem useful unless patient’s history supports they need to be done. Unclassified patients were followed-up closely for 2 years. Copyright: © 2018 SecretarÍa de Salud

Discoveries and controversies in cutaneous mosaicism.

PubMed

Castori, Marco; Tadini, Gianluca

2016-06-01

Genetic mosaicism is thought to be a common phenomenon in inherited skin disorders. It is the leading molecular mechanism explaining cutaneous hamartomas and nevoid disorders, skin manifestations of most X-linked genodermatoses and specific forms of clinical variability and topographic distribution in autosomal skin disorders. The developmental (in utero) origin and timing dependence are two major attributes for the current definition of cutaneous mosaicism. Chromosomal mosaicism, lyonization in X-linked genodermatoses, and various types of mosaicism (i.e. type 1, type 2 and revertant mosaicism) in autosomal skin disorders are mechanisms well defined at the molecular level. All these concepts have been fully included in the current medical terminology in dermatology and genetics. Mitotic crossing-over, paradominant inheritance, monoallelic expression of autosomal traits and mosaicism in acquired skin disorders remain without a formal molecular proof and still represent sources of debate in the scientific community. This review summarizes current concepts, discoveries and controversies in the field of cutaneous mosaicism for practitioners and clinical researchers to enhance their understanding of such a underestimated clinical phenomenon and its biological basis.

Compound heterozygous TYK2 mutations underlie primary immunodeficiency with T-cell lymphopenia.

PubMed

Nemoto, Michiko; Hattori, Hiroyoshi; Maeda, Naoko; Akita, Nobuhiro; Muramatsu, Hideki; Moritani, Suzuko; Kawasaki, Tomonori; Maejima, Masami; Ode, Hirotaka; Hachiya, Atsuko; Sugiura, Wataru; Yokomaku, Yoshiyuki; Horibe, Keizo; Iwatani, Yasumasa

2018-05-03

Complete tyrosine kinase 2 (TYK2) deficiency has been previously described in patients with primary immunodeficiency diseases. The patients were infected with various pathogens, including mycobacteria and/or viruses, and one of the patients developed hyper-IgE syndrome. A detailed immunological investigation of these patients revealed impaired responses to type I IFN, IL-10, IL-12 and IL-23, which are associated with increased susceptibility to mycobacterial and/or viral infections. Herein, we report a recessive partial TYK2 deficiency in two siblings who presented with T-cell lymphopenia characterized by low naïve CD4 + T-cell counts and who developed Epstein-Barr virus (EBV)-associated B-cell lymphoma. Targeted exome-sequencing of the siblings' genomes demonstrated that both patients carried novel compound heterozygous mutations (c.209_212delGCTT/c.691C > T, p.Cys70Serfs*21/p.Arg231Trp) in the TYK2. The TYK2 protein levels were reduced by 35% in the T cells of the patient. Unlike the response under complete TYK2 deficiency, the patient's T cells responded normally to type I IFN, IL-6, IL-10 and IL-12, whereas the cells displayed an impaired response to IL-23. Furthermore, the level of STAT1 was low in the cells of the patient. These studies reveal a new clinical entity of a primary immunodeficiency with T-cell lymphopenia that is associated with compound heterozygous TYK2 mutations in the patients.

Dermatoscopic features of cutaneous non-facial non-acral lentiginous growth pattern melanomas

PubMed Central

Keir, Jeff

2014-01-01

Background: The dermatoscopic features of facial lentigo maligna (LM), facial lentigo maligna melanoma (LMM) and acral lentiginous melanoma (ALM) have been well described. This is the first description of the dermatoscopic appearance of a clinical series of cutaneous non-facial non-acral lentiginous growth pattern melanomas. Objective: To describe the dermatoscopic features of a series of cutaneous non-facial non-acral lentiginous growth pattern melanomas in an Australian skin cancer practice. Method: Single observer retrospective analysis of dermatoscopic images of a one-year series of cutaneous non-facial, non-acral melanomas reported as having a lentiginous growth pattern detected in an open access primary care skin cancer clinic in Australia. Lesions were scored for presence of classical criteria for facial LM; modified pattern analysis (“Chaos and Clues”) criteria; and the presence of two novel criteria: a lentigo-like pigment pattern lacking a lentigo-like border, and large polygons. Results: 20 melanomas occurring in 14 female and 6 male patients were included. Average patient age was 64 years (range: 44–83). Lesion distribution was: trunk 35%; upper limb 40%; and lower limb 25%. The incidences of criteria identified were: asymmetry of color or pattern (100%); lentigo-like pigment pattern lacking a lentigo-like border (90%); asymmetrically pigmented follicular openings (APFO’s) (70%); grey blue structures (70%); large polygons (45%); eccentric structureless area (15%); bright white lines (5%). 20% of the lesions had only the novel criteria and/or APFO’s. Limitations: Single observer, single center retrospective study. Conclusions: Cutaneous non-facial non-acral melanomas with a lentiginous growth pattern may have none or very few traditional criteria for the diagnosis of melanoma. Criteria that are logically expected in lesions with a lentiginous growth pattern (lentigo-like pigment pattern lacking a lentigo-like border, APFO’s) and the novel

Dermatoscopic features of cutaneous non-facial non-acral lentiginous growth pattern melanomas.

PubMed

Keir, Jeff

2014-01-01

The dermatoscopic features of facial lentigo maligna (LM), facial lentigo maligna melanoma (LMM) and acral lentiginous melanoma (ALM) have been well described. This is the first description of the dermatoscopic appearance of a clinical series of cutaneous non-facial non-acral lentiginous growth pattern melanomas. To describe the dermatoscopic features of a series of cutaneous non-facial non-acral lentiginous growth pattern melanomas in an Australian skin cancer practice. Single observer retrospective analysis of dermatoscopic images of a one-year series of cutaneous non-facial, non-acral melanomas reported as having a lentiginous growth pattern detected in an open access primary care skin cancer clinic in Australia. Lesions were scored for presence of classical criteria for facial LM; modified pattern analysis ("Chaos and Clues") criteria; and the presence of two novel criteria: a lentigo-like pigment pattern lacking a lentigo-like border, and large polygons. 20 melanomas occurring in 14 female and 6 male patients were included. Average patient age was 64 years (range: 44-83). Lesion distribution was: trunk 35%; upper limb 40%; and lower limb 25%. The incidences of criteria identified were: asymmetry of color or pattern (100%); lentigo-like pigment pattern lacking a lentigo-like border (90%); asymmetrically pigmented follicular openings (APFO's) (70%); grey blue structures (70%); large polygons (45%); eccentric structureless area (15%); bright white lines (5%). 20% of the lesions had only the novel criteria and/or APFO's. Single observer, single center retrospective study. Cutaneous non-facial non-acral melanomas with a lentiginous growth pattern may have none or very few traditional criteria for the diagnosis of melanoma. Criteria that are logically expected in lesions with a lentiginous growth pattern (lentigo-like pigment pattern lacking a lentigo-like border, APFO's) and the novel criterion of large polygons may be useful in increasing sensitivity and

Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation.

PubMed

Liu, Xiaohua; Green, Kathryn J; Ford, Zachary K; Queme, Luis F; Lu, Peilin; Ross, Jessica L; Lee, Frank B; Shank, Aaron T; Hudgins, Renita C; Jankowski, Michael P

2017-02-01

Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRG). However, specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. Growth hormone modulates homeostasis and tissue repair after injury, but how GH affects nociception in neonates is not known. To determine whether GH played a role in modulating sensory neuron function and hyperresponsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-DRG-spinal cord preparation. Results show that inflammation of the hairy hind paw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated through an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that after GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRG.

Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation

PubMed Central

Liu, Xiaohua; Green, Kathryn J.; Ford, Zachary K.; Queme, Luis F.; Lu, Peilin; Ross, Jessica L.; Lee, Frank B.; Shank, Aaron T.; Hudgins, Renita C.; Jankowski, Michael P.

2016-01-01

Cutaneous inflammation alters the function of primary afferents and gene expression in the affected dorsal root ganglia (DRGs). However specific mechanisms of injury-induced peripheral afferent sensitization and behavioral hypersensitivity during development are not fully understood. Recent studies in children suggest a potential role for growth hormone (GH) in pain modulation. GH modulates homeostasis and tissue repair after injury, but how GH effects nociception in neonates is not known. To determine if GH played a role in modulating sensory neuron function and hyper-responsiveness during skin inflammation in young mice, we examined behavioral hypersensitivity and the response properties of cutaneous afferents using an ex vivo hairy skin-saphenous nerve-dorsal root ganglion (DRG)-spinal cord preparation. Results show that inflammation of the hairy hindpaw skin initiated at either postnatal day 7 (P7) or P14 reduced GH levels specifically in the affected skin. Furthermore, pretreatment of inflamed mice with exogenous GH reversed mechanical and thermal hypersensitivity in addition to altering nociceptor function. These effects may be mediated via an upregulation of insulin-like growth factor 1 receptor (IGFr1) as GH modulated the transcriptional output of IGFr1 in DRG neurons in vitro and in vivo. Afferent-selective knockdown of IGFr1 during inflammation also prevented the observed injury-induced alterations in cutaneous afferents and behavioral hypersensitivity similar to that following GH pretreatment. These results suggest that GH can block inflammation-induced nociceptor sensitization during postnatal development leading to reduced pain-like behaviors, possibly by suppressing the upregulation of IGFr1 within DRGs. PMID:27898492

Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

PubMed

J Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

2018-06-01

Patients treated with intravesical bacillus Calmette-Guérin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side-effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry.

PubMed

Manarang, Joseph C; Otteson, Deborah C; McDermott, Alison M

2017-11-01

Antimicrobial peptides (AMPs) have been implicated in the pathogenesis of several cancers, although there is also evidence suggesting potential for novel, AMP-based antitumor therapies. Discerning potential roles of AMPs in tumor pathogenesis may provide valuable insight into the mechanisms of novel AMP-based antitumor therapy. mRNA expression of the AMPs α defensin (HNP-1); cathelicidin (LL-37); and β defensins (hBD-1, hBD-2, hBD-3, hBD-4) in human uveal and cutaneous melanoma cell lines, primary human uveal melanocytes, and primary human uveal melanoma cells was determined by reverse transcriptase polymerase chain reaction. An in vitro scratch assay and custom Matlab analysis were used to determine the AMP effects on melanoma cell migration. Last, the effect of specific AMPs on vasculogenic mimicry was determined by three-dimensional (3D) culture and light and fluorescence microscopy. Low-to-moderate AMP transcript levels were detected, and these varied across the cells tested. Overall, LL-37 expression was increased while hBD-4 was decreased in most melanoma cell lines, compared to primary cultured uveal melanocytes. There was no observable influence of HNP-1 and LL-37 on tumor cell migration. Additionally, aggressive cutaneous melanoma cells grown in 3D cultures exhibited vasculogenic mimicry, although AMP exposure did not alter this process. Collectively, our data show that although AMP mRNA expression is variable between uveal and cutaneous melanoma cells, these peptides have little influence on major characteristics that contribute to tumor aggressiveness and progression.

Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

PubMed Central

Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

2016-01-01

Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

Primary cutaneous melanoma of the scalp: Patterns of recurrence.

PubMed

Sparks, David S; Read, Tavis; Lonne, Michael; Barbour, Andrew P; Wagels, Michael; Bayley, Gerard J; Smithers, B Mark

2017-03-01

Patients with primary melanoma of the scalp have been reported to have worse disease-related outcomes compared with other anatomical regions. There are few studies in the literature specifically addressing recurrence patterns and treatment outcomes for primary scalp melanoma as a discrete anatomical sub-region. We sought to identify key features adversely influencing disease control and survival and to clarify the role of resection plane, margin, and method of reconstruction in the management of this disease process. A retrospective clinical study of medical records was performed evaluating all patients with primary melanoma of the scalp treated at two hospitals in southeast Queensland between 2004 and 2014. A total of 107 patients were eligible for analysis. There were 46 recurrences in 38 patients in the cohort accounting for a recurrence rate of 35.5%. The local recurrence rate was 15.9% with 12 in-transit metastases after diagnosis. Regional and distant recurrence rates were 12.1% and 15%, respectively. At a median follow up of 30.5 months, disease-free survival was 47% and overall survival was also 47%. On multi-variate analysis, the deeper resection plane (sub-galeal) had a lower disease-free survival rate compared with the supra-galeal resection plane (P = 0.032). Our results support the hypothesis that primary scalp melanoma represents a unique aggressive subcategory with high rates of in-transit disease and poor disease-related and survival outcomes. There is a need for robust prospective comparative studies to address the significance of resection plane in the management of patients with scalp melanoma. © 2016 Wiley Periodicals, Inc.

The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy

PubMed Central

Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

2017-01-01

Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

PubMed

Tzeng, Jann-Inn; Wang, Jieh-Neng; Wang, Jhi-Joung; Chen, Yu-Wen; Hung, Ching-Hsia

2016-05-04

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] μmol/kg) greater than dopamine (190 [181-203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Primary tumor sites in relation to ultraviolet radiation exposure and skin visibility correlate with survival in cutaneous melanoma.

PubMed

Gordon, Daniela; Hansson, Johan; Eloranta, Sandra; Gordon, Max; Gillgren, Peter; Smedby, Karin E

2017-10-01

The prognostic value of detailed anatomic site and ultraviolet radiation (UVR) exposure patterns has not been fully determined in cutaneous melanoma. Thus, we reviewed medical records for detailed site in a population-based retrospective Swedish patient cohort diagnosed with primary invasive melanoma 1976-2003 (n = 5,973). We followed the patients from date of diagnosis until death, emigration or December 31 st 2013, and evaluated melanoma-specific survival by subsite in a multivariable regression model adjusting for established prognostic factors. We found that melanoma on chronic UVR exposure sites (face, dorsum of hands; adjusted HR 0.6; CI 0.4-0.7) and moderately intermittent UVR sites (lateral arms, lower legs, dorsum of feet; HR 0.7; CI 0.6-0.8) were associated with a favorable prognosis compared with highly intermittent sites (chest, back, neck, shoulders and thighs). Further, melanoma on poorly visible skin sites upon self-examination (scalp, retroauricular area, back, posterior upper arms and thighs, buttocks, pubic area; HR 1.3; CI 1.1-1.5) had a worse prognosis than those on easily visible sites (face, chest, abdomen, anterior upper arms and thighs, lower arms and legs, dorsum of hands and feet, palms). In conclusion, highly intermittent UVR exposure sites and poor skin visibility presumably correlate with reduced melanoma survival, independent of established tumor characteristics. A limitation of the study was the lack of information on actual individual UVR exposure. © 2017 UICC.

Paraneoplastic cutaneous manifestations: concepts and updates*

PubMed Central

da Silva, Josenilson Antônio; Mesquita, Kleyton de Carvalho; Igreja, Ana Carolina de Souza Machado; Lucas, Isabella Cristina Rodrigues Naves; Freitas, Aline Ferreira; de Oliveira, Sandra Maximiano; Costa, Izelda Maria Carvalho; Campbell, Iphis Tenfuss

2013-01-01

The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis. In this review article, we discuss the paraneoplastic cutaneous manifestations strongly associated with neoplasms, which include acanthosis nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trélat sign and paraneoplastic pemphigus. We also review the clinical manifestations of each condition and include updated knowledge on disease pathogenesis. PMID:23538999

Drug Discovery Algorithm for Cutaneous Leishmaniasis

PubMed Central

Grogl, Max; Hickman, Mark; Ellis, William; Hudson, Thomas; Lazo, John S.; Sharlow, Elizabeth R.; Johnson, Jacob; Berman, Jonathan; Sciotti, Richard J.

2013-01-01

Cutaneous leishmaniasis is clinically widespread but lacks treatments that are effective and well tolerated. Because all present drugs have been grandfathered into clinical use, there are no examples of a pre-clinical product evaluation scheme that lead to new candidates for formal development. To provide oral agents for development targeting cutaneous leishmaniasis, we have implemented a discovery scheme that incorporates in vitro and in vivo testing of efficacy, toxicity, and pharmacokinetics/metabolism. Particular emphasis is placed on in vivo testing, progression from higher-throughput models to those with most clinical relevance, and efficient use of resources. PMID:23390221

Cutaneous cytomegalovirus infection in a patient with acquired immunodeficiency syndrome.

PubMed

AbdullGaffar, Badr; Raman, Lakshmiah G; Al Muala, Alia

2008-09-01

Abstract Cytomegalovirus (CMV) infection in immunocompromised patients is a common opportunistic systemic infection which can lead to death, and usually presents with visceral manifestations, especially of the lung, brain, eye, and gastrointestinal tract. Cutaneous CMV infection is, however, relatively rare in immunocompromised patients. Cutaneous CMV infection can have variable clinical and histologic manifestations, and thus can be easily missed. We report a case of cutaneous CMV infection in a patient with acquired immunodeficiency syndrome, presenting as a generalized, pruritic, erythematous, maculopapular eruption.

Source and risk factors of a cutaneous anthrax outbreak, Jiangsu, Eastern China, 2012.

PubMed

Hu, J L; Cui, L L; Bao, C J; Tan, Z M; Rutherford, S; Ying, L; Zhang, M L; Zhu, F C

2016-09-01

Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas.

Propylthiouracil-induced cutaneous vasculitis. Case presentation and review of the literature.

PubMed

Vasily, D B; Tyler, W B

1980-02-01

A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy.

Nitric oxide-mediated cutaneous microvascular function is impaired in polycystic ovary sydrome but can be improved by exercise training.

PubMed

Sprung, V S; Cuthbertson, D J; Pugh, C J A; Daousi, C; Atkinson, G; Aziz, N F; Kemp, G J; Green, D J; Cable, N T; Jones, H

2013-03-15

Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m(-2)) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m(-2)). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m(-2)) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l-N(G)-monomethyl-l-arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO-mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg(-1) min(-1) (95% confidence interval, 0.9, 9.2; P = 0.03) and NO-mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training.

Nitric oxide-mediated cutaneous microvascular function is impaired in polycystic ovary sydrome but can be improved by exercise training

PubMed Central

Sprung, V S; Cuthbertson, D J; Pugh, C J A; Daousi, C; Atkinson, G; Aziz, N F; Kemp, G J; Green, D J; Cable, N T; Jones, H

2013-01-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m−2) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m−2). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m−2) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l-NG-monomethyl-l-arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO-mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg−1 min−1 (95% confidence interval, 0.9, 9.2; P = 0.03) and NO-mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training. PMID:23318877

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

PubMed

Remenschneider, Aaron K; Dilger, Amanda E; Wang, Yingbing; Palmer, Edwin L; Scott, James A; Emerick, Kevin S

2015-04-01

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Bronchopleural cutaneous fistula due to Eikenella corrodens.

PubMed

Wong, Kin-Sun; Huang, Yhu-Chering

2005-01-01

The aim of this paper is to review the subject and to report on and discuss a case of bronchopleural cutaneous fistula due to Eikenella corrodens. A 16-year-old girl was brought to our hospital with fever and blood-tinged sputum 2 weeks prior to her admission. She suffered from neurologic sequelae of herpetic encephalitis and had been bed-ridden since 5 years of age. A longitudinal paraspinal soft mass had been noted in the previous week by her mother. She had been given oral feeding despite frequent choking for the past few years. On palpation, the mass can be squeezed to follow the least resistance of subcutaneous space longitudinally extending to the lower thoracic region. Chest computed tomography scan revealed right lower lobe necrotizing pneumonitis and a pleuro-cutaneous fistula leading to the subcutaneous air locules. A protracted course of antibiotics was prescribed and subcutaneous air trapping decreased in size over 8 weeks. Eikenella corrodens has increasingly been implicated as a potential causative pathogen in pleuropulmonary infections. Pleuro-cutaneous fistula and abscess formation complicating empyema and necrotizing pneumonitis due to E. corrodens infection have not been reported. A bulging thoracic subcutaneous lesion waxes and wanes with respiration suggest the possibility of a pleruo-cutaneous fistula. Treatment of Eikenella empyema using antibiotics without surgical decortication requires a prolonged course of antibiotic therapy.

[Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi].

PubMed

Nenoff, P; Reinel, D; Krüger, C; Grob, H; Mugisha, P; Süß, A; Mayser, P

2015-07-01

Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic

Th17 cytokine differentiation and loss of plasticity after SOCS1 inactivation in a cutaneous T-cell lymphoma.

PubMed

Ehrentraut, Stefan; Schneider, Björn; Nagel, Stefan; Pommerenke, Claudia; Quentmeier, Hilmar; Geffers, Robert; Feist, Maren; Kaufmann, Maren; Meyer, Corinna; Kadin, Marshall E; Drexler, Hans G; MacLeod, Roderick A F

2016-06-07

We propose that deregulated T-helper-cell (Th) signaling underlies evolving Th17 cytokine expression seen during progression of cutaneous T-cell lymphoma (CTCL). Accordingly, we developed a lymphoma progression model comprising cell lines established at indolent (MAC-1) and aggressive (MAC-2A) CTCL stages. We discovered activating JAK3 (V722I) mutations present at indolent disease, reinforced in aggressive disease by novel compound heterozygous SOCS1 (G78R/D105N) JAK-binding domain inactivating mutations. Though isogenic, indolent and aggressive-stage cell lines had diverged phenotypically, the latter expressing multiple Th17 related cytokines, the former a narrower profile. Importantly, indolent stage cells remained poised for Th17 cytokine expression, readily inducible by treatment with IL-2 - a cytokine which mitigates Th17 differentiation in mice. In indolent stage cells JAK3 expression was boosted by IL-2 treatment. Th17 conversion of MAC-1 cells by IL-2 was blocked by pharmacological inhibition of JAK3 or STAT5, implicating IL2RG - JAK3 - STAT5 signaling in plasticity responses. Like IL-2 treatment, SOCS1 knockdown drove indolent stage cells to mimic key aggressive stage properties, notably IL17F upregulation. Co-immunoprecipitation experiments showed that SOCS1 mutations abolished JAK3 binding, revealing a key role for SOCS1 in regulating JAK3/STAT5 signaling. Collectively, our results show how JAK/STAT pathway mutations contribute to disease progression in CTCL cells by potentiating inflammatory cytokine signaling, widening the potential therapeutic target range for this intractable entity. MAC-1/2A cells also provide a candidate human Th17 laboratory model for identifying potentally actionable CTCL markers or targets and testing their druggability in vitro.

Delayed Cutaneous Hypersensitivity Reactions to Antibiotics: Management with Desensitization.

PubMed

McNulty, Caitlin M G; Park, Miguel A

2017-11-01

Successful desensitization to mild to moderate delayed cutaneous adverse reaction to antibiotics has been described in a limited number of antibiotics and found to be safe. However, there are ample opportunities to standardize protocols for delayed cutaneous adverse reactions to antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with primary closed angle glaucoma

PubMed Central

Michael, Shazia; Qamar, Raheel; Akhtar, Farah; Khan, Wajid Ali

2008-01-01

Purpose To determine whether or not there is an association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with disease in cohorts of primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG) from Pakistan. Methods This was a prospective study consisting of 150 patients (90 POAG and 60 PCAG) and 70 control subjects. Genomic DNA was extracted from leukocytes of the peripheral blood. MTHFR C677T polymorphism analysis was performed by the polymerase chain reaction-restriction fragment length polymorphism (RFLP) technique. Results The prevalence of the MTHFR C/T genotype was 22.2% in POAG, 13.3% in PACG, and 18.6% in controls whereas the MTHFR T/T genotype was present solely in the PACG group (6.9%). The difference regarding the T/T genotype between PACG and controls was statistically significant (p<0.01). Conclusions The MTHFR C677T polymorphism was found to be associated with PCAG but not POAG in patients of Pakistani origin. PMID:18385801

An unusual presentation of listeriosis: anemia and cutaneous manifestations.

PubMed

Teo, Hooi Khee; Yap, Jonathan; Fong, Yuke Tien

2014-03-01

Listeria monocytogenes is an intracellular pathogen causing food-borne disease. It usually affects the young as well as immunocompromised individuals and is associated with high mortality rates. Cutaneous manifestations have rarely been described. We describe an interesting case of a traveller from the tropics presenting with cutaneous listeriosis and anemia.

[Hypochondria sine materia as a psychosomatic problem: a model of hypochondriac disorders realized in the cutaneous sphere].

PubMed

Smulevich, A B; Dorozhenok, I Iu; Romanov, D V; L'vov, A N

2012-01-01

Hypochondria sine materia is a disorder with physical complains corresponding to no any somatic diagnosis. Hypochondria sine materia is a more complicated psychopathological condition compared to hypochondria cum materia. Hypochondria sine materia could be diagnosed not only in psychiatry, but mainly in general medicine. It is especially prevalent in dermatology. As a result of analysis of hypochondriac disorders involving cutaneous sphere in patients without dermatological diseases, a binary model of psychodermatological syndromes presenting with hypochondria sine materia in dermatology was developed. The binary structure of the psychodermatological syndromes includes secondary psychiatric symptoms based on primary coenesthesiopathic phenomena. The heterogeneous psychodermatological syndromes (cutaneous organ neurosis, impulsive excoriations syndrome, circumscripta hypochondria, coenesthesiopathic paranoia) could be arranged in a continuum of consecutively worsening conditions from neurotic to psychotic severity register. The syndromes differ in clinical and social prognosis requiring different approach to diagnosis and treatment.

Correction to: Molecular identification of Leishmania spp. isolates causes cutaneous leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic.

PubMed

Gurses, Gulcan; Ozaslan, Mehmet; Yıldız Zeyrek, Fadile; Kılıç, Ibrahim H; Yentür Doni, Nebiye; Karagoz, I Didem; Uluca, Nermin

2018-05-01

In published article (Molecular Identification of Leishmania spp. Isolates Causes Cutaneous Leishmaniasis (CL) in Sanliurfa Province, Turkey, Where CL is Highly Endemic) Table 1 titled "The pH values of yogurts collected from villages in Turkey" doesn't belong to this article.

Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

PubMed

Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

2017-05-01

Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

Palatogenesis and cutaneous repair: a two headed coin

PubMed Central

Biggs, Leah C.; Goudy, Steven L.; Dunnwald, Martine

2014-01-01

The reparative mechanism that operates following post-natal cutaneous injury is a fundamental survival function that requires a well-orchestrated series of molecular and cellular events. At the end, the body will have closed the hole using processes like cellular proliferation, migration, differentiation and fusion. These processes are similar to those occurring during embryogenesis and tissue morphogenesis. Palatogenesis, the formation of the palate from two independent palatal shelves growing towards each other and fusing, intuitively, shares many similarities with the closure of a cutaneous wound from the two migrating epithelial fronts. In this review, we summarize the current information on cutaneous development, wound healing, palatogenesis and orofacial clefting and propose that orofacial clefting and wound healing are conserved processes that share common pathways and gene regulatory networks. PMID:25370680

Prophylactic immunization against experimental leishmaniasis. III. Protection against fatal Leishmania tropica infection induced by irradiated promastigotes involves Lyt-1/sup +/2/sup -/ T cells that do not mediate cutaneous DTH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liew, F.Y.; Howard, J.G.; Hale, C.

1984-01-01

Protective immunity against fatal L. tropica infection in genetically vulnerable BALB/c mice can be induced by prophylactic immunization with irradiated promastigotes even when heat-killed. Such immunity is adoptively transferable transiently into intact or durably into sub-lethally irradiated (200 or 550 rad) syngeneic recipients by splenic T but not B cells. The effector T cells are of the Lyt-1/sup +/2/sup -/ phenotype, devoid of demonstrable cytotoxic activity. The immune splenic T cell population expresses specific helper activity for antibody synthesis. A causal role for helper T cells in this capacity, however, seems unlikely, because it was shown that antibody does notmore » determine the protective immunity against L. tropica. The immunized donors show no detectable cutaneous DTH or its early memory recall in response to live or killed promastigotes or a soluble L. tropica antigen preparation. Spleen, lymph node, and peritoneal exudate cells from protectively immunized donors similarly fail to transfer DTH locally or systemically. These cells also lack demonstrable suppressive activity against the expression or induction of DTH to L. tropica. Thus, protection against L. tropica induced by prophylactic i.v. immunization with irradiated promastigotes appears to be conferred by Lyt-1/sup +/2/sup -/ T cells that are distinguishable from T cells mediating either both DTH and T help, or cytotoxicity.« less

Inhibition of TGF-β and NOTCH Signaling by Cutaneous Papillomaviruses

PubMed Central

Meyers, Jordan M.; Grace, Miranda; Uberoi, Aayushi; Lambert, Paul F.; Munger, Karl

2018-01-01

Infections with cutaneous papillomaviruses have been linked to cutaneous squamous cell carcinomas that arise in patients who suffer from a rare genetic disorder, epidermodysplasia verruciformis, or those who have experienced long-term, systemic immunosuppression following organ transplantation. The E6 proteins of the prototypical cutaneous human papillomavirus (HPV) 5 and HPV8 inhibit TGF-β and NOTCH signaling. The Mus musculus papillomavirus 1, MmuPV1, infects laboratory mouse strains and causes cutaneous skin warts that can progress to squamous cell carcinomas. MmuPV1 E6 shares biological and biochemical activities with HPV8 E6 including the ability to inhibit TGF-β and NOTCH signaling by binding the SMAD2/SMAD3 and MAML1 transcription factors, respectively. Inhibition of TGF-β and NOTCH signaling is linked to delayed differentiation and sustained proliferation of differentiating keratinocytes. Furthermore, the ability of MmuPV1 E6 to bind MAML1 is necessary for wart and cancer formation in experimentally infected mice. Hence, experimental MmuPV1 infection in mice will be a robust and valuable experimental system to dissect key aspects of cutaneous HPV infection, pathogenesis, and carcinogenesis. PMID:29568286

In vitro characterization of cutaneous immunotoxicity of immortalized human keratinocytes (HaCaT) exposed to reactive and disperse textile dyes.

PubMed

Leme, Daniela Morais; Sehr, Andrea; Grummt, Tamara; Gonçalves, Jenifer Pendiuk; Jacomasso, Thiago; Winnischofer, Sheila Maria Brochado; Potrich, Francine Bittencourt; Oliveira, Carolina Camargo de; Trindade, Edvaldo da Silva; de Oliveira, Danielle Palma

2018-05-01

Several synthetic dyes are used by textile industry for supplying the market of colored clothes. However, these chemicals have been associated with a variety of adverse human health effects, including textile dermatitis. Thus, there is a growing concern to identify textile dyes potentially as skin immunotoxicants. The aim of this in vitro study was to characterize the immunotoxic potential of reactive (Reactive Green 19 [RG19], Reactive Blue 2 [RB2], Reactive Black 5 [RB5]) and disperse (Disperse Red 1 [DR1]) textile dyes using a dermal cell line. For this purpose, a cell-based approach was conducted with immortalized human keratinocytes (KC) (HaCaT) using selected biomarkers of cutaneous inflammation including modulation of matrix metalloproteinases (MMP), oxidative stress such as reactive oxygen species (ROS) generation, and inflammatory cytokine profile. DR1 was the only dye able to trigger an immune response such as release of IL-12 cytokine, a potent co-stimulator of T helper 1 cell, which may be considered as a skin immunotoxicant. The reactive dyes including RB5 that were previously reported as skin sensitizers failed to induce inflammatory reactions under the conditions tested. The reactive dyes studied may pose a risk to human KC by induction of effects related to modulation of MMP-2 (RB5) and -9 (RB5 and RB2) and generation of ROS (RG19 and RB2). Thus, all these dyes need to be used with caution to avoid undesirable effects to consumers who may be exposed dermally.

Serum paraoxonase activity and oxidative stress levels in patients with cutaneous anthrax.

PubMed

Karadas, S; Aslan, M; Ceylan, M R; Sunnetcioglu, M; Bozan, N; Kara, H; Demir, H

2017-07-01

Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) levels in patients with cutaneous anthrax. Fifteen patients with cutaneous anthrax and 15 healthy controls were enrolled in this study. The serum MDA levels, SOD levels, paraoxonase, arylesterase, and catalase activities were measured using a spectrophotometer. The serum SOD levels, paraoxonase, arylesterase, and catalase activities were significantly lower in patients with cutaneous anthrax than in controls (for all, p < 0.001), whereas MDA levels were significantly higher ( p < 0.001). No significant correlation was found between serum paraoxonase activity, arylesterase activity, SOD levels, and MDA levels (all, p > 0.05) in patients with cutaneous anthrax. The current study was the first to show decreased antioxidant levels and increased oxidant levels in patients with cutaneous anthrax. Therefore, decreased PON1 activity may play a role in the pathogenesis of cutaneous anthrax.

Cutaneous chancroid in a visitor from Vanuatu.

PubMed

McBride, William J H; Hannah, Rory C S; Le Cornec, Genevera M; Bletchly, Cheryl

2008-05-01

A 23-year-old woman from Vanuatu presented to an Australian hospital with a 3-week history of a non-healing ulcer on the lower leg. A swab was submitted for a multiplex polymerase chain reaction designed to investigate genital ulcerative conditions. Haemophilus ducreyi was detected and the gene product was subsequently sequenced, confirming the diagnosis of cutaneous chancroid. The lesion responded to intramuscular benzathine penicillin. This report adds further evidence that cutaneous chancroid should be considered in the evaluation of skin ulcers in the south Pacific.

Primary pulmonary NK/T-cell lymphoma: A case report and literature review.

PubMed

Qiu, Yajuan; Hou, Junna; Hao, Dexun; Zhang, Dandan

2018-06-01

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is an aggressive disease with poor prognosis. The lung is a relatively rare site of involvement. The current study presents a case of primary pulmonary ENKTL with fever and dyspnea, mimicking pneumonia and initially treated with empirical antibiotics. The patient demonstrated rapid deterioration and died shortly following diagnosis. To the best of our knowledge, large-scale investigations referring to primary pulmonary ENKTL are not available. As a result, the exact incidence and clinical features of primary pulmonary ENKTL are unknown. In the current report, a literature review is presented to discuss the clinical characteristics, diagnosis, treatment, and prognosis factors of this malignant disease.

Deceptively bland cutaneous angiosarcoma on the nose mimicking hemangioma-A clinicopathologic and immunohistochemical analysis.

PubMed

Mitteldorf, Christina; Llamas-Velasco, Mar; Schulze, Hans-Joachim; Thoms, Kai-Martin; Mentzel, Thomas; Tronnier, Michael; Kutzner, Heinz

2018-05-15

We investigated 2 cases of deceptively bland cutaneous angiosarcoma (AS), which showed a uniform clinical presentation with a rapidly growing tumor on the nose. It remains unclear whether this was a primary cutaneous manifestation or a metastasis. Both tumors initially presented a high histologic overlap with a benign vascular tumor. The diagnosis was primarily based on the rapidly progressing clinical course and on the results of the staging procedures. Immunohistochemical stains were performed for cytokeratin (AE1/AE3 and MNF116), CD31, ERG, CD34 (HPCA1/my10), D2-40/podoplanin, LYVE-1, Ki67, PHH3, αSMA (1A4), MYC, FOS-B, CAMTA-1, TFE-3, WT1, nestin, VEGFR-2(KDR), VEGFR-3(FLT4), HHV8. MYC amplification was also investigated by fluorescence in situ hybridization. The tumor cells were negative for MYC and revealed no D2-40/podoplanin expression. SMA-positive pericytes formed rims around the vessel. The proliferative activity (Ki-67) was elevated, in one case only in a later stage. Cutaneous ASs can be rather bland and may easily be mistaken for benign vascular tumors. Both cases presented a uniform clinical picture, which implied a malignant vascular tumor. In contrast, the cytomorphology of the endothelial cells and the immunohistochemical profile were not suspicious. We worked out subtle histological criteria, which should allow an early detection of such tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical Manifestations and Distribution of Cutaneous Leishmaniasis in Pakistan

PubMed Central

Afghan, Abaseen Khan; Kassi, Masoom; Kasi, Pashtoon Murtaza; Ayub, Adil; Kakar, Niamatullah; Marri, Shah Muhammad

2011-01-01

Cutaneous leishmaniasis (CL) is a rising epidemic in Pakistan. It is a major public health problem in the country especially alongside regions bordering the neighboring Afghanistan and cities that have had the maximum influx of refugees. The purpose of our paper is to highlight the diverse clinical manifestations of the disease seen along with the geographic areas affected, where the hosts are particularly susceptible. This would also be helpful in presenting the broad spectrum of the disease for training of health care workers and help in surveillance of CL in the region. The increased clinical diversity and the spectrum of phenotypic manifestations noted underscore the fact that the diagnosis of CL should be not only considered when dealing with common skin lesions, but also highly suspected by dermatologists and even primary care physicians even when encountering uncommon pathologies. Hence, we would strongly advocate that since most of these patients present to local health care centers and hospitals, primary care practitioners and even lady health workers (LHWs) should be trained in identification of at least the common presentations of CL. PMID:22174721

Epicutaneous challenge of orally immunized mice redirects antigen-specific gut-homing T cells to the skin.

PubMed

Oyoshi, Michiko K; Elkhal, Abdallah; Scott, Jordan E; Wurbel, Marc-Andre; Hornick, Jason L; Campbell, James J; Geha, Raif S

2011-06-01

Patients with atopic dermatitis (AD) often suffer from food allergy and develop flares upon skin contact with food allergens. However, it is unclear whether T cells sensitized to allergens in the gut promote this skin inflammation. To address this question, we orally immunized WT mice and mice lacking the skin-homing chemokine receptor Ccr4 (Ccr4-/- mice) with OVA and then challenged them epicutaneously with antigen. Allergic skin inflammation developed in the WT mice but not in the mutants and was characterized by epidermal thickening, dermal infiltration by eosinophils and CD4+ T cells, and upregulation of Th2 cytokines. T cells purified from mesenteric lymph nodes (MLNs) of orally immunized WT mice transferred allergic skin inflammation to naive recipients cutaneously challenged with antigen, but this effect was lost in T cells purified from Ccr4-/- mice. In addition, the ability of adoptively transferred OVA-activated T cells to home to the skin following cutaneous OVA challenge was ablated in mice that lacked lymph nodes. These results indicate that cutaneous exposure to food antigens can reprogram gut-homing effector T cells in LNs to express skin-homing receptors, eliciting skin lesions upon food allergen contact in orally sensitized AD patients.

Cutaneous metastases of a mammary carcinoma in a llama.

PubMed Central

Leichner, T L; Turner, O; Mason, G L; Barrington, G M

2001-01-01

An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

Guidelines for the Diagnosis and Treatment of Cutaneous Mastocytosis in Children

PubMed Central

Castells, Mariana; Metcalfe, Dean D.; Escribano, Luis

2012-01-01

Mastocytosis is a disease with many variants, all of which are characterized by a pathologic increase in mast cells in cutaneous tissue and extracutaneous organs such as the bone marrow, liver, spleen and lymph nodes. The disease presents in two primary age-related patterns: pediatric-onset mastocytosis and adult-onset mastocytosis, which may differ in their clinical manifestations and disease course. Pediatric-onset mastocytosis commonly is diagnosed prior to 2 years of age, and usually consists of cutaneous disease, with urticaria pigmentosa (UP) the most common pattern. The course of pediatric-onset mastocytosis is variable. This is in contrast to adult onset disease which generally presents with systemic findings and increases in extent and severity over time. Because pediatric forms of mastocytosis often differ in presentation and prognosis from adult variants, it is most important to understand pediatric mastocytosis and not rely on adult approaches as a guide on how to identify and manage disease. This is especially important in selecting therapy where antiproliferative agents have a very different set of concerns when used to treat adult mastocytosis compared to pediatric mastocytosis, especially in terms of long-term toxicity. This review is directed at providing age-specific information surrounding the care of the child with mastocytosis. PMID:21668033

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

PubMed

Malysz, Jozef; Talamo, Giampaolo; Zhu, Junjia; Clarke, Loren E; Bayerl, Michael G; Ali, Liaqat; Helm, Klaus F; Chung, Catherine G

2016-05-01

Disease-specific skin lesions are rare in patients with multiple myeloma (MM). We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. We identified 13 patients with cutaneous lesions of MM. Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. The study group was relatively small. Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cost consequences of point-of-care troponin T testing in a Swedish primary health care setting

PubMed Central

Andersson, Agneta; Janzon, Magnus; Karlsson, Jan-Erik; Levin, Lars-Åke

2014-01-01

Abstract Objective. To evaluate the safety and cost-effectiveness of point-of-care troponin T testing (POCT-TnT) for the management of patients with chest pain in primary care. Design. Prospective observational study with follow-up. Setting. Three primary health care (PHC) centres using POCT-TnT and four PHC centres not using POCT-TnT in south-east Sweden. Patients. All patients ≥ 35 years of age, contacting one of the PHC centres for chest pain, dyspnoea on exertion, unexplained weakness and/or fatigue, with no other probable cause than cardiac, were included. Symptoms must have commenced or worsened during the previous seven days. Main outcome measures. Emergency referral rates, diagnoses of acute myocardial infarction (AMI) or unstable angina (UA), and costs were collected for 30 days after the patient sought care at the PHC centre. Results. A total of 196 patients with chest pain were included: 128 in PHC centres with POCT-TnT and 68 in PHC centres without POCT-TnT. Fewer patients from the PHC centres with POCT-TnT (n = 32, 25%) were emergently referred to hospital than from centres without POCT-TnT (n = 29, 43%; p = 0.011). Eight patients (6.2%) from PHC centres with POCT-TnT were diagnosed with AMI or UA compared with six patients (8.8%) from centres without POCT-TnT (p = 0.565). Two patients with AMI or UA were classified as missed cases from PHC centres with POCT-TnT and there were no missed cases from PHC centres without POCT-TnT. SKr290 000 was saved per missed case of AMI or UA. Conclusion. The use of POCT-TnT in primary care may be cost saving but at the expense of missed cases. PMID:25434410

An Innovative Field-Applicable Molecular Test to Diagnose Cutaneous Leishmania Viannia spp. Infections

PubMed Central

Saldarriaga, Omar A.; Castellanos-Gonzalez, Alejandro; Porrozzi, Renato; Baldeviano, Gerald C.; Lescano, Andrés G.; de Los Santos, Maxy B.; Fernandez, Olga L.; Saravia, Nancy G.; Costa, Erika; Melby, Peter C.; Travi, Bruno L.

2016-01-01

Cutaneous and mucosal leishmaniasis is widely distributed in Central and South America. Leishmania of the Viannia subgenus are the most frequent species infecting humans. L. (V.) braziliensis, L. (V.) panamensis are also responsible for metastatic mucosal leishmaniasis. Conventional or real time PCR is a more sensitive diagnostic test than microscopy, but the cost and requirement for infrastructure and trained personnel makes it impractical in most endemic regions. Primary health systems need a sensitive and specific point of care (POC) diagnostic tool. We developed a novel POC molecular diagnostic test for cutaneous leishmaniasis caused by Leishmania (Viannia) spp. Parasite DNA was amplified using isothermal Recombinase Polymerase Amplification (RPA) with primers and probes that targeted the kinetoplast DNA. The amplification product was detected by naked eye with a lateral flow (LF) immunochromatographic strip. The RPA-LF had an analytical sensitivity equivalent to 0.1 parasites per reaction. The test amplified the principal L. Viannia species from multiple countries: L. (V.) braziliensis (n = 33), L. (V.) guyanensis (n = 17), L. (V.) panamensis (n = 9). The less common L. (V.) lainsoni, L. (V.) shawi, and L. (V.) naiffi were also amplified. No amplification was observed in parasites of the L. (Leishmania) subgenus. In a small number of clinical samples (n = 13) we found 100% agreement between PCR and RPA-LF. The high analytical sensitivity and clinical validation indicate the test could improve the efficiency of diagnosis, especially in chronic lesions with submicroscopic parasite burdens. Field implementation of the RPA-LF test could contribute to management and control of cutaneous and mucosal leishmaniasis. PMID:27115155

Subcutaneous L-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats.

PubMed

Hung, Ching-Hsia; Chiu, Chong-Chi; Liu, Kuo-Sheng; Chen, Yu-Wen; Wang, Jhi-Joung

2015-10-15

The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. We showed that both L-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88-5.38] μmol)>L-tyrosine (39.1 [36.5-41.8] μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by L-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with L-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone. Copyright © 2015 Elsevier B.V. All rights reserved.

Prolonged (9 h) poikilocapnic hypoxia (12% O2) augments cutaneous thermal hyperaemia in healthy humans.

PubMed

Lawley, Justin S; Oliver, Samuel J; Mullins, Paul G; Macdonald, Jamie H; Moore, Jonathan P

2014-06-01

The primary aim of this study was to investigate the effect of systemic poikilocapnic hypoxia on forearm cutaneous thermal hyperaemia. A secondary aim was to examine the relationship between the individual susceptibility to oxygen desaturation and cutaneous vasodilator capacity. Twelve healthy participants (seven male) were exposed to 9 h of normoxia and 12% poikilocapnic hypoxia in a temperature- and humidity-controlled environmental chamber. Skin blood flow was assessed at the ventral forearm using laser Doppler flowmetry combined with rapid local heating. After 6 min at baseline (skin temperature clamped at 33°C), local skin temperature was elevated at a rate of 0.5°C every 5 s up to 42°C to elicit a sensory axon response and then held constant for 30 min to cause a plateau. Skin blood flow was calculated as cutaneous vascular conductance [CVC; in perfusion units/mean arterial blood pressure (APU mmHg(-1))] and expressed in raw format and relative to heating at 44°C in normoxia (%CVC44). During hypoxaemia, vasodilatation was greater during the initial peak (raw, Δ0.35 APU mmHg(-1), P = 0.09; %CVC44, Δ18%, P = 0.05) and the plateau phase (raw, Δ0.55 APU mmHg(-1), P = 0.03; %CVC44, Δ26%, P = 0.02). The rate of rise in cutaneous blood flow during the initial peak was significantly greater during poikilocapnic hypoxia (P < 0.01). We observed a negative relationship between oxygen saturation in poikilocapnic hypoxia and the change in baseline (P = 0.06), initial peak (P = 0.01) and plateau phase of thermal hyperaemia (P = 0.01). Prolonged poikilocapnic hypoxia causes robust increases in CVC during both phases of thermal hyperaemia that are dependent on the oxygen saturation of the individual. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

PubMed

Ross, Kate; Cherpelis, Basil; Lien, Mary; Fenske, Neil

2013-12-01

Topical photodynamic therapy (PDT) is an option for the treatment of cutaneous malignancy. To present an update and expansion on a previous review of the use of PDT in the current literature in the treatment of actinic keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC), squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL), malignant melanoma, and its use in chemoprevention. Extensive PubMed search January 2013. We find sufficient evidence to recommend the use of PDT in certain patients in the treatment of AK, Bowen's disease, sBCC, and nBCC. It is especially useful in those with contraindications to surgery, widespread areas of involvement, and large lesions. Not only can it be considered superior to other therapies as far as recovery time, tolerance, and cosmetic outcomes, but it also should be considered, when indicated, as first-line treatment in the above conditions. Investigations continue for the use of PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

The cutaneous bacterium Janthinobacterium lividum inhibits the growth of Trichophyton rubrum in vitro.

PubMed

Ramsey, Jeremy P; Mercurio, Albert; Holland, Jessica A; Harris, Reid N; Minbiole, Kevin P C

2015-02-01

Tinea pedis (athlete's foot) is a fungal infection that is both widespread and challenging to treat. Standard treatments consist of topical and systemic therapies of antifungal agents, such as miconazole, itraconazole, and terbinafine. The extended nature of topical therapy and the toxicity of long-term systemic therapy limit the utility of current treatments. An alternate approach relies on an understanding of bacterial-fungal interactions. Specifically, a probiotic antifungal bacterium such as Janthinobacterium lividum can counter infection; Janthinobacterium is a major constituent of the human skin microbiota. Janthinobacterium lividum has been shown to ameliorate the effects of the cutaneous fungal disease chytridiomycosis in a vertebrate species (Rana muscosa). Dual-culture plate challenge assays were performed using J. lividum and Trichophyton rubrum, the leading cause of athlete's foot. In all cases, T. rubrum colonies grew significantly smaller when co-cultured with J. lividum. These in vitro results suggest that J. lividum merits further investigation as a human cutaneous probiotic. © 2013 The International Society of Dermatology.

Cutaneous sarcoidosis in Asians: a report of 25 patients from Singapore.

PubMed

Chong, W-S; Tan, H-H; Tan, S-H

2005-03-01

Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin involving multiple organ systems. There has been no report so far to describe the epidemiological pattern of cutaneous involvement in sarcoidosis in South-East Asia with diverse ethnic groups. A retrospective study examining the clinicopathological features of all patients diagnosed with sarcoidosis at a tertiary dermatology centre in Singapore from 1980 to 2003 was conducted. Cutaneous sarcoidosis was diagnosed in 25 patients: 13 were Indian, 11 were Chinese and one was Eurasian. Cutaneous manifestations included papules, nodules, plaques and scarring alopecia. Extracutaneous involvement of lymph nodes (four patients), lungs (eight patients) and eyes (two patients) was seen. Eight patients had abnormal chest radiographic findings. Histopathological examination of skin lesions revealed noncaseating, epithelioid granulomatous infiltration in the dermis without evidence of mycobacterial infection, deep fungal infection or polarizable birefringent material. Treatment modalities included corticosteroids, hydroxychloroquine, isotretinoin, methotrexate and surgical excision. Five patients had complete resolution of the cutaneous lesions. Cutaneous sarcoidosis is rare in Asia and indeed in Singapore. Extracutaneous involvement is not uncommon and a thorough clinical evaluation should be undertaken.

Cutaneous metastasis revealing a relapse of gastric linitis: Another case.

PubMed

Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

2013-01-01

Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Cutaneous metastasis revealing a relapse of gastric linitis: Another case

PubMed Central

Kairouani, Mouna; Perrin, Julie; Dietemann-Barabinot, Anne; Diab, Rafiq; Ruck, Stephane

2012-01-01

INTRODUCTION Cutaneous metastasis from gastric cancer is a rare occurrence. The linitis gastric carcinoma accounts only 8.7% of all gastric cancers. PRESENTATION OF CASE We report a case of female patient who was followed for linits cancer with peritoneal metastasis treated by six cycles of chemotherapy. After seventeen months of control, the relapse of the disease revealed by occurrence of cutaneous metastatsis. DISCUSSION Cutaneous metastasis from linit gastric is rare and the prognostic remains poor. The treatment is palliative. CONCLUSION This rare presentation should encourage the practitioners to biopsy any suspicion skin lesion. PMID:23276763

Cutaneous leishmaniasis in three Dutch military cohorts following jungle training in Belize.

PubMed

van Thiel, P P A M; Zeegelaar, J E; van Gool, T; Faber, W R; Kager, P A

2011-05-01

Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective. Copyright © 2011 Elsevier Ltd. All rights reserved.

Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre-defined institutional treatment policy in a region with a high prevalence of skin cancer.

PubMed

Huo, Michael; Panizza, Benedict; Bernard, Anne; Porceddu, Sandro V

2018-02-01

To determine the rate of subsequent primary site failure in patients with head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) in a region with a high prevalence of cutaneous squamous cell carcinoma, according to a pre-determined institutional policy. Secondary aims included regional and distant control, and overall survival. Patients presenting between April 2005 and June 2016 to the Princess Alexandra Hospital Head and Neck Multidisciplinary Meeting with UKP HNSCC from either presumed mucosal or cutaneous sites treated with curative intent were eligible. Patients with presumed mucosal origin were treated with radiation therapy (RT) with or without chemotherapy, while patients with presumed cutaneous SCC were treated with surgery and post-operative RT with or without chemotherapy. A total of 63 patients met the inclusion criteria. Median follow up duration was 3.9 years (IQR 2.07-5.14). There were no subsequent primary site failures. The rate of nodal failure among presumed mucosal patients was 11.5%, and 8.1% among presumed cutaneous patients. The rate of distant metastatic failure was 11.1% among all patients. The estimated 5 year overall survival was 71.2% (95% CI 59.2-85.7%). Treatment according to our pre-defined institutional policy for UKP HNSCC in a region with a high prevalence of cutaneous SCC appears to be safe and effective with low rates of mucosal primary emergence and nodal failure. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Efficient Transduction of Human and Rhesus Macaque Primary T Cells by a Modified Human Immunodeficiency Virus Type 1-Based Lentiviral Vector.

PubMed

He, Huan; Xue, Jing; Wang, Weiming; Liu, Lihong; Ye, Chaobaihui; Cong, Zhe; Kimata, Jason T; Qin, Chuan; Zhou, Paul

2017-03-01

Human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors efficiently transduce genes to human, but not rhesus, primary T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-1 vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-1 vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-1 vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus primary T cells. Recently, HIV-1 variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus primary T cells. Thus, the present study tested whether HIV-1 vectors packaged by a packaging construct containing these CA substitutions could efficiently transduce both human and rhesus primary CD4 T cells. To accomplish this, LNEIE mutations were made in the packaging construct CEMΔ8.9, and recombinant HIV-1 vectors packaged by Δ8.9 WT or Δ8.9 LNEIE were generated. Transduction rates, CA stability, and vector integration in CEMss-CCR5 and CEMss-CCR5-rhTRIM5α/green fluorescent protein cells, as well as transduction rates in human and rhesus primary CD4 T cells by Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors, were compared. Finally, the influence of rhesus TRIM5α variations in transduction rates to primary CD4 T cells from a cohort of 37 Chinese rhesus macaques was studied. While it maintains efficient transduction for human T-cell line and primary CD4 T cells, Δ8.9 LNEIE-packaged HIV-1 vector overcomes rhesus TRIM5α-mediated CA degradation, resulting in significantly higher transduction efficiency of rhesus primary CD4 T cells than Δ8.9 WT-packaged HIV-1 vector. Rhesus TRIM5α variations strongly influence transduction efficiency of rhesus primary CD4 T cells by both Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-1 vectors. Thus, it is concluded that Δ8.9 LNEIE-packaged HIV-1

Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat.

PubMed

Wu, Bor-Tsang; Chen, Kuan-Ting; Liu, Kuo-Sheng; Chen, Yu-Wen; Hung, Ching-Hsia; Wang, Jhi-Joung

2015-06-01

The purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. Cutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. On the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95-4.18) μmol]>lidocaine [5.81 (5.70-5.98) μmol] (p<0.01). Clonidine at a dose of 0.12 μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12 μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. Our resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Cutaneous metastatic tuberculous abcess in a patient with cervico-mediastinal lymphatic tuberculosis.

PubMed

Dekeyzer, S; Moerman, F; Callens, S; Vandekerckhove, L

2013-01-01

Metastatic tuberculous abcess or tuberculous gumma is a rare form of cutaneous tuberculosis resulting from haematogenous spread from a non-cutaneous tuberculous focus. A 26-year old patient of Pakistani origin presented at our clinic with an abcess on his right thigh that had slowly grown over a period of two months to a total size of 30 cm. Based on clinical findings, microbiology, CT thigh and CT chest, our patient was diagnosed with a tuberculous abcess and cervico-mediastinal tuberculous lymphadenitis. Antituberculosis drugs were initiated. Cutaneous tuberculosis should be included in the differential diagnosis of chronic cutaneous abcesses, especially in patients from tuberculosis endemic nations.

Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600 mutations in cutaneous melanoma patients.

PubMed

Kim, Dae Won; Haydu, Lauren E; Joon, Aron Y; Bassett, Roland L; Siroy, Alan E; Tetzlaff, Michael T; Routbort, Mark J; Amaria, Rodabe N; Wargo, Jennifer A; McQuade, Jennifer L; Kemnade, Jan; Hwu, Patrick; Woodman, Scott E; Roszik, Jason; Kim, Kevin B; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

2017-04-15

BRAF V600 , NRAS, TP53, and BRAF Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF Non-V600 mutations. This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). The prevalence of BRAF V600 , NRAS, TP53, and BRAF Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF Non-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. These results add to the understanding of the clinical features associated with TP53 and BRAF Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society. © 2016 American Cancer Society.

[Primary peripheral T-cell lymphoma of the penis: a case report and review of the literature].

PubMed

Shi, Yan-Lin; Yin, Hong-Lin; Zhou, Xiao-Jun; Zhou, Hang-Bo; Lu, Zhen-Feng

2008-11-01