Ultraviolet light-induced collagen degradation inhibits melanoma invasion.

Ultraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.

Female Immunity Protects from Cutaneous Squamous Cell Carcinoma.

PURPOSE: Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women present with less aggressive primary cutaneous squamous cell carcinoma (cSCC) and early strong immune activation. EXPERIMENTAL DESIGN: We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients with primary cSCC (N = 738, N = 160), advanced-stage cSCC (N = 63, N = 20) and FVB/N mice exposed to equal doses of DMBA, as well as in human keratinocytes by whole-exome, bulk, and single-cell RNA sequencing. RESULTS: We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test whether sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present with more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T-cell infiltration independently of mutations, a response that is absent in prednisolone-treated animals. In contrast, males increase the rate of mitosis and proliferation in response to carcinogen. Women's skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at UV radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women. CONCLUSIONS: This work shows the immune response is sex biased in cSCC and highlights female immunity offers greater protection than male immunity.

Poikilodermatous plaque-like hemangioma: Case series of a newly defined entity.

BACKGROUND: We present a distinctive type of acquired vascular proliferation, for which we propose the name of poikilodermatous plaque-like hemangioma. OBJECTIVE: The aim of this study was to summarize the clinical and histopathologic features in a case series of poikilodermatous plaque-like hemangioma. METHODS: Sixteen cases were identified from the routine clinical and referral practices of the authors. Clinical characteristics, including demographic details and clinical morphology, were collated. The salient histopathologic features, including immunohistochemical staining results, were summarized. RESULTS: The lesions were usually solitary erythematous-to-violaceous poikilodermatous plaques on the lower extremities and pelvic girdle, with an indolent clinical course. Mean age of affected patients was 72 (range 58-80) years, and there was a male predominance. Histology comprised a distinctive band-like proliferation of vascular channels suggestive of postcapillary venules within the superficial dermis with a background of fibrosis, edema, and loss of elastic fibers. Despite the clinical atrophic appearance, acanthosis was a frequent finding. LIMITATIONS: Retrospective study. CONCLUSION: Poikilodermatous plaque-like hemangioma is a distinctive and previously undescribed vascular proliferation defined by a constellation of consistent and reproducible clinical and histologic features.

Malignant proliferating trichilemmal tumour.

Proliferating trichilemmal tumours are benign but locally aggressive skin neoplasms arising from hair follicles. Rarely, they can become malignant and must be appropriately managed to prevent recurrence and metastasis. One must have a low threshold for diagnosing this rare neoplasm.

Disfiguring facial pyoderma vegetans with an excellent outcome.

We describe a case of disfiguring facial pyoderma vegetans in order to highlight the challenges in managing this rare skin condition and review the literature.A 54-year-old woman presented to dermatology clinic with a 3-month history of a left-sided facial lesion, which had been treated as an infected sebaceous cyst. The lesion had dramatically increased in size in the weeks prior to presentation. There was a history of Crohn's disease and ileal adenocarcinoma, both of which were in remission. A clinical diagnosis of pyoderma vegetans was made and the patient responded well to immunosuppressive therapy with oral ciclosporin. Carbon dioxide (CO2) laser resurfacing to residual scarring contributed to an excellent cosmetic result.

A case of secondary erythromelalgia with unusual histological findings.

Erythromelalgia clinically presents with episodic burning, erythema, and warmth of acral sites. It can be divided into primary and secondary associated with myeloproliferative and autoimmune conditions. Histology commonly shows capillary proliferation, swelling of endothelial cells, perivascular edema, and chronic inflammation with sparse lymphocytic infiltrate. We report a case of a 55-year-old man with classical secondary erythromelalgia clinically; however, he had unusual histological findings on biopsy comprising of acute perivascular infiltrate and perivascular mucin. This is the first report of such findings in the context of secondary erythromelalgia.

Thermal fusion: effects and interactions of temperature, compression, and duration variables.

BACKGROUND: The constraints imposed by minimal access surgery have driven the need for enabling technologies for thermal vessel occlusion or "tissue welding." The objective of this study was to determine the values of, and interaction between, tissue temperature, apposition force, and clamp time for optimum tissue welding. METHODS: A dedicated experimental device with heated occluding jaws was used for ex vivo experiments on harvested sheep carotid vessels. The device allowed individual variation of temperature (60, 70, 80, and 90 °C), compression force (20, 40, 60, and 80 N) and clamp time (5, 10, 15 s). Weld strength was measured by burst pressure. RESULTS: The best seal quality was obtained at a temperature of 90 °C (p = 0.03), a compression force between 60 and 80 N (p = 0.03), and clamp time of 10 s (p = 0.058). The individual effects of temperature, compression force, and clamp time were all significant at p < 0.001. Although all three were considered to have large effects, clamp time had a reduced effect, relative to temperature and compression force. CONCLUSIONS: Temperature, compression force, and clamp time influence the quality of thermal welding, but the interaction between temperature and apposition force appears to be more dominant.

Are primary cutaneous carcinisarcomas underdiagnosed? Five cases and a review of the literature.

Primary cutaneous carcinosarcoma is a biphasic tumour containing both malignant epithelial and malignant mesenchymal elements. To date, only 26 cases have been reported in the literature. However, our findings suggest that this may reflect underreporting and possibly underdiagnosis. We present five cases and a comprehensive review of the literature: The disease most commonly presents in the eighth and ninth decades of life, is twice as common in males and may be related to sun exposure. Surgery is the primary therapeutic modality. Despite treatment, 27% of cases developed metastatic disease. Both epithelial and mesenchymal elements have been implicated in disease spread. We hope to raise awareness of this uncommon but serious disease and to assist clinicians in its management.

Crystal deposition in a case of cutaneous Rosai-Dorfman disease.

Rosai-Dorfman Disease (RDD) is an idiopathic reactive proliferation of distinctive histiocytes that have abundant cytoplasm and commonly exhibit intracytoplasmic ingestion of inflammatory cells (emperipolesis). The histiocytes are immunopositive for S100 protein and are typically associated with an infiltrate of lymphocytes, plasma cells, and neutrophils. The classic clinical presentation is massive enlargement of (usually) cervical lymph nodes with a histologic appearance that mimics exaggerated sinus histiocytosis. RDD can also involve extra-nodal sites and skin involvement is common either as part of disseminated disease or as a result of primary disease. We report an exceptional case of cutaneous RDD with crystal deposition in a young male presenting with skin nodules. Skin biopsy showed classic features of cutaneous RDD with the additional feature of conspicuous rhomboidal and needle-shaped crystals within the cytoplasm of many lesional plasma cells, histiocytes, and also in an extra-cellular location. The plasma cells were polyclonal by light chain immunostaining. Crystal deposition has not been reported to date in RDD and is likely a result of the reactive plasma cell proliferation.

Descripcion de una cohorte de pacientes con Lupus Eritematoso Sistemico (LES) en un Hospital de Bogota-Colombia / Systemic Lupus Erithematosus in Bogota

Introducción. El Lupus Eritematoso Sistémico (LES) es un grupo de desórdenes inflamatorios, de carácter autoinmune y causa desconocida que afecta simultáneamente múltiples órganos. Objetivo. Establecer diferencias clínicas y paraclínicas en cuanto al género en pacientes diagnosticados con LES, en el Hospital Militar Central, tanto en el momento del diagnóstico como en la evolución de la enfermedad. Justificación. La mayoría de los pacientes de esta institución son de sexo masculino y están expuestos a radiación luz ultravioleta tipo B por períodos prolongados, factor vinculado a la fisiopatología del LES. Se realiza un estudio que describe y analiza el comportamiento de la enfermedad en dicha población, comparándola con mujeres con diagnóstico de LES atendidas en este centro. Materiales y métodos. El análisis de asociación y la diferencia de proporciones se elaboraron con base en la prueba de X2 y el test exacto de Fisher para variables categóricas, utilizando para la comparación de los dos grupos la prueba de t de 2 colas para variables de distribución normal y Kruskal Wallis en los casos en que los grupos fueran no homogéneos. Resultados. 73 de 88 pacientes cumplieron criterios de inclusión, 62 mujeres y 11 hombres con una relación global por género de 5,6:1. La edad promedio al momento del diagnóstico fue 39 años para los hombres y 34 para las mujeres. Las tres manifestaciones clínicas más frecuentes en los hombres fueron: las alteraciones renales, la artritis y la serositis; y en las mujeres: la artritis, las alteraciones renales y la fotosensibilidad; siendo la serositis significativamente más frecuente en hombres (45 por ciento vs. 19 por ciento, p<0,05) y la artritis (45 por ciento vs. 79 por ciento, p<0,01) en mujeres. La leucopenia (40 por ciento vs. 14 por ciento, p<0,05) y trombocitopenia (36 por ciento vs. 9 por ciento, p<0,01) con más frecuencia en hombres y en menor proporción la hipocomplementemia (57 por ciento vs. 88 por ciento, p<0,05) al momento del diagnóstico. Durante la evolución de la enfermedad las manifestaciones pulmonares fueron más frecuentes en hombres (45 por ciento vs. 16 por ciento, p<0,02) y la alopecia y el fenómeno de Raynaud más en mujeres (0 por ciento vs. 25 por ciento, p<0,05). Conclusiones. Existen diferencias en la presentación clínica y paraclínica del LES respecto al género, guardando cierta uniformidad en la población colombiana en contraste con estudios publicados anteriormente