Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

Angioqueratomas de fordyce múltiplos de vulva associados à cirrose hepática.

Fordyce angiokeratoma is a benign skin neoplasm, characterized by erythematous-violet keratotic papules with mamillated surface, which follows a chronic and minimally symptomatic course. However, symptoms can be related such as itching, burning, bleeding, dyspareunia; aesthetic and social concerns may prompt request for treatment. The condition mainly affects men and usually occurs in the scrotum, but rarely may occur in women. A 30-year-old woman with liver cirrhosis and portal hypertension is described. Over a period of two years she developed multiple angiokeratomas of the vulva, complicated by frequent bleeding. Histopathologic analysis of the lesion confirmed the diagnosis of angiokeratoma and all lesions were surgically removed. The results of the treatment were very satisfactory, with no relapses or complications.Angioqueratoma de Fordyce é uma dermatose incomum que compõe o grupo das neoplasias cutâneas benignas, caracterizando-se pelo aparecimento de lesões papuloceratósicas, eritemato-violáceas de superfície mamilonada, que apresentam curso crônico e oligossintomático. No entanto, outros sintomas podem estar associados, como prurido, ardência, sangramento e dispareunia, além de problemas estéticos e de ordem social. Afeta principalmente homens, acometendo a região escrotal, sendo raro seu surgimento em mulheres. Relata-se caso de uma paciente com 30 anos de idade, portadora de cirrose hepática e hipertensão portal evoluindo há 2 anos com múltiplos angioqueratomas na vulva de sangramento frequente. A análise histopatológica confirmou o diagnóstico de angioqueratoma e a paciente foi submetida à exérese cirúrgica das lesões. Os resultados terapêuticos foram satisfatórios, sem recidivas ou complicações.

Presence of Merkel cell polyomavirus DNA and large-T antigen in keratinocyte carcinomas and its correlation with immunohistochemical markers p16, p53 and ki67.

BACKGROUND: Merkel cell polyomavirus (MCPyV), a human polyomavirus that is unequivocally linked to merkel cell carcinoma (MCC), has been found in association with keratinocytes carcinomas (KC), especially basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). Nevertheless, there is scarce information about the possible involvement of MCPyV in the development of KC. OBJECTIVES: To assess the presence of MCPyV DNA and Large-T Antigen (LT-Ag) via Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) in cases of KC, and to correlate its presence with immunohistochemical markers p16, p53, and ki67, tumor type and subtype, sun-exposed location, and epidemiological data. METHODS: The prevalence of MCPyV DNA, LT-Ag, and immunohistochemical markers p16, p53, and ki67 was assessed by PCR and Immunohistochemistry (IHC) in 127 cases of KC, these results were correlated with tumor type and subtype, sun-exposed location, and epidemiological data. RESULTS: The MCPyV DNA was detected in 42.57% (43 of 101) cases by PCR, the LT-Ag was detected in 16.4% (20 of 122) of cases, p16 in 81.5% (97 of 119), p53 in 66.4% (83 of 125), ki67 in 89% (73 of 82). No correlation between MCPyV LT-Ag and DNA confronted with tumor type, subtype, location site, and immunohistochemical markers was found. A single correlation between the MCPyV LT-Ag and cSCC tumors and peri-tumoral lymphocyte cells was noted. STUDY LIMITATIONS: Further steps need to be taken to better evaluate the MCPyV influence and its possible role in KC carcinogenesis, as the evaluation of the virus genome state, the gene sequence that encodes LT-Ag in the KC tumor cells, and in situ hybridization for viral DNA or RNA in these cells. CONCLUSIONS: Despite the frequent detection of MCPyV in KC, the data available so far does not support the hypothesis of a causal relationship between them.

Merkel cell polyomavirus and its etiological relationship with skin tumors.

Viruses have been frequently identified in several human neoplasms, but the etiological role of these viruses in some tumors is still a matter of controversy. Polyomaviruses stand out among the main viruses with oncogenic capacity, specifically the Merkel cell polyomavirus (MCPyV). Recent revisions in the taxonomy of polyomaviruses have divided the Polyomaviridae family into six genera, including 117 species, with a total of 14 currently known human-infecting species. Although the oncogenicity of polyomaviruses has been widely reported in the literature since 1950, the first description of a polyomavirus as an etiological agent of a neoplasm in humans was made only in 2008 with the description of MCPyV, present in approximately 80% of cases of Merkel cell carcinoma (MCC), with the integration of its genome to that of the tumor cells and tumor-specific mutations, and it is considered the etiological agent of this neoplasm since then. MCPyV has also been detected in keratinocyte carcinomas, such as basal cell carcinoma and squamous cell carcinoma of the skin in individuals with and without immunosuppression. Data on the occurrence of oncogenic viruses potentially involved in oncogenesis, which cause persistence and tissue injury, related to the Merkel cell polyomavirus are still scarce, and the hypothesis that the Merkel cell polyomavirus may play a relevant role in the genesis of other cutaneous carcinomas in addition to MCC remains debatable. Therefore, the present study proposes to explore the current knowledge about the presence of MCPyV in keratinocyte carcinomas.

Evaluation of vitamin D plasma levels after mild exposure to the sun with photoprotection.

BACKGROUND: Most of the organism's vitamin D (VD) is obtained through the cutaneous synthesis after exposure to the sun's UVB radiation. Sunscreens are indicated for the prevention of actinic damage to the skin, however, there are few clinical trials assessing the synthesis of cutaneous VD in real-life situations of sun exposure with ordinary clothing and usual photoprotection. OBJECTIVES: To evaluate the synthesis of VD with suberythemal sun exposure in healthy adults using topical photoprotection (SPF 30). METHODS: Quasi-experimental study, conducted at Rio de Janeiro (Brazil), during winter, with 95 healthy adults who had 25-OH-VD checked twice, 24 hours apart, and were exposed to the sun (UVB=20 mJ/cm2), according to a randomized grouping: SC - use of SPF 30 on the face, neck and chest (n=64), NO - no sunscreens (n=10), CO - confined from sun exposure for 24h (n=21). The groups were matched according to the propensity score related to gender, age, phototype, body mass index, glycosylated hemoglobin and baseline levels of VD. The outcome evaluated was the variation (ΔVD) in serum level of 25-OH-VD (ng/ml) between the groups. RESULTS: A statistically significant difference was identified between CO and SC groups [median (p25-p75)]: ΔVD =1.4 (-0.3-3.6) vs. 5.5 (4.8-6.6); p<0.01. There was no difference between SC and NO groups: 5.4 (3.1-6.1) vs. 4.1 (2.5-6.0); p=0.17. STUDY LIMITATIONS: Laboratory analysis technique (chemiluminescence) with great variability, loss of food intake standardatization, unbalanced groups. CONCLUSIONS: Suberythemal sun exposure with sunscreen (SPF 30) provides similar vitamin D serum variation than without photoprotection in healthy adults.

Merkel cell polyomavirus and its etiological relationship with skin tumors

Abstract Viruses have been frequently identified in several human neoplasms, but the etiological role of these viruses in some tumors is still a matter of controversy. Polyomaviruses stand out among the main viruses with oncogenic capacity, specifically the Merkel cell polyomavirus (MCPyV). Recent revisions in the taxonomy of polyomaviruses have divided the Polyomaviridae family into six genera, including 117 species, with a total of 14 currently known human-infecting species. Although the oncogenicity of polyomaviruses has been widely reported in the literature since 1950, the first description of a polyomavirus as an etiological agent of a neoplasm in humans was made only in 2008 with the description of MCPyV, present in approximately 80% of cases of Merkel cell carcinoma (MCC), with the integration of its genome to that of the tumor cells and tumor-specific mutations, and it is considered the etiological agent of this neoplasm since then. MCPyV has also been detected in keratinocyte carcinomas, such as basal cell carcinoma and squamous cell carcinoma of the skin in individuals with and without immunosuppression. Data on the occurrence of oncogenic viruses potentially involved in oncogenesis, which cause persistence and tissue injury, related to the Merkel cell polyomavirus are still scarce, and the hypothesis that the Merkel cell polyomavirus may play a relevant role in the genesis of other cutaneous carcinomas in addition to MCC remains debatable. Therefore, the present study proposes to explore the current knowledge about the presence of MCPyV in keratinocyte carcinomas.

Demographics and spatial distribution of the Brazilian dermatologists.

The medical-dermatological demographics favors health planning and guides expansion of the specialty. We conducted an ecological study of dermatologists members of the Brazilian Society of Dermatology (SBD). We evaluated: gender, age, address; which were compared with population and human development index indicators of municipalities. We evaluated 8384 members, distributed in 527 (9.5%) municipalities throughout Brazil. The female sex represented 78.4% of the members and the median age was 43 (36-54) years. The median density of dermatologists was 0.35 (0.21-0.37) per 10,000 inhabitants. The correlation (Spearman's rho) between density of dermatologists and human development index was 0.39 (p <0.01). The Brazilian dermatologist is characterized as: female, age <50 years and presenting an heterogeneous distribution throught the country.

Profile of dermatological consultations in Brazil (2018).

BACKGROUND: Dermatological diseases are among the primary causes of the demand for basic health care. Studies on the frequency of dermatoses are important for the proper management of health planning. OBJECTIVES: To evaluate the nosological and behavioral profiles of dermatological consultations in Brazil. METHODS: The Brazilian Society of Dermatology invited all of its members to complete an online form on patients who sought consultations from March 21-26, 2018. The form contained questions about patient demographics, consultation type according to the patient's funding, the municipality of the consultation, diagnosis, treatments and procedures. Diagnostic and therapeutic decisions were compared between subgroups. RESULTS: Data from 9629 visits were recorded. The most frequent causes for consultation were acne (8.0%), photoaging (7.7%), nonmelanoma skin cancer (5.4%), and actinic keratosis (4.7%). The identified diseases had distinct patterns with regard to gender, skin color, geographic region, type of funding for the consultation, and age group. Concerning the medical conducts, photoprotection was indicated in 44% of consultations, surgical diagnostic procedures were performed in 7.3%, surgical therapeutic procedures were conducted in 19.2%, and cosmetic procedures were performed in 7.1%. STUDY LIMITATIONS: Nonrandomized survey, with a sample period of one week. CONCLUSION: This research allowed us to identify the epidemiological profiles of the demands of outpatients for dermatologists in various contexts. The results also highlight the importance of aesthetic demands in privately funded consultations and the significance of diseases such as acne, nonmelanoma skin cancer, leprosy, and psoriasis to public health.

Reticulohistiocytosis.

Reticulohistiocytoses consist of a rare group of diseases caused by CD68+ macrophage proliferation. Several advances have been achieved in relation to the receptors involved in these diseases. This knowledge will clarify the physiopathologic mechanisms of the reticulohistiocytoses and direct better therapeutic approaches for patients.

Multicentric reticulohistiocytosis: a proliferation of macrophages with tropism for skin and joints, part II.

In this second part of the review of multicentric reticulohistiocytosis, the authors discuss its association with other diseases, in particular, cancer, and laboratory and therapeutic aspects of this incapacitating and disfiguring disease. Histopathologic aspects are characteristic: dense mononuclear infiltrate with typical multinucleated cells that contain periodic acid-Schiff-positive and diastasis-resistant material, conferring a "ground glass" aspect when stained with hematoxylineosin.

Multicentric reticulohistiocytosis: a proliferation of macrophages with tropism for skin and joints, part I.

The authors present part I of a review of multicentric reticulohistiocytosis, a rare systemic proliferative disease of histiocytes of unknown cause. It is clinically characterized by cutaneous and mucosal nodules and by osteoarticular lesions. The disease occurs in outbreaks that progress in severity, with spontaneous regression, but usually leaving incapacitating arthritis and disfiguring facial lesions. The authors discuss the historical, epidemiologic, and clinical aspects of this disease.

Merkel cell carcinoma in an immunosuppressed patient.

Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

Cicatrização de feridas diabéticas com fator de crescimento epidérmico: revisão integrativa / Healing of diabetic wounds with epidemic growth factor: integrative review / Curación de heridas diabéticas con factor de crecimiento epidérmico: revisión integrativa

Objetivo: Analisar as produções científicas sobre a efetividade do Fator de crescimento epitelial recombinante humano na cicatrização de feridas diabéticas. Métodos: Trata-se de uma revisão sistemática da literatura, a busca foi realizada nas bases de dados: Pubmed; Scopus e Lilacs. Resultados: Foram selecionados 21 artigos, sendo a maioria estudos experimentais (48%). A cicatrização completa de lesões tratadas com Fator de crescimento epitelial recombinante humano foi relatada por 17 artigos (81%). O aumento do tecido de granulação foi relatado em nove publicações (43%). Da mesma maneira, a diminuição da área da lesão foi descrita em dois artigos incluídos (10%). Duas publicações descrevem a diminuição do número de amputações e do estresse oxidativo e 62% dos artigos abordaram eventos adversos associados ao uso do produto (13/21), dos quais foram prioritários a ocorrência de tremores, dor local, calafrios, náuseas, infecção superficial, sensação de queimação e hematomas, considerados eventos adversos leves. Apenas um estudo apresentou a ocorrência de dor no peito como evento adverso grave. Conclusão: O fator de crescimento epitelial recombinante humano é indicado para uso tópico no tratamento de feridas diabéticas, evidenciando boa eficácia, porém mais estudos clínicos devem ser desenvolvidos. (AU)

Objective: To analyse the scientific studies of Human recombinant epithelial growth factor for the healing of diabetic wounds. Methods: A thorough review of the literature was performed in the following databases: PubMed, Scopus and LILACS. Results: 21 articles were selected, most studies were experimental (48%). Complete healing of Human recombinant epithelial growth factor-treated lesions has been reported by 17 articles (81%). Increased granulation tissue has been reported in nine publications (43%). Similarly, the reduction of the lesion area was described in two included articles (10%). Two publication describes the decrease in the number of amputations and oxidative stress and 62% of the articles addressed adverse events associated with the use of the product (13/21), of which the occurrence of tremors, local pain, chills, nausea, superficial infection, burning sensation and bruising were considered priority, considered adverse events light. Only one study showed chest pain as a serious adverse event. Conclusion: Although Human recombinant epithelial growth factor is indicated for topical use in the treatment of diabetic wounds and demonstrates good efficacy, more clinical studies should be developed. (AU)

Objetivo: Analizar la producción científica sobre la efectividad de Factor de crecimiento epitelial humano recombinante en la curación de heridas diabéticas. Métodos: Esta es una revisión sistemática de la literatura, la búsqueda se realizó en las bases de datos: Pubmed; Scopus y lilas. Resultados: Se seleccionaron 21 artículos. La mayoría de los estudios fueron experimentales (48%). 17 artículos informaron sobre la curación completa de lesiones tratadas con factor de crecimiento epitelial humano recombinante (81%). El aumento en el tejido de granulación se informó en nueve publicaciones (43%). Asimismo, se utilizó una reducción en el área de la lesión en dos artículos incluidos (10%). Dos publicaciones describen una disminución en el número de amputaciones y estrés oxidativo y el 62% de los artículos abordaron eventos adversos asociados con el uso del producto (13/21), que son las prioridades prioritarias en la aparición de temblores, dolor local, escalofríos, náuseas, infección superficial, sensación de ardor y hematomas, reflejos de eventos adversos leves. Solo un estudio muestra la aparición de dolor torácico como un evento adverso grave. Conclusión: Factor de crecimiento epitelial humano recombinante está indicado para uso tópico en el tratamiento de heridas diabéticas, mostrando buena eficacia, pero se deben desarrollar más estudios clínicos. (AU)

Analysis of effectiveness of a surgical treatment algorithm for basal cell carcinoma.

BACKGROUND:: Surgical excision is the treatment of choice for basal cell carcinoma and micrographic surgery considered the gold standard, however not yet used routinely worldwide available, as in Brazil. Considering this, a previously developed treatment guideline, which the majority of tumors were treated by conventional technique (not micrographic) was tested. OBJECTIVE:: To establish the recurrence rate of basal cell carcinomas treated according to this guideline. METHOD:: Between May 2001 and July 2012, 919 basal cell carcinoma lesions in 410 patients were treated according to the proposed guideline. Patients were followed-up and reviewed between September 2013 and February 2014 for clinical, dermatoscopic and histopathologic detection of possible recurrences. RESULTS:: After application of exclusion criteria, 520 lesions were studied, with 88.3% primary and 11.7% recurrent tumors. Histological pattern was indolent in 85.5%, 48.6% were located in high risk areas and 70% small tumors. Only 7.3% were treated by Mohs micrographic surgery. The recurrence rate, in an average follow-up period of 4.37 years, was 1.3% for primary and 1.63% for recurrent tumors. Study limitations: unicenter study, with all patients operated on by the same surgeon. CONCLUSION:: The treatment guideline utilized seems a helpful guide for surgical treatment of basal cell carcinoma, especially if micrographic surgery is not available.

Immunohistochemical profile of multicentric reticulohistiocytosis.

BACKGROUND: There is enough evidence to support the knowledge that multicentric reticulohistiocytosis (MR) is a histiocytic proliferative disorder; however, the type of histiocytes involved is not well established. OBJECTIVE AND METHODS: To study the nature of cells present in MR lesions by studying the immunohistochemical profile of three new cases and reviewing 23 cases reported in the literature. RESULTS: MR histiocytic cells are positive for vimentin, CD68, and CD45, negative for S-100 protein, CD34, and XIIIa factor, and weak reactors for thrombomodulin. Small activated histiocytes are MAC387 positive. Lymphocytes, mainly CD4+ cells, are found in MR infiltrates. CONCLUSIONS: The MR immunophenotypic pattern does not suggest a type I or type II dendrocyte or a Langerhans cell origin. On the other hand, it points to a different cell derived from the monocyte-macrophage line. CD4+ cells may be responsible for activating the proliferation of histiocytic cells. Small histiocytic MAC387+ cells are likely to become the MR multinucleated giant cells.

Surgical treatment of basal cell carcinoma: an algorithm based on the literature.

Although basal cell carcinoma can be effectively managed through surgical excision, the most suitable surgical margins have not yet been fully determined. Furthermore, micrographic surgery is not readily available in many places around the world. A review of the literature regarding the surgical treatment of basal cell carcinoma was conducted in order to develop an algorithm for the surgical treatment of basal cell carcinoma that could help the choice of surgical technique and safety margins, considering the major factors that affect cure rates. Through this review, it was found that surgical margins of 4mm seem to be suitable for small, primary, well-defined basal cell carcinomas, although some good results can be achieved with smaller margins and the use of margin control surgical techniques. For treatment of high-risk and recurrent tumors, margins of 5-6 mm or margin control of the surgical excision is required. Previous treatment, histological subtype, site and size of the lesion should be considered in surgical planning because these factors have been proven to affect cure rates. Thus, considering these factors, the algorithm can be a useful tool, especially for places where micrographic surgery is not widely available.

Surgical treatment of axillary hyperhidrosis by suction-curettage of sweat glands.

UNLABELLED: Suction curettage is a dermatologic surgery technique for the treatment of axillary hyperhidrosis, which is becoming more popular. OBJECTIVE: The purpose of this study is to describe the current technique of removal of axillary sweat glands, and evaluate its efficacy and safety. CONCLUSION: Suction-curettage of sweat glands is a minimally invasive surgical technique that is easy to perform, safe, has high rates of success and relatively few side-effects. It is generally well tolerated by patients and requires shorter time away from daily activities, when compared with other surgical modalities.