Merkel cell carcinoma: epidemiology, clinical features, diagnosis and treatment of a rare disease

Abstract Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment.

Mohs micrographic surgery in rare cutaneous tumors: a retrospective study at a Brazilian tertiary university hospital

Abstract Background Mohs micrographic surgery is an established technique in the treatment of cutaneous neoplasms. It offers higher cure rates and the main indications are non-melanoma malignant skin tumors. Few studies have been performed on the treatment of rare tumors through this technique. Objective To study rare skin tumors and rare variants of basal cell carcinoma and squamous cell carcinoma submitted to Mohs micrographic surgery in a tertiary service in relation to frequency, disease-free evolution, and applicability of this surgical procedure for this group of tumors. Methods This was a retrospective observational study including rare skin tumors and less common variants of basal cell carcinoma and squamous cell carcinoma treated using Mohs micrographic surgery, between October 2008 and April 2021. Results During the study period, 437 tumors were treated using Mohs micrographic surgery, and 22 (5%) rare skin tumors were selected. The tumors comprised three dermatofibrosarcomas protuberans, two atypical fibroxanthomas, two spiradenomas, two hypercellular fibrohistiocytomas, one primary cutaneous adenocarcinoma, one trichoblastoma, one porocarcinoma, one chondroid syringoma, one cutaneous angiosarcoma, one Merkel cell carcinoma, and one sebaceous carcinoma. Six other cases of rare basal cell carcinoma variants with trichoepitheliomatous differentiation, metatypical basal cell carcinoma, and clear cell squamous cell carcinoma were included. There were no cases of recurrence after an average of six years of follow-up. Study limitations This is a retrospective study on rare neoplasms carried out in a single referral center, and this surgical technique isn't widely available in the public service. Conclusion This retrospective case series showed that Mohs micrographic surgery is an appropriate treatment for rare skin tumors. They corresponded to 5% of the tumors treated by the technique during a 12-year-period, with no recurrences identified.

Carcinoma de células de Merkel: múltiplas lesões cutâneas primárias no membro inferior / Merkel cell carcinoma: multiple primary skin lesions in the lower limb

Carcinoma de células de Merkel é um tumor neuroendócrino raro e agressivo de pele que usualmente apresenta-se como lesão única na região de cabeça ou pescoço. Relata-se um caso de topografia e apresentação atípicas, com presença de múltiplos e simultâneos tumores na perna esquerda de rápida evolução, associados à linfonodomegalia inguinal palpável, com diagnóstico confirmado por meio de histopatologia e imuno-histoquímica. Realizada exérese de linfonodo inguinal esquerdo e das lesões cutâneas com margem de segurança

Merkel cell carcinoma is a rare and aggressive neuroendocrine skin tumor usually presenting as a single lesion in the head or neck region. We report a case of atypical topography and presentation, with multiple and simultaneous tumors on the left leg of rapid progression associated with palpable inguinal lymphadenopathy and diagnostic confirmation by histopathology and immunohistochemistry. Exeresis of the left inguinal lymph node and skin lesions with a safety margin was performed

Carcinoma de Células de Merkel Metastático: Relato de Caso / Metastatic Merkel cell Carcinoma: Case Report / Carcinoma de Células de Merkel Metastásico: Relato de Caso

Introdução: O carcinoma de células de Merkel é um raro tumor neuroendócrino cutâneo, que se origina das células responsáveis pela sensibilidade tátil, possui caráter agressivo, evolução rápida e difícil tratamento. Relato do caso: Paciente do sexo masculino, 49 anos, caucasiano, que, ao atendimento dermatológico, apresentou nódulo indolor, infiltrando tecidos profundos, não ulcerado e localizado na região do braço esquerdo. O resultado da biópsia incisional foi positivo para carcinoma de células de Merkel. Após ressecção da lesão, os exames complementares evidenciaram doença metastática na axila e parede torácica. Com o tratamento quimioterápico, houve um benefício inicial com redução tumoral, porém, não durável, uma vez que foram reveladas novas áreas com metástases tumorais em regiões superiores do corpo, sendo submetido a novo procedimento cirúrgico, o qual, após novo regime quimioterápico, não obteve sucesso. Conclusão: Na ocasião do tratamento desse paciente, os anticorpos monoclonais, como o avelumab, não estavam disponíveis. O diagnóstico precoce com cirurgia de exérese da lesão imediata, antes do acometimento de outras regiões, permanece sendo a melhor opção para um prognóstico favorável ao paciente. Contudo, a despeito disso, com as limitações à época do tratamento, o paciente evoluiu a óbito.

Introduction: The Merkel cell carcinoma is a rare cutaneous neuroendocrine tumor that originates from cells responsible for tactile sensitivity, it has an aggressive character, fast evolution and difficult treatment. Case report: 49 years Caucasian male patient, with a painless nodule, infiltrating deep tissue, not ulcerated and located in left arm identified during the dermatological consultation. The result of the incisional biopsy was positive for Merkel cell carcinoma. After resection of the lesion, complementary exams revealed metastatic disease in the axilla and chest wall. The chemotherapy treatment brought an initial improvement with tumor reduction, however, it was not durable, because new areas with tumor metastases in upper regions of the body were revealed, the patient was submitted to an another surgical procedure, after which a new chemotherapy regimen failed. Conclusion:At the time of the treatment of this patient, monoclonal antibodies, such as avelumab, were not available. Early diagnosis with immediate lesion excision surgery, before the involvement of other regions, remains the best option for a better prognosis. However, regardless of this, because of the limitations at the time of the treatment, the patient died.

Introducción: El carcinoma de células de Merkel es un tumor neuroendocrino cutáneo raro, que se origina en células responsables de la sensibilidad táctil, tiene un carácter agresivo, una evolución rápida y un tratamiento difícil. Relato del caso: Paciente masculino, de 49 años, caucásico, que en atención dermatológica encontró nódulo indoloro, infiltrando tejidos profundos, no ulcerados y ubicados en la región del brazo izquierdo. El resultado de la biopsia incisional fue positivo para el carcinoma de células de Merkel. Después de la resección de la lesión, los exámenes complementarios mostraron enfermedad metastásica en la axila y la pared torácica. Con el tratamiento de quimioterapia, hubo un beneficio inicial con la reducción del tumor, sin embargo, no es duradero, ya que se revelaron nuevas áreas con metástasis tumorales en las regiones superiores del cuerpo, que se sometieron a un nuevo procedimiento quirúrgico, que después de un nuevo régimen de quimioterapia no tuvo éxito. Conclusión: En el momento del tratamiento de este paciente, los anticuerpos monoclonales, como avelumab, no estaban disponibles. El diagnóstico temprano con cirugía para la escisión de la lesión inmediata, antes de la participación de otras regiones, sigue siendo la mejor opción para un pronóstico favorable para el paciente. Sin embargo, a pesar de esto, con las limitaciones al momento del tratamiento, el paciente falleció.

Merkel cell carcinoma metastatic to the testis: report of a rare diagnosis and review of the literature

Merkel cell carcinoma is an aggressive malignancy that frequently recurs/disseminates, but metastases to the genitourinary tract are rare. Only eight cases of Merkel cell carcinoma metastatic to the testis are reported. We describe the ninth case of this event and provide a review of the literature. A 58-year-old man diagnosed with Merkel cell carcinoma of the wrist, presented, 37 months later, a recurrence in the form of a testicular metastasis. The tumor consisted of a monotonous proliferation of small, blue, round cells, with immunoexpression of neuroendocrine markers and the typical dot-like paranuclear immunostaining for cytokeratin 20, in the absence of immunostaining for cytokeratin 7. The patient is alive with no evidence of disease. Clinicians should be aware of the possibility of metastatic dissemination to the testis since genital examination/imaging is not part of routine follow-up for these patients, but timely orchiectomy may be curative.

Carcinoma de células de Merkel de región glútea. Reporte de un caso / Merkel cell carcinoma of the gluteal region. Report of a case / Carcinoma de células de Merkel de região glútea. Relato de caso

Resumen: Introducción: el carcinoma de células de Merkel es un tumor primario maligno de piel que afecta fundamentalmente regiones expuestas a las radiaciones solares. Pocos casos han sido comunicados en una región no expuesta al factor de riesgo mencionado, como es la glútea. El objetivo de este trabajo es comunicar un caso clínico de carcinoma de células de Merkel de región glútea. Caso clínico: paciente de 63 años, sexo masculino, que consultó por tumoración de 2 cm de diámetro en región glútea derecha, de rápido crecimiento, que se operó de coordinación con anestesia, realizándose su resección completa. El resultado del estudio anatomopatológico informó carcinoma de células de Merkel. No se evidenció diseminación a distancia, por lo que de acuerdo con la clasificación TNM se determinó como estadio I. Se completó el tratamiento con radioterapia local. Actualmente el paciente sigue en seguimiento y asintomático. Discusión: los carcinomas de células de Merkel son tumores altamente agresivos. Además de la radiación solar como factor de riesgo, se mencionan la inmunodeficiencia y un nuevo poliomavirus, el poliomavirus de células de Merkel. Se presentan como tumoraciones de color violáceo y rápido crecimiento, y es frecuente el compromiso ganglionar sincrónico o metacrónico. La resección quirúrgica con márgenes suficientes y vaciamiento ganglionar, en caso de haber compromiso o estudio de ganglio centinela en caso de no haberlo, es lo indicado. El pronóstico depende del estadio y se ha reportado hasta 30% de recidiva a dos años.

Summary: Introduction: Merkel cell carcinoma is a malign primary tumour that mainly affects regions that are exposed to solar radiation. Few cases have been reported in a region that is not exposed to the above mentioned risk factor, as the gluteal regions. The study aims to communicate the clinical case of a Merkel cell carcinoma of the gluteal region. Clinical case: 63-year-old male patient who consulted for a tumour with a 2cm diameter in the right gluteal region, rapidly growing, being completely resected in a cordinaterd surgery under anesthesia. Pathology study revealed that it was Merkel cell carcinoma. No distance dissemination was seen, and thus as per the TNM staging system it was classified as stage I. Therapy was completed with local radiotherapy, It is currently under follow up and asymptomatic. Discussion: Merkel cell carcinoma are highly aggressive tumours. Apart from solar radiation as a risk factor, it is worth mentioning immunodeficiency and a new polyomavirus, the Merkel cell polyomavirus. This condition can be seen as purple, rapidly growing tumours and they frequently involve synchronic or metachronic lymph node compromise. Surgical resection with sufficient margins and lymph node emptying, in the event of lymph node compromise or sentinel node biopsy is recommended. Prognosis depends on the stage and a 30% relapse has been reported after 2 years.

Resumo: Introdução: o carcinoma de células de Merkel é um tumor primário maligno de pele que afeta fundamentalmente regiões expostas às radiações solares. São poucos os casos relatados em uma região não exposta a esse fator de risco, como é a glútea. O objetivo desta comunicação é apresentar o caso clínico de um carcinoma de células de Merkel de região glútea. Caso clínico: paciente de 63 anos, sexo masculino que consultou por tumoração de 2 cm de diâmetro, na região glútea direita, com rápido crescimento que foi ressecada completamente em uma cirurgia eletiva com anestesia. O laudo anatomopatológico foi: carcinoma de células de Merkel. Não se evidenciou disseminação a distância por isso foi classificado como estádio I de acordo com a classificação TNM. O tratamento foi completado com radioterapia local. Atualmente em seguimento e assintomático. Discussão: os carcinomas de células de Merkel são tumores altamente agressivos. Além da radiação solar, a imunodeficiência e um novo poliomavirus, o poliomavirus de células de Merkel, são mencionados como fator de risco. Apresentam-se como tumorações de cor violácea e crescimento rápido e frequentemente se observa compromisso ganglionar sincrônico ou metacrônico. A ressecção cirúrgica com margens suficientes e esvaziamento ganglionar, quando há compromisso ou estudo de gânglio sentinela quando não há, é a conduta indicada. O prognóstico depende do estádio e há registros de até 30% de recidiva a 2 anos.

Merkel cell carcinoma: A series of seven cases

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy affecting the skin, for which timely diagnosis and aggressive treatment are essential. MCC has most often been reported in Caucasians, and case reports in Asians are rare. This study presents our experiences with the surgical treatment and radiotherapy of MCC in Asian patients. METHODS: We retrospectively reviewed the records of seven MCC patients between 2000 and 2018 from a single institution, and analyzed patient characteristics, tumor characteristics, surgical treatment, sentinel lymph node evaluation, reconstruction, adjuvant radiation therapy, and prognosis. RESULTS: Eight MCC lesions occurred in seven patients, most commonly in the head and neck region. All patients underwent surgical excision with reconstruction. The final surgical margin was 1.0 cm in most cases, and reconstruction was most commonly performed with a split-thickness skin graft. Five patients received adjuvant radiotherapy, and two patients received sentinel lymph node biopsy. During the follow-up period, three patients remained well, two died from other causes, one experienced recurrence, and one was lost to follow-up. CONCLUSIONS: We treated seven Asian MCC patients and our series confirmed that MCC is a very dangerous cancer in Asians as well. Based on our experiences, thorough surgical excision of MCC with histopathological clearance should be considered, with sentinel lymph node evaluation if necessary, followed by appropriate reconstruction and careful postoperative observation. Adjuvant radiation therapy is also recommended for all Asian MCC patients. The results of this case series may provide guidance for the treatment of Asian MCC patients in the future.

Two separate nodules of Merkel cell carcinoma occurring concomitantly on one cheek

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroectodermal carcinoma arising from mechanoreceptor Merkel cells. Multiple MCCs are even rarer. We report a case of two independent MCCs simultaneously present in the cheek of a patient, which were effectively and esthetically treated using a cheek flap. Punch biopsy performed in a 60-year-old woman admitted with a chief complaint of two skin-colored hard nodules in her left cheek, accompanied by an itching sensation, was suggestive of MCC. Accordingly, we performed sentinel lymph node biopsy through the modified Blair incision under general anesthesia, in cooperation with the head and neck surgery department. The defect was covered with a cheek flap by slightly extending the existing incision following wide excision with a safety margin of 1 cm. This paper is significant in that it introduces an effective reconstruction technique that maintains function using a cheek flap for the management of this rare case. In addition, this paper is the first to classify multiple MCCs according to the time of onset. We believe that this paper presents an effective alternative reconstruction technique with sentinel node biopsy through the modified Blair incision.

Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

Clinical and pathological features of cutaneous Merkel cell carcinoma: a retrospective analysis of 171 cases / 中华皮肤科杂志

Objective To investigate clinicopathological features,diagnosis and treatment of cutaneous Merkel cell carcinoma (MCC).Methods CNKI,Wanfang,Vip databases were searched for reported domestic cases of MCC from January 1,1986 to October 1,2017,and clinical data were collected,and retrospectively analyzed and summarized.Results During 31 years between 1986 and 2017,a total of 171 domestic cases of MCC were reported.There were 78 males and 93 females,and the ratio of male to female was 1:1.19.Of the 171 patients,136 (79.5％) were aged more than 50 years,and lesions mostly occurred on the head and face or extremities in 139 (81.3％) patients.Clinically,149 (87.1％) patients were misdiagnosed as tumor of unknown origin (89 cases,52％),malignant lymphoma (34 cases,19.9％),benign tumors (15 cases,8.8％) or non-tumor diseases (11 cases,6.4％).As for clinical stage,84 (49.1％) patients had stage Ⅰ MCC,and 49 (28.6％)had stage Ⅱ MCC.One patient received immunotherapy,and 165 patients underwent surgical resection,including 91 patients receiving surgery alone,24 patients treated with postoperative radiotherapy,19 patients treated with postoperative chemotherapy,and 31 patients receiving postoperative chemoradiotherapy.Five patients did not describe the treatment.Among 74 patients who were followed up after the surgery,one-year survival rate and five-year survival rate were 52.7％ and 6.8％ respectively.The five-year survival rate was 6.1％ in the patients with stage Ⅰ MCC,5.6％ in those with stage Ⅱ MCC,and 0 in those with stage Ⅲ and Ⅳ MCC.Conclusions In China,cutaneous MCC mostly occurs on the head,face,neck and extremities of the middle-aged or elderly,with a high misdiagnosis rate.Surgical excision combined with radiotherapy or chemotherapy is a frequently used treatment protocol in China,but the prognosis is always poor.

Merkel cell carcinoma in an immunosuppressed patient

Abstract 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.

Carcinoma de células de Merkel com imunofenótipo atípico: desafio diagnóstico / Merkel cell carcinoma with atypical immunophenotype: diagnostic challenge

O carcinoma de células de Merkel (CCM) é um tumor raro de origem neuroendócrina e epidérmica, de mau prognóstico. Está classicamente associado à imunossupressão, exposição solar e, mais recentemente, ao poliomavírus (MCPyV). Caracteristicamente, o carcinoma de células de Merkel apresenta positividade para marcadores epiteliais e neuroendócrinos. A expressão combinada desses marcadores é o dado que corrobora o diagnóstico. Tumores MCPyV- possuem prognóstico desfavorável. Relata-se um caso de carcinoma de células de Merkel com imunofenótipo atípico (CK20 negativo) e comportamento agressivo. Este relato se justifica para reforçar a importância do conhecimento, pelos dermatologistas, de diferentes imunofenótipos que podem estar associados ao carcinoma de células de Merkel.

The Merkel cell carcinoma is a rare tumor of neuroendocrine and epidermal origin and with poor prognosis. It is classically associated with immunosuppression, exposure to the sunlight and, more recently, with the polyomavirus. It is positive for epithelial and neuroendocrine markers. The combined expression of these markers confirms the diagnosis. Polyomavirus tumors have an unfavorable prognosis. The authors report a case of Merkel cell carcinoma with atypical immunophenotype (CK20 negative) and aggressive behavior. The present report is aimed at highlighting the importance of dermatologists having knowledge of different immunophenotypes that may be associated with the Merkel cell carcinoma.

Carcinoma metastático de células de Merkel de origem desconhecida: relato de caso / Metastatic Merkel cell carcinoma of unknown origin: a case report

Carcinoma de células de Merkel é um tumor cutâneo raro, de origem neuroendócrina, de grande potencial metastático e prognóstico ruim. Geralmente, se manifesta em homens como massa nodular firme, de crescimento rápido, que aparece com mais frequência em áreas expostas ao sol, como cabeça e pescoço. A baixa incidência da doença e suas características clínicas pouco específicas dificultam o diagnóstico precoce, que deve ser realizado por meio de análise histológica e confirmado por cuidadoso estudo imuno-histoquímico. As altas taxas de recorrência e a grande incidência de metástases à distância confirmam a agressividade do tumor, o que exige tratamento multimodal com cirurgia, quimioterapia e radioterapia para a maior parte dos pacientes acometidos. Seguimento rigoroso deve ser mantido, uma vez que a recorrência da doença ocorre em 6 a 12 meses após diagnóstico inicial. Carcinoma de células de Merkel metastático de origem desconhecida aumenta consideravelmente o desafio diagnóstico e terapêutico. Neste estudo apresentamos um caso de carcinoma de células de Merkel em axila direita, em mulher de 55 anos, com sítio primário desconhecido.

Merkel cell carcinoma is a rare skin tumor of neuroendocrine origin, high metastatic potential and poor prognosis. Usually, manifests itself in men as firm and fast growing nodular mass, appearing most frequently in sun-exposed areas, such as head and neck. The low incidence of disease and its nonspecific clinical features difficult early diagnosis, which needs to be supported by a careful immunohistochemical study. The high recurrence rates and the high incidence of distant metastases confirm the tumor aggressiveness, which requires multimodal treatment with surgery, chemotherapy and radiotherapy for the majority of affected patients. Strict compliance must be maintained, since the recurrence of the disease occurs in 6 to 12 months after initial diagnosis. Carcinoma metastatic Merkel cell of unknown origin significantly increases the diagnostic and therapeutic challenge. Here we present a case of Merkel cell carcinoma in the right axilla of a 55 years woman with unknown primary site.

Tumores cutâneos raros em cabeça e pescoço: experiência de 4 anos em uma instituição terciária / Head and neck rare skin tumors: 4 years of experience in a tertiary institution

Introdução: O câncer de pele é o mais incidente dentre as neoplasias. Os tipos histológicos mais comuns são Carcinoma Basocelular (CBC), Carcinoma Espinocelular (CEC) e, menos frequente, o Melanoma. Geralmente acometem segmentos corporais expostos aos raios ultravioletas, principalmente a região de cabeça e pescoço. Porém, há outros tipos mais de tumores que acometem esta área e que fazem parte da prática da oncologia cutânea encaminhada aos cirurgiões de cabeça e pescoço. Objetivo: O objetivo deste trabalho é descrever estas neoplasias percutâneas raras que foram operadas no Instituto do Câncer do Estado de São Paulo (ICESP) nos últimos 4 anos. Resultados: As entidades Carcinoma de células de Merkel, Dermatofibrossarcoma protuberans, Angiossarcoma, Fibroxantoma atípico, Porocarcinoma, Carcinoma triquilemal, Carcinoma de células claras, Carcinoma sarcomatoide e Carcinoma apócrino compuseram 4,4% dos atendimentos de oncologia cutânea realizada pela Cirurgia de Cabeça e Pescoço. Uma breve revisão de cada entidade foi realizada. Discussão: A compreensão dos tipos histológicos raros é importante no tratamento de tumores cutâneos na prática da cirurgia de cabeça e pescoço.

Introduction: Skin cancer is the most frequent cancer among neoplasms. The most common histological types are Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC) and, less frequent, Melanoma. They generally affect body segments exposed to ultraviolet rays, especially the head and neck region. However, there are other types of tumors involving this area and they are part of the practice of cutaneous oncology referred to head and neck surgeons. Objective: The objective of this paper is to describe these rare cutaneous neoplasms, which were treated at the Instituto do Câncer do Estado de São Paulo (ICESP) in the last 4 years. Results: Merkel cell carcinoma, Dermatofibrosarcoma protuberans, Angiosarcoma, Atypical Fibroxanthoma, Porocarcinoma Trichilemmal carcinoma, Sarcomatoid carcinoma and Apocrine carcinoma comprised 4.4 % of cases of cutaneous oncology conducted by Head and Neck Surgery. A brief review of each neoplasm was performed. Discussion: understanding of the rare histological types is important in the treatment of skin tumors in the practice of head and neck surgery.

Virus como inductores de neoplasias cutáneas / Viruses as agents inducing cutaneous neoplasms

El rol oncogénico de los virus en las neoplasias cutáneas es conocido por el hombre desde hace más de un siglo, cuando se atribuía el origen de la verruga vulgar al virus papiloma humano (VPH). En la actualidad, las neoplasias inducidas por virus pueden agruparse en tumores sólidos y procesos linfoproliferativos. Destacan entre los primeros el VPH, del cual ahora conocemos numerosos serotipos, cada uno vinculado a una neoplasia específica, el herpesvirus humano tipo 8 que produce el sarcoma de Kaposi y el poliomavirus vinculado al carcinoma de Merkel. Entre los procesos linfoproliferativos debemos mencionar al virus linfotrópico de células T humanas tipo 1 (HTLV-1) responsable de los linfomas de células T, en los cuales el compromiso cutáneo es inespecífico, con un amplio espectro de presentaciones clínicas y, que por consiguiente, plantean un reto para el diagnóstico diferencial. En este grupo también se encuentra el virus Epstein Barr vinculado a los linfomas nasales de Células NK/T y a los linfomas tipo Hidroa, de reciente descripción. En esta era en la que lo genético y lo molecular priman en las investigaciones en cáncer, no podemos dejar de lado el concepto de neoplasia como resultado de la infección por un agente viral, lo que abre una nueva veta de posibilidades de tratamiento anticanceroso basado en medicamentos antivirales.

The oncogenic role of viruses in cutaneous neoplasms has been known by humankind for more than a century, when the origin of the common wart, or verruca vulgaris, was attributed to the human papilloma virus (HPV). Currently, virus-induced cutaneous neoplasms may be grouped into solid tumors and lymphoproliferative disorders. HPV, from which various serotypes are now known, each being linked to a specific neoplasm, the human herpes virus type 8 producing Kaposi sarcoma, and the Merkel cell polyomavirus, highlight among the first group. Regarding the lymphoproliferative disorders, we should mention the human T-lymphotropic virus type I (HTLV-1), which is responsible for the T-cell lymphomas, in which the cutaneous manifestations are non-specific and have a wide spectrum, thus posing a challenge for differential diagnosis. The Epstein Barr virus, linked to nasal lymphomas of NK/T-cells and Hydroa-like cutaneous lymphomas, is also part of this group. In an era in which the genetic and molecular aspects of cancer research prevail, we may not leave behind the concept of neoplasms as a result an infection with a viral agent, which opens a wide array of new possibilities for cancer treatment based on antiviral drugs.

Merkel cell carcinoma polyomavirus-positive primary cutaneous Merkel cell carcinoma: two case reports / 中华皮肤科杂志

Objective To estimate the value of detection of Merkel cell carcinoma polyomavirus (MCPyV)in the diagnosis of Merkel cell carcinoma (MCC).Methods Two cases of MCC were studied using light microscopy and immunohistochemistry.PCR was performed to detect DNA sequences encoding MCPyV large T antigen(LT)and viral protein 1 (VP1) in paraffin-embedded tissue specimens from the two patients with MCC,five patients with T cell lymphoma,two normal human controls,as well as in two T cell lymphoma cell lines MAC 1 and MAC2.DNA sequencing was also carried out.Results Both of the patients with MCC were male.The patient 1 presented with a mass in the right anterior shin for more than one year,and the patient 2 had a mass in the left knee for more than six months.Skin examination revealed densely distributed pink nodules in the right anterior shin,with confluence into an indurated plaque which measured 10 cm × 8 cm with superficial erosion,exudates and crusts and was surrounded by multiple irregularly sized erythematous nodules with limited mobility in the patient 1,as well as a royal blue,hard,poorly marginated nodular mass measuring 5 cm × 4 cm in the left medial knee with limited mobility in the patient 2.Pathological manifestations were similar in the two patients.Tumor cells were uniform with large hyperchromatic nuclei,eosinophilic and sparse cytoplasm,and fine chromatin.Mitotic figures were easily seen.Immunohistochemistry revealed that the tumor cells stained positive for pan-cytokeratin,synuclein (Syn),neuron-specific enolase (NSE),chromogranin (CgA),CK20,and Ki-67 (＞ or =60％),but negative for S100 protein,HMB45,CD34,thyroid transcription factor 1 (TTT-1),CK7 and leukocyte common antigen (LCA).MCPyV DNA was detected in both MCC specimens,but absent in the other skin specimens or T cell lymphoma cell lines.Conclusions MCC has distinctive clinical and pathological appearance.Immunohistochemistry and detection of MCPyV DNA sequences using PCR may be beneficial to the definitive diagnosis of MCC.

Carcinoma de células de Merkel em extremidade inferior / Merkel cell carcinoma in lower end

Merkel Cells Carcinoma is a rare cutaneous neoplasia. Studies revealed an increase in the occurrence from 0.15 to 0.44 cases for every 100.000 inhabitants between 1986 and 2001. Around 50% of the patients, eventually, develop systemic disease, being the most common sites the liver, the bones and the brain. The etiology is still unknown. The present study presents a new case of Merkel cells carcinoma in extremity, treated with local resection and adjuvant radiotherapy.

Carcinoma de células de Merkel: reporte de caso / Merkel cell carcinoma: a case report

El carcinoma de células de Merkel es un tumor cutáneo inusual de características agresivas, clasificado dentro de los carcinomas neuroendocrinos; clínicamente polimorfos y su forma histológica es muy similar a otros tumores cutáneos, lo que dificulta su diagnóstico precoz. Dada su baja incidencia, la etiopatogenia de este tumor, la reciente descripción de una asociación viral y su tratamiento, son todavía motivo de investigación; por esta razón es importante conocer su fisiopatología y sus manifestaciones clínicas para hacer un diagnóstico claro, en estadios tempranos, y un tratamiento de acuerdo con la condición del paciente. Se describe el caso de un paciente inmunosuprimido con un carcinoma de células de Merkel en cara y cuero cabelludo, recidivante y metastásico, con un comportamiento conforme a lo descrito en la literatura.

Merkel cell carcinoma is an unusual cutaneous neoplasm of aggressive characteristics, classified within neuroendocrine carcinomas; clinically polymorphic and histologically similar to other skin tumors making it difficult for early diagnosis. Given its low incidence; the pathogenesis of this tumor, the recent description of a viral association and its treatment, are still matter of research; for this reason it is important to know its pathophysiology and clinical manifestations in order to perform a clear diagnostic approach in early stages, and treatment in accordance with the patient's condition. We describe the case of an inmunosupressed patient with a Merkel cell carcinoma on face and scalp, recurrent and metastatic, with an evolution consistent to reports in the literature.

A importância da linfocintilografia no tratamento do carcinoma de células de Merkel / The role of lymphoscintigraphy in the treatment of Merkel´s cells carcinoma

O carcinoma de Células de Merkel constitui neoplasia cutânea maligna, rara e grave, de origem neuroendócrina, com comprometimento linfonodal em metade dos pacientes e metástases disseminadas em 20 por cento quando do diagnóstico anatomopatológico. Seu tratamento não está completamente estabelecido, entretanto a pesquisa do linfonodo sentinela vem sendo considerada indispensável e pode trazer benefícios na condução terapêutica dos pacientes.

The Merkel cell carcinoma is a rare, serious, neuroendocrine, malignant skin cancer with lymph node involvement in half of patients and disseminated metastases in 20 percent of cases at the time of pathological diagnosis. Its treatment is not fully established, though the sentinel lymph node has been considered essential and may bring benefits to the therapeutic armamentarium of patients.

Carcinoma das células de merkel: relato de 2 casos / Merkel cell carcinoma: two cases report

Introdução: O carcinoma das células de Merkel (CCM) corresponde a uma forma incomum e agressiva de neoplasia maligna cutânea. Normalmente acomete pacientes acima de 60 anos em áreas cronicamente expostas ao sol. As células de Merkel se localizam na camada basal da epiderme, estão associadas aos mecanorreceptores locais e têm função neuroendócrina pouco compreendida. Integram o sistema neuroendócrino-imuno-cutâneo (N.I.C.S.). Com o uso de novos marcadores imunohistoquímicos, houve aumento no número de casos relatados. No entanto, a baixa incidência desta neoplasia dificulta a realização de estudos com maior nível de evidência científica. O tratamento do CCM envolve cirurgia, radioterapia e quimioterapia, persistindo na literatura discussões a respeito da abordagem mais efetiva. O prognóstico não é bom, sendo observados elevados índices de recidivas locais e metástases, linfonodais e à distância. Objetivo: Este trabalho tem como objetivo o relato de dois casos de CCM tratados em nosso serviço, bem como a revisão da literatura. Relato dos casos: Em ambos os casos, o CCM não foi a suspeita clínica inicial, sendo confirmado após biópsia incisional, que demonstrou neoplasia neuroendócrina. Em relação ao primeiro caso, com lesão na região anterior do tronco, foi realizado tratamento cirúrgico e indicada radioterapia complementar, a qual não foi realizada por óbito do paciente, 4 semanas após a cirurgia, por causas não relacionadas. No segundo caso, de localização pré-auricular, houve perda do seguimento ambulatorial após diagnóstico.

Introduction: Merkel cell carcinoma (MCC) is an uncommon and aggressive cutaneous malignant tumor. It usually occurs in patients above the seventh decade of life, in chronically sun-exposed areas. Merkel cells are located in the basal layer of epidermis, are associated with the local mechanoreceptors, and have neuroendocrine function poorly understood. They integrate the neuroendocrine-imune-cutaneous system (N.I.C.S.). With new imunohistochemistry markers, there was an increase in the number of the cases reported. Nevertheless, the low incidence of this tumor difficult realization of studies with higher scientific level. The treatment of MCC comprehends surgery, radiotherapy and chemotherapy, remaining in the literature discussion about the better treatment. The prognostic isn’t good, being observed high levels of local recidives and metastatic disease, in linfonodes and distant sites. Objective: This paper has the objective of two case reports of MCC treated in our institution, including the literature review. Case reports: In both cases, the MCC wasn’t the first clinical suspect, based on their appearance, being confirmed after incisional biopsy, which demonstraded neuroendocrine tumor. In the first case, the lesion was located in the anterior chest, the surgical treatment has been done and the radiotherapy was indicated; this treatment has not been done because the patient died four weeks after the surgery, for no related causes. In the second, the lesion was in the pre auricular location, the patient did not return to consult after the diagnosis.