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.

A case of Merkel cell carcinoma of the head and neck

Merkel cell carcinoma (MCC) is a relatively rare and aggressive cutaneous neuroendocrine malignancy. It is characterized by high rates of recurrence and metastasis, both to regional lymph nodes and to distant locations. Its characteristic clinical manifestation is a single, painless, hard, erythematous nodule on a sun-exposed area, particularly in older men. Surgical management of both the primary site and the sentinel lymph node is the standard of care. In this article, we describe the diagnosis and treatment of a case of MCC in the left cheek.

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.

Carcinoma cutáneo de células de Merkel, a propósito de un caso y revisión de la literatura / Cutaneous carcinoma of merkel cells, purpose of a case and review of literature

El carcinoma de células de Merkel o también llamado carcinoma neuroendocrino cutáneo es una neoplasia muy rara y agresiva. Se caracteriza por su tendencia a la recurrencia, diseminación ganglionar y metástasis a gran distancia. Se presenta el caso de un paciente masculino de 88 años de edad, con antecedente de carcinoma baso celular en región dorsal, que presenta hace 3 meses una tumoración cutánea en tobillo derecho de gran tamaño, que produce metástasis ganglionar a distancia, el estudio de inmunohistoquímica revela que se trata de un carcinoma neuroendocrino cutáneo, se realiza excéresis del mismo con bordes histológicos negativos, pero a los pocos meses recidiva por lo que se realiza cirugía más profunda y se acompaña de quimioterapia. Se pone énfasis en lo agresivo y tendencia a la recidiva de esta rara enfermedad que podría pasar desapercibida en centros de menor complejidad.

The Merkel cell carcinoma, also known as cutaneous neuroendocrine carcinoma, is a very rare and aggressive neoplasm. It is characterized by its tendency to recurrence, lymph node dissemination and distant metastasis. We present the case of a 88-year-old male patient with a history of basal cell carcinoma in the dorsal region, who presented a large right cutaneous tumor in the right ankle 3 months ago, which produces distant lymph node metastasis. The immunohistochemical study reveals that it is a cutaneous neuroendocrine carcinoma, exeresis is performed with negative histological edges, but after a few months it relapses, so a deeper surgery is performed and it is accompanied by chemotherapy. Emphasis is placed on the aggressiveness and tendency to recurrence of this rare disease that could go unnoticed in centers of less complexity.

Merkel cell carcinoma in the community setting: a case report

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin initially believed to arise from the Merkel cells. In the community setting a general radiation oncologist may only encounter this pathology in a handful of cases over the course of their career. Due to the low incidence of this malignancy, few prospective randomized controlled trials have ever been conducted and therefore guidelines are based on relatively lower levels of evidence upon which the clinical recommendations are made. We discuss the case of a female in her 90s presenting with a classic MCC primary lesion, as well as satellite lesions proximal to both the primary and the draining regional lymph nodes with no evidence of nodal involvement. Here we discuss the presentation, management, treatment planning, underlying pathology, results and sequelae of treatment. We also review new treatment modalities, and the most current staging systems and guidelines.

Development of a new haptic perception instrument: a pilot study / Desenvolvimento de um novo instrumento de avaliação da percepção háptica: um estudo piloto

ABSTRACT Objective Hand sensory tests do not consider distinct physiological receptors, nor detect normal range variations concerning developmental or pathological changes. We developed an instrument with a set of tests with timing and scoring for assessing haptic perception, which is the interaction between sensory and motor systems, in surfaces exploration, by moving hands. Method Firstly, group meetings were set for test/manual conception and materials testing. The test/manual were submitted to 30 reviewers in 3 stages (10 reviewers on each stage). Results The Hand Haptic Perception Instrument (HHPI) evaluates hand sensorimotor performance on six domains: depression, elevation, texture, compressibility, weight (barognosis) and form perception. Each domain requires specific materials. Score ranges from 0 to 57, being 0 the worst rating. Conclusion This methodological process allowed the development of six domains and instructions to assess haptic perception. This version of HHPI is a pilot model. Further studies will determine reliability and normality ranges.

RESUMO Objetivo Testes de sensibilidade manual não consideram receptores fisiológicos distintos, tampouco variações do desenvolvimento normal ou patológico. Desenvolvemos um instrumento, com pontuação e tempo de desempenho, para avaliar percepção háptica, que é a interação sensório-motora na exploração de superfícies, pelo movimento das mãos. Método Reuniões de grupo foram estabelecidas para desenvolver os testes/ manual e testar materiais. O instrumento e seu manual foram submetidos a 30 revisores, em 3 estágios (com 10 revisores em cada estágio). Resultados O instrumento de avaliação da percepção háptica manual (IAPHM) avalia o desempenho sensório-motor da mão em seis domínios: depressão, elevação, textura, compressibilidade, peso (barognosia) e percepção de forma. Cada domínio requer materiais específicos. A pontuação vai de 0 a 57, sendo 0 a pior pontuação. Conclusão Esse método permitiu o desenvolvimento do instrumento para avaliar percepção háptica. Essa versão do IAPHM é um modelo piloto. Estudos futuros determinarão confiabilidade e variações de normalidade.

Carcinoma de Merkel (carcinoma neuroendocrino) / Merkel cell carcinoma (neuroendocrine carcinoma)

Desde que el carcinoma de Merkel fue descrito por primera vez, hace poco más de cuatro décadas por Cyril Toker en el año de 1972; ha despertado el interés de los colegas médicos. Factores de esta patología como: su célula de origen, etiología, evolución y tratamiento al día de hoy se mantienen en discusión y se modifican con el paso del tiempo. El advenimiento de la microscopía electrónica y la inmunohistoquímica han colaborado en la definición etiológica de esta neoplasia y otros descubrimientos como el del poliomavirus de células de Merkel, han brindado información importante sobre la génesis de este proceso. El tratamiento del carcinoma de células de Merkel sigue sufriendo leves variaciones con el paso del tiempo y se mantiene en discusión a la fecha. Presentamos el caso de una paciente con un carcinoma de células de Merkel con revisión de la literatura actual.

Since Merkel carcinoma was first described more than four decades ago by Cyril Toker little in the year 1972; has attracted interest from medical colleagues. Factors of this disease as their cell of origin, etiology, course and treatment today remain under discussion and change over time. The advent of electron microscopy and immunohistochemistry have collaborated in the etiological definition of this neoplasm and other discoveries such as the Merkel cell polyomavirus, have provided important information on the genesis of this process. The treatment of Merkel cell carcinoma is still suffering slight variations over time and remains in discussion to date. We report a patient with Merkel cell carcinoma with review of the current literature.

Reconstruction with Anterolateral Thigh Perforator Free Flap in Patients with Merkel Cell Carcinoma: Report of Two Cases

PURPOSE: Merkel cell carcinoma, also called neuroendocrine carcinoma, is a very rare type of skin cancer that develops as Merkel cells grow out of control. Merkel cell carcinoma is reported below 1% of whole skin neoplasms in the United States and is known that the 2-year survival rate is about 50~70%. The principles of treatment are wide excision of primary lesion with radiotherapy and/or chemotherapy that decrease the local recurrent rate. There has been no report of reconstruction with free flap after resection of Merkel cell carcinoma in Korea. METHODS: We reconstructed the skin and soft tissue defect after wide excision of Merkel cell carcinoma with anterolateral thigh perforator free flap in two cases. No distant metastasis was found at the preoperative imaging work-up. In one case, preoperative chemotherapy was performed and the size of lesion was decreased. RESULTS: There were no recurrence and significant complications. Functionally and aesthetically satisfactory results were obtained with reconstruction. CONCLUSION: Wide excision and reconstruction with anterolateral thigh perforator free flap for Merkel cell carcinoma patient is the first report in Korea. We regard this method as the treatment of choice in Merkel cell carcinoma.

Tumor de células de merkel: revisión de la literatura / Merkel cell tumor: review of literature

El carcinoma de Merkel es un carcinoma primario cutáneo infrecuente. Es una enfermedad potencialmente fatal, con escasa sobrevida en los casos avanzados. Recientemente Feng y col. (2008) identificaron ADN de un nuevo poliomavirus clonalmente integrado en varios casos de carcinoma de Merkel. Esto apoya la posibilidad que dicho virus se encuentre implicado al menos en algunos casos de esta patología. El carcinoma de Merkel carece de características clínicas distintivas, aunque un dato significativo es su rápido crecimiento. Afecta principalmente áreas fotoexpuestas (la mitad de los tumores se localizan en cabeza y cuello) de pacientes añosos. La gran mayoría de ellos se presentan con enfermedad localizada hasta un 30% tiene compromiso de ganglios linfáticos regionales. A pesar de la resección local, las metástasis linfáticas regionales y a distancia son frecuentes y generalmente ocurren en los primeros 2 años del diagnóstico. El tratamiento óptimo aún es incierto, pero los mejores resultados se alcanzan con un manejo interdisciplinario.

Expression of Low Molecular Weight Keratin (K8/18) in Fetal Skin Development / 대한피부과학회지

BACKGROUND: The epidermis and adnexal epithelium might express different types of keratin (K) during fetal development. OBJECTIVE: The objective is to observe the distribution of K8/18 in the skin of fetuses and to find out the distinction of expressions of K8/18 during fetal development. METHODS: Immunohistochemical analysis was applied to the skin of the scalp and sole of 42 fetuses ranging from 10 to 39 weeks of gestation. Immunohistochemical staining with monoclonal antibodies with CAM5.2 using LSAB kit against K8/18 was conducted. RESULTS: In the skin of the scalp, K8/18 was expressed in the periderm and basal layer of epidermis from the 10th week to the 31st week of fetal gestation. K8/18 was expressed in the hair germ, bulge and basal cells of fetal the infundibulum and sebaceous glands. Root sheath cells were weakly positive but matrix cells were negative. The expression of K8/18 was negative in the basal layer of the sole. Merkel cells, which are located in the basal layer and upper dermis, were positive from the 12th week of gestation. Terminal eccrine ducts and acinar cells were positive after the 20th week of gestation. CONCLUSION: K8/18 in the skin of the scalp and sole of fetuses were expressed in different ways. The expression of K8/18 in the basal cells of the sole were negative while basal cells of the epidermis of the scalp were positive transiently from the 12th to the 31st week of gestation. Early hair germ cells and bulge cells were expressed strongly in hair follicles. Terminal eccrine ducts and acini were expressed strongly in the eccrine gland. Merkel cells located in the basal layer and papillary dermis also express K8/18.

A Case of Merkel Cell Carcinoma in a Renal Transplant Patient / 대한이식학회지

Merkel cell carcinoma (MCC) is a rare, frequently lethal, primary neuroendocrine carcinoma of the skin. Histopathologically, it appears as a dermal nodule of small undifferentiated malignant cells. Historically, MCC was considered to be an eccrine carcinoma. Recognition of its neuroendocrine features later led to the hypothesis that it arose from Merkel cells in the skin, although recent evidences revisit the question of an epithelial origin. We recently experienced a Mercel cell carcinoma. So, we report a MCC case originated from skin in renal transplant patient who was administrated immunosuppressive agent.

Carcinoma de células de Merkel / Merkel cell carcinoma

El carcinoma de Células de Merkel es un tumor maligno primario cutáneo, poco frecuente, con tendencia a la recidiva local y a producir metástasis tanto ganglionares como sistémicas. El tratamiento de elección es la cirugía. La linfedenectomía estaría indicada cuando hay adenopatías regionales palpables; sin embargo, llevarla a cabo como intervención profiláctica es hoy un tema de controversia. El tumor es radiosensible y quimiosensible, sobre todo con esquemas de poliquimioterapia. El objetivo de esta comunicación es presentar dos pacientes con diagnóstico clínico, histopatológico e inmunohistoquímico de carcinoma de células de Merkel y la revisión de esta patología

Células de Merkel em crescimento com mau alinhamento da unha do primeiro pododáctilo / Merkel cells in growth malalignment of the great toe nail

Crescimento congênito com mau alinhamento da unha do primeiro pododáctilo (CGMAUPP)é uma das doenças ungueais congênitas mais comuns e cujas causas não são completamente conhecidas. A matriz ventral, que é rica em células de Merkel (CM) intraepiteliais, é responsável pelo crescimento e direcionamento da placa ungueal. Para esclarecer se as CMs da matriz ventral poderiam ser envolvidas, biópsias ungueais de 3 de casa 12 pacientes com CGMAUPP foram tratados com anticorpos Cam 5.2 contra queratina tipo simples. A densidade de CM na matriz ventral do CGMAUPP foi calculada como sendo 21,2 mais ou menos 9,3 mm2, o que não foi significativamente diferente da densidade da CM em pacientes com paroníquia que não apresentava CGMAUPP. Resumindo, a síndrome congênita CGMAUPP não pode ser explicada por uma alteração da CM paraecrinológica ativa na matriz ungueal ventral

The Nerve-dependency of Merkel Cell Proliferation in Cultured Human Fetal Glabrous Skin

Merkel cells are thought to function as slowly adapting mechanoreceptors and are known as targets for sensory nerves. However, the nerve-dependency of Merkel cells remains controversial. In this respect, some investigators have found interregional differences between hairy and glabrous skin and others have shown intraregional differences within denervated rat touch domes. Differences between species have also been reported. This study was performed to determine whether Merkel cells proliferate in vitro in the absence of the systemic factors, blood vessels and the intact nerves in human skin. Suspension organ culture was performed using fetal digits to investigate their in vitro proliferation. Merkel cells and cutaneous nerves were identified using antibodies to cytokeratin 20 and protein gene product 9.5 (PGP 9.5), respectively. Fetal digits of 56-82 day gestational age were cultured in serum free medium in a high O2 (45%) environment. Tissues were harvested before starting culture (D0) and 1,4,7,14, 28d after culture. Merkel cells were observed in the volar pads and dorsal nail matrices at D0. After 28d of suspension organ culture, digits looked healthy structurally and the number of Merkel cells had increased. However, PGP 9.5-immunoreactive nerves were markedly diminished after 1 day of culture and almost disappeared after 4 days. Merkel cell proliferation in vitro suggested that Merkel cell development is probably nerve-independent in human fetal glabrous skin.

Immunohistochemical Studies of bc1-2 Protein in a Skin Tumor of Neuroectodermal Origin / 대한피부과학회지

BACKGROUND: Protooncogene, bcl-2 is known to inhibit, apoptosis induced by various stimuli. Its expression has been reported in various fetal and adult tissues, and also in tumors of neural origin. OBJECTIVE: The purpose of this study was to evaluate the expression of bcl-2 in a skin tumor of neuroectodermal origin and to estimate whether this expression was useful in the different,ial diagnosis of tumors of neural origin or not. METHOD: Immunohistochemical stains by the LSAB(labelled streptavidin biotin) method for bcl-2 protein were performed in normal special nerve end-organs and a skin tumor of neural origin. RESULTS: The immunohistochemical findings revealed strong positive results in Meissners corpuscles, but weak week positive results in Vater-Pacini corpuscles. There were also strong positive results in neurilernmomas which were mostly composed of Schwann cells, but results were mostly negative in neurofibromas and neurofibrosarcomas which were composed primarily of endoneurial fibroblasts of mesodermal origin except a few cells of Schwann cell origin. Benign granular cell tumors arising from Schwann cells, and Merkel cell carcinoma known to arise from the Merkel cells of neural crest origin showed strong positive reactions. CONCLUSION: The strong expression of bcl-2 protein exclusively in the tumor of neuroectodermal origin suggests a useful indicator for the differential diagnosis of skin tumors of neural origin.

CAM 5.2 Positive Cells in the Epidermis of Nevus Sebaceus

BACKGROUND: In the course of the study of keratin expression in the epidermis of nevus sebaceus, several cells in the epidermis of nevus sebaceus were positively stained with CAM 5.2 antibody, which is known to be specific for the lower molecular weight cytokeratin and used as a marker of Merkel cell. OBJECTIVE: This study was intended to verify that CAM 5.2 positive cells found in the epidermis of nevus sebaceus are Merkel cells and to understand the meaning of CAM 5.2 positive j cells in the epidermis of nevus sebaceus. METHODS: The immunohistochemical stainings with CAM 5.2 and antibody to epithelial membrane antigen (EMA) performed on specimens of normal skin, epidermal nevus, nevus sebaceus and some appendage tumors. In order to confirm the nature of CAM 5.2 positive cells, the distribution of those were compared to that of Merkel cells and double labeling with CAM 5.2 and neurofilament was performed. RESULTS: CAM 5.2 positive cells were also found in trichilemmoma developed associated with nevus sebaceus and the epidermis of normal paimoplantar skin. CAM 5.2 positive cells were also stained with antibody to EMA on serial sections cut from the same tissue blocks. The association of CAM 5.2 positive cell and nerve fiber was also demonstrated. CONCLUSION: CAM 5.2 positive cells are seemed to be Merkel cells and their presence in the covering epidermis of nevus sebaceus suggests to the epidermis of nevus sebaceus may not be nevoid proliferation of epidermal keratinocytes.

CAM 5.2 Positive Cells in the Epidermis of Nevus Sebaceus

BACKGROUND: In the course of the study of keratin expression in the epidermis of nevus sebaceus, several cells in the epidermis of nevus sebaceus were positively stained with CAM 5.2 antibody, which is known to be specific for the lower molecular weight cytokeratin and used as a marker of Merkel cell. OBJECTIVE: This study was intended to verify that CAM 5.2 positive cells found in the epidermis of nevus sebaceus are Merkel cells and to understand the meaning of CAM 5.2 positive j cells in the epidermis of nevus sebaceus. METHODS: The immunohistochemical stainings with CAM 5.2 and antibody to epithelial membrane antigen (EMA) performed on specimens of normal skin, epidermal nevus, nevus sebaceus and some appendage tumors. In order to confirm the nature of CAM 5.2 positive cells, the distribution of those were compared to that of Merkel cells and double labeling with CAM 5.2 and neurofilament was performed. RESULTS: CAM 5.2 positive cells were also found in trichilemmoma developed associated with nevus sebaceus and the epidermis of normal paimoplantar skin. CAM 5.2 positive cells were also stained with antibody to EMA on serial sections cut from the same tissue blocks. The association of CAM 5.2 positive cell and nerve fiber was also demonstrated. CONCLUSION: CAM 5.2 positive cells are seemed to be Merkel cells and their presence in the covering epidermis of nevus sebaceus suggests to the epidermis of nevus sebaceus may not be nevoid proliferation of epidermal keratinocytes.