Merkel cell carcinoma: Critical review with guidelines for multidisciplinary management

Abstract

Merkel cell carcinoma (MCC) is a relatively rare cutaneous malignancy that occurs predominantly in the older white population. The incidence of MCC appears to have tripled during the past 20 years; an increase that is likely to continue because of the growing number of older Americans. The pathogenesis of MCC remains largely unknown. However, ultraviolet radiation and immunosuppression are likely to play a significant pathogenetic role. Many questions currently remain unanswered regarding the biologic behavior and optimal treatment of MCC. Large, prospective, randomized studies are not available and are unlikely to be performed because of the rarity of the disease. The objective of this review was to provide a comprehensive reference for MCC based on a critical evaluation of the current data. The authors investigated the importance of sentinel lymph node biopsy as a staging tool for MCC to assess the status of the regional lymph node basin and to determine the need for additional therapy to the lymph node basin. In an attempt to standardize prospective data collection with the intention to define prognostic indicators, the authors also present histopathologic profiles for primary MCC and sentinel lymph nodes. The controversies regarding the appropriate surgical approach to primary MCC, the use of adjuvant radiation therapy, and the effective- A n increasing number of patients presenting with Merkel cell carcinoma (MCC) during the past 2 decades has focused attention on this cutaneous malignancy, which is seen primarily in older individuals. Based on the projection that, by 2030, 1 in 5 Americans will be aged !65 years, the increasing trend in MCC incidence is likely to continue.1 Currently, information regarding the biologic behavior and optimal treatment of MCC is limited given the paucity of high-level evidence and the absence of prospective, randomized trials. The objective of this review was to create a current reference for those involved in the care of patients with MCC or the investigation of this potentially aggressive malignancy. This review was based on a critical evaluation of the available data using an extensive PubMed search combined with our experience in the University of Michigan Comprehensive Cancer Center Multidisciplinary MCC program. EpidemiologyThe incidence of MCC is low compared with the incidence of other cutaneous malignancies. However, the trend is toward an increasing

MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

“…[12][13][14][15] The incidence of Merkel cell carcinoma has increased, presumably due to an increasing elderly population. 4 Merkel cell carcinoma typically presents as a solitary, red to purple, firm, raised, painless nodule on the skin, ranging in size from 2-3 mm to several centimeters. 1,2,4 It typically occurs in the sun-exposed areas of elderly patients, especially on the head and neck location, followed by the extremities.…”

“…2,3 It is currently recommended that patients be screened for small cell carcinoma of the lung to exclude the possibility of cutaneous metastasis of small cell carcinoma once a diagnosis of cutaneous Merkel cell carcinoma is made, illustrating the importance of determining reliable pathological markers to distinguish these lesions. 4 Small cell carcinomas in general are now believed to originate from totipotential stem cells that can differentiate into various cell types that are native to the tissues, eg, TTF-1-positive stem cell for pulmonary small cell carcinoma. 3 This hypothesis may explain occasional cases of small cell carcinoma with other components such as squamous cell carcinoma 17 and adenocarcinoma, 18 the findings described in a variety of organs including skin and lung.…”

“…2,3 It is morphologically very similar to small cell carcinomas of the lung and other organs, 3 and its diagnosis requires confirmation by immunohistochemistry study, in conjunction with careful clinical and radiographic information, to rule out a metastatic small cell carcinoma, particularly from the lung. 4 Achaete-scute complex-like 1 (ASCL1), also called mammalian or human achaetescute complex homolog-1 (MASH1, HASH1), is a basic helix-loop-helix transcription factor crucial for neuroendocrine cell differentiation. MASH1 has been reported to be expressed in some neuroendocrine neoplasms, including small cell carcinoma of the lung.…”

Merkel Cells and Merkel Cell Carcinoma of Genitourinary System Tumor with Aggressive Behavior and Poor Prognosis

“…Mortality of the cancer is estimated to be between 33% and 46% [27,36] and the rate of mortality is higher than in patients with melanoma [27,37]. MCC is the second most common cause of death after melanoma [37,38]. Metastasis most commonly involved regional lymph nodes, followed by distant lung, skin, CNS, liver and bone [39].…”

Phosphorylation of Merkel Cell Polyomavirus Large Tumor Antigen at Serine 816 by ATM Kinase Induces Apoptosis in Host Cells

“…It is one of the most aggressive skin cancers, with an extremely high mortality rate of 33%, exceeding that of melanoma (5), and Ͻ45% 5-year survival rate (6). The incidence of MCC increased from 1.5 to 6/million people between 1986 and 2006, and ϳ1500 new cases of MCC are diagnosed each year in the United States (7,8). Epidemiological surveys of anti-MCV antibodies and sequencing analyses of healthy human skin have indicated that MCV may represent a natural component of the human skin microflora (9 -11).…”