S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – update 2018

Abstract

Summary Merkel cell carcinoma (MCC, ICD‐O M8247 / 3) is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. The neoplastic cells share many morphological, immunohistochemical and ultrastructural characteristics with Merkel cells of the skin. The diagnosis of MCC is rarely made on clinical grounds. Histological and immunohistochemical studies are usually required to confirm the clinical suspicion. Given the frequent occurrence of occult lymph node metastasis, sentinel lymph node biopsy should be performed once distant metastasis has been ruled out by cross‐sectional imaging. Primary tumors without evidence of organ metastases are treated with complete surgical excision with appropriate surgical margins. Radiation therapy should be considered at all stages of the disease. For advanced MCC that is no longer amenable to curative treatment by surgery or radiation therapy, there is currently no established systemic therapy for which an improvement in recurrence‐free survival or overall survival has been demonstrated in a prospective randomized trial. However, immunotherapy using PD‐1/PD‐L1 blockade seems to be superior to chemotherapy. Various factors warrant that further diagnostic and therapeutic interventions be determined by an interdisciplinary tumor board. These factors include the tumor's aggressiveness, the frequent indication for sentinel lymph node biopsy along with the frequent occurrence in the head and neck region, the potential indication for adjuvant radiation therapy as well as the complexity of the required diagnostic workup.

Merkel Cell Carcinoma Treatment in Finland in 1986–2016—A Real-World Data Study

“…In 2016, two separate studies proved the efficacy of immunotherapy in metastatic MCC with two molecules, avelumab and pembrolizumab [19,20]. Targeting the PD-L1/PD-1 pathway has revolutionized MCC treatment and survival and bypassed the use of cytotoxic agents in the advanced stages of MCC [17,45]. The role of RT in treatment of metastatic MCC is also undergoing a revolution.…”

Patched 1 expression in Merkel cell carcinoma

“…Indeed, involvement of the sentinel node is a negative prognostic marker associated with a poor prognosis, namely a 5-year survival rate of only 42-52%. 1,2 Major risk factors for MCC are ultraviolet exposure, old age and immune suppression, suggesting a possible viral carcinogenesis which was confirmed in 2008. 3 Notably, Merkel cell polyomavirus (MCPyV) is clonally integrated into approximately 80% of MCC in patients of the Northern Hemisphere.…”

Expression of Lefty predicts Merkel cell carcinoma‐specific death

“…MCC was initially diagnosed by two experienced dermato-histopathologists according to standard histopathological and immunohistochemical criteria. 1 Complete clinical work-up, staging, follow-up and treatment were performed according to current national guidelines. 1 Clinical data were collected both by chart review and by contacting patients, relatives, general practitioners and dermatologists.…”

“…1 Complete clinical work-up, staging, follow-up and treatment were performed according to current national guidelines. 1 Clinical data were collected both by chart review and by contacting patients, relatives, general practitioners and dermatologists. The study was approved by the ethics review board of the Ruhr-University Bochum (#4749-13) and conducted according to the Declaration of Helsinki principles.…”

“…Interestingly, like other cancer entities, MCC shows a left-sided lateral distribution as recently shown by us and other researchers. [1][2][3][4][5] Two transforming growth factor b (TGFb)-related secreted proteins, Nodal and Lefty, are asymmetrically expressed and play central roles in establishing left/right asymmetry during early embryonic development. Specifically, Nodal expression is restricted to the left side of the lateral-plate mesoderm of which the dermis and subcutaneous layer are derivates.…”