Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options

Abstract

Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation.Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.

Merkel Cell Carcinoma Display PIEZO2 Immunoreactivity

“…The common ectodermal origin of both neuroendocrine and epidermal lineages might explain that mixed phenotype. Here, we demonstrate that, similarly to MCs, MCC display PIEZO2 immunoreactivity, with a similar dot-like pattern presented by other antigens such as intermediate filaments, typical of neuroendocrine malignancies [ 10 , 31 ]. The expression of this MCs essential protein is another of the many features shared by MCs and MCC cells.…”

“…In any case, although in the presented MCC cases there is no evidence of a prognostic value of PIEZO2, MCC could benefit from a possible PIEZO related therapy, as long as both types of PIEZO channels are known to be inhibited by the toxin GsMTx4 and stimulated by Yoda1 [ 34 ]. Other promising therapies are in study or already in use, such as PD-1/PDL-1 pathway blocking agents, multi-targeted tyrosine kinase inhibitors, MCPyV-related immunotherapy and AURKA inhibitors, potentially useful in MCPyV-negative MCC, among others [ 9 , 10 , 35 , 36 ].…”

“…In any case, most evidences lend support to an origin from MC [ 8 ]. The etiology for MCC is currently divided between Merkel cell polyomavirus (MCPyV) and solar exposure with UV-induced mutations [ 9 , 10 ].…”

Cytology coupled with immunocytochemistry identifies Merkel cell carcinoma: A rare intruder in the cerebrospinal fluid

“…Merkel cell carcinoma is an uncommon aggressive skin tumour that is known for its recurrence and metastasis 15 . Patients with metastatic MCC are treated with systemic therapy, radiation therapy, surgery or multimodality therapy with a combination of the above.…”

Therapeutic targets for vaccination in polyomavirus‐driven Merkel cell carcinoma

“…As the authors discuss, although immune checkpoint inhibitors have shown notable efficacy in advanced-stage MCC, approximately half of patients fail to respond or develop treatment refractory disease. 1,2 Based on these properties of MCC and the need for greater efficacy with therapy, vaccination for polyomavirus-driven MCC is an additional emerging treatment option that must be discussed. Vaccination in MCC is based on the rationale that MCPyV-encoded oncoproteins are amenable to vaccine construction and that MCPyV viral antigens are inherently immunogenic (Table 1).…”