Plasticity of neuropeptidergic neoplasm cells in the primary and metastatic Merkel cell carcinoma

Abstract

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous carcinoma with characteristics of neuroendocrine tumor. We performed immunohistochemical analysis to demonstrate the presence of various neuropeptides within cells of MCC resected from a 75-year old woman. The cells of primary tumor of cheek were compared with the cells of regional right submandibular metastatic tumor which was found eight months later. A double-staining IHC for the pan-neuronal marker, PGP 9.5, and selected neuropeptides in the tissue material obtained from both locations was performed. Single multipolar cells in the main mass of primary tumor stained positively for PGP 9.5 and such neuropeptides as GAL, VIP, PACAP, NPY and CGRP. Moreover, we demonstrated for the first time the presence of neuropeptides in metastatic MCC cells. In the metastatic tumor, cells showing the co-localization of PGP-9.5 and neuropeptides were more numerous, mostly of oval shape, and significantly smaller than in the primary tumor. Thus, the progression of MCC may be associated with the acquisition by its cells of new morphological and biological features.

Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review

“…Hence, these “trabecular carcinomas” were suggested to derive from MCs, leading to their reclassification as MCC (29). Further immunohistochemical studies corroborated these initial findings by revealing a shared expression of many common markers in MCs and MCC (10, 30) but only a limited number of markers distinguishing them from each other (Table 1; Figures 1, 2). Indeed, both MCs and MCC express cytokeratin 20 (CK20) (13, 15, 31), neuroendocrine markers chromogranin A and synaptophysin (11, 37) and neuropeptides (30, 47).…”

“…Further immunohistochemical studies corroborated these initial findings by revealing a shared expression of many common markers in MCs and MCC (10, 30) but only a limited number of markers distinguishing them from each other (Table 1; Figures 1, 2). Indeed, both MCs and MCC express cytokeratin 20 (CK20) (13, 15, 31), neuroendocrine markers chromogranin A and synaptophysin (11, 37) and neuropeptides (30, 47). In contrast, the expression of vasoactive intestinal peptide and metenkephalin (44) are specific to MCs, whereas CD117 and CD171 are detected in only MCC cells (49, 61).…”

Merkel cell carcinoma: is this a true carcinoma?

“…The presence of chromogranin A, a neuropeptide precursor, as well as numerous neuropeptides themselves has been confirmed both in primary and metastatic MCC cells (11)(12)(13)(14) supporting the hypothesis of true Merkel cell origin of MCC. However, the expression of chromogranin A, although common, is almost exclusively focal and highly variable ranging from 5% to 80% of positive cells compared with the whole tumor's cellularity (12).…”

“…According to Godlewski et al., only single cells in primary MCC stain positively for neuroendocrine marker PGP 9.5 and such neuropeptides as GAL, VIP, PACAP, NPY and CGRP, while a high percentage of neuropeptide‐positive cells is linked with MCC metastases. Expression of PGP 9.5, initially regarded as a specific marker for neural and neuroendocrine cell, has recently been shown in a subset of non‐human and human lymphomas .…”

MicroRNAs as Potential Biomarkers in Merkel Cell Carcinoma

“…The exact origin of Merkel cells remains controversial. It has been suggest that these cells originate from one of the neurocrest derivatives [ 39 , 40 , 41 ], keratinocytes, epidermal fibroblasts, early B cells or hair follicle stem cells [ 42 , 43 , 44 , 45 ].…”