Combined Merkel cell carcinoma and cutaneous squamous cell carcinoma with lymph node metastases: Report of two cases

Abstract

Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.combined Merkel cell carcinoma, combined Merkel cell carcinoma and squamous cell carcinoma, Merkel cell carcinoma, Merkel cell polyomavirus, nodal metastasis, squamous cell carcinoma | INTRODUCTIONMerkel cell carcinoma (MCC), also known as primary cutaneous neuroendocrine tumor, is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and patients with a history of immunosuppression. [1][2][3][4][5][6] Although the histogenesis of MCC has been the object of considerable debate since its original description, and the cell of origin is still unknown, two distinct subtypes of MCC have now been proposed based on their pathogenesis: one that is related to the Merkel cell polyomavirus (MCPyV), that represents the majority of all cases (with variable percentages, estimated at 80% based on some studies), hypothesized to be of possible dermal (fibroblastic) origin, and another one unrelated to MCPyV infection, that appears to be caused by UV radiation, considered to be of probable epidermal origin (keratinocytic). 1,2,[7][8][9] Because a significant subset of MCC is closely related to UV radiation, it is not unusual for this tumor to be found in close association (as a collision tumor) to other UV-related neoplasms, and this has been reported in the literature with variable frequency. On the other hand, combined MCC tumors (MCC that differentiating into other neoplasms, sharing a

Detection of Merkel Cell Polyomavirus (MCPyV) DNA and Transcripts in Merkel Cell Carcinoma (MCC)

“…Another explanation for the discrepancy between the viral genome state in the primary tumor and the metastatic lymph node could be the presence of combined MCC, which occurs in 5–20% of all MCC cases [ 30 , 31 ]. Combined MCC with SCC in lymph node metastasis has been described [ 32 , 33 , 34 ]. Further studies are required to support this hypothesis.…”

Combined Merkel Cell Carcinoma and Squamous Cell Carcinoma: A Systematic Review

“…Although combined SCC and MCC are considered to be relatively rare [2,9,29,30], the association of in situ (and/or invasive) SCC and MCC in close proximity has been observed in as many as 38% of cases in some MCPyV-negative MCC series [3,29,31,32]. These tumors have generally been depicted as collision tumors, and it remains a matter of debate whether one component derives from the other or they rather represent a casual association of two tumors that share UV radiation as a common etiological agent (Figure 2) [2,3].…”

“…These tumors have generally been depicted as collision tumors, and it remains a matter of debate whether one component derives from the other or they rather represent a casual association of two tumors that share UV radiation as a common etiological agent (Figure 2) [2,3]. The vast majority of collision tumors reported to date were MCPyV-negative [2,3,19,30], with only a few exceptional MCPyV-positive cases [24,30,33]. On the other hand, a few case series and reports have studied the much rarer divergent MCC, also known as MCC, with aberrant differentiation [9,30,[34][35][36][37].…”

“…The vast majority of collision tumors reported to date were MCPyV-negative [2,3,19,30], with only a few exceptional MCPyV-positive cases [24,30,33]. On the other hand, a few case series and reports have studied the much rarer divergent MCC, also known as MCC, with aberrant differentiation [9,30,[34][35][36][37]. These tumors display areas of abrupt transition to SCC within the MCC tumor, and both elements appear morphologically intermingled, with the merging of the neuroendocrine cells into squamous differentiation (Figures 3 and 4).…”

“…have also been reported [9]. Again, most of them are MCPyV-negative [2,9,19,30,35,36]. MCC with divergent differentiation has consensually been considered a single tumor with aberrant transformation into other lineages [2,9].…”