A case of combined Merkel cell carcinoma and squamous cell carcinoma: Molecular insights and diagnostic pitfalls

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine cutaneous tumor with a high mortality rate.1 Evidence supports 2 molecular subclasses of MCC: virus-positive MCC associated with oncogenic Merkel cell polyomavirus (MCPyV), and virus-negative MCC (VN-MCC) associated with UV signature mutations.1, 2, 3 Typically, MCC presents as a pink papule or nodule on sun-exposed skin of white, elderly individuals.1 MCC most frequently presents in the head and neck area, followed by the upper extremities.1 MCC commonly metastasizes to regional lymph nodes and skin, with potential for distant metastases to skin, lung, liver, central nervous system, and bone.3 Patients may have a high burden of satellite and in-transit cutaneous metastases, which may be histologically identical to primary MCC tumors.1, 3 In approximately 1% to 2% of patients with MCC, a second MCC tumor will arise that is clinically compatible with a new primary MCC.1, 4 In such cases, molecular analyses may be useful in distinguishing a second primary MCC tumor from a distant cutaneous metastasis.4, 5, 6, 7, 8 Some MCC tumors have concurrent squamous cell carcinoma (SCC), either in situ or invasive, which has been proposed to favor primary MCC over a cutaneous metastasis.1 Concurrent SCC/MCC is a distinct phenomenon from MCC “mixed tumors” with intratumoral squamous differentiation (multiple foci of squamous differentiation dispersed throughout the tumor, rather than a discrete squamous lesion).1 MCC associated with SCC is usually MCPyV-negative, with rare exceptions.9 Although both SCC and MCC may arise in association with photodamage, it is unknown if concurrent SCC/MCC represent biologically related neoplasms. We present a case of an elderly man found to have MCC of the left forehead. A second focus of MCC was subsequently identified on the left zygoma, in association with a previously diagnosed invasive SCC. Single nucleotide polymorphism (SNP) array analysis confirmed clonal relationship between the foci of MCC, supporting a metastatic process, and demonstrated the SCC to be unrelated. Our findings suggest that concurrent SCC and MCC can represent unrelated collision tumors. Our case also indicates that nonmelanoma skin cancers (NMSCs) in the lymphatic draining area of MCC tumors should be scrutinized for potential involvement by MCC.