Merkel cell carcinoma: an updated overview of clinico-pathological aspects, molecular genetics and therapy

TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions

“…MCC is a rare cutaneous malignant tumor with neuroendocrine differentiation, increasing incidence, high risk of recurrence, and aggressive behavior [ 1 , 2 , 3 , 29 , 30 ]. Patients with localized MCC are treated with surgery followed by adjuvant radiotherapy and, usually, show low rates of tumor relapse and mortality [ 12 , 31 ].…”

“…TRK expression is not involved in MCC carcinogenesis and tumor progression since it was not associated with prognostic and clinicopathological features, except for the nuclear localization of the receptor in MCPyV-negative tumors. MCPyV-negative cases belong to the group of MCC with the greatest amount of molecular alteration [ 2 , 3 ]; indeed, MCPyV-negative MCC has been associated to the UV radiation mutational signature, namely, a predominance of cytosine to thymidine transition at DNA dipyrimidine sites, and to a tumor mutational burden 25–90-fold higher than the MCPyV-positive counterpart [ 2 , 42 , 43 , 44 ]; thus, the nuclear TRK expression observed in some MCC cases may be due to an aberrant protein product of mutated NTRK genes. Another possible explanation could be that TRK is wild-type and the incorrect localization depends on alterations in other pathways that cause the internalization and nuclear migration of the receptor.…”

“…Merkel cell carcinoma (MCC) is a rare primary malignant tumor of the skin with neuroendocrine differentiation [ 1 , 2 , 3 ]. The reported incidence of MCC has increased in recent years and varies across the world, ranging from 0.3 to 1.6 per 100,000 people per year depending on the distribution of the two etiologic factors, namely, ultra-violet (UV) radiation exposure and Merkel cell polyomavirus (MCPyV) infection [ 4 , 5 , 6 , 7 ].…”

“…MCC is usually diagnosed in the seventh decade of age in advanced stage of disease and features a highly aggressive and rapid course with an overall 5-year survival rate of about 40% in some series [ 4 , 7 , 8 , 9 ]. MCPyV-negative MCC is associated with a higher number of molecular alterations and a worse prognosis than its MCPyV-positive counterpart [ 3 ]. MCC systemic treatment was based on platinum agents and etoposide chemotherapy until recently, when the paradigm shifted to immune checkpoint inhibitors that were demonstrated to be much more effective in attaining a durable response in many cases [ 1 , 8 , 10 , 11 , 12 ]; however, approximatively half the patients were unresponsive, thus underscoring a critical need to find novel treatments [ 1 ].…”

Das periokuläre Merkel-Zell-Karzinom – eine Übersicht klinischer Aspekte und aktueller Therapieoptionen

“…Especially when located in the eye, MCC can be mistaken for a hordeolum or chalazion 13 . Accordingly, when faced with a rapidly expanding, painless, nodular or plaque-like tumor, it is important to always include malignant processes among the differential diagnoses; in such cases, MCC should also be considered 1 , 5 . Although the eyelids are the site of predilection for periocular MCC, there have been case reports of MCC occurring on the conjunctiva, in the area of the lacrimal gland, and as distant metastases in the iris and orbit 9 .…”