Merkel cell carcinoma (neuroendocrine carcinoma of the skin): a lecture with a brief overview of 19 cases and demonstration of two clinical observations

Abstract

The lecture deals with epidemiology, clinical morphological and genetic characteristics of a rare aggressive neuroendocrine carcinoma of the skin, or Merkel cell carcinoma (MC). We describe the algorithms for the differential diagnosis of these tumors and their treatment approaches, and focus on the main unresolved issues, such as delayed and erroneous diagnosis, the search for new diagnostic markers and targets for the development of more effective treatment methods. We provide a brief clinical and morphological analysis of 19 own observations of MC in 10 men and 9 women aged 40 to 85 years (57.9% of the patients were above 60 years, 31.6% from 50 to 60 years, and 10.5%, below 50 years). In 42.1% of the cases, the tumors were located in the head, in 15.8% in the limbs, and in 15.8% in the trunk and soft tissues; in the rest of the cases the primary tumor location was not identified. Only in 4 cases MC was diagnosed immediately; in all other cases, the initial diagnoses had been wrong. The diagnosis of MC was established after the analysis of medical files, histological and immunohistochemical biopsy studies and was confirmed by immunohistochemistry. All the tumors were expressing synaptophysin, chromogranin A, CD56; in all cases except one, cytokeratin 20 of the dote-like type, type 2A somatostatin receptors in 66.7%, nuclear survivin in 100%, p53 in 88.9%, CD117 in 57.1%. To illustrate the topic, we present 2 clinical observations of MC. The first case was an 82-year old man who had been living for a long time in the territory with increased sun radiation. A bright red tumor developed on his left upper eyelid, becoming gigantic (5 cm in diameter) within 2 months and bleeding. Despite the radical excision of the tumor, at 2 months after the surgery he developed local recurrence and metastases in regional lymph nodes. Thereafter, he underwent the orbital exenteration and lymphodissection of the affected lymph nodes. The second observation was a 63-year old man. At 10 years after he had had his renal transplant, he developed a mixed skin tumor on the anterior neck surface. The tumor was represented by MC and porocarcinoma with signs of squamous and sebaceous differentiation. These observations demonstrate MC rapid growth, its aggressive potential and such risk factors as prolonged high insolation and long-term drug immunosuppression after organ transplantation.Conclusion: At present, the rarity and low understanding of MC, its rapid growth, late diagnosis, aggressive biological potential and the lack of uniform treatment standards do not allow for cure in most such patients. The solution to the problem lies in the search for the cellular targets that would allow for the development of new effective targeted treatments for these aggressive tumors. In addition, integration of any results obtained in multicenter studies of the disease is essential.