Combined Merkel cell carcinoma with squamous cell carcinoma
Histopathology:
Predominantly solid diffuse and infiltrative pattern, comprising of both small cell and squamous component. Small cell shows high N:C ratio, round / oval / molded nuclei, finely salt and pepper chromatin pattern, indistinct nucleoli and scant cytoplasm. Squamous component shows nests of squamous cells with moderate degree of atypia and keratinization is seen. apoptosis and mitoses present.
Points of Pathoclinics:
- Combined cutaneous squamous and Merkel cell carcinoma (Merkel cell polyomavirus -) is distinct from primary neuroendocrine (Merkel) cell carcinoma (Merkel cell polyomavirus +) genetically and morphologically.
- Highly mutated genetic profile is seen in combined tumors than pure merkel cell carcinoma
- P53 is strong and diffuse positive in almost 100% squamous component and approximately 80% small cell component. It is associated with poor outcome.
- P63 is mostly positive in squamous component but less likely to be positive in small cell component
- CK20 is positive in 60 % of cases in both squamous and small cell component
- Mutation in NOTCH1 and ERBB4 genes are very high in combined tumors but not in pure merkel cell carcinoma
- Combined tumors show mutations in p53 and RB1 genes, which is consistent with a UV-related pathogenesis.
- The identification of P53+, RB1–, neurofilament– immunohistochemical profile along with highly mutated, p53 and RB1 mutated molecular profile with a high rate of C>T mutations are consistent with an UV light signature, which is common in combined tumor than pure Merkel cell carcinoma.
- Combined tumor has higher chances of metastasis to skin and lymph node. In present case smaller lesion may be considered as metastatic satellite lesion.
Reference: Pulitzer, M., Brannon, A., Berger, M. et al. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma. Mod Pathol 28, 1023–1032 (2015). https://doi.org/10.1038/modpathol.2015.60