Trisomy of chromosome 6 in Merkel cell carcinoma within lymph nodes

Abstract

Merkel cell carcinoma (MCC) of the skin is a neuroendocrine tumor with characteristic histological and immunohistochemical features. Among various cytogenetic changes, trisomy of chromosome 6 has been reported in 47% of cases using in situ hybridization. Primary tumors, morphologically and immunohistochemically identical to MCCs of the skin, have been described in other organs, including lymph nodes. Here, a cytogenetic study of four cases of MCC of lymph nodes is presented. Four cases of primary MCCs of lymph nodes and ten cases of cutaneous MCCs were studied for chromosome 6 using fluorescent in situ hybridization (FISH). All cases showed typical features of MCC both at hematoxylin and eosin (H&E) and immunohistochemistry. FISH showed trisomy 6 in two out of the four cases ofMCCs of lymph node as well as in 6 out 10 cases of MCCs of skin. Lymph nodal and cutaneous MCCs share same histological and immunohistochemical features, as well as same cytogenetic alteration for chromosome 6. It seems that there are more similarities than differences between cutaneous and lymph nodal MCCs. Whether lymph nodal MCCs are primary tumors or metastases from regressed skin lesions is still questionable, although several findings indicate a primary origin.

Extracutaneous Merkel cell carcinomas harbor polyomavirus DNA

“…Tumors sharing the same features have been reported in other sites such as lymph nodes [20,21], parotid gland [16,17], oral cavity [18], breast [14,15], and vagina [19]. Trisomy of chromosome 6, the most frequent cytogenetic alteration reported in 47% of cutaneous MCCs, has been also detected in 50% of nodal MCCs [21]. Whether extracutaneous MCCs are true primary tumors rather than metastases from regressed skin lesions is still a matter of debate [20,24].…”

“…Tumors identical to MCC of the skin in terms of histology, immunohistochemistry, and cytogenetics have been reported in several organs including breast [14,15], salivary glands [16,17], oral mucosa [18] and vaginal wall [19] as well as lymph nodes [20,21].…”

Aneuploidy in mitosis of PtK1 cells is generated by random loss and nondisjunction of individual chromosomes

“…Most cancer cells display a complex pattern of chromosomal abnormalities, showing both chromosome losses and gains, and concomitant structural aberrations (http://cgap.nci.nih.gov/Chromosomes/Mitelman). Interestingly, recurrent gains or losses of specific chromosomes or chromosome regions (Holloway et al, 1999;Streblow et al, 2007;Vasuri et al, 2008) are frequently observed in tumours, although Chromosome lagging at anaphase and migration of both sister chromatids to the same pole, i.e. nondisjunction, are two chromosome-segregation errors producing aneuploid cell progeny.…”

Atypical presentation of Merkel cell carcinoma positive to polyomavirus DNA detection: Experience from a single center

“…Although this latter hypothesis is generally not accepted because Merkel cells have never been identified in lymph nodes, we favour this hypothesis for three reasons. First, MCC may arise de novo in lymph nodes from epithelial or stem cells of the lymph reticular system [22,23] and Second, PET-TC failed to disclose lesions elsewhere. Third, the long disease-free survival in our patient with primary MCC nodal presentation is unusual for metastatic MCC.…”