Histogenesis of pure and combined Merkel cell carcinomas: An immunohistochemical study of 14 cases

Abstract

The histogenesis of Merkel cell carcinoma (MCC) has remained unresolved. Moreover, one of the questions is whether pure MCC and combined MCC represent the same histogenesis and entity. The existence of combined MCC suggests that MCC likely arise from pluripotent stem cells. Merkel cells (MC) localize within the bulge area, which is populated by hair follicle stem cells. We used hair follicle stem cell markers to investigate whether MCC share certain characteristics of these stem cells. Fourteen MCC specimens were examined histologically and immunohistochemically. There were six pure MCC and eight combined MCC. In six combined MCC, both MCC components and squamous components at least focally shared the expression of one or more of cytokeratin (CK)15, CK19 and CD200, which are hair follicle stem cell markers. On the other hand, four cases of pure MCC showed partially distinct CK19 expression, but did not show CK15 and/or CD200 expression. There was a distinct difference between pure MCC and combined MCC on the expression of hair follicle stem cell markers. The normal skin expressed CK15, CK19 and CD200 in the bulge area, whereas CK15 and CD200 were absent in the MC-rich glabrous skin and touch domes. The results led us to hypothesize that combined MCC originate from the hair follicle stem cells. We postulate that combined MCC undergo multidirectional differentiation into squamous, glandular, mesenchymal and Merkel cells. Further investigation is warranted to confirm the histogenesis of pure MCC and combined MCC.

Merkel cell carcinoma

“…MCC has been observed contiguous to or intermingled with other skin malignancies, particularly cutaneous squamous cell carcinoma, including Bowen disease 90,91 (a red and scaly patch on the skin that is the sign of very early cutaneous squamous cell carcinoma). The relatively frequent association between MCC and cutaneous squamous cell carcinoma could be explained by both tumours originating from a common multipotent stem cell, divergent differentiation of neoplastic cells or simultaneous growth of two unrelated malignancies.…”

Merkel Cell Carcinoma

“…Evidence builds, however, that MCC with squamous differentiation is clinically different and harbors histologic and molecular signatures, similar to CK20-negative MCC, 32 of UV-related squamous epithelial tumors. 4,16,17 Such tumors show less CK20 and NF positivity and more p53 and follicular stem cell markers 16–18 and are always negative for MCV. Well-differentiated SCC is easily diagnosed.…”

“…NF is more frequently negative in MCV-negative cases with combined morphology. 16 These cases are more highly represented among the CK20-negative MCC population and have been shown to uniquely express follicular stem cell markers 17 and higher labeling with p53. 16,18 …”

Merkel Cell Carcinoma Masquerading As Cellulitis: A Case Report and Review of the Literature

“…Merkel cell carcinoma generally presents as a cutaneous disease, but local recurrence, regional lymph node metastases, and systemic disease are common 12 . It usually manifests as a solitary dome-shaped nodule or firm plaque, typically red, violaceous, or purple, with most lesions occurring in the head or neck 3 .…”

“…These immunohistochemical markers are summarized in Table II. It is worth noting that ttf-1 is typically negative in mcc 12,20,21 . The pd-L1 marker was found to be expressed in 42% to 69% of cases of mcc.…”