title: 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.
authors.affiliation: Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Narisawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Koba
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nagase
mesh_terms: D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000737:chemistry* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D005260:Female; D018859:Hair Follicle / Q000737:chemistry; D006801:Humans; D053569:Keratin-15 / Q000032:analysis; D053539:Keratin-19 / Q000032:analysis; D008297:Male; D018193:Neoplasms, Complex and Mixed / Q000737:chemistry* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000737:chemistry; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D053569:Keratin-15; D053539:Keratin-19; C042739:antigens, CD200
keywords: CD200; Merkel cell; Merkel cell carcinoma; bulge; stem cell