title: The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions.
abstract: C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient's age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.
authors.affiliation: Department of Cytomorphology, Division of Pathology, University of Cagliari, via Ospedale, 54, 09124 Cagliari, Italy. lucpilloni@tiscali.it
authors.forename: L
authors.initials: L
authors.lastname: Pilloni
authors.forename: P
authors.initials: P
authors.lastname: Bianco
authors.forename: E
authors.initials: E
authors.lastname: Difelice
authors.forename: S
authors.initials: S
authors.lastname: Cabras
authors.forename: M E
authors.initials: ME
authors.lastname: Castellanos
authors.forename: L
authors.initials: L
authors.lastname: Atzori
authors.forename: C
authors.initials: C
authors.lastname: Ferreli
authors.forename: P
authors.initials: P
authors.lastname: Mulas
authors.forename: S
authors.initials: S
authors.lastname: Nemolato
authors.forename: G
authors.initials: G
authors.lastname: Faa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D049109:Cell Proliferation; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009506:Nevus / Q000378:metabolism* / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit