title: Clear cell melanoma: a cutaneous clear cell malignancy.
abstract: Clear cell melanoma is a rare clear cell malignancy. Accurate diagnosis of clear cell melanoma requires integration of immunohistochemical and morphologic findings, with molecular studies to rule out clear cell sarcoma. The differential diagnosis includes melanoma, carcinoma, perivascular epithelioid cell tumor, and epidermotropic clear cell sarcoma. We use a case of a lesion on the helix of an 86-year-old man as an example. Histologic examination revealed an ulcerated clear cell malignant tumor. Tumor cell cytoplasm contained periodic acid-Schiff-positive, diastase-sensitive glycogen. Tumor cells showed positive labeling for S100, HMB-45, and Melan-A, and negative labeling for cytokeratins, p63, and smooth muscle actin. Molecular studies demonstrated BRAF V600E mutation, copy gains at the 6p25 (RREB1) and 11q13 (CCND1) loci, and absence of EWSR1-ATF1 fusion. These findings supported a diagnosis of clear cell melanoma. The rare pure clear cell morphology occurs due to accumulation of intracytoplasmic glycogen. We review the differential diagnosis of clear cell melanoma and describe the utility of immunohistochemical and molecular studies in confirming this diagnosis.
authors.affiliation: From the Departments of Pathology (Drs Pletneva, Andea, Palanisamy, Betz, Wang, Patel, Fullen, and Harms, and Ms Carskadon) and Dermatology (Drs Andea Patel, Fullen, and Harms), and the Michigan Center for Translational Pathology (Drs Palanisamy and Harms, and Ms Carskadon), University of Michigan Medical Center, Ann Arbor.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pletneva
authors.forename: Aleodor
authors.initials: A
authors.lastname: Andea
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Betz
authors.forename: Shannon
authors.initials: S
authors.lastname: Carskadon
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Rajiv M
authors.initials: RM
authors.lastname: Patel
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Fullen
authors.forename: Paul W
authors.initials: PW
authors.lastname: Harms
mesh_terms: D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003937:Diagnosis, Differential; D054644:Ear Auricle; D018628:Gene Dosage; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D054973:Perivascular Epithelioid Cell Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D018227:Sarcoma, Clear Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; C101743:RREB1 protein, human; D014157:Transcription Factors; D019938:Cyclin D1; D006003:Glycogen; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf