title: Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests.
abstract: Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.
authors.affiliation: Dermatopathologie Friedrichshafen, Friedrichshafen, Germany. kutzner@w-4.de
authors.forename: Heinz
authors.initials: H
authors.lastname: Kutzner
authors.forename: Gisela
authors.initials: G
authors.lastname: Metzler
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Argenyi
authors.forename: Luis
authors.initials: L
authors.lastname: Requena
authors.forename: Gabriele
authors.initials: G
authors.lastname: Palmedo
authors.forename: Thomas
authors.initials: T
authors.lastname: Mentzel
authors.forename: Arno
authors.initials: A
authors.lastname: Rütten
authors.forename: Markus
authors.initials: M
authors.lastname: Hantschke
authors.forename: Bruno E
authors.initials: BE
authors.lastname: Paredes
authors.forename: Leo
authors.initials: L
authors.lastname: Schärer
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hesse
authors.forename: Laila
authors.initials: L
authors.lastname: El-Shabrawi-Caelen
authors.forename: Leila El
authors.initials: LE
authors.lastname: Shabrawi-Caelen
authors.forename: Isabella
authors.initials: I
authors.lastname: Fried
authors.forename: Helmut
authors.initials: H
authors.lastname: Kerl
authors.forename: Cerroni
authors.initials: C
authors.lastname: Lorenzo
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Murali
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiesner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor