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. Modern Pathology (2012) 25, 838-845; doi:10.1038/modpathol.2012; published online 2 March 2012 Keywords: chromosomal aberrations; comparative genomic hybridization; fluorescence in-situ hybridization; melanocytic tumors; melanoma Cutaneous melanomas are characterized by a diverse range of histological appearances, and several morphological variants have been described. The most common subtypes in histological classification systems are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. 1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign

O Tamanho dos Ninhos Expansivos Juncionais pode Predizer o Comportamento dos Melanomas in situ

“…Eighteen cases (4.04%) presented almost exclusively by large irregular nests, matching the description of the variant reported by Kutzner et al 5 Among these, we identified a patient who developed recurrence 61 months after the diagnosis. Five patients between the other 427 cases presented recurrence and three developed regional metastasis.…”

“…The authors emphasized that the 11 cases were initially diagnosed as MIS and, after several serial sections, atypical melanocytes infiltrating the dermis were identified in five cases. 5 We identified 445 cases of primary MIS in two hospitals of Rio de Janeiro state, between 1998 and 2010, reviewing the slides to classify them as "large nests in situ melanomas" and other histopathological aspects. All cases were treated surgically with, at least, 5 mm free margins.…”

Molecular and pathomorphological prognostic markers for melanoma: Current approaches and prospects

“…Можно также отметить, что ряд меланом с характерными молекулярными изменениями характеризуется патомор-фологическими особенностями. Так, при поверхностно распространяющихся меланомах, мутантных по CDKN2A, наблюдается педжетоидный вариант и высокий уровень содержания пигмента [11].…”

Nested melanoma

“…1 The recognition of this particular pattern without a pagetoid element has been delayed as the histopathology masquerades as an unusual nevus. The clinical features, dermoscopy, the distinctive histopathology and now the application of comparative genomic hybridization, all help to identify this as a melanoma variant.…”