Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests Journal Article


Authors: Kutzner, H.; Metzler, G.; Argenyi, Z.; Requena, L.; Palmedo, G.; Mentzel, T.; Rütten, A.; Hantschke, M.; Paredes, B. E.; Schärer, L.; Hesse, B.; Shabrawi-Caelen, L. E.; Fried, I.; Kerl, H.; Lorenzo, C.; Murali, R.; Wiesner, T.
Article 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. © 2012 USCAP, Inc. All rights reserved.
Keywords: adult; clinical article; aged; aged, 80 and over; middle aged; cancer growth; reproducibility of results; phenotype; in situ hybridization, fluorescence; genetic predisposition to disease; melanoma; skin defect; sun exposure; skin neoplasms; melanocytes; tumor markers, biological; biopsy; keratinocyte; chromosome aberration; fluorescence in situ hybridization; predictive value of tests; austria; cell size; cell shape; chromosome aberrations; comparative genomic hybridization; morphological trait; chromosomal aberrations; melanocytic tumors; fluorescence in-situ hybridization
Journal Title: Modern Pathology
Volume: 25
Issue: 6
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2012-06-01
Start Page: 838
End Page: 845
Language: English
DOI: 10.1038/modpathol.2012.35
PROVIDER: scopus
PUBMED: 22388759
DOI/URL:
Notes: --- - "Export Date: 2 July 2012" - "CODEN: MODPE" - "Source: Scopus"
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  1. Rajmohan Murali
    219 Murali
  2. Thomas Wiesner
    38 Wiesner