[486] Fluorescent In-Situ Hybridization (FISH) as a Tool To Assess for Chrosome Changes in Malignant Melanoma with Co-Existing Melanocytic Nevus.

Alejandro A Gru, Andrea L Salavaggione, Florencia Anatelli, Louis P Dehner, Dongsi Lu. Washington University in St. Louis School of Medicine, MO

Background: Malignant melanomas are not uncommonly seen in association with pre-existing melanocytic nevi. However, whether the pre-existing nevi are precusor lesions or by-stander is not clear. Specific chromsome changes have been reported in malignant melanomas by FISH. In order to understand whether the pre-existing melanocytic nevi are precursor lesions, the chromosome changes in malignant melanoma and the pre-existing melanocytic nevi were evaluated by FISH.
Design: A total of 37 cases were retrieved from our database of patients with malignant melanoma. The main inclusion criteria was the presence of melanoma with co-existing melanocytic nevus. An algorithm-using signal counts from a combination of five probes targeting chromosome 6p25 (RREB1), 6q23 (MYB), 6 centromere and 11q13 (CCND1) with 11 centromere was used. A total of 50 cells in both the area of melanoma and nevus was counted. Benign and malignant areas were mapped out on the H&E sections. Criteria for a positive FISH result included (1) gain in RREB1 relative to CEP6 greater than 55% or (2) gain in RREB1 greater than 29%, (3) loss in MYB relative to CEP6 greater than 40% and (3) gain in CCND1 greater than 38%. Analysis using SPSS 12.0 software was performed for t-test, Fisher test and chi-quare.
Results: The two most common types of melanoma included lentiginous type (n=11) and superficial spreading (n=19). Two cases of MM with spitzoid features with co-existing congenital nevi were also included. The malignant melanomas had a mean Breslow thickness of 0.61mm and most of them extended to the papillary-reticular dermal junction. FISH detected RREB1 gain or RREB1/CEP6 imbalance in 19/37 cases (51.7%), MYB loss in 12/37 cases (32.4%) and CCND1/CEP11 imbalance in 22/37 cases (59.4%). 6 of 37 (16%) cases had no chromosomal gains or losses. Among the associated nevi, 1/37 (2.7%) had RREB1 gains, 2/37 (5.4%) had MYB loss and 5/37 cases (13.5%) had CCND1 gains. Compared to the benign part of the nevi, melanoma had genetic alterations more frequently (84 vs 16%, p=0.0001). The prevalence of coexisting genetic alterations in both lesions was 19%.
Conclusions: Concordant genetic gain/losses are relatively uncommon in melanomas with pre-existing melanocytic nevi (19%). This may indicate a diverse mechanism of precursor lesions for malignant melanomas and additional studies are warranted.
Category: Dermatopathology

Monday, February 28, 2011 2:00 PM

Platform Session: Section F, Monday Afternoon

 

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