Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi.

The histopathologic distinction of desmoplastic melanomas from sclerosing (desmoplastic) melanocytic nevi can be difficult, especially when evaluating a partial or superficial biopsy. In the study reported herein, we applied and explored the use of a novel ancillary method, a four-probe fluorescence in situ hybridization (FISH) assay targeting RREB1, MYB, Cep6 and CCND1, to this diagnostic problem. Fifteen sclerosing melanocytic nevi, including desmoplastic Spitz nevi, conventional nevi with prominent stromal sclerosis and sclerotic blue nevi, as well as 15 examples of desmoplastic melanoma, were examined. None of the sclerosing melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for melanoma. Seven of the 15 desmoplastic melanomas were 'positive' (had documented chromosomal aberrations) by FISH. Thus, a positive FISH test strongly supports the diagnosis of melanoma in this context. However, in this setting a negative FISH test is of limited diagnostic value. Our findings suggest that prior reports about the high sensitivity of the FISH test for melanoma diagnosis need to be adjusted according to melanoma subtype.

Fluorescence in situ hybridization for distinguishing nevoid melanomas from mitotically active nevi.

Nevoid melanoma may resemble benign compound or intradermal nevi by their silhouette and profile on low power. Higher power usually reveals nuclear atypia, confluence of cells, incomplete maturation and dermal mitotic activity. However, to some extent all of these features maybe seen in benign compound or intradermal nevi and no single criteria can be used to differentiate nevoid melanoma from a benign nevus. The distinction can be particularly problematic in nevi that show mitotic activity and we have noted a recent trend in diagnosis of melanocytic neoplasms with dermal mitosis as nevoid melanoma despite the presence of normal maturation in the dermis and lack of significant nuclear atypia. Therefore in this study we evaluated 10 nevoid melanomas, 4 of which resulted in metastasis and 10 mitotically active nevi with fluorescence in situ hybridization targeting key chromosomal loci previously shown to effectively discriminate been malignant and benign melanocytic neoplasms. All 10 nevoid melanomas showed copy number abnormalities by fluorescence in situ hybridization in either chromosome 6 or 11 while none of the 10 mitotically active nevi did. The results demonstrate that fluorescence in situ hybridization targeting key chromosomal loci on chromosomes 6 and 11 can be effective in discriminating nevoid melanomas from mitotically active nevi. Additionally, our study presents further evidence that dermal mitoses alone without other diagnostic features such as nuclear atypia and lack of maturation does not constitute sufficient evidence alone for a diagnosis of melanoma.