A Diagnostic Algorithm Combining Immunohistochemistry and Molecular Cytogenetics to Diagnose Challenging Melanocytic...

Some melanocytic tumors are diagnostic challenges and require ancillary tools in helping the pathologists to determine their potential of malignancy. We intend to propose a diagnostic algorithm in helping to classify challenging melanocytic tumors combining histology, immunohistochemistry, and cytogenetics. We report on 24 spitzoid and/or misdiagnosed melanocytic tumors studied with a triple p16, Ki-67, and HMB45 immunohistochemistry score, fluorescent in situ hybridization (FISH) with melanoma-dedicated and non-melanoma-dedicated probes and comparative genomic hybridization on DNA microarray (CGH array). Melanoma-dedicated FISH probe classified as favor malignant 8/8 melanomas, 1/2 atypical spitzoid tumor, and 4/14 nevi with polyploidy. Only 10 CGH array assays were contributive and concluded in complex chromosomal patterns as hallmarks of malignancy in 5 melanomas, single isolated imbalances in 3 nevi, and no chromosomal gain or loss in 2 nevi. The p16-Ki-67-HMB45 immunohistochemistry score was favor benign (ie, 0 to 3) in 13/14 nevi and in the favor benign atypical spitzoid tumor according to FISH analyses. The FISH-favor malignant atypical spitzoid tumor, 8/8 melanomas, and 1 tumor initially diagnosed as a Spitz nevus had favor malignant p16-Ki-67-HMB45 immunohistochemistry scores (ie, 4 to 9). Additional FISH analyses detected a 9p21/CDKN2A double deletion, frequently reported in melanomas but not in nevi, in the tumor initially diagnosed as a Spitz nevus with a favor malignant p16-Ki-67-HMB45 score. To conclude, in our opinion, histology and p16-Ki-67-HMB45 immunohistochemistry could consist in first-line tools to diagnose a difficult melanocytic tumor, followed by cytogenetics analyses in cases of discrepancies between histology and immunohistochemistry.