Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma

Pedram Gerami, Susan S. Jewell, Larry E. Morrison, Beth Blondin, John Schulz, Teresa Ruffalo, Paul Matushek IV, Mona Legator, Kristine Jacobson, Scott R. Dalton, Susan Charzan, Nicholas A. Kolaitis, Joan Guitart, Terakeith Lertsbarapa, Susan Boone, Philip E. LeBoit, Boris C. Bastian

Research output: Contribution to journalArticlepeer-review

364 Scopus citations


Although the clinical and pathologic diagnosis of some melanomas is clear-cut, there are many histopathologic simulators of melanoma that pose problems. Over-diagnosis of melanoma can lead to inappropriate therapy and psychologic burdens, whereas under-diagnosis can lead to inadequate treatment of a deadly cancer. We used existing data on DNA copy number alterations in melanoma to assemble panels of fluorescence in situ hybridization (FISH) probes suitable for the analysis of paraffin-embedded tissue. Using FISH data from a training set of 301 tumors, we established a discriminatory algorithm and validated it on an independent set of 169 unequivocal nevi and melanomas as well as 27 cases with ambiguous pathology, for which we had long-term follow-up data. An algorithm-using signal counts from a combination of 4 probes targeting chromosome 6p25, 6 centromere, 6q23, and 11q13 provided the highest diagnostic discrimination. This algorithm correctly classified melanoma with 86.7% sensitivity and 95.4% specificity in the validation cohort. The test also correctly identified as melanoma all 6 of 6 cases with ambiguous pathology that later metastasized. There was a significant difference in the metastasis free survival between test-positive and negative cases with ambiguous pathology (P=0.003). Sufficient chromosomal alterations are present in melanoma that a limited panel of FISH probes can distinguish most melanomas from most nevi, providing useful diagnostic information in cases that cannot be classified reliably by current methods. As a diagnostic aid to traditional histologic evaluation, this assay can have significant clinical impact and improve classification of melanocytic neoplasms with conflicting morphologic criteria.

Original languageEnglish (US)
Pages (from-to)1146-1156
Number of pages11
JournalAmerican Journal of Surgical Pathology
Issue number8
StatePublished - Aug 2009


  • FISH
  • Melanoma
  • Spitz nevi
  • Spitz tumor

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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