Diagnosing Ambiguous Melanocytic Tumors in a Tertiary Referral Center: The Contribution of Fluorescence In Situ Hybridization (FISH) to Conventional Histopathologic and Immunophenotypic Analyses
Tiffani L Milless, Curry L Jonathan, Torres-Cabala A Carlos, Wang Wei-Lien, McLemore S Michael, Ivan Doina, Prieto G Victor, Tetzlaff T Michael. UT MD Anderson Cancer Center, Houston, TX
Background: The distinction of benign from malignant melanocytic proliferations remains a diagnostic challenge with critical clinical implications. The current diagnostic algorithm includes assessment of histopathologic (architecture, cytology, mitotic activity) and immunohistochemical (HMB-45 and Ki-67) parameters. Recently, FISH has been reported as a useful ancillary diagnostic tool in melanocytic lesions, but most studies have assessed the performance of FISH in unequivocal melanomas and nevi. Thus, the diagnostic utility of FISH in ambiguous melanocytic tumors remains controversial.
Design: 32 histopathologically ambiguous melanocytic proliferations from our consultation service were reviewed. The histopathologic, immunophenotypic and FISH parameters (NeoGenomics; using probes for 6p25, 6q23, 11q13 and Cen6) informing our diagnostic impression were correlated with the final consensus diagnosis and clinical follow-up.
Results: 32 melanocytic tumors from 13 females and 18 males with a mean age of 28 years (range: 2 to 64) were examined. Prior to FISH testing, cases were designated as “favor benign” (n=22) or “favor malignant” in (n=10) by a consensus group (up to 7 dermatopathologists) based on an assessment of clinical, histopathologic and immunophenotypic parameters. FISH testing was positive in 3/22 “favor benign” lesions (two with a pattern consistent with polypoloidy) and in 5/10 “favor malignant” lesions. In all 32 cases, the final diagnosis correlated with the initial consensus impression rendered independently of FISH. In this series of melanocytic tumors, the sensitivity of FISH for the diagnosis of melanoma was 50%; the specificity was 86.4%; the positive predictive value (PPV) was 62.5%; the negative predictive value (NPV) was 79.2%. Follow-up (range: 2-21 months) was available for 25 patients (17/8 with benign/malignant diagnosis, respectively). Among benign lesions: 2 were not treated, 15 underwent wide local excision (WLE), and a single patient also underwent sentinel lymph node sampling (SLNS) which was negative for metastasis. Among the 8 malignant lesions, all underwent WLE-SLNS. A single lymph node metastasis was identified in a 4 year old girl with FISH-negative melanoma.
Conclusions: The diagnosis of ambiguous melanocytic tumors requires a multi-faceted assessment of clinical, histopathologic and immunophenotypic parameters. Given its apparent low sensitivity and PPV in the setting of ambiguous lesions, FISH testing does not significantly impact the final diagnosis.
Category: Quality Assurance
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 299, Monday Morning