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Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases Vergier B; Prochazkova-Carlotti M; de la Fouchardiere A; Cerroni L; Massi D; De Giorgi V; Bailly C; Wesselmann U; Karlseladze A; Avril MF; Jouary T; Merlio JPMod Pathol 2011[May]; 24 (5): 613-23Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (A-) or 'favor malignant' (A+). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.|Adolescent[MESH]|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Child[MESH]|Child, Preschool[MESH]|Chromosome Aberrations[MESH]|DNA, Neoplasm/analysis[MESH]|Female[MESH]|Humans[MESH]|In Situ Hybridization, Fluorescence[MESH]|Lymph Nodes/pathology[MESH]|Male[MESH]|Melanocytes/*pathology[MESH]|Melanoma/*diagnosis/genetics/secondary[MESH]|Middle Aged[MESH]|Neoplasm Staging[MESH]|Nevus/*diagnosis/genetics[MESH]|Predictive Value of Tests[MESH]|Reproducibility of Results[MESH]|Skin Neoplasms/*diagnosis/genetics[MESH]|Young Adult[MESH] |
