Melanocytic nevi existing in lymph nodes create a diagnostic challenge by mimicking metastases. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) stain can differentiate one from another. FLI‐1 IHC expression has been shown in malignant melanoma with variable sensitivity while melanocytic nevi were reported to be negative. We hypothesized that FLI‐1/Melan‐A dual IHC staining may be used in the distinction of metastatic melanoma from nodal nevi and can be an alternative and/or complementary to PRAME. In this study, we examined 13 lymph nodes with metastatic melanoma and 13 lymph nodes with benign deposits. We stained all of the lymph nodes with FLI‐1, FLI‐1/Melan‐A dual, and PRAME IHC stains. In addition, we stained paired skin samples of the metastatic lymph nodes with FLI‐1 and PRAME. In primary cutaneous melanomas, 11 of 13 were positive for FLI‐1 and PRAME expression (85%). Malignant cells in 12 and 13 lymph nodes showed positive expression of PRAME and FLI‐1, respectively. Only one case with a nevic cell deposit was weakly positive for FLI‐1 and the remaining benign cases were negative for both FLI‐1 and PRAME. Our results show that FLI‐1/Melan‐A dual stain is as sensitive and specific as PRAME in distinguishing lymph nodes with metastatic melanoma from nodal nevi. Further studies with larger case numbers are needed to support our significant results.

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Background: Cutaneous mixed tumors (CMTs) include benign, atypical, and malignant chondroid syringomas. This spectrum of entities is known to be a part of myoepithelial neoplasms, which display considerable genetic heterogeneity. In a previous report, a malignant chondroid syringoma (MCS) demonstrated PHF1-TFE3 gene fusion and strong TFE3 immunohistochemical (IHC) staining. The authors suggested that the MCS is genetically related to tumors with TFE3 rearrangements such as renal cell carcinoma and might have genetic heterogeneity. In this study, we aim to investigate potential TFE3 gene fusions with TFE3 IHC stain in a spectrum of CMTs. Materials: Eleven benign chondroid syringoma (BCS), one atypical chondroid syringoma (ACS), and one malignant chondroid syringoma cases were identified, stained with TFE3 IHC stain, and interpreted based on preset criteria. Results: ACS and MCS cases did not show any staining. In 7 of 11 BCS cases, weak (1+) staining was observed in less than 20% of the tumor cells and were considered negative. Additionally, in one BCS case, weak (1+) and (2+) staining was shown in approximately 15% and less than 1% of the tumor cells, respectively. Based on our positivity criteria, this case was also interpreted as negative. Conclusions: Our study failed to reveal possible TFE3 gene fusion by IHC staining in benign, atypical, and malignant chondroid syringomas. Although the negative staining in MCS suggests a genetic heterogeneity in this entity, further studies with larger case groups are needed for a more definitive conclusion.