(P 151) MOLECULAR ANALYSIS OF CUTANEOUS SARCOMATOID NEOPLASMS FREQUENTLY IDENTIFIES MELANOMA DRIVER VARIANTS

Objective: Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group of tumors with diverse prognoses and management options. These tumors can include undifferentiated and dedifferentiated melanomas (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), sarcomatoid squamous cell carcinoma and other rare tumors. Due to several overlapping features, diagnosis can be challenging and requires careful correlation of clinical, pathologic and, increasingly, molecular features. The finding of a MAPK pathway variant commonly associated with melanoma may support a diagnosis of melanoma over other tumors in this group.

Methods: We performed a retrospective analysis of prospectively collected data on 37 cases of primary cutaneous sarcomatoid neoplasms that were immuno-histologically unclassifiable, and which had undergone targeted NGS analysis. All cases lacked a demonstrable past history of melanoma, and all were either entirely negative for four melanocytic markers (S100, SOX10, HMB45, and Melan-A), or only focally positive for one or two of these markers.

Results: We identified a typical melanoma driver variant in seven cases (7/37, 19%), involving NRAS (5/37, 14%), KIT (1/37, 3%) and GNAQ (1/37, 3%). The mean age of these patients was 76 years (median 84, range 55 to 89), most were male (6/7, 85%) and tumors were mostly located on the head and neck (6/7, 85%). There was no statistically significant difference in age, sex, site of tumor and mitotic rate between cases with a melanoma driver variant and those without. Melanoma cases were thicker (16.3 mm versus 9.25 mm, p = 0.041) and more likely to have an epithelioid cell phenotype (p = 0.013).

Conclusion: Our findings show that nearly 20% of our patients with immunohistologically unclassifiable cutaneous tumours could be re-classified as primary UM or DM after testing for typical melanoma driver variants, thereby opening alternative management pathways. Patient age, gender and body site were similar between the two groups, which were typically older males with tumours located on the head and neck. Epithelioid cell type was associated with the presence of a melanoma driver variant. We were unable to assess for the presence of NF1 variant, which is a potential limitation.

Molecular testing of primary cutaneous sarcomatoid neoplasms, which are otherwise unclassifiable by light microscopy and immunohistochemistry alone, has the potential to improve the detection of UM and DM.