New observations in tumor cell plasticity: mutational profiling in a case of metastatic melanoma with biphasic sarcomatoid transdifferentiation

We describe a highly unusual case of metastatic melanoma in a 61-year-old female that manifested as a single groin lymph node metastasis accompanied by two distinct, subcutaneous sarcomatoid tumors on the same leg, without evidence of a primary tumor. Characterization encompassed extensive immunohistochemical staining as well as next-generation sequencing (NGS). The lymph node metastasis showed obvious features of melanoma. The two subcutaneous lesions, however, were morphologically and immunohistochemically consistent with high-grade myxofibrosarcoma and soft tissue mixed tumor, respectively. All three lesions were BRAF wild-type and found to harbor an identical NRAS p.Q61R mutation. Metachronic intestinal metastases, showing intermingled conventional and sarcomatoid morphology, as well as an identical genetic phenotype, corroborated these findings. The concordant genetic profile provided evidence of biphasic sarcomatoid transdifferentiation of melanoma. Interestingly, the lack of genetic heterogeneity between the three morphologically distinct tumors suggests factors other than genetic mutations to be involved in melanoma transdifferentiation.