Cutaneous Neurotrophic Tyrosine Receptor Kinase-Rearranged Spindle Cell Neoplasm: A Diagnostic Dilemma.

NTRK (Neurotrophic Tyrosine Receptor Kinase)-rearranged spindle cell neoplasms are a group of molecularly defined tumors with a varied morphological spectrum, displaying overlapping features of infantile fibrosarcoma, lipofibromatosis, and malignant peripheral nerve sheath tumors (Surrey and Davis JL. Cancer Genet. 2022;260-261:6-13). This report discusses a case of an NTRK-rearranged spindle cell neoplasm arising from the left forearm of a 32-year-old patient. The lesion histologically comprised an infiltrative, nodular tumor with heterogeneous stroma displaying myxoid, scar-like and lipofibromatosis-like areas. Areas of hypercellularity with increased mitotic activity were noted. The tumor cells displayed diffuse, strong expression of S100 and CD34. Granular cytoplasmic expression of Pan-TRK immunohistochemistry favored the presence of an NTRK rearrangement. RNA-based next-generation sequencing was performed for confirmation and detected an ETV6::NTRK3 fusion, thereby confirming the diagnosis of an NTRK-rearranged spindle cell neoplasm. The vast morphological spectrum of this entity poses a diagnostic challenge for dermatopathologists, necessitating consideration of a broad range of differential diagnoses. Accurate assessment and reporting of this emerging entity requires correlation of histology and immunohistochemistry, and detection of an NTRK fusion using next-generation sequencing.

Abstract from PubMed