An addition to the evolving spectrum of lipofibromatosis and lipofibromatosis-like neural tumor: Molecular findings in an unusual phenotype aid in accurate classification

Abstract

Lipofibromatosis (LPF) and lipofibromatosis-like neural tumor (LPF-NT) are histologically and prognostically similar neoplasms having differences in immunophenotype as well as molecular biology. In most cases, LPF-NT is driven by fusions in the NTRK gene, whereas LPF has been associated with fusions in a variety of receptor tyrosine kinases. The distinction between the driver fusion event holds clinical significance because of the profound clinical response to tropomyosin receptor kinase (Trk) inhibitors (larotrectinib) in the NTRK-driven tumors. Immunohistochemically, and consistent with its namesake, to-date all reported cases classified as LPF-NT have shown positivity for S100-protein staining. Consequently, as S100-protein staining is widely available, it represents a cost-effective screening tool for LPF-NT where the more specific studies such as the pan-Trk stain or fluorescence in situ hybridization for NTRK rearrangement are not available. Herein, we present a case of presumed LPF-NT harboring the recurrent NTRK1-LMNA fusion, but which was negative for S100-protein immunostaining and was previously classified as classical LPF. This case reveals a potential pitfall in distinguishing these rare subcutaneous tumors by S100-protein staining and highlights the challenges in reconciling the rapid and novel discoveries made in the field of diagnostic pathology.

Keywords: LMNA; Lipofibromatosis; Lipofibromatosis-like neural tumor; NTRK; Pan-Trk; S100.