Posted: Wednesday, January 18, 2023
Arnault Tauziède-Espariat, MD, of GHU Paris-Psychiatry and Neuroscience, Sainte-Anne Hospital, and colleagues aimed to identify the lineage of NTRK-rearranged spindle cell neoplasms and to further characterize their molecular and histopathologic features. Published in the journal Histopathology, the results of this study indicated this population of tumors may share similar infiltrative patterns, transcriptomic and epigenetic profiles, and myofibroblastic lineage across multiple patient groups.
“Spindle cell neoplasm–NTRK [tumors] have a common myofibroblastic differentiation throughout the many affected organs and represent a new methylation class distinct from their differential histomolecular diagnoses, including infantile fibrosarcomas,” the authors concluded. “Further studies may support the use of new terminology to better describe their myofibroblastic nature.”
The investigators focused on 16 cases of mesenchymal tumors harboring kinase gene fusions. Patient demographics and clinical data, such as sex, medical history, and age at presentation, were retrieved from hospital records. Cases were analyzed and characterized via immunohistochemistry, DNA-methylation profiling, ultrastructural analysis, and whole-RNA sequencing.
All cases demonstrated areas of fibrous stroma, and five of eight cases in the novel methylation class presented with perivascular hyalinization-forming collagen rings. Immunohistochemical analysis revealed that CD34 and S100 were co-expressed in all tumors in this population, although smooth muscle actin was focally expressed in just two cases. This group also commonly exhibited a deletion of CDKN2A and demonstrated variable histopathologic grades.
Through unsupervised, t-distributed, stochastic neighbor–embedding analysis, it was found that all but one tumor, which was originally diagnosed as infantile fibrosarcoma, clustered in a specific methylation class. However, all other tumors formed a new and unique methylation cluster—independently of their location and histopathologic subtype. Moreover, all but one tumor formed a single cluster within the hierarchic clustering of data from whole-RNA sequencing.
Disclosure: The study authors reported no conflicts of interest.