NTRK3-EML4-rearranged spindle cell tumor with co-expression of S100 and CD34: an unusual mesenchymal tumor in the spectrum of the bland-looking spindle cell lesions of the oral cavity.

A novel category of spindle cell tumors characterized by Neurotrophic Tyrosine Receptor Kinase (NTRK) rearrangements with a dual immunoreactivity for S-100 and CD34 has emerged in the last years as a distinct entity among soft tissue neoplasms. These genetic alterations lead to the continuous activation of NTRK genes, driving tumorigenesis and offering a unique prospect for targeted therapy. We herein present a rare case of NTRK3-rearranged spindle cell tumor with a hitherto unreported gene fusion involving the exon 14 of NTRK3 with the exon 2 of Echinoderm Microtubule-Associated Protein-Like 4, arising in the head and neck region. Tumor occurred in a 45-year-old patient who presented with a painful nodule in the oral mucosa. Due to the possibility of personalizing the treatment strategy for such tumors, pathologists should be aware of this emerging group of spindle cell tumors to promptly recognize them even when they occur in uncommon locations, including the oral cavity.

ARID1A Mutations in Gastric Cancer: A Review with Focus on Clinicopathological Features, Molecular Background and Diagnostic Interpretation.

AT-rich interaction domain 1 (ARID1A) is a pivotal gene with a significant role in gastrointestinal tumors which encodes a protein referred to as BAF250a or SMARCF1, an integral component of the SWI/SNF (SWItch/sucrose non-fermentable) chromatin remodeling complex. This complex is instrumental in regulating gene expression by modifying the structure of chromatin to affect the accessibility of DNA. Mutations in ARID1A have been identified in various gastrointestinal cancers, including colorectal, gastric, and pancreatic cancers. These mutations have the potential to disrupt normal SWI/SNF complex function, resulting in aberrant gene expression and potentially contributing to the initiation and progression of these malignancies. ARID1A mutations are relatively common in gastric cancer, particularly in specific adenocarcinoma subtypes. Moreover, such mutations are more frequently observed in specific molecular subtypes, such as microsatellite stable (MSS) cancers and those with a diffuse histological subtype. Understanding the presence and implications of ARID1A mutations in GC is of paramount importance for tailoring personalized treatment strategies and assessing prognosis, particularly given their potential in predicting patient response to novel treatment strategies including immunotherapy, poly(ADP) ribose polymerase (PARP) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors.