DOG1 Expression in Low-Grade Fibromyxoid Sarcoma: A Study of 11 Cases, With Molecular Characterization.

DOG1 is a highly sensitive marker for gastrointestinal stromal tumor (GIST) and is in the routine diagnostic antibody repertoire of many surgical pathology laboratories. Moreover, GIST is well recognized by both pathologists and clinicians in the differential diagnosis of intra-abdominal and pelvic neoplasms. Low-grade fibromyxoid sarcoma (LGFMS) is, however, much less frequently anticipated, particularly when occurring at unusual sites, because of its rarity and bland histology, particularly on core biopsy. We describe a case of a 53-year-old male with a large pelvic and pararectal mass, which on biopsy showed a moderately cellular spindle cell neoplasm within fibrous stroma. Immunohistochemistry at the referring center showed diffuse and strong expression of DOG1 with negativity for other markers. After referral to a tertiary center, repeat DOG1 immunohistochemistry again showed diffuse expression, but MUC4 was also positive, and this was confirmed to be LGFMS, harboring FUS-CREB3L2 fusion transcripts by reverse transcription-polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization. In view of this we assessed DOG1 expression in 10 other LGFMS (all MUC4 positive, and 9 molecularly confirmed to harbor FUS-CREB3L2 fusion transcripts and/or FUS or EWSR1 gene rearrangement), of which 5 showed DOG1 expression in up to 75% of tumor cells, varying in intensity from weak to strong. While LGFMS and GIST are generally morphologically dissimilar, less typical variants of each exist, and both can contain bland spindled cells within fibrous stroma. As the morphologic spectrum of LGFMS is wide, and as it can occur in unusual sites and may not be well recognized by general pathologists and non-soft tissue pathologists, we highlight the potential for diagnostic confusion with GIST owing to aberrant DOG1 expression. This is clinically pertinent, as the management and prognosis of these 2 neoplasms differs significantly.