Smooth muscle actin (SMA)-negative uninodular plexiform fibromyxoma: case report of a challenging atypical presentation of a rare gastric mesenchymal tumor in a 25-year-old female

Background: Plexiform fibromyxoma (PFM) is an uncommon, benign mesenchymal tumor typically arising in the gastric antrum and usually characterized by a multinodular, plexiform growth pattern of smooth muscle actin (SMA)-expressing myofibroblastic-like cells. Rare variants with uninodular architecture and absence of SMA expression pose significant diagnostic challenges, as they may mimic gastrointestinal stromal tumors (GISTs) and require comprehensive histopathologic, immunohistochemical, and molecular evaluation to avoid misdiagnosis and inappropriate therapy.

Case Description: Here, we present a case of PFM with a rare uninodular architecture, complete absence of SMA expression and no detectable MALAT1-GLI1 translocation in a 25-year-old female with unremarkable laboratory work-up (hemoglobin 13.9 g/dL, normal blood count and biochemistry) presented with diffuse upper abdominal discomfort and a palpable epigastric mass noted on self-examination. Physical examination revealed a firm, non-tender mid-abdominal mass without peritonism. The tumor measured 13 cm and was discovered as a palpable mass on self-examination during diagnostic work-up for upper abdominal discomfort. Histologically, the lesion was composed of bland spindle cells embedded in a loose myxoid stroma, lacking the classic multinodular configuration. Immunohistochemistry was negative for SMA, DOG1, S100, CD34, desmin, and anaplastic lymphoma kinase (ALK). Molecular analysis revealed no pathogenic mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) and no detectable gene fusions. The final diagnosis was most consistent with uninodular PFM as diagnosed by exclusion.

Conclusions: This case highlights the importance of an early multimodal diagnostic work-up (including histology, immunohistochemistry, and next-generation sequencing) in atypical gastric mesenchymal tumors, e.g., PFMs, to avoid misdiagnosis as a GIST and inappropriate tyrosine kinase inhibitor therapy. Complete surgical resection with negative margins using stomach-preserving techniques is curative and associated with an excellent prognosis.