DNA-based characterization of primary hepatic MALT lymphoma reveals a rare FAT3 missense variant and Hippo pathway activation: a case report and literature review

Primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is exceedingly rare, and molecular evidence specific to this anatomic site remains sparse. DNA-based profiling represents a powerful tool for elucidating the molecular mechanisms underlying lymphoid neoplasms; however, its application to primary hepatic MALT lymphoma remains largely unexplored. Here, we report a localized, virus-negative hepatic MALT case characterized by targeted DNA sequencing and paired tumor–normal tissue assessment of Hippo pathway activity. A 55-year-old asymptomatic woman was found to have a 2.68-cm hypervascular hepatic nodule on screening ultrasound. Contrast-enhanced ultrasonography showed rapid arterial enhancement with early washout, and cross-sectional staging showed no evidence of extrahepatic disease. Laparoscopic wedge resection achieved R0 margins; histology confirmed MALT lymphoma with lymphoepithelial lesions and plasmacytoid differentiation (Lugano stage IE). Targeted DNA sequencing using a mature lymphoma panel identified a rare FAT3 missense variant with no other canonical coding drivers detected. Paired tumor versus adjacent liver analyses demonstrated increased YAP1 and TEAD1 readouts in tumor tissue. Postoperatively, PET–CT and quarterly ultrasound surveillance were performed for 24 months, with no evidence of recurrence. DNA-based profiling of this rare, virus-negative primary hepatic MALT lymphoma revealed a FAT3 missense variant and concomitant upregulation of YAP1 and TEAD1 expression in tumor tissue, providing hypothesis-generating evidence of Hippo pathway dysregulation specific to hepatic MALT lymphoma, which requires validation in larger, independent cohorts.