Hellmuth JC, et al. - Given that duodenal-type follicular lymphoma (DTFL) is a rare and highly indolent follicular lymphoma (FL) variant, and it is morphologically and immunophenotypically indistinguishable from typical FL, with restricted involvement of intestinal mucosa and lacking extra-intestinal manifestations, researchers intended to determine the molecular determinants of this distinct clinical behavior. For this investigation, they assessed 38 diagnostic biopsies from patients with DTFL. They found that the mutational landscape of DTFL was highly associated with typical FL. They discovered that the lower frequency of multiple mutations in KMT2D in DTFL and limited-stage typical FL (LSTFL) shows an increasing selection pressure for complete KMT2D loss in advanced-stage typical FL (ASTFL) pathogenesis. A central role in the biology of this disease is inferred by the highly dissimilar immune microenvironment of DTFL.