NOTCH1, TP53, and MAP2K1Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease

Supplemental Digital Content is available in the text.Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHVgenes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGHrearrangements in 3, with PAX5and potentially TCL1as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1and MAP2K1were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1were mutated each in single cases. No mutations were found in NOTCH2or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1(2 cases), TP53(1 case), and MAP2K1(1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.