Splenic diffuse red pulp lymphoma has a distinct pattern of somatic mutations amongst B-cell malignancies

Area of Science:

• Hematology
• Oncology
• Immunology

Background:

• Splenic Diffuse Red Pulp Lymphoma (SDRPL) is a provisional entity requiring clear differential diagnosis from other splenic lymphomas due to distinct therapeutic strategies.
• Recurrent mutations and CD180 expression are emerging as key markers for distinguishing SDRPL.

Purpose of the Study:

• To further characterize Splenic Diffuse Red Pulp Lymphoma (SDRPL) in a larger cohort.
• To investigate the diagnostic utility of specific mutations (IGHV, BRAF, MYD88, NOTCH2) and CD180 expression in SDRPL.

Main Methods:

• Analysis of 53 patients with characteristic villous cells in peripheral blood and specific immunophenotype.
• Mutation analysis for IGHV, BRAF, MYD88, and NOTCH2.
• Assessment of CD180 and BRAF protein expression.

Main Results:

• 79% of cases exhibited IGHV mutations, with IGHV3-23 and IGHV4-34 overrepresented.
• Rare MYD88 L265P and NOTCH2 mutations were detected; no BRAF V600E mutations or expression were found.
• All SDRPL cases showed high CD180 expression.

Conclusions:

• The findings support SDRPL as a distinct lymphoma entity.
• High CD180 expression and specific mutation profiles aid in differentiating SDRPL from other splenic lymphomas with circulating lymphocytes.