Composite CLL/SLL and Lymphoplasmacytic Lymphoma with IgM Anti-MAG Neuropathy: Clinicopathologic and Molecular Characterization of a Diagnostically Challenging Case.

OBJECTIVE

Composite lymphoma, defined by the coexistence of two or more distinct lymphoma types at the same anatomic site, is rare and diagnostically challenging. Composite chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and lymphoplasmacytic lymphoma (LPL) has been reported only rarely.

CASE REPORT: A 75-year-old woman with long-standing CLL/SLL developed progressive sensorimotor neuropathy. Serum studies detected elevated IgM (988 mg/dL), an IgM lambda paraprotein (0.5 g/dL), and IgM anti-myelin-associated glycoprotein antibody. Imaging studies identified a dominant pelvic lymph node. Biopsy revealed two B-cell neoplasms: a predominant CLL/SLL component (CD5+, CD23+, CD200+, dim monotypic lambda, CD10-), and a minor LPL component (CD38+, bright monotypic lambda, CD5-, CD10-, CD23-, CD200-). Targeted sequencing detected MYD88 L252P mutation in peripheral blood and pelvic lymph node, supporting LPL. The patient was treated with intrathecal methotrexate and cytarabine together with zanubrutinib, which led to neurological improvement and clearance of CLL/SLL cells from cerebrospinal fluid.

CONCLUSIONS

This case highlights the diagnostic complexity of composite indolent B-cell lymphomas and underscores the importance of integrated clinical, morphologic, immunophenotypic, and molecular assessment to inform management and surveillance.