Composite monoclonal B-cell lymphocytosis and MYD88 L265P-positive lymphoplasmacytic lymphoma in a patient with IgM light chain amyloidosis: Case report.

Monoclonal B-cell lymphocytosis (MBL) is an early or precursor asymptomatic proliferation of chronic lymphocytic lymphoma (CLL)-like B-cells. Lymphoplasmacytic lymphoma (LPL), often clinically associated with Waldenström macroglobulinemia, is a B-cell neoplasm characterized by frequent MYD88 L265P mutation. Here, we report a rare composite MBL and LPL in a patient with IgM light chain (AL) amyloidosis. A 74-year-old male with a known IgM monoclonal protein developed proteinuria. No lymphocytosis was detected. Renal biopsy showed deposition of AL λ amyloid in the glomeruli and vessels. Subsequent bone marrow biopsy revealed nodular atypical CLL-like small B-cell proliferation and scattered peripheral LPL. Immunohistochemistry and/or flow cytometry revealed that the atypical CLL-like population expressed CD19, CD20, CD5, weak CD23, LEF-1 and diminished surface Igκ. The LPL was positive for CD19, CD20 and surface Igλ. Using laser-capture microdissection and allele-specific polymerase chain reaction, we confirmed that MYD88 L265P was detectable in the LPL but not in the atypical CLL-like population. Thus, we demonstrated that these two populations were clonally independent, and made the diagnosis of composite MBL and LPL. An integrated clinical, pathological, immunophenotypic and genetic assessment is essential in such complicated cases, and especially 'clone-specific' MYD88 genotyping may facilitate the differential diagnoses of low-grade B-cell lymphomas.