Diagnosis and Management of Dual B-Cell and Plasma Cell Disorder

Introduction to Diagnostic Criteria

The absence of CD5 and CD23 in the B-cell population excludes chronic lymphocytic leukemia (CLL), according to the National Comprehensive Cancer Network 1, 2, 3.
Negative CD5 and CD23 also exclude mantle cell lymphoma, which typically expresses CD5 and can be distinguished by cyclin D1 positivity or t(11;14) on FISH, as per the Journal of the National Comprehensive Cancer Network 2, 4.
The American Society of Clinical Oncology recommends that follicular lymphoma be excluded based on negative CD10 expression, characterized by CD10+, BCL2+, and BCL6+ expression 5.

The National Comprehensive Cancer Network suggests performing comprehensive serum and urine protein evaluation, including serum protein electrophoresis (SPEP) with immunofixation, serum free light chain assay with kappa:lambda ratio calculation, 24-hour urine collection with urine protein electrophoresis (UPEP) and immunofixation, and quantitative immunoglobulins (IgG, IgA, IgM) 6, 8.
Immediate assessment of renal function is crucial, including serum creatinine, eGFR, and electrolytes, as well as urinalysis for proteinuria, according to the Nature Reviews Nephrology 7, 8.

A complete blood count with differential should be performed to assess absolute lymphocyte count, presence of cytopenias, and circulating plasma cells, as recommended by the American Society of Hematology 1, 2, 4.
Bone marrow aspirate and biopsy with plasma cell quantification, flow cytometry, and FISH for high-risk cytogenetics are essential for diagnosis, according to the Leukemia journal 6, 8.

CT scans of chest, abdomen, pelvis, and cervical regions should be performed to evaluate for lymphadenopathy, splenomegaly, and hepatomegaly, as suggested by the Blood journal 1, 6.

The presence of lambda-restricted plasma cells with atypical immunophenotype mandates MGRS workup, including evaluation for light chain cast nephropathy, light chain deposition disease, AL amyloidosis, and immunoglobulin-mediated glomerulonephritis, according to the Nature Reviews Nephrology and Praxis Medical Insights 7, 8.

The American Society of Clinical Oncology recommends that treatment initiation for the B-cell lymphoproliferative disorder depends on the presence of symptoms and cytopenias, with observation appropriate for asymptomatic patients and rituximab-based therapy standard for CD20+ B-cell lymphomas 1, 6.
For the lambda-restricted plasma cell clone, treatment depends on plasma cell burden and presence of organ damage, with observation only if plasma cells <10% and no organ damage, and immediate clone-directed therapy if evidence of MGRS with renal involvement, as per the Nature Reviews Nephrology and Praxis Medical Insights 7, 8.

If both clones require treatment, prioritize based on organ-threatening complications, with renal dysfunction from light chains taking precedence, and a multidisciplinary approach involving hematology and nephrology is essential, according to the American Journal of Kidney Diseases and Nature Reviews Nephrology 7, 8, 9.