Marginal zone lymphoma (MZL) with plasmacytic differentiation can mimic other B-cell entities—particularly CLL/SLL and lymphoplasmacytic lymphoma (LPL)—and often presents in the elderly with cytopenias rather than bulky nodal disease. Correct classification is critical, as comorbidity and frailty frequently constrain treatment intensity. We report a bone marrow–dominant, plasmacytoid MZL in an 84-year-old woman successfully managed with rituximab monotherapy.

We conducted a single-patient, retrospective case review of prospectively collected clinical, laboratory, pathology, and imaging data. Diagnostic workflow integrated complete blood count, immunoglobulin quantification, bone marrow histology with immunohistochemistry (IHC), multiparameter flow cytometry, and FDG-PET/CT. Treatment selection followed a frailty-adapted decision process.

An 84-year-old woman presented with progressive fatigue and dyspnea on exertion. Baseline labs showed leukocytosis with marked lymphocytosis and macrocytic pancytopenia (WBC 22.2 × 10^9/L; absolute lymphocytes 18.4 × 10^9/L; Hb 8.1 g/dL; MCV 105 fL; platelets 42 × 10^9/L). Immunoglobulins were not suggestive of LPL/WM (IgM 0.73 g/L; IgG 13.6 g/L; IgA 1.7 g/L). FDG-PET/CT revealed mediastinal/abdominal lymphadenopathy, splenomegaly, and a sternal cortical irregularity suspicious for osseous involvement.

Bone marrow biopsy was hypercellular (∼95%) with ∼90% interstitial/patchy small-to-intermediate B-cell infiltration; reticulin fibrosis 0/4; Congo red negative. IHC supported a non-CLL, non-mantle phenotype: CD20 strong positive; CD5, CD23, CD10, cyclin D1, annexin A1, TRAP all negative. Flow cytometry demonstrated a clonal mature B-cell population (CD19+, CD20+, CD38+, cCD79a+) without CLL-type markers (CD5/CD23 negative). Plasmacytic differentiation was present, yet serum IgM remained normal, arguing against LPL/WM. Overall, findings established marginal zone lymphoma with plasmacytic differentiation, stage IV-A (marrow ± splenic/possible bone involvement).

Given advanced age, cytopenias, and frailty, cytotoxic chemo-immunotherapy was deferred. The patient received rituximab monotherapy with antiviral prophylaxis and supportive care (transfusion as needed). Treatment was well tolerated; early follow-up showed clinical improvement with rising hemoglobin and platelet counts and reduction in lymphocytosis.

This case highlights three practice points. First, plasmacytic differentiation in MZL can masquerade as CLL or LPL/WM; a disciplined panel—CD5/CD23/cyclin D1 negativity with strong CD20 and compatible flow cytometry—prevents misclassification. Second, serological context matters: normal IgM helped exclude LPL/WM despite plasmacytoid histology. Third, in the very elderly/frail, rituximab monotherapy is a rational, lower-toxicity strategy that can reverse cytopenias and improve function when marrow disease predominates. The possible osseous signal on imaging further underlines the heterogeneity of MZL dissemination. Educationally, the case underscores integrating morphology, IHC, flow, and serology to secure diagnosis and tailor therapy beyond one-size-fits-all chemo-immunotherapy.

Bone marrow-dominant MZL with plasmacytic differentiation presents diagnostic challenges but can be accurately classified through integrated morphology, IHC, flow cytometry, and serology. In very elderly or frail patients, rituximab monotherapy represents a rational and effective treatment strategy, offering hematologic recovery and functional benefit while minimizing toxicity.