A 38-year-old Indian woman presents with a 3-month history of progressive abdominal distension and early satiety. On examination, she has a palpable left upper quadrant mass and mild hepatomegaly. Laboratory investigations show hemoglobin 9.2 g/dL, WBC 7,200/μL, and platelets 1,20,000/μL. Abdominal CT reveals a large splenic mass (12 cm) with involvement of para-aortic lymph nodes. Bone marrow biopsy shows infiltration by large cells with "wrinkled tissue paper" appearance and positive CD20, CD5, and FMC7 markers. What is the most likely diagnosis?

Explanation

## Diagnosis: Splenic Marginal Zone Lymphoma (SMZL) ### Clinical Presentation **Key Point:** SMZL typically presents with massive splenomegaly (>5 cm in 90% of cases) and cytopenias due to bone marrow infiltration and splenic sequestration. - Indolent course with insidious onset - Abdominal distension and early satiety from splenic enlargement - Cytopenias (anemia, thrombocytopenia) common - Lymph node involvement is extranodal (splenic hilum, para-aortic) rather than nodal ### Morphology & Immunophenotype **High-Yield:** The "wrinkled tissue paper" or "crumpled silk" appearance is pathognomonic for marginal zone cells. | Feature | SMZL | CLL/SLL | LPL | |---------|------|---------|-----| | **Morphology** | Marginal zone cells (wrinkled nuclei) | Small lymphocytes | Lymphocytes + plasma cells | | **CD5** | Negative | Positive | Negative | | **CD20** | Positive | Positive | Positive | | **FMC7** | Positive | Negative | Negative | | **Splenomegaly** | Massive (>5 cm) | Mild–moderate | Mild–moderate | | **Bone marrow** | Infiltration common | Infiltration common | Infiltration variable | **Key Point:** The **CD5-negative, CD20-positive, FMC7-positive** phenotype is diagnostic of marginal zone lymphoma and excludes CLL/SLL (which is CD5+, FMC7−). ### Cytogenetic & Molecular Features - Trisomy 3 (60–70% of cases) — most common abnormality - del(7q) and mutations in TP53 associated with worse prognosis - No t(11;14) or t(9;14) (unlike lymphoplasmacytic lymphoma) ### Staging & Prognosis **Clinical Pearl:** SMZL is Ann Arbor stage IV at diagnosis (bone marrow involvement), but prognosis is relatively favorable with median survival 10–15 years. ### Why Splenic Involvement Dominates 1. Marginal zone cells preferentially home to splenic white pulp (marginal zone) 2. Massive splenic infiltration → cytopenias from bone marrow replacement and splenic sequestration 3. Secondary lymph node involvement (para-aortic) is extranodal spread, not primary nodal disease ### Differential Diagnosis Exclusion **CLL/SLL:** CD5+ (this patient is CD5−), FMC7− (this patient is FMC7+). CLL also presents with lymphocytosis, not marginal zone morphology. **Lymphoplasmacytic lymphoma:** Lacks the characteristic wrinkled nuclei; shows plasma cell differentiation; associated with Waldenström macroglobulinemia; CD5− but FMC7− as well. **Nodal marginal zone lymphoma:** Primarily involves lymph nodes (not spleen); splenomegaly is incidental; less common than SMZL. [cite:Robbins 10e Ch 13]