A 72-year-old woman from Bangalore is referred to hematology for evaluation of a 2-year history of progressive lymphocytosis. She reports no B symptoms. Physical examination reveals mild lymphadenopathy in the cervical and axillary regions. CBC: Hb 11.8 g/dL, WBC 28,000/μL (lymphocytes 78%), platelets 95,000/μL. Peripheral blood smear shows small, mature-appearing lymphocytes with scant cytoplasm and a characteristic 'smudge cell' appearance. Flow cytometry: CD5+, CD19+, CD23+, surface immunoglobulin (weak), CD10 negative. Serum LDH is normal. What is the most likely diagnosis?

Explanation

## Diagnosis: Chronic Lymphocytic Leukemia (CLL) ### Clinical Presentation The patient demonstrates classic CLL features: - Insidious onset over years (indolent course) - Asymptomatic (no B symptoms) - Mild lymphadenopathy - Incidental discovery of lymphocytosis ### Laboratory & Flow Cytometry Findings | Feature | Finding | Significance | |---------|---------|---------------| | WBC | 28,000/μL with 78% lymphocytes | Lymphocytosis | | Morphology | Small, mature lymphocytes with scant cytoplasm | Characteristic of CLL | | Smudge cells | Present on smear | Fragile lymphocytes, pathognomonic for CLL | | CD5 | Positive | T-cell antigen on B cells (aberrant co-expression) | | CD19 | Positive | B-cell marker | | CD23 | Positive | Marker of CLL (vs. mantle cell lymphoma) | | Surface Ig | Weak expression | Typical of CLL | | CD10 | Negative | Excludes follicular lymphoma | | LDH | Normal | Low tumor burden, indolent course | ### Diagnostic Criteria (Matutes Score) **Key Point:** CLL is diagnosed by **≥5,000/μL clonal B-lymphocytes** with **CD5+, CD19+, CD23+ co-expression**. This patient has 21,840/μL (78% of 28,000) B-lymphocytes with the classic immunophenotype. **High-Yield:** The **CD5+/CD19+/CD23+ triad** is the gold standard for CLL diagnosis. CD5 is a T-cell marker aberrantly expressed on CLL B cells, distinguishing CLL from other B-cell lymphomas. **Mnemonic: CLL Immunophenotype** **CD5-23** = **C**hronic **L**ymphocytic **L**eukemia (CD5+, CD19+, CD23+) **Clinical Pearl:** **Smudge cells** (Gumprecht shadows) are fragile, damaged lymphocytes that appear as pale, amorphous material on blood smear. They are virtually pathognomonic for CLL and result from mechanical trauma during slide preparation. ### Why CLL and Not Other Lymphomas? The **CD23+ status** is critical: - **CLL = CD5+, CD23+** (this patient) - **Mantle cell lymphoma = CD5+, CD23−** (would have different morphology and prognosis) - **Follicular lymphoma = CD10+, CD23+, CD5−** (this patient is CD10−, CD5+) [cite:Robbins 10e Ch 13]