A 72-year-old Indian woman is found to have WBC 52,000/μL on routine blood work during evaluation for anemia. She reports a 4-month history of progressive dyspnea and mild abdominal discomfort. On examination, the spleen is palpable 6 cm below the costal margin. Peripheral blood smear shows numerous small lymphocytes with scant cytoplasm, occasional smudge cells, and rare prolymphocytes. Flow cytometry reveals CD5+, CD19+, CD23+ B cells with weak surface immunoglobulin. Bone marrow biopsy shows interstitial and nodular infiltration by small lymphocytes. Cytogenetics shows deletion 13q. What is the most likely diagnosis?

Explanation

## Diagnosis: Chronic Lymphocytic Leukemia (CLL) ### Clinical Presentation **Key Point:** CLL is the most common adult leukemia in Western countries and typically presents in elderly patients with insidious onset of lymphocytosis, often discovered incidentally on routine labs. ### Diagnostic Criteria Met | Feature | Finding | Diagnostic Significance | |---------|---------|------------------------| | **Lymphocyte count** | 52,000/μL | Absolute lymphocytosis (>5,000/μL) | | **Morphology** | Small lymphocytes + smudge cells | Smudge cells (basket cells) are pathognomonic for CLL | | **Flow cytometry** | CD5+, CD19+, CD23+ | Classic CLL immunophenotype | | **Surface Ig** | Weak expression | Monoclonal B-cell population | | **Bone marrow** | Interstitial and nodular infiltration | Confirms marrow involvement | | **Cytogenetics** | del(13q) | Favorable prognostic marker | | **Splenomegaly** | 6 cm | Present in ~50% of CLL cases | ### Immunophenotypic Profile **High-Yield:** CLL is defined by the **CD5+, CD19+, CD23+ B-cell phenotype**. This is the only B-cell lymphoma that co-expresses CD5 (a T-cell marker) — a unique feature. **Mnemonic:** **CLL = CD5 + CD19 + CD23 + Weak Ig + Smudge cells** — the classic pentad. ### Prognostic Markers | Cytogenetic Finding | Prognosis | Median Survival | |---------------------|-----------|------------------| | **del(13q)** | Favorable | >10 years | | **Trisomy 12** | Intermediate | 5–8 years | | **del(11q)** | Unfavorable | 5–7 years | | **del(17p)** | Very unfavorable | <3 years | This patient has del(13q), which carries the best prognosis and may not require immediate treatment if asymptomatic. ### Why Not Prolymphocytic Leukemia? **Clinical Pearl:** Prolymphocytic leukemia (PLL) presents with higher WBC counts (often >100,000/μL), abundant prolymphocytes (>55% of lymphocytes), and **CD23 negativity**. This patient has CD23+ cells with rare prolymphocytes — classic CLL. ### Bone Marrow Involvement Pattern - **Interstitial:** Scattered infiltration between normal hematopoietic cells - **Nodular:** Focal aggregates of lymphocytes - Both patterns are seen in CLL; nodular pattern alone suggests lymphoma **Clinical Pearl:** Many CLL patients are asymptomatic at diagnosis and may not require immediate treatment. Watch-and-wait is appropriate for early-stage, asymptomatic disease. Treatment is indicated for progressive marrow failure, massive organomegaly, or symptomatic disease. [cite:Robbins 10e Ch 13]