A 58-year-old man from Mumbai presents with a 6-month history of progressive fatigue and early satiety. On examination, he has marked splenomegaly (8 cm below the costal margin) and hepatomegaly. His CBC shows: Hb 9.2 g/dL, WBC 185,000/μL with left shift (myelocytes 18%, metamyelocytes 12%, bands 8%, segmented neutrophils 45%, eosinophils 8%, basophils 3%), and platelets 420,000/μL. Bone marrow aspirate shows myeloid hyperplasia with increased eosinophils and basophils. Cytochemistry: MPO positive, PAS negative. Fluorescence in situ hybridization (FISH) reveals t(9;22) with BCR-ABL1 fusion. What is the most likely diagnosis?

Explanation

## Diagnosis: Chronic Myeloid Leukemia (CML), Chronic Phase ### Clinical Presentation The patient presents with classic CML features: - Insidious onset with fatigue and early satiety (from splenomegaly) - Marked splenomegaly and hepatomegaly - Incidental discovery on routine blood work ### Laboratory Findings | Feature | Finding | Significance | |---------|---------|---------------| | WBC count | 185,000/μL | Marked leukocytosis | | Differential | Left shift with all myeloid stages | Myeloid hyperplasia | | Eosinophils & Basophils | Increased (8% + 3%) | Characteristic of CML | | Platelets | 420,000/μL | Often elevated in chronic phase | | MPO | Positive | Confirms myeloid lineage | | PAS | Negative | Rules out ALL | | t(9;22) BCR-ABL1 | Present | Pathognomonic for CML | ### Diagnostic Criteria Met **Key Point:** The **t(9;22) translocation with BCR-ABL1 fusion** is the defining molecular hallmark of CML and is present in >95% of cases. This Philadelphia chromosome is diagnostic. **High-Yield:** CML chronic phase is defined by: 1. <5% blasts in peripheral blood 2. <5% blasts in bone marrow 3. <5% basophils + eosinophils combined (this patient has 11%, but the presence of t(9;22) overrides morphology) 4. No Auer rods **Clinical Pearl:** The **left shift with all myeloid maturation stages present** (myelocytes through segmented neutrophils) is characteristic of CML and distinguishes it from AML, where blasts dominate. ### Why Chronic Phase? Despite the eosinophil + basophil count being slightly elevated (11% vs. <5% criterion), the **presence of t(9;22) BCR-ABL1 is diagnostic of CML**, and the overall morphology (mature neutrophils predominate, <5% blasts) confirms **chronic phase**. Accelerated phase would show 5–19% blasts; blast crisis would show ≥20% blasts. ### Mnemonic: CML Features **SPLEEN** = **S**plenomegaly, **P**hiladelphia chromosome, **L**eft shift, **E**osinophilia, **E**levated platelets, **N**eutrophilia [cite:Robbins 10e Ch 13]