Paper I
Question
A 30-year-old female presented with history of easy fatiguability, weight loss, recurrent fever and gum bleeding. Clinical examination revealed severe pallor with hepatosplenomegaly. Blood routine examination showed Hb 8gm%, total count- 75000/mm3, platelet count 40000/mm3
- (a) What is your provisional diagnosis 2 mark(s)
- (b) Mention the classification systems of the disease and enlist the types 5 mark(s)
- (c) Describe the peripheral smear and bone marrow findings of the disease 8 mark(s)
Answer
(a) Provisional diagnosis
- Acute Leukaemia — the combination of a young patient with constitutional symptoms (fatiguability, weight loss, fever), bleeding manifestations (gum bleeding, from thrombocytopenia), severe pallor (anaemia), hepatosplenomegaly (leukaemic infiltration), markedly elevated total leucocyte count (75,000/mm³), and thrombocytopenia (40,000/mm³) is characteristic of acute leukaemia (marrow failure from leukaemic blast infiltration causing anaemia and thrombocytopenia, with circulating blasts driving the elevated total count)
(b) Classification systems and types
FAB (French-American-British) classification
- Based on morphology and cytochemistry
- AML (Acute Myeloid Leukaemia): M0 (undifferentiated) through M7 (megakaryoblastic) — e.g., M3 (acute promyelocytic leukaemia)
- ALL (Acute Lymphoblastic Leukaemia): L1, L2, L3 (based on cell size/morphology)
WHO classification (current standard)
- Incorporates cytogenetic, molecular, and immunophenotypic features in addition to morphology
- AML: AML with recurrent genetic abnormalities (e.g., t(15;17) APL, t(8;21)), AML with myelodysplasia-related changes, therapy-related AML, AML not otherwise specified
- ALL (now termed lymphoblastic leukaemia/lymphoma): B-lymphoblastic leukaemia/lymphoma (with recurrent genetic abnormalities), T-lymphoblastic leukaemia/lymphoma
(c) Peripheral smear and bone marrow findings
Peripheral smear
- Presence of numerous blast cells — large cells with high nuclear:cytoplasmic ratio, fine/dispersed chromatin, and prominent nucleoli
- Auer rods may be seen in the cytoplasm of myeloblasts (pathognomonic for AML when present, absent in ALL)
- Reduced normal mature neutrophils, red cells, and platelets (“hiatus leukaemicus” — gap between blasts and mature cells, with few intermediate maturation forms)
- Anaemia (normocytic normochromic) and thrombocytopenia
Bone marrow findings
- Hypercellular marrow, replaced by a monotonous population of blast cells (≥20% blasts required for diagnosis of acute leukaemia per WHO criteria)
- Suppression of normal trilineage haematopoiesis
- Cytochemistry: Myeloperoxidase (MPO)/Sudan Black B positive in myeloblasts; Periodic Acid-Schiff (PAS) positive (block pattern) in lymphoblasts
- Immunophenotyping (flow cytometry): Confirms lineage — myeloid markers (CD13, CD33, MPO) for AML; lymphoid markers (CD19, CD10, TdT for B-ALL; CD3, CD7 for T-ALL)
- Cytogenetics/molecular studies: For prognostic stratification and detection of specific recurrent abnormalities (e.g., t(9;22) Philadelphia chromosome in some ALL, t(15;17) in APL)