Q1 LONG ANSWER 10M ★ High-yield

Classify leukaemias. Describe the clinical features and laboratory diagnosis of acute leukaemia and differentiate AML from ALL.

Pathology · 2nd Professional — Para-Clinical

Definition and Classification

Leukaemia is a malignant neoplasm of the haemopoietic stem cells, in which the marrow is replaced by neoplastic cells that usually spill into the blood.

Basis	Types
Rate of progression	Acute — immature blast cells predominate; rapidly fatal if untreated. Chronic — mature cells predominate; indolent
Cell line	Myeloid and lymphoid
The four classical types	AML, all, CML, CLL

WHO definition of acute leukaemia — 20% or more blasts in the marrow or blood (the older FAB criterion was 30%)
Age distribution — all peaks at 2 to 5 years and is the commonest childhood malignancy; AML rises with age; CLL is a disease of the elderly; CML of middle life

Aetiology

Ionising radiation — the shortest latency of any radiation-induced cancer
Chemicals — benzene; previous alkylating agent chemotherapy and topoisomerase inhibitors (therapy-related AML)
Genetic — down syndrome (20-fold increased risk), Fanconi anaemia, ataxia telangiectasia, Bloom syndrome, neurofibromatosis
Viruses — HTLV-1 causes adult T cell leukaemia/lymphoma
Preceding marrow disorders — myelodysplasia, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, myeloproliferative disease

Clinical Features

Mechanism	Features
Marrow failure — from crowding out	Anaemia → pallor, fatigue, breathlessness. Neutropenia → fever, mouth ulcers, recurrent and severe infection (the commonest cause of death). Thrombocytopenia → petechiae, purpura, bleeding gums, epistaxis
Organ infiltration	Hepatosplenomegaly and lymphadenopathy — far more prominent in all; bone pain and tenderness (marrow expansion) — a child refusing to walk; CNS involvement and testicular infiltration in all, both sanctuary sites
Features specific to AML	Gum hypertrophy and skin infiltration in monocytic types (M4, M5); chloroma (granulocytic sarcoma) — a greenish tumour mass; DIC in acute promyelocytic leukaemia (M3)
Metabolic	Hyperuricaemia and tumour lysis syndrome on starting treatment

Differentiating AML from ALL

Feature	Acute myeloid leukaemia	Acute lymphoblastic leukaemia
Age	Adults; rises with age	Children — peak 2 to 5 years
Blast morphology	Larger; abundant cytoplasm; fine chromatin; 2–4 nucleoli; AUER rods (pathognomonic)	Smaller; scanty cytoplasm; coarse chromatin; indistinct nucleoli; NO Auer rods
Myeloperoxidase and Sudan black	Positive	Negative
PAS	Negative or diffuse	Positive — coarse block positivity
Non-specific esterase	Positive in monocytic types	Negative
TdT	Negative	Positive
Immunophenotype	CD13, CD33, CD117, MPO	B-all — CD19, CD10 (CALLA), CD20. T-all — CD3, CD7
Lymphadenopathy and organomegaly	Less marked	Prominent
CNS and testicular involvement	Uncommon	Characteristic
Prognosis	Worse; cure in about 35–40% of the young	Better — over 80% cure in children

CLINICAL PEARL

Auer rods settle the question instantly when present. They are needle-shaped crystalline inclusions of azurophilic granules, seen only in myeloid blasts, and are abundant in acute promyelocytic leukaemia. Their absence proves nothing — they are seen in only a minority of AML — but their presence excludes all.

Laboratory Diagnosis

Full blood count — anaemia, thrombocytopenia; the white count may be high, normal or low (aleukaemic leukaemia), so a normal count never excludes it
Peripheral smear — blasts; a "leukaemic hiatus" in AML, meaning blasts and mature cells with the intermediate forms missing
Bone marrow aspirate — hypercellular with 20% or more blasts; essential for diagnosis
Cytochemistry — myeloperoxidase, Sudan black, PAS, non-specific esterase
Immunophenotyping by flow cytometry — now the definitive method of lineage assignment
Cytogenetics and molecular studies — the single most important prognostic factor; t(15;17) in M3, t(8;21), inv(16) are favourable; complex karyotype and Philadelphia-positive all unfavourable

The Fab and WHO Classifications

System	Basis	Note
FAB (French–American–British)	Morphology and cytochemistry alone	AML M0 to M7; all L1 to L3. Still widely used and still examined
WHO	Morphology plus immunophenotype, cytogenetics and clinical features	Blast threshold lowered to 20%; genetically defined entities recognised separately

FAB subtype	Name	Feature
M0	Minimally differentiated	Diagnosed only by immunophenotype
M1, M2	Myeloblastic	M2 carries t(8;21) — favourable
M3	Acute promyelocytic	T(15;17); heavy granulation with FAGGOT cells (bundles of Auer rods); DIC; responds to ATRA
M4	Myelomonocytic	Inv(16) with eosinophilia — favourable
M5	Monocytic	Gum hypertrophy and skin infiltration
M6	Erythroleukaemia	Dysplastic erythroid precursors
M7	Megakaryoblastic	Associated with down syndrome; marrow fibrosis and a dry tap
L3 (all)	Burkitt-type	Deeply basophilic vacuolated cytoplasm; t(8;14)

Applied Aspects

Acute promyelocytic leukaemia (M3) is a medical emergency — the granules release procoagulant material causing DIC, which worsens when chemotherapy lyses the cells. ATRA (all-trans retinoic acid) differentiates the cells rather than killing them and has converted the worst-prognosis AML into the best
Tumour lysis syndrome — hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia with acute renal failure; prevented by hydration and allopurinol or rasburicase
CNS prophylaxis is mandatory in all — intrathecal methotrexate, because the blood–brain barrier makes the CNS a sanctuary from systemic chemotherapy
Neutropenic fever is an emergency — broad-spectrum antibiotics within an hour, before any culture result
Childhood all is one of the great successes of modern oncology, with cure rates above 80% where full treatment is available — which makes access, not biology, the limiting factor in much of India

All questions in Haematology II: Leukaemias, Lymphomas & Haemostasis

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