Leukaemia and lymphoma

Sorting blood cancers

• Acute leukaemia presents with marrow failure: anaemia, infections from neutropenia, bleeding from low platelets (petechiae, epistaxis, bleeding gums), plus bone pain and infiltration (gum hypertrophy in monocytic AML).
• Diagnosis: a bone marrow aspirate and trephine biopsy confirms leukaemia, with flow cytometry and cytogenetics. Lymphoma needs an excision biopsy of a whole node (architecture matters; FNA is not enough). Leukaemia is the commonest cancer after radiation exposure and the commonest childhood cancer.

Acute leukaemias

• Acute promyelocytic leukaemia: t(15;17), PML–RARA; faggot cells full of Auer rods; presents with DIC; treated with all-trans retinoic acid plus arsenic trioxide, which make promyelocytes mature. Differentiation syndrome a few days into treatment: fever, breathlessness, weight gain, pulmonary infiltrates, effusions, rising WBC and renal impairment; give dexamethasone at once.
• T-lymphoblastic lymphoma/leukaemia: adolescent boys with a large anterior mediastinal mass, stridor when lying flat; avoid supine general anaesthesia.
• Testicular relapse: painless firm testicular enlargement after ALL treatment, even with a normal blood count, because the blood–testis barrier shields blasts from chemotherapy.
• Myeloid sarcoma (chloroma): a mass of myeloblasts outside the marrow, often orbital in children, turning green in air (MPO); it counts as AML.
• FAB L3 ALL is mature B-cell (Burkitt) leukaemia with t(8;14).

Myelodysplastic syndrome

• Clonal, ineffective haematopoiesis in older adults: pancytopenia with macrocytosis and normal B12 and folate, bilobed hypogranular neutrophils (pseudo-Pelger), ring sideroblasts, hypercellular marrow with under 20% blasts. It can progress to AML.

Chronic leukaemias

• CML: t(9;22), Philadelphia chromosome, BCR–ABL tyrosine kinase. Very high WBC with myeloid cells at every stage, basophilia, massive splenomegaly, low leucocyte alkaline phosphatase. BCR–ABL testing confirms it. Imatinib blocks the kinase; response is tracked by quantitative PCR for BCR–ABL transcripts, because a normal count does not mean the clone has gone. Untreated, it enters blast crisis.
• CLL: commonest leukaemia of older adults; small mature B cells (CD5, CD19, CD20, CD23), smudge cells. Often found by chance with lymphocytosis and small nodes: early asymptomatic disease is managed by watch and wait. Complications: warm autoimmune haemolysis, hypogammaglobulinaemia and infections (give non-live vaccines early), Richter transformation. Treatment when needed: BTK inhibitors, venetoclax.
• Hairy cell leukaemia: middle-aged men; splenomegaly, pancytopenia with monocytopenia, dry tap; TRAP-positive, BRAF V600E; cladribine.

Lymphomas

• Hodgkin subtypes: nodular sclerosis (commonest; young women; mediastinal mass; lacunar cells), mixed cellularity (EBV), lymphocyte-rich (best prognosis), lymphocyte-depleted (worst; HIV).

• B symptoms: fever over 38 °C, drenching sweats, over 10% weight loss in 6 months. Ann Arbor staging: I one region, II two or more on one side of the diaphragm, III both sides, IV extranodal.

Plasma cell disorders

• Multiple myeloma: monoclonal plasma cells making IgG (commonest), IgA or light chains only. Hypercalcaemia, renal failure (light-chain cast nephropathy), anaemia, bone lesions (punched-out lytic lesions, fractures; bone scan often normal because osteoblasts are suppressed). Rouleaux, very high ESR, Bence Jones proteinuria.
• Infections are frequent despite high total globulin because the normal polyclonal antibodies are suppressed (immunoparesis).
• Urine dipstick detects albumin, not free light chains, so heavy light-chain proteinuria can give a negative dipstick; use urine electrophoresis and immunofixation.
• AL amyloidosis complicates myeloma: macroglossia, periorbital purpura after coughing, nephrotic syndrome, and restrictive cardiomyopathy with thick walls but low-voltage ECG; Congo red shows apple-green birefringence.
• MGUS: small paraprotein, under 10% marrow plasma cells, no organ damage; about 1% a year progress. Solitary plasmacytoma: one lesion with normal marrow and no CRAB; radiotherapy; many later become myeloma.
• Waldenström macroglobulinaemia: IgM, hyperviscosity (visual upset, headache, bleeding), nodes, no lytic lesions; plasmapheresis.

Myeloproliferative neoplasms and polycythaemia

• Secondary polycythaemia comes from chronic hypoxia (high altitude, as in soldiers returning from Siachen, COPD, cyanotic heart disease) or EPO-secreting tumours: EPO is high and the spleen is normal.
• Gout is common in myeloproliferative disease because high cell turnover releases purines, raising urate.

Reactive white cell changes

• Infection: neutrophilia with band forms, toxic granulation and Döhle bodies (left shift): marrow releasing immature neutrophils. Steroids raise neutrophils by demargination without a left shift.
• Leukaemoid reaction (very high WBC in severe infection) has a high LAP score, unlike CML.
• Marked lymphocytosis in children: pertussis (very high counts in infants predict severe disease).
• Infectious mononucleosis (EBV): fever, exudative tonsillitis, posterior cervical nodes, splenomegaly, atypical lymphocytes; amoxicillin causes a widespread rash; avoid contact sports for several weeks because the spleen can rupture.
• Langerhans cell histiocytosis: children with punched-out skull lesions, scaly scalp rash, otitis; cells are CD1a and S100 positive with Birbeck granules (rod or tennis-racket shaped).

Haematological emergencies

• Neutropenic sepsis (fever with neutrophils under 0.5 × 10⁹/L): IV broad-spectrum antibiotics within 1 hour, even if the patient looks well; avoid rectal examination. G-CSF (filgrastim) speeds recovery and commonly causes bone pain; rarely splenic rupture.
• Leucostasis: very high blast counts (often over 100 × 10⁹/L, mostly AML) plug small vessels: headache, confusion, blurred vision, retinal haemorrhages, hypoxia and infiltrates. Reduce the count urgently (hydroxycarbamide, leukapheresis, chemotherapy) and avoid red cell transfusion, which raises viscosity. Blasts consume oxygen in an arterial blood sample (leucocyte larceny), giving a falsely low PaO₂; pulse oximetry is not affected.
• Tumour lysis syndrome (Burkitt, ALL, high-count AML): high potassium, phosphate and urate, low calcium, acute kidney injury. Tetany occurs because phosphate precipitates with calcium; avoid calcium in asymptomatic patients. Prevent with hydration and allopurinol or rasburicase.
• Pseudohyperkalaemia: in very high white counts (CLL), fragile cells leak potassium during clotting or pneumatic-tube transport; the ECG is normal and a carefully handled heparinised sample is normal.
• Myeloma hypercalcaemia: first IV 0.9% saline, then a bisphosphonate (dose for renal function).
• Spinal cord compression (back pain, leg weakness, sensory level): dexamethasone and urgent MRI of the whole spine, then radiotherapy or surgery.

The spleen

• White pulp: the periarteriolar lymphoid sheath (PALS) holds T cells; follicles hold B cells; the marginal zone mounts rapid responses to polysaccharide capsules. Red pulp filters old or damaged red cells.
• Splenic rupture: the commonly injured solid organ in blunt trauma, especially with left lower rib fractures. Left upper quadrant pain referred to the left shoulder tip (Kehr sign) because blood irritates the diaphragm, supplied by the phrenic nerve (C3–C5). A haemodynamically stable patient, even with a grade III laceration, is managed non-operatively with monitoring (angioembolisation if needed); instability needs splenectomy.
• Delayed rupture of a subcapsular haematoma can occur days to weeks later. An acutely enlarged spleen in malaria or infectious mononucleosis can rupture with little or no trauma.
• After splenectomy: reactive thrombocytosis peaking in the first one to two weeks; Howell–Jolly bodies and target cells on the film. If ITP relapses and Howell–Jolly bodies are absent, suspect an accessory spleen. Pancreatic tail injury can cause a fistula or subphrenic collection.
• Overwhelming post-splenectomy infection, most often Streptococcus pneumoniae, causes rapid septic shock. Vaccinate against pneumococcus, meningococcus and Haemophilus (2 weeks before elective surgery or 2 weeks after emergency surgery), give prophylactic penicillin and a standby antibiotic.

Remember CML: Philadelphia, basophils, low LAP. CLL: smudge cells, CD5. APL: t(15;17), DIC, ATRA.

Exam trap A stable patient with splenic laceration is observed, not operated on; shoulder tip pain with shock days after a fall suggests delayed rupture.

How FCPS asks about this

• Myeloid cells at all stages, basophilia, huge spleen: CML; confirm with BCR–ABL; monitor with quantitative PCR.
• Bleeding gums, petechiae and blasts: acute leukaemia; confirm with bone marrow aspirate and biopsy.
• Asymptomatic lymphocytosis with smudge cells: CLL; watch and wait.
• ATRA-treated APL with fever, infiltrates and weight gain: differentiation syndrome; dexamethasone.
• Myeloma with infections despite high globulin: suppressed normal immunoglobulins; negative dipstick because it misses light chains.
• WBC 180 with confusion and hypoxia: leucostasis; tetany after induction is phosphate precipitating calcium.
• Septic shock months after splenectomy: Streptococcus pneumoniae; absent Howell–Jolly bodies after splenectomy suggest an accessory spleen.