Haematology & Oncology — Disease Index & Clinical Criteria

Written by Betra Youhanna, a medical student and not a doctor — check every detail against your own teaching.

Disease Index · 45 entries across 11 categories · finals-triage

Criteria & Scores · 65 scoring systems, classifications, comparison tables, frameworks

C/P — Clinical Presentation

Inves — Investigations

Mng — Management

Special — Pathognomonic / disease-unique

Membrane & Enzyme Haemolytic Anaemias

4 entries

Hereditary Spherocytosis

C/P

Most common inherited anaemia in Northern Europe
Autosomal dominant (rarely recessive)
Onset any age — infancy if severe, adulthood if mild
Jaundice — marked if co-inherited Gilbert's (impaired conjugation compounds haemolytic bilirubin load)
Pigment gallstones (frequent)
Splenomegaly (most patients)
Aplastic crisis — precipitated by parvovirus B19

Inves

Blood film — microspherocytes: small diameter, densely stained, no central pallor
Reticulocytes raised (5–20%)
Coombs (DAT) negative — excludes autoimmune haemolysis
Osmotic fragility test — increased
Family history — anaemia severity similar across relatives

Mng

Folic acid — severe cases, to prevent deficiency from high red-cell turnover
Splenectomy — only if clinically indicated (severe anaemia or gallstones); anaemia improves but spherocytes persist
Delay splenectomy as long as possible — preserve immune function, post-splenectomy sepsis risk
Blood transfusion — if severe

Special

Coombs-negative spherocytes — distinguishes from AIHA (Coombs-positive, also produces spherocytes)
Vertical membrane-protein defect (skeleton–lipid bilayer uncoupling) → surface-area loss → sphere trapped in splenic microcirculation (extravascular haemolysis)
Splenectomy = clinical cure only; genetic defect remains so spherocytes stay on film

Hereditary Elliptocytosis

C/P

Similar to HS (clinical + labs), usually milder
Often no haemolysis — discovered by chance on blood film

Inves

Blood film — elliptical / oval red cells

Mng

Usually none — most patients asymptomatic, no treatment required

Special

Elliptocytes — the "milder cousin" of HS

G6PD Deficiency

C/P

X-linked recessive — males affected, females carriers
Asymptomatic at baseline; symptoms only on oxidative challenge
Acute haemolytic attack — headache, back pain, fever; haemoglobinuria (dark urine), jaundice
Neonatal haemolytic anaemia + jaundice — mother ingesting fava beans / mothball (naphthalene) exposure

Inves

Blood film (during crisis) — bite cells, Heinz bodies (oxidised denatured Hb), contracted/fragmented cells
Hb fallen (6–10 g/dL), reticulocytes raised
LDH raised, haptoglobin decreased, haemoglobinuria
Enzyme assay — screening (dye-reduction) confirmed by direct quantitative assay
Time the enzyme assay AFTER crisis resolves — false-normal during acute haemolysis (surviving young retics carry high enzyme levels)

Mng

Avoid triggers — fava beans, oxidant drugs; good hygiene to prevent infection
Stop offending drug / treat underlying infection
Maintain high urine output — renal protection against haemoglobin
Blood transfusion — if severe anaemia
Neonatal — phototherapy + exchange transfusion if severe jaundice
Folic acid — severe cases

Special

Bite cells + Heinz bodies = signature film
Triggers — fava beans, mothballs (naphthalene), vitamin K analogues; drugs: sulfonamides, nitrofurantoin, chloramphenicol, quinolones, primaquine, chloroquine (caution), high-dose aspirin, phenazopyridine; illness (e.g. DKA), infections
Gene Xq28; sole RBC source of NADPH → reduced glutathione (protects Hb/membrane from oxidant stress); variants Type B (Western), Type A (African)

Pyruvate Kinase Deficiency

C/P

Autosomal recessive (>100 mutations described)
Anaemia varies (Hb 4–10 g/dL) — symptoms milder than the Hb suggests
Jaundice usual; gallstones frequent
Frontal bossing may be present

Inves

Blood film — poikilocytosis
Autohaemolysis NOT corrected by glucose
Direct enzyme assay

Mng

Splenectomy — if severe anaemia with frequent transfusions

Special

Right-shifted O₂ dissociation curve from raised 2,3-DPG → enhanced tissue O₂ delivery → mild symptoms despite low Hb
Rigid cells from reduced ATP (last glycolysis step blocked)

Haemoglobinopathies

4 entries

Alpha Thalassaemia

C/P

Quantitative defect — reduced α-chain synthesis (contrast: HbS = qualitative/structural)
Historically malaria-endemic distribution; heterozygote carriers partially protected from malaria
Severity tracks number of deleted α-genes (4 total, 2 per chromosome)
Silent carrier –α/αα (1 gene lost) — asymptomatic
α-trait ––/αα or –α/–α (2 genes lost) — microcytosis, mild/no anaemia
HbH disease ––/–α (3 genes lost) — excess β chains form HbH tetramers → haemolytic anaemia
Hb Barts / hydrops fetalis ––/–– (4 genes lost) — incompatible with life

Inves

MCV / MCH decreased
HbA2 decreased or normal — key discriminator from β-trait (which raises HbA2)
HbH disease — inclusion bodies (precipitated β chains; "golf-ball" cells) on reticulocyte prep
DNA — MLPA + multiplex PCR (α defects are deletions → look for gaps); α-globin sequencing 2nd line

Mng

HbH / severe forms — transfusion + iron chelation as for β-major (see entry 6)
Silent carrier / trait — no treatment, genetic counselling

Special

α defects = gene deletions (→ MLPA/PCR); 4-gene deletion = Hb Barts, hydrops fetalis
HbH inclusion bodies on reticulocyte prep (precipitated β chains; "golf-ball" cells)

Beta Thalassaemia

C/P

Point mutations (β⁰ = no synthesis, β⁺ = reduced), >200 types
Trait (minor) β/β⁺ or β/β⁰ — usually asymptomatic, normal or mild anaemia (Hb 9–14 g/dL)
Major β⁰/β⁰ or β⁺/β⁺ — severe, transfusion-dependent; onset 1–2 months after birth (as HbF declines)
Major physical — hepatosplenomegaly, skeletal deformities (marrow expansion), growth failure

Inves

Trait — MCV low (<77 fL), MCH low, RBC count raised (unique feature), RDW often normal
Trait diagnostic — raised HbA2 (>3.5%)
Major — markedly low Hb; film microcytic hypochromic with nucleated RBCs; electrophoresis HbF dominant/only, variable HbA2
DNA — β-globin sequencing (β defects are point mutations); MLPA del/dup 2nd line

Mng

Transfusion — every 3–4 weeks, target mean Hb 12 g/dL (suppresses ineffective marrow → prevents skeletal deformity)
Iron chelation — start after 10–20 transfusions OR serum ferritin ≥1000 µg/L OR age 3 years
Chelation monitoring — serum ferritin, liver iron concentration (LIC), echo + endocrine labs
Curative — allogeneic bone marrow transplant
Prevention — antenatal diagnosis / screening; gene therapy (future)
Folic acid supplementation

Special

Vicious cycle — unpaired globin precipitates → ineffective erythropoiesis (marrow) + haemolysis (spleen) → EPO ↑ → massive marrow expansion + ↑ gut iron absorption
Iron overload (transfusion + gut absorption) — non-transferrin-bound iron → free hydroxyl radicals → pituitary/pancreas (diabetes)/parathyroid, heart (failure/arrhythmia — leading cause of death), liver (cirrhosis)
β-trait + triplicated α gene → worse chain imbalance → thalassaemia intermedia
Extramedullary haematopoiesis (can form masses)

Sickle Cell Disease

C/P

Autosomal recessive; β6 Glu→Val substitution → HbS polymerises when deoxygenated → sickling
Commonest genetic disorder in the UK; 1:10 black carriers; heterozygotes malaria-protected; distribution — Africa, Middle East, Mediterranean basin, India
Genotype severity — severe: HbSS (commonest/most severe), HbS/β⁰-thal; milder: HbSC (but retinopathy & avascular necrosis are particular problems), HbS/β⁺-thal (HbF-protective); also HbSD, HbSO Arab
Two overlapping mechanisms — haemolysis-driven vasculopathy (pulmonary HTN, priapism, leg ulcers) vs viscosity/vaso-occlusion (pain crises, ACS, osteonecrosis)
Vaso-occlusive crisis — bones/joints (back, ribs, hips), most common; not dangerous itself but → bone infarction; precipitants: infection, cold/damp, dehydration, unaccustomed exercise, stress
Dactylitis (hand-foot syndrome) — infants/children <2y, small bones of hands/feet, often first presentation, may deform
Girdle syndrome — mesenteric sickling → lower abdominal pain + localised ileus (mimics acute abdomen)
Crisis types — vaso-occlusive, aplastic, sequestration, haemolytic + infections
Chronic / vaso-occlusive complications — avascular necrosis, leg ulcers, retinopathy, renal (papillary necrosis), CNS disease, hyposplenism, gallstones, delayed growth & puberty, acute multi-organ failure
Natural history — birth well (HbF); infancy: pneumococcal sepsis, splenic sequestration, dactylitis; childhood: ischaemic CVA, sepsis, sequestration, pain crises; adulthood: pain crises, ACS, haemorrhagic CVA, irreversible organ damage
Causes of death — childhood acute ~67% (infection, hypersplenism, CVA, pulmonary); adulthood chronic ~56% (lung, renal, CNS)

Inves

Hb 6–9 g/dL (normocytic anaemia; higher in HbSC), reticulocytes raised (10–14%; lower in HbSC)
Bilirubin / LDH variable (haemolysis); creatinine often below normal (renal hyperfiltration)
Sickle solubility test — positive for HbS but CANNOT distinguish carrier (AS) from disease (SS)
Definitive genotyping — Hb electrophoresis or HPLC
Blood film — sickle cells; target cells (prominent in HbSC)
Transcranial Doppler (TCD) — stroke screening; high risk if velocity >200 cm/s (10% children overt stroke, 30% silent infarcts on MRI)
ACS workup — FBC (vs steady state), U&E/LFT/CRP, ABG on air, group & screen, CXR (serial), blood cultures + atypical serology; findings: leucocytosis, sudden Hb drop, platelets <200 predict severe ACS; CXR alveolar consolidation (lower lobes), may be delayed ≤12 h

Mng

Pain — paracetamol + NSAIDs (first-line/adjunct); opioids (morphine, diamorphine, oxycodone; oral, bolus or PCA); adjuvants — antiemetics, laxatives, antihistamine
AVOID pethidine (norpethidine metabolite → seizures) and Entonox (relative avoid)
Acute mainstay — oxygen (only if hypoxic), fluids (oral preferred), analgesia; antibiotics (esp chest & girdle syndromes); DVT prophylaxis; transfusion if very anaemic (sequestration/aplastic); exchange transfusion (ACS, CVA); incentive spirometry
ACS — exchange transfusion preferred (lowers HbS% without raising viscosity); IV fluids (avoid overload); IV antibiotics (as for CAP); respiratory support — high-flow O₂, chest physio, incentive spirometry, bronchodilators (if wheezy/asthma), CPAP/ventilation if deteriorating
Aplastic crisis (parvovirus B19) — single top-up transfusion, self-limiting 1–2 weeks
Sequestration — emergency (hypovolaemic shock); blood/fluid support; prevent via parent education (palpate spleen)
Stroke prevention (high-risk TCD) — regular transfusions (STOP protocol → risk <1%/yr)
Priapism — prompt drainage + alpha-adrenergic drugs + blood transfusion; prevent with diethylstilbestrol / vasoconstrictors
Infection prophylaxis — lifelong penicillin V; vaccines — pneumococcal conjugate (7-valent <2y, 23-valent >2y), HiB, meningococcal, influenza, Hep B
Hydroxycarbamide — disease-modifying agent (raises HbF)

Special

Pathophysiology (4) — HbS polymerisation → red-cell dehydration → endothelial damage/adherence → inflammation from oxidant damage
Acute Chest Syndrome — 2nd commonest admission cause, up to 25% of deaths, recurrence ≤80%, commonest ITU cause; unique to SCD, can progress to ARDS; = new pulmonary infiltrate on CXR + fever OR respiratory symptoms (hypoxia predicts severity); causes — pulmonary infection (54%; atypicals Chlamydia/Mycoplasma/RSV), fat embolism (marrow), pulmonary infarction, hypoventilation (pain/opioid splinting)
Aplastic crisis (parvovirus B19 cytotoxic to erythroid precursors → LOW reticulocytes) vs sequestration (organ pooling → HIGH reticulocytes) — key differential, both cause sudden severe anaemia
Priapism — by adulthood ~89% of males have had ≥1 episode; prolonged/stuttering → impotence
Hyposplenism / functional asplenia → encapsulated organisms (pneumococcus, meningococcus, HiB, E. coli, Salmonella) → pneumonia / UTI / osteomyelitis; often triggers a vaso-occlusive crisis; Salmonella osteomyelitis classically associated
Girdle syndrome — mesenteric-circulation sickling
Osteomyelitis — commonest organisms Salmonella and Staphylococcus, in long bones; key diagnostic challenge is distinguishing vaso-occlusive crisis / bone infarction from infection

physiology · background · low-yield

Other

Osteomyelitis imaging — ultrasound: periosseous abscess; MRI: bone marrow oedema, subperiosteal fluid, increased vascularity, contrast enhancement

Haemoglobinopathy — Lab Diagnosis

CBC & Blood Film

CBC first — red-cell indices (MCV, MCH key); thalassaemia = hypochromic microcytic with raised RBC count (distinguishes from other microcytic anaemias)
Blood film (May-Giemsa stain) — polychromasia (↑ reticulocytes), spherocytes (HS / haemolysis), schistocytes (MAHA), sickle cells (sickle cell anaemia), Heinz bodies & basophilic stippling (inclusions)
Absence of these cells does NOT rule out haemolysis, but their presence suggests the anaemia type

Iron Studies

Serum ferritin/iron, total iron-binding capacity (TIBC), transferrin saturation — purpose: exclude iron deficiency anaemia
Zinc protoporphyrin (ZPP) — increased in lead poisoning or low iron

Hb Electrophoresis & HPLC

Cellulose acetate electrophoresis (CAE) — alkaline pH 8.4–8.6; Hb negatively charged → migrates to anode (+)
Citrate agar electrophoresis — acid pH; separates Hb S and Hb C (different migration patterns)
HPLC — charged groups on ion-exchange material interact with charged groups on Hb → identifies Hb types

Tests for Hb S

Sickling in whole blood — sickle cells seen in a thin wet film sealed with paraffin wax
Hb S solubility test — Hb S insoluble in high-molarity phosphate buffer → solution turbidity

DNA Analysis

Alpha thalassaemia — MLPA + multiplex PCR (deletions); alpha-globin sequencing
Beta thalassaemia — beta-globin sequencing; beta-globin del/dup by MLPA

physiology · background · low-yield

Physiology

Hb types — HbA (α₂β₂), HbF (α₂γ₂), HbA2 (α₂δ₂); 4 heme groups per Hb (one per globin chain); O₂ binds the Fe within heme

Background

Globin gene loci — β-globin cluster on chromosome 11, α-globin cluster on chromosome 16; fetal→adult switch (γ→β) around birth / first 6 months — explains delayed onset of β-thalassaemia & sickle disease

Acute Leukaemias

2 entries

Acute Myeloid Leukaemia (AML)

C/P

Proliferation of myeloid blasts/granulocytes; abrupt, dramatic onset
Mostly adults (median 67y; only ~6% under 20y)
Marrow failure — anaemia, thrombocytopenia (bleeding), neutropenia (infection)
Leukaemic infiltration — splenomegaly, hepatomegaly, bone pain, meningeal irritation, oral lesions (chloromas / gum hypertrophy — classic M4/M5 monocytic)
Metabolic — hyperuricaemia (tumour lysis), acute renal failure
Pre-existing — MDS, Fanconi anaemia, Down syndrome

Inves

CBC — WBC usually elevated (50–100k, can be normal/low); anaemia + thrombocytopenia
Blood film — blast cells; Auer rods
Bone marrow — hypercellular, blasts >20%
Cytochemistry — Sudan Black + myeloperoxidase (MPO) positive (confirms myeloid lineage)
Flow cytometry — CD34, CD33, CD117, CD13, MPO
Cytogenetics / FISH + molecular genetics — for WHO classification
MRD (minimal residual disease) — RT-PCR for fusion transcripts (AML1-ETO), mutant NPM1, or flow immunophenotype

Mng

Stabilise — transfuse, treat infection, stop bleeding
Induction chemotherapy (start ASAP) → remission; then consolidation/intensification (high-dose, post-remission, destroys MRD)
Allogeneic stem cell transplant — high-risk / relapse; graft-vs-leukaemia (GVL) effect; CD33 target (gemtuzumab)
APL (M3) — ATRA (specific treatment; manage DIC risk)
Supportive — RBC transfusion Hb 80–100 g/L; platelet prophylaxis if <10×10⁹/L (no bleeding); febrile neutropenia (neutrophils <0.5×10⁹/L) → Pip-Tazo + gentamicin; antifungal prophylaxis itraconazole; systemic antifungal caspofungin (resistant fever/lung infiltrate); aciclovir (viral) + co-trimoxazole (PCP) if lymphopenia (T-cells <0.2)

Special

Auer rods — pathognomonic myeloblast inclusion (never in ALL/lymphoblasts)
FAB M0–M7 (see Criteria); M3/APL = t(15;17) PML-RARA → DIC from promyelocyte pro-coagulant granules → ATRA
Prognosis — APL/CBF good, complex/monosomal karyotype bad; older age & poor performance status worse

Acute Lymphoblastic Leukaemia (ALL)

C/P

Immature lymphoid blasts; most common childhood cancer, but adults affected 10:1 in absolute numbers; M>F slightly
Marrow failure + tissue infiltration — LAD, organomegaly, testis, CNS

Inves

Examination — lymph nodes, abdominal organomegaly, testis, CNS
CBC — blasts
Bone marrow — >20% blasts (required for diagnosis)
Immunophenotyping — B vs T lineage
Cytogenetics — molecular aberrations (e.g. Philadelphia chromosome)
CSF — cranial-nerve / CNS infiltration (sanctuary site)

Mng

4 phases — remission induction → remission consolidation → maintenance → bone marrow transplant
Long course (2–3 y); sanctuary-site coverage (testis, CNS — chemo penetrates poorly)
Antibiotic prophylaxis before/after treatment; therapeutic if febrile

Special

Subtypes — common (pre-B), B-cell, T-cell, undifferentiated; most common childhood cancer, peak age 3y (peak B-cell precursors in marrow), boys > girls, whites
B-ALL presents as leukaemia (marrow); T-ALL presents as lymphoma — large mediastinal/thymic mass ± pleural effusions in adolescent males (airway-compression emergency)
Blast morphology — scant basophilic cytoplasm, high N:C ratio, stippled chromatin, inconspicuous nucleoli; NO Auer rods (distinguishes from AML)
IHC — TdT+ (95%, only in immature lymphoblasts) & PAS+ (coarse granules); B-ALL = CD20 + TdT, T-ALL = CD3 + TdT; CD34 blast marker
Common childhood NHLs — ALL, Burkitt, anaplastic large-cell lymphoma
Congenital risk — Down, Fanconi, Bloom, Klinefelter, ataxia-telangiectasia; HTLV-I → adult T-cell leukaemia-lymphoma; EBV → Burkitt

physiology · background · low-yield

Background

Precursor B-cell neoplasm — clinical split by presentation: >25% marrow blasts = leukaemia; presenting as a mass = lymphoma (same underlying entity)

Chronic Leukaemias & Myeloproliferative Neoplasms

5 entries

Chronic Myeloid Leukaemia (CML)

C/P

Excess proliferation & accumulation of functional mature myeloid cells
20–40% asymptomatic; fatigue, weight loss, abdominal discomfort/early satiety (splenomegaly), night sweats
Most diagnosed in chronic phase; mean age ~42y (Egypt data; global median ~67y)
Course — chronic phase → (accelerated, now omitted in new classification) → blast phase

Inves

t(9;22) Philadelphia chromosome → BCR-ABL1 fusion gene → constitutive tyrosine kinase activity
Blast phase (new criteria) — blasts ≥20% in blood/marrow, extramedullary blast proliferation, or ↑ lymphoblasts
Monitoring — BCR-ABL transcript levels; deep molecular response MR4.5 = log-4.5 reduction (ratio 1:32,000)

Mng

Tyrosine kinase inhibitors (TKIs) — imatinib (Gleevec, 1st-gen, 2001); nilotinib (Tasigna, 2nd-gen) 300 mg BID newly-diagnosed Ph+ CML-CP / 400 mg BID if resistant/intolerant to imatinib
Historical — hydroxyurea, interferon, transplant

Special

Philadelphia t(9;22) / BCR-ABL = defining lesion (BCR-ABL+ separates CML from Ph-negative MPNs)
MPN classification — BCR-ABL⁺ = CML; BCR-ABL⁻ classic = PV/ET/PMF; non-classic = mastocytosis, chronic neutrophilic leukaemia, chronic eosinophilic leukaemia
~20% of all leukaemias; 10-yr overall survival 80–90% on TKI; untreated → inevitable blast crisis (AML- or ALL-like)

Chronic Lymphocytic Leukaemia (CLL)

C/P

Clonal mature small B-lymphocytes; most common leukaemia in Western world; peak 7th decade
Often incidental lymphocytosis on CBC; indolent course
Recurrent infections (hypogammaglobulinaemia — pneumonia/sinusitis), autoimmune disease (AIHA, ITP), LAD/hepatosplenomegaly
Late — bone marrow failure

Inves

CLL = clonal B-cells >5×10⁹/L; MBL (monoclonal B-lymphocytosis) <5×10⁹/L (pre-malignant)
Blood smear — smear/smudge cells (fragile lymphocytes crushed on preparation)
Flow cytometry — CD19 (or CD20), CD5 (aberrant T-marker), CD23
Clonality — light-chain restriction (kappa or lambda; normal λ:κ ≈ 2:3)
IgVH mutation status — mutated (memory-B origin, less aggressive) vs unmutated (naïve origin, aggressive); CLL surface Ig = IgM

Mng

Watch and wait — early/asymptomatic (early treatment doesn't improve survival)
Chemotherapy + anti-CD20 monoclonal (rituximab)
BCR-signalling inhibitors — ibrutinib (BTK), idelalisib (PI3K-δ)
BCL-2 inhibitor — venetoclax
Glucocorticoids — autoimmune manifestations
Vaccinations (influenza, pneumococcal); immunoglobulin replacement (recurrent bacterial infection)
MBL — yearly FBC + lymph node exam

Special

CD5+ (aberrant) CD23+ B-cell = signature immunophenotype; smudge/smear cells
Survival = apoptosis failure — BCL-2, NF-κB driven by BCR (BTK, PI3K, Lyn) + TLR (MyD88)
Rai & Binet staging (see Criteria); T-cell CLL has worse prognosis

physiology · background · low-yield

Microbiology

HTLV-II associated with atypical hairy cell leukaemia

Background

Key determinants of clinical course — diagnosis stage (early vs late), disease biology (aggressiveness/resistance), responsiveness to treatment, age & health state (variables not entirely independent)

Polycythaemia Vera (PV)

C/P

Overproduction of red cells (± raised platelets & WBCs); onset 55–60y
Vascular — major thrombosis (arterial/venous/unusual sites e.g. splanchnic), microvascular (headache, dizziness, tinnitus, paraesthesia, erythromelalgia)
Aquagenic pruritus — classically associated with PV

Inves

Diagnostic Hb >16.2 g/dL
JAK2 mutation (80–95%)
EPO low (suppressed — autonomous production, cells hypersensitive to EPO) — distinguishes from secondary polycythaemia (high EPO)

Mng

Fatal if untreated
Venesection (phlebotomy) — first-line; target HCT <0.45 (lowers viscosity → prevents stroke/clot)
Aspirin
Hydroxyurea — cytoreduction for high-risk; carries AML-transformation risk

Special

Low EPO + JAK2 = distinguishes primary from secondary polycythaemia
Can transform to AML / myelofibrosis

Essential Thrombocythaemia (ET)

C/P

Overproduction of platelets
Vascular — thrombosis (arterial/venous), microvascular (headache, dizziness, erythromelalgia)

Inves

Platelet count >450×10⁹/L (sustained ≥2 months), no other cause
Driver mutations — JAK2 (50–60%), CALR, MPL

Mng

Low risk (age <40, no RF) — aspirin alone
Intermediate risk (age 40–60, no RF) — probably aspirin only
High risk (age >60 OR plt >1500 OR thrombosis history) — aspirin + hydroxyurea

Special

Can transform to AML

Primary Myelofibrosis (PMF)

C/P

Disease of the elderly; gradual replacement of bone marrow by fibrosis
Anaemia (marrow failure)
Massive splenomegaly — extramedullary haematopoiesis (infarcts, compression)
Constitutional — fever, sweats, weight loss

Inves

Blood film — leucoerythroblastic picture, teardrop cells (tear-drop poikilocytes)
Bone marrow — fibrosis
Driver mutations — JAK2 (50–60%), CALR, MPL

Mng

Mostly palliative — blood transfusions, splenectomy, radiotherapy, chemotherapy, interferon, androgens, immunomodulators, erythropoiesis-stimulating agents
JAK inhibitor — ruxolitinib (shrinks spleen, improves symptoms; not curative)
Allogeneic stem cell transplant — only curative option

Special

Teardrop cells + leucoerythroblastic film; massive spleen
Can transform to AML

Lymphomas

5 entries

Hodgkin Lymphoma

C/P

Germinal-centre B-cell origin; Reed-Sternberg cell is the (scarce) neoplastic cell (<10% of tumour; >90% reactive inflammatory background)
Bimodal age — peak 20s, second peak 60s–70s; FHx risk 7× for siblings, 100× for identical twins
Painless enlarged rubbery greyish-tan nodes — cervical/axillary/inguinal; arises in single node/chain with orderly contiguous spread
Localised to axial node groups (cervical, mediastinal, para-aortic); mesenteric nodes / Waldeyer ring & extranodal spread uncommon
B-symptoms — fever, drenching night sweats, weight loss >10%; pruritus classic

Inves

Excisional lymph node biopsy (preserves architecture) — diagnosis requires tissue
Bone marrow — stage III/IV or B-symptoms present
Staging — CT neck/chest/abdomen/pelvis; PET/CT (staging, response, relapse — used in HL & DLBCL)
Ann Arbor stage I–IV + A/B/X/E modifiers (see Criteria)
IHC — classic RS: CD15+, CD30+, CD20−; NLPHL popcorn: CD20+, CD15−, CD30−
Lumbar puncture — indicated for CNS disease or paranasal / testicular / breast involvement; MRI — vertebral or neurological disease

Mng

Stage IA–IIA — ABVD ×3 courses + consolidation radiotherapy
Stage IIB–IV — ABVD ×6–8 courses (by response); consolidation if no further response after 6
Relapse — achieve 2nd complete remission → PBSCT (peripheral blood stem cell transplant)
Immunotherapy — brentuximab vedotin (anti-CD30 ADC → traffics to lysosome → MMAE → microtubule disruption → G2/M arrest → apoptosis)
Pre-treatment — fertility preservation (sperm cryopreservation / embryo banking), cardiac assessment (>70y or cardiac/resp/diabetes), tumour-lysis prophylaxis: allopurinol >24h pre-chemo, rasburicase for high-risk/established TLS, IV hydration + electrolyte correction + urine alkalinisation

Special

Reed-Sternberg cell — large bi/multinucleated "owl-eye", prominent eosinophilic nucleoli (~lymphocyte-sized); EBV in 30% of biopsies; RS cells secrete cytokines recruiting reactive lymphocytes + eosinophils
4 RS variants — classic, mononuclear, lacunar (pale cytoplasm retracts → formalin artifact; nodular sclerosis), L&H "popcorn" (NLPHL)
Classic HL (95%) subtypes — Nodular sclerosis (65–75%, most common; young adults, cervical/mediastinal, EBV uncommon, excellent prognosis; collagen bands + lacunar cells), Mixed cellularity (20–25%, older, EBV 70%, plentiful classic/mononuclear RS + excess eosinophils, good prognosis), Lymphocyte-rich, Lymphocyte-depleted
NLPHL (5%) — isolated cervical/axillary nodes, no EBV, no B-symptoms, excellent prognosis (late relapse / can relapse as NHL); popcorn L&H cells CD20+; classic RS rare, eosinophils scanty

Diffuse Large B-Cell Lymphoma (DLBCL)

C/P

Most common high-grade NHL; aggressive, fast-growing — but potentially curable
Arises from germinal-centre dark zone (centroblasts)

Inves

CD20+ mature B-cell
Staging as lymphoma — CT, PET/CT (metabolically active), bone marrow (all NHL patients)

Mng

Never "watch and wait" — treat immediately to aim for cure
Stage I non-bulky — R-CHOP ×3 courses + involved-field radiotherapy
Advanced/bulky (all others) — R-CHOP ×6–8 courses
Partial responders — consolidation or 2nd-line chemotherapy
Primary refractory / first relapse — 2nd-line chemotherapy → PBSCT

Special

R-CHOP = rituximab + CHOP (gold standard first-line)
Molecular — DLBCL bcl-6 (3q27), can carry c-myc; both DLBCL & Burkitt arise from germinal-centre dark zone (somatic hypermutation)
Burkitt lymphoma — the other high-grade dark-zone B-cell NHL: t(8;14) c-myc, EBV-associated (endemic)
Can arise from transformation of follicular lymphoma (Richter transformation)

physiology · background · low-yield

Microbiology

NHL viral/risk associations — EBV, HIV, HHV-8 (KSHV), HTLV-1; plus immunodeficiency (HIV/transplant) and environmental toxins

Follicular Lymphoma

C/P

Mature B-cell neoplasm from germinal-centre (light-zone) B-cells
Most common indolent lymphoma; 2nd most common NHL overall
Widespread painless lymphadenopathy (cervical/axillary/inguinal) — 85% widespread at diagnosis; indolent wax-and-wane course; usually incurable

Inves

Morphology — diffuse effacement by back-to-back, crowded, uniform-sized nodules; neoplastic follicles: similar-sized, non-polarised, attenuated/absent mantle zones, NO tingible-body macrophages, infrequent mitoses (vs varied reactive follicles)
IHC — CD20+; CD10+ & BCL2+ (germinal-centre origin); BCL2+ in neoplastic follicles [t(14;18)] vs BCL2− in reactive follicles
Ki67 — randomly high/moderate (vs high & polarised in reactive follicles)

Mng

Stage I — involved-field radiotherapy
Stage II–IV asymptomatic — watch and wait
Stage II–IV symptomatic — chemotherapy R-CVP ×8 + maintenance rituximab
Young (<35y) in 1st remission — low-intensity allograft option
Relapse — induce 2nd complete remission → BMT

Special

BCL2+ from t(14;18) → neoplastic follicles resist apoptosis (reactive follicles are BCL2−) — the key discriminator
Can transform to DLBCL (more common) or B-lymphoblastic leukaemia/lymphoma (if TdT+)

Mycosis Fungoides (Cutaneous T-cell Lymphoma)

C/P

Most common cutaneous T-cell lymphoma (CTCL); malignant peripheral CD4+ helper T-cells
Adults/elderly (median 55–60); chronic progressive skin lesions — Patch → Plaque → Tumour
"Great imitator" — often treated as eczema for years before biopsy

Inves

Skin biopsy (correlate with clinical history); exclude eczema, psoriasis, drug reactions, cutaneous spread of extracutaneous peripheral T-cell lymphoma first
Patch — epidermotropism, linear basal-layer lymphocytes ("string of pearls"), haloed lymphocytes, wiry papillary-dermis collagen
Plaque — Pautrier microabscesses (intra-epidermal malignant T-cell clusters), cerebriform (hyperconvoluted) nuclei, lichenoid/perivascular dermal infiltrate
Tumour — extensive dermal pleomorphic infiltrate, ++mitoses, ± blast transformation (DDx large B-cell lymphoma on IHC), loss of epidermotropism
IHC — CD3+, CD4+ (or CD8+, monoclonal), CD20−

Mng

Patch & plaque stages may respond to chemotherapy; tumour stage is aggressive & resistant

Special

Epidermotropism + Pautrier microabscesses + cerebriform nuclei = signature triad
Sézary syndrome = leukaemic/disseminated variant (peripheral T-cell neoplasm)
Tumour stage = vertical growth, epidermis destroyed → loss of epidermotropism

Reactive (Benign) Lymphadenopathy

C/P

Node enlargement from inflammatory stimuli, neoplastic proliferation, or metastasis
Painful/tender + red hot overlying skin → acute infection (rapid capsular stretch); painless firm → think neoplastic
Reactive lymphadenitis — acute or chronic; specific examples toxoplasmosis, cat-scratch

Inves

Acute nonspecific — swollen grey-red engorged nodes; pyogenic organisms → neutrophilic infiltrate (pathognomonic), severe → necrosis/abscess (fluctuant)
Chronic patterns — follicular hyperplasia (B-cell: RA, toxoplasmosis, early HIV), paracortical hyperplasia (T-cell: EBV, post-vaccination, phenytoin), sinus histiocytosis (macrophage expansion draining cancers)
Follicular hyperplasia morphology — varied-sized follicles, preserved architecture, distinct mantle zones, polymorphic cells, tingible-body macrophages ("starry sky"; RA, SLE)

Mng

Treat underlying cause; biopsy if malignancy suspected

Special

Tingible-body macrophages = hallmark of REACTIVE follicles (B-cells dying naturally) — absent in follicular lymphoma
Reactive = polyclonal (mixed B + T); neoplastic = monoclonal (single-cell origin, light-chain restriction)
CD3+/CD20+ mixed = reactive; CD3+/CD20− = T-cell lymphoma; CD3−/CD20+ = B-cell lymphoma
CD45 (LCA)+ = lymphoma anywhere; CD45− node mass = metastasis (carcinoma/melanoma/sarcoma)

physiology · background · low-yield

Background

Lineage CD markers — B-cell: CD19, 20, 22, 23; T-cell: CD2, 3, 4, 5, 7, 8

Investigations, Procedures & Transplant

3 entries

MALT / Marginal Zone Lymphoma

C/P

Low-grade (indolent) mature B-cell non-Hodgkin lymphoma arising from marginal-zone B cells
Frequently extranodal — most common site is the stomach (gastric MALToma)

Special

Gastric MALToma classically associated with Helicobacter pylori infection

Stem-Cell / Bone Marrow Transplant (HSCT)

Types & Sources

Stem-cell types — adult (largest reservoir = marrow; also skin/brain/prostate/muscle/peripheral blood), umbilical cord blood (collected post-delivery; children/small adults; double-cord for adults), embryonic (from early fertilised embryos)
Autologous — patient's own cells; NO immunologic conflict; "rescue" from a marrow-lethal dose of high-dose chemo
Allogeneic — donor cells (related/unrelated/cord); minor HLA disparity; high-dose therapy + immunotherapy → "reject" the cancer & build new immunity

Indications

Cancer — leukaemia, myelodysplasia, lymphoma, paediatric tumours, multiple myeloma, solid tumours
Non-cancer — autoimmune disease (RA, MS, scleroderma, SLE), immune deficiency, sickle cell anaemia, thalassaemia

Process

Donor selection — HLA tissue typing of 6–10 antigens (allogeneic)
Harvest — large-volume marrow aspiration (1–2 L) or peripheral-blood apheresis after growth-factor stimulation; cord = sterile empty of cord/placenta into a bag at delivery; cryopreserve 5–10 y
Conditioning/preparative — chemo-radiation → myeloablation + immunosuppression → marrow "space", eradicate malignant cells, reset immune system, allow engraftment
Infusion — IV; cells "home" to marrow + spleen niches (recognise stromal adhesion + growth factors); donor T lymphocytes essential for engraftment
Reconstitution — marrow cellularity decreased; immunologic reconstruction >100 days; T + B dysfunction, low Ig ~3 months → fungal/viral/bacterial risk; GVHD delays it
Post-transplant care — autologous 100 days, allogeneic 180 days or longer (tolerance)

Eligibility & Immunology

Age — autologous 0–70y; allogeneic matched-related 55–60y; mismatched/unrelated 50–55y; up to 70 with reduced-intensity / non-myeloablative conditioning
GVHD risk rises significantly age >45
HLA = immunologic "password" (self vs non-self); donor T-cells react to foreign HLA → acute rejection (solid organ) / GVHD (BMT)
BMT rejection is bi-directional (graft rejection AND graft-vs-host); immunosuppression NOT lifelong — tolerance develops
Graft-vs-leukaemia (GVL) — donor immune system kills residual leukaemia

Special

Tandem transplant — two transplants within 3–4 months (auto-auto or auto-allo; auto-allo separates high-dose from immunotherapy); myeloma, testicular cancer, medulloblastoma, neuroblastoma
Long-term complications — prolonged infection (GVHD), infertility (women >> men; TBI >> cyclophosphamide), hypothyroidism 15–25% (TBI), cataracts (TBI/steroids), avascular necrosis (steroids), autoimmune dysfunction (GVHD), dry mouth/caries (GVHD/TBI), secondary malignancy (5–6× risk: PTLD + non-haematologic)

physiology · background · low-yield

Mechanism

Conditioning intensity — marrow-failure states need more immunosuppression; immune deficiency without an empty marrow → graft rejection

Background

Autoimmune-disease transplant threshold — reserved for severe disease: life-threatening / major morbidity (diffuse scleroderma), unresponsive to standard therapy (SLE), or early progressive relapse (MS)

Imaging in Haematology

Overview

Blood disorders by cell type — red cell, white cell, platelet
Mechanisms — increased production, decreased production, increased destruction, abnormal production
Haematological tumours affect blood, bone marrow, lymph nodes — lymphoid (lymphoma, lymphocytic leukaemia, myeloma) vs myeloid (AML, CML, myelodysplasia, myelofibrosis)
5 vital roles of imaging — correct diagnosis of cause/source, staging, monitoring treatment response, detecting relapse, therapeutic interventions (biopsy/venous access)

GI Malignancy Imaging

Options — colonoscopy (gold standard, allows biopsy), CT pneumocolon / virtual colonoscopy, minimal-prep CT, barium enema
"Apple core" — constricting colonic lesion suspicious for cancer
CT — caecal mass + liver metastases (staging)
GI malignancies — oesophagus (adeno/squamous), stomach (adeno), small bowel (lymphoma = commonest), large bowel (adeno); may present with anaemia / active bleeding
Active upper GI bleed — angiography + embolisation (interventional radiology)

Sickle Cell Imaging

Spine X-ray — dense sclerotic bones, "H-shaped vertebrae" (central end-plate infarction)
MRI — vertebral end-plate infarction; red marrow low signal on T1W
AVN — hips/femoral heads: dense, collapsed, "mushroom" appearance + surrounding radiolucent separation line
Skull X-ray — widened diploic space (marrow hyperplasia)
Extramedullary haematopoiesis — paraspinal (also liver, spleen, adrenals); CT + MRI delineate
Osteomyelitis — long bones; Salmonella/Staph; US periosseous abscess; MRI (marrow oedema, subperiosteal fluid, ↑ vascularity, contrast enhancement); hard to distinguish crisis/infarct from infection
Musculoskeletal — dactylitis, osteomyelitis, septic arthritis, osteonecrosis, gout, acute synovitis; systemic — cardiomegaly/CHF, pulmonary infarcts/pneumonia, cholelithiasis, autosplenectomy, renal infarcts/haematuria, stroke/brain infarcts

Thalassaemia Imaging

Iron overload (multiple transfusions) — heart + liver; liver intensely black on MRI (T2* shortening); special MRI quantifies iron deposition to guide chelation
Bone disease + extramedullary haematopoiesis + massive splenomegaly

Lymphoma Imaging

Diagnosis requires histology (biopsy); 12 nodal sites (Waldeyer ring, cervical, infra/supraclavicular, axillary/pectoral, mediastinal, hilar, spleen, para-aortic, mesenteric, iliac, inguinal/femoral)
CT — modality of choice for staging & follow-up (reproducibility)
US — confirm mass is nodal, guide biopsy
MRI — soft-tissue discrimination, pelvic staging, brain/spinal involvement, problem-solving
PET — NO role in primary diagnosis; post-treatment problem-solving (residual node active vs not), SUV measurement; isotope bone scan occasional (lymphoma spreads to bone late)

Myeloma Imaging

Most common primary bone tumour arising in bone; median 70y; IgG (60%) > IgA (25%); urine Bence-Jones (free light chains)
Bone destruction — increased osteoclastic resorption; skeletal survey 80% sensitive; rounded "punched-out" osteolytic lesions
Radio-isotope bone scan typically NEGATIVE (process is osteoclastic, not osteoblastic)
MRI — best for spine/bone/brain (early marrow infiltration); CT — disseminated soft-tissue disease + biopsy aid
Complications — spinal cord compression, pathological fractures, secondary amyloidosis, renal failure (protein deposition in tubules), recurrent pneumonias, thromboembolism

Venous Access & Interventions

PICC line — thin soft catheter into arm/leg/neck vein, tip in a large vein entering the heart; for long-term IV antibiotics, nutrition, medications (chemo), blood draws
Hickman line — tunnelled central venous catheter (often chemotherapy)
Guided interventions — biopsy, venous access (Hickman/PICC), radioablation/embolisation, drainage of abscesses/haematomas

Treatment Complications

Immunosuppression, opportunistic/fungal infection (lung, oesophagus, liver, brain), septicaemia, bleeding, secondary malignancies

physiology · background · low-yield

Background

Clinical care team — haematological problems managed by haematologists, oncologists, physicians and surgeons

Plasma Cell & Paraprotein Disorders

2 entries

Multiple Myeloma

C/P

Neoplastic plasma cells arising in bone marrow; median ~70y; commoner in men + Afro-Caribbeans
Presents de novo clinically, but preceded by MGUS in virtually all cases
CRAB — hyperCalcaemia, Renal failure, Anaemia, Bone lesions (pain, lytic, pathological fractures) + infections + hyperviscosity
Incidental triad — raised ESR/plasma viscosity, raised total protein/globulin, monoclonal band
Solitary plasmacytoma — single lesion, no systemic CRAB

Inves

Serum protein electrophoresis (SPEP) — monoclonal M-spike (dense narrow gamma-region band)
Immunofixation (serum + urine) — types the paraprotein (heavy G/A/M + light kappa/lambda; e.g. IgG kappa)
Urine Bence Jones protein (free light chains); serum free light chains — for oligo-secretory / light-chain-only / non-secretory disease
Skeletal survey — punched-out lytic lesions (80% sensitive); skull "pepper-pot"; MRI — suspected cord compression
Bone marrow biopsy — clonal plasma cells (aspirate >10–15%); blood film — rouleaux (RBC stacking from high protein)
Bloods — FBC, ESR/plasma viscosity raised, U&E, Ca²⁺, creatinine clearance; β2-microglobulin + albumin (prognostic → ISS)
Serum immunoglobulins — immune paresis (suppression of normal Ig)
Paraproteins — IgG (~80%) > IgA (~20%); light-chain only 20%; rare: non-secretory (~2%), IgD/IgE/IgM, plasma cell leukaemia; rest of Ig repertoire suppressed (immune paresis)
Radiography — multiple well-circumscribed punched-out lytic lesions with NO reactive bone (osteoclasts activated + osteoblasts inhibited); endosteal scalloping; diffuse demineralisation; false-negative technetium bone scan (no osteoblast activity to detect); normal ALP (lytic without osteoblastic activity)

Mng

SCT-eligible (younger/fitter) — 3-drug induction → autologous stem cell transplant → maintenance
SCT-ineligible — induction → continuous therapy
Targeted agents — proteasome inhibitors (bortezomib), thalidomide, steroids
Bone — bisphosphonates (ingested by osteoclasts → directly kill them) / denosumab (RANKL inhibitor, upstream); surgery / radiotherapy
Renal — dialysis; anaemia — EPO / transfusion; infection — antibiotics; hypercalcaemia management

Special

CRAB + SLiM myeloma-defining events (see Criteria)
Purely lytic lesions → bone scan false-negative (osteoblasts inhibited)
IgH switch-region translocations — t(11;14) cyclin D1 (commonest), t(4;14) FGFR3/MMSET, t(6;14) cyclin D3, t(14;16) c-maf; high-risk cytogenetics = t(4;14), t(14;16), del(17p); R-ISS staging (see Criteria)

MGUS / Smouldering Myeloma

C/P

Asymptomatic paraprotein states — no CRAB (both)
MGUS is the most common cause of an M-spike — always exclude malignancy before labelling

Inves

MGUS — M-protein <30 g/L, plasma cells <10%, CRAB absent
Smouldering — M-protein >30 g/L, plasma cells >10%, CRAB absent
Distinction is tumour burden (M-protein mass + marrow plasma-cell %)

Mng

MGUS — yearly monitoring; exclude MM, Waldenström's, lymphoma, AL amyloidosis first
Progression to CRAB → becomes active myeloma

Special

CRAB present → active myeloma (the dividing line)

Plasma Proteins, Paraproteinaemia & Amyloid

4 entries

Paraproteinaemia & Monoclonal Gammopathy

Definition

Monoclonal immunoglobulin band (M-protein / paraprotein) in serum — synthesis from a single plasma-cell clone (clonal expansion)
Monoclonal = sharp narrow spike (M-spike); polyclonal = broad diffuse gamma band

Causes (frequency order)

MGUS → multiple myeloma → AL amyloidosis → Waldenström's macroglobulinaemia (IgM) → solitary plasmacytoma → low-grade NHL/B-cell disorders → other
Hypergammaglobulinaemia — monoclonal (benign MGUS, myeloma, Waldenström IgM, heavy chain disease, leukaemia, lymphoma) vs polyclonal (chronic major infection, chronic liver disease, autoimmune, sarcoidosis)

M-protein & Free Light Chains

Types — whole molecule (heavy + light) OR free light chains only
Free light chains — small, filtered by kidney; appear in serum only if GFR compromised; otherwise in urine (Bence Jones)
Must test URINE as well — light-chain disease missed if only serum tested
Bence Jones protein — urinary Ig light chain; present in 75% of myeloma, light-chain-only 11%; readily cleared (low molecular mass)
Immunofixation (serum + urine) — detects & types the monoclonal Ig (heavy G/A/M + light kappa/lambda)

Special

Polyclonal (many clones → broad band) vs monoclonal (one clone → sharp spike)
Cirrhosis — polyclonal rise in all Ig, high IgA → β-γ bridging
Hypogammaglobulinaemia — pale gamma zone; ALWAYS check urine for BJP (light-chain myeloma is invisible on serum SPEP); causes: inherited/acquired ↓synthesis, loss (nephrotic syndrome, protein-losing enteropathy)
Waldenström's = IgM-secreting lymphoplasmacytic lymphoma

AL Amyloidosis

C/P

Deposition of amyloid (AL) fibrils from light-chain precursors → tissue deposition (heart, kidneys, nerves)
Occurs in 6–15% of myeloma patients; more common when the major paraprotein is free light chains

Inves

Serum/urine paraprotein detection — supportive finding
Definitive — amyloid fibrils on BIOPSY (rectal mucosa or abdominal fat)
Congo red stain → apple-green birefringence under polarised light (pathognomonic)

Mng

Treat the underlying clonal plasma-cell disorder / myeloma (deck: not detailed further)

Special

Congo red + apple-green birefringence = pathognomonic
Amyloid classification — AL (paraproteinaemia/primary/myeloma), AA (chronic inflammation/infection or Familial Mediterranean Fever), ASc (senile/cardiac), PA (neuropathy)

Serum Protein Electrophoresis (SPEP) & Plasma Proteins

Basics

Serum = blood allowed to clot (fibrinogen removed); plasma = collected into anticoagulant (fibrinogen present)
SPEP requires SERUM not plasma — fibrinogen band would mimic an M-spike
Separates by charge + size; proteins negatively charged at buffer pH → migrate cathode(−) → anode(+)
Bands (anode → cathode) — Albumin → Alpha-1 → Alpha-2 → Beta → Gamma

Functions & Synthesis

7 protein functions — nutrition, buffering, oncotic pressure (albumin), transport (albumin/transferrin/caeruloplasmin), enzyme inhibition (α1-antitrypsin), immunity (immunoglobulins, C3, C4), clotting (fibrinogen)
Liver-synthesised — albumin, clotting factors, alpha-fetoprotein, α1-antitrypsin, caeruloplasmin, transferrin; NOT immunoglobulins (made by plasma cells)
Total serum protein ↑ haemoconcentration/↑synthesis; ↓ haemodilution / loss (renal, gut, redistribution) / ↓synthesis

Band Constituents

Albumin — 60% of serum protein; carries Ca/bilirubin/Mg/drugs/hormones/H⁺; oncotic pressure; ↑ standing/venous stasis/dehydration, ↓ dilution/↓synthesis/loss/redistribution
Alpha-1 — α1-antitrypsin (+ α1-lipoprotein); acute-phase reactant ↑; inherited deficiency ↓ (emphysema/liver disease)
Alpha-2 — α2-macroglobulin, haptoglobin, caeruloplasmin, lipoproteins; ↑ acute phase, chronic infection, nephrotic syndrome
Haptoglobin — binds free Hb (complex cleared by RES); ↑ acute-phase, ↓ intravascular haemolysis (consumed)
Beta — transferrin, C3, lipoprotein
Gamma — immunoglobulins (bulk IgG; IgM & IgA more anodal → β-γ bridging)

Immunoglobulins

Structure — 2 heavy + 2 light chains, disulfide-linked; Fab (antigen binding, variable-region tips/CDR) + Fc (effector: complement); variable (N-terminal) vs constant (C-terminal)
IgG — secondary response, crosses placenta; IgA — mucosal surfaces; IgM — primary response + B-cell antigen receptor; IgD — B-cell antigen receptor; IgE — immediate hypersensitivity

Special

Low haptoglobin = intravascular haemolysis marker (consumed binding free Hb)
Nephrotic syndrome — α2 spike (α2-macroglobulin too large to filter) while albumin is lost

physiology · background · low-yield

Other

Myoglobin — released from damaged muscle (crush injury) and infarcted cardiac muscle; renally excreted if damage severe; gives a false-positive 'haem' result on urine reagent strip (mimics haematuria — heme peroxidase activity)

Background

Tumour markers — CEA, CA125; measured by specific immunoassays

Urine & CSF Protein Analysis

Urine

Dipstick — sensitive to albumin only (>200 mg/L); will NOT detect Bence Jones / globulins; false+ concentrated or alkaline urine, gross haematuria; false− dilute urine, tubular overload, Bence Jones protein
Quantification — PCR (protein:creatinine) significant >50 mg/mmol; ACR (albumin:creatinine) >30 mg/mmol; ACR diabetic >3 mg/mmol (microalbuminuria)
Proteinuria causes — benign, overflow (paraprotein/BJP), glomerular (albumin), tubular (low-MW: NAG, retinol-binding protein), urinary tract
Algorithm — +1 on dipstick → repeat → if positive exclude UTI & menstruation → check eGFR + random urine ACR + measure BP

CSF

Blood-brain barrier normally keeps proteins out; tests protein + glucose (fluoride-oxalate tube)
↑ CSF protein — contamination (blood), infection, chronic inflammatory disorders, tumours (spinal block)
SAH — spontaneous arterial bleed into subarachnoid space; diagnose by CT/angiography or CSF xanthochromia (if scan equivocal); xanthochromia detects bilirubin (from Hb), sample ≥12h post-bleed
Oligoclonal bands — local Ig synthesis (bands in CSF but NOT serum) → multiple sclerosis

Special

Standard dipstick misses Bence Jones (albumin-only) — check urine electrophoresis in suspected myeloma
Xanthochromia (bilirubin, ≥12h) distinguishes true SAH from a traumatic tap
Oligoclonal bands in CSF-only = MS (compare with serum)

Bone Marrow Failure

5 entries

Aplastic Anaemia

C/P

Pancytopenia with a hypocellular ("empty") marrow
Anaemia (tiredness, dyspnoea, angina), neutropenia (infection), thrombocytopenia (bleeding)

Inves

CBC — pancytopenia; marrow — reduced cellularity, replaced by fat
Hallmark = pancytopenia + hypocellular marrow (rules out peripheral destruction/sequestration)

Mng

Remove the cause — stop offending drug/toxin
Supportive — RBC/platelet transfusions, antibiotics
Severe — bone marrow transplant (curative, esp. young); immunosuppression (anti-thymocyte globulin + ciclosporin) if no donor

Special

Causes — congenital (Fanconi's) vs acquired: idiopathic/autoimmune (T-cell attack on stem cells, most common), radiation, drugs, chemicals (benzene), viruses (hepatitis)
Marrow fat-replacement histology

Fanconi Anaemia

C/P

Inherited (recessive, mostly autosomal recessive) anaemia causing bone marrow failure; ≥11 mutations; defective DNA repair
Onset first decade — often presents initially with thrombocytopenia or leukopenia
Physical — short stature; thumb/forearm/skeletal, eye, kidney/urinary tract, ear, heart, GI, oral, CNS anomalies; hearing loss, hypogonadism, developmental delay
Symptoms — fatigue, frequent infections, nosebleeds, easy bruising

Inves

Pancytopenia (low WBC, RBC, platelets); often macrocytic

Mng

Bone marrow transplant — curative for the haematological disease
Growth factors (G-CSF — WBC production); androgens (RBC/platelet production)

Special

"Fanconi thumbs" (absent/hypoplastic) = key clinical clue
Early AML risk + high squamous cell carcinoma risk (head/neck, anogenital) from broken DNA repair

Myelodysplastic Syndrome (MDS)

C/P

Clonal disorder — cytopenias with a HYPERcellular marrow (overworking factory; defective products die before leaving = ineffective haematopoiesis)
Stable cytopenias (most often anaemia) or pancytopenia; slow, smouldering, often transfusion-dependent

Inves

Marrow — hypercellular + dysplastic changes (ring sideroblasts, hypogranular/hyposegmented neutrophils / Pelger-Huët, dysplastic megakaryocytes)
Peak age — elderly (>80y)
IPSS prognostic factors — number of cytopenias, number of blasts, cytogenetics (see Criteria)

Mng

Supportive care (EPO / transfusions) — low-risk disease
Cytotoxic chemotherapy — advanced
Demethylation / hypomethylating agent — azacitidine (re-activates methyl-silenced tumour-suppressor genes)
Allogeneic stem cell transplant

Special

"Pre-leukaemia" — transforms to AML (risk rises with marrow blast %)
Hypercellular marrow (contrast aplastic anaemia = hypocellular)

physiology · background · low-yield

Epidemiology/Risk

Incidence — ~89 per 100,000 in the elderly (peak >80y)

Bone Marrow Examination

Indication

Pancytopenia / reduction in normal circulating blood cells across multiple lineages

Findings

Hypocellular — aplastic anaemia, cytotoxic therapy (drugs, radiation)
Hypercellular — secondary cancers, haematological malignancies (leukaemia/lymphoma/myeloma), myelodysplasia
Aspirate vs trephine — aspirate gives cytological detail (normoblastic vs megaloblastic morphology, myeloid:erythroid ratio, cells foreign to the marrow); trephine biopsy gives a panoramic view (overall cellularity, fibrosis, abnormal infiltrates)
Prussian blue (Perls) stain — assesses marrow iron stores (deficient vs normal)

Special

Hypocellular = empty factory (production failure); hypercellular = crowded/ineffective (cells non-functional or fail to exit → peripheral cytopenia)

Marrow Failure — Cytopenia Management & Thresholds

Anaemia

Symptoms — tiredness, dyspnoea, angina; sign — pallor (best assessed in mucous membranes/conjunctiva)
Transfuse to keep Hb ~10 g/dL (higher buffer than the usual 7–8 g/dL, to protect the heart)
Cardiac failure — potential complication of the anaemia in marrow failure

Neutropenia

Bacterial infection risk rises sharply when neutrophils <0.5×10⁹/L; typical source — skin flora via minor injury (IV cannula)
Febrile neutropenia = emergency → prompt broad-spectrum antibiotics after taking cultures
Oral candida — non-absorbable antifungal (nystatin swish-and-swallow); antibiotic-resistant fever / lung infiltrates — systemic antifungal (caspofungin)
Lymphopenia (T-cells <0.2) → viral + PCP risk → aciclovir + co-trimoxazole

Thrombocytopenia

Bleeding risk proportional to count; low risk if platelets >50×10⁹/L
Prophylactic platelet transfusion threshold 10×10⁹/L (no bleeding); invasive procedures (LP, central line) 50×10⁹/L
Platelet refractoriness — anti-HLA antibodies → require HLA-matched platelets
Bleeding signs — purpura (fine red spots, do NOT blanch on pressure), retinal haemorrhage (fundoscopy)

Special

Anti-HLA antibodies → "zero increment" after platelet transfusion unless HLA-matched
Bedside marrow-failure signs — oral candida (white plaques on mucosa), purpura, retinal bleeds

Spleen & Reticuloendothelial

4 entries

Spleen — Structure & Function

Anatomy

Chief organ of the reticuloendothelial system (RES); largest filter in the body
Lies under the left costal margin, upper left quadrant; palpable only when length >14 cm
Red pulp — venous sinuses + cords: resident macrophages, plasma cells, RBCs, platelets, granulocytes, lymphocytes
White pulp — lymphoid: T cells in PALS (para-arteriolar lymphoid sheath), B cells in follicles (primary = naïve/virgin B; secondary = germinal centres with memory cells)
Marginal zone — dendritic cells + macrophages expose blood-borne antigens to T & B lymphocytes

Function (4)

Filtration — pitting (removes intra-erythrocytic inclusions e.g. Heinz bodies, keeps the RBC) + culling (removes aged/abnormal RBCs whole)
Pooling & storage — ~5% RBC mass, reticulocyte maturation 1–2 days, ~⅓ of platelets; pooling increases in splenomegaly
Haematopoiesis — main RBC source in first 5 months of fetal life; extramedullary haematopoiesis (dormant splenic stem cells or homing marrow stem cells) in BM failure (e.g. myelofibrosis, irradiation)
Immunity — antigen exposure in white pulp → antibody + cell-mediated response; guards against encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae)

Special

Pitting (keep cell, remove inclusion) vs culling (remove whole cell)
Asplenia → delayed/low IgM → vaccinate post-splenectomy to prevent overwhelming post-splenectomy infection

Splenomegaly

Causes (7 categories)

Reactive — acute (bacterial endocarditis, typhoid, infectious mononucleosis) + chronic infections (TB, brucellosis, syphilis, malaria, leishmaniasis, schistosomiasis)
Congestive — CHF, portal hypertension, portal/splenic vein thrombosis
Storage — Gaucher (children), Niemann-Pick (lysosomal, Gaucher-like + neuro), histiocytosis X
Systemic disease — sarcoidosis, amyloidosis, collagen disease
Haematological — thalassaemia major/intermedia, chronic haemolytic anaemia, myelofibrosis, marrow infiltration
Primary splenic lesions — tumours or cysts
Tropical splenomegaly — malaria

Inves

Confirm palpable spleen (>14 cm); identify mechanism from the 7 categories

Special

Tropical splenomegaly — abnormal host response to chronic malaria antigen → benign lymphoproliferative disorder; huge spleen + hepatomegaly + lymphadenopathy, severe anaemia (± marked lymphocytosis), moderate thrombocytopenia, high malaria titre + high serum IgM
Visceral leishmaniasis (kala-azar) — reactive cause of massive splenomegaly

Hypersplenism

C/P

Overactive spleen (a clinical syndrome — does not imply a specific causal mechanism) → cytopenias
Sequestration — RBC pool up to 40%, platelet pool up to 90%

Inves

Bone marrow — hyperplasia (compensatory)
Must confirm the cytopenia is splenic sequestration, NOT primary bone-marrow failure

Mng

Splenectomy — counts improve afterwards (removes the sequestration site)

Special

Thrombocytopenia most prominent (platelet pooling up to 90%)

Hyposplenism / Post-splenectomy

C/P

Causes — splenectomy, sickle cell anaemia (auto-splenectomy), splenic artery thrombosis

Inves

Blood film — Howell-Jolly bodies (nuclear remnants no longer pitted); WBC + platelet counts typically rise

Mng

Vaccinate (pneumococcal, meningococcal, HiB) — prevent overwhelming post-splenectomy infection (OPSI); asplenia delays/lowers IgM
Prophylactic penicillin

Special

Howell-Jolly bodies = signature post-splenectomy film
Encapsulated-organism sepsis risk (OPSI)

Blood-Film Reaction Patterns

7 entries

Neutrophilia

Definition

Absolute neutrophil count >8×10⁹/L (some labs >7×10⁹/L); absolute = neutrophil % × WBC / 100

Causes

Bacterial infection (localised/disseminated)
Inflammation / necrosis (MI, vasculitis)
Malignant disease
Drugs — corticosteroids (demarginate neutrophils)
Myeloproliferative disease (CML)

Inves

History — exclude smoking, stress (physical or emotional)
Examination — signs of infection, temperature, inflammatory process
Suspected leukaemia — bone marrow aspirate/trephine + BM cytogenetics

Special

"Left shift" — neutrophil precursors (myelocyte, metamyelocyte) or excess bands (>6%); causes: severe infection (bacterial pneumonia), severe haemorrhage/haemolysis, malignancy, massive tissue damage (trauma/burns)
Neutrophil maturation — blast → promyelocyte → myelocyte → metamyelocyte → band → polymorph
CML film — full spectrum of myeloid precursors

Neutropenia

Definition

Absolute neutrophil count <2×10⁹/L; <0.5×10⁹/L → urgent haematology referral (severe, sepsis risk)

Causes

Drugs — co-trimoxazole, carbimazole, antipsychotics, phenylbutazone, cytotoxics
Racial — African, Middle-Eastern (benign ethnic neutropenia)
Other — congenital, autoimmune, post-viral, malaria

Special

<0.5×10⁹/L = severe → life-threatening bacterial sepsis; benign ethnic neutropenia is a normal constitutional variant

Eosinophilia

Definition

Absolute eosinophil count >0.5×10⁹/L; morphology — bilobed nucleus with orange/red granules

Causes

Parasites — Ankylostoma, Ascaris, Filaria
Allergies — asthma, drugs, hayfever
Skin — eczema, psoriasis, dermatitis herpetiformis
Malignancy — Hodgkin lymphoma, eosinophilic leukaemia
Inflammatory/other — sarcoidosis, polyarteritis nodosa, hypereosinophilic syndrome

Inves

History — foreign travel, drugs, allergies
Examination — skin, lungs, joints
Stool examination for parasites

Special

Pulmonary eosinophilia — pulmonary infiltrates that clear with corticosteroids

Lymphocytosis

Definition

Absolute lymphocyte count >4×10⁹/L

Causes

Acute infection — usually viral (rubella, mumps, infectious mononucleosis)
Chronic infection — TB, brucellosis, hepatitis
Malignancy — CLL, other leukaemias/lymphomas

Inves

History — viral illness, night sweats, weight loss
Examination — throat, lymph node regions, liver/spleen
Viral serology (EBV); immunophenotyping — flow cytometry / IHC (monoclonal antibodies)

Special

Persistent lymphocytosis in a patient >60 = CLL until proven otherwise
Atypical lymphocytes (larger, abundant cytoplasm, irregular nucleus) = infectious mononucleosis (EBV); smudge cells = CLL

physiology · background · low-yield

Background

Normal lymphocyte — small cell, round dark nucleus, scant cytoplasm (baseline for comparison with atypical/smudge cells)

Leucoerythroblastic Change

Definition

Nucleated RBCs AND immature WBCs together in peripheral blood

Causes

Marrow invasion — metastatic tumour, haematological malignancy (myeloma, lymphoma), fibrosis
Severe illness — trauma, septicaemia, massive haemolysis

Inves

Gold standard — bone marrow aspirate + trephine biopsy

Special

Ominous sign — blood-marrow barrier disrupted; always requires marrow investigation

Pancytopenia

Definition

Reduction in all normal circulating blood cells (RBC, WBC, platelets)

Inves

Bone marrow examination (aspirate + trephine) — cellularity distinguishes the cause
Hypocellular — aplastic anaemia, cytotoxic therapy (drugs, radiation)
Hypercellular — haematological malignancies (leukaemia/lymphoma/myeloma), secondary cancers, myelodysplasia; infiltration (ALL, hairy cell leukaemia crowd out haematopoiesis)

Special

Cellularity distinguishes empty (aplastic) from packed/ineffective (infiltrated/dysplastic) marrow

Haematological Changes in Systemic Disease

Liver Disease

Bleeding — deficiency of clotting factors (II, V, VII, IX, X, fibrinogen), functional fibrinogen abnormalities, increased fibrinolysis, thrombocytopenia (hypersplenism/alcohol), varices

Renal Failure

Primary abnormality — anaemia (normochromic normocytic) from decreased erythropoietin production
Treatment — recombinant erythropoietin

Special

Liver = complex coagulopathy across all arms of haemostasis; renal = EPO-deficient anaemia

Ann Arbor Staging (Lymphoma)

Stages

Stage	Involvement
I	Single lymph node region (I) or single extra-lymphatic organ/tissue (IE)
II	≥2 lymph node regions on the SAME side of the diaphragm
III	Lymph node regions on BOTH sides of the diaphragm
IV	Multiple/disseminated foci in one or more extra-lymphatic organs (e.g. bone marrow), ± nodal disease

Modifying features

Suffix	Meaning
A	No systemic symptoms
B	Fever, drenching night sweats, weight loss >10% in 6 months
X (bulky)	>⅓ mediastinal widening OR nodal mass >10 cm
E	Single contiguous/proximal extranodal site

Rai Staging (CLL)

Stage	Features	Risk
0	Lymphocytosis only (blood)	Low
1	Lymphocytosis + enlarged nodes	Intermediate
2	Lymphocytosis + organomegaly (hepatosplenomegaly)	Intermediate
3	Lymphocytosis + anaemia (Hb <11)	High
4	Lymphocytosis + thrombocytopenia (Plt <100k)	High

Anatomical: 0 = blood, 1 = nodes, 2 = organs, 3 = red cells down, 4 = platelets down. Stages 3–4 = marrow failure = high risk.

Binet Staging (CLL)

Stage	Criteria
A	Hb ≥10, Plt ≥100k, <3 enlarged areas
B	Hb ≥10, Plt ≥100k, ≥3 enlarged areas
C	Hb <10 and/or Plt <100k (marrow failure)

5 areas counted — neck, axilla, groin, spleen, liver. Stage C ≈ Rai III/IV.

Active Myeloma Definition — CRAB + SLiM

Myeloma-Defining Events — CRAB (organ damage)

	Feature
C	Hypercalcaemia (>11 mg/dL or >1 mg/dL above ULN)
R	Renal insufficiency (CrCl <40 mL/min or Cr >2 mg/dL)
A	Anaemia (Hb <100 g/L or >20 g/L below LLN)
B	Bone lesions (≥1 osteolytic on X-ray/CT/PET)

Biomarkers of Early Progression — SLiM

Sixty — clonal BM plasma cells ≥60%
Light chains — involved:uninvolved free light-chain ratio ≥100
MRI — >1 focal lesion

MGUS vs Smouldering vs Active Myeloma

	M-protein	Plasma cells	CRAB
MGUS	<30 g/L	<10%	Absent
Smouldering	>30 g/L	>10%	Absent
Active MM	—	≥10% (or plasmacytoma)	Present (CRAB or SLiM)

ISS / R-ISS (Myeloma)

ISS measures — albumin + β2-microglobulin (tumour burden)
R-ISS combines tumour burden (ISS) with aggressive biology (LDH + high-risk genetics)

R-ISS Stage	Definition	Median survival
I	ISS I + normal LDH + no high-risk genetics	Standard risk 6–7 y
II	Not stage I or III	—
III	ISS III + (high LDH OR high-risk genetics)	High risk <2–3 y

High-risk genetics — t(4;14), t(14;16), del(17p).

FAB Classification of AML (M0–M7)

Subtype	Type
M0	AML without maturation
M1	AML with minimal maturation
M2	AML with maturation
M3	Acute promyelocytic leukaemia (APL) — DIC risk, ATRA
M4	Acute myelomonocytic leukaemia
M5	Acute monocytic/monoblastic leukaemia (gum hypertrophy)
M6	Acute erythroid leukaemia
M7	Acute megakaryoblastic leukaemia

IPSS (MDS Prognosis)

Number of cytopenias
Number of blasts in marrow
Cytogenetic / chromosomal abnormalities

Alpha Thalassaemia Genetic Classification

Genotype	Genes lost	Phenotype
αα/αα	0	Normal
−α/αα	1	Silent carrier
−−/αα or −α/−α	2	α-thalassaemia trait (microcytosis)
−−/−α	3	HbH disease (β₄ tetramers, haemolysis)
−−/−−	4	Hb Barts / hydrops fetalis (incompatible with life)

α defects = gene deletions → MLPA/multiplex PCR.

C10

Beta Thalassaemia Genetic Classification

Genotype	Phenotype
β/β	Normal
β/β⁺ or β/β⁰	β-thalassaemia trait (minor)
β⁰/β⁰ or β⁺/β⁺	β-thalassaemia major

Two carriers → 25% chance of major child. β defects = point mutations → β-globin sequencing.

C11

IDA vs Beta-Thalassaemia Trait

Parameter	IDA	β-Thal trait
RBC count	<5.0 ×10⁶/µL (low)	>5.0 ×10⁶/µL (relatively high)
RDW	Elevated (anisocytosis)	≤14% (often normal)
HbA2	Normal/low	Raised (>3.5%)

Quickest CBC discriminator — RBC count is HIGH in thalassaemia trait, LOW in IDA.

C12

Iron Chelation Agents (Thalassaemia)

Agent	Route	Dose	Key point
Deferoxamine (Desferal)	SC/IV infusion 8–12h, 5–7 nights/wk	30–60 mg/kg	Old standard; poor compliance
Deferasirox (Exjade)	Oral, once daily	20 mg/kg (adjust 5–10)	Modern oral standard; hold if ferritin <500 µg/L
Deferiprone	Oral	—	Effective (heart); risk neutropenia/agranulocytosis → weekly CBC

Chelation start — after 10–20 transfusions OR ferritin ≥1000 µg/L OR age 3.

C13

Amyloidosis Classification

Fibril	Association
AL	Paraproteinaemia (primary / myeloma)
AA	Chronic inflammation/infection OR Familial Mediterranean Fever
ASc	Senile type (cardiac)
PA	Neuropathy

Diagnosis — Congo red stain → apple-green birefringence under polarised light.

C14

Acute vs Chronic Leukaemia

Feature	Acute	Chronic
Age	All ages	Adults
Onset	Sudden	Insidious
Leukaemic cells	Immature (blasts)	Mature
Anaemia/thrombocytopenia	Mild–severe	Mild
WBC count	Variable	Increased
Organomegaly	Mild	Prominent

Leukaemia lab characterisation (WHO) — morphology, immunophenotyping (flow/IHC), cytogenetics (G-banding/FISH), molecular genetics (PCR/sequencing).

C15

Chemotherapy Regimens & Immunotherapy (Haem-Onc)

Regimen	Components	Main use
CHOP	Cyclophosphamide + Doxorubicin (Hydroxydaunorubicin) + Vincristine (Oncovin) + Prednisone	DLBCL (given as R-CHOP)
R-CHOP	Rituximab + CHOP	DLBCL first-line (gold standard)
CVP	Cyclophosphamide + Vincristine + Prednisone	Follicular NHL (given as R-CVP)
R-CVP	Rituximab + CVP	Follicular NHL
ABVD	Adriamycin (Doxorubicin) + Bleomycin + Vinblastine + Dacarbazine	Hodgkin lymphoma

Combination chemotherapy is given to induce response/remission. Rituximab (anti-CD20 monoclonal) can also be used as single-agent maintenance in follicular lymphoma to clear residual subclinical disease → longer disease-free survival.

Other modalities: corticosteroids · targeted therapy — tyrosine kinase inhibitors (e.g. imatinib in CML) · immunotherapy.

Immunotherapy: (1) Monoclonal antibodies — preformed antibodies targeting surface antigens on the malignant cell (e.g. rituximab, anti-CD20). (2) CAR-T cell therapy — chimeric antigen receptor T cells: the patient's own T-lymphocytes are manipulated in vitro to become more active against cancer cells.