Pathology
MBBS Pathology — high-yield long questions and short notes from Robbins & Cotran and Harsh Mohan, covering general pathology (cell injury, inflammation, haemodynamics, immunopathology, neoplasia), haematology, and systemic pathology of the cardiovascular, respiratory, GI, hepatobiliary, renal, endocrine and other systems, written to the marks with definitions, mechanisms, morphology, classification, clinical correlation and pearls.
12chapters144questions99High-Yield
Definition
Leukaemia is a malignant clonal proliferation of haematopoietic cells in bone marrow with spill-over into blood; acute leukaemia involves immature blasts.
Classification
- Acute — AML (myeloid) and ALL (lymphoblastic)
- Chronic — CML and CLL
- Acute: immature blasts ≥20% in marrow
- Chronic: mature-appearing cells, insidious course
Acute Leukaemia — Features
- ALL — children (peak 2–5 years); AML — adults
- Marrow failure: anaemia, infections, bleeding
- Bone pain, lymphadenopathy, hepatosplenomegaly; CNS and testicular involvement (ALL)
- Auer rods in AML (myeloperoxidase positive)
- ALL: PAS positive, TdT positive; CD10, CD19 markers
Blasts crowd out normal marrow, producing the classic triad. Feature ALL AML Age Children Adults Marker TdT, PAS Auer rods, MPO Prognosis Better Worse Applied
- Acute promyelocytic leukaemia t(15;17) → DIC; treated with ATRA
- Diagnosis: peripheral film, marrow aspirate, flow cytometry
🔑KEY POINTS TO REMEMBER- Acute leukaemia = ≥20% blasts; ALL in children, AML in adults.
- Presents with anaemia, infection and bleeding from marrow failure.
- Auer rods and MPO mark AML; TdT and PAS mark ALL.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Chronic leukaemias are clonal proliferations of relatively mature haematopoietic cells with an insidious onset.
Chronic Myeloid Leukaemia (CML)
- Middle age; Philadelphia chromosome t(9;22) → BCR-ABL fusion, tyrosine kinase
- Massive splenomegaly, weight loss, fatigue
- Blood: marked leucocytosis with full spectrum of myeloid cells, basophilia
- Leucocyte alkaline phosphatase (LAP) score low
- Phases: chronic → accelerated → blast crisis
Chronic Lymphocytic Leukaemia (CLL)
- Elderly; commonest leukaemia in the West; monoclonal B cells
- Generalised lymphadenopathy, hepatosplenomegaly; often asymptomatic
- Blood: absolute lymphocytosis with smudge (basket) cells
- Complications: autoimmune haemolytic anaemia, hypogammaglobulinaemia, infections
Cell lineage and age separate the two chronic leukaemias. Feature CML CLL Cell Myeloid B lymphocyte Marker BCR-ABL Smudge cells Spleen Massive Moderate Applied
- Imatinib (tyrosine kinase inhibitor) transformed CML prognosis
- CLL may transform to high-grade lymphoma (Richter syndrome)
🔑KEY POINTS TO REMEMBER- CML: Philadelphia chromosome t(9;22), BCR-ABL, massive splenomegaly, low LAP.
- CLL: elderly, B-cell, lymphadenopathy, smudge cells.
- Imatinib targets BCR-ABL in CML.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Lymphomas are malignant neoplasms of lymphoid tissue, divided into Hodgkin and non-Hodgkin types.
Hodgkin Lymphoma
- Reed-Sternberg cell — diagnostic (owl-eye, mirror-image nuclei; CD15 and CD30 positive)
- Bimodal age; contiguous, orderly spread along lymph node groups
- Usually cervical nodes, rarely extranodal
- B symptoms: fever, night sweats, weight loss; Pel-Ebstein fever, alcohol-induced pain
- Types: nodular sclerosis (commonest), mixed cellularity, lymphocyte-rich, lymphocyte-depleted
Non-Hodgkin Lymphoma
- Heterogeneous; mostly B cell (85%)
- Non-contiguous, unpredictable spread; extranodal common
- Often disseminated at presentation
- Examples: diffuse large B-cell (commonest), follicular t(14;18), Burkitt t(8;14), MALT lymphoma
Presence of Reed-Sternberg cells and pattern of spread separate the two. Feature Hodgkin Non-Hodgkin Cell Reed-Sternberg Varied Spread Contiguous Non-contiguous Extranodal Rare Common Applied
- Ann Arbor staging is used for both
- Hodgkin lymphoma has a better prognosis and is often curable
🔑KEY POINTS TO REMEMBER- Hodgkin lymphoma is defined by Reed-Sternberg cells and contiguous spread.
- Non-Hodgkin lymphoma is mostly B-cell with extranodal, non-contiguous spread.
- Follicular t(14;18); Burkitt t(8;14).
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Multiple myeloma is a malignant clonal proliferation of plasma cells in bone marrow producing a monoclonal immunoglobulin (M protein).
Clinical Features (CRAB)
- C — hyperCalcaemia (bone resorption)
- R — Renal failure (light-chain cast nephropathy, ‘myeloma kidney’)
- A — Anaemia (marrow replacement)
- B — Bone lesions: punched-out lytic lesions, back pain, pathological fracture
- Recurrent infections (immune paresis); ↑ ESR, rouleaux formation
Investigations
- Serum electrophoresis → M band (monoclonal spike)
- Bence Jones protein (light chains) in urine
- Marrow >10% plasma cells
- Skeletal survey — punched-out lytic lesions, pepper-pot skull
- ↑ β₂-microglobulin (prognostic)
One plasma cell clone produces both bone destruction and renal injury. Test Finding Electrophoresis M band Urine Bence Jones protein X-ray Lytic lesions Applied
- Lytic lesions with normal alkaline phosphatase (no osteoblastic reaction)
- Bone scan may be negative — use skeletal survey or MRI
🔑KEY POINTS TO REMEMBER- Multiple myeloma is clonal plasma cell malignancy producing M protein.
- CRAB: hypercalcaemia, renal failure, anaemia, bone lesions.
- Diagnosis: M band, Bence Jones protein, >10% marrow plasma cells.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Bleeding disorders result from defects of vessels, platelets or coagulation factors, impairing haemostasis.
Classification
- Vascular — Henoch-Schönlein purpura, scurvy, senile purpura
- Platelet — quantitative (ITP, aplastic anaemia, DIC) or qualitative (Glanzmann thrombasthenia, Bernard-Soulier, aspirin)
- Coagulation — haemophilia A (factor VIII), B (factor IX), von Willebrand disease, vitamin K deficiency, liver disease
- Mixed — DIC
Clinical Clues
- Platelet/vascular — petechiae, purpura, mucosal bleeding, immediate bleeding after injury
- Coagulation — deep haematomas, haemarthroses, delayed bleeding
- Screening: platelet count, bleeding time, PT, aPTT
The site and pattern of bleeding point to the defective component. Disorder PT aPTT Haemophilia Normal Prolonged Vitamin K deficiency Prolonged Prolonged ITP Normal Normal Applied
- Platelet count <20,000/μL carries spontaneous bleeding risk
- Mixing study distinguishes factor deficiency from inhibitor
🔑KEY POINTS TO REMEMBER- Causes: vascular, platelet (quantitative/qualitative) and coagulation defects.
- Petechiae and mucosal bleeding suggest platelet disorders.
- Haemarthrosis and deep haematomas suggest coagulation factor deficiency.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Acute and chronic leukaemias differ in cell maturity, onset, clinical course and untreated survival.
Acute Leukaemia
- Immature blasts ≥20% in marrow
- Abrupt onset, rapidly progressive
- Marked marrow failure — anaemia, infection, bleeding
- Survival weeks to months if untreated
- Leukaemic hiatus (blasts and mature cells with gap in between)
Chronic Leukaemia
- Mature-appearing cells predominate
- Insidious onset; often detected incidentally
- Marked organomegaly (especially spleen in CML)
- Survival years; may transform to blast crisis
- Marrow failure appears late
Degree of cell maturation drives the entire clinical difference. Feature Acute Chronic Cells Blasts Mature Onset Sudden Insidious Survival Months Years Applied
- Acute leukaemia is a medical emergency needing prompt treatment
- Chronic leukaemia may be observed initially (watch and wait in CLL)
🔑KEY POINTS TO REMEMBER- Acute: ≥20% blasts, rapid onset, marrow failure, short untreated survival.
- Chronic: mature cells, insidious, organomegaly, survival in years.
- Chronic leukaemia may transform into blast crisis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm characterised by the Philadelphia chromosome.
Genetics & Findings
- t(9;22) → BCR-ABL fusion gene → constitutively active tyrosine kinase
- Present in over 90% of cases; diagnostic
- Blood: marked leucocytosis (often >100,000/μL) with all stages of granulocytes
- Basophilia and eosinophilia
- Low leucocyte alkaline phosphatase (LAP) score — distinguishes from leukaemoid reaction
Clinical Course
- Middle-aged adults; fatigue, weight loss, night sweats
- Massive splenomegaly — dragging abdominal pain
- Phases: chronic (years) → accelerated → blast crisis (behaves like acute leukaemia)
- Treatment: imatinib and other tyrosine kinase inhibitors; transplant in resistant cases
A single fusion gene drives the entire disease and is the drug target. Feature CML Leukaemoid reaction LAP score Low High BCR-ABL Present Absent Basophilia Present Absent Applied
- Imatinib has made CML a largely controllable chronic disease
- Blast crisis carries a poor prognosis
🔑KEY POINTS TO REMEMBER- CML is defined by t(9;22) Philadelphia chromosome producing BCR-ABL.
- Marked leucocytosis, basophilia, massive splenomegaly, low LAP score.
- Treated with imatinib; may progress to blast crisis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
The Reed-Sternberg (RS) cell is the neoplastic cell of Hodgkin lymphoma and is essential for its diagnosis.
Morphology & Immunophenotype
- Large cell with bilobed or double nucleus — ‘owl-eye’ / mirror-image appearance
- Prominent eosinophilic inclusion-like nucleoli
- Abundant amphophilic cytoplasm
- CD15 and CD30 positive; CD45 negative
- B-cell origin (germinal centre) despite loss of B-cell markers
Variants & Significance
- Lacunar cell — nodular sclerosis type
- Popcorn (L&H) cell — lymphocyte-predominant type
- Mummified cell — degenerate form
- RS cells are few amid a rich reactive infiltrate of lymphocytes, eosinophils and plasma cells
- Not absolutely specific — similar cells occur in infectious mononucleosis and some NHL
A few malignant cells recruit a large reactive population around them. Marker RS cell CD15 Positive CD30 Positive CD45 Negative Applied
- Diagnosis of Hodgkin lymphoma requires RS cells in the correct background
- Lacunar variant indicates nodular sclerosis, the commonest subtype
🔑KEY POINTS TO REMEMBER- RS cell has owl-eye mirror-image nuclei with prominent nucleoli.
- CD15 and CD30 positive, CD45 negative; B-cell origin.
- Essential for diagnosing Hodgkin lymphoma but not fully specific.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Bence Jones protein is monoclonal immunoglobulin light chain (kappa or lambda) excreted in urine, characteristic of multiple myeloma.
Properties & Detection
- Low molecular weight → freely filtered by the glomerulus
- Classic heat test: precipitates at 40–60°C, redissolves on boiling, reappears on cooling
- Not detected by routine urine dipstick (which detects albumin only)
- Confirmed by urine electrophoresis and immunofixation
Clinical Significance
- Found in multiple myeloma (about 60–80%), light-chain disease, Waldenström macroglobulinaemia, primary AL amyloidosis
- Causes cast nephropathy (‘myeloma kidney’) → renal failure
- Contributes to AL amyloid deposition
- Useful for diagnosis and monitoring disease response
Light chains overwhelm tubular reabsorption and damage the kidney. Feature Detail Nature Light chains (κ or λ) Dipstick Negative Complication Cast nephropathy Applied
- A negative dipstick with heavy proteinuria on lab testing suggests light chains
- Serum free light chain assay is now preferred
🔑KEY POINTS TO REMEMBER- Bence Jones protein = monoclonal free light chains in urine.
- Precipitates at 40–60°C and redissolves on boiling; dipstick negative.
- Seen in myeloma; causes cast nephropathy and AL amyloidosis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Haemophilia is an X-linked recessive coagulation disorder caused by deficiency of factor VIII (A) or factor IX (B).
Types & Genetics
- Haemophilia A — factor VIII deficiency (about 80%, commoner)
- Haemophilia B (Christmas disease) — factor IX deficiency
- X-linked recessive — affects males, females are carriers
- Severity by factor level: severe <1%, moderate 1–5%, mild >5%
Features & Investigations
- Haemarthrosis (knee, ankle, elbow) → chronic arthropathy
- Deep muscle haematomas, prolonged bleeding after surgery or dental extraction
- Intracranial haemorrhage — a leading cause of death
- Prolonged aPTT with normal PT, bleeding time and platelet count
- Corrected by mixing study; confirmed by factor assay
Intrinsic pathway failure causes delayed, deep-tissue bleeding. Test Result aPTT Prolonged PT Normal Platelets Normal Applied
- Treatment: factor concentrate replacement; desmopressin in mild haemophilia A
- Avoid intramuscular injections, aspirin and NSAIDs
🔑KEY POINTS TO REMEMBER- Haemophilia A (factor VIII) and B (factor IX) are X-linked recessive.
- Haemarthrosis and deep haematomas; prolonged aPTT with normal PT.
- Treated with factor replacement; avoid aspirin and IM injections.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Immune thrombocytopenic purpura (ITP) is autoimmune destruction of platelets by antiplatelet antibodies, producing isolated thrombocytopenia.
Pathogenesis & Types
- IgG antibodies against platelet glycoproteins (GPIIb/IIIa)
- Antibody-coated platelets destroyed by splenic macrophages (Type II hypersensitivity)
- Acute — children, follows viral infection, self-limiting
- Chronic — adults, especially young women; persistent
- Secondary ITP: SLE, CLL, HIV, drugs
Features & Investigations
- Petechiae, purpura, epistaxis, menorrhagia; gum bleeding
- No splenomegaly — important negative
- ↓ Platelet count, prolonged bleeding time; normal PT and aPTT
- Marrow: normal or increased megakaryocytes
- Diagnosis of exclusion
Peripheral destruction, not marrow failure, causes the low count. Finding ITP Platelets Low Megakaryocytes Normal/increased Spleen Not enlarged Applied
- Treatment: corticosteroids first-line; IV immunoglobulin if urgent; splenectomy if refractory
- Platelet transfusion only for life-threatening bleeding
🔑KEY POINTS TO REMEMBER- ITP is antibody-mediated platelet destruction in the spleen.
- Petechiae with low platelets, normal PT/aPTT and no splenomegaly.
- Marrow shows normal or increased megakaryocytes; treat with steroids.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.Definition
Prothrombin time (PT) assesses the extrinsic and common pathways, while activated partial thromboplastin time (aPTT) assesses the intrinsic and common pathways.
Prothrombin Time
- Reagent: tissue thromboplastin + calcium
- Tests factors VII (extrinsic) and X, V, II, fibrinogen (common)
- Normal 11–16 seconds; expressed as INR
- Prolonged in: warfarin, vitamin K deficiency, liver disease, DIC
- Used to monitor oral anticoagulant therapy
Activated Partial Thromboplastin Time
- Reagent: phospholipid + activator + calcium
- Tests factors XII, XI, IX, VIII (intrinsic) and the common pathway
- Normal 25–40 seconds
- Prolonged in: haemophilia A and B, von Willebrand disease, heparin, lupus anticoagulant, DIC
- Used to monitor unfractionated heparin
Which test is prolonged localises the defective pathway. Condition PT aPTT Warfarin Prolonged Normal/mild Heparin Normal Prolonged Haemophilia Normal Prolonged DIC Prolonged Prolonged Applied
- Both prolonged → common pathway defect, DIC or liver disease
- Mixing study distinguishes factor deficiency from an inhibitor
🔑KEY POINTS TO REMEMBER- PT tests extrinsic pathway (factor VII); monitored as INR for warfarin.
- aPTT tests intrinsic pathway (VIII, IX); monitors heparin and detects haemophilia.
- Both prolonged in DIC, liver disease and common-pathway defects.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); de Gruchy’s Clinical Haematology in Medical Practice.