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
Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia from defective insulin secretion, insulin action, or both.
Types & Diagnosis
- Type 1 — autoimmune β-cell destruction; absolute insulin deficiency
- Type 2 — insulin resistance with relative deficiency; ~90% of cases
- Gestational; secondary (pancreatitis, steroids, Cushing, acromegaly); MODY
- Diagnosis: fasting glucose ≥126 mg/dL, 2-hour post-prandial ≥200 mg/dL, HbA1c ≥6.5%
Complications
- Acute — diabetic ketoacidosis (type 1), hyperosmolar state (type 2), hypoglycaemia
- Microvascular — retinopathy, nephropathy (Kimmelstiel-Wilson nodules), neuropathy
- Macrovascular — accelerated atherosclerosis: ischaemic heart disease, stroke, peripheral vascular disease
- Infections, diabetic foot, cataract
- Mechanisms: non-enzymatic glycation (AGEs), polyol pathway, oxidative stress
Persistent hyperglycaemia damages vessels through glycation and osmotic stress. Complication Lesion Nephropathy Kimmelstiel-Wilson nodules Retinopathy Microaneurysms Vessels Hyaline arteriolosclerosis Applied
- HbA1c reflects control over the preceding 2–3 months
- Nephropathy is the leading cause of end-stage renal disease
🔑KEY POINTS TO REMEMBER- Diabetes = chronic hyperglycaemia from insulin deficiency or resistance.
- Diagnosed by fasting glucose ≥126, post-prandial ≥200 or HbA1c ≥6.5%.
- Microvascular (retina, kidney, nerve) and macrovascular (atherosclerosis) complications.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Thyroid disorders include hyperfunction, hypofunction, inflammation, goitre and neoplasia.
Hyperthyroidism & Hypothyroidism
- Hyperthyroidism — Graves disease (commonest; TSH receptor antibody), toxic multinodular goitre, toxic adenoma; ↓ TSH, ↑ T3/T4
- Features: weight loss, heat intolerance, tremor, tachycardia, exophthalmos (Graves only)
- Hypothyroidism — Hashimoto thyroiditis (commonest with iodine sufficiency), iodine deficiency, thyroidectomy
- Features: weight gain, cold intolerance, lethargy, myxoedema; cretinism in infants
Thyroiditis & Goitre
- Hashimoto — autoimmune; anti-TPO and anti-thyroglobulin antibodies; lymphocytic infiltration with Hurthle cells and germinal centres
- De Quervain (subacute granulomatous) — painful, post-viral, self-limiting
- Riedel — dense fibrosis, stony-hard gland
- Simple (colloid) goitre — iodine deficiency; may become multinodular
The TSH level is the most sensitive indicator of thyroid status. Disorder TSH T4 Hyperthyroid Low High Primary hypothyroid High Low Hashimoto (late) High Low Applied
- Hashimoto thyroiditis carries a risk of thyroid lymphoma
- Iodisation of salt has greatly reduced endemic goitre
🔑KEY POINTS TO REMEMBER- Graves disease is the commonest cause of hyperthyroidism (TSH receptor antibody).
- Hashimoto thyroiditis causes hypothyroidism; anti-TPO antibodies, Hurthle cells.
- TSH is the most sensitive test of thyroid function.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Breast carcinoma is the commonest malignancy in women, usually arising from the terminal duct lobular unit.
Risk Factors
- Female sex, increasing age
- Prolonged oestrogen exposure — early menarche, late menopause, nulliparity, late first pregnancy, hormone therapy
- BRCA1 and BRCA2 mutations; family history
- Previous breast cancer, atypical hyperplasia, radiation, obesity, alcohol
Types & Spread
- Invasive ductal carcinoma NOS — commonest (~75%); hard, gritty, stellate mass
- Invasive lobular — Indian-file pattern, often bilateral
- In situ: DCIS (comedo necrosis), LCIS
- Paget disease of nipple; inflammatory carcinoma (peau d’orange)
- Commonest site: upper outer quadrant; spreads to axillary nodes, then bone, lung, liver, brain
Breaching the basement membrane marks the shift to invasive disease. Marker Significance ER/PR positive Hormone therapy, better prognosis HER2 positive Trastuzumab Triple negative Poor prognosis Applied
- Triple assessment: clinical examination, imaging, biopsy
- Axillary node status is the single most important prognostic factor
🔑KEY POINTS TO REMEMBER- Arises from the terminal duct lobular unit; invasive ductal NOS is commonest.
- Prolonged oestrogen exposure and BRCA mutations are key risks.
- ER, PR and HER2 status guide therapy; nodal status determines prognosis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Bone tumours may be benign or malignant, primary or metastatic; metastases are far commoner than primary tumours.
Benign Tumours
- Osteoma — skull and facial bones
- Osteoid osteoma — <2 cm nidus; night pain relieved by aspirin
- Osteochondroma (exostosis) — commonest benign bone tumour; metaphysis
- Giant cell tumour (osteoclastoma) — epiphysis of long bones; ‘soap-bubble’ appearance; locally aggressive
- Enchondroma — small bones of hands
Malignant Tumours
- Osteosarcoma — commonest primary malignant; adolescents; metaphysis around knee; Codman triangle, sunburst appearance
- Ewing sarcoma — children; diaphysis; onion-skin periosteal reaction; t(11;22), small round blue cells
- Chondrosarcoma — older adults; pelvis, shoulder
- Metastases — from breast, prostate, lung, thyroid, kidney; usually lytic (prostate is osteoblastic)
Site within the bone and age narrow the diagnosis considerably. Tumour Site X-ray Osteosarcoma Metaphysis Codman triangle Ewing sarcoma Diaphysis Onion-skin Giant cell tumour Epiphysis Soap-bubble Applied
- Age, site and radiological pattern together suggest the diagnosis before biopsy
- Biopsy remains essential for confirmation
🔑KEY POINTS TO REMEMBER- Metastases are the commonest bone tumours.
- Osteosarcoma: metaphysis around knee, Codman triangle, adolescents.
- Ewing sarcoma: diaphysis, onion-skin, t(11;22); giant cell tumour: epiphysis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Metabolic bone diseases are disorders of bone mineralisation, turnover or matrix affecting the whole skeleton.
Osteoporosis and Osteomalacia
- Osteoporosis — reduced bone mass with normal mineralisation; postmenopausal (oestrogen loss), senile, steroid-induced, immobilisation
- Normal calcium, phosphate and alkaline phosphatase; fractures of vertebrae, hip, wrist; DEXA scan
- Osteomalacia — defective mineralisation of normal osteoid; vitamin D deficiency
- ↓ Calcium, ↓ phosphate, ↑ alkaline phosphatase; bone pain, Looser zones; called rickets in children
Other Disorders
- Hyperparathyroidism — osteitis fibrosa cystica, brown tumours; ↑ calcium, ↓ phosphate
- Paget disease of bone — disordered remodelling; mosaic pattern of lamellar bone; markedly ↑↑ alkaline phosphatase; risk of osteosarcoma
- Renal osteodystrophy in chronic kidney disease
Quantity versus quality of bone distinguishes these two. Disease Ca PO₄ ALP Osteoporosis Normal Normal Normal Osteomalacia Low Low High Hyperparathyroidism High Low High Paget Normal Normal Very high Applied
- Biochemistry pattern is the fastest way to distinguish these conditions
- Osteoporosis: calcium, vitamin D and bisphosphonates
🔑KEY POINTS TO REMEMBER- Osteoporosis: ↓ bone mass, normal biochemistry.
- Osteomalacia: defective mineralisation, ↓ Ca, ↓ PO₄, ↑ ALP.
- Paget disease shows mosaic bone with markedly raised alkaline phosphatase.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Type 1 and type 2 diabetes mellitus differ fundamentally in pathogenesis, age of onset and management.
Type 1 Diabetes
- Autoimmune destruction of β cells — insulitis; anti-GAD, anti-islet antibodies
- Absolute insulin deficiency; HLA-DR3/DR4 association
- Usually <30 years, lean build; abrupt onset
- Prone to ketoacidosis; insulin dependent
- Twin concordance ~50%
Type 2 Diabetes
- Insulin resistance with progressive β-cell dysfunction; amyloid deposits in islets
- ~90% of cases; adults, usually obese; insidious onset
- Ketoacidosis uncommon; hyperosmolar state instead
- Strong genetic predisposition (twin concordance ~90%); no HLA link
- Managed with diet, oral agents ± insulin
Absent insulin versus ineffective insulin drives every other difference. Feature Type 1 Type 2 Age <30 years Adults Build Lean Obese Ketoacidosis Common Uncommon Islets Insulitis Amyloid Applied
- Both share the same long-term vascular complications
- Type 2 is increasingly seen in obese adolescents
🔑KEY POINTS TO REMEMBER- Type 1: autoimmune β-cell destruction, lean, young, ketosis-prone, HLA-linked.
- Type 2: insulin resistance, obese adults, islet amyloid, ~90% of cases.
- Complications are identical in both types.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Thyroid carcinoma is the commonest endocrine malignancy, usually presenting as a solitary thyroid nodule.
Types
- Papillary (~80%) — commonest; radiation exposure; Orphan Annie nuclei, nuclear grooves, psammoma bodies; lymphatic spread; excellent prognosis
- Follicular (~10–15%) — iodine-deficient areas; haematogenous spread to bone and lung; capsular/vascular invasion needed for diagnosis
- Medullary (~5%) — from parafollicular C cells; secretes calcitonin; amyloid stroma; part of MEN 2 (RET gene)
- Anaplastic (<5%) — elderly; highly aggressive; almost uniformly fatal
Diagnosis & Management
- Fine-needle aspiration cytology — investigation of choice (not for follicular)
- Ultrasound, radioiodine scan (cold nodule suspicious)
- Treatment: thyroidectomy ± radioiodine; thyroxine suppression
- Thyroglobulin for follow-up (papillary/follicular); calcitonin for medullary
FNAC directs management for nearly all thyroid nodules. Type Spread Prognosis Papillary Lymphatic Excellent Follicular Blood Good Anaplastic Local, rapid Very poor Applied
- Psammoma bodies and Orphan Annie nuclei are hallmarks of papillary carcinoma
- Screen for RET mutation in medullary carcinoma
🔑KEY POINTS TO REMEMBER- Papillary carcinoma is commonest — Orphan Annie nuclei, psammoma bodies, lymphatic spread.
- Follicular spreads by blood; medullary secretes calcitonin with amyloid (MEN 2).
- Anaplastic carcinoma is rapidly fatal; FNAC is the key investigation.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Graves disease is an autoimmune disorder and the commonest cause of hyperthyroidism, caused by stimulating TSH receptor antibodies.
Pathogenesis & Pathology
- IgG antibodies against the TSH receptor (thyroid-stimulating immunoglobulin) — Type II hypersensitivity (stimulatory)
- Continuous stimulation independent of pituitary control
- Young women; HLA-DR3 association; other autoimmune diseases
- Gland: diffusely enlarged, hyperplastic follicles with scalloped colloid, tall columnar epithelium, lymphoid aggregates
Clinical Features
- Triad: hyperthyroidism, diffuse goitre with bruit, exophthalmos
- Pretibial myxoedema and thyroid acropachy (specific to Graves)
- Weight loss, heat intolerance, palpitations, tremor, anxiety, lid lag
- ↓↓ TSH, ↑ free T3/T4; diffusely increased uptake on radioiodine scan
Antibodies mimic TSH, bypassing normal feedback control. Feature Detail Antibody TSH receptor (TSI) Goitre Diffuse Eyes Exophthalmos Applied
- Thyroid storm — life-threatening decompensation
- Treatment: antithyroid drugs, radioiodine or surgery; β-blockers for symptoms
🔑KEY POINTS TO REMEMBER- Graves disease results from stimulating TSH receptor antibodies.
- Triad: hyperthyroidism, diffuse goitre, exophthalmos; pretibial myxoedema is specific.
- Low TSH with high T3/T4 and diffusely raised radioiodine uptake.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Fibroadenoma is the commonest benign breast tumour in young women, arising from the terminal duct lobular unit.
Features
- Peak age 20–30 years
- Oestrogen-dependent — may enlarge in pregnancy, regress after menopause
- Clinically: firm, smooth, well-defined, freely mobile — the ‘breast mouse’
- Painless, usually solitary; commonly upper outer quadrant
- Gross: well-circumscribed, encapsulated, grey-white, whorled cut surface
Histology & Management
- Proliferation of both stromal and epithelial elements (biphasic)
- Intracanalicular pattern — stroma compresses ducts into slits; pericanalicular — round ducts
- Diagnosis: triple assessment — examination, ultrasound, FNAC
- Management: excision if large, symptomatic or growing; small ones may be observed
- Not premalignant; distinguish from phyllodes tumour (larger, rapidly growing, may be malignant)
Both components proliferate, which is why it is called biphasic. Feature Fibroadenoma Phyllodes Age 20–30 years Older Growth Slow Rapid Behaviour Benign May be malignant Applied
- Highly mobile nature gives it the name ‘breast mouse’
- Ultrasound is preferred over mammography in young dense breasts
🔑KEY POINTS TO REMEMBER- Fibroadenoma is the commonest benign breast tumour in young women.
- Firm, mobile, painless ‘breast mouse’; biphasic stromal and epithelial proliferation.
- Not premalignant; must be distinguished from phyllodes tumour.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Osteosarcoma is a malignant tumour of bone in which tumour cells produce osteoid — the commonest primary malignant bone tumour.
Epidemiology & Site
- Bimodal: adolescents (10–20 years) and elderly (secondary)
- Metaphysis of long bones around the knee — lower femur and upper tibia (~60%)
- Secondary causes: Paget disease, previous radiation
- Genetic: Rb and p53 mutations; hereditary retinoblastoma survivors
Features & Radiology
- Painful, progressively enlarging swelling; pathological fracture; ↑ alkaline phosphatase
- X-ray: Codman triangle (elevated periosteum), sunburst / sunray appearance, bone destruction with soft-tissue extension
- Histology: malignant osteoid produced by pleomorphic tumour cells — diagnostic
- Early haematogenous metastasis to lungs (cannonball)
- Treatment: neoadjuvant chemotherapy + limb-salvage surgery
Osteoid production by malignant cells defines the tumour. Feature Detail Site Metaphysis around knee X-ray Codman triangle, sunburst Metastasis Lung Applied
- Chemotherapy has raised survival from about 20% to over 60%
- Chest CT is mandatory for staging
🔑KEY POINTS TO REMEMBER- Osteosarcoma produces malignant osteoid — diagnostic on histology.
- Adolescents, metaphysis around the knee; Codman triangle and sunburst on X-ray.
- Early haematogenous spread to lungs; associated with Rb and p53 mutations.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Cushing syndrome is the clinical state resulting from chronic excess of glucocorticoids.
Causes
- Exogenous (iatrogenic) steroids — commonest cause overall
- Cushing disease — pituitary ACTH-secreting adenoma (commonest endogenous cause); bilateral adrenal hyperplasia
- Adrenal — adenoma or carcinoma (ACTH-independent)
- Ectopic ACTH — small cell carcinoma of lung; marked pigmentation and hypokalaemia
Features & Investigations
- Central obesity, moon face, buffalo hump, thin limbs
- Purple striae, thin skin, easy bruising, proximal myopathy
- Hypertension, hyperglycaemia, osteoporosis, hirsutism, amenorrhoea, psychiatric changes
- Screening: 24-hour urinary free cortisol, late-night salivary cortisol, overnight dexamethasone suppression test
- ACTH level and high-dose dexamethasone localise the cause
Catabolic effects on protein with anabolic fat redistribution explain the habitus. Cause ACTH Suppression Pituitary High By high dose Adrenal tumour Low None Ectopic Very high None Applied
- Always ask about steroid use before extensive investigation
- Never stop long-term steroids abruptly — risk of adrenal crisis
🔑KEY POINTS TO REMEMBER- Exogenous steroids are the commonest cause; Cushing disease is a pituitary adenoma.
- Central obesity, moon face, buffalo hump, purple striae, hypertension, diabetes.
- ACTH level and dexamethasone suppression localise the cause.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Phaeochromocytoma is a catecholamine-secreting tumour of chromaffin cells of the adrenal medulla causing episodic hypertension.
The Rule of 10
- 10% bilateral, 10% extra-adrenal (paraganglioma, organ of Zuckerkandl)
- 10% malignant, 10% familial, 10% in children
- Familial associations: MEN 2A and 2B (RET), von Hippel-Lindau, neurofibromatosis type 1
- Secretes adrenaline and noradrenaline
Features & Diagnosis
- Classic triad: episodic headache, palpitations and profuse sweating
- Paroxysmal hypertension (may be sustained), pallor, anxiety, tremor, weight loss
- Attacks precipitated by exercise, stress, palpation, anaesthesia
- Diagnosis: plasma free metanephrines or 24-hour urinary metanephrines and VMA
- Localisation: CT/MRI, MIBG scan
Episodic catecholamine release explains the paroxysmal symptoms. Feature Detail Triad Headache, palpitations, sweating Test Urinary metanephrines Imaging CT / MIBG Applied
- α-blockade (phenoxybenzamine) before β-blockade — otherwise hypertensive crisis
- Surgical excision is curative
🔑KEY POINTS TO REMEMBER- Phaeochromocytoma follows the rule of 10; arises from adrenal chromaffin cells.
- Triad of episodic headache, palpitations and sweating with paroxysmal hypertension.
- Diagnosed by urinary/plasma metanephrines; α-blockade must precede β-blockade.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.