NEET MDS General Pathology Syllabus

What are the three progressive stages of shock?

Nonprogressive (compensated, reflex mechanisms maintain perfusion), progressive (tissue hypoperfusion, metabolic acidosis), and irreversible (organ damage incompatible with survival).

Contrast the inheritance and a classic example of autosomal dominant vs autosomal recessive disorders.

Autosomal dominant: one mutant allele suffices, often structural proteins/receptors (e.g., familial hypercholesterolemia, Marfan). Autosomal recessive: both alleles mutated, often enzymes (e.g., phenylketonuria, sickle cell).

What is the underlying genetic defect in Marfan syndrome and its mode of inheritance?

Autosomal dominant mutation in the FBN1 gene encoding fibrillin-1, a component of microfibrils in the extracellular matrix.

What chromosomal abnormality causes Down syndrome and what is its most common mechanism?

Trisomy 21. Most cases (~95%) result from meiotic nondisjunction, with maternal age being the major risk factor; a minority are due to Robertsonian translocation.

Give the karyotypes for Klinefelter and Turner syndromes.

Klinefelter syndrome: 47,XXY (or more X chromosomes). Turner syndrome: 45,X (monosomy X).

What is a multifactorial (polygenic) disorder? Give two examples.

A disorder resulting from the combined effect of multiple genes and environmental factors. Examples: type 2 diabetes, hypertension, coronary heart disease, and cleft lip/palate.

What is trinucleotide repeat expansion, and name a disease caused by it.

Amplification of a sequence of three nucleotides beyond a normal threshold, causing dysfunction. Examples: Fragile X syndrome (CGG), Huntington disease (CAG), myotonic dystrophy (CTG).

What is the difference between a benign and a malignant neoplasm in terms of nomenclature suffixes?

Benign tumors usually end in '-oma' (e.g., adenoma, lipoma). Malignant tumors of epithelial origin are 'carcinomas' and of mesenchymal origin are 'sarcomas'.

What are the two broad classes of cancer genes and how do their mutations behave?

Oncogenes (gain-of-function, dominant, e.g., RAS, MYC) and tumor suppressor genes (loss-of-function, usually require two hits, e.g., RB, TP53).

Explain the Knudson two-hit hypothesis using retinoblastoma.

Both alleles of the RB tumor suppressor gene must be inactivated for tumor development. In familial cases one mutation is inherited (germline) and a second somatic hit is needed; in sporadic cases both hits are somatic.

What is the role of TP53 and why is it called the 'guardian of the genome'?

TP53 senses DNA damage and induces cell-cycle arrest (allowing repair), senescence, or apoptosis. Loss permits propagation of damaged DNA; it is the most commonly mutated gene in human cancer.

What are the hallmarks that define tumor-host interactions enabling cancer survival?

Sustained angiogenesis (VEGF-driven), evasion of immune destruction, tumor-promoting inflammation, and cachexia (host wasting from TNF/cytokines).

What are the three classes of carcinogenic agents?

Chemical carcinogens (initiators and promoters), radiant energy (UV and ionizing radiation), and microbial/oncogenic agents (HPV, HBV, EBV, H. pylori).

Describe the steps of the metastatic cascade.

Local invasion (loss of E-cadherin, ECM degradation by matrix metalloproteinases), intravasation, survival in circulation, extravasation, and colonization at a distant site.

What is tumor grading versus tumor staging?

Grading assesses the degree of differentiation/anaplasia (how the tumor looks). Staging assesses the extent of spread using TNM (Tumor size, Node involvement, Metastasis). Staging has greater clinical/prognostic value.

What are paraneoplastic syndromes? Give two classic examples.

Symptom complexes from a tumor not explained by local spread or hormones expected from the tissue. Examples: SIADH and ACTH (Cushing) from small cell lung carcinoma; hypercalcemia from squamous cell carcinoma (PTHrP).

What vitamin deficiencies cause scurvy and rickets, and what is the defect in each?

Scurvy: vitamin C deficiency, impaired collagen hydroxylation causing poor wound healing and bleeding gums. Rickets: vitamin D deficiency, defective bone mineralization in children (osteomalacia in adults).

Differentiate marasmus from kwashiorkor.

Marasmus: severe total calorie deficiency with marked muscle/fat wasting, preserved albumin. Kwashiorkor: severe protein deficiency with edema, hypoalbuminemia, fatty liver, and 'flaky paint' skin.

What are the major virulence mechanisms by which microbes cause disease?

Adherence/colonization, invasion, production of exotoxins and endotoxins (LPS), evasion of host immunity, and induction of host damaging immune responses.

Name the histologic hallmark of tuberculosis and the causative organism's stain.

Caseating epithelioid granuloma with Langhans giant cells. Mycobacterium tuberculosis is acid-fast (Ziehl-Neelsen stain positive).

What cytopathic changes are characteristic of herpesvirus and CMV infections?

Herpes: Cowdry type A intranuclear inclusions, multinucleated cells with molding (Tzanck cells). CMV: large cells with 'owl's eye' intranuclear inclusions and basophilic cytoplasmic inclusions.

What special stains are used to identify fungi in tissue?

PAS (periodic acid-Schiff) and GMS (Gomori methenamine silver) stains highlight fungal cell walls.

What are the four types (Gell and Coombs) of hypersensitivity reactions?

Type I: immediate/IgE-mediated (anaphylaxis). Type II: antibody-mediated/cytotoxic. Type III: immune complex-mediated. Type IV: cell-mediated/delayed (T cells).

What is the difference between central and peripheral immune tolerance?

Central tolerance: deletion of self-reactive lymphocytes in the thymus (T cells) and bone marrow (B cells). Peripheral tolerance: control of self-reactive cells that escape, via anergy, suppression by Tregs, or deletion.

Name the autoantibody most associated with SLE and the most specific one.

Antinuclear antibody (ANA) is most sensitive (screening). Anti-double-stranded DNA and anti-Smith (anti-Sm) antibodies are most specific for SLE.

What is the difference between primary and secondary immunodeficiency? Give an example of each.

Primary: genetic/congenital (e.g., DiGeorge syndrome, SCID, X-linked agammaglobulinemia). Secondary: acquired (e.g., HIV/AIDS, malnutrition, immunosuppressive therapy).

What is amyloid, and which stain confirms it with what characteristic appearance?

Amyloid is a pathologic, misfolded protein with beta-pleated sheet structure deposited extracellularly. Congo red stain shows apple-green birefringence under polarized light.

What are the two most common chemical forms of amyloid and their associated conditions?

AL (amyloid light chain) from plasma cell dyscrasias/multiple myeloma; AA (amyloid-associated/serum SAA) in chronic inflammatory conditions.

What is the most common cause of myocardial infarction and which artery is most frequently involved?

Coronary atherosclerosis with acute plaque disruption and superimposed thrombosis. The left anterior descending (LAD) artery is most commonly involved.

What are the cardiac biomarkers for MI and their time course?

Troponins I and T are most specific, rise in 2-4 hours, peak at ~48 hours, remain elevated 7-10 days. CK-MB rises in 2-4 hours, peaks at 24 hours, normalizes by 72 hours (useful for re-infarction).

What is the characteristic cardiac change in systemic hypertensive heart disease?

Concentric left ventricular hypertrophy (LV wall thickening) without dilation, due to pressure overload.

What organism causes acute rheumatic fever and what valvular lesion results chronically?

Group A beta-hemolytic Streptococcus (via molecular mimicry). Chronically it causes mitral stenosis with 'fish-mouth' deformity; Aschoff bodies are the pathognomonic cardiac lesion.

Differentiate dilated, hypertrophic, and restrictive cardiomyopathy by their primary functional defect.

Dilated: systolic (contractile) dysfunction with all-chamber dilation. Hypertrophic: diastolic dysfunction with septal hypertrophy. Restrictive: impaired ventricular filling (compliance) with normal-sized chambers.

Differentiate emphysema from chronic bronchitis (obstructive lung diseases).

Emphysema: permanent enlargement of airspaces distal to terminal bronchioles with alveolar wall destruction (anatomic). Chronic bronchitis: productive cough for >=3 months in >=2 consecutive years (clinical), with mucus gland hyperplasia (Reid index increased).

What characterizes restrictive lung disease and name a classic interstitial example.

Reduced lung compliance and decreased total lung capacity with preserved/increased FEV1/FVC ratio. Idiopathic pulmonary fibrosis (usual interstitial pneumonia with honeycomb lung) is a classic example.

What is the most common lung cancer overall and the one most strongly linked to smoking centrally?

Adenocarcinoma is the most common overall (and in non-smokers, peripheral). Squamous cell carcinoma and small cell carcinoma are most strongly smoking-related and typically central.

What is Barrett esophagus and what malignancy does it predispose to?

Metaplastic replacement of the distal esophageal squamous epithelium by columnar epithelium with goblet cells, due to chronic GERD. It predisposes to esophageal adenocarcinoma.

What organism causes most peptic ulcers and chronic gastritis, and what gastric cancers is it linked to?

Helicobacter pylori. It is linked to gastric adenocarcinoma (intestinal type) and gastric MALT lymphoma.

Differentiate Crohn disease from ulcerative colitis.

Crohn: transmural, skip lesions, any GI site (terminal ileum common), non-caseating granulomas, cobblestone mucosa, fistulae. UC: mucosal/submucosal, continuous, limited to colon/rectum, crypt abscesses, no granulomas, increased cancer risk.

What is the irreversible end-stage of chronic liver disease and its two histologic hallmarks?

Cirrhosis. Hallmarks are diffuse bridging fibrosis and regenerative parenchymal nodules disrupting normal architecture.

What pigment and condition characterize cholelithiasis-related cholecystitis, and what are the two main gallstone types?

Cholesterol stones (yellow, associated with obesity/female/fertile/forty) and pigment stones (black/brown, associated with hemolysis and infection). Stones cause obstruction leading to cholecystitis.

What enzymes are elevated in acute pancreatitis and what is the most common cause?

Serum amylase and lipase (lipase more specific) are elevated. The most common causes are gallstones and alcohol; mechanism is autodigestion by activated pancreatic enzymes.

What is the most common type of renal stone and the most common cause of nephrotic syndrome in adults?

Calcium oxalate stones are most common. Membranous nephropathy (and FSGS) are leading causes of adult nephrotic syndrome; minimal change disease is most common in children.

What is the most common malignancy of the urinary bladder and its main risk factor?

Urothelial (transitional cell) carcinoma. Major risk factors are smoking and exposure to aromatic amines (aniline dyes); painless hematuria is the typical presentation.

What is the most common cancer in men's prostate and where does it typically arise?

Prostatic adenocarcinoma, typically arising in the peripheral zone (posterior); benign prostatic hyperplasia arises in the transitional zone. Gleason score grades it.

What HPV types cause cervical cancer and what precursor lesion precedes it?

High-risk HPV types 16 and 18. The precursor is cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesion, progressing to squamous cell carcinoma.

What receptors are tested in breast cancer to guide therapy, and which subtype has the worst prognosis?

Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. Triple-negative (ER-, PR-, HER2-) breast cancer has the worst prognosis.

What is the most common pituitary adenoma and the hormone it secretes?

Prolactinoma (lactotroph adenoma), secreting prolactin, causing amenorrhea/galactorrhea in women and decreased libido in men.

What are the nuclear features and histologic hallmark of papillary thyroid carcinoma?

Orphan Annie eye nuclei (clear/empty), nuclear grooves, and intranuclear pseudoinclusions, with psammoma bodies. It is the most common thyroid cancer with the best prognosis.

What is the most common cause of primary hyperparathyroidism and its classic effect on bone?

Parathyroid adenoma. Excess PTH causes hypercalcemia and osteitis fibrosa cystica ('brown tumors' of bone), plus 'stones, bones, groans, and psychiatric moans'.

What adrenal tumor causes episodic hypertension and follows the 'rule of 10s'?

Pheochromocytoma (catecholamine-secreting tumor of adrenal medulla chromaffin cells). Rule of 10s: 10% extra-adrenal, 10% bilateral, 10% malignant, 10% familial.

What is the most common functional pancreatic endocrine tumor and its classic triad?

Insulinoma. Whipple triad: hypoglycemic symptoms, low blood glucose (<50 mg/dL), and relief of symptoms after glucose administration.

What is the most common cause of ischemic stroke and the classic brain lesion of hypertension?

Embolic/thrombotic occlusion (atherosclerosis, cardiac emboli) causing ischemic infarct. Chronic hypertension causes lacunar infarcts and Charcot-Bouchard microaneurysm rupture (basal ganglia hemorrhage).

What organisms cause meningitis in neonates versus young adults?

Neonates: Group B Streptococcus, E. coli, Listeria. Young adults: Neisseria meningitidis (and Streptococcus pneumoniae across ages).

What are the histologic hallmarks of Alzheimer disease?

Neuritic (senile) plaques of extracellular beta-amyloid and intracellular neurofibrillary tangles of hyperphosphorylated tau protein, with cortical atrophy.

What is the most common primary malignant CNS tumor in adults and its histologic hallmark?

Glioblastoma (GBM, grade IV astrocytoma). Hallmarks are microvascular/endothelial proliferation and pseudopalisading necrosis.

What metabolic bone disease shows decreased bone mass with normal mineralization, and what shows defective mineralization?

Osteoporosis: decreased bone mass with normal mineralization (normal Ca/phosphate). Osteomalacia/rickets: defective mineralization of osteoid due to vitamin D deficiency.

What crystals are deposited in gout versus pseudogout, and how are they distinguished?

Gout: monosodium urate crystals, needle-shaped, negatively birefringent (yellow when parallel). Pseudogout: calcium pyrophosphate crystals, rhomboid, positively birefringent.

What is the autoimmune muscle disease caused by antibodies to acetylcholine receptors and its clinical hallmark?

Myasthenia gravis. Anti-AChR antibodies cause fluctuating muscle weakness worsening with activity (fatigability), notably ptosis and diplopia; associated with thymic hyperplasia/thymoma.

What is the histologic triad of eczematous (spongiotic) dermatitis?

Spongiosis (intercellular edema of epidermis), with a superficial perivascular lymphocytic infiltrate; chronic lesions show acanthosis and hyperkeratosis.

Differentiate pemphigus vulgaris from bullous pemphigoid (blistering diseases).

Pemphigus vulgaris: anti-desmoglein (desmosome) antibodies, intraepidermal (suprabasal) flaccid bullae, positive Nikolsky sign, 'fish-net' IF. Bullous pemphigoid: anti-hemidesmosome (BPAG) antibodies, subepidermal tense bullae, linear IF, negative Nikolsky.

What are the three most common skin cancers and which is most lethal?

Basal cell carcinoma (most common, locally invasive, rarely metastasizes), squamous cell carcinoma, and melanoma (most lethal due to high metastatic potential).

What is the difference between agenesis, aplasia, and atresia in congenital anomalies?

Agenesis: complete absence of an organ and its primordium. Aplasia: absence of an organ due to failed development of its primordium (rudimentary present). Atresia: absence of an opening/lumen of a normally tubular organ.

What is erythroblastosis fetalis and its main cause?

Hemolytic disease of the newborn from maternal antibodies crossing the placenta against fetal red cells, classically Rh(D) incompatibility (Rh-negative mother, Rh-positive fetus), causing fetal hemolysis, anemia, and hydrops.

What is the most common solid malignant tumor of childhood arising from the adrenal medulla/sympathetic chain?

Neuroblastoma. It arises from neural crest cells, may show N-MYC amplification (poor prognosis), elevated urinary catecholamines (VMA/HVA), and Homer-Wright rosettes histologically.

What is the most common primary renal malignancy of childhood and its classic histology?

Wilms tumor (nephroblastoma). It shows a triphasic pattern of blastemal, epithelial (abortive tubules/glomeruli), and stromal elements; associated with WT1 gene mutations.