FMGE Pathology Syllabus

Define the difference between dysplasia, carcinoma in situ, and invasive carcinoma.

Dysplasia is disordered, atypical growth that is reversible and does not breach the basement membrane. Carcinoma in situ is full-thickness dysplasia confined above the basement membrane. Invasive carcinoma penetrates the basement membrane.

What are the routes of metastatic spread and the typical route for carcinomas versus sarcomas?

Routes: lymphatic, hematogenous, and transcoelomic (seeding of body cavities). Carcinomas classically spread first via lymphatics; sarcomas spread preferentially via the bloodstream (hematogenous).

Distinguish oncogenes from tumor suppressor genes, with a key example of each.

Oncogenes are gain-of-function, dominant, promote growth (e.g., RAS, MYC, HER2). Tumor suppressor genes are loss-of-function, usually require both alleles inactivated (two-hit hypothesis), and brake growth (e.g., TP53, RB1).

List the four types of hypersensitivity reactions with the immune mechanism of each.

Type I: IgE-mediated immediate (anaphylaxis). Type II: antibody-mediated cytotoxic (autoimmune hemolytic anemia). Type III: immune-complex mediated (SLE, serum sickness). Type IV: T-cell mediated delayed (TB, contact dermatitis).

What are the major classifications of amyloid and their associated proteins?

AL (primary) from immunoglobulin light chains (plasma cell dyscrasias); AA (secondary) from serum amyloid-associated protein (chronic inflammation); ATTR (transthyretin); and Abeta (Alzheimer disease). All show apple-green birefringence with Congo red under polarized light.

How are anemias classified morphologically by MCV, and give a cause for each.

Microcytic (MCV <80): iron deficiency, thalassemia. Normocytic (80-100): acute blood loss, anemia of chronic disease, hemolysis. Macrocytic (MCV >100): B12/folate deficiency (megaloblastic), liver disease, hypothyroidism.

What peripheral smear and lab findings characterize iron deficiency anemia?

Microcytic, hypochromic RBCs with anisopoikilocytosis and pencil cells; low serum ferritin and serum iron, high TIBC, low transferrin saturation, and increased RDW.

What distinguishes megaloblastic anemia on smear and what causes it?

Macro-ovalocytes and hypersegmented neutrophils (>5 lobes) due to impaired DNA synthesis from vitamin B12 or folate deficiency; the bone marrow shows nuclear-cytoplasmic dyssynchrony.

Differentiate intravascular from extravascular hemolysis in lab findings.

Intravascular: hemoglobinemia, hemoglobinuria, hemosiderinuria, markedly low haptoglobin, high LDH. Extravascular (splenic): splenomegaly, increased unconjugated bilirubin, spherocytes, less hemoglobinuria.

What is the molecular defect and smear finding in hereditary spherocytosis?

Defects in RBC membrane cytoskeletal proteins (most commonly ankyrin or spectrin) producing spherocytes; increased osmotic fragility and a positive eosin-5-maleimide (EMA) binding test, with negative Coombs test.

What is the pathophysiology of sickle cell disease and the key mutation?

A point mutation (GAG to GTG) at codon 6 of the beta-globin gene substitutes valine for glutamic acid (HbS). Deoxygenated HbS polymerizes, sickling RBCs, causing vaso-occlusion and chronic hemolysis.

How are alpha and beta thalassemias differentiated in terms of globin chains and electrophoresis?

Alpha thalassemia: reduced alpha-globin chains (gene deletions), excess beta/gamma chains (HbH, Hb Barts). Beta thalassemia: reduced beta-globin chains, with elevated HbA2 and HbF on electrophoresis.

What are the FAB and WHO distinctions between acute and chronic leukemia?

Acute leukemia: predominance of immature blasts (≥20% blasts in marrow per WHO), rapid course. Chronic leukemia: predominance of mature/maturing cells, insidious course. Lineage is myeloid (AML/CML) or lymphoid (ALL/CLL).

What genetic marker and clinical phase define chronic myeloid leukemia?

The Philadelphia chromosome t(9;22) producing the BCR-ABL1 fusion gene with constitutive tyrosine kinase activity; CML progresses through chronic, accelerated and blast crisis phases.

How do Hodgkin and non-Hodgkin lymphoma differ, including the diagnostic cell of Hodgkin?

Hodgkin lymphoma spreads contiguously, is localized, and contains Reed-Sternberg cells (CD15+, CD30+, 'owl-eye' binucleate). Non-Hodgkin lymphoma spreads non-contiguously, is often disseminated, and lacks Reed-Sternberg cells.

What are the key features of multiple myeloma on labs and marrow?

Monoclonal (M) spike on serum protein electrophoresis, Bence-Jones light chains in urine, >10% clonal plasma cells in marrow, lytic 'punched-out' bone lesions, hypercalcemia, renal failure, and rouleaux formation.

Differentiate the bleeding pattern of platelet disorders from coagulation factor disorders.

Platelet/vascular disorders cause mucocutaneous bleeding (petechiae, epistaxis, gum bleeding) with prolonged bleeding time. Coagulation factor disorders cause deep bleeding (hemarthroses, hematomas) with prolonged PT and/or aPTT.

What clotting tests are abnormal in hemophilia A and von Willebrand disease?

Hemophilia A (factor VIII deficiency): prolonged aPTT, normal PT, normal platelets/bleeding time. Von Willebrand disease: prolonged bleeding time and aPTT, with decreased ristocetin cofactor activity and factor VIII levels.

What are the characteristic lab findings in disseminated intravascular coagulation (DIC)?

Prolonged PT and aPTT, low fibrinogen, low platelets, elevated D-dimer/fibrin degradation products, and schistocytes (microangiopathic hemolysis) on smear.

List the major ABO blood groups and the rule of compatibility for transfusion.

Groups A, B, AB (universal recipient) and O (universal donor for packed RBCs). Individuals have naturally occurring antibodies against absent antigens; donor RBC antigens must not react with recipient plasma antibodies.

What is the difference between the direct and indirect Coombs (antiglobulin) test?

Direct Coombs detects antibodies/complement already bound to the patient's RBCs (e.g., autoimmune hemolytic anemia, hemolytic disease of newborn). Indirect Coombs detects free antibodies in the patient's serum (used in crossmatching and antibody screening).

What is the most common cause of fatal acute hemolytic transfusion reaction, and its mechanism?

ABO incompatibility, usually from clerical/identification error, causing complement-mediated intravascular hemolysis (Type II hypersensitivity) with fever, flank pain, hemoglobinuria, hypotension and DIC.

Distinguish stable, unstable and Prinzmetal angina pathophysiologically.

Stable angina: fixed atherosclerotic stenosis, pain on exertion relieved by rest. Unstable angina: disrupted plaque with non-occlusive thrombus, pain at rest. Prinzmetal (variant) angina: coronary vasospasm, often at rest with ST elevation.

Describe the time course of gross and microscopic changes after myocardial infarction.

0-4 h: none. 4-12 h: wavy fibers, early coagulative necrosis. 1-3 days: neutrophil infiltrate. 3-7 days: macrophages remove dead myocytes. 1-2 weeks: granulation tissue. >2 months: dense collagenous scar.

What are the major morphologic types of cardiomyopathy?

Dilated (systolic dysfunction, four-chamber dilation), hypertrophic (asymmetric septal hypertrophy, diastolic dysfunction, often genetic), and restrictive (impaired filling from stiff myocardium, e.g., amyloidosis).

What are the gross and microscopic hallmarks of pulmonary tuberculosis (Ghon complex)?

A Ghon focus is a subpleural caseating granuloma; the Ghon complex adds hilar lymph node involvement. Microscopy shows caseating granulomas with epithelioid cells, Langhans giant cells, and acid-fast bacilli on Ziehl-Neelsen stain.

Differentiate centriacinar from panacinar emphysema and their associations.

Centriacinar (centrilobular) emphysema affects respiratory bronchioles in upper lobes and is associated with smoking. Panacinar emphysema affects the whole acinus in lower lobes and is associated with alpha-1 antitrypsin deficiency.

Contrast small cell and non-small cell lung carcinoma in origin, behavior and treatment.

Small cell carcinoma: central, neuroendocrine origin, strongly smoking-related, early metastasis, paraneoplastic syndromes (SIADH, ACTH), treated with chemo/radiation (not surgery). Non-small cell (adeno, squamous, large cell): often resectable if localized.

What distinguishes Crohn disease from ulcerative colitis pathologically?

Crohn disease: transmural, skip lesions anywhere mouth-to-anus, non-caseating granulomas, cobblestoning, fistulae, fissures. Ulcerative colitis: mucosal/submucosal, continuous from rectum, crypt abscesses, pseudopolyps, no granulomas.

List the morphologic types of cirrhosis and the key complications of cirrhosis.

Micronodular (alcohol) and macronodular (viral hepatitis) cirrhosis. Complications: portal hypertension (varices, ascites, splenomegaly, caput medusae), hepatic encephalopathy, hepatorenal syndrome, and hepatocellular carcinoma.

Differentiate nephrotic from nephritic syndrome.

Nephrotic syndrome: massive proteinuria (>3.5 g/day), hypoalbuminemia, edema, hyperlipidemia, lipiduria. Nephritic syndrome: hematuria with RBC casts, hypertension, oliguria, azotemia, and mild-to-moderate proteinuria.

What are the characteristic glomerular findings in post-streptococcal glomerulonephritis?

Diffuse proliferative GN with subepithelial 'humps' on electron microscopy, granular IgG and C3 immunofluorescence, hypercellular glomeruli, and low serum C3, typically 1-3 weeks after streptococcal infection.

What are the most common renal stones and their urinary associations?

Calcium oxalate/phosphate (most common, hypercalciuria), struvite (magnesium-ammonium-phosphate, urease-producing organisms, 'staghorn' calculi, alkaline urine), uric acid (acidic urine, gout, radiolucent), and cystine stones.

Differentiate the histologic types of diabetes mellitus pancreatic and the diagnostic Whipple criteria are not asked; instead, list the four common thyroid carcinomas and one key feature each.

Papillary (Orphan Annie nuclei, psammoma bodies, best prognosis), follicular (capsular/vascular invasion), medullary (calcitonin, amyloid stroma, MEN2), and anaplastic (highly aggressive, elderly).

How are breast carcinomas classified and what is the most common type?

Invasive ductal carcinoma (no special type) is most common, forming a hard, gritty desmoplastic mass. Invasive lobular carcinoma shows single-file 'Indian file' cells with loss of E-cadherin. Receptor status (ER, PR, HER2) guides therapy.

Name the most common primary brain tumors in adults and children.

Adults: glioblastoma multiforme (supratentorial, pseudopalisading necrosis), meningioma (psammoma bodies, whorls). Children: pilocytic astrocytoma (Rosenthal fibers) and medulloblastoma (cerebellar, Homer-Wright rosettes).

Differentiate osteosarcoma, Ewing sarcoma and giant cell tumor of bone.

Osteosarcoma: metaphysis of long bones (knee), young, malignant osteoid, Codman triangle/sunburst. Ewing sarcoma: diaphysis, children, t(11;22), 'onion-skin' periosteum, small round blue cells. Giant cell tumor: epiphysis, 'soap-bubble', osteoclast-like giant cells.

What casts in urine indicate which renal conditions?

RBC casts: glomerulonephritis. WBC casts: pyelonephritis/interstitial nephritis. Granular ('muddy brown') casts: acute tubular necrosis. Fatty casts: nephrotic syndrome. Waxy/broad casts: chronic renal failure. Hyaline casts: nonspecific/normal in concentrated urine.

How is a pleural/ascitic fluid classified as transudate vs exudate (Light's criteria principle)?

An exudate meets any of: fluid-to-serum protein ratio >0.5, fluid-to-serum LDH ratio >0.6, or fluid LDH greater than two-thirds the upper normal serum limit. Failing all suggests a transudate.

What are the principles and main advantage of fine-needle aspiration cytology (FNAC)?

FNAC uses a fine needle to aspirate cells for cytologic examination; it is rapid, inexpensive, minimally invasive and OPD-based, but assesses cytomorphology only (individual cells/clusters) and cannot evaluate tissue architecture/invasion like histopathology.

Match these special stains to their target: PAS, Congo red, Prussian blue, Ziehl-Neelsen, reticulin.

PAS: glycogen, fungi, basement membranes. Congo red: amyloid (apple-green birefringence). Prussian blue (Perls): iron/hemosiderin. Ziehl-Neelsen: acid-fast bacilli (TB, leprosy). Reticulin: reticulin/type III collagen framework.

What is immunohistochemistry and name common markers for epithelial, mesenchymal, lymphoid and melanocytic tumors.

IHC uses antibodies against specific antigens to identify cell lineage. Epithelial: cytokeratin, EMA. Mesenchymal: vimentin. Lymphoid: LCA/CD45. Melanocytic: S-100, HMB-45, Melan-A.

What is the difference between autolysis, putrefaction and an autopsy's purpose?

Autolysis is sterile self-digestion by the body's own enzymes after death; putrefaction is bacterial decomposition. An autopsy (necropsy) is a systematic post-mortem dissection to establish cause/manner of death and correlate clinical with pathologic findings.