Last Minute Revision: High-Yield Pathology Concepts for Exams

Cardiovascular Pathology Highlights

The blog began with a focus on the cardiovascular system. A classic, frequently tested concept is the autopsy diagnosis of myocardial infarction (MI). This can be done by dipping tissue slices in a solution of TPTC (Triphenyl tetrazolium chloride). TPTC is particularly useful within the first 4 hours of an MI. It stains LDH1, an enzyme. Normal heart tissue, rich in LDH, appears brick red, while the ischemic area lacking LDH becomes pale.

Microscopically, the earliest change in MI, visible within the first 30 minutes by electron microscopy, is mitochondrial swelling. Light microscopy reveals waviness and vacuolization of cardiac fibers within 30 minutes to 4 hours. Gross changes, such as modeling (color change), are typically seen only after 4 hours. This absence of gross change in the initial 4 hours underscores the utility of TPTC staining during this early period.

Moving to fixatives, neutral buffered formalin is the standard for light microscopy. For specific applications like Pap smears in gynecology, 95% ethanol is used as a fixative.

The discussion then covered endocarditis, focusing on vegetations, also sometimes referred to as verruka. Four types of endocarditis were highlighted:

Rheumatic Heart Disease (RHD)

Caused by Group A beta hemolytic streptococcus (Streptococcus pyogenes). Characterized by small, warty vegetation. The most characteristic lesion is the Ashoff body, found in the myocardium. Ashoff bodies feature central fibrinoid necrosis surrounded by large macrophages called Anitschkow cells. These cells can have a zigzag (caterpillar) or round (owly) appearance. Fibrinoid necrosis is a general pathology concept also seen in conditions like Polyarteritis Nodosa, SLE, and malignant hypertension.

Infective Endocarditis

Caused by various bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans. Features large and bulky vegetation.

Nonbacterial Thrombotic Endocarditis (NBTE)

Not caused by infection. Strongly associated with certain cancers, particularly lung adenocarcinoma and pancreatic adenocarcinoma. These tumors produce mucin, which is thrombogenic and leads to thrombus formation on heart valves. These thrombi can easily break off, resulting in embolism. NBTE can also occur in AML M3 leukemia, known for causing DIC.

Libman-Sacks Endocarditis (LSE)

Associated with SLE. Vegetations occur on both upper and lower valve surfaces, but are more common on the lower surface. Cardiomyopathies were extensively discussed, focusing on their key features and genetic associations:

Hypertrophic Cardiomyopathy (HCM)

A major cause of sudden cardiac death in young individuals. Often seen in athletes. It is an autosomal dominant disorder, frequently with a family history of sudden death at a young age. The most common gene mutation is in the beta myosin heavy chain (MYH/beta MHC). Grossly, there is marked thickening of the interventricular septum, making the left ventricle appear banana-shaped and often causing obstruction (Hypertrophic Obstructive Cardiomyopathy - HOCM). This obstruction can lead to symptoms like exertional chest pain and shortness of breath, and patients are at risk of ventricular fibrillation. Microscopically, the cardiac fibers show a characteristic helter skelter appearance, being disorganized and not aligned.

Dilated Cardiomyopathy (DCM)

The most common type of cardiomyopathy overall. More than 50% of cases are idiopathic. If idiopathic is not an option, alcohol is a frequent cause. The most common gene mutation is in the Titan gene. Grossly, all four heart chambers are dilated. Microscopically, the nuclei of cardiac fibers can show a ninja star appearance.

Takotsubo Cardiomyopathy

Known colloquially as "broken heart syndrome" or stress cardiomyopathy. Triggered by severe emotional or physical stress, leading to a surge in catecholamines. It primarily affects and dilates the left ventricle, the chamber with the highest concentration of catecholamine receptors.

Restrictive Cardiomyopathy

Impairs the heart's ability to relax during diastole. The most common cause is infiltration of the heart muscle, often by amyloid. Amyloid can be detected using Congo Red stain, which gives a distinctive apple green birefringence under polarized light. Congo Red positivity in the heart is a key indicator.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVCM)

(Higher yield for NEET PG/INI-CET) Primarily affects the right ventricle, characterized by replacement of heart muscle with fat deposition. This leads to arrhythmias. It's associated with Naxos syndrome, which includes ARVCM, woolly hair, and hyperkeratosis of palms and soles. ARVCM is an autosomal dominant disorder and is related to defects in desmosome proteins, specifically plakoglobin in Naxos syndrome.

Several cardiac tumors were reviewed. The most common malignancy of the heart is metastasis, frequently from cancers of the breast or lung. Primary heart tumors are often benign. Two key primary tumors are:

Myxoma

The most common primary heart tumor in adults. Typically located in the left atrium. Grossly, it has a gelatinous, myxoid appearance. Microscopically, it may show lepidic cells. Myxomas are associated with the Carney complex, which involves the PRKAR1A gene mutation (referred to as Genus one mutation in the transcript). Carney complex is part of syndromes like NAME (Nevi, Atrial myxoma, Myxoid neurofibromas, Endocrine hyperactivity/effluids) and LAMB (Lentigines, Atrial myxoma, Mucocutaneous myxomas, Blue nevi).

Rhabdomyoma

The most common primary heart tumor in children. Usually found in the left ventricle. Histologically characterized by pathognomonic spider cells. Rhabdomyomas are associated with Tuberous sclerosis (TSC1 and TSC2 gene mutations).

Other Vascular Tumors

Beyond cardiac tumors, other vascular lesions were discussed. Glomus tumors are found in the nail bed (subungual) and are known for causing exquisite/excruciating pain. They arise from glomus bodies and are mainly a clinical diagnosis. Cystic hygroma is a type of lymphangioma (tumor of lymphatic channels), specifically a cavernous lymphangioma, commonly found in the neck, and associated with Turner syndrome (45XO).

Exposure to certain chemicals can cause angiosarcoma of the liver. These include the VAT chemicals: Vinyl chloride (used in PVC plastics), Arsenic (found in pesticides), and Thorotrast (an old thorium-based contrast dye). Other chemical associations include benzene with AML and benzidine with urinary bladder cancer. Tobacco smoking is a significant risk factor for many cancers, including being the single most important risk factor for Renal Cell Carcinoma (RCC).

Kaposi Sarcoma is a vascular tumor seen in HIV-positive patients, often presenting as reddish-purple skin lesions. The most common site is the skin of the lower legs, with the lymph node being the second most common site. It is associated with Human Herpes Virus 8 (HHV8). While it can occur at CD4 counts below 500, it is typically seen when the CD4 count drops below 200.

Understanding Vasculitis

Vasculitis, inflammation of blood vessels, is classified by vessel size using the Chapel Hill classification.

Large Vessel Vasculitis

Includes Takayasu Arteritis and Giant Cell Arteritis (Temporal Arteritis). Takayasu Arteritis affects individuals under 50, often called Pulseless disease or Aortoarteritis, primarily involving the subclavian artery. Giant Cell Arteritis is seen in those over 50 (the most common adult vasculitis), involves granulomatous inflammation, most commonly affects the superficial temporal artery, causes headache (most common symptom), jaw claudication (most specific), and potential blindness (most dangerous). Treatment for Giant Cell Arteritis requires immediate steroid administration without waiting for a biopsy report due to the risk of irreversible blindness.

Medium Vessel Vasculitis

Key examples are Polyarteritis Nodosa (PAN), Kawasaki Disease, and Buerger's Disease. PAN involves multiple organs but characteristically spares pulmonary vessels ("P is not for P"). It shows fibrinoid necrosis and is associated with Hepatitis B (Australia antigen). The most commonly affected vessel in PAN is the renal artery, but it does not cause glomerulonephritis; instead, it can lead to a flea-bitten kidney. Kawasaki Disease affects kids (<5 years) and is characterized by fever plus specific criteria (CREAM): Conjunctivitis (bilateral, non-purulent), Rash, Edema, Adenopathy (unilateral cervical), Mucosal involvement (strawberry tongue). It is associated with anti-endothelial cell antibodies. Buerger's Disease (Thromboangiitis Obliterans) is strongly linked to smoking, affects arteries and veins causing pain, and notably does not involve lymphatics.

Small Vessel Vasculitis

Examples include Henoch-Schonlein Purpura (HSP) and Wegener's Granulomatosis. HSP (IgA vasculitis) occurs in kids, involves IgA deposition, and affects skin (palpable purpura on lower limbs), abdomen (pain, occult bleeding), joints (arthralgia), and kidneys (hematuria - most common site). Platelet count is normal in HSP. Wegener's Granulomatosis (Granulomatosis with Polyangiitis) is a granulomatous vasculitis affecting the lungs, kidneys, and ENT region (otitis media, nasal septal perforation, strawberry gums). It is strongly associated with c-ANCA (PR3-ANCA). Microscopic Polyangiitis and Churg-Strauss Syndrome are associated with p-ANCA (MPO-ANCA).

A helpful inter-system concept presented was the various "strawberry" appearances: Strawberry Tongue (Kawasaki, Scarlet fever), Strawberry Gums (Wegener's), Strawberry Cervix (Trichomonas vaginalis), Strawberry Gallbladder (Cholesterolosis), Strawberry Polyp (Rhinosporidiosis), and Strawberry Skull (Edward syndrome).

Respiratory Pathology: Sputum and Tumors

Sputum examination can reveal important clues in respiratory diseases. Charcot-Leyden crystals are needle-like crystals made of Galectin-10 from eosinophils. They are characteristic of Asthma but can also be seen in parasitic infections and other allergies. Curschmann spirals are mucus casts seen in asthma sputum, and Creola bodies are clumps of epithelial cells also seen in asthma.

Exposure to asbestos (shipyard, cement industries) can lead to lung pathology. In sputum, asbestos exposure is indicated by asbestos bodies (ferruginous bodies), which are dumbbell-shaped asbestos fibers coated with iron. Iron is detected by the Prussian blue stain (Perls stain). Asbestos primarily affects the pleura, causing pleural plaques (first change), then nodules, and eventually cancer. The most specific tumor caused by asbestos is mesothelioma (of the pleura), while the most common lung cancer caused is adenocarcinoma. Mesothelioma is associated with Samoma bodies, chromosome 9 deletion, BAP1 mutation, SV40 virus, and the marker Calretinin.

Lung tumors were discussed, emphasizing types and associations. The most common lung malignancy is metastasis, often appearing as cannonball lesions on radiology. Among primary lung cancers, adenocarcinoma is the most common overall. Smoking is strongly linked to squamous cell carcinoma and small cell carcinoma.

Squamous Cell Carcinoma

Shows keratin pearls microscopically. Markers are P40 (best) and P63.

Adenocarcinoma

Forms glands. Markers include Napsin A, TTF-1, and MUC-1. A variant, adenocarcinoma in situ (lepidic pattern), shows tumor cells lining alveolar walls ("butterfly on fence"). A paraneoplastic syndrome is migratory thrombophlebitis (Trousseau phenomena), linked to mucin production and also seen in pancreatic adenocarcinoma.

Small Cell Carcinoma (Oat Cell Cancer)

Very aggressive (Grade 4). Microscopically shows the Azopardi effect (blue blood vessels due to DNA coating). DNA can be confirmed with Feulgen stain. Markers include Synaptophysin, Chromogranin, and NSE (INH markers: IN, IN, IN). It has the longest list of paraneoplastic syndromes, most commonly SIADH, but also Cushing's and Lambert-Eaton.

Large Cell Carcinoma

Rare. Can cause gynecomastia as a paraneoplastic syndrome. Other lung lesions mentioned include hamartoma, the most common benign primary lung tumor. Pulmonary hamartomas are coin lesions on radiology, may show popcorn calcification, and contain disorganized native tissue, mainly cartilage. Choristoma refers to normal tissue in an ectopic location, like pancreatic or gastric tissue in a Meckel's diverticulum.

Alpha-1 Antitrypsin (A1AT) deficiency, an autosomal recessive condition, is associated with panacinar emphysema in the lungs and cirrhosis in the liver. It's caused by mutations in the SERPINA1 gene on chromosome 14. A1AT globules in the liver stain PAS positive. This led to a review of PAS positive substances: Glycogen (PAS-D sensitive) and others (BM, Whipple's, Kimmelstiel-Wilson, lymphoblasts, fungus - all PAS-D resistant).

GIT and Liver Pathology

Focusing on the liver, the most common malignancy is metastasis, usually from colorectal cancer. Primary liver cancers include Hepatocellular Carcinoma (HCC). Classical HCC is linked to chronic hepatitis B/C and alcohol, is more common in men aged 40-45, and is associated with the tumor marker Alpha-fetoprotein (AFP) (also seen in yolk sac tumor and hepatoblastoma). HCC typically spreads hematogenously. A variant, Fibrolamellar Carcinoma (FLC), occurs in very young patients (e.g., 19), is associated with chromosome 19 deletion, has Neurotensin as a marker, is not linked to hepatitis/alcohol, affects both sexes equally, spreads via lymphatics, and has a good prognosis.

Stomach pathology included Menetrier's disease, characterized by giant, cerebriform gastric rugae. This leads to protein loss and edema, is more common in men, caused by increased TGF alpha, and shows foveolar cell hyperplasia microscopically. Linitis Plastica (Diffuse Gastric Cancer) presents as a rigid, leather-bottle stomach. It is associated with loss of the cell adhesion molecule E-cadherin (CDH1 gene). This same genetic defect is seen in Invasive Lobular Carcinoma of the breast. Diffuse gastric cancer is characterized by the presence of signet ring cells, where the nucleus is pushed to the periphery by cytoplasmic mucin. Signet ring cells are also seen in Krukenberg tumors (metastasis to ovary, often from gastric cancer).

Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal tumor of the GI tract, most often in the stomach. It arises from the interstitial cells of Cajal (GI pacemakers). The most common mutation is CD117 (c-KIT), leading to increased tyrosine kinase activity, making Imatinib the treatment of choice. Other mutations include PDGFR and SDH (associated with pediatric GIST). Markers are CD117/c-KIT (most sensitive) and DOG1 (most specific), along with CD34. CD99 is another marker mentioned, seen in ovarian granulosa cell tumors (old women) and Ewing sarcoma (bone tumor in adolescents, also called MIC2).

Whipple's disease, caused by the bacterium Tropheryma whipplei, presents with chronic diarrhea, weight loss, and joint pain. Intestinal biopsy (duodenum) shows characteristic foamy macrophages packed with PAS-positive granules in the lamina propria.

Celiac disease (Gluten-sensitive enteropathy) is an immune-mediated condition triggered by gluten consumption (barley, rye, oat, wheat) in genetically predisposed individuals (HLA DQ2/DQ8). Serology shows IgA antibodies (anti-tTG, anti-endomysial). Biopsy of the duodenum/jejunum shows villus atrophy/flattening, crypt hyperplasia, and increased intraepithelial lymphocytes (CD8 T cells). It leads to malabsorption (iron deficiency anemia, steatorrhea) and is associated with dermatitis herpetiformis, an IgA-mediated skin condition treated with Dapson. The primary treatment is a gluten-free diet. Patients are at increased risk for Enteropathy-associated T-cell lymphoma (EATL).

Various types of polyps were discussed. Juvenile polyps are common in children (<5 years) and a frequent cause of rectal bleeding. Putz-Jeghers syndrome features mucocutaneous pigmentation and hamartomatous polyps (Christmas tree appearance), often in the jejunum, starting after age 11, due to STK11/LKB1 gene mutations, with a risk of intussusception and various cancers. Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome are linked to P10 gene mutations (on chromosome 10) and associated with polyps and increased cancer risks (breast, thyroid, endometrial for Cowden). Cronkhite-Canada syndrome is the only non-hereditary syndrome discussed, presenting with polyps in older individuals (>50), along with hair loss, skin pigmentation, and nail atrophy.

Lastly, Myotonic Dystrophy, an autosomal dominant disorder with CTG repeats (on chromosome 19), features inability to terminate grip and Christmas tree cataract. Patients may also have a characteristic hatchet face.

Renal Pathology Essentials

Entering renal pathology, Lupus Nephritis, associated with SLE, shows a full house deposition pattern (multiple immunoglobulins and complement) on immunofluorescence. Light microscopy shows wire loop lesions (most prominent in class 4), corresponding to the thumbprint sign on electron microscopy.

Post-Streptococcal Glomerulonephritis (PSGN) occurs after a streptococcal infection, typically in children, with a 10-14 day latency period before presenting with nephritic syndrome (cola-colored urine, edema, hypertension). It involves transient hypocomplementemia. Grossly, the kidney can be flea-bitten. Immunofluorescence shows a granular pattern, described as starry sky appearance. Electron microscopy reveals subepithelial humps. In contrast, IgA Nephropathy (Berger's disease) is seen in adults, presents rapidly (3-4 days) after infection, and involves mesangial deposition of IgA1. Goodpasture syndrome features antibodies to collagen IV and a linear immunofluorescence pattern.

Turning to nephrotic syndromes (characterized by heavy proteinuria, leading to edema and frothy urine):

Minimal Change Disease (MCD)

Most common nephrotic syndrome in children. Characterized by selective albuminuria and excellent response to steroids. Light microscopy is normal ("minimal change" or lipoid nephrosis, with lipid in PCT). Immunofluorescence shows no deposits ("nail deposit disease"). Diagnosis relies on electron microscopy showing effacement/flattening of podocyte foot processes.

Focal Segmental Glomerulosclerosis (FSGS)

Most common nephrotic syndrome in adults. Can also show foot process effacement. Associated with various conditions (HRS pneumonic: HIV, Hypertension, Heroin, Reflux, Renal tissue loss, Sickle cell). The collapsing type, the worst prognosis, is linked to HIV (HIVAN).

Membranous Glomerulonephropathy (MGN)

Often seen in the elderly. Associated with antibodies to PLA2R, drugs (NSAIDs, gold, penicillamine), infections (Hepatitis B/C, syphilis, schistosoma), and cancers. Features subepithelial deposits and a characteristic spike and dome pattern on silver stain.

Membranoproliferative Glomerulonephritis (MPGN)

• Type 1: Can be associated with Hepatitis B/C. Shows subendothelial deposits and a tram track appearance on silver stain (split basement membrane).
• Type 2 (Dense Deposit Disease - DDD): Associated with C3 Nephritic Factor (C3 NeF) and shows dense intramembranous deposits.

Renal casts, formed by Tamm-Horsfall protein (produced in the loop of Henle), are cylindrical structures in urine. Hyaline casts are normal. RBC casts indicate glomerulonephritis. WBC casts suggest pyelonephritis. Muddy brown casts point to acute tubular necrosis (e.g., ethylene glycol poisoning). Broad/waxy casts are seen in chronic renal failure.

Various renal crystals can be found in urine. Key shapes include six-sided cystine crystals (cystinuria), thin needles of tyrosine crystals (tyrosinemia), apple thorn/datura shape of ammonium borate crystals (laxative abuse), dumbbell shape of calcium oxalate monohydrate, envelope shape of calcium oxalate dihydrate, broken chips of cholesterol crystals, pleomorphic uric acid crystals (gout), and coffin lid shape of triple phosphate/struvite crystals. Struvite stones can form staghorn calculi in alkaline urine, often associated with Proteus bacteria.

Brain Tumors and Neurodegeneration

The final section covered brain pathology, starting with neurodegenerative diseases. Huntington's disease is linked to CAG repeats in the exon of the gene on chromosome 4. It involves increased Huntington and ubiquitin proteins, with ubiquitin depositing in the caudate nucleus, causing chorea (jerky movements).

Alzheimer's disease, the most common cause of dementia, is characterized by neurofibrillary tangles (flame cells) composed of hyperphosphorylated Tau protein, amyloid plaques made of A-beta amyloid, and Hirano bodies made of actin. Genetic associations (INI-CET) include APP gene (chromosome 21), PS1/PS2 genes, and ApoE4.

Parkinson's disease involves the loss of dopaminergic neurons in the substantia nigra, which appears pale. Key pathological finding is Lewy bodies, composed of Alpha-synuclein.

Brain tumors discussed included those associated with Neurofibromatosis type 2 (NF2), linked to chromosome 22. NF2 features bilateral acoustic schwannomas (CN VIII tumors, ice cream cone appearance on MRI), as well as meningiomas and ependymomas. Schwannomas show Antoni A (hypercellular with Verocay bodies - palisading nuclei) and Antoni B (hypocellular) areas. Meningiomas are more common in females, hormone-dependent, show a dural tail on radiology, whirling cells and Samoma bodies microscopically.

Astrocytomas vary by grade and age. Pilocytic astrocytoma (Grade 1) is the most common benign primary brain tumor in children, often cystic in the cerebellum (3 C's). Histology shows Rosenthal fibers, and it's associated with BRAF gene mutations/fusions. Glioblastoma (GBM) (Grade 4) is highly aggressive. It may show a butterfly appearance, serpentine necrosis, and Gliod bodies. Most common molecular alteration is IDH wild type. Oligodendroglioma is characterized by a fried egg appearance, IDH mutant type mutation, and 1p/19q co-deletion.

Differentiation between true and pseudo rosettes is important. True rosettes (Flexner-Wintersteiner) have a clear central lumen and are seen most commonly in Retinoblastoma. Pseudo rosettes (Homer Wright) have pink fibrillary material in the center and are seen in Medulloblastoma, Neuroblastoma, and Ewing sarcoma.

Thyroid Pathology Focus

Finally, the session touched upon thyroid tumors. Papillary Carcinoma Thyroid (PTC) is the most common thyroid cancer. Histological features include Orphan Annie eye nuclei (clear/empty nuclei, formalin artifact), intranuclear inclusions, and intranuclear grooves (coffee bean appearance). It also shows Samoma bodies. Genetics: BRAF V600E mutation. Associated with radiation exposure and Hashimoto's thyroiditis. PTC spreads via lymphatics and has an excellent prognosis.

Follicular Carcinoma Thyroid (FTC) cannot be diagnosed on FNAC because diagnosis requires showing capsule and/or vascular invasion. It is associated with RAS gene mutations.

Anaplastic Carcinoma is very aggressive.

Medullary Carcinoma Thyroid (MCT) arises from C cells, produces Calcitonin (tumor marker), which can deposit as amyloid (Congo Red positive, apple green birefringence). It is associated with RET gene mutations (gain-of-function) and the MEN 2A/2B syndromes. This contrasts with Hirschsprung's disease where RET mutation is loss-of-function. A pneumonic for MCT genetics is Red 10 Med Men (RET, chromosome 10, Medullary, MEN).

Also read: Pharmacology Important Topics For NEET PG 2025

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