LRR Pathology Analysis

GIST (Gastrointestinal Stromal Tumor)

• Origin: Cells of Cajal (Pacemaker cells).
• Best Marker: DOG-1 (Discovered on GIST-1) - Most Specific.
• Mutations: c-KIT (CD117), PDGFRA, Succinate Dehydrogenase.

CDH1 Mutation (E-Cadherin Loss)

Associated with two specific cancers:

1. Diffuse Gastric Cancer: Linitis Plastica (Leather Bottle Stomach). Shows Signet Ring Cells.
2. Invasive Lobular Carcinoma (Breast): Shows Indian File Pattern (Single file cells).

Liver Pathology Highlights

Mallory Hyaline Bodies (CK 8/18)

Mnemonic: "New Indian Watch"

• Non-Alcoholic Fatty Liver Disease (NAFLD)
• Indian Childhood Cirrhosis
• Wilson's Disease (Copper) - NOT Hemochromatosis
• Alpha-1 Antitrypsin Deficiency
• Tumors (HCC)
• Cholestasis
• Alcoholic Liver Disease

Angiosarcoma of Liver

Caused by 3 chemicals ("Liver ki WAT lagayi"):

• Vinyl Chloride (Plastics)
• Arsenic (Pesticides)
• Thorotrast (Contrast dye)

Biliary Tract Diseases

Asthma Triad (Sputum)

• Charcot-Leyden Crystals: Made of Galectin-10 (from Eosinophils). Needle-like.
• Curschmann Spirals: Mucus plugs.
• Creola Bodies: Clumps of sloughed epithelial cells.

Lung Tumors

Brain Tumors (Adults)

• Glioblastoma Multiforme (GBM): "Butterfly Glioma". Serpentine Necrosis (Snake-like). Grade 4.
• Meningioma: Females (Progesterone receptors). Psammoma Bodies. Dural Tail sign.
• Oligodendroglioma: Fried Egg Appearance (Perinuclear halo). Chicken wire capillaries. 1p19q co-deletion (Most specific), IDH mutation (Most common).
• Schwannoma (NF2): Antoni A (Cellular, Verocay bodies - Palisading nuclei) & Antoni B (Hypocellular). CP Angle.

Rosettes

• Homer-Wright (Pseudo-rosette): Central pink fibrils. Seen in Medulloblastoma, Neuroblastoma, Ewing's. ("Men are Right/Fake").
• Flexner-Wintersteiner (True rosette): Central clear lumen. Seen in Retinoblastoma.

Thyroid Carcinoma

• Papillary (Best Prognosis): Lymphatic spread. Orphan Annie Eye Nuclei (Empty), Coffee bean nuclei, Psammoma bodies. Mutation: BRAF V600E.
• Follicular: Hematogenous spread (Bone/Scalp). Diagnosis requires Capsular/Vascular Invasion (Cannot diagnose on FNAC). Mutation: RAS.
• Medullary: Neuroendocrine (C-Cells). Amyloid (A-Cal). Marker: Calcitonin. Mutation: RET (MEN 2A/2B).

Glomerulonephritis (Immunofluorescence Patterns)

• Linear Pattern: Goodpasture Syndrome (Anti-GBM, Collagen Type IV Alpha-3 chain). RPGN Type 1.
• Starry Sky / Granular Pattern: PSGN (Lumpy Bumpy), RPGN Type 2.
• Full House Effect: SLE (Lupus Nephritis). All antibodies/complements positive.
• Pauci-Immune: Wegener's (c-ANCA), Microscopic Polyangiitis (p-ANCA). RPGN Type 3.

Kidney Appearances

• Flea-Bitten Kidney: PSGN, Malignant Hypertension.
• Putty Kidney: Renal Tuberculosis (Sterile Pyuria).
• Large White Kidney (Waxy): Amyloidosis.
• Leather Grain Kidney: Benign Hypertension.

Iron Profile Interpretation

ACD Mechanism: IL-6 increases Hepcidin (Liver) → Blocks Iron absorption & release.

Hemolytic Anemias

• Hereditary Spherocytosis: AD. Ankyrin mutation (MC). Osmotic Fragility Test (Screening), EMA Binding (Confirmatory).
• G6PD Deficiency: X-linked. Bite Cells (Degmacytes), Heinz Bodies (Denatured Hb, Crystal Violet stain). Triggers: Fava beans, Antimalarials, Infection.
• Sickle Cell: Glutamate → Valine at Beta-6 (or 7). Crew Cut Skull on X-ray. Osteomyelitis by Salmonella.
• PNH (Paroxysmal Nocturnal Hemoglobinuria): Acquired defect (PIG-A gene). CD55/59 deficiency. Ham's test (+). Screening: Flow Cytometry. Rx: Eculizumab.

Leukemias

• AML M3 (APML): Medical Emergency (DIC). Auer Rods (Faggot Cells). t(15;17) PML-RARA. Rx: ATRA + Arsenic.
• CML: Massive Splenomegaly. t(9;22) BCR-ABL (Philadelphia). Low LAP score. Basophilia. Ix of Choice: FISH (for translocation), Flow Cytometry otherwise.
• Hairy Cell Leukemia: Massive Splenomegaly (Red pulp). Dry Tap. TRAP Positive. Annexin A1. BRAF mutation. Fried Egg on Biopsy.

Hodgkin Lymphoma

• Reed-Sternberg Cells: Owl Eye (CD15+, CD30+, Pax-5+).
• Subtypes:
  • Nodular Sclerosis: Lacunar cells. MC in females/world. Least EBV association.
  • Mixed Cellularity: MC in India. Associated with EBV.
  • Lymphocyte Depleted: Worst prognosis. Mummified cells.
• Non-Classical: Popcorn Cells (NLPHL). CD20+, CD45+. Best Prognosis.

Vacutainer Order of Draw (Stop Light Red Green)

1. Culture Bottles (Sterile)
2. Light Blue (Citrate): Coagulation (PT/APTT).
3. Red/Gold (No additive/Clot activator): Serum (LFT, KFT, Hormones).
4. Green (Heparin): ABG, Electrolytes.
5. Lavender/Purple (EDTA): CBC, ESR, HbA1c, Peripheral Smear.
6. Grey (Na Fluoride + K Oxalate): Glucose.
7. Black: ESR (Westergren automated).

Storage

• Platelets: 20-24°C (Room Temp) with agitation. 5 days.
• FFP: -18°C or lower. 1 year.
• RBCs: 2-6°C. Life depends on preservative (CPDA-1 = 35 days, SAGM = 42 days).

Immunodeficiency Disorders

• Chediak-Higashi: Giant granules in neutrophils. Albinism. LYST gene.
• CGD: NADPH Oxidase defect. Nitroblue Tetrazolium (NBT) test negative (No blue color). Susceptible to Catalase+ organisms (Staph, Aspergillus).
• LAD-1: CD18/Integrin defect. Delayed umbilical cord separation.

Genetics

• Prader-Willi: Paternal deletion 15q. Obesity, Ghrelin increased.
• Angelman: Maternal deletion 15q. Happy Puppet.
• Fragile X: CGG repeats (>200). FMR1 gene. Macro-orchidism, Long face.
• Barr Body: n-1 (Number of X chromosomes minus 1).