Iran Specialty Board Pathology cheat sheet

Cell injury: ATP depletion inhibits Na+/K+ ATPase → cell swelling; irreversible injury is marked by mitochondrial membrane rupture and membrane integrity loss.

Apoptosis is caspase-dependent, energy-requiring, and inflammation-poor; necrosis is oncotic, membrane-disrupting, and inflammation-rich.

Liquefactive necrosis: brain infarct and abscess; caseous: tuberculosis; coagulative: ischemic infarct of solid organs except brain; fibrinoid: vasculitis and malignant hypertension.

Metaplasia is a reversible change of one mature epithelial type to another (Barrett esophagus: squamous to columnar); dysplasia is disordered growth with atypia but intact basement membrane.

Acute inflammation: vasodilation, increased permeability (histamine, bradykinin, leukotrienes), neutrophil emigration via selectins (rolling), integrins (adhesion), PECAM-1 (transmigration).

Granuloma: epithelioid macrophages + Langhans giant cells; caseating in TB, non-caseating in sarcoidosis and Crohn disease.

Wound healing: primary intention has minimal granulation; healing by secondary intention shows prominent granulation tissue and wound contraction.

Amyloid is Congo red positive with apple-green birefringence under polarized light; AA type in chronic inflammation, AL type in plasma cell dyscrasias.

Edema mechanisms: increased hydrostatic pressure, reduced oncotic pressure, lymphatic obstruction, sodium retention, inflammation.

Breast: invasive ductal carcinoma graded by tubule formation, nuclear pleomorphism, and mitotic count (Nottingham/Elston-Ellis); ER/PR and HER2 status are mandatory.

Lung adenocarcinoma classification: lepidic, acinar, papillary, micropapillary, solid; lepidic-predominant pattern has better prognosis.

Colorectal carcinoma: TNM staging requires depth of invasion, number of positive nodes, and distant metastasis; MSI/MMR testing guides Lynch syndrome screening.

Gastric cancer: Lauren classification (intestinal vs diffuse); diffuse type shows signet-ring cells and loss of E-cadherin (CDH1).

Prostate: Gleason/Grade Group system; Gleason 3+4 = Grade Group 2, 4+3 = Grade Group 3, 8 = Grade Group 4, 9-10 = Grade Group 5.

Thyroid: papillary carcinoma shows optically clear nuclei (Orphan Annie), nuclear grooves, and psammoma bodies; BRAF V600E is common.

Liver: hepatocellular carcinoma shows trabecular pattern, pseudoglandular formation, and vascular invasion; cirrhosis is a major risk factor.

Kidney: clear cell RCC shows nests of cells with clear cytoplasm and delicate vasculature; papillary RCC shows papillae with fibrovascular cores.

Skin: melanoma Breslow thickness and ulceration are the strongest prognostic factors; Clark level is secondary.

Bethesda system: NILM, ASC-US, LSIL, ASC-H, HSIL, SCC, AGC, and adequacy criteria (minimum 5,000 squamous cells for conventional smear).

LSIL reflects HPV cytopathic effect (koilocytes); HSIL reflects high-grade squamous intraepithelial lesion with reduced maturation.

ASC-US management: HPV triage; if HPV positive, colposcopy; if negative, repeat screening per age guidelines.

HSIL cytology warrants colposcopy with biopsy and excision; do not rely on cytology alone for diagnosis.

Non-gynecologic: FNA of thyroid uses Bethesda categories I-VI; category VI is malignant (papillary, medullary, anaplastic).

Salivary gland FNA: pleomorphic adenoma shows fibrillary chondromyxoid stroma; adenoid cystic carcinoma shows cribriform cylinders.

Serous effusions: malignant mesothelioma vs adenocarcinoma requires immunostains (calretinin, WT1, CK5/6 vs MOC-31, Ber-EP4, CEA).

Cerebrospinal fluid cytology: malignant cells in CSF indicate leptomeningeal spread; must distinguish from reactive lymphocytes.

Fine needle aspiration of lymph nodes: granulomatous inflammation, metastatic carcinoma, lymphoma, and reactive hyperplasia are key differentials.

Anemia classification by MCV: microcytic (<80 fL), normocytic (80-100 fL), macrocytic (>100 fL).

Iron deficiency: low ferritin, low serum iron, high TIBC, low transferrin saturation; anemia of chronic disease: low iron, low TIBC, normal/high ferritin.

Acute myeloid leukemia: ≥20% blasts in marrow or blood; Auer rods indicate myeloid lineage; APL (t(15;17)) is a medical emergency treated with ATRA.

Chronic myeloid leukemia: t(9;22) BCR-ABL1; detected by FISH or RT-PCR; treated with tyrosine kinase inhibitors.

Lymphoma: Hodgkin shows Reed-Sternberg cells (CD15+, CD30+); non-Hodgkin classification uses immunophenotype and cytogenetics.

Multiple myeloma: ≥10% clonal plasma cells, M protein, CRAB features (hypercalcemia, renal failure, anemia, bone lesions).

Bone marrow transplant engraftment monitoring uses STR chimerism analysis.

Myelodysplastic syndrome: cytopenias with dysplastic morphology and <20% blasts; ring sideroblasts in MDS with SF3B1 mutation.

Reference intervals: central 95% of a healthy population; results outside are flagged but not automatically pathologic.

Analytical imprecision: CV = (SD/mean) × 100%; total allowable error combines bias and imprecision.

Sodium correction for hyperglycemia: add 1.6 mEq/L to measured Na+ for every 100 mg/dL glucose above 100 mg/dL.

Anion gap = Na+ − (Cl− + HCO3−); normal 8-12 mEq/L; elevated in ketoacidosis, lactic acidosis, renal failure, toxins.

Cardiac troponin is the preferred biomarker for myocardial injury; serial measurement shows rise/fall pattern.

HbA1c reflects average glucose over ~3 months; affected by hemoglobin variants and red cell lifespan.

Creatinine-based eGFR (CKD-EPI) estimates renal function; cystatin C is an alternative less affected by muscle mass.

Liver enzymes: ALT more liver-specific than AST; AST/ALT ratio >2 suggests alcoholic liver disease.

Quality control: Westgard rules (1-3s, 2-2s, R-4s, 4-1s, 10x) detect random and systematic error.

Gram stain: gram-positive retain crystal violet (thick peptidoglycan); gram-negative decolorize and take safranin.

Acid-fast stain (Ziehl-Neelsen) detects mycobacteria; auramine-rhodamine fluorescence is a sensitive alternative.

Culture media: blood agar for fastidious organisms, MacConkey for gram-negative enterics, chocolate agar for Haemophilus and Neisseria.

Antimicrobial susceptibility: disk diffusion (Kirby-Bauer), broth microdilution (MIC), and E-test; interpret using CLSI/EUCAST breakpoints.

Viral diagnosis: PCR is the method of choice for most acute viral infections; serology for immunity and chronic infections.

Sepsis blood cultures: obtain before antibiotics, two sets from different sites; incubation typically 5 days.

Tuberculosis: sputum AFB smear and culture on Lowenstein-Jensen or liquid media; NAAT for rapid detection and resistance.

Fungal stains: PAS and silver stain for fungi; calcofluor white fluorescence; germ tube test for Candida albicans.

Hypersensitivity types: I (IgE, mast cells), II (antibody-mediated), III (immune complex), IV (T-cell mediated, delayed).

Primary immunodeficiency: SCID (T-cell defect), X-linked agammaglobulinemia (BTK, no B cells), chronic granulomatous disease (NADPH oxidase).

Autoimmune disease: ANA, anti-dsDNA (SLE), anti-Smith (SLE), anti-centromere (limited scleroderma), anti-Scl-70 (diffuse scleroderma).

Complement: C3 low in active SLE and post-streptococcal glomerulonephritis; C4 low in hereditary angioedema.

Flow cytometry immunophenotyping: CD4/CD8 ratio, CD markers for leukemia/lymphoma, and HLA-B27 testing.

Transplant rejection: hyperacute (preformed antibodies), acute cellular (T cells), acute humoral (donor-specific antibodies), chronic (fibrosis).

ELISA and Western blot are used for HIV screening and confirmation; NAT detects early infection.

PCR: exponential amplification of target DNA; real-time PCR quantifies with fluorescent probes (TaqMan, SYBR).

Sanger sequencing remains the gold standard for single-gene confirmation; NGS enables panel and exome sequencing.

FISH detects chromosomal translocations and gene amplifications (e.g., HER2, ALK, BCR-ABL1).

Germline vs somatic variants: germline variants are present in all cells and heritable; somatic variants are tumor-restricted.

Variant classification uses ACMG/AMP criteria: pathogenic, likely pathogenic, VUS, likely benign, benign.

Mismatch repair (MMR) proteins: MLH1, MSH2, MSH6, PMS2; loss by immunohistochemistry suggests MSI-high tumor.

Liquid biopsy detects circulating tumor DNA (ctDNA) for monitoring and resistance mutations.

Pharmacogenomics: TPMT/NUDT15 for thiopurines, CYP2C19 for clopidogrel, HLA-B*57:01 for abacavir.

Cause of death is the disease or injury producing the fatal termination; manner of death is natural, accident, suicide, homicide, or undetermined.

Postmortem changes: livor mortis (dependent lividity), rigor mortis (begins 1-2 h, peaks 12 h, resolves 24-36 h), algor mortis, decomposition.

Autopsy types: complete (all cavities), limited/partial, and medicolegal (coroner/medical examiner).

Gunshot wounds: entrance wound shows abrasion collar and soot/tattooing at close range; exit wound is typically larger and everted.

Asphyxia: petechiae, cyanosis, and congestion; ligature marks help distinguish hanging from strangulation.

Toxicology samples: blood (cardiac and femoral), vitreous humor, urine, liver, and gastric contents.

Sudden cardiac death: coronary atherosclerosis is the most common cause; requires histologic examination of the conduction system when indicated.

Chain of custody ensures admissibility of forensic specimens; document every transfer.

ISO 15189 specifies quality and competence requirements for medical laboratories; CAP accreditation uses checklists and inspections.

Quality indicators: turnaround time (TAT), specimen rejection rate, corrected reports, and proficiency testing performance.

Proficiency testing (PT) is required for accredited tests; unacceptable PT results trigger root cause analysis.

Document control: policies, procedures, and records must be version-controlled and reviewed periodically.

Internal quality control (IQC) monitors daily performance; external quality assessment (EQA) compares against peer laboratories.

Risk management: failure mode and effects analysis (FMEA) identifies and prioritizes potential failures.

Competency assessment of staff includes direct observation, review of results, and continuing education.

Biosafety: standard precautions, PPE, and waste segregation per institutional and national regulations.

Whole-slide imaging (WSI) digitizes glass slides; scanner resolution is expressed in microns per pixel (0.25 µm/px at 40x).

Digital pathology validation must demonstrate concordance with glass slides before clinical use.

LIS interfaces use HL7 standards for order entry and result reporting; DICOM is used for images.

Image file formats: SVS, NDPI, and TIFF; lossless compression preserves diagnostic quality.

Telepathology modes: static (store-and-forward), dynamic (real-time), and hybrid.

Data security: HIPAA compliance, access controls, audit trails, and encrypted transmission.

AI-assisted diagnosis requires regulatory clearance and ongoing performance monitoring.

Bar coding and specimen tracking reduce identification errors in the preanalytical phase.

Study designs: randomized controlled trial (strongest for causality), cohort, case-control, cross-sectional, and ecological.

Sensitivity = TP/(TP+FN); specificity = TN/(TN+FP); PPV and NPV depend on prevalence.

Randomization reduces selection bias; blinding reduces measurement and observer bias.

p-value is the probability of observing results as extreme under the null hypothesis; it is not the probability the null is true.

Confidence interval expresses precision; a 95% CI excluding the null value corresponds to p<0.05.

Intention-to-treat analysis preserves randomization; per-protocol analysis may introduce bias.

Levels of evidence: systematic reviews and RCTs rank above observational studies and expert opinion.

Number needed to treat (NNT) = 1/absolute risk reduction; smaller NNT indicates greater clinical benefit.