(a) (i) Enumerate any five risk factors for oral cancer. Describe its morphology. 5+5=10 (ii) Enumerate five causes of membranous…

Pathology of Oral Cancer and Membranous Glomerulonephritis

Oral Cancer: Major risk factors include tobacco use (smoking and smokeless forms like gutkha), heavy alcohol consumption, betel nut (areca nut) chewing, infection with high-risk Human Papillomavirus (predominantly HPV-16), and chronic mucosal irritation from poor dentition or poor oral hygiene. Grossly, oral cancer manifests as an exophytic/fungating mass, an endophytic ulcerative lesion with indurated, raised margins, or a verrucous leukoplakic plaque. Microscopically, over 90% are squamous cell carcinomas characterized by invasive nests of atypical squamous cells, variable keratinization (keratin pearls), intercellular bridges, nuclear pleomorphism, mitotic figures, and subepithelial stromal invasion, often against a background of field cancerization.

Membranous Glomerulonephritis (MGN): Primary MGN is idiopathic (autoantibodies against phospholipase A2 receptor, PLA2R). Secondary causes include chronic infections (Hepatitis B, Hepatitis C, malaria), autoimmune diseases (Systemic Lupus Erythematosus—Class V), malignancies (carcinomas of lung, colon, stomach), and drugs (NSAIDs, penicillamine, gold). Light microscopy reveals diffuse, uniform thickening of the glomerular basement membrane (GBM) without notable hypercellularity. Silver methenamine stain demonstrates a pathognomonic "spike and dome" appearance. Immunofluorescence shows diffuse, granular deposition of IgG and C3 along the GBM. Electron microscopy confirms electron-dense subepithelial deposits separated by GBM spikes, accompanied by diffuse effacement of podocyte foot processes.

Applied Pharmacology of Aspirin and Cyclosporine

Aspirin: Indications include secondary prevention of myocardial infarction and ischemic stroke (antiplatelet, 75–150 mg/day), mild-to-moderate pain and fever (analgesic/antipyretic), and acute rheumatic fever or Kawasaki disease (anti-inflammatory). Drug interactions involve displacement of and synergism with warfarin (severe hemorrhage risk), decreased renal clearance of methotrexate leading to toxicity, and attenuation of the antihypertensive actions of ACE inhibitors. Adverse effects include gastric mucosal ulceration with upper gastrointestinal bleeding, Reye syndrome in febrile children, aspirin-exacerbated respiratory disease (bronchospasm), and tinnitus in salicylism.

Cyclosporine: Indications include prophylaxis of organ transplant rejection (kidney, liver, heart) and severe autoimmune disorders such as refractory psoriasis, rheumatoid arthritis, and steroid-resistant nephrotic syndrome. Interactions occur with CYP3A4 inhibitors (ketoconazole, erythromycin) which elevate blood levels, CYP3A4 inducers (rifampicin, phenytoin) which precipitate graft rejection, and nephrotoxic agents (aminoglycosides, amphotericin B) which potentiate renal damage. Major side effects are dose-dependent nephrotoxicity, secondary systemic hypertension, gingival hyperplasia, hirsutism, and hepatotoxicity.

**Microbiology of Plasmodium falciparum and Human Herpes Viruses**

***Plasmodium falciparum* Asexual Life Cycle & RDT:** The cycle begins when an infective female Anopheles mosquito injects sporozoites into the bloodstream. Sporozoites invade hepatocytes, initiating exo-erythrocytic schizogony to form tissue schizonts containing thousands of merozoites, without a hypnozoite phase. Ruptured liver cells release merozoites into the circulation to invade erythrocytes (erythrocytic schizogony). Intracellular parasites mature through ring forms (early trophozoites), mature trophozoites, and erythrocytic schizonts. Schizont rupture releases new merozoites and pyrogens, producing tertian fever paroxysms.

Rapid Diagnostic Tests (RDTs) operate on lateral flow immunochromatography, using labeled monoclonal antibodies to capture parasite-specific antigens: Histidine-Rich Protein-2 (HRP-2) or parasite Lactate Dehydrogenase (pLDH). Advantages: Rapid results (15 minutes), requires no electricity or skilled microscopy, and enables point-of-care diagnosis under national health programs. Disadvantages: Inability to quantify parasitemia, false positives due to persistent HRP-2 circulation post-cure, and false negatives arising from pfhrp2/3 gene deletions.

Human Herpes Viruses (HHV) & HSV Diagnosis: The eight HHVs and primary target cells are: HHV-1 (HSV-1): Mucoepithelial cells and sensory ganglia; HHV-2 (HSV-2): Mucoepithelial cells and sacral ganglia; HHV-3 (VZV): T cells, epithelial cells, and sensory ganglia; HHV-4 (EBV): B lymphocytes and epithelial cells; HHV-5 (CMV): Monocytes, granulocytes, and endothelial cells; HHV-6 & HHV-7: CD4+ T lymphocytes; HHV-8 (KSHV): Endothelial cells and B lymphocytes.

Laboratory diagnosis of HSV utilizes: Cytology: Tzanck smear of vesicle scrapings stained with Giemsa reveals multinucleated giant cells and Cowdry A inclusion bodies. Direct Antigen Detection: Direct immunofluorescence assay (DFA) on lesion smears. Polymerase Chain Reaction: Real-time PCR detecting HSV DNA (gold standard for HSV encephalitis and neonatal infections). Viral Culture: Inoculation into human diploid fibroblast cell lines showing characteristic cytopathic effect. Serology: Type-specific ELISA detecting IgG and IgM against glycoprotein G1 (HSV-1) and G2 (HSV-2) for sero-epidemiology and primary infection confirmation.