(a) Define 'metastasis'. Enumerate the steps involved in metastasis. Write briefly about the role of stromal elements in…

(a) Metastasis

Metastasis is the spread of malignant cells from the primary tumour to a distant site, where they form a secondary tumour not in continuity with the primary. Spread is lymphatic (typical of carcinomas), haematogenous (typical of sarcomas) or by seeding of body cavities.

Steps (invasion–metastasis cascade): (1) loss of cell–cell adhesion (E-cadherin) and epithelial–mesenchymal transition; (2) degradation of basement membrane and matrix by metalloproteinases (MMP-2, MMP-9) and cathepsins; (3) attachment to matrix and migration; (4) intravasation; (5) survival in circulation as tumour emboli with platelets, resisting shear stress and immune attack; (6) arrest and extravasation at a distant site; (7) colonisation and growth, with angiogenesis.

Stroma: cancer-associated fibroblasts remodel matrix, make a stiffer collagen track and secrete growth factors. Tumour-associated macrophages and other immune cells supply proteases and cytokines. Endothelium supports angiogenesis (VEGF) and entry or exit of cells. Primary tumour factors condition a pre-metastatic niche in distant organs ("seed and soil").

(b)(i) Immunoglobulin classes and T-cell subsets

• IgG: main serum antibody; opsonisation, neutralisation, complement activation, crosses placenta (FcRn).
• IgM: pentamer; first antibody in primary response, strongest complement activator, isohaemagglutinins.
• IgA: secretory dimer in mucosal secretions, milk and tears; blocks microbial attachment.
• IgE: binds mast cells and basophils; type I hypersensitivity and anti-helminth defence.
• IgD: B-cell surface receptor with IgM; role in B-cell activation.

T-cell subsets: CD4+ helper cells (Th1: IFN-γ, activates macrophages; Th2: IL-4, IL-5, IL-13, helps IgE and eosinophils; Th17: IL-17, recruits neutrophils; Tfh: IL-21, helps B cells in germinal centres), regulatory T cells (FOXP3, IL-10, TGF-β) and CD8+ cytotoxic cells (perforin–granzyme and Fas–FasL killing).

(b)(ii) Manifestations of amoebiasis

Intestinal (Entamoeba histolytica): asymptomatic cyst passage; amoebic dysentery or colitis with blood and mucus; flask-shaped ulcers of caecum and colon; fulminant colitis and toxic megacolon; amoeboma; perforation and peritonitis; stricture.

Extraintestinal: amoebic liver abscess is the commonest (usually a solitary right-lobe abscess with fever and tender hepatomegaly); pleuropulmonary disease (rupture through the diaphragm, empyema, hepatobronchial fistula); pericardial extension from a left-lobe abscess; brain abscess (rare); cutaneous amoebiasis (perianal, genital); genitourinary involvement.

(c) Long-acting insulin analogues and insulin therapy

Long-acting analogues give a peakless basal supply. Insulin glargine (glycine at A21, two arginines added at B31–B32) is soluble at acidic pH and precipitates in subcutaneous tissue at neutral pH, acting for about 24 hours (U300 for longer). Insulin detemir (myristic acid at B29) binds albumin, acting for 12–24 hours. Insulin degludec (B30 deleted, fatty diacid at B29) forms multihexamers, lasting beyond 40 hours with flexible dosing.

Difference from NPH or regular insulin: NPH has a peak at 4–8 hours and variable absorption; analogues give a flatter, more reproducible profile with less nocturnal hypoglycaemia. Glargine should not be mixed with other insulins.

Uses of insulin: type 1 diabetes, type 2 diabetes with failed oral drugs or severe hyperglycaemia, diabetic ketoacidosis and hyperosmolar state, gestational diabetes, perioperative and critical-illness control, and hyperkalaemia (with glucose).

Adverse effects: hypoglycaemia, weight gain, lipodystrophy at injection sites, local allergy, insulin oedema, hypokalaemia and antibody formation.

(d) Chronic inflammation

Chronic inflammation is a prolonged inflammatory response, lasting weeks to years, in which inflammation, tissue injury and repair (fibrosis, angiogenesis) go on together, with infiltration by mononuclear cells (macrophages, lymphocytes, plasma cells).

Causes: persistent infections (tuberculosis, leprosy, syphilis, some fungal and parasitic infections); prolonged exposure to toxic agents (silica, asbestos, lipids in atherosclerosis); autoimmune diseases (rheumatoid arthritis, SLE, inflammatory bowel disease); foreign bodies; and unresolved acute inflammation.

Role of macrophages: they arise from circulating monocytes and are the dominant cells. They phagocytose microbes and debris, present antigen to T cells and secrete IL-1, TNF, IL-6 and chemokines. M1 macrophages (induced by IFN-γ) are microbicidal; M2 macrophages (induced by IL-4 and IL-13) promote repair through TGF-β, PDGF and FGF, driving fibrosis and angiogenesis. In granulomatous inflammation they become epithelioid cells and multinucleate giant cells.

(e) Data of identification and fingerprinting

Data of identification are the features used to establish a person's identity: age, sex, stature, built, complexion, hair, eyes, teeth, deformities, scars, tattoos, occupational marks, handwriting, anthropometry, fingerprints (dactylography), footprints and DNA profile.

Fingerprinting: friction ridges form by the fourth month of fetal life and are permanent and unique even in identical twins. Main patterns are loops (about 60–65%, ulnar or radial), whorls (about 30–35%) and arches (about 5%). Individuality rests on minutiae (ridge endings, bifurcations, dots, islands, lakes). The Henry system classifies prints, and AFIS compares digital records. Fingerprints are collected under the Criminal Procedure (Identification) Act, 2022 (which replaced the Identification of Prisoners Act, 1920) and are expert evidence under Section 39 of the Bharatiya Sakshya Adhiniyam, 2023 (old Section 45, Indian Evidence Act). No fixed number of matching points is prescribed in India; courts weigh the clarity and number of points and the expert's opinion.