100+ Free CMSA FC Path(SA) Anatomical Pathology — South Africa Practice Questions

Explanation: Mixed Lineage Kinase Domain-Like Protein (MLKL) is phosphorylated by RIPK3 within the necrosome complex during necroptosis. Phosphorylated MLKL oligomerizes and translocates to the plasma membrane, directly forming pore complexes that disrupt membrane integrity and lead to cell lysis. RIPK1 and RIPK3 are upstream kinases in the signaling pathway, while Caspase-8 inhibits necroptosis by cleaving RIPK1 and RIPK3.

Explanation: Xanthine oxidase is generated during ischemia when xanthine dehydrogenase is proteolytically converted. Upon reperfusion and reoxygenation, xanthine oxidase uses molecular oxygen to convert hypoxanthine into xanthine and uric acid, generating massive amounts of superoxide anions and hydrogen peroxide. Superoxide dismutase, catalase, and glutathione peroxidase are antioxidant enzymes that clear ROS rather than generating them.

Explanation: Interferon-gamma (IFN-gamma) is secreted by activated CD4+ Th1 T-cells and natural killer cells. It activates tissue macrophages, causing them to enlarge, increase cytoplasmic volume, and transform into epithelioid histiocytes and multinucleated Langhans giant cells characteristic of granulomas. IL-4 drives Th2 activation and M2 macrophage polarization, while IL-10 and TGF-beta are anti-inflammatory cytokines.

Explanation: Calcineurin is a calcium-dependent phosphatase activated by sustained intracellular calcium elevation during cardiac pressure overload. Active calcineurin dephosphorylates Nuclear Factor of Activated T-cells (NFAT), enabling its translocation into the nucleus to drive the embryonic cardiac gene program (such as ANP and beta-MHC) characteristic of pathologic hypertrophy. JAK/STAT, Wnt/beta-catenin, and Notch pathways play roles in immunity, renewal, and development rather than pressure-overload cardiac hypertrophy.

Explanation: Amyloid fibrils, regardless of precursor protein origin (e.g., AL, AA, ATTR), share a pathognomonic anti-parallel cross-beta-pleated sheet tertiary structure. When stained with Congo red dye, the linear alignment of dye molecules along the beta-sheet groves produces pathognomonic apple-green birefringence under cross-polarized light microscopy. Alpha-helices and collagenous triple-helices do not exhibit this specific dye-binding property.

Explanation: Burkitt lymphoma is defined cytogenetically by reciprocal translocations involving the MYC gene on chromosome 8q24. The most common is t(8;14)(q24;q32), which translocates MYC to the immunoglobulin heavy chain (IGH) locus on 14q32, resulting in constitutive overexpression of the MYC transcription factor. t(11;14) defines mantle cell lymphoma (CCND1), t(14;18) defines follicular lymphoma (BCL2), and t(9;22) forms the BCR-ABL1 fusion in CML.

Explanation: TP53 functions as 'guardian of the genome'. Following DNA damage, ATM/ATR kinases phosphorylate p53, preventing MDM2-mediated ubiquitination. Stabilized p53 acts as a transcription factor to upregulate p21 (CIP1/WAF1), a potent pan-cyclin-dependent kinase inhibitor that inhibits CDK2/cyclin E and CDK4/cyclin D complexes, freezing the cell cycle at the G1/S checkpoint for DNA repair. p16 is encoded by CDKN2A, whereas p27 and p57 are distinct CIP/KIP family members.

Explanation: Cancer cells preferentially express the PKM2 isoform of pyruvate kinase (produced by alternative splicing of the PKM gene). PKM2 exists in a low-activity dimeric state that slows the conversion of phosphoenolpyruvate to pyruvate, accumulating upstream glycolytic intermediates that are shunted into biosynthetic pathways (nucleic acid, lipid, and amino acid synthesis) necessary for rapid cell proliferation. PKM1 is expressed in differentiated tissues, PKL in liver, and PKR in erythrocytes.

Explanation: Loss of E-cadherin expression (often mediated by transcriptional repressors Snail, Slug, Twist, or ZEB1) is the functional hallmark of Epithelial-to-Mesenchymal Transition (EMT). This loss dissolves adherens junctions between epithelial cells, enabling detachment, acquisition of a mesenchymal phenotype (gaining N-cadherin and vimentin), and local tissue invasion. Gain of N-cadherin ('cadherin switching') and vimentin occur secondary to E-cadherin loss.

Explanation: Alternative Lengthening of Telomeres (ALT) is a homologous recombination-based telomere maintenance mechanism observed in neuroblastomas, pancreatic neuroendocrine tumors, and astrocytomas. Inactivating mutations in ATRX (Alpha-Thalassemia/Mental Retardation Syndrome X-Linked) or DAXX (Death Domain-Associated Protein), which encode chromatin remodeling complexes at telomeric repeats, lead to telomeric chromatin destabilization and ALT activation. BRCA1/2 are homologous recombination repair genes, MLH1/MSH2 MMR genes, and STK11/KEAP1 tumor suppressor pathways.