INICET Pathology Previous Year Questions (2018–2026)

The correct answer is AA (amyloid associated) protein.

Secondary (reactive) amyloidosis is driven by chronic inflammation. Sustained inflammatory activity makes the liver overproduce Serum Amyloid A (SAA), an acute-phase reactant. Persistently elevated SAA is cleaved and deposited extracellularly as insoluble AA fibrils, most prominently in the kidney, where proteinuria and nephrotic syndrome are the leading cause of morbidity. Classic triggers include rheumatoid arthritis, inflammatory bowel disease, chronic infections such as tuberculosis, osteomyelitis and bronchiectasis, and Familial Mediterranean Fever.

The closest distractor is AL. Both are systemic amyloidoses, but AL arises from monoclonal immunoglobulin light chains in a plasma-cell dyscrasia, a clonal rather than inflammatory process. The discriminator is the source protein: chronic inflammation points to SAA and AA, whereas a plasma-cell clone points to light chains and AL.

Incorrect Options:

• AL (immunoglobulin light chain): Derived from monoclonal light chains in plasma-cell dyscrasia or multiple myeloma (primary amyloidosis), not from inflammation.
• Transthyretin (ATTR): Causes senile cardiac amyloidosis (wild-type) and hereditary familial amyloid polyneuropathy or cardiomyopathy (mutant), unrelated to chronic inflammation.
• Beta-2 microglobulin: Causes dialysis-related amyloidosis in long-standing renal failure, depositing in the carpal tunnel and joints.

High-Yield Facts:

• AA amyloid is derived from SAA, a liver-made acute-phase reactant.
• All amyloid stains Congo red and shows apple-green birefringence under polarized light.
• AA amyloidosis most commonly presents with renal involvement and proteinuria.
• Familial Mediterranean Fever is the classic genetic cause of AA amyloidosis.

Figure 1: Congo red stain - amyloid in vessel walls appears salmon to brick-red on standard light microscopy.

Figure 2: Same field under crossed polarizers - amyloid shows pathognomonic apple-green birefringence.

The correct answer is A generation is skipped.

Penetrance is the proportion of individuals carrying a disease genotype who actually express the phenotype. With incomplete (reduced) penetrance, some genotype-positive individuals remain phenotypically normal. Such an unaffected obligate carrier can still transmit the mutant allele to offspring, who then express the disease. On a pedigree this gives an affected grandparent and an affected grandchild with a phenotypically normal parent in between, so the trait appears to skip a generation. Penetrance is an all-or-none property (expressed or not), which distinguishes it from variable expressivity, the differing severity among those who do express the trait.

The closest distractor is "multiple affected in one generation". That vertical, every-generation pattern reflects a fully penetrant autosomal dominant trait, whereas the apparent generation skip via an unaffected carrier is the feature that specifically reveals reduced penetrance.

Incorrect Options:

• Multiple affected in one generation: Describes the vertical, every-generation transmission of fully penetrant autosomal dominant inheritance, not the skip caused by reduced penetrance.
• Only females are affected: Implies an X-linked or sex-limited pattern, unrelated to penetrance, which affects both sexes equally.
• No individual is affected: Represents complete non-penetrance or absence of the allele, not the partial expression seen with incomplete penetrance.

High-Yield Facts:

• Penetrance is all-or-none, whereas expressivity describes severity.
• Incomplete penetrance makes a dominant trait appear to skip a generation.
• An unaffected obligate carrier can still transmit the mutant allele.
• Polydactyly is a classic example of incomplete penetrance.

Figure 1: Incomplete penetrance - a genotype-positive (Cc) individual remains unaffected (white) and can silently transmit the allele.

Figure 2: Standard pedigree chart - squares are males, circles females, filled symbols affected. An unaffected person linking two affected generations signals a skipped generation.

The correct answer is Dependence on a single oncogenic pathway.

Oncogene addiction (a term coined by Bernard Weinstein) is the phenomenon whereby a cancer cell, despite harbouring many genetic lesions, becomes critically dependent on the continued activity of one dominant activated oncogene or oncogenic pathway for its proliferation and survival. Acutely inhibiting that single driver tilts the balance toward apoptosis, which is the rationale for molecular targeted therapy. Classic examples are CML addicted to BCR-ABL (treated with imatinib), HER2-amplified breast cancer (trastuzumab), and EGFR-mutant lung cancer (gefitinib or erlotinib).

The closest distractor is "dependence on multiple tumor suppressors". It mirrors the survival-dependence wording but is wrong on two counts. Oncogene addiction is a gain-of-function dependence on one oncogene, not loss of several tumor suppressor genes, and it is dependence on a single driver rather than multiple genes.

Incorrect Options:

• Dependence on multiple tumor suppressors: Oncogene addiction is gain-of-function reliance on one oncogene, not loss of several tumor suppressor genes.
• Immune checkpoint evasion of immunity: Describes immune evasion, a separate cancer hallmark targeted by checkpoint inhibitors, not oncogene addiction.
• Oncogene expression limited to embryogenesis: Oncogenes are abnormally activated in somatic tumour cells, not confined to embryonic development.

High-Yield Facts:

• The term oncogene addiction was coined by Bernard Weinstein.
• BCR-ABL in CML, targeted by imatinib, is the prototype.
• Addiction to a single driver is the basis of targeted therapy.
• Acquired resistance (e.g., BCR-ABL T315I) eventually limits targeted therapy.

Figure: An oncogene-addicted cell depends on one driver pathway (EGFR, panel A). Targeted agents - anti-EGFR antibody, TKI and downstream inhibitors - block that single pathway (panel B).