Robbins & Cotran 10th Ed. Pathology Test Bank | Chapter-
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 3-year-old boy has recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation in a gene
encoding a DNA repair enzyme important for V(D)J
recombination. Which mechanism best explains the
immunodeficiency?
A. Decreased transcription of immunoglobulin genes due to
promoter methylation
B. Impaired double-strand break repair during V(D)J
recombination
C. Reduced mitochondrial ATP production in lymphocytes
D. Defective cytokine receptor signaling downstream of
JAK/STAT
,Correct Answer: B
Rationale (correct): V(D)J recombination requires controlled
double-strand DNA breaks and their repair; a frameshift in a
repair enzyme disrupts this process, preventing formation of
diverse B and T cell receptors and causing severe
immunodeficiency.
Rationale (A): Promoter methylation can silence genes but
would not specifically disrupt V(D)J recombination machinery.
Rationale (C): Mitochondrial ATP deficiency impairs many
cell functions but does not explain the specific defect in receptor
gene rearrangement.
Rationale (D): JAK/STAT defects impair cytokine signaling
but would not directly block DNA rearrangements required for
receptor diversity.
Teaching Point: V(D)J recombination requires precise double-
strand break repair to generate lymphocyte receptor diversity.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A patient’s tumor cells show high microsatellite
instability (MSI) on testing. Which genomic defect most likely
produced MSI?
A. Defective mismatch repair proteins (MLH1, MSH2)
B. Loss of tumor suppressor p53 function
,C. Increased activity of DNA polymerase proofreading
D. Elevated levels of base excision repair enzymes
Correct Answer: A
Rationale (correct): MSI arises from defective DNA mismatch
repair (MMR) leading to accumulation of insertion/deletion
errors at microsatellite repeats; MLH1/MSH2 dysfunction is
classic.
Rationale (B): p53 loss promotes genomic instability broadly
but is not the specific cause of MSI.
Rationale (C): Increased proofreading would reduce MSI, not
cause it.
Rationale (D): Base excision repair corrects small base lesions,
not microsatellite slippage errors.
Teaching Point: Defective mismatch repair causes
microsatellite instability and predisposes to certain cancers.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A patient with chronic alcohol use has hepatocytes loaded
with Mallory bodies—aggregates of cytokeratin filaments.
Which cellular process failed to prevent their accumulation?
A. Autophagy (macroautophagy) of protein aggregates
B. Mitochondrial oxidative phosphorylation
, C. Lysosomal uptake of extracellular matrix
D. Nuclear export of misfolded proteins
Correct Answer: A
Rationale (correct): Macroautophagy removes intracellular
protein aggregates and damaged organelles; failure or overload
of autophagy leads to cytoplasmic inclusions like Mallory
bodies.
Rationale (B): Oxidative phosphorylation impairment affects
energy but not directly formation of cytokeratin aggregates.
Rationale (C): Lysosomes degrade intracellular material
brought by autophagy or endocytosis; “lysosomal uptake of
ECM” is not relevant.
Rationale (D): Nuclear export is not the main pathway for
clearing cytoplasmic protein aggregates.
Teaching Point: Macroautophagy clears intracellular
aggregates; impairment causes inclusion bodies.
4
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A biopsy shows cells with abundant residual bodies
(lipofuscin) in cardiac muscle of an elderly patient. Lipofuscin
accumulation most likely indicates which process?
A. Excessive deposition of extracellular collagen
B. Incomplete lysosomal degradation of oxidized lipids and
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
1
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A 3-year-old boy has recurrent infections and failure to
thrive. Genetic testing shows a frameshift mutation in a gene
encoding a DNA repair enzyme important for V(D)J
recombination. Which mechanism best explains the
immunodeficiency?
A. Decreased transcription of immunoglobulin genes due to
promoter methylation
B. Impaired double-strand break repair during V(D)J
recombination
C. Reduced mitochondrial ATP production in lymphocytes
D. Defective cytokine receptor signaling downstream of
JAK/STAT
,Correct Answer: B
Rationale (correct): V(D)J recombination requires controlled
double-strand DNA breaks and their repair; a frameshift in a
repair enzyme disrupts this process, preventing formation of
diverse B and T cell receptors and causing severe
immunodeficiency.
Rationale (A): Promoter methylation can silence genes but
would not specifically disrupt V(D)J recombination machinery.
Rationale (C): Mitochondrial ATP deficiency impairs many
cell functions but does not explain the specific defect in receptor
gene rearrangement.
Rationale (D): JAK/STAT defects impair cytokine signaling
but would not directly block DNA rearrangements required for
receptor diversity.
Teaching Point: V(D)J recombination requires precise double-
strand break repair to generate lymphocyte receptor diversity.
2
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — The Genome
Stem: A patient’s tumor cells show high microsatellite
instability (MSI) on testing. Which genomic defect most likely
produced MSI?
A. Defective mismatch repair proteins (MLH1, MSH2)
B. Loss of tumor suppressor p53 function
,C. Increased activity of DNA polymerase proofreading
D. Elevated levels of base excision repair enzymes
Correct Answer: A
Rationale (correct): MSI arises from defective DNA mismatch
repair (MMR) leading to accumulation of insertion/deletion
errors at microsatellite repeats; MLH1/MSH2 dysfunction is
classic.
Rationale (B): p53 loss promotes genomic instability broadly
but is not the specific cause of MSI.
Rationale (C): Increased proofreading would reduce MSI, not
cause it.
Rationale (D): Base excision repair corrects small base lesions,
not microsatellite slippage errors.
Teaching Point: Defective mismatch repair causes
microsatellite instability and predisposes to certain cancers.
3
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A patient with chronic alcohol use has hepatocytes loaded
with Mallory bodies—aggregates of cytokeratin filaments.
Which cellular process failed to prevent their accumulation?
A. Autophagy (macroautophagy) of protein aggregates
B. Mitochondrial oxidative phosphorylation
, C. Lysosomal uptake of extracellular matrix
D. Nuclear export of misfolded proteins
Correct Answer: A
Rationale (correct): Macroautophagy removes intracellular
protein aggregates and damaged organelles; failure or overload
of autophagy leads to cytoplasmic inclusions like Mallory
bodies.
Rationale (B): Oxidative phosphorylation impairment affects
energy but not directly formation of cytokeratin aggregates.
Rationale (C): Lysosomes degrade intracellular material
brought by autophagy or endocytosis; “lysosomal uptake of
ECM” is not relevant.
Rationale (D): Nuclear export is not the main pathway for
clearing cytoplasmic protein aggregates.
Teaching Point: Macroautophagy clears intracellular
aggregates; impairment causes inclusion bodies.
4
Chapter Reference – Chapter 1: The Cell as a Unit of Health
and Disease — Cellular Housekeeping
Stem: A biopsy shows cells with abundant residual bodies
(lipofuscin) in cardiac muscle of an elderly patient. Lipofuscin
accumulation most likely indicates which process?
A. Excessive deposition of extracellular collagen
B. Incomplete lysosomal degradation of oxidized lipids and
