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
Chapter Reference: Chapter 1 — The Genome
Stem: A 28-year-old man with early-onset colon cancer
undergoes tumor testing showing high microsatellite instability
(MSI-high). Which inherited defect is most likely responsible?
A. BRCA1 mutation
B. MSH2 mutation
C. TP53 mutation
D. APC mutation
Answer: B
Rationale — Correct (B): MSH2 is a DNA mismatch repair
gene; germline mutations in MSH2 (Lynch syndrome) cause
defective mismatch repair leading to microsatellite instability
and early colon cancer. The MSI-high phenotype is the hallmark
of mismatch repair deficiency.
,Rationale — Incorrect:
A. BRCA1 predisposes to breast/ovarian cancer via homologous
recombination defects, not MSI.
C. TP53 mutations drive genomic instability broadly but are not
the canonical cause of MSI.
D. APC mutations cause colorectal cancer via Wnt pathway
dysfunction and chromosomal instability, not MSI.
Teaching Point: Defects in mismatch-repair genes (e.g., MSH2)
cause MSI and Lynch syndrome.
2.
Chapter Reference: Chapter 1 — The Genome
Stem: A newborn screen reveals an infant with elevated
phenylalanine levels. The underlying defect is most likely which
type of genetic alteration?
A. Mitochondrial DNA deletion
B. Autosomal dominant gain-of-function mutation
C. Autosomal recessive loss-of-function mutation in an enzyme
D. Trinucleotide repeat expansion in a regulatory gene
Answer: C
Rationale — Correct (C): Phenylketonuria results from
autosomal recessive loss-of-function mutations in phenylalanine
hydroxylase (or cofactor metabolism), causing accumulation of
phenylalanine. Enzymatic deficiency due to biallelic loss is
classic.
Rationale — Incorrect:
A. Mitochondrial DNA deletions produce mitochondrial
,syndromes (e.g., MELAS), not PKU.
B. Gain-of-function AD mutations are uncommon for inborn
errors of metabolism like PKU.
D. Trinucleotide repeat expansions cause diseases like
Huntington disease, not PKU.
Teaching Point: Many inborn errors of metabolism are
autosomal recessive enzyme loss-of-function disorders.
3.
Chapter Reference: Chapter 1 — Cellular Housekeeping
Stem: A patient receiving a proteasome inhibitor for multiple
myeloma develops peripheral neuropathy. Proteasome inhibition
primarily disrupts which cellular process?
A. Lysosomal degradation of phagocytosed pathogens
B. Ubiquitin-dependent degradation of misfolded proteins
C. Mitochondrial ATP synthesis
D. Autophagic clearance of organelles
Answer: B
Rationale — Correct (B): The ubiquitin-proteasome system
tags damaged/misfolded proteins with ubiquitin for proteasomal
degradation; blocking the proteasome leads to accumulation of
abnormal proteins and cellular dysfunction. Proteasome
inhibitors target this pathway therapeutically.
Rationale — Incorrect:
A. Lysosomal degradation is a separate pathway
(phagocytosis/endocytosis), not the proteasome.
C. Proteasome inhibition does not directly block oxidative
, phosphorylation.
D. Autophagy uses lysosomes to degrade organelles and can be
functionally linked but is distinct from proteasomal degradation.
Teaching Point: The ubiquitin-proteasome system selectively
degrades misfolded proteins tagged with ubiquitin.
4.
Chapter Reference: Chapter 1 — Cellular Housekeeping
Stem: A biopsy shows accumulation of lipofuscin pigment in
long-lived cardiac myocytes of an elderly patient. This pigment
is mainly a product of which process?
A. Impaired peroxisomal β-oxidation
B. Oxidative modification of proteins and lipids within
lysosomes
C. Excess glycogen storage within cytosol
D. Deposition of advanced glycation end products in
extracellular matrix
Answer: B
Rationale — Correct (B): Lipofuscin ("wear-and-tear"
pigment) accumulates from oxidative degradation products of
membranes and proteins in lysosomes of long-lived cells. It
reflects oxidative stress and imperfect lysosomal clearance.
Rationale — Incorrect:
A. Peroxisomal β-oxidation defects cause accumulation of very
long chain fatty acids, not lipofuscin.
C. Glycogen accumulation produces clear cytoplasmic vacuoles,
not brown lipofuscin pigment.
by-Chapter Questions & Verified Solutions
Robbins & Cotran Pathologic Basis of Disease
10th Edition
• Author(s)Vinay Kumar; Abul K. Abbas; Jon C. Aster
Chapter Reference: Chapter 1 — The Genome
Stem: A 28-year-old man with early-onset colon cancer
undergoes tumor testing showing high microsatellite instability
(MSI-high). Which inherited defect is most likely responsible?
A. BRCA1 mutation
B. MSH2 mutation
C. TP53 mutation
D. APC mutation
Answer: B
Rationale — Correct (B): MSH2 is a DNA mismatch repair
gene; germline mutations in MSH2 (Lynch syndrome) cause
defective mismatch repair leading to microsatellite instability
and early colon cancer. The MSI-high phenotype is the hallmark
of mismatch repair deficiency.
,Rationale — Incorrect:
A. BRCA1 predisposes to breast/ovarian cancer via homologous
recombination defects, not MSI.
C. TP53 mutations drive genomic instability broadly but are not
the canonical cause of MSI.
D. APC mutations cause colorectal cancer via Wnt pathway
dysfunction and chromosomal instability, not MSI.
Teaching Point: Defects in mismatch-repair genes (e.g., MSH2)
cause MSI and Lynch syndrome.
2.
Chapter Reference: Chapter 1 — The Genome
Stem: A newborn screen reveals an infant with elevated
phenylalanine levels. The underlying defect is most likely which
type of genetic alteration?
A. Mitochondrial DNA deletion
B. Autosomal dominant gain-of-function mutation
C. Autosomal recessive loss-of-function mutation in an enzyme
D. Trinucleotide repeat expansion in a regulatory gene
Answer: C
Rationale — Correct (C): Phenylketonuria results from
autosomal recessive loss-of-function mutations in phenylalanine
hydroxylase (or cofactor metabolism), causing accumulation of
phenylalanine. Enzymatic deficiency due to biallelic loss is
classic.
Rationale — Incorrect:
A. Mitochondrial DNA deletions produce mitochondrial
,syndromes (e.g., MELAS), not PKU.
B. Gain-of-function AD mutations are uncommon for inborn
errors of metabolism like PKU.
D. Trinucleotide repeat expansions cause diseases like
Huntington disease, not PKU.
Teaching Point: Many inborn errors of metabolism are
autosomal recessive enzyme loss-of-function disorders.
3.
Chapter Reference: Chapter 1 — Cellular Housekeeping
Stem: A patient receiving a proteasome inhibitor for multiple
myeloma develops peripheral neuropathy. Proteasome inhibition
primarily disrupts which cellular process?
A. Lysosomal degradation of phagocytosed pathogens
B. Ubiquitin-dependent degradation of misfolded proteins
C. Mitochondrial ATP synthesis
D. Autophagic clearance of organelles
Answer: B
Rationale — Correct (B): The ubiquitin-proteasome system
tags damaged/misfolded proteins with ubiquitin for proteasomal
degradation; blocking the proteasome leads to accumulation of
abnormal proteins and cellular dysfunction. Proteasome
inhibitors target this pathway therapeutically.
Rationale — Incorrect:
A. Lysosomal degradation is a separate pathway
(phagocytosis/endocytosis), not the proteasome.
C. Proteasome inhibition does not directly block oxidative
, phosphorylation.
D. Autophagy uses lysosomes to degrade organelles and can be
functionally linked but is distinct from proteasomal degradation.
Teaching Point: The ubiquitin-proteasome system selectively
degrades misfolded proteins tagged with ubiquitin.
4.
Chapter Reference: Chapter 1 — Cellular Housekeeping
Stem: A biopsy shows accumulation of lipofuscin pigment in
long-lived cardiac myocytes of an elderly patient. This pigment
is mainly a product of which process?
A. Impaired peroxisomal β-oxidation
B. Oxidative modification of proteins and lipids within
lysosomes
C. Excess glycogen storage within cytosol
D. Deposition of advanced glycation end products in
extracellular matrix
Answer: B
Rationale — Correct (B): Lipofuscin ("wear-and-tear"
pigment) accumulates from oxidative degradation products of
membranes and proteins in lysosomes of long-lived cells. It
reflects oxidative stress and imperfect lysosomal clearance.
Rationale — Incorrect:
A. Peroxisomal β-oxidation defects cause accumulation of very
long chain fatty acids, not lipofuscin.
C. Glycogen accumulation produces clear cytoplasmic vacuoles,
not brown lipofuscin pigment.
