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 – The Genome
Stem: A 42-year-old man develops multiple colon
adenomas and early-onset colorectal cancer. Tumor testing
shows high levels of microsatellite instability (MSI). Which
germline defect most likely explains this phenotype?
A. BRCA1 mutation
B. Mismatch repair gene mutation (e.g., MLH1, MSH2)
C. TP53 missense mutation
D. APC truncating mutation
Answer: B. Mismatch repair gene mutation (e.g., MLH1,
MSH2)
Rationale — correct: Defective DNA mismatch repair
(MLH1/MSH2) causes accumulation of replication errors at
microsatellites, producing high MSI and hereditary
nonpolyposis colorectal cancer.
, Rationale — A: BRCA1 predisposes to breast/ovarian
cancer via homologous recombination defects, not MSI.
Rationale — C: TP53 mutations cause loss of cell-cycle
arrest/apoptosis control but are not the primary cause of
MSI.
Rationale — D: APC mutations drive familial adenomatous
polyposis with numerous polyps, typically without high
MSI.
Teaching Point: Mismatch repair defects produce
microsatellite instability and early colorectal cancer.
2. Chapter Reference – The Genome
Stem: A tumor shows amplification of the MYC oncogene.
Which mechanism best explains how oncogene
amplification contributes to cancer?
A. Loss of function of a tumor suppressor
B. Increased dosage and overexpression of growth-
promoting genes
C. Enhanced DNA repair fidelity
D. Epigenetic silencing of cell-cycle inhibitors
Answer: B. Increased dosage and overexpression of
growth-promoting genes
Rationale — correct: Gene amplification increases copy
number and expression of proto-oncogenes (e.g., MYC),
driving unchecked proliferation.
Rationale — A: Loss-of-function of tumor suppressors is
, different (deletions/mutations), not amplification.
Rationale — C: Amplification does not enhance DNA
repair; it promotes oncogenic signaling.
Rationale — D: Epigenetic silencing is another mechanism
but is not the consequence of oncogene amplification.
Teaching Point: Oncogene amplification increases proto-
oncogene expression, promoting malignancy.
3. Chapter Reference – The Genome
Stem: A patient’s leukemic cells have a balanced
translocation creating a novel BCR-ABL fusion protein with
constitutive tyrosine kinase activity. Which cancer
mechanism is exemplified here?
A. Chromosomal translocation activating a proto-oncogene
B. Point mutation causing loss of kinase function
C. Microsatellite instability from mismatch repair failure
D. Inactivation of tumor suppressor by methylation
Answer: A. Chromosomal translocation activating a
proto-oncogene
Rationale — correct: The BCR-ABL fusion from t(9;22) is a
classic translocation that creates a constitutively active
tyrosine kinase, driving leukemia.
Rationale — B: This is an activating fusion, not a loss-of-
function point mutation.
Rationale — C: MSI is unrelated to balanced chromosomal
translocations.
, Rationale — D: Methylation can inactivate tumor
suppressors but does not explain a fusion kinase.
Teaching Point: Chromosomal translocations can create
oncogenic fusion proteins with constitutive activity.
4. Chapter Reference – Cellular Housekeeping
Stem: A hepatocyte biopsy shows abundant Mallory-Denk
bodies composed of cytokeratin intermediate filaments.
Which intracellular quality-control failure explains this
finding?
A. Defective lysosomal enzyme import
B. Impaired ubiquitin–proteasome degradation of
misfolded proteins
C. Loss of mitochondrial ATP production
D. Increased autophagic removal of organelles
Answer: B. Impaired ubiquitin–proteasome degradation
of misfolded proteins
Rationale — correct: Accumulation of misfolded
cytokeratin filaments (Mallory bodies) reflects failure of
the ubiquitin–proteasome system to clear abnormal
proteins.
Rationale — A: Lysosomal enzyme import defects produce
storage disease patterns, not intermediate filament
inclusions.
Rationale — C: Mitochondrial ATP loss can impair many
processes but does not specifically form Mallory bodies.
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 – The Genome
Stem: A 42-year-old man develops multiple colon
adenomas and early-onset colorectal cancer. Tumor testing
shows high levels of microsatellite instability (MSI). Which
germline defect most likely explains this phenotype?
A. BRCA1 mutation
B. Mismatch repair gene mutation (e.g., MLH1, MSH2)
C. TP53 missense mutation
D. APC truncating mutation
Answer: B. Mismatch repair gene mutation (e.g., MLH1,
MSH2)
Rationale — correct: Defective DNA mismatch repair
(MLH1/MSH2) causes accumulation of replication errors at
microsatellites, producing high MSI and hereditary
nonpolyposis colorectal cancer.
, Rationale — A: BRCA1 predisposes to breast/ovarian
cancer via homologous recombination defects, not MSI.
Rationale — C: TP53 mutations cause loss of cell-cycle
arrest/apoptosis control but are not the primary cause of
MSI.
Rationale — D: APC mutations drive familial adenomatous
polyposis with numerous polyps, typically without high
MSI.
Teaching Point: Mismatch repair defects produce
microsatellite instability and early colorectal cancer.
2. Chapter Reference – The Genome
Stem: A tumor shows amplification of the MYC oncogene.
Which mechanism best explains how oncogene
amplification contributes to cancer?
A. Loss of function of a tumor suppressor
B. Increased dosage and overexpression of growth-
promoting genes
C. Enhanced DNA repair fidelity
D. Epigenetic silencing of cell-cycle inhibitors
Answer: B. Increased dosage and overexpression of
growth-promoting genes
Rationale — correct: Gene amplification increases copy
number and expression of proto-oncogenes (e.g., MYC),
driving unchecked proliferation.
Rationale — A: Loss-of-function of tumor suppressors is
, different (deletions/mutations), not amplification.
Rationale — C: Amplification does not enhance DNA
repair; it promotes oncogenic signaling.
Rationale — D: Epigenetic silencing is another mechanism
but is not the consequence of oncogene amplification.
Teaching Point: Oncogene amplification increases proto-
oncogene expression, promoting malignancy.
3. Chapter Reference – The Genome
Stem: A patient’s leukemic cells have a balanced
translocation creating a novel BCR-ABL fusion protein with
constitutive tyrosine kinase activity. Which cancer
mechanism is exemplified here?
A. Chromosomal translocation activating a proto-oncogene
B. Point mutation causing loss of kinase function
C. Microsatellite instability from mismatch repair failure
D. Inactivation of tumor suppressor by methylation
Answer: A. Chromosomal translocation activating a
proto-oncogene
Rationale — correct: The BCR-ABL fusion from t(9;22) is a
classic translocation that creates a constitutively active
tyrosine kinase, driving leukemia.
Rationale — B: This is an activating fusion, not a loss-of-
function point mutation.
Rationale — C: MSI is unrelated to balanced chromosomal
translocations.
, Rationale — D: Methylation can inactivate tumor
suppressors but does not explain a fusion kinase.
Teaching Point: Chromosomal translocations can create
oncogenic fusion proteins with constitutive activity.
4. Chapter Reference – Cellular Housekeeping
Stem: A hepatocyte biopsy shows abundant Mallory-Denk
bodies composed of cytokeratin intermediate filaments.
Which intracellular quality-control failure explains this
finding?
A. Defective lysosomal enzyme import
B. Impaired ubiquitin–proteasome degradation of
misfolded proteins
C. Loss of mitochondrial ATP production
D. Increased autophagic removal of organelles
Answer: B. Impaired ubiquitin–proteasome degradation
of misfolded proteins
Rationale — correct: Accumulation of misfolded
cytokeratin filaments (Mallory bodies) reflects failure of
the ubiquitin–proteasome system to clear abnormal
proteins.
Rationale — A: Lysosomal enzyme import defects produce
storage disease patterns, not intermediate filament
inclusions.
Rationale — C: Mitochondrial ATP loss can impair many
processes but does not specifically form Mallory bodies.
