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 newborn presents with jaundice and hypotonia.
Genetic testing reveals a single-base substitution in a gene
encoding a DNA repair enzyme that abolishes its
endonuclease activity. Which consequence is most likely to
increase the child’s long-term risk of cancer?
A. Global hypomethylation of DNA
B. Accumulation of unrepaired DNA lesions leading to
mutations in proto-oncogenes and tumor suppressors
C. Increased telomerase activity leading to immortalization
of somatic cells
D. Failure of X-chromosome inactivation causing dosage
imbalance
Answer: B
,Rationale (Correct): Loss of DNA repair endonuclease activity
allows unrepaired DNA lesions to persist and be fixed as
mutations during replication; mutations in proto-oncogenes or
tumor suppressors increase cancer risk.
Rationale (A): Global hypomethylation can occur in cancer but
is not the direct consequence of defective DNA endonuclease
repair.
Rationale (C): Increased telomerase is associated with
immortalization but is not the immediate consequence of
defective endonuclease DNA repair.
Rationale (D): X-inactivation failure affects dosage of X-linked
genes; unrelated to general DNA repair enzyme defects.
Teaching Point: Faulty DNA repair permits mutation
accumulation and promotes oncogenesis.
2. Chapter Reference – The Genome
Stem: A mutagen causes formation of pyrimidine dimers in
skin cell DNA after UV exposure. Which DNA repair
pathway is primarily responsible for removing these
dimers?
A. Base excision repair (BER)
B. Nucleotide excision repair (NER)
C. Mismatch repair (MMR)
D. Homologous recombination (HR)
Answer: B
,Rationale (Correct): NER recognizes and excises bulky helix-
distorting lesions such as pyrimidine dimers caused by UV, then
fills the gap by DNA synthesis.
Rationale (A): BER removes small, non-helix-distorting base
lesions, not bulky dimers.
Rationale (C): MMR corrects replication mispairs, not UV-
induced dimers.
Rationale (D): HR repairs double-strand breaks using a
homologous template, not pyrimidine dimers.
Teaching Point: NER removes bulky, helix-distorting DNA lesions
like UV-induced dimers.
3. Chapter Reference – Cellular Housekeeping
Stem: A neuron shows accumulation of ubiquitin-positive
cytoplasmic inclusions and progressive dysfunction. Which
malfunction best explains these findings?
A. Excessive autophagy of mitochondria
B. Impaired ubiquitin–proteasome system leading to
accumulation of abnormal proteins
C. Overactive lysosomal hydrolases causing cytoplasmic
digestion
D. Increased phagocytosis of extracellular debris
Answer: B
Rationale (Correct): The ubiquitin–proteasome system tags
misfolded proteins with ubiquitin for proteasomal degradation;
impairment leads to ubiquitin-positive inclusions and neuronal
, dysfunction, as seen in some neurodegenerative diseases.
Rationale (A): Excessive mitophagy would reduce mitochondria,
not produce ubiquitin-positive cytoplasmic inclusions.
Rationale (C): Overactive lysosomal hydrolases typically
produce autophagic/lysosomal pathology, not ubiquitin-tagged
inclusions from proteasomal failure.
Rationale (D): Phagocytosis of extracellular debris is performed
by phagocytes, not neuronal intracellular inclusion formation.
Teaching Point: Proteasomal failure causes ubiquitin-positive
aggregates and cellular dysfunction.
4. Chapter Reference – Cellular Housekeeping
Stem: A patient with a lysosomal storage disorder
accumulates undigested substrates within macrophage
lysosomes. Which cellular process is primarily defective?
A. Proteasomal degradation of ubiquitinated proteins
B. Lysosomal enzyme activity or trafficking
C. Mitochondrial oxidative phosphorylation
D. Autocrine growth factor secretion
Answer: B
Rationale (Correct): Lysosomal storage disorders result from
deficiencies in lysosomal hydrolases or their trafficking, causing
accumulation of substrates within lysosomes.
Rationale (A): The proteasome degrades ubiquitinated proteins
in the cytosol; lysosomal storage involves lysosomal enzymes.
Rationale (C): Mitochondrial defects affect energy, not selective
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 newborn presents with jaundice and hypotonia.
Genetic testing reveals a single-base substitution in a gene
encoding a DNA repair enzyme that abolishes its
endonuclease activity. Which consequence is most likely to
increase the child’s long-term risk of cancer?
A. Global hypomethylation of DNA
B. Accumulation of unrepaired DNA lesions leading to
mutations in proto-oncogenes and tumor suppressors
C. Increased telomerase activity leading to immortalization
of somatic cells
D. Failure of X-chromosome inactivation causing dosage
imbalance
Answer: B
,Rationale (Correct): Loss of DNA repair endonuclease activity
allows unrepaired DNA lesions to persist and be fixed as
mutations during replication; mutations in proto-oncogenes or
tumor suppressors increase cancer risk.
Rationale (A): Global hypomethylation can occur in cancer but
is not the direct consequence of defective DNA endonuclease
repair.
Rationale (C): Increased telomerase is associated with
immortalization but is not the immediate consequence of
defective endonuclease DNA repair.
Rationale (D): X-inactivation failure affects dosage of X-linked
genes; unrelated to general DNA repair enzyme defects.
Teaching Point: Faulty DNA repair permits mutation
accumulation and promotes oncogenesis.
2. Chapter Reference – The Genome
Stem: A mutagen causes formation of pyrimidine dimers in
skin cell DNA after UV exposure. Which DNA repair
pathway is primarily responsible for removing these
dimers?
A. Base excision repair (BER)
B. Nucleotide excision repair (NER)
C. Mismatch repair (MMR)
D. Homologous recombination (HR)
Answer: B
,Rationale (Correct): NER recognizes and excises bulky helix-
distorting lesions such as pyrimidine dimers caused by UV, then
fills the gap by DNA synthesis.
Rationale (A): BER removes small, non-helix-distorting base
lesions, not bulky dimers.
Rationale (C): MMR corrects replication mispairs, not UV-
induced dimers.
Rationale (D): HR repairs double-strand breaks using a
homologous template, not pyrimidine dimers.
Teaching Point: NER removes bulky, helix-distorting DNA lesions
like UV-induced dimers.
3. Chapter Reference – Cellular Housekeeping
Stem: A neuron shows accumulation of ubiquitin-positive
cytoplasmic inclusions and progressive dysfunction. Which
malfunction best explains these findings?
A. Excessive autophagy of mitochondria
B. Impaired ubiquitin–proteasome system leading to
accumulation of abnormal proteins
C. Overactive lysosomal hydrolases causing cytoplasmic
digestion
D. Increased phagocytosis of extracellular debris
Answer: B
Rationale (Correct): The ubiquitin–proteasome system tags
misfolded proteins with ubiquitin for proteasomal degradation;
impairment leads to ubiquitin-positive inclusions and neuronal
, dysfunction, as seen in some neurodegenerative diseases.
Rationale (A): Excessive mitophagy would reduce mitochondria,
not produce ubiquitin-positive cytoplasmic inclusions.
Rationale (C): Overactive lysosomal hydrolases typically
produce autophagic/lysosomal pathology, not ubiquitin-tagged
inclusions from proteasomal failure.
Rationale (D): Phagocytosis of extracellular debris is performed
by phagocytes, not neuronal intracellular inclusion formation.
Teaching Point: Proteasomal failure causes ubiquitin-positive
aggregates and cellular dysfunction.
4. Chapter Reference – Cellular Housekeeping
Stem: A patient with a lysosomal storage disorder
accumulates undigested substrates within macrophage
lysosomes. Which cellular process is primarily defective?
A. Proteasomal degradation of ubiquitinated proteins
B. Lysosomal enzyme activity or trafficking
C. Mitochondrial oxidative phosphorylation
D. Autocrine growth factor secretion
Answer: B
Rationale (Correct): Lysosomal storage disorders result from
deficiencies in lysosomal hydrolases or their trafficking, causing
accumulation of substrates within lysosomes.
Rationale (A): The proteasome degrades ubiquitinated proteins
in the cytosol; lysosomal storage involves lysosomal enzymes.
Rationale (C): Mitochondrial defects affect energy, not selective
