COMSAE Phase 1 Pathology Practice Exam
WITH ACTUAL QUESTIONS AND VERIFIED
ANSWERS, PLUS EXPLAINED
RATIONALES/EXPERT VERIFIED FOR
GUARANTEED 100% PASS 2026/LATEST
UPDATE/INSTANT DOWNLOAD PDF
1. A 58-year-old man with a 45-pack-year smoking history presents
with a persistent cough and hemoptysis. CT imaging demonstrates
a central hilar lung mass. Biopsy shows nests of malignant
polygonal cells with abundant eosinophilic cytoplasm, intercellular
bridges, and concentric keratin pearls. Which molecular
abnormality is most characteristic of the initiating pathogenesis of
this tumor?
A. Activating mutation of EGFR
B. Inactivation of RB1
C. Inactivation of TP53 and exposure-related genomic damage
D. ALK rearrangement
E. BRAF V600E mutation
Answer: C. Inactivation of TP53 and exposure-related genomic
damage
Rationale: Squamous cell carcinoma of the lung is strongly associated
with cigarette smoking and commonly develops through accumulation
of genetic alterations involving tumor suppressors such as TP53 and
CDKN2A, followed by squamous metaplasia, dysplasia, and
carcinoma. Histologically, keratin pearls and intercellular bridges
establish squamous differentiation. EGFR mutations and ALK
rearrangements are more characteristic of certain lung
adenocarcinomas, particularly in never-smokers.
1
, 2. A 7-year-old boy develops generalized edema and frothy urine.
Urinalysis reveals 4+ protein without hematuria. Serum albumin is
markedly decreased, and renal biopsy by light microscopy appears
essentially normal. Electron microscopy demonstrates diffuse
effacement of podocyte foot processes. Which mechanism best
explains the renal disease?
A. Immune-complex deposition in the subendothelial space
B. Autoantibodies against α3 chains of type IV collagen
C. T-cell–mediated cytokine injury to podocytes
D. Amyloid deposition in glomerular capillary loops
E. Mesangial deposition of IgA
Answer: C. T-cell–mediated cytokine injury to podocytes
Rationale: Minimal change disease is the most common cause of
nephrotic syndrome in children. Light microscopy is typically normal,
immunofluorescence is negative, and electron microscopy shows
diffuse podocyte foot-process effacement. A circulating permeability
factor, likely related to immune dysregulation and T-cell cytokines, is
thought to alter podocyte function. The disease generally responds
dramatically to corticosteroids.
3. A 64-year-old woman develops progressive fatigue, weight loss,
and abdominal distention. Colonoscopy reveals an obstructing
mass in the sigmoid colon. Histologic examination demonstrates
infiltrating malignant glands containing abundant extracellular
mucin. Molecular analysis identifies loss of mismatch-repair
function with microsatellite instability. Which additional finding is
most likely?
2
,A. Numerous APC mutations exclusively in the germline
B. High frequency of BRAF mutation and MLH1 promoter
hypermethylation in sporadic disease
C. RET proto-oncogene activation
D. BCR-ABL fusion
E. EWSR1-FLI1 fusion
Answer: B. High frequency of BRAF mutation and MLH1 promoter
hypermethylation in sporadic disease
Rationale: Sporadic microsatellite instability–high colorectal
carcinomas frequently result from epigenetic silencing of MLH1, often
accompanied by a BRAF mutation. In contrast, Lynch syndrome
results from germline mutations in mismatch-repair genes such as
MLH1, MSH2, MSH6, or PMS2. Mismatch-repair deficiency
produces accumulation of insertion/deletion errors in repetitive DNA
sequences and predisposes to colorectal and several extracolonic
malignancies.
4. A 46-year-old woman presents with fatigue and exertional
dyspnea. Laboratory studies show hemoglobin 8.1 g/dL, MCV 68
fL, low ferritin, increased total iron-binding capacity, and
decreased serum iron. Peripheral smear demonstrates microcytosis
and hypochromia. Which bone marrow finding would be
expected?
A. Ring sideroblasts
B. Increased iron stores with normal erythropoiesis
C. Decreased stainable iron stores
D. Megaloblastic erythroid precursors
E. Abundant hemophagocytosis
Answer: C. Decreased stainable iron stores
3
, Rationale: Iron-deficiency anemia produces microcytic, hypochromic
erythrocytes with decreased ferritin and decreased marrow iron stores.
TIBC is increased because hepatic transferrin synthesis rises in
response to iron deficiency. Ring sideroblasts are associated with
sideroblastic anemia, whereas megaloblastic changes reflect impaired
DNA synthesis from vitamin B12 or folate deficiency.
5. A 22-year-old woman presents with recurrent episodes of
abdominal pain and bloody diarrhea. Colonoscopy reveals
continuous mucosal inflammation beginning in the rectum and
extending proximally. Histology demonstrates crypt abscesses and
mucosal ulceration. Which complication is particularly associated
with longstanding disease?
A. Toxic megacolon and colorectal carcinoma
B. Fistulas involving the terminal ileum
C. Transmural strictures throughout the small intestine
D. Calcium oxalate nephrolithiasis due to ileal disease
E. Perianal fistula formation as the dominant complication
Answer: A. Toxic megacolon and colorectal carcinoma
Rationale: Ulcerative colitis is a chronic inflammatory disease limited
primarily to the colonic mucosa and submucosa, characteristically
beginning in the rectum and extending continuously. Severe acute
disease can produce toxic megacolon, while long-standing extensive
inflammation increases the risk of colorectal dysplasia and carcinoma.
Crohn disease more characteristically produces transmural
inflammation, skip lesions, fistulas, strictures, and perianal disease.
6. A 35-year-old man presents with fever, night sweats, and painless
cervical lymphadenopathy. Lymph-node biopsy demonstrates large
4
WITH ACTUAL QUESTIONS AND VERIFIED
ANSWERS, PLUS EXPLAINED
RATIONALES/EXPERT VERIFIED FOR
GUARANTEED 100% PASS 2026/LATEST
UPDATE/INSTANT DOWNLOAD PDF
1. A 58-year-old man with a 45-pack-year smoking history presents
with a persistent cough and hemoptysis. CT imaging demonstrates
a central hilar lung mass. Biopsy shows nests of malignant
polygonal cells with abundant eosinophilic cytoplasm, intercellular
bridges, and concentric keratin pearls. Which molecular
abnormality is most characteristic of the initiating pathogenesis of
this tumor?
A. Activating mutation of EGFR
B. Inactivation of RB1
C. Inactivation of TP53 and exposure-related genomic damage
D. ALK rearrangement
E. BRAF V600E mutation
Answer: C. Inactivation of TP53 and exposure-related genomic
damage
Rationale: Squamous cell carcinoma of the lung is strongly associated
with cigarette smoking and commonly develops through accumulation
of genetic alterations involving tumor suppressors such as TP53 and
CDKN2A, followed by squamous metaplasia, dysplasia, and
carcinoma. Histologically, keratin pearls and intercellular bridges
establish squamous differentiation. EGFR mutations and ALK
rearrangements are more characteristic of certain lung
adenocarcinomas, particularly in never-smokers.
1
, 2. A 7-year-old boy develops generalized edema and frothy urine.
Urinalysis reveals 4+ protein without hematuria. Serum albumin is
markedly decreased, and renal biopsy by light microscopy appears
essentially normal. Electron microscopy demonstrates diffuse
effacement of podocyte foot processes. Which mechanism best
explains the renal disease?
A. Immune-complex deposition in the subendothelial space
B. Autoantibodies against α3 chains of type IV collagen
C. T-cell–mediated cytokine injury to podocytes
D. Amyloid deposition in glomerular capillary loops
E. Mesangial deposition of IgA
Answer: C. T-cell–mediated cytokine injury to podocytes
Rationale: Minimal change disease is the most common cause of
nephrotic syndrome in children. Light microscopy is typically normal,
immunofluorescence is negative, and electron microscopy shows
diffuse podocyte foot-process effacement. A circulating permeability
factor, likely related to immune dysregulation and T-cell cytokines, is
thought to alter podocyte function. The disease generally responds
dramatically to corticosteroids.
3. A 64-year-old woman develops progressive fatigue, weight loss,
and abdominal distention. Colonoscopy reveals an obstructing
mass in the sigmoid colon. Histologic examination demonstrates
infiltrating malignant glands containing abundant extracellular
mucin. Molecular analysis identifies loss of mismatch-repair
function with microsatellite instability. Which additional finding is
most likely?
2
,A. Numerous APC mutations exclusively in the germline
B. High frequency of BRAF mutation and MLH1 promoter
hypermethylation in sporadic disease
C. RET proto-oncogene activation
D. BCR-ABL fusion
E. EWSR1-FLI1 fusion
Answer: B. High frequency of BRAF mutation and MLH1 promoter
hypermethylation in sporadic disease
Rationale: Sporadic microsatellite instability–high colorectal
carcinomas frequently result from epigenetic silencing of MLH1, often
accompanied by a BRAF mutation. In contrast, Lynch syndrome
results from germline mutations in mismatch-repair genes such as
MLH1, MSH2, MSH6, or PMS2. Mismatch-repair deficiency
produces accumulation of insertion/deletion errors in repetitive DNA
sequences and predisposes to colorectal and several extracolonic
malignancies.
4. A 46-year-old woman presents with fatigue and exertional
dyspnea. Laboratory studies show hemoglobin 8.1 g/dL, MCV 68
fL, low ferritin, increased total iron-binding capacity, and
decreased serum iron. Peripheral smear demonstrates microcytosis
and hypochromia. Which bone marrow finding would be
expected?
A. Ring sideroblasts
B. Increased iron stores with normal erythropoiesis
C. Decreased stainable iron stores
D. Megaloblastic erythroid precursors
E. Abundant hemophagocytosis
Answer: C. Decreased stainable iron stores
3
, Rationale: Iron-deficiency anemia produces microcytic, hypochromic
erythrocytes with decreased ferritin and decreased marrow iron stores.
TIBC is increased because hepatic transferrin synthesis rises in
response to iron deficiency. Ring sideroblasts are associated with
sideroblastic anemia, whereas megaloblastic changes reflect impaired
DNA synthesis from vitamin B12 or folate deficiency.
5. A 22-year-old woman presents with recurrent episodes of
abdominal pain and bloody diarrhea. Colonoscopy reveals
continuous mucosal inflammation beginning in the rectum and
extending proximally. Histology demonstrates crypt abscesses and
mucosal ulceration. Which complication is particularly associated
with longstanding disease?
A. Toxic megacolon and colorectal carcinoma
B. Fistulas involving the terminal ileum
C. Transmural strictures throughout the small intestine
D. Calcium oxalate nephrolithiasis due to ileal disease
E. Perianal fistula formation as the dominant complication
Answer: A. Toxic megacolon and colorectal carcinoma
Rationale: Ulcerative colitis is a chronic inflammatory disease limited
primarily to the colonic mucosa and submucosa, characteristically
beginning in the rectum and extending continuously. Severe acute
disease can produce toxic megacolon, while long-standing extensive
inflammation increases the risk of colorectal dysplasia and carcinoma.
Crohn disease more characteristically produces transmural
inflammation, skip lesions, fistulas, strictures, and perianal disease.
6. A 35-year-old man presents with fever, night sweats, and painless
cervical lymphadenopathy. Lymph-node biopsy demonstrates large
4
