COMSAE Comprehensive Examination 2026–2027
Study Guide | Comprehensive Osteopathic Medical
Self-Assessment Exam Prep, COMLEX-USA Review,
Practice Questions, Clinical Reasoning, Osteopathic
Principles, Medical Sciences, Detailed Answers &
Rationales
Question 1: A 45-year-old man presents with sudden onset of severe tearing
chest pain radiating to the back. He is hypertensive and has a history of
Marfan syndrome. Which of the following is the most likely diagnosis?
A. Acute myocardial infarction
B. Aortic dissection
C. Pulmonary embolism
D. Pericarditis
CORRECT ANSWER: B. Aortic dissection
Rationale: Sudden severe tearing chest pain radiating to the back in a hypertensive
patient with Marfan syndrome is classic for aortic dissection. Marfan syndrome
predisposes to cystic medial degeneration of the aorta. MI typically presents with
crushing substernal pain, PE with pleuritic pain and dyspnea, and pericarditis with
positional pain.
Question 2: A 62-year-old woman presents with fatigue, weight gain, cold
intolerance, and constipation. Physical exam reveals dry skin, bradycardia,
and delayed deep tendon reflexes. Which of the following is the most likely
diagnosis?
A. Hyperthyroidism
B. Hypothyroidism
C. Cushing syndrome
D. Adrenal insufficiency
CORRECT ANSWER: B. Hypothyroidism
Rationale: Fatigue, weight gain, cold intolerance, constipation, dry skin, bradycardia, and
delayed deep tendon reflexes are hallmark features of hypothyroidism. Hyperthyroidism
causes weight loss and heat intolerance. Cushing syndrome causes weight gain but with
central obesity and hypertension. Adrenal insufficiency causes hypotension and
hyperpigmentation.
Question 3: A 28-year-old man presents with recurrent episodes of severe
abdominal pain, hypertension, and palpitations. He reports that his urine
turns dark on standing. Which of the following is the most likely diagnosis?
A. Acute intermittent porphyria
B. Pheochromocytoma
C. Lead poisoning
D. Porphyria cutanea tarda
,CORRECT ANSWER: A. Acute intermittent porphyria
Rationale: Acute intermittent porphyria presents with the classic triad of severe
abdominal pain, neuropsychiatric symptoms, and autonomic dysfunction (hypertension,
palpitations). Dark urine on standing is due to porphobilinogen. Pheochromocytoma
causes episodic hypertension but not dark urine. Lead poisoning causes abdominal pain
but with anemia and gingival lead lines. Porphyria cutanea tarda causes photosensitivity,
not abdominal pain.
Question 4: A 55-year-old man with a 40-pack-year smoking history presents
with hemoptysis, weight loss, and a right hilar mass on chest X-ray. Which of
the following is the most likely diagnosis?
A. Squamous cell carcinoma of the lung
B. Adenocarcinoma of the lung
C. Small cell carcinoma of the lung
D. Mesothelioma
CORRECT ANSWER: A. Squamous cell carcinoma of the lung
Rationale: Squamous cell carcinoma is strongly associated with smoking, typically
presents as a central/hilar mass, and commonly causes hemoptysis due to cavitation
and airway involvement. Adenocarcinoma is more peripheral. Small cell carcinoma is
also central but is characterized by rapid growth and early metastasis. Mesothelioma is
associated with asbestos exposure and presents with pleural thickening.
Question 5: A 32-year-old woman presents with a butterfly-shaped facial rash,
photosensitivity, oral ulcers, and arthralgias. Laboratory tests reveal anemia,
thrombocytopenia, and positive ANA. Which of the following is the most likely
diagnosis?
A. Rheumatoid arthritis
B. Systemic lupus erythematosus
C. Dermatomyositis
D. Scleroderma
CORRECT ANSWER: B. Systemic lupus erythematosus
Rationale: Malar (butterfly) rash, photosensitivity, oral ulcers, arthralgias, and cytopenias
with positive ANA are diagnostic criteria for SLE. Rheumatoid arthritis primarily causes
symmetric joint deformities without rash. Dermatomyositis causes heliotrope rash and
Gottron papules. Scleroderma causes skin thickening and Raynaud phenomenon.
Question 6: A 70-year-old man presents with progressive difficulty initiating
urination, nocturia, and a weak urinary stream. Digital rectal exam reveals a
smooth, enlarged prostate. Which of the following is the most likely diagnosis?
A. Prostate cancer
B. Benign prostatic hyperplasia
,C. Prostatitis
D. Neurogenic bladder
CORRECT ANSWER: B. Benign prostatic hyperplasia
Rationale: Progressive difficulty initiating urination, nocturia, weak stream, and a
smooth enlarged prostate on DRE are classic for BPH. Prostate cancer typically presents
with a nodular or hard prostate. Prostatitis causes painful urination and fever.
Neurogenic bladder causes retention without prostate enlargement.
Question 7: A 24-year-old woman presents with palpitations, heat intolerance,
weight loss, and exophthalmos. Laboratory tests reveal low TSH and elevated
free T4. Which of the following is the most likely diagnosis?
A. Graves disease
B. Toxic multinodular goiter
C. Thyroiditis
D. Pituitary adenoma
CORRECT ANSWER: A. Graves disease
Rationale: Palpitations, heat intolerance, weight loss, exophthalmos, low TSH, and
elevated free T4 are diagnostic of Graves disease. Exophthalmos is specific to Graves.
Toxic multinodular goiter causes hyperthyroidism without ophthalmopathy. Thyroiditis
causes transient hyperthyroidism. Pituitary adenoma causes elevated TSH.
Question 8: A 60-year-old man presents with crushing substernal chest pain
radiating to the left arm, diaphoresis, and nausea. ECG shows ST elevation in
leads II, III, and aVF. Which of the following is the most likely diagnosis?
A. Anterior myocardial infarction
B. Inferior myocardial infarction
C. Lateral myocardial infarction
D. Posterior myocardial infarction
CORRECT ANSWER: B. Inferior myocardial infarction
Rationale: ST elevation in leads II, III, and aVF indicates inferior wall MI, typically due
to right coronary artery occlusion. Anterior MI shows ST elevation in V1-V4. Lateral MI
shows ST elevation in I, aVL, V5, V6. Posterior MI shows reciprocal ST depression in
V1-V2.
Question 9: A 3-year-old child presents with fever, barking cough, and
inspiratory stridor. Symptoms worsen at night. Which of the following is the
most likely diagnosis?
A. Epiglottitis
B. Croup
C. Bronchiolitis
D. Asthma
, CORRECT ANSWER: B. Croup
Rationale: Fever, barking cough, inspiratory stridor, and worsening at night in a young
child are classic for croup (laryngotracheobronchitis), usually caused by parainfluenza
virus. Epiglottitis causes drooling and tripod positioning. Bronchiolitis causes wheezing
in infants. Asthma causes wheezing without barking cough.
Question 10: A 50-year-old woman presents with a painless breast mass.
Mammography reveals a spiculated mass with microcalcifications. Biopsy
shows ductal carcinoma in situ. Which of the following is the most important
prognostic factor?
A. Tumor size
B. Histologic grade
C. Lymph node status
D. Hormone receptor status
CORRECT ANSWER: B. Histologic grade
Rationale: In ductal carcinoma in situ (DCIS), histologic grade is the most important
prognostic factor for recurrence and progression to invasive disease. Tumor size and
lymph node status are more relevant in invasive cancer. Hormone receptor status guides
treatment but is not the primary prognostic factor in DCIS.
Question 11: A 65-year-old man presents with progressive memory loss,
disorientation, and personality changes over 2 years. MRI shows generalized
cortical atrophy. Which of the following is the most likely diagnosis?
A. Alzheimer disease
B. Vascular dementia
C. Frontotemporal dementia
D. Lewy body dementia
CORRECT ANSWER: A. Alzheimer disease
Rationale: Progressive memory loss, disorientation, personality changes, and
generalized cortical atrophy on MRI are classic for Alzheimer disease. Vascular
dementia has stepwise progression and focal deficits. Frontotemporal dementia presents
with personality changes first but affects frontal/temporal lobes. Lewy body dementia
includes visual hallucinations and parkinsonism.
Question 12: A 40-year-old man presents with recurrent kidney stones, bone
pain, and fatigue. Laboratory tests reveal hypercalcemia, hypophosphatemia,
and elevated PTH. Which of the following is the most likely diagnosis?
A. Primary hyperparathyroidism
B. Malignancy-associated hypercalcemia
C. Vitamin D toxicity
D. Sarcoidosis
Study Guide | Comprehensive Osteopathic Medical
Self-Assessment Exam Prep, COMLEX-USA Review,
Practice Questions, Clinical Reasoning, Osteopathic
Principles, Medical Sciences, Detailed Answers &
Rationales
Question 1: A 45-year-old man presents with sudden onset of severe tearing
chest pain radiating to the back. He is hypertensive and has a history of
Marfan syndrome. Which of the following is the most likely diagnosis?
A. Acute myocardial infarction
B. Aortic dissection
C. Pulmonary embolism
D. Pericarditis
CORRECT ANSWER: B. Aortic dissection
Rationale: Sudden severe tearing chest pain radiating to the back in a hypertensive
patient with Marfan syndrome is classic for aortic dissection. Marfan syndrome
predisposes to cystic medial degeneration of the aorta. MI typically presents with
crushing substernal pain, PE with pleuritic pain and dyspnea, and pericarditis with
positional pain.
Question 2: A 62-year-old woman presents with fatigue, weight gain, cold
intolerance, and constipation. Physical exam reveals dry skin, bradycardia,
and delayed deep tendon reflexes. Which of the following is the most likely
diagnosis?
A. Hyperthyroidism
B. Hypothyroidism
C. Cushing syndrome
D. Adrenal insufficiency
CORRECT ANSWER: B. Hypothyroidism
Rationale: Fatigue, weight gain, cold intolerance, constipation, dry skin, bradycardia, and
delayed deep tendon reflexes are hallmark features of hypothyroidism. Hyperthyroidism
causes weight loss and heat intolerance. Cushing syndrome causes weight gain but with
central obesity and hypertension. Adrenal insufficiency causes hypotension and
hyperpigmentation.
Question 3: A 28-year-old man presents with recurrent episodes of severe
abdominal pain, hypertension, and palpitations. He reports that his urine
turns dark on standing. Which of the following is the most likely diagnosis?
A. Acute intermittent porphyria
B. Pheochromocytoma
C. Lead poisoning
D. Porphyria cutanea tarda
,CORRECT ANSWER: A. Acute intermittent porphyria
Rationale: Acute intermittent porphyria presents with the classic triad of severe
abdominal pain, neuropsychiatric symptoms, and autonomic dysfunction (hypertension,
palpitations). Dark urine on standing is due to porphobilinogen. Pheochromocytoma
causes episodic hypertension but not dark urine. Lead poisoning causes abdominal pain
but with anemia and gingival lead lines. Porphyria cutanea tarda causes photosensitivity,
not abdominal pain.
Question 4: A 55-year-old man with a 40-pack-year smoking history presents
with hemoptysis, weight loss, and a right hilar mass on chest X-ray. Which of
the following is the most likely diagnosis?
A. Squamous cell carcinoma of the lung
B. Adenocarcinoma of the lung
C. Small cell carcinoma of the lung
D. Mesothelioma
CORRECT ANSWER: A. Squamous cell carcinoma of the lung
Rationale: Squamous cell carcinoma is strongly associated with smoking, typically
presents as a central/hilar mass, and commonly causes hemoptysis due to cavitation
and airway involvement. Adenocarcinoma is more peripheral. Small cell carcinoma is
also central but is characterized by rapid growth and early metastasis. Mesothelioma is
associated with asbestos exposure and presents with pleural thickening.
Question 5: A 32-year-old woman presents with a butterfly-shaped facial rash,
photosensitivity, oral ulcers, and arthralgias. Laboratory tests reveal anemia,
thrombocytopenia, and positive ANA. Which of the following is the most likely
diagnosis?
A. Rheumatoid arthritis
B. Systemic lupus erythematosus
C. Dermatomyositis
D. Scleroderma
CORRECT ANSWER: B. Systemic lupus erythematosus
Rationale: Malar (butterfly) rash, photosensitivity, oral ulcers, arthralgias, and cytopenias
with positive ANA are diagnostic criteria for SLE. Rheumatoid arthritis primarily causes
symmetric joint deformities without rash. Dermatomyositis causes heliotrope rash and
Gottron papules. Scleroderma causes skin thickening and Raynaud phenomenon.
Question 6: A 70-year-old man presents with progressive difficulty initiating
urination, nocturia, and a weak urinary stream. Digital rectal exam reveals a
smooth, enlarged prostate. Which of the following is the most likely diagnosis?
A. Prostate cancer
B. Benign prostatic hyperplasia
,C. Prostatitis
D. Neurogenic bladder
CORRECT ANSWER: B. Benign prostatic hyperplasia
Rationale: Progressive difficulty initiating urination, nocturia, weak stream, and a
smooth enlarged prostate on DRE are classic for BPH. Prostate cancer typically presents
with a nodular or hard prostate. Prostatitis causes painful urination and fever.
Neurogenic bladder causes retention without prostate enlargement.
Question 7: A 24-year-old woman presents with palpitations, heat intolerance,
weight loss, and exophthalmos. Laboratory tests reveal low TSH and elevated
free T4. Which of the following is the most likely diagnosis?
A. Graves disease
B. Toxic multinodular goiter
C. Thyroiditis
D. Pituitary adenoma
CORRECT ANSWER: A. Graves disease
Rationale: Palpitations, heat intolerance, weight loss, exophthalmos, low TSH, and
elevated free T4 are diagnostic of Graves disease. Exophthalmos is specific to Graves.
Toxic multinodular goiter causes hyperthyroidism without ophthalmopathy. Thyroiditis
causes transient hyperthyroidism. Pituitary adenoma causes elevated TSH.
Question 8: A 60-year-old man presents with crushing substernal chest pain
radiating to the left arm, diaphoresis, and nausea. ECG shows ST elevation in
leads II, III, and aVF. Which of the following is the most likely diagnosis?
A. Anterior myocardial infarction
B. Inferior myocardial infarction
C. Lateral myocardial infarction
D. Posterior myocardial infarction
CORRECT ANSWER: B. Inferior myocardial infarction
Rationale: ST elevation in leads II, III, and aVF indicates inferior wall MI, typically due
to right coronary artery occlusion. Anterior MI shows ST elevation in V1-V4. Lateral MI
shows ST elevation in I, aVL, V5, V6. Posterior MI shows reciprocal ST depression in
V1-V2.
Question 9: A 3-year-old child presents with fever, barking cough, and
inspiratory stridor. Symptoms worsen at night. Which of the following is the
most likely diagnosis?
A. Epiglottitis
B. Croup
C. Bronchiolitis
D. Asthma
, CORRECT ANSWER: B. Croup
Rationale: Fever, barking cough, inspiratory stridor, and worsening at night in a young
child are classic for croup (laryngotracheobronchitis), usually caused by parainfluenza
virus. Epiglottitis causes drooling and tripod positioning. Bronchiolitis causes wheezing
in infants. Asthma causes wheezing without barking cough.
Question 10: A 50-year-old woman presents with a painless breast mass.
Mammography reveals a spiculated mass with microcalcifications. Biopsy
shows ductal carcinoma in situ. Which of the following is the most important
prognostic factor?
A. Tumor size
B. Histologic grade
C. Lymph node status
D. Hormone receptor status
CORRECT ANSWER: B. Histologic grade
Rationale: In ductal carcinoma in situ (DCIS), histologic grade is the most important
prognostic factor for recurrence and progression to invasive disease. Tumor size and
lymph node status are more relevant in invasive cancer. Hormone receptor status guides
treatment but is not the primary prognostic factor in DCIS.
Question 11: A 65-year-old man presents with progressive memory loss,
disorientation, and personality changes over 2 years. MRI shows generalized
cortical atrophy. Which of the following is the most likely diagnosis?
A. Alzheimer disease
B. Vascular dementia
C. Frontotemporal dementia
D. Lewy body dementia
CORRECT ANSWER: A. Alzheimer disease
Rationale: Progressive memory loss, disorientation, personality changes, and
generalized cortical atrophy on MRI are classic for Alzheimer disease. Vascular
dementia has stepwise progression and focal deficits. Frontotemporal dementia presents
with personality changes first but affects frontal/temporal lobes. Lewy body dementia
includes visual hallucinations and parkinsonism.
Question 12: A 40-year-old man presents with recurrent kidney stones, bone
pain, and fatigue. Laboratory tests reveal hypercalcemia, hypophosphatemia,
and elevated PTH. Which of the following is the most likely diagnosis?
A. Primary hyperparathyroidism
B. Malignancy-associated hypercalcemia
C. Vitamin D toxicity
D. Sarcoidosis
