NSG 526 – Differential Diagnosis Questions
& Verified Answers with Rationale Latest
Edition 2026/2027
Question 1
A 45-year-old female presents to the advanced practice nurse
complaining of recurrent, severe headaches occurring 2 to 3 times per
week, typically localized to the left frontotemporal region. The
headaches are throbbing in nature, moderate-to-severe in intensity, and
accompanied by nausea and marked photophobia. Each episode lasts
between 12 and 24 hours and is exacerbated by routine physical activity.
Which diagnosis is most consistent with this clinical presentation?
A. Tension-type headache
B. Cluster headache
C. Migraine headache without aura
D. Temporal arteritis
CORRECT ANSWER: C
RATIONALE: Migraine headaches are characterized by unilateral,
throbbing pain of moderate-to-severe intensity lasting 4 to 72 hours,
aggravated by physical activity, and accompanied by autonomic
symptoms such as nausea, photophobia, or phonophobia. Tension
headaches are typically bilateral and pressure-like, whereas cluster
headaches present with excruciating unilateral periorbital pain
accompanied by ipsilateral autonomic signs and much shorter durations.
Question 2
A 68-year-old male presents with a 3-month history of progressive,
painless jaundice, dark urine, pale stools, and an unintentional weight
loss of 15 pounds. Physical examination reveals a non-tender, palpable
gallbladder in the right upper quadrant (Courvoisier's law). Which
,condition is the most likely underlying diagnosis requiring urgent
specialist referral?
A. Cholelithiasis with acute cholecystitis
B. Pancreatic head adenocarcinoma
C. Alcoholic cirrhosis
D. Acute viral hepatitis A
CORRECT ANSWER: B
RATIONALE: Painless jaundice accompanied by weight loss and a
palpable, non-tender gallbladder (Courvoisier sign) is a classic
presentation of a malignant obstruction of the biliary tree, most
commonly adenocarcinoma of the head of the pancreas. Cholelithiasis
typically presents with biliary colic and a tender right upper quadrant
(Murphy's sign), while viral hepatitis presents with acute systemic
symptoms and elevated transaminases rather than progressive
obstructive jaundice.
Question 3
A 22-year-old college student presents with a 4-day history of sore
throat, profound fatigue, low-grade fever, and posterior cervical
lymphadenopathy. Physical examination reveals enlarged, erythematous
tonsils with a gray-white exudate and mild splenomegaly. Which
diagnostic test is most specific for confirming the suspected primary
differential diagnosis?
A. Rapid streptococcal antigen test (Strep screen)
B. Heterophile antibody test (Monospot) or Epstein-Barr virus
(EBV) serology
C. Throat culture for Neisseria gonorrhoeae
D. Complete blood count with peripheral smear for blast cells
CORRECT ANSWER: B
,RATIONALE: The clinical triad of severe fatigue, pharyngitis, and
posterior cervical lymphadenopathy combined with splenomegaly
strongly suggests infectious mononucleosis caused by Epstein-Barr virus
(EBV). The Monospot test or specific EBV viral capsid antigen (VCA)
antibodies confirm the diagnosis. A rapid strep test targets group A
Streptococcus, which typically presents without marked generalized
lymphadenopathy or splenomegaly.
Question 4
A 54-year-old male with a 30 pack-year smoking history presents with a
2-month history of a persistent, hacking cough, occasional blood-tinged
sputum, and dyspnea. He also notes a 10-pound weight loss. Chest
radiography reveals a central 3 cm hilar mass with ipsilateral mediastinal
lymphadenopathy. Which diagnosis is highest on the differential list?
A. Community-acquired lobar pneumonia
B. Squamous cell carcinoma of the lung
C. Idiopathic pulmonary fibrosis
D. Pulmonary sarcoidosis
CORRECT ANSWER: B
RATIONALE: Squamous cell carcinoma is typically centrally located
near the hilum, strongly associated with smoking, and frequently
presents with cough, hemoptysis, and weight loss. While pneumonia can
cause cough and hemoptysis, it presents with acute fever, purulent
sputum, and focal consolidation rather than a chronic hilar mass in a
smoker.
Question 5
A 32-year-old female presents with episodic shortness of breath, a dry
nocturnal cough, and chest tightness that are consistently triggered by
exercise and exposure to cold air. Spirometry demonstrates a post-
bronchodilator improvement in forced expiratory volume in one second
, (FEV1) of 15% and 200 mL. Which diagnosis is established by these
findings?
A. Chronic obstructive pulmonary disease (COPD)
B. Bronchial asthma
C. Congestive heart failure
D. Pulmonary embolism
CORRECT ANSWER: B
RATIONALE: Reversible obstructive airflow limitation (demonstrated
by a significant FEV1 increase of greater than 12% and 200 mL after
bronchodilator administration) combined with classic triggers like
exercise and cold air confirms bronchial asthma. COPD typically
presents in older patients with a heavy smoking history and fixed, non-
reversible airflow obstruction.
Question 6
A 60-year-old male presents with acute onset of severe, tearing chest
pain radiating straight through to his back between the scapulae. His
medical history is significant for poorly controlled chronic hypertension.
On examination, his blood pressure is 180/100 mmHg in the right arm
and 130/70 mmHg in the left arm. Which emergent condition must be
immediately ruled out?
A. Acute ST-elevation myocardial infarction (STEMI)
B. Acute aortic dissection
C. Pulmonary embolism
D. Acute pericarditis
CORRECT ANSWER: B
RATIONALE: Acute, tearing chest pain radiating to the back,
accompanied by a significant blood pressure differential between the
upper extremities and a history of hypertension, is the hallmark
presentation of an aortic dissection (Stanford Type A or B). While
& Verified Answers with Rationale Latest
Edition 2026/2027
Question 1
A 45-year-old female presents to the advanced practice nurse
complaining of recurrent, severe headaches occurring 2 to 3 times per
week, typically localized to the left frontotemporal region. The
headaches are throbbing in nature, moderate-to-severe in intensity, and
accompanied by nausea and marked photophobia. Each episode lasts
between 12 and 24 hours and is exacerbated by routine physical activity.
Which diagnosis is most consistent with this clinical presentation?
A. Tension-type headache
B. Cluster headache
C. Migraine headache without aura
D. Temporal arteritis
CORRECT ANSWER: C
RATIONALE: Migraine headaches are characterized by unilateral,
throbbing pain of moderate-to-severe intensity lasting 4 to 72 hours,
aggravated by physical activity, and accompanied by autonomic
symptoms such as nausea, photophobia, or phonophobia. Tension
headaches are typically bilateral and pressure-like, whereas cluster
headaches present with excruciating unilateral periorbital pain
accompanied by ipsilateral autonomic signs and much shorter durations.
Question 2
A 68-year-old male presents with a 3-month history of progressive,
painless jaundice, dark urine, pale stools, and an unintentional weight
loss of 15 pounds. Physical examination reveals a non-tender, palpable
gallbladder in the right upper quadrant (Courvoisier's law). Which
,condition is the most likely underlying diagnosis requiring urgent
specialist referral?
A. Cholelithiasis with acute cholecystitis
B. Pancreatic head adenocarcinoma
C. Alcoholic cirrhosis
D. Acute viral hepatitis A
CORRECT ANSWER: B
RATIONALE: Painless jaundice accompanied by weight loss and a
palpable, non-tender gallbladder (Courvoisier sign) is a classic
presentation of a malignant obstruction of the biliary tree, most
commonly adenocarcinoma of the head of the pancreas. Cholelithiasis
typically presents with biliary colic and a tender right upper quadrant
(Murphy's sign), while viral hepatitis presents with acute systemic
symptoms and elevated transaminases rather than progressive
obstructive jaundice.
Question 3
A 22-year-old college student presents with a 4-day history of sore
throat, profound fatigue, low-grade fever, and posterior cervical
lymphadenopathy. Physical examination reveals enlarged, erythematous
tonsils with a gray-white exudate and mild splenomegaly. Which
diagnostic test is most specific for confirming the suspected primary
differential diagnosis?
A. Rapid streptococcal antigen test (Strep screen)
B. Heterophile antibody test (Monospot) or Epstein-Barr virus
(EBV) serology
C. Throat culture for Neisseria gonorrhoeae
D. Complete blood count with peripheral smear for blast cells
CORRECT ANSWER: B
,RATIONALE: The clinical triad of severe fatigue, pharyngitis, and
posterior cervical lymphadenopathy combined with splenomegaly
strongly suggests infectious mononucleosis caused by Epstein-Barr virus
(EBV). The Monospot test or specific EBV viral capsid antigen (VCA)
antibodies confirm the diagnosis. A rapid strep test targets group A
Streptococcus, which typically presents without marked generalized
lymphadenopathy or splenomegaly.
Question 4
A 54-year-old male with a 30 pack-year smoking history presents with a
2-month history of a persistent, hacking cough, occasional blood-tinged
sputum, and dyspnea. He also notes a 10-pound weight loss. Chest
radiography reveals a central 3 cm hilar mass with ipsilateral mediastinal
lymphadenopathy. Which diagnosis is highest on the differential list?
A. Community-acquired lobar pneumonia
B. Squamous cell carcinoma of the lung
C. Idiopathic pulmonary fibrosis
D. Pulmonary sarcoidosis
CORRECT ANSWER: B
RATIONALE: Squamous cell carcinoma is typically centrally located
near the hilum, strongly associated with smoking, and frequently
presents with cough, hemoptysis, and weight loss. While pneumonia can
cause cough and hemoptysis, it presents with acute fever, purulent
sputum, and focal consolidation rather than a chronic hilar mass in a
smoker.
Question 5
A 32-year-old female presents with episodic shortness of breath, a dry
nocturnal cough, and chest tightness that are consistently triggered by
exercise and exposure to cold air. Spirometry demonstrates a post-
bronchodilator improvement in forced expiratory volume in one second
, (FEV1) of 15% and 200 mL. Which diagnosis is established by these
findings?
A. Chronic obstructive pulmonary disease (COPD)
B. Bronchial asthma
C. Congestive heart failure
D. Pulmonary embolism
CORRECT ANSWER: B
RATIONALE: Reversible obstructive airflow limitation (demonstrated
by a significant FEV1 increase of greater than 12% and 200 mL after
bronchodilator administration) combined with classic triggers like
exercise and cold air confirms bronchial asthma. COPD typically
presents in older patients with a heavy smoking history and fixed, non-
reversible airflow obstruction.
Question 6
A 60-year-old male presents with acute onset of severe, tearing chest
pain radiating straight through to his back between the scapulae. His
medical history is significant for poorly controlled chronic hypertension.
On examination, his blood pressure is 180/100 mmHg in the right arm
and 130/70 mmHg in the left arm. Which emergent condition must be
immediately ruled out?
A. Acute ST-elevation myocardial infarction (STEMI)
B. Acute aortic dissection
C. Pulmonary embolism
D. Acute pericarditis
CORRECT ANSWER: B
RATIONALE: Acute, tearing chest pain radiating to the back,
accompanied by a significant blood pressure differential between the
upper extremities and a history of hypertension, is the hallmark
presentation of an aortic dissection (Stanford Type A or B). While
