Pathology Test 1 — Questions and Answers

Question 1: A 16-year-old boy is undergoing evaluation for jaundice. Laboratory studies show normal hepatic enzyme activities, a negative direct antiglobulin (Coombs) test, increased mean corpuscular hemoglobin concentration, and increased osmotic fragility of erythrocytes. Which of the following types of erythrocyte is most likely to be seen on a peripheral blood smear?

Ovalocyte
Schistocyte
Spherocyte (Correct answer)
Target cell
Teardrop cell

Correct answer: Spherocyte

The combination of jaundice, normal hepatic enzymes, negative Coombs test, increased mean corpuscular hemoglobin concentration (MCHC), and increased osmotic fragility is highly characteristic of hereditary spherocytosis. This genetic disorder causes red blood cells to be spherical, rigid, and more fragile, leading to their premature destruction in the spleen. Spherocytes are the hallmark finding on a peripheral blood smear in this condition.

Question 2: A 34-year-old woman is brought to the emergency department by her husband because of confusion for 2 hours. She is unconscious on arrival. Her husband says that she has a 1-year history of episodes of nervousness, light-headedness, and dizziness that resolve after she eats a meal. Physical examination shows no other abnormalities. Her serum glucose concentration is 25 mg/dL. After an intravenous infusion of 0.9% saline and glucose, she regains consciousness. Which of the following is the most likely diagnosis?

Cushing syndrome
Insulinoma (Correct answer)
Multiple endocrine neoplasia syndrome
Pancreatic gastrinoma
Pheochromocytoma

Correct answer: Insulinoma

The patient's presentation of recurrent episodes of neuroglycopenic symptoms (confusion, unconsciousness, nervousness, light-headedness) that resolve with food intake, coupled with a critically low serum glucose (25 mg/dL), is classic for an insulinoma. An insulinoma is a tumor of the pancreatic beta cells that secretes excessive insulin, leading to profound hypoglycemia. The resolution of symptoms with glucose administration further supports this diagnosis.

Question 3: A 60-year-old man comes to the physician because of a cough for 2 months. He says that he has noticed changes in his face during the past 3 months. He has smoked 2 packs of cigarettes daily for 30 years. His temperature is 37°C (98.6°F), pulse is 72/min, respirations are 19/min, and blood pressure is 160/95 mm Hg. Physical examination shows a round face, central obesity, excess fat over the posterior neck and back, and abdominal striae. His serum calcium concentration is 9 mg/dL. Urine dipstick of a clean-catch midstream specimen shows 3+ glucose. A chest x-ray shows a 3-cm mass in the left upper lobe with enlargement of hilar nodes. A biopsy specimen of the mass shows small cell carcinoma. Further serum studies are most likely to show an increased concentration of which of the following proteins?

Adrenocorticotropic hormone (Correct answer)
Epidermal growth factor
IgM
Parathyroid hormone-related protein
Serotonin

Correct answer: Adrenocorticotropic hormone

The patient presents with classic signs of Cushing syndrome (round face, central obesity, 'buffalo hump,' abdominal striae, hypertension, hyperglycemia) in conjunction with a lung mass diagnosed as small cell carcinoma. Small cell lung carcinoma is well-known for its paraneoplastic syndromes, particularly the ectopic production of Adrenocorticotropic Hormone (ACTH). This ectopic ACTH stimulates the adrenal glands to produce excess cortisol, leading to Cushing syndrome.

Question 4: A 45-year-old man with chronic pancreatitis has a 9-kg (20-lb) weight loss and diarrhea. Analysis of a 24-hour stool sample shows 28 g of fat. A deficiency of which of the following enzymes is the most likely cause?

Amylase
Carboxypeptidase
Lactase
Lipase (Correct answer)
Lipoprotein lipase

Correct answer: Lipase

Chronic pancreatitis leads to exocrine pancreatic insufficiency, meaning the pancreas cannot produce sufficient digestive enzymes. The presence of significant fat in the stool (steatorrhea), along with weight loss and diarrhea, is a direct result of impaired fat digestion and absorption. Pancreatic lipase is the primary enzyme responsible for breaking down dietary fats, so its deficiency is the most likely cause of the patient's symptoms.

Question 5: A 70-year-old man comes to the physician because of a 2-year history of shortness of breath and progressive chest pain. He worked as a carpenter installing insulation from the ages of 21 to 31 years. Physical examination shows absent breath sounds and dullness to percussion over the right lung base. A chest x-ray shows thickened pleura on the right side and a medium-sized pleural effusion. Pleural fluid studies show a protein concentration greater than 3 g/dL (N=1–2). A pleural biopsy specimen shows spindle cells. Which of the following is the most likely diagnosis?

Emphysema
Lung abscess
Mesothelioma (Correct answer)
Small cell carcinoma of the lung
Viral pneumonia

Correct answer: Mesothelioma

The patient's history of asbestos exposure (carpenter installing insulation) combined with progressive shortness of breath, chest pain, thickened pleura, and a pleural effusion is highly suggestive of mesothelioma. The pleural fluid with high protein and the biopsy showing spindle cells are characteristic pathological features of this aggressive malignancy arising from the pleura, which is strongly linked to asbestos exposure.

Question 6: A previously healthy 28-year-old man dies in a motor vehicle collision. At autopsy, the kidneys are enlarged bilaterally, and each weighs 3 kg. The external surface of the kidneys appears to be a mass of cysts. Microscopic examination of the kidneys shows intact nephrons interspersed between the cysts. The most likely cause of these changes in the kidneys involves which of the following modes of inheritance?

Autosomal recessive
Autosomal dominant (Correct answer)
Chromosome 22q11.2 deletion
Mitochondrial
X-linked

Correct answer: Autosomal dominant

The autopsy findings of massively enlarged, cystic kidneys with intact nephrons in a young adult are characteristic of Autosomal Dominant Polycystic Kidney Disease (ADPKD). This genetic disorder, caused by mutations in PKD1 or PKD2 genes, leads to the progressive development of numerous fluid-filled cysts that eventually destroy renal parenchyma. It is the most common inherited kidney disease and typically manifests in adulthood.

Question 7: An autopsy of a 24-year-old woman shows pleuritis, membranous thickening of glomerular capillary walls, concentric rings of collagen around splenic arterioles, and excrescences on the underside of the mitral valve. Analysis of blood is most likely to show which of the following?

Antinuclear antibody (Correct answer)
Increased C3 concentration
Lymphocytosis
Monoclonal gammopathy
Positive bacterial culture

Correct answer: Antinuclear antibody

The constellation of findings—pleuritis, membranous glomerulonephritis, 'onion-skinning' of splenic arterioles, and Libman-Sacks endocarditis (excrescences on the mitral valve)—are all classic pathological hallmarks of Systemic Lupus Erythematosus (SLE). SLE is an autoimmune disease characterized by the production of various autoantibodies, with antinuclear antibodies (ANA) being present in nearly all patients and serving as a key diagnostic marker.

Question 8: At autopsy, the heart of a 30-year-old man weighs 550 g. The left ventricle is dilated and hypertrophied. The aortic root is markedly dilated, and the aortic valve cusps are intact. The external iliac arteries contain irregular, focal cystic areas within the media with pools of mucopolysaccharide and fraying fragmentation of the elastica. Which of the following is the most likely diagnosis?

Ankylosing spondylitis
Cardiovascular syphilis
Osteogenesis imperfecta, type II (recessive)
Systemic lupus erythematosus
Marfan syndrome (Correct answer)

Correct answer: Marfan syndrome

The combination of a dilated and hypertrophied left ventricle, markedly dilated aortic root, and specific arterial changes (cystic medial necrosis with mucopolysaccharide pools and elastica fragmentation) in a young man is highly indicative of Marfan syndrome. This genetic disorder affects connective tissue due to a mutation in the FBN1 gene, leading to characteristic cardiovascular manifestations like aortic root dilation and dissection.

Question 9: A 10-year-old boy is brought to the emergency department 15 minutes after he sustained abdominal injuries in a motor vehicle collision. Physical examination shows massive ecchymoses over the trunk and abdomen. A CT scan shows internal bleeding. The patient undergoes operative removal of a portion of the lower left lobe of the lung, the left lobe of the liver, half of the left kidney, half of the spleen, and a 2-foot section of the small intestine. Assuming survival of the acute trauma, which of the following organs is likely to have the most complete regeneration in this patient?

Kidney
Liver (Correct answer)
Lung
Small intestine
Spleen

Correct answer: Liver

Among the listed organs, the liver possesses a remarkable capacity for regeneration, capable of restoring its mass and function even after significant tissue loss. This regenerative ability is primarily due to the proliferation of existing hepatocytes. In contrast, the kidney, lung, spleen, and small intestine have more limited regenerative capabilities, typically undergoing repair by fibrosis or partial restoration rather than complete regeneration of lost tissue.

Question 10: A previously healthy 2-year-old boy is brought to the emergency department because of bloody stools for 2 days. His vital signs are within normal limits. Abdominal examination shows no abnormalities. Laboratory studies show: Hemoglobin 11 g/dL Hematocrit 37% Leukocyte count 9500/mm3 Platelet count 250,000/mm3 Test of the stool for occult blood is positive. During an emergency laparotomy, a 3 × 2-cm protrusion is found on the antimesenteric border of the small intestine approximately 50 cm proximal to the ileocecal valve. Which of the following is the most likely cause of this patient’s condition?

Carcinoid tumor
Ectopic adrenal gland
Meckel diverticulum (Correct answer)
Retrocecal appendix
Umbilical hernia

Correct answer: Meckel diverticulum

The patient's presentation of painless bloody stools in a 2-year-old boy, combined with the surgical finding of a 3x2 cm protrusion on the antimesenteric border of the small intestine approximately 50 cm proximal to the ileocecal valve, is classic for a Meckel diverticulum. This congenital anomaly is a remnant of the omphalomesenteric duct, and often contains ectopic gastric or pancreatic tissue that can cause ulceration and bleeding.

Question 11: A 50-year-old man comes to the physician because of progressive fatigue and darkening of his skin during the past 2 years. He has not spent much time in the sun during this period. Physical examination shows slate-gray skin and hepatomegaly. Serum studies show: Ferritin 500 ng/mL Transferrin saturation 70% (N=20%–60%) AST 41 U/L ALT 45 U/L A liver biopsy specimen stained with Prussian blue is positive. Which of the following best describes the altered function of mutated HFE gene product in this patient?

Decreased lysozyme synthesis
Decreased NADPH production
Decreased oxidase activity
Increased fatty acid absorption
Increased iron absorption (Correct answer)

Correct answer: Increased iron absorption

The patient's symptoms of fatigue, skin darkening, hepatomegaly, elevated ferritin, and high transferrin saturation, along with positive Prussian blue staining on liver biopsy (indicating iron deposition), are classic for hemochromatosis. This condition is most commonly caused by a mutation in the HFE gene, which leads to inappropriately increased iron absorption from the gastrointestinal tract, resulting in systemic iron overload and organ damage.

Question 12: A 69-year-old woman is brought to the emergency department because of progressive difficulty with her vision during the past day. She also has a 3-month history of headache and scalp tenderness. She says, “This morning I had a blind spot in my left eye, and it just grew bigger as the day went on.” Her vital signs are within normal limits. Ophthalmologic examination shows visual acuity of 20/100 in the left eye and 20/40 in the right eye. Physical examination shows no other abnormalities. Laboratory studies show an erythrocyte sedimentation rate of 129 mm/h. Which of the following is the most likely diagnosis?

Acute occipital infarction
Glaucoma
Left carotid dissection
Systemic lupus erythematosus
Temporal arteritis (Correct answer)

Correct answer: Temporal arteritis

The patient's age, new-onset headache, scalp tenderness, and acute, progressive monocular vision loss are highly suggestive of giant cell (temporal) arteritis. The markedly elevated erythrocyte sedimentation rate (ESR) strongly supports this diagnosis, as it is a hallmark of this systemic vasculitis affecting large and medium-sized arteries, which can lead to permanent blindness if untreated.

Question 13: A 30-year-old woman comes to the physician because of a 2-month history of unsteady gait and numbness of both legs. Eight years ago, she underwent resection of the terminal ileum because of severe Crohn disease. Physical examination shows mild spastic weakness. Sensation to pinprick, vibration, and fine touch is decreased in the upper and lower extremities. A deficiency of which of the following is the most likely underlying cause of these findings?

Folic acid
Iron
Protein
Vitamin B1 (thiamine)
Vitamin B12 (cobalamin) (Correct answer)

Correct answer: Vitamin B12 (cobalamin)

Resection of the terminal ileum, as seen in severe Crohn disease, significantly impairs the absorption of vitamin B12 (cobalamin), which is the primary site for its absorption. A deficiency in vitamin B12 can lead to subacute combined degeneration of the spinal cord, causing demyelination of the dorsal columns (impaired vibration/proprioception) and lateral corticospinal tracts (spastic weakness), explaining the patient's neurological symptoms.

Question 14: A 10-month-old girl is brought to the physician by her father because she does not seem to be gaining weight despite an increased appetite. He says that she passes 8 to 10 stools daily. She has no history of major medical illness, but during the past winter she had several infections of the ear and respiratory tract that were treated with antibiotics. She appears malnourished but is in no apparent distress. She is at the 5th percentile for length and weight. Diffuse crackles are heard over the lower lung fields on auscultation. Her sweat chloride concentration is 69 mmol/L. Which of the following is the most likely underlying cause of these findings?

Abnormal cystic fibrosis transmembrane conductance regulator gene function (Correct answer)
Acid phosphatase deficiency
Atypical conjugation of arylsulfatase A, B, and C
α-l-Fucosidase deficiency
Impaired production of phosphatidylcholine (lecithins)

Correct answer: Abnormal cystic fibrosis transmembrane conductance regulator gene function

The combination of failure to thrive despite increased appetite, steatorrhea (frequent stools), recurrent respiratory infections (crackles), and a high sweat chloride concentration (69 mmol/L is diagnostic) is pathognomonic for cystic fibrosis. This genetic disorder is caused by mutations in the CFTR gene, leading to abnormal function of the cystic fibrosis transmembrane conductance regulator protein, which impairs chloride transport and results in thick, viscous secretions.

Question 15: The chairman of a large pathology department is planning for the personnel that he will need in the future. He is trying to decide whether his department will have more need for a dermatopathologist or a cytopathologist. He decides against the cytopathologist because he expects the number of Pap smears to fall off dramatically in the future. The development of which of the following is the most likely reason for this expected decrease in the number of Pap smears?

Highly effective oral drugs that prevent dysplasia of the uterine cervix
Operative guidelines requiring the amputation of the cervix for mild squamous dysplasia
Three-dimensional conformal radiation treatment
A vaccine against high-risk human papillomaviruses (Correct answer)
Vaginal suppositories that markedly reduce the number of bacteria in the vagina

Correct answer: A vaccine against high-risk human papillomaviruses

Pap smears are a screening tool for cervical dysplasia and cancer, which are primarily caused by persistent infection with high-risk human papillomaviruses (HPV). The development and widespread use of HPV vaccines, which protect against the most common oncogenic HPV types, significantly reduce the incidence of HPV infection and subsequent cervical pathology. Consequently, as vaccinated cohorts age, the need for Pap smear screening is expected to decrease.

Question 16: A 22-year-old woman comes to the physician because of a 1-day history of fever and right flank pain. Her temperature is 39°C (102.2°F). Physical examination shows right flank tenderness. Urinalysis shows bacteria, numerous WBC/hpf, and WBC casts. Complete blood count shows leukocytosis. Which of the following is the most likely diagnosis?

Cervicitis
Cystitis
Pyelonephritis (Correct answer)
Urethritis
Vaginitis

Correct answer: Pyelonephritis

The patient's presentation with fever, flank pain, and tenderness, along with urinalysis findings of bacteria, numerous white blood cells, and specifically white blood cell casts, is classic for acute pyelonephritis. WBC casts indicate inflammation within the renal tubules, localizing the infection to the kidney parenchyma rather than just the bladder or urethra. Leukocytosis further supports a systemic inflammatory response.

Question 17: A previously healthy 30-year-old woman comes to the physician for a follow-up visit after a chest x-ray shows bilateral hilar adenopathy and a calcified 1-cm nodule in the periphery of the right lower lobe. Physical examination shows no abnormalities. Her serum calcium concentration is 11 mg/dL. Pulmonary function test results are within normal limits. Bronchoscopy with bronchoalveolar lavage yields 40% lymphocytes and 60% macrophages, with a CD4:CD8 T-lymphocyte ratio of 10:1. A bronchial biopsy specimen shows a nonnecrotizing granuloma. Specially stained sections of a bronchial biopsy specimen show no acid-fast bacilli or fungi. Cultures of lung tissue grow no organisms. Which of the following is the most likely diagnosis?

Coccidioidomycosis
Hypersensitivity pneumonitis
Sarcoidosis (Correct answer)
Silicosis
Tuberculosis
Granulomatosis with polyangiitis

Correct answer: Sarcoidosis

The classic triad of bilateral hilar adenopathy, noncaseating granulomas on biopsy, and elevated serum calcium in a young adult, along with a high CD4:CD8 ratio in bronchoalveolar lavage fluid, is highly characteristic of sarcoidosis. The exclusion of infectious causes (negative stains and cultures for acid-fast bacilli and fungi) further supports this diagnosis, as sarcoidosis is a diagnosis of exclusion for noncaseating granulomatous disease.

Question 18: A 3-year-old girl is brought to the emergency department 30 minutes after she tripped and fell. Physical examination shows blue sclera and edema and tenderness over the right proximal lower extremity. X-rays show a fracture of the right femur, as well as several fractures of varying ages of the left clavicle, right humerus, and right fibula. Which of the following is the most likely diagnosis?

Achondroplasia
Ehlers-Danlos syndrome
Hurler syndrome
Marfan syndrome
Osteogenesis imperfecta (Correct answer)

Correct answer: Osteogenesis imperfecta

The combination of blue sclera and recurrent fractures from minimal trauma, especially fractures of varying ages, is pathognomonic for osteogenesis imperfecta (OI). This genetic disorder is caused by defects in type I collagen synthesis, leading to brittle bones that fracture easily. Blue sclera occurs because the thin sclera allows the underlying choroidal veins to show through.

Question 19: A 50-year-old man with type 2 diabetes mellitus has a 1-week history of swelling and a feeling “like electric shocks” in his right wrist and hand. He is a computer programmer, and the shock-like feeling is worse with activity and at the end of the day. There is atrophy of the right thenar eminence. With the hand hyperextended, pain radiates into the fingers when the examiner taps the flexor surface of the distal wrist. Which of the following nerves is most likely compressed in this patient?

Deep radial
Median (Correct answer)
Musculocutaneous
Radial ulnar
Superficial radial

Correct answer: Median

The symptoms of 'electric shocks' (paresthesias) radiating into the fingers, worsening with activity, thenar eminence atrophy, and a positive Tinel's sign at the wrist are classic indicators of carpal tunnel syndrome. This condition involves compression of the median nerve as it passes through the carpal tunnel in the wrist, often exacerbated by repetitive hand movements and common in patients with diabetes due to nerve susceptibility.

Question 20: A 3-year-old boy is brought to the physician because of a 2-day history of fever and an itchy rash. The rash began on his face and then spread to his trunk, arms, and legs. Several children at his day-care center have had similar symptoms. His temperature is 38.9°C (102°F), pulse is 100/min, respirations are 20/min, and blood pressure is 110/60 mm Hg. Physical examination shows multiple red papules and vesicles over the face, trunk, and upper and lower extremities. Some vesicles contain clear fluid, whereas others are crusted. Which of the following is the most likely causal virus?

Cytomegalovirus
Epstein-Barr virus
Herpes simplex virus 2
Human papillomavirus
Varicella-zoster virus (Correct answer)

Correct answer: Varicella-zoster virus

The clinical presentation of a febrile illness with a highly pruritic rash that starts on the face/trunk and spreads centrifugally, characterized by lesions in various stages of development (papules, vesicles, crusts—'dewdrop on a rose petal' appearance), is classic for varicella (chickenpox). This highly contagious disease is caused by the varicella-zoster virus (VZV) and commonly spreads in settings like day-care centers.

Pathology Test 1

A 16-year-old boy is undergoing evaluation for jaundice.
Laboratory studies show normal hepatic enzyme activities, a negative direct antiglobulin (Coombs) test, increased mean corpuscular hemoglobin concentration, and increased osmotic fragility of erythrocytes.
Which of the following types of erythrocyte is most likely to be seen on a peripheral blood smear?