All questions
Question 1
A 48-year-old man from northern Wisconsin presents with a non-productive cough, fever, and weight loss over the past month. Physical examination reveals several well-demarcated, verrucous skin lesions on his arms. A chest X-ray shows a mass-like infiltrate in the left lung. A biopsy of a skin lesion is obtained.
Which of the following microscopic findings is most likely to be seen in the biopsy specimen?
- Small yeasts within macrophages
- Encapsulated yeasts with narrow-based budding
- Large yeasts with a single, broad-based bud (correct answer)
- Spherules containing endospores
Explanation: The patient's geographic location (Great Lakes region, Wisconsin), combined with pulmonary disease and characteristic wart-like (verrucous) skin lesions, points to blastomycosis. The causative agent, Blastomyces dermatitidis, is a dimorphic fungus. In tissue specimens, it is identified by its characteristic large, round yeast form with a single, broad-based bud. Small yeasts within macrophages are seen in histoplasmosis. Encapsulated yeasts are seen in cryptococcosis. Spherules are seen in coccidioidomycosis.
Question 2
A 38-year-old man with untreated HIV infection is admitted with progressive dyspnea, a dry cough, and fever. His CD4 count is 35 cells/μL. A chest X-ray shows diffuse, bilateral interstitial infiltrates. A bronchoalveolar lavage is performed, and the fluid is stained with methenamine silver.
The silver stain is expected to reveal which of the following characteristic structures?
- Cigar-shaped yeasts
- Saucer-shaped cysts (correct answer)
- Barrel-shaped arthroconidia
- Germ tubes
Explanation: This patient has a classic presentation of Pneumocystis pneumonia (PCP), caused by Pneumocystis jirovecii, in the setting of advanced AIDS. Diagnosis is typically made by identifying the organism in respiratory specimens. Methenamine silver stain is used to visualize the cyst form of P. jirovecii, which appears as characteristic oval, indented, or saucer-shaped structures. Cigar-shaped yeasts are characteristic of Sporothrix schenckii. Arthroconidia are the infectious form of Coccidioides. Germ tubes are formed by Candida albicans.
Question 3
A 22-year-old woman presents with multiple, well-demarcated hypopigmented macules on her upper back and chest that became more noticeable after sun exposure. A KOH preparation of skin scrapings shows a 'spaghetti and meatballs' pattern of hyphae and yeast cells.
The hypopigmentation seen in this condition is caused by the organism's production of an acid that inhibits which of the following enzymes involved in melanin synthesis?
- Phenylalanine hydroxylase
- Tyrosinase (correct answer)
- Homogentisate oxidase
- Lysyl oxidase
Explanation: The patient has tinea versicolor, a superficial fungal infection caused by Malassezia furfur. The characteristic hypopigmentation occurs because the organism produces azelaic acid, a dicarboxylic acid that inhibits tyrosinase. Tyrosinase is the key enzyme in the metabolic pathway that converts tyrosine to melanin. Inhibition of this enzyme leads to decreased melanin production in the affected skin. Phenylalanine hydroxylase deficiency causes phenylketonuria. Homogentisate oxidase deficiency causes alkaptonuria. Lysyl oxidase is involved in collagen cross-linking.
Question 4
A 45-year-old man with a history of HIV infection, who has not been compliant with his antiretroviral therapy, presents with painful swallowing and removable white plaques on his tongue and buccal mucosa. A KOH preparation of a scraping from a lesion is examined under a microscope.
Which of the following microscopic findings is most characteristic of the causative organism?
- Spherules containing endospores
- Pseudohyphae and budding yeasts (correct answer)
- Broad-based budding yeasts
- Nonseptate hyphae with right-angle branching
Explanation: The patient has oral candidiasis (thrush), a common opportunistic infection in individuals with advanced HIV. The causative agent, Candida albicans, is a dimorphic fungus that can exist as both a budding yeast and in a filamentous form. On microscopic examination of clinical specimens, it is characteristically seen as a combination of budding yeasts and pseudohyphae. Spherules with endospores are characteristic of Coccidioides. Broad-based budding yeasts are seen with Blastomyces. Nonseptate hyphae with right-angle branching are characteristic of Mucorales.
Question 5
A 31-year-old man, an amateur cave explorer, presents with a 2-week history of fever, cough, and myalgias. He recently returned from a trip exploring caves in Kentucky. A chest X-ray shows diffuse reticulonodular infiltrates and hilar lymphadenopathy. A bronchoalveolar lavage is performed for diagnosis.
Microscopic examination of the lavage fluid is most likely to reveal which of the following?
- Large spherules filled with endospores
- Broad-based budding yeasts
- Small, oval yeasts within macrophages (correct answer)
- Septate hyphae with acute-angle branching
Explanation: The patient's history of cave exploration (spelunking) in the Ohio/Mississippi River Valley region (Kentucky) is a major risk factor for histoplasmosis, caused by Histoplasma capsulatum. This dimorphic fungus is found in soil contaminated with bat or bird droppings. In tissue samples, such as from a bronchoalveolar lavage, H. capsulatum characteristically appears as small, oval yeasts located intracellularly within macrophages. Spherules are characteristic of Coccidioides. Broad-based budding yeasts are characteristic of Blastomyces. Septate hyphae are characteristic of Aspergillus.
Question 6
A 25-year-old archaeology student develops fever, cough, and arthralgias two weeks after returning from an excavation project in Phoenix, Arizona. A chest X-ray shows a right upper lobe infiltrate. Sputum is sent for fungal culture.
At 25°C, the culture of the causative organism would most likely demonstrate which of the following forms?
- Mold form with arthroconidia (correct answer)
- Cigar-shaped yeast
- Spherule with endospores
- Pseudohyphae
Explanation: The geographic location (Southwestern US) and symptoms are highly suggestive of coccidioidomycosis ('valley fever'), caused by Coccidioides immitis. This is a dimorphic fungus. In the environment and on culture at room temperature (25°C), it grows as a mold consisting of hyphae that fragment into barrel-shaped arthroconidia. In the host's body (at 37°C), it exists as large spherules containing endospores. Cigar-shaped yeasts are characteristic of Sporothrix schenckii in its yeast form. Pseudohyphae are seen with Candida.
Question 7
A 62-year-old woman with poorly controlled type 2 diabetes mellitus presents with altered mental status. Her blood glucose is 650 mg/dL, and an arterial blood gas shows metabolic acidosis. Physical examination reveals a black, necrotic eschar over her right nasal turbinate.
A biopsy of the lesion is taken for microscopic examination. Which of the following findings is most expected?
- Septate hyphae with dichotomous, acute-angle branching
- Broad, nonseptate hyphae with right-angle branching (correct answer)
- Pseudohyphae with budding yeast forms
- Small yeasts contained within macrophages
Explanation: This patient's presentation with diabetic ketoacidosis (DKA) and a black necrotic eschar in the nasal cavity is pathognomonic for rhinocerebral mucormycosis. The causative agents are fungi of the order Mucorales, such as Rhizopus and Mucor species. Histopathologic examination of infected tissue characteristically reveals broad, ribbon-like, nonseptate (or sparsely septate) hyphae that branch at wide, often 90-degree, angles. Acute-angle branching is seen with Aspergillus. Pseudohyphae are seen with Candida. Small yeasts in macrophages are seen with Histoplasma.
Question 8
A 28-year-old man develops profuse, watery, foul-smelling diarrhea, abdominal cramping, and bloating five days after returning from a camping trip where he drank unfiltered stream water. He denies seeing any blood in his stool. Stool analysis reveals pear-shaped, flagellated organisms.
The pathogenesis of this patient's diarrhea is primarily due to which of the following mechanisms?
- Invasion of the colonic mucosa leading to flask-shaped ulcers
- Production of a toxin that increases intracellular cGMP
- Adherence to the small intestinal wall causing villous atrophy and malabsorption (correct answer)
- Toxin-mediated activation of adenylate cyclase
Explanation: The patient's symptoms and history are classic for giardiasis, caused by Giardia lamblia. The primary pathogenic mechanism of Giardia involves the attachment of trophozoites to the epithelial surface of the small intestine. This attachment, along with host immune responses, leads to inflammation, villous blunting (atrophy), and crypt hyperplasia, resulting in malabsorption of fats and carbohydrates and causing the characteristic foul-smelling, fatty diarrhea (steatorrhea). Invasion of colonic mucosa with ulcer formation is characteristic of Entamoeba histolytica. Toxin-mediated increases in cGMP or cAMP are mechanisms of certain bacterial diarrheas (e.g., ETEC, Cholera).
Question 9
A 30-year-old woman returns from a trip to sub-Saharan Africa and presents with cyclical high fevers, chills, and sweats. A peripheral blood smear reveals multiple ring-form trophozoites within some erythrocytes, and some red blood cells are infected with more than one parasite. The patient develops confusion and lapses into a coma.
The severe neurologic manifestations of this infection are primarily attributed to which pathogenic mechanism?
- Formation of a polysaccharide capsule preventing phagocytosis
- Sequestration of infected erythrocytes in cerebral microvasculature (correct answer)
- Release of a neurotoxin that blocks inhibitory neurotransmission
- Chronic granulomatous inflammation in the brain parenchyma
Explanation: The patient has severe, complicated malaria, most likely due to Plasmodium falciparum, which is known for high parasitemia and severe manifestations. A key virulence mechanism of P. falciparum is the expression of proteins on the surface of infected erythrocytes that cause them to adhere to the endothelial lining of capillaries. This sequestration in the microvasculature of vital organs, including the brain, leads to obstruction, ischemia, and inflammation, causing complications like cerebral malaria. The other options describe mechanisms for different pathogens: capsule (Cryptococcus), neurotoxin (Clostridium tetani), and granulomas (Mycobacterium tuberculosis or Taenia solium).
Question 10
A 40-year-old soldier returns from a deployment in Iraq and presents with a 2-month history of intermittent high fevers, weakness, and significant weight loss. Physical examination reveals marked splenomegaly. Laboratory studies show pancytopenia. A bone marrow aspirate is performed.
Microscopic examination of the aspirate is most likely to reveal which of the following?
- Ring-form trophozoites in erythrocytes
- Trypomastigotes in the blood
- Macrophages containing amastigotes (correct answer)
- Spherules containing endospores
Explanation: The patient's symptoms (fever, weight loss), physical findings (splenomegaly), lab results (pancytopenia), and geographic exposure (Middle East) are classic for visceral leishmaniasis (kala-azar), caused by Leishmania donovani. The diagnosis is confirmed by identifying the parasite in tissue samples. The form of Leishmania found within host cells is the amastigote, a small, oval, non-motile form that multiplies within macrophages of the reticuloendothelial system (e.g., bone marrow, spleen, liver). Ring forms are seen in malaria. Trypomastigotes are seen in Chagas disease or African trypanosomiasis. Spherules are seen in coccidioidomycosis.
Question 11
A 25-year-old man from Egypt presents with a complaint of painless terminal hematuria. He reports a history of frequently swimming in the Nile River as a child. Urinalysis confirms the presence of blood and reveals oval-shaped parasite eggs with a prominent terminal spine.
Chronic infection with this organism is a major risk factor for which of the following malignancies?
- Hepatocellular carcinoma
- Transitional cell carcinoma of the bladder
- Cholangiocarcinoma
- Squamous cell carcinoma of the bladder (correct answer)
Explanation: The patient's history, symptoms, and the finding of eggs with a terminal spine are characteristic of urinary schistosomiasis, caused by Schistosoma haematobium. The adult worms live in the venous plexus of the bladder and release eggs that become trapped in the bladder wall. The resulting chronic inflammation, granuloma formation, and fibrosis are a well-established risk factor for developing squamous cell carcinoma of the bladder. Transitional cell carcinoma is the most common type of bladder cancer in the Western world, but it is not the type associated with schistosomiasis. Hepatocellular carcinoma is associated with Schistosoma mansoni and japonicum (due to liver fibrosis), and cholangiocarcinoma is associated with liver flukes like Clonorchis sinensis.
Question 12
A 65-year-old man from Southeast Asia with rheumatoid arthritis is started on high-dose prednisone. Two weeks later, he is admitted to the ICU with gram-negative sepsis and respiratory failure. A stool sample reveals numerous filariform and rhabditiform larvae.
Which feature of this parasite's life cycle best explains the development of overwhelming infection in this immunocompromised patient?
- Ability to form dormant cysts in muscle tissue
- Requirement of an intermediate snail host
- Presence of an autoinfection cycle (correct answer)
- Transmission via ingestion of eggs
Explanation: This patient has Strongyloides hyperinfection syndrome, a life-threatening condition triggered by immunosuppression (in this case, corticosteroids). Strongyloides stercoralis is unique among intestinal nematodes because of its autoinfection cycle. Non-infective rhabditiform larvae can develop into infective filariform larvae within the host's intestine. These larvae can then penetrate the intestinal mucosa or perianal skin to re-enter circulation and establish a new infection, leading to a massive increase in worm burden and dissemination when host immunity is suppressed. Dormant cysts in muscle are characteristic of Trichinella. An intermediate snail host is required for Schistosoma. Transmission via egg ingestion is typical for Ascaris or Enterobius.
Question 13
A 55-year-old man who immigrated from a rural area of Bolivia 20 years ago presents with progressive shortness of breath and difficulty swallowing. An echocardiogram shows dilated cardiomyopathy. A barium swallow study reveals a markedly dilated esophagus.
This patient's condition is most likely caused by a parasite transmitted by which of the following vectors?
- Sandfly
- Tsetse fly
- Reduviid bug (correct answer)
- Aedes mosquito
Explanation: The clinical presentation of dilated cardiomyopathy and megaesophagus in a patient from South America (Bolivia) is highly characteristic of chronic Chagas disease, caused by the protozoan Trypanosoma cruzi. This parasite is transmitted to humans through the feces of the reduviid bug (also known as the 'kissing bug'). The sandfly transmits Leishmania, the tsetse fly transmits Trypanosoma brucei (African sleeping sickness), and the Aedes mosquito transmits viruses like dengue and Zika.
Question 14
A 34-year-old woman with AIDS and a CD4 count of 45 cells/μL is brought to the emergency department due to a severe headache, fever, and neck stiffness. A lumbar puncture is performed. Cerebrospinal fluid (CSF) analysis reveals an elevated opening pressure, increased lymphocytes, low glucose, and high protein. An India ink stain of the CSF is performed.
This special stain is most likely to reveal which of the following?
- Intracellular gram-negative diplococci
- Encapsulated yeasts (correct answer)
- Acid-fast bacilli
- Trophozoites with ingested red blood cells
Explanation: The clinical presentation of meningitis in a patient with a very low CD4 count is highly suggestive of Cryptococcus neoformans infection. C. neoformans is a yeast characterized by a thick polysaccharide capsule. The India ink stain is a classic method used to visualize this capsule in CSF; the ink particles are excluded by the capsule, creating a clear halo around the yeast cells. Gram-negative diplococci suggest Neisseria meningitidis. Acid-fast bacilli suggest Mycobacterium tuberculosis. Trophozoites with ingested RBCs are characteristic of Entamoeba histolytica in stool samples from patients with amebic dysentery.
Question 15
A 32-year-old man who recently emigrated from Honduras presents to the emergency department after experiencing a generalized tonic-clonic seizure. He has no prior history of seizures. An MRI of the brain reveals multiple small, round, cystic lesions with surrounding edema; some lesions contain a small scolex.
This patient's condition most likely resulted from which of the following exposures?
- Ingestion of larvae in undercooked pork
- Ingestion of eggs from food contaminated with human feces (correct answer)
- Skin penetration by cercariae in freshwater
- Bite from an infected Anopheles mosquito
Explanation: The patient's presentation with seizures and characteristic brain lesions on MRI is diagnostic of neurocysticercosis, which is caused by the larval stage of the pork tapeworm, Taenia solium. Humans develop cysticercosis by ingesting T. solium eggs, which are passed in the feces of a human who is harboring the adult tapeworm. This typically occurs via the fecal-oral route, often through contaminated food or water. Ingesting larvae in undercooked pork leads to intestinal taeniasis (the adult tapeworm), not cysticercosis. Skin penetration by cercariae is the route of infection for Schistosoma. Mosquito bites transmit malaria.
Question 16
A 35-year-old man who recently traveled to rural India presents with a 2-week history of bloody diarrhea, lower abdominal pain, and fever. An abdominal CT scan reveals a single, large, well-defined lesion in the right lobe of the liver, consistent with an abscess.
Microscopic examination of a fresh stool sample would most likely reveal which of the following findings?
- Pear-shaped trophozoites with 'falling leaf' motility
- Trophozoites containing ingested red blood cells (correct answer)
- Oocysts that are acid-fast
- Rhabditiform larvae
Explanation: This clinical picture of bloody diarrhea (amebic dysentery) and a liver abscess ('anchovy paste' consistency) is classic for amebiasis, caused by Entamoeba histolytica. A pathognomonic finding on microscopic examination of a fresh stool specimen is the presence of trophozoites that have ingested erythrocytes (erythrophagocytosis). Pear-shaped trophozoites are characteristic of Giardia. Acid-fast oocysts in stool are seen with Cryptosporidium. Rhabditiform larvae are seen with Strongyloides.
Question 17
A 6-year-old girl is brought to the pediatrician due to intense perianal itching, which is worse at night and has been disrupting her sleep. Several other children in her daycare class have had similar symptoms.
Which of the following is the most appropriate method to confirm the suspected diagnosis?
- Stool for ova and parasites
- Peripheral blood smear for eosinophilia
- Application of transparent tape to the perianal skin (correct answer)
- Serologic testing for specific antibodies
Explanation: The clinical presentation is classic for pinworm infection, caused by Enterobius vermicularis. The adult female worm migrates to the perianal region at night to lay her eggs, which causes intense pruritus. The most reliable and standard diagnostic method is the 'Scotch tape test' or paddle test. Transparent adhesive tape is pressed against the perianal skin in the morning before bathing, and the tape is then examined under a microscope for the characteristic eggs. The eggs are not typically found in stool, so a stool O&P is not the preferred test. While eosinophilia can be present with helminth infections, it is not diagnostic. Serology is not used for diagnosis.
Question 18
A 29-year-old pregnant woman at 10 weeks gestation expresses concern about toxoplasmosis. She owns a cat, is an avid gardener, and enjoys eating rare steak. Serologic testing is ordered to assess her risk.
Acquisition of a primary infection with Toxoplasma gondii during pregnancy poses the greatest risk of congenital transmission. Which of the following is a primary mode of transmission for this organism to humans?
- Inhalation of airborne spores from bird droppings
- Ingestion of oocysts from cat feces or tissue cysts from undercooked meat (correct answer)
- Bite from an Anopheles mosquito
- Skin penetration by filariform larvae from contaminated soil
Explanation: Toxoplasma gondii is primarily transmitted to humans through two routes: ingestion of tissue cysts found in undercooked or raw meat (especially pork, lamb, and venison) and ingestion of oocysts shed in the feces of infected cats, which can contaminate soil, water, or unwashed vegetables. The other options describe transmission routes for different pathogens: Histoplasma (inhalation of spores), Plasmodium (mosquito bite), and Strongyloides or hookworm (skin penetration by larvae).
Question 19
A 55-year-old gardener presents with a small, painless papule on her right index finger that developed a week after she pricked her finger on a rose thorn. Over the next three weeks, several similar nodules appeared in a linear pattern ascending her forearm.
This presentation is characteristic of an infection caused by a dimorphic fungus that grows as which of the following forms in human tissue at 37°C?
- Spherule
- Cigar-shaped yeast (correct answer)
- Branching, septate hyphae
- Broad-based budding yeast
Explanation: This is a classic case of lymphocutaneous sporotrichosis, often called 'rose gardener's disease', caused by Sporothrix schenckii. The organism is introduced into the skin via trauma (e.g., a thorn prick) and spreads along the lymphatic channels. S. schenckii is a dimorphic fungus. In human tissue (at 37°C), it grows as a yeast, which is characteristically elongated or cigar-shaped. In the environment (at 25°C), it grows as a mold with branching, septate hyphae. Spherules are seen with Coccidioides. Broad-based budding is characteristic of Blastomyces.
Question 20
A 58-year-old man with a history of tuberculosis treated 10 years ago presents with a 2-month history of coughing up blood. A chest X-ray reveals a round mass located within a pre-existing apical lung cavity. Bronchoscopy with biopsy is performed, and microscopic examination of the tissue reveals septate hyphae branching at 45-degree angles.
Which of the following organisms is the most likely cause of this patient's condition?
- Aspergillus fumigatus (correct answer)
- Mucor species
- Pneumocystis jirovecii
- Blastomyces dermatitidis
Explanation: This patient's presentation with a fungal ball (aspergilloma) within a pre-existing lung cavity (from prior tuberculosis) is classic for Aspergillus fumigatus infection. The microscopic finding of septate hyphae with acute-angle (45-degree) branching is characteristic of Aspergillus. Mucor species have nonseptate hyphae with right-angle branching. Pneumocystis jirovecii is a yeast-like fungus that causes diffuse pneumonia, not fungal balls, in immunocompromised hosts. Blastomyces dermatitidis is a dimorphic fungus that appears as broad-based budding yeast in tissue samples.