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1
Question:

A 54-year-old man is brought to the emergency department due to a week of progressive headaches and confusion.  He was treated for viral esophagitis 6 months ago and Pneumocystis pneumonia 2 months ago.  Temperature is 38 C (100.4 F), blood pressure is 142/86 mm Hg, and pulse is 64/min.  The patient is lethargic and oriented to person and place only.  CT scan of the head shows a mildly increased ventricle size but no other abnormalities.  Lumbar puncture reveals an elevated opening pressure, and cerebrospinal fluid analysis shows moderately increased protein concentration and pleocytosis.  The latex agglutination test is positive for soluble polysaccharide antigen.  Light microscopy of this patient's cerebrospinal fluid is most likely to reveal which of the following?

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Explanation:

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Cryptococcus neoformans

Morphology

  • Yeast with a polysaccharide capsule
  • Round/oval cells with narrow-based buds

Epidemiology

  • Soil and pigeon droppings
  • Respiratory transmission
  • Opportunistic infection in patients with AIDS (CD4 <100/mm3)

Infection

  • Meningoencephalitis: Progressive headache, fever, confusion
  • Possible disseminated disease

Diagnosis

  • India ink stain of cerebrospinal fluid
  • Latex agglutination of cerebrospinal fluid
  • Culture using Sabouraud agar

Treatment

  • Amphotericin B and flucytosine (induction)
  • Fluconazole (maintenance)

This patient's opportunistic infections (viral esophagitis, Pneumocystosis pneumonia) raise suspicion for untreated AIDS.  He now has headache, fever, confusion, and polysaccharide antigens in the cerebrospinal fluid (CSF) indicating likely cryptococcal meningitis.  This opportunistic infection is caused by Cryptococcus neoformans, a yeast with a thick polysaccharide capsule.  Diagnosis is often made by identifying polysaccharide (cryptococcal) antigens in the CSF.  Round or oval budding yeast can also be visualized with India ink stain.  Most patients have elevated opening pressures on lumbar puncture due to increased vascular permeability secondary to inflammation and/or yeasts obstructing CSF outflow from the arachnoid villi.

(Choice B)  Candida albicans forms germ tubes (true hyphae) if incubated in 37 C (98.6 F) serum for 3 hours.  This test helps differentiate C albicans from other Candida species.  C albicans meningitis is extremely rare (even in patients with HIV) and would not be associated with a positive polysaccharide antigen.

(Choice C)  Mucor and Rhizopus species are characterized by nonseptate hyphae that branch at wide angles.  These fungi cause severe infections of the paranasal sinuses (mucormycosis) in patients who are immunosuppressed (eg, diabetes mellitus).

(Choice D)  Coccidioides immitis is associated with the formation of spherules, which then rupture to release endospores.  This fungus primarily causes community-acquired pneumonia in endemic areas (eg, Arizona desert); central nervous system infection is quite rare and would not be associated with a positive polysaccharide antigen.

(Choice E)  Mold fungi (eg, Rhizopus) form sporangia, which produce and contain spores.  Cryptococcus is a yeast and does not reproduce with sporangia.

Educational objective:
Cryptococcus neoformans causes meningoencephalitis in patients with untreated AIDS.  Diagnosis can be made by detecting the polysaccharide capsule in cerebrospinal fluid using the latex agglutination test.  India ink staining of cerebrospinal fluid is also used for diagnosis and can demonstrate round or oval budding yeast.