Page 101 - AIDSBK23C

Page 101

(CSF) obtained from lumbar puncture with an India ink preparation that will highlight the
budding nuclei. The CSF cell counts and chemistries can be abnormal, and cryptococcal antigen
is positive in 90% of cases when the CSF culture is positive for C neoformans.[454]
In about a third to half of cryptococcal infections, there is a pneumonitis. Pulmonary
involvement is usually seen along with dissemination, though isolated pulmonary disease may be
present. Fever, cough, and dyspnea are non-specific manifestations of pulmonary
cryptococcosis. Persistent prostatic infection, which is difficult to detect, may serve as a
reservoir that is difficult to eradicate.[454]
If large numbers of cryptococci with capsules are present, a grossly apparent mucoid
exudate may be seen in the cerebral ventricles or on the meningeal surfaces of the central
nervous system. Sometimes variably sized pale soft granulomas are grossly visible in the lungs
or elsewhere. In a few cases, the granulomas have surrounding hemorrhage. The lungs may
show patchy areas of consolidation. In some cases, the only grossly identifiable pathologic
change is organomegaly.
Microscopically, C neoformans organisms are pale narrow-based budding yeasts that
average 2 to 7 microns in size with a prominent surrounding capsule. The yeast cells appear pale
blue and ovoid while the capsule is round and clear with routine hematoxylin-eosin-stained
tissue sections or on Papanicolaou-stained cytologic material. With the capsule, the organisms
are 5 to 20 microns. Pale or clear areas at low power magnification in examined tissues may be
found at high power to contain large numbers of cryptococci. The accompanying scanty
inflammation contains a few small, scattered lymphocytes or macrophages with phagocytized
organisms.
The capsule, when present, can be stained in tissue sections or cytologic smears with
most mucin stains. Methenamine silver and PAS stains readily demonstrate the nuclei of the
organisms. In many cryptococcal infections with AIDS, there are present only very poorly or
non-encapsulated cryptococci. The presence of these poorly encapsulated forms may explain the
paucity of gross pathologic findings. This appearance is similar to subcultures of cryptococci on
growth media in the laboratory. Such capsule-deficient forms may be difficult to distinguish
from Candida and Histoplasma capsulatum. The cellular pleomorphism of Cryptococcus, larger
cell size, and lack of pseudohyphae help to distinguish it from Candida. The football-shaped C
neoformans yeasts are much larger than the small round cells of H capsulatum organisms.[455]
Cryptococcal organisms can also be distinguished by the presence of a melanin-like
pigment that is identified with the Fontana-Masson stain. The Alcian blue stain will help to
distinguish the capsule of C neoformans (if present) as well as the wall of Blastomyces
dermatitidis. The PAS stain will highlight the cell walls of each of these latter two
organisms.[456]
When antiretroviral therapy (ART) is begun, within 2 months there may be immune
restoration disease (IRD), loss of anergy, and development of more florid inflammatory
responses from delayed-type hypersensitivity restoration. With cryptococcal infections, IRD is
most often manifested by lymphadenitis, particularly within the mediastinum.[285]
Antifungal therapies with amphotericin B, flucytosine, and triazoles (fluconazole,
itraconazole), are successful in many cases. Fluconazole or itraconazole are the drugs most often
used for secondary prophylaxis, since many patients with treated C neoformans infections will
have a recurrence without continued suppressive therapy. About half of AIDS patients infected
with Cryptococcus are found to have died of their cryptococcal disease, most often from CNS
involvement.[208,417]