Page 142 - AIDSBK23C

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Pulmonary involvement by C neoformans is second only to central nervous system
involvement in frequency in AIDS (Table 5). Cryptococcosis tends to be a disseminated disease,
though death with C neoformans often results from pulmonary involvement. The gross patterns
of C neoformans involvement within the pulmonary parenchyma include a bronchopneumonia-
like pattern with either diffuse or patchy consolidation, interstitial infiltrates, or a mixture of
these two patterns. Solitary or multiple nodules, which are granulomas, may appear similar to
those seen with mycobacterial infection or other fungi, and they typically have a soft, mucoid
appearance. When well-defined masses or nodules are seen, they are often gelatinous because
numerous organisms with minimal inflammatory infiltrates are present.[453,454]
Microscopically, the 4 to 7 micron pale cryptococci are found filling the alveoli or
infiltrating the alveolar septae. Often, poorly encapsulated or non-encapsulated cryptococci are
present that are only 2 to 5 microns in size that may be difficult to distinguish from Candida and
Histoplasma capsulatum.[450] Granulomas, if present, tend to be small and poorly formed. The
interstitium or alveoli may show only a minimal inflammatory response consisting mainly of
scattered macrophages with few lymphocytes or neutrophils. The more common pattern of
involvement consists of focal small lesions. A pneumonic pattern of numerous cryptococci in
alveolar spaces along with mixed inflammatory infiltrates is seen less frequently.[454]
Both cellular pleomorphism of C neoformans and its lack of hyphae help to distinguish
this organism from Candida. Gomori methenamine silver (GMS) and PAS stains readily
demonstrate the organisms. Cryptococci can also be distinguished from other fungi from the
presence in C neoformans of a melanin-like pigment seen with Fontana-Masson staining.[455]

HISTOPLASMOSIS.-- Histoplasma capsulatum infection with AIDS often produces a
disseminated infection, and pulmonary involvement is frequent. Clinically the onset of disease is
insidious, with weight loss and fever the most common symptoms. A chest roentgenogram
shows diffuse interstitial infiltrates in about half of all patients, and in these patients, cough and
dyspnea are often present as well, but only one-sixth of AIDS patients with histoplasmosis
present with respiratory problems. The Histoplasma polysaccharide antigen (HPA) test can be
performed on serum, urine, cerebrospinal fluid, or bronchoalveolar lavage fluid for initial
diagnosis of disseminated histoplasmosis. Although the urine and serum HPA test is sensitive in
disseminated histoplasmosis, it is often negative in isolated pulmonary disease. Blood culture or
tissue biopsy with culture are the main means for confirming the diagnosis.[479,598]
The initial response to infection is neutrophilic, but soon shifts to mononuclear
phagocytes. Grossly visible small tan to white granulomas may be present in lung tissue, but
often they are not. The organisms consist of small, oval 2 to 4 micron budding yeasts that are
most often identified within macrophages in the interstitium, but they may also be free in the
alveolar spaces. Intracellular organisms may be seen in routine hematoxylin-eosin-stained
sections due to a small artefactual clear zone surrounding them, though they are best seen by
either Gomori methenamine silver (GMS) or periodic acid-Schiff (PAS) stains. In older fibrotic
or calcified granulomas, H capsulatum may be visible only with methenamine silver stain.
Histological confirmation of H capsulatum infection can sometimes be difficult, since the
yeasts are small and can sometimes resemble Candida, Pneumocystis jiroveci (carinii),
Leishmania, or poorly encapsulated Cryptococcus neoformans organisms.
Immunohistochemical staining of smears and tissue sections with anti-histoplasma antibody can
be utilized to specifically diagnose pulmonary histoplasmosis. Microbiologic culture can aid in
confirming the diagnosis of Histoplasma pneumonitis.