Although cryptococcosis is almost always a sequela of inhalation of organisms, pulmonary cryptococcosis is rarely diagnosed compared to cryptococcal meningoencephalitis. Cryptococcosis is a rare (but not unheard of) disease in immunocompetent people, but is increased in immunocompromised people, including patients with AIDS and those on corticosteroid therapy (including transplant recipients). Since the incidence of exposure is greater than the incidence of disease, most individuals are probably resistant to serious infections. However, the true incidence is unknown as a reliable skin test is unavailable.

Diagnosis: Sputum culture and bronchial washings are unreliable in diagnosing pulmonary cryptococcosis due both to false positive results in patients with incidental colonization and frequent false negative results in patients with invasive disease. Definitive diagnosis requires identification of the organism from surgical specimens, either by direct examination or by culture. In tissue stained with hematoxylin and eosin, the encapsulated yeast appears surrounded by empty space, a reproducible artifact of poor capsular staining. A muci9carmine stain highlights the capsule. Four distinct histopathologic patterns have been observed: granulomata, granulomatous pneumonia, intracapillary infection, and massive pulmonary involvement. All of these subtypes have been associated with dissemination, and each has been documented to cause fatalities in the absence of dissemination. In culture, the white to cream colored mucoid colonies will usually develop within 2 to 5 days. Cryptococcus neoformans will grow at 37C and produces phenol oxidase, which leads to the formation of melanin when the colony is grown on caffeic acid. They do not produce pseudomycelia when grown on cornmeal agar. The serotypes can be identified by DNA or enzymatic methods.

Therapy: Once a diagnosis of pulmonary cryptococcosis is made, the presence of disseminated disease should be ascertained. At a minimum, a lumbar puncture should be performed with India ink staining and culture of the cerebrospinal fluid. Cultures of other sites may be helpful. Detection of cryptococcal antigen serum is also potentially useful when there is significant organisms and pathology. The laboratory uses an ELISA test (rather than latex agglutination) as it has a lower false positive rate and is easier to interpret. Pulmonary cryptococcosis in immunocompetent patients with no evidence of dissemination does not need to be treated because the majority will spontaneously heal, with no marked residua such as cavities or calcifications. Pulmonary cryptococcosis in immunocompromised patients and those with disseminated disease (and possibly those with high serum titers of cryptococcal antigen) needs to be treated with amphotericin B. Flucytosine, a pyrimidine antagonist, is used in combination with amphotericin as it results in more rapid clearance of the organism and permits lower doses of amphotericin, thus reducing nephrotoxicity. The use of azole compounds, particularly fluconazole is the treatment for some forms of disease.