Final Diagnosis -- Cryptococcus neoformans


Positive for organisms. Negative for malignant cells. Acute and chronic inflammatory cells and numerous encapsulated fungal yeast forms with some budding, morphologically compatible with cryptococcus sp. No viral inclusions present.


Cryptococcus neoformans has been presumptively identified in the mycology culture.


Cryptococcus neoformans, a saprophytic basidiomycete, is believed to lead to cryptococcosis following inhalation of the organism (1). Most cases occur in immunocompromised patients. Factors predisposing to cryptococcal infection include corticosteroid administration, lymphoreticular malignancies (especially Hodgkin's disease), sarcoidosis and HIV infection; however, 50% of cases have no recognized predisposing condition. Approximately 80-90% of cryptococcosis occurs in AIDs patients (2). The most frequently affected site is the central nervous system, however, the organism has been isolated from almost every organ. Pulmonary cryptococcal infection is often asymptomatic, as was seen in this patient (3). Temperate climates are the primary location for Cryptococcus neoformans var. neoformans (4). The organism is surrounded by a polysaccharide capsule, composed of glucuronoxylomannan, of which there are four serotypes (5, 6). The capsule of the organism inhibits phagocytosis(6).

The radiographic appearance of lung involvement by cryptococcosis may vary depending upon the immune status of the host. Interstitial infiltrates are commonly noted in HIV positive patients (7). However, immunocompromised hosts who are not HIV positive, as in the present case, have been shown to commonly have single or multiple nodules, which may suggest a neoplasm (8). Interestingly, in tissue, cryptococcal organisms produce minimal direct injury. The inflammatory response ranges from none to chronic inflammation with macrophages, lymphocytes, foreign body giant cells/granulomas, and occasionally neutrophils, followed by fibrosis; calcification is uncommon.

The diagnosis of pulmonary cryptococcosis by fine needle aspiration has been previously described (9, 10, 11, 12). The diagnostic yield of fine needle aspiration in theses cases has been shown to be higher than that of bronchoscopy with biopsy (12). Direct cryptococcal antigen determinations on lung aspirates may provide a rapid method to the diagnosis of pulmonary cryptococcosis (13). Direct cryptococcal antigen determinations in serum (12, 14, 15), pleural effusions (16), and bronchoalveolar fluid (17) have also previously been utilized in the diagnosis of pulmonary cryptococcosis.


  1. Ellis DH, Pfeiffer TJ. Ecology, life cycle, and infectious propagule of Cryptococcus neoformans. Lancet 1990;336:923-25.
  2. Diamond RD. Principles and Practice of Infectious Diseases (1995, 4th edn) (Mandell GL, Bennett JE, and Dolin R eds), 2232-2340, Churchill Livingstone.
  3. Littman ML, Walter JE. Cryptococcosis: current status. Amer J Med 1968;45:922-33.
  4. Kwon-Chung KJ, Bennett JE. Epidemiologic differences between the two varieties of Cryptococcus neoformans. Amer J Epid 1984;120:123-30.
  5. Cherniak R, Reiss E, Slodki ME, Plattner RD, Blumer SO. Structure and antigenic activity of the capsular polysaccharide of Cryptococcus neoformans serotype A. Mol Immunol 1980;17:1025-1032.
  6. Kozel TR. Virulence factors of Cryptococcus neoformans. Trends Microbiol 1995;3:295-99.
  7. Friedman EP, Miller RF, Severn A, Williams IG, Shaw PJ. Cryptococcal pneumonia in patients with the acquired immunodeficiency syndrome. Clin Radiol 1995;50:756-60.
  8. Khoury MB, Godwin JD, Ravin CE, Gallis HA, Halvorsen RA, Putman CE. Thoracic cryptococcosis: immunologic competence and radiologic appearance. Amer J Roent 1984;141:893-96.
  9. Whitaker D. Cryptococcus neoformans diagnosed by fine needle aspiration cytology of the lung. Acta Cyto 1976;20:105-107.
  10. Walts AE. Localized pulmonary cryptococcosis: diagnosis by fine needle aspiration. Acta Cyto 1983;27:457-59.
  11. Silverman JF, Johnsrude IS. Fine needle aspiration cytology of granulomatous cryptococcosis of the lung. Acta Cyto 1985;29:157-61.
  12. Lee LN, Yang PC, Kuo SH, Luh KT, Chang DB, Yu CJ. Diagnosis of pulmonary cryptococcosis by ultrasound guided percutaneous aspiration. Thorax 1993;48:75-78.
  13. Liaw YS, Yang PC, Yu CJ, Chang DB, Wang HJ, Lee LN, Kuo SH, Luh KT. Direct determination of cryptococcal antigen in transthoracic needle aspirate for diagnosis of pulmonary cryptococcosis. J Clin Microbiol 1995;33:1588-91.
  14. Jensen WA, Rose RM, Hammer SM, Karchmer AW. Serologic diagnosis of focal pneumonia caused by cryptococcus neoformans. Am Rev Respir Dis 1985;132:189-91.
  15. Maesaki S, Kohno S, Mashimoto H, Araki J, Asai S, Hara K. Detection of Cryptococcus neoformans in Bronchial Lavage Cytology: report of four cases. Intern Med 1995;34:54-57.
  16. Young EJ, Hirsh DD, Fainstein V, Williams TW. Pleural effusions due to Cryptococcus neoformans: a review of the literature and report of two cases with cryptococcal antigen determinations. Am Rev Respir Dis 1980;121:743-47.
  17. Baughman RP, Rhodes JC, Dohn MN, Henderson H, Frame PT. Detection of cryptococcal antigen in bronchoalveolar lavage fluid: a prospective study of diagnostic utility. Am Rev Respir Dis 1992;145:1226-29.

Contributed by Valerie A. Holst, MD and Sheldon Bastacky, MD


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