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Diagnosis: Cryptococcus infection of the kidney graft

Cryptococcosis is the third most common invasive fungal infection in organ transplant recipients after candidiasis and aspergillosis.

Cryptococcus neoformans is a ubiquitous saprophytic fungus with worldwide distribution. The fungus is found in nature primarily in association with bird droppings. The reason for the high frequency of Cryptococcus in avian excreta is not clear, but may be related to the ability of the fungus to assimilate xanthine, urea, uric acid and creatinine, all of which are abundant in bird droppings.

Cryptococcosis is thought to result from failure of host defenses to contain the organism after inhalation of aerosolized particles from an environmental source. The organism is tropic to the central nervous system (CNS) and the majority of the recognized infections in humans involve meningitis. The disease is not contagious. Most infections in healthy subjects are asymptomatic or mildly symptomatic but self-limited; antifungal therapy is seldom required.

Current data suggest that 20–60% of the cases of cryptococcosis in HIV-negative patients occurred in organ transplant recipients. Cryptococcosis usually occurs more than 6 months after transplantation. As the majority of these fungal infections occur months to years after transplantation, these cases of cryptococcosis are most likely primary infection rather than reactivation. Renal transplant recipients have the lowest incidence of fungal infections compared with other organ transplants. Infection of the graft is rare, and it is possible that our patient had systemic infection, however it was only demonstrated in skin (in addition to the kidney graft).

In H&E-stained tissue sections, C. neoformans appears as eosinophilic or lightly basophilic, uninucleate, thin-walled, spherical, oval, and elliptical yeast-like cells that vary in size from 2 to 20 µm, but commonly measure 4 to 10 µm in diameter. Tipically, the fungal cells are surround by wide, clear to faintly stained spherical zones or "halos" that represent mucinous capsules (Figures 5 and 6). The mucopolysaccharide capsular material is readily demonstrated with mucin stains such as mucicarmin, alcian blue or colloidal iron. This staining reaction is a diagnostic marker, but it may be absent or equivocal if have been digested by phagocytes. This staining reaction is not present in Histoplasma, and it has a more small and less variable size than Cryptococcus (usually 2-5 µm). C. neoformans is the only pathogenic fungus that has a mucinous capsule.

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Bibliography

• Sun HY, Wagener MM, Singh N. Cryptococcosis in solid-organ, hematopoietic stem cell, and tissue transplant recipients: evidence-based evolving trends. Clin Infect Dis. 2009;48(11):1566-76. [PubMed link]
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• Abraham KA, Little MA, Casey R, Smyth E, Walshe JJ. A novel presentation of cryptococcal infection in a renal allograft recipient. Ir Med J. 2000;93(3):82-4. [PubMed link]

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