Diagnosis -- Cryptococcal Meningitis


FINAL DIAGNOSIS

Cryptococcal meningitis.

DISCUSSION

Cryptococcosis is a systemic mycosis caused by the fungi Cryptococcus neoformans and, less commonly, Cryptococcus gattii. The organisms are 5-20 m single budding yeasts found in the soil and in bird droppings, and are characterized by the presence of a thick polysaccharide capsule that stains with mucicarmine and Alcian blue. The fungi are also identified by PAS or Grocott methenamine silver stains. In the CNS, the organisms can be mistaken for corpora amylacea, which are round structures with similar distribution, sizes, and staining properties on H&E and PAS staining. The lung is typically the primary site of infection with subsequent hematogenous dissemination to involve other organs, which not uncommonly includes the central nervous system (CNS).

CNS involvement by cryptococci is usually a consequence of immunosuppression and typically manifests as meningitis, with varying clinical presentations ranging from acute signs of meningeal irritation and intracranial hypertension to protracted and waxing and waning changes in the mental status. The latter can lead to delays in diagnosis, especially since imaging findings may be subtle in the absence of florid meningeal inflammation. HIV infection underlies most cases of cryptococcal meningitis, which is one of the AIDS-defining illnesses. While Candida albicans is the most common fungal organism to cause localized infection in HIV patients (oral candidiasis), cryptococcosis is the most common systemic fungal infection. Other settings conferring susceptibility to cryptococcal CNS infection include malnutrition, lymphoproliferative diseases, transplant, chemotherapy for cancer, immunosuppression by steroids, and cirrhosis, the latter which was present in this patient. However, up to 30% of cases of cryptococcal meningitis occur in individuals without an underlying condition. Rarely, more often in immunocompetent individuals, cryptococcal CNS infection may appear as localized masses (cryptococcomas) which give rise to focal neurologic deficits. Those cases are more frequently associated with infection by Cryptococcus gattii.

In this case, autopsy cultures of the lung and spleen were positive for Cryptococcus neoformans. The finding of cryptococcal meningitis in the setting of disseminated cryptococcosis in this patient's autopsy was unexpected. Organisms were restricted to leptomeningeal and Virchow-Robin spaces with relatively limited associated inflammation, which gave rise to mild gross abnormalities and would likely yield only subtle imaging alterations. Diagnosis of cryptococcal meningitis can be further challenging when the presentation is nonspecific and subacute. CSF examination with cryptococcal antigen testing can be useful in establishing a pre mortem diagnosis in challenging cases. The cause of death was ultimately deemed multifactorial. The patient was found to have an underlying cardiomyopathy, a history of heart blocks, uncontrolled diabetes, and cirrhosis with elevated ammonia, all of which could have contributed to episodes of altered mental status and cardiac arrhythmias.

REFERENCES

  1. Searls DE, Sico JJ, Omay SB, Bannykh S, Kuohung V, Baehring J. Unusual presentations of nervous system infection by Cryptococcus neoformans. Clin Neurol Neurosurg. 2009;111:638-642
  2. Williamson PR, Jarvis JN, Panackal AA, Fisher MC, Molloy SF, Loyse A, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nat Rev Neurol. 2017;13:13-24.
  3. Colombo AC, Rodrigues ML. Fungal colonization of the brain: anatomopathological aspects of neurological cryptococcosis. An Acad Bras Cienc. 2015;87:1293-1309
  4. Lee SC, Dickson DW, Casadevall A. Pathology of cryptococcal meningoencephalitis: analysis of 27 patients with pathogenetic implications. Hum Pathol. 1996;27:839-847
  5. Klock C, Cerski M, Goldani LZ. Histopathological aspects of neurocryptococcosis in HIV-infected patients: autopsy report of 45 patients. Int J Surg Pathol 2009;17:444-448
  6. McMullan BJ, Sorrell TC, Chen SC. Cryptococcus gattii infections: contemporary aspects of epidemiology, clinical manifestations and management of infection. Future Microbiol 2013;8:1613-1631


Contributed by Osorio Lopes Abath Neto, MD, PhD, and Scott Kulich, MD, PhD




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