Cryptococcosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.

Overview

Pathophysiology

  • Infective cryptococcal species are ubiquitous and natural exposure is very common.
  • Infection occurs by inhalation of aerosolized, dessicated basidiospores.
  • Once these spores reach the alveoli, they are phagocytosed by the alveolar macrophages without prior opsonization (usually required for yeast forms).
  • Cryptococci are intracellular pathogens. Once they are phagocytosed, they germinate and multiply within the macrophages.
  • Activated macrophages are capable of destroying the yeast forms that develop; however, non-activated macrophages act as germination centers for cryptococci.
  • Cryptococci have the ability of forming giant cells that resist phagocytosis and have been hypothesized to play a role in latent infections and reactivation.
  • Cryptococci also have the ability of changing the number of sets of chromosomes during infection, this has been associated with heteroresistance to certain antifungal agents.
  • After exposure to desiccated yeast cells or spores, patients may clear infection or contain it within granulomata as a latent infection, or it may disseminate depending on host immune status or other less well understood mechanisms.
  • Disseminated disease occurs among patients with compromised cell-mediated immunity.
  • The immune response to cryptococcal infection is highly dependent on host T-cell function, and interferon-γ and TNF-α signaling.
  • Granuloma formation can also be seen and may also be responsible for reactivation in patients with immunocompromised states.[1][2]

Microscopic Pathology

Cryptococcosis of the lung in patient with AIDS (Mucicarmine stain)
Cryptococcosis in the cerebrospinal fluid with light India ink staining


  • Cryptococcus exists in yeast form.
  • It is round/ovoid and approximately 5-15 μm (resembles Histoplasma or Candida, but often larger).
  • It is characterized by a thick mucopolysaccharde capsule with a refractile center.
  • India ink staining is used for easy visualization of the capsule in cerebrospinal fluid.[3]
  • It has a tear drop-shaped budding pattern which is useful in differentiating Cryptococcus from Blastomyces and Histoplasma.
  • Cryptococcal infections are usually accompanied by very little inflammation.
  • Cryptococcus stain positive with methenamine silver, Alcian blue, and PAS (may be confused with corpora amylacea in the CNS).[4]

Multimedia

Cryptococcosis (PAS stain)

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References

  1. Brizendine KD, Baddley JW, Pappas PG (2011). "Pulmonary cryptococcosis". Semin Respir Crit Care Med. 32 (6): 727–34. doi:10.1055/s-0031-1295720. PMID 22167400.
  2. May RC, Stone NR, Wiesner DL, Bicanic T, Nielsen K (2015). "Cryptococcus: from environmental saprophyte to global pathogen". Nat Rev Microbiol. doi:10.1038/nrmicro.2015.6. PMID 26685750.
  3. Zerpa R, Huicho L, Guillén A (1996). "Modified India ink preparation for Cryptococcus neoformans in cerebrospinal fluid specimens". J Clin Microbiol. 34 (9): 2290–1. PMC 229234. PMID 8862601.
  4. Fungi. Libre Pathology (2015). http://librepathology.org/wiki/index.php/Fungi#Cryptococcosis. Accessed on December 31, 2015.