This case was originally published in 2017. The information provided in this case was accurate and correct at the time of initial program release. Any changes in terminology since the time of initial publication may not be reflected in this case.
Clinical History
A 45-year-old man with a five-year history of HIV infection (CD4 count 195 cells/µL) and headaches presents with worsening headaches and blurred vision. Five years ago, MRI revealed a right temporal fossa cystic mass. The patient reports that he was told at the time that the lesion was "inoperable." Re-imaging now reveals a cystic lesion involving the skull base in the right anterior temporal fossa and extending into the right maxillary sinus (Image A). The cyst is described as containing material that is isointense to CSF on T2-weighted imaging. A biopsy was performed.
Tissue Site
Temporal fossa
Whole Slide Image
The whole slide image provided is an H&E stain from a temporal fossa biopsy.
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What is the diagnosis?
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Arachnoid cyst
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Epidermoid cyst
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Idiopathic hypertrophic pachymeningitis
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Infection by Blastomyces dermatitidis
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Infection by Cryptococcus neoformans
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Which of the following is the MOST LIKELY cause for this process?
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Epithelial heterotopia
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Inhalation of contaminated soil or bird excrement
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Malformation of the leptomeninges
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Patent foramen ovale
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Penetrating trauma
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Which of the following imaging findings would be MOST SPECIFIC for an arachnoid cyst?
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Extra-axial cyst with homogeneous diffusion restriction on MRI
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Intraparenchymal cyst with enhancing mural nodule
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Intraparenchymal cyst with surrounding edema
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Superficial cyst with contents isointense to CSF on T2-weighted imaging
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Superficial cyst with T1-hyperintense contents
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Discussion and Diagnosis
The diagnosis is CNS cryptococcosis with mass lesion. The MR image in this case shows a cyst containing material that is isointense to CSF on T2-weighted imaging. This finding is unusual for cryptococcal CNS infection and more consistent with an arachnoid or epidermoid cyst. The lesion in this case is focal, yet the overwhelming majority of cryptococcal CNS infections result in a more diffuse meningoencephalitis that preferentially involves the basal meninges. In immunocompetent individuals, a granulomatous immune response may form a solid mass lesion, often referred to as a "cryptococcoma." The H&E stained images in this case (Image B, Image C, and Image D) show fibrous tissue containing indented and empty-appearing glassy organisms measuring 5 to 15 microns. Each organism is surrounded by a clear capsule. No immune response is apparent. The refractile inner capsule and cell wall of the yeasts stain positively with GMS (Image E), PAS (Image F), and mucicarmine (Image G). The presence of mucicarmine staining and large "haloes" around the organisms is particularly helpful in distinguishing cryptococcus from Blastomyces yeasts.
Cryptococcus is an encapsulated yeast found throughout the world in soil, bird droppings, and on some plants. Most cryptococcal infections in humans are due to the species C. neoformans. The vast majority of C. neoformans infections are caused by the variety grubii, also known as serotype A. A minority of cryptococcosis cases are caused by another species, C. gattii (formerly known as C. neoformans var. gattii). In contrast to neoformans, C. gattii is more frequently observed in immunocompetent patients, where exposure is thought to be by inhalation of spore-bearing material from certain species of trees. Most cases of C. gatti infection occur in tropical and subtropical climates, with a small number also in the Pacific Northwest of the United States and in British Columbia.
Although exposure to C. neoformans is thought to be common, it is relatively rare for humans to become infected unless the host is immunocompromised. Prior to the worldwide HIV epidemic, cryptococcal infection was a rare cause of meningoencephalitis in patients with other forms of immune compromise. Cirrhosis and pregnancy are also risk factors associated with cryptococcal infection. In rare cases, C. neoformans can infect people with no known risk factors. Currently, C. neoformans infection is most common in HIV patients with CD4 counts of <100/ µL. Humans are thought to become infected through inhalation of organisms which then spread hematogenously to the CNS. As in this case, there is usually little or no immune response to the organisms because the polysaccharide capsule helps to evade immunologic surveillance ("crypto" derives from the Greek word for "hidden"). The capsule also allows adherence to mucosal surfaces. Grossly the capsule imparts a gelatinous appearance, typically in the basal meninges and along adjacent penetrating arteries. Although not visible on H&E, small amounts of melanin are present in the cell wall and capsule that mitigate oxidative damage from attacking leukocytes. This melanin can best be demonstrated histochemically by Fontana-Masson staining.
Treatment for CNS cryptococcosis is a two-week course of amphotericin B in combination with flucytosine. In order to prevent recurrence of dormant cryptococci, patients with HIV and CD4+ lymphocyte counts less than 200 cells/µL are then treated with fluconazole until CD4 counts rise above that threshold. Patients with a CNS cryptococcoma may be treated only medically if asymptomatic, or in combination with surgical excision if the mass is symptomatic.
Take Home Points
- Cryptococcal infections are usually caused by C. neoformans (grubii variety) in immunocompromised patients.
- C. gattii causes fewer cases of cryptococcosis and is more likely to infect immunocompetent patients.
- Cryptococci are identified histopathologically by their thick polysaccharide capsules and cell walls which are mucicarmine positive.
References
- C. gattii infection. Centers for Disease Control and Prevention website. Updated December 16, 2015. Accessed May 8, 2016.
- C. neoformans infection. Centers for Disease Control and Prevention website. Updated November 28, 2015. Accessed May 8, 2016.
- Ellis D. Cryptococcus neoformans. University of Adelaide Mycology Online. Updated May 5, 2016. Accessed May 8, 2016.
- Lazcano O, Speights VO Jr, Bilbao J, et al. Combined Fontana-Masson-mucin staining of Cryptococcus neoformans. Arch Pathol Lab Med. 1991;115:1145-9.
- Lucas S, Bell J, Chimelli L. Parasitic and fungal infections. In: Love S, Louis DN, Ellison DW, eds. Greenfield's Neuropathology. 8th ed. London, UK: Hodder Arnold; 2008:1447-1511.
- O’Meara TR, Alpaugh JA. The Cryptococcus neoformans capsule: a sword and a shield. Clin Microbiol Rev. 2012;25:387-404.
Answer Key
- What is the diagnosis?
- A. Arachnoid cyst
- B. Epidermoid cyst
- C. Idiopathic hypertrophic pachymeningitis
- D. Infection by Blastomyces dermatitidis
- E. Infection by Cryptococcus neoformans
- Which of the following is the MOST LIKELY cause for this process?
- A. Epithelial heterotopia
- B. Inhalation of contaminated soil or bird excrement
- C. Malformation of the leptomeninges
- D. Patent foramen ovale
- E. Penetrating trauma
- Which of the following imaging findings would be MOST SPECIFIC for an arachnoid cyst?
- A. Extra-axial cyst with homogeneous diffusion restriction on MRI
- B. Intraparenchymal cyst with enhancing mural nodule
- C. Intraparenchymal cyst with surrounding edema
- D. Superficial cyst with contents isointense to CSF on T2-weighted imaging
- E. Superficial cyst with T1-hyperintense contents