Table 1.

Reported cases of cerebral cryptococcomas.

Case	Location	Age (Years)	Sex	Medical, Surgical, or Social History	Causative Pathogen	Clinical Manifestations, Duration	Number and Location of Lesion(s)	Treatment Course	Outcome
Amburgy et al., 2016 [18]	U.S.	Middle age †	M	Cocaine use, travel to Hawaii, Philippines, Thailand, Australia, Japan, and China over the last 30 years, otherwise unremarkable	C. gattii	Fevers, chills, headache, back pain, vomiting, 28 days	Multiple: basal ganglia, and subcortical white matter (also had evidence of a T11-12 cryptococcoma)	ABLC 5–6 mg/kg/day + flucytosine x 83 days Serial LPs then VPS placed INF-γ three times per week started during week 3 for refractory disease Dexamethasone 4 mg every 6 h × 10 days during week 8 for spinal cord edema and paradoxical IRIS Oral voriconazole 300 mg twice daily and dexamethasone taper as maintenance therapy	Improving white matter lesions and no evidence of spinal lesion on MRI after 10 days of dexamethasone
Bayardelle, et al., 1982 [19]	Canada	42	M	Unremarkable	C. neoformans	Headache, seizure, 30 days	3: upper L parietal region, R rolandic area, cerebral parenchyma posterior to the frontal opercular region	AmB-d 20 mg/day + flucytosine 150 mg/kg/day × 6 weeks, then AmB-d 50 mg every other day monotherapy until total dose of 2160 mg	Asymptomatic with near complete regression of cerebral lesions on CT at 1-year follow-up
Brunasso et al., 2021 [20]	Italy	32	F	Tonic-clonic seizures	Cryptococcus spp.	Asymptomatic	1: R temporo-mesial lesion	Complete surgical resection without antifungal therapy	Asymptomatic at 6-month follow-up
Colom et al., 2005 [21]	Spain	60	M	Diabetes mellitus	C. gattii	Headaches, somnolence, several days	1: basal ganglia	L-AMB 200 mg/day + fluconazole 800 mg/day + flucytosine 2500 mg every 6 h × 6 months AmB-d was administered directly into the abscess at 3 months Oral voriconazole as maintenance therapy	Asymptomatic at 16-month follow-up
Coppens, et al., 2006 [22]	Belgium	63	M	Diabetes mellitus	C. neoformans	Weight loss, fatigue, headache, somnolence, hemianopsia, disorientation to time and place, 210 days	3: R parietal, R frontal, and L occipital lobes	AmB-d 0.7 mg/kg/day + flucytosine 150 mg/kg/day × 2 weeks, then transitioned to oral fluconazole 400 mg/day × 3 weeks Underwent intraventricular drain placement into L occipital abscess due to mental deterioration, then replaced by VPS and transitioned to IV voriconazole 400 mg every 12 h × 1 day then 200 mg every 12 h thereafter	MRI at 3-month follow-up showed reduction of initial mass, dural enhancement and thickening, new contrast enhancing lesions in the brain parenchyma, and cortical necrosis Died due to refractory hydrocephalus uncontrolled cryptococcosis
Guha, et al., 2015 [23]	U.S.	66	F	Hypertension, diabetes mellitus, hyperlipidemia	C. neoformans	Global limb weakness, anorexia, cough, seizures, night sweats, 7 days	1: postcentral gyrus (1.1 cm)	Surgical resection of the lesion followed by L-AMB × 6 weeks, then fluconazole × 1 year	Improved neurologic function and no new symptoms at 1-year follow-up
Guhjjar et al., 2021 [24]	U.S.	58	M	JAK2 positive polycythemia vera, MGUS, hypertension	C. neoformans	Confusion, drowsiness, auditory hallucinations, L sided weakness, 7 days	1: R basal ganglia (0.8 × 0.5 cm)	L-AMB + flucytosine × 6 days, then discharged to receive fluconazole	Remained on fluconazole with improved neurologic function and no new symptoms at 2-year follow-up
Hagan et al., 2014 [25]	Brazil	25	F	Unremarkable	Cryptococcus spp.	Word-finding difficulty, R sided numbness and weakness	1: L thalamus (3 × 2 cm)	Amphotericin B, followed by IV fluconazole 800 mg/day × 2 months, then 600 mg/day × 8 months, then 300 mg/day × 9 months	Complete resolution of lesion on MRI, mild residual neuromotor symptoms at 4-year follow-up
Hiraga et al., 2015 [26]	Japan	71	F	Hypertension, hyperthyroidism	C. neoformans	R lower limb weakness, headache, loss of appetite, diplopia, 3 days	1: L frontal lobe	L-AMB + flucytosine	Died 20 days after hospitalization
Ho et al., 2005 [27]	Taiwan	55	F	Unremarkable	C. neoformans	Headache, facial palsy, 365 days	1: R frontal lobe	Surgical resection of the lesion, followed by AmB-d 0.6–0.7 mg/kg/day + fluconazole 400 mg/day × 10 weeks	No new symptoms at 8-month follow-up
Hu et al., 2013 [28]	China	19	M	HIV-infected (CD4 0 cells/μL)	C. neoformans	Headache, confusion, 14 days	Bilateral basal ganglia	AmB-d 0.7 mg/kg/day + flucytosine 100 mg/kg/day × 11 weeks, followed by fluconazole 400 mg/day as maintenance therapy	Asymptomatic with near complete resolution of lesions on MRI after 6 months of antifungal therapy and 4 months of ART 1 month later, remained on fluconazole 400 mg/day and ART, MRI with worsening lesions in bilateral basal ganglia treated with AmB-d + voriconazole 200 mg every 12 h + flucytosine × 6 weeks, followed by fluconazole 400 mg/day combined with corticosteroids over a 6-month period resulting in near complete resolution of brain lesions 15 months after ART initiation while on fluconazole, MRI demonstrated new L temporal lobe lesions treated with AmB-d + voriconazole + flucytosine × 6 weeks, followed by voriconazole 200 mg every 12 h No new symptoms at 10-month follow-up while remaining on voriconazole
Kelly et al., 2018 [29] and Kelly et al., 2020 [30]	South Africa	19	M	Unremarkable	C. neoformans	Headache, blurry vision, R upper extremity weakness, tonic-clonic seizure	2: L frontal lobe, temporal lobe	Surgical resection of the lesions, followed by oral fluconazole 800 mg/day × 8 weeks	Non-adherent to antifungal therapy × 6 months post-discharge, then represented with headache and L upper extremity weakness due to 2 R parietal lobe lesions for which he underwent surgical resection, followed by oral fluconazole 800 mg/day × 8 weeks with symptom improvement [30]
King et al., 2014 [31]	Australia	59	M	Unremarkable	C. gattii	Flashing lights and intermittent blindness in R eye, 270 days	2: R temporal lobe, L occipital lobe	Surgical resection of both lesions, followed by amphotericin B + flucytosine × 4 weeks, then oral antifungal therapy † × 12 months	Resolution of lesions on MRI at 12-month follow-up
Krishnan et al., 2004 [32]	Australia	72	M	Parkinson’s disease, diabetes mellitus	C. neoformans	Depression, confusion, falls, 42 days	2: L parietal lobe, R superior cerebellar peduncle	Amphotericin B × 4 weeks, followed by oral fluconazole as maintenance therapy	Mild improvement in mental state initially, but died 2 months later due to septic shock
Kumar et al., 2020 [33]	India	48	M	Unremarkable	Cryptococcus spp.	Headache, giddiness, vomiting, bilateral papilledema, 90 days	1: cerebellar hemisphere (3 × 3 × 4 cm)	Surgical resection of the lesion, followed by AmB-d 1 mg/kg/day, then fluconazole 400 mg/day × 10 weeks total	Clinical improvement and resolution of lesion on MRI at 5-month follow-up
Li et al., 2010 [34]	China	49	F	Unremarkable	C. neoformans	Headache, dizziness, vomiting, 30 days	1: R occipital lobe (5 × 4 × 4.5 cm)	Surgical resection of the lesion, followed by AmB-d 25 mg/day × 20 days	Resolution of symptoms and lesion on MRI at 1-month follow-up
McMahon et al., 2008 [35]	Australia	68	F	Hypertension	C. gattii	Falls, 30 days	2: L pons and middle cerebellar peduncle	ABLC + flucytosine × 6 weeks, then fluconazole 400 mg/day to 600 mg/day	Died 48 days after treatment initiation from torsades de pointes attributed to fluconazole
Musubire et al., 2012 [36]	Uganda	35	M	HIV-infected on ART (VL UD, CD4 89 cells/μL), treated for CM 7 months prior	C. neoformans	Headache, photophobia, dizziness, anorexia, behavioral changes	1: R parietal lobe	Died prior to surgery and antifungal therapy initiation	Not applicable
Nadkarni et al., 2005 [37]	India	22	M	Seizures	C. neoformans	Seizures, L hemiparesis, bilateral papilledema	1: R parietal lobe	Surgical resection of the lesion, followed by L-AMB	Resolution of symptoms at 9-month follow-up
Nakwan et al., 2009 [38]	Thailand	23	M	Migraine headaches	Cryptococcus spp.	Headache, vomiting, ataxia, dysmetria, dysdiadochokinesia, 365 days	Multiple: cerebellum	Surgical resection of the lesion, followed by amphotericin B × 4 weeks, then oral fluconazole 800 mg/day × 6 months	Resolution of symptoms at 6-month follow-up
Nucci et al., 1999 [39]	Brazil	29	F	Pregnant (2nd trimester)	C. neoformans	Sleepiness, vomiting, bilateral 6th nerve palsy, nuchal rigidity, papilledema, 120 days	Multiple: basal ganglia, R lateral ventricle	Diagnosis established postmortem 9 days after presentation	Not applicable
Oliveira et al., 2007 [40]	Brazil	64	M	Unremarkable	C. gattii	Fever, anorexia, disorientation, weakness, bilateral papilledema, 7 days	1: R temporal lobe, multiple nodules throughout brain parenchyma	Aspiration of temporal lobe lesion, followed by amphotericin B + dexamethasone	Died 2 days after treatment initiation
Paiva et al., 2017 [41]	Brazil	54	F	Hypertension, direct contact with several bird species including pigeons	C. neoformans	Behavioral disturbances, confusion, weakness, 60 days	2: L occipital lobe	Surgical resection of the lesions, followed by amphotericin B + fluconazole	Died from disease and medication related complications
Pettersen et al., 2015 [42]	U.S.	30	M	HIV-infected on ART (CD4 157 cells/µL), treated for recurrent CM 2 months prior	Cryptococcus spp.	Headache, fever, nuchal rigidity, night sweats, seizures	Multiple: R caudate, R temporal lobe	L-AMB 3 mg/kg/day + flucytosine 25 mg/kg every 6 h × 2 weeks EVD placed and prednisone 60 mg/day started due to hydrocephalus on repeat CT Fluconazole 1200 mg/day and prednisone taper as maintenance therapy	Calcification of the caudate head without evidence of cryptococcoma on CT at 2-week follow-up, but eventually transitioned to hospice
Pettersen et al., 2015 [42]	U.S.	40	M	HIV-infected on ART (CD4 84 cells/µL), treated for CM 3 months prior	Cryptococcus spp.	Headache, expressive aphasia, R facial weakness, weight loss	2: L frontotemporal region	L-AMB 5 mg/kg/day + flucytosine 21 mg/kg every 6 h × 6 weeks Oral dexamethasone 4 mg every 8 h started due to increased ICP despite serial LPs Fluconazole 800 mg/day as maintenance therapy for up to 18 months	Resolution of symptoms and lesions on MRI at 2-month follow-up
Popovich et al., 1990 [43]	U.S.	52	M	HIV-infected	Cryptococcus spp.	Headache, altered mental status, photophobia, nausea, vomiting, 1 day	Multiple: bilateral cerebral hemispheres	Amphotericin B	Resolution of symptoms during hospitalization and gradual resolution of lesions on CT
Popovich et al., 1990 [43]	U.S.	47	F	Unremarkable	Cryptococcus spp.	Headache, nausea, vomiting, somnolence, L hemianopsia, 3 days	1: temporal horn of R lateral ventricle	Craniotomy and R temporal lobe incision with placement of ventriculojugular shunt, followed by amphotericin B + flucytosine	Resolution of symptoms at discharge
Popovich et al., 1990 [43]	U.S.	30	M	HIV-infected, previously treated for CM	Cryptococcus spp.	Headache, nausea, vomiting, 28 days	Multiple: bilateral basal ganglia	Amphotericin B + flucytosine	Decrease in size and number of lesions on CT several months after discharge
Popovich et al., 1990 [43]	U.S.	50	M	HIV-infected, treated for CM 2 months prior	Cryptococcus spp.	Not specified	Multiple: bilateral thalamus and basal ganglia	Amphotericin B + intrathecal amphotericin B	Resolution of symptoms at discharge, but died 1 month later due to PJP
Rai et al., 2012 [44]	India	50	M	Idiopathic CD4 lymphocytopenia (CD4 204 cells/µL)	C. neoformans	Headache, dysmetria, dysdiadochokinesia, impaired gait, impaired gag reflex, weak hand grip, 365 days	2: vermis (largest 3.25 × 3.18 × 3.16 cm)	Craniotomy and aspiration of the larger lesion, followed by L-AMB + corticosteroid taper × 8 weeks with addition of fluconazole after 4 weeks, followed by fluconazole + flucytosine × additional 2 weeks, then oral fluconazole as maintenance therapy	Reduction in lesion size and symptom improvement after 10 weeks of treatment
Sabbatani, et al., 2004 [45]	Italy	46	M	Homocystinuria, renal dysfunction, anemia	C. neoformans	Time–space disorientation	1: R frontal lobe	Surgical resection, followed by IV fluconazole 600 mg/day × 32 days, then IV voriconazole 400 mg/day × 60 days	Residual cerebral damage on MRI and progressive cognitive decline at 14-month follow-up, but died due to post-operative cardiovascular complications
Saigal et al., 2005 [46]	U.S.	49	M	Cleaned pigeon droppings from coop 1 month prior to presentation, otherwise unremarkable	C. neoformans	Headache, syncope, confusion, mental status changes, 30 days	Multiple: bilateral basal ganglia	Amphotericin B × 2 months, followed by fluconazole + flucytosine + corticosteroids × 2 months	Clinical improvement and resolution of lesions on MRI at 2-year follow-up
Santander et al., 2019 [47]	Spain	41	F	Unremarkable	C. neoformans	Gait disturbance, urinary incontinence, impaired memory, 120 days	1: biventricular mass (1.6 cm diameter)	Surgical resection of the lesion, followed by amphotericin B 400 mg/day + IV flucytosine 1500 mg every 6 h	Died 10 days after antifungal therapy initiation
Sellers et al., 2012 [48]	U.S.	70	M	Unremarkable	C. gattii	Stupor, lethargy, 3 days	Multiple: bilateral basal ganglia	L-AMB + flucytosine x 4 weeks	Resolution of symptoms initially, but readmitted 1 week later with worsening neurologic symptoms
Sitapati et al., 2010 [9]	U.S.	28	M	HIV-infected (CD4 149 cells/μL), treated for CM 22 months prior	Cryptococcus spp.	Seizures, expressive aphasia, R sided weakness	1: L temporal lobe (6.0 × 3.4 × 3.3 cm)	L-AMB + flucytosine + IV dexamethasone × 1 week, followed by 2-week dexamethasone taper + fluconazole 800 mg/day as maintenance therapy Clinically deteriorated over the next 5 months prompting administration of adalimumab 40 mg SQ every 2 weeks	No change in lesion on MRI after 4 weeks of adalimumab Cognitive and motor improvement after 10 weeks of adalimumab
Solis et al., 2017 [49]	Australia	54	M	Worked with timber in New South Wales, Australia, otherwise unremarkable	C. gattii	Dysarthria, L facial droop	1: R frontal lobe (1.9 × 3.0 × 2.5 cm)	Surgical resection, followed by L-AMB 3 mg/kg/day × 4 weeks + flucytosine × 2 weeks, then transitioned to itraconazole × 12 months as maintenance therapy	Resolution of lesion on MRI and symptoms at 4-month and 9-month follow-up, respectively
Troncoso, et al., 2002 [50]	Argentina	28	M	HIV-infected (CD4 28 cells/μL)	C. neoformans	Fever, headache, hallucinations, altered mental status, seizures, 14 days	1: L occipital lobe (2 cm)	IV AmB-d 0.7 mg/kg/day + dexamethasone 28 mg/day × 6 weeks, followed by lifelong oral fluconazole 200 mg/day	Discharged after 8 weeks following subjective and objective improvement; MRI at 1-year follow-up demonstrated reduction in size of lesion
Ulett et al., 2017 [51]	Australia	55	M	Hypertension, gout, diabetes mellitus	C. gattii	Headache, R papilledema, L pronator drift, 30 days	1: R frontoparietal (4 × 5 × 4.8 cm)	Surgical resection, followed by ABLC 5 mg/kg/day + flucytosine 66 mg/kg/day + dexamethasone taper × 34 days, then oral fluconazole 800 mg/day × 9 months	Improvement in lesion on MRI at 10-month follow-up
Uppar, et al., 2018 [52]	India	55	M	Unremarkable	C. neoformans	Fever, altered sensorium, headache, vomiting, behavioral changes, hemiparesis, papilledema, L 6th nerve palsy, L upper motor neuron facial palsy	1: R parieto-occipital lobe	Surgical resection, followed byAmB-d 1 mg/kg/day × 6 weeks + oral fluconazole 400 mg/day × 18 weeks	Healthy at 8-year follow-up
Uppar, et al., 2018 [52]	India	45	M	Unremarkable	C. neoformans	Giddiness, headache, vomiting, cerebellar signs	1: R cerebellum	Surgical resection with EVD placement, followed by AmB-d 1 mg/kg/day × 8 weeks + oral fluconazole 400 mg/day × 18 weeks	Healthy at 12-year follow-up
Uppar, et al., 2018 [52]	India	74	M	Unremarkable	C. gattii	Headache, reduced appetite, vomiting, cerebellar signs	1: R cerebellum	Surgical resection, followed by AmB-d 1 mg/kg/day × 6 weeks + oral fluconazole 400 mg/day × 18 weeks	Healthy at 4-year follow-up
Uppar, et al., 2018 [52]	India	30	M	Unremarkable	C. neoformans	Headache, vomiting, fever, visual disturbances, papilledema	1: R frontal lobe	AmB-d 1 mg/kg/day × 6 weeks + oral fluconazole 400 mg/day × 18 weeks	Healthy at 6-month follow-up
Uppar, et al., 2018 [52]	India	24	M	Unremarkable	C. neoformans	Headache, vomiting, fever, behavioral changes, altered sensorium, visual disturbances, papilledema, bilateral 6th nerve palsy	1: R caudate region	Surgical resection, followed by AmB-d 1 mg/kg/day × 6 weeks + oral fluconazole 400 mg/day × 8 weeks	Died 2 months following surgery
Velamakanni et al., 2014 [53]	Uganda	45	M	HIV-infected (CD4 4 cells/µL), treated for CM 2 months prior	C. neoformans	Headache, cough, vomiting, fever, seizures, R-sided hemiparesis, 7 days	1: occipital lobe	AmB-d 50 mg/day, in addition to prednisone started on day 11	Died 2 weeks after diagnosis of cryptococcoma
Wei, et al., 2020 [54]	China	40	M	Unremarkable	C. neoformans	Altered consciousness, apathy, 7 days	Multiple: corpus callosum, centrum ovale	Initially received IV methylprednisolone 500 mg/day × 3 weeks, followed by prednisone 60 mg/day tapered over by 5 mg/week Clinically deteriorated after 3 months, then treated with AmB-d 25 mg/day increased to 50 mg/day + oral flucytosine 6 g/day	Died 3 weeks following antifungal therapy initiation
Yeh, et al., 2014 [55]	Taiwan	75	M	Unremarkable	Cryptococcus spp.	R sided weakness, several days	1: L parietal lobe	Surgical resection, followed by IV fluconazole	Died on post-operative day 17 from systemic sepsis
Zheng et al., 2011 [56]	China	53	F	Poultry farmer, otherwise unremarkable	Cryptococcus spp.	Headache, vomiting, ataxia, wide-based gait, dysmetria, 180 days	Multiple: posterior fossa	Surgical resection, followed by fluconazole x 12 weeks	Resolution of symptoms and decrease in size of lesions on MRI at follow-up

ABLC, amphotericin B lipid complex; AmB-d, amphotericin B deoxycholate; ART, antiretroviral therapy; CM, cryptococcal meningoencephalitis; EVD, external ventricular drain; HIV, human immunodeficiency virus; INF, interferon; IRIS, immune reconstitution inflammatory syndrome; IV, intravenous; JAK, Janus kinase 2; L, left; L-AMB, liposomal amphotericin B; MGUS, monoclonal gammopathy of undetermined significance; MRI, magnetic resonance imaging; PJP, Pneumocystis jirovecii pneumonia; R, right; UD, undetectable; U.S., United States; VPS, ventriculoperitoneal shunt; VL, HIV RNA viral load. ^†, not specified.