cryptococcus infection is mainly caused by cryptococcus neoformans and c. gattii ( 1 - 4 ) . c. neoformans infection is a major worldwide cryptococcosis that primarily affects immunocompromised hosts ( 2 - 5 ) . c. gattii has traditionally been considered to be exclusive to tropical and subtropical climates , where it infects both healthy and immunocompromised patients ( 2,5 ) . recently , a reported outbreak of c. gattii in the temperate climate of the pacific northwest of north america has challenged our understanding of this disease ( 1 - 10 ) . reported high morbidity and mortality among patients with c. gattii infections in the united states , with over 90% of patients requiring hospitalization and a case fatality rate of over 30% ( 6 ) . among the four c. gattii genotypes ( vgi to vgiv , each containing subtypes ) , vgiia isolates predominate in the northwest of north america ( 3,4,6,7 ) . in japan , where c gattii infections are recognized as an imported infectious disease , sporadic cases have been documented since 2001 ( 5,8,11 - 14 ) . we herein report a case of cerebral and pulmonary cryptococcosis caused by c. gattii genotype vgiia in an immunocompetent japanese man who had not recently traveled overseas . to the best of our knowledge , this is the first reported case of c. gattii vgiia infection in an otherwise healthy japanese patient , and the second reported case in japan . in 2015 , a 39-year - old man presented to our hospital with a four - week history of headache and a two - week history of low - grade fever . he was a current smoker ( 15 pack - years ) and occasionally consumed alcohol . although he had traveled to hawaii in 2005 , dalian in china in 2008 , and hong kong in 2010 , he had no other history of overseas travel . he had been working as electrical engineering technician , and had not been exposed to any imported timber or animals . a physical examination revealed mild neck stiffness and a low - grade fever of 37.2c . a chest x - ray showed a tumor of approximately 50 mm in size in the right lower field , and a chest computed tomography ( ct ) scan showed a 4835 mm tumor with spiculation and notching on the right s9/10 ( fig . a gadolinium - enhanced brain magnetic resonance imaging ( mri ) scan showed multiple brain tumors with ring enhancement ( fig . the patient 's white blood cell ( wbc ) and platelet counts were high [ wbc , 12,900/mm ( normal range 4,000 - 9,000/mm ) ; platelet , 444,000/mm ( normal range 150,000 - 370,000/mm ) ] , and the blood chemistry findings were normal , including the levels of glucose , hemoglobin a1c , tumor markers , immunoglobulin , and autoimmune antibodies . a ) a chest x - ray film showing a tumor of approximately 50 mm in size in the right lower field . b ) a chest ct scan showing a 4835 mm tumor with spiculation and notching on the right s9/10 . c , d ) a gadolinium - enhanced brain mri scan showing multiple brain tumors with ring enhancement . based on the chest ct and brain mri findings , we suspected lung cancer with multiple brain metastases , and performed a bronchoscopic examination . a histopathological examination of the transbronchial lung biopsy ( tblb ) specimen from the right s9/10 revealed numerous fungal elements that appeared as encapsulated yeast with clear halos ( fig . the yeast was observed after periodic acid - schiff and grocott methenamine silver staining ( fig . a lumbar puncture had an elevated opening pressure ( 33 cm h2o ) , and the cerebrospinal fluid sample contained 264/mm cells , 84.1% of which were lymphocytes . india ink staining of the patients ' cerebrospinal fluid revealed encapsulated cryptococci as a halo against a black background ( fig . additional serological tests revealed that the patient was negative for hiv-1/2 antibodies and positive for cryptococcal antigen ; the cd4 + lymphocyte level in the patient 's peripheral blood was normal . the cryptococcal strain isolated from the bronchial lavage and cerebrospinal fluid was identified as c. gattii genotype vgiia using multi - locus sequence typing ( mlst ) , based on a dna sequence analysis of a set of polymorphic loci ( 8,15 ) . the transbronchial lung biopsy ( tblb ) specimens from the right s9/10 and india ink staining of cerebrospinal fluid . a ) numerous fungal elements are visible as encapsulated yeast with clear halos ( hematoxylin and eosin staining , tblb ) . b ) yeast ( cryptococcus ) is visible after staining with periodic acid - schiff and grocott methenamine silver stains ( tblb ) . c ) encapsulated cryptococci is visible as a halo against a black background ( india ink staining , cerebrospinal fluid ) . as a result , the patient was diagnosed with pulmonary and cerebral cryptococcosis induced by c. gattii genotype vgiia infection . he was treated with liposomal amphotericin b ( 5 mg / kg / day for more than 8 weeks ) , flucytosine ( 6,000 mg / body for more than 8 weeks ) . percutaneous lumbar drainage was performed more than 15 times within the first month to manage his increased intracranial pressure . after induction therapy , we are planning consolidation therapy and maintenance therapy with oral fluconazole . we herein describe a rare case of c. gattii infection that was diagnosed by the analysis of bronchoscopic and cerebrospinal fluid specimens . both specimen cultures were positive for a cryptococcal strain , and mlst based on a dna sequence analysis of a set of polymorphic loci was useful for identifying the isolates as c. gattii genotype vgiia . to the best of our knowledge , there are no previous reports of c. gattii vgiia infection in a healthy japanese individual without a history of recent travel to an endemic area . c. gattii is a basidiomycetous yeast that is present in the environment , namely in eucalyptus trees and soil and within animal hosts such as koalas ( 1 ) . although c. gattii is recognized as an endemic pathogen in australia , there have also been outbreaks of c. gattii in the pacific northwest of north america since the 1990s ( 1 - 3,7 - 10 ) . c. gattii has been isolated from more than 50 tree species and a broad range of animals , including dogs and cats ( 1,8,16 ) . the most common sites of c. gattii infection , which has an incubation period of 2 to 11 months , are the central nervous system ( cns ) and lungs ( 1 ) . although the risk factors for c. gattii infection are not well defined , several risk factors , such as a history of smoking and host genetic factors , have been reported ( 1 ) . headache , vomiting , and neck stiffness are the common neurological manifestations , and cough , dyspnea , chest pain and hemoptysis are common symptoms of lung involvement . systemic features such as chills , fever and weight loss are also common symptoms . although the clinical features of cryptococcosis caused by c. neoformans and c. gattii are similar , c. gattii is associated with large mass lesions of the lungs and brain and tends to be resistant to antifungal drugs ( 1,6,12,13 ) . c. gattii requires lengthy antifungal treatment and , particularly in infections of the cns , the aggressive management of increased intracranial pressure along with percutaneous lumbar drainage ( 1,2,13,17 ) . thus , from a clinical point of view , the differential diagnosis of c. neoformans and c. gattii is very important . nonetheless , in japan , as there is no commercial laboratory test to distinguish between c. neoformans and c. gattii , c. gattii infections may have been misdiagnosed as c. neoformans . since 2001 , there have been five reported cases of c. gattii infection in japan ( table ) . the first reported case was a healthy 71-year - old man who had traveled to australia for one week ( genotype : unknown ) ( 11 ) . the second reported case was a 44-year - old man with untreated diabetes mellitus and no recent history of overseas travel ( genotype : vgiia ) ( 5 ) . the third reported case was a 34-year - old woman who had traveled to korea and china , who had been treated for uterine cervical cancer one year previously ( genotype : vgi ) ( 12 ) . the fourth reported case was an immunocompetent 33-year - old man with no history of overseas travel ; however , he had been importing trees and soils from abroad to feed beetles ( genotype : unknown ) ( 13 ) . the fifth reported case was a 41-year - old previously healthy man who had traveled to several cities in china ( genotype : vgiib ) ( 8,14 ) . none of the five cases noted the presence of hiv infection and/or immunosuppressive drug use . in addition , brain mri scans showed cerebral cryptococcomas in all of the reported japanese cases . the sources of c. gattii infection were suspected to have originated from overseas in four of the five patients . the characteristics of our case , including the patient 's age , sex , and underlying disease status , are similar to these reported cases . the present case represents the second report of c. gattii vgiia infection in a japanese patient . the reported cases of c. gattii infection in japan . * : the location of hospital which the case was reported . # ; m : male , f : female . because the patient in the present case had no history of recent overseas travel , the c. gattii infection appears to have originated in japan . including our case , two cases are thought to have been infected with c. gattii within japan , and the cryptococcal strain in both of these cases was genotype vgiia . this also happens to be the strain that is most commonly isolated in the temperate climate of the pacific northwest of north america ( 5 ) . in the clinical setting of japanese hospitals , it is very difficult to distinguish c. neoformans and c. gattii in patients who are positive for cryptococcus spp . japanese commercial laboratory tests report c. gattii as c. neoformans ; thus , the number of c. gattii infections in japan may have been underestimated . nationwide investigations on cryptococcosis are necessary to assess the potential spread of c. gattii . in conclusion , we experienced a case of c. gattii genotype vgiia infection in a healthy japanese man without a history of recent overseas travel furthermore , particularly in immunocompetent patients with cryptococcoma , the present case emphasizes the importance of excluding c. gattii infection . lastly , ecological and environmental investigations are warranted in japan to better understand the epidemiological aspects of c. gattii infection .
a 39-year - old man presented to our hospital with a four - week history of headache and a two - week history of low - grade fever . 
 chest x - rays showed a tumor of approximately 50 mm in size in the right lower field . 
 a histopathological examination of a transbronchial lung biopsy specimen from the right s9/10 revealed numerous fungal elements that appeared as encapsulated yeast with clear halos . 
 gadolinium - enhanced brain magnetic resonance images showed multiple cerebral nodules . 
 cryptococcus gattii ( genotype vgiia ) was isolated from the bronchial lavage and cerebrospinal fluid specimens . 
 the patient was an immunocompetent japanese man who had not recently traveled to a c. gattii - endemic area .