a 5-year - old boy who presented with a one - month history of headache and vomiting two years after being cured of burkitt lymphoma was admitted to our cancer center on march 7 , 2011 . prior to being admitted to our center , he was initially treated at a local hospital with mannitol - induced dehydration and dexamethasone for suspected relapse of lymphoma involving the brain . his symptoms were partially controlled with mannitol and dexamethasone but worsened with regular exacerbation of mental and movement retrogression . he manifested with abnormal gait and declined ability to play games without fever . during each exacerbation , anti - infection therapy including meropenem , itraconazole , voriconazole , and aciclovir was initiated ; he recovered consciousness and headache disappeared on the following day . at the age of 3 years , the patient was diagnosed with stage iv burkitt lymphoma in our cancer center . fluorescence in situ hybridization ( fish ) examination showed positive for myc / igh translocation . treatment consisted of non - hodgkin 's lymphoma - berlin - frankfurt - milan-90 ( nhl - bfm-90 ) protocol and rituximab . there was a family history of fulminant infectious mononucleosis ( fim ) ; his older brother and maternal male cousin died of this condition at the age of 10 months and 2 years , respectively . the patient was diagnosed with confirmed mutation in sh2d1a , a c > t nonsense substitution mutation . magnetic resonance imaging ( mri ) revealed multiple non - homogeneous , hypodense masses along the bilateral cortex , diffusing edema of the cerebral white matter , and demyelination ( figure 1 ) . cerebrospinal fluid ( csf ) was grey yellow , and laboratory examinations showed a slight decrease in glu ( 1.13 mmol / l , normal 2.54.5 mmol / l ) and cl ( 110.4 mmol / l , normal 120130 mmol / l ) . in the csf , protein levels were elevated ( 1,950 mg / l , normal 80430 mg / l ) , and cell concentration was 6  10/l . csf culture showed gram - positive bacteria ; there was no evidence of the pathogens cryptococcosis , mycete , or mycobacterium . glu and cl levels in csf were lower than normal ( 0.79 mmol / l and 117.2 mmol / l , respectively ) , whereas protein levels were high ( 1,910 the patient 's worsening mental and motor conditions were not resolved by two - week anti - infection therapy . mri scans of his brain showed multiple non - homogeneous , hypodense masses along the bilateral cortex , diffuse abnormal signals in the bilateral cerebral cortex , and extensive edema in the bilateral white matter . biopsy was performed on masses in the right cerebral front lobe to exclude burkitt lymphoma relapse involving the central nervous system . immunohistochemistry revealed moderate cd68 , cd3 , cd2 , cd5 , cd8 , cytotoxic granule - associated rna binding protein ( tia1 ) , and glial fibrillary acidic protein ( gfap ) staining and mild ki-67 staining ( 1% ) . t - cell receptor ( tcr ) rearrangment , cd4 , and eber were negative ( figure 2 ) . special staining for ag , periodic acid - schiff ( pas ) , and anti - acid was negative . pathologic presentation coincided with chronic inflammatory changes , and pathologic diagnosis was cerebral vasculitis in the brain . on follow - up , mri scans of the brain with contrast - t1 sagittal ( a ) and axial ( b ) views show multiple non - homogeneous , hypodense masses along the bilateral cortex as indicated by arrows . a and b , histologic examination of the cerebral tissue showing lymphocyte infiltration and hyperplasia with neurogliocytes and vessels ( he , 100 ) . immunochemistry stains positive for cd3 ( c , 100 ) and cd8 ( d , 100 ) , negative for epstein - barr virus - encoded early rna ( eber ) ( e , 200 ) , and positive for glial fibrillary acidic protein ( gfap ) ( f , 100 ) . x - linked lymphoproliferative disease ( xlp ) , also known as duncan disease , is a rare immunodeficiency disease characterized by severe immune dysregulation . since xlp was initially described in 1975 , more than 270 boys with the condition have been identified in 80 kindreds ( table 1 ) . xlp affects 1 to 3 million boys , with disease onset occurring in childhood or early adolescence . xlp , x - linked lymphoproliferative disease ; fim , fulminant infectious mononucleosis ; hlh , hemophagocytic lymphohistiocytosis . the patients were born between 1941 and 2005 ; 63 were born in or after 1990 . the other types included lymphoproliferative disorders ( 82 cases , 30% ) , aplastic anemia ( 8 cases , 3% ) , and vasculitis and lymphomatoid granulomatosis ( 7 cases , 3% ) . xlp is caused by mutations in the sh2d1a / sap gene on the x chromosome at position xq25 . the sh2d1a gene encodes the adaptor molecule sap that binds to cell surface receptors from the signaling lymphocyte activation molecule ( slam ) family . sap is an important regulator of normal immune function in t cells , natural killer cells , natural killer t ( nkt ) cells , and possibly b cells , . defects in this gene result in sap protein deficiency , limiting sap 's ability to compete with other sh2 domain - containing proteins to bind slam . other inhibitory signals via binding slam competitively lead to immune defects . furthermore , humoral defects arise from the interaction between impaired mature b lymphocytes and cd4 t cells , resulting in the expansion of lymphocytes that are primarily reactive cd8 t cells , . in the case reported here , cerebral pathology showed infiltration of lymphocytes positive for cd8 and negative for cd4 . lymphocyte expansion can lead to infiltration of several organs , including the liver and bone marrow . a diagnosis of confirmed xlp1 is established on clinical features of xlp1 and mutation in sh2d1a in a male patient . clinical diagnosis is based on clinical manifestations and family history in absence of genetic status . clinical manifestations of xlp vary , ranging from lymphoma , hlh , dysgammaglobulinemia , and fim to aplastic anemia . patients often manifest more than one clinical type , or the clinical type may change from one type to another . this patient presented with stage iv burkitt lymphoma at the age of 3 years and progressed to cerebral vasculitis . although ebv was initially identified as a catalyst for xlp , there was no evidence of ebv infection in either disease , suggesting that some clinical features of xlp are independent of ebv . reported that 30% of patients with xlp can develop lymphoma and dysgammaglobulinemia , which occur in both ebv - positive and ebv - negative patients . moreover , 10% of patients with xlp are reported to have immunological abnormality before ebv exposure . sap - deficient patients , like the patient in this case , can also be diagnosed with a lymphoproliferative disorder defined as cerebral vasculitis after infection and cerebral tumor are excluded . this presentation is rarely seen in xlp patients and should be distinguished from burkitt lymphoma relapse involving the central nervous system . one proposition is that cerebral vessels may be attacked upon activation of cd8 cells , which can be caused by antigens independent of ebv or altered clearance of viruses such as ebv . although ebv was not detected in the patient 's blood in this case , ebv infection can not be fully excluded without evidence that ebv is absent in the brain , lung , or skin tissue by pcr . based on this case presentation , we infer that cerebral vasculitis associated with xlp can be characterized by retrogression in mentality , movement , and cognition . prognosis for burkitt lymphoma treated with standard chemotherapy is better than that for xlp1 . in a clinical study , the overall mortality for patients with xlp after undergoing chemotherapy or anti - virus or steroid therapy was 75% . in contrast , the cure rate exceeds 80% for burkitt lymphoma treated with nhl-95 protocol . the prognosis for xlp1 has greatly improved since 1995 , when seemayer et al . reported an overall survival of 25% . indeed , 71.4% of patients in the european registry for xlp were alive at the time of data analysis . because the prognosis for hlh in xlp1 without hematopoietic stem cell transplantation ( hsct ) is extremely poor , mortality in the untransplanted group of xlp1 secondary to hlh remains as high as 81.3% . although more than 60% of patients survive without hsct , it will be important to follow patients carefully , as this group manifested as lymphoma or dysgammaglobulinemia may progress to hlh or fim in clinical course . for this case , wherein the patient consistently showed no evidence of ebv infection , hsct should have been a better strategy . however , before onset of cerebral vasculitis , when the patient is stable and relatively well , it is challenging to make the decision to perform a transplant . notably , the survival rate for xlp patients without transplant was 84.4% , and these patients did not manifest hlh . an allogenic transplant procedure , on the other hand , will be associated with mortality . central nervous system vasculitis can be seen in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythmatosis . remission is achievable with methylprednisone and cyclophosphamide or agents targeting b cells or tumor necrosis factor-. myeloabative or reduced intensity allogeneic hsct targets activated cd8 t cells and corrects the underlying immune defect , thereby curing xlp - associated central nervous system vasculitis . clinicians should inquire family history when facing a lymphoma patient with a family history of unexplained death in male cousins . if primary diagnosis of lymphoma with xlp is made , hsct is considered in options of treatment after thorough evaluation . lymphoma relapse in the brain after several years for a patient in complete remission is rare . after being cured for several years , any patient with lymphoma who has signs associated with the brain should undergo brain biopsy if possible . the prognosis of xlp - cerebral vasculitis may improve if methylprednisone and cyclophosphamide treatments are started as soon as possible .
lymphoma is seen in up to 30% of patients with x - linked lymphoproliferative disease ( xlp ) , but cerebral vasculitis related with xlp after cure of burkitt lymphoma is rarely reported . 
 we describe a case of a 5-year - old boy with xlp who developed cerebral vasculitis two years after cure of burkitt lymphoma . 
 he had burkitt lymphoma at the age of 3 years and received chemotherapy ( non - hodgkin 's lymphoma - berlin - frankfurt - milan-90 protocol plus rituximab ) , which induced complete remission over the following two years . at the age of 5 years , the patient first developed headache , vomiting , and then intellectual and motorial retrogression . 
 his condition was not improved after anti - infection , dehydration , or dexamethasone therapy . 
 no tumor cells were found in his cerebrospinal fluid . 
 magnetic resonance imaging showed multiple non - homogeneous , hypodense masses along the bilateral cortex . 
 pathology after biopsy revealed hyperplasia of neurogliocytes and vessels , accompanied by lymphocyte infiltration but no tumor cell infiltration . despite aggressive treatment , 
 his cognition and motor functions deteriorated in response to progressive cerebral changes . 
 the patient is presently in a vegetative state . 
 we present this case to inform clinicians of association between lymphoma and immunodeficiency and explore an optimal treatment for lymphoma patients with compromised immune system .