intravascular lymphomatosis ( ivl ) is an uncommon systemic disease in which malignant proliferation of lymphocytes occurs exclusively in the vessels . the clinical symptoms are nonspecific in most cases , making an early diagnosis difficult [ 1 , 2 ] . a unique characteristic of this disorder is that the proliferation of malignant lymphocytes occurs only within the vessels , in contrast to primary central nervous system lymphoma ( pcnsl ) . we herein report a patient with ivl who presented with fever of unknown origin ( fuo ) and in whom a brain mass developed , mimicking pcnsl . a 75-year - old right - handed female patient was admitted to our hospital for the evaluation of recurrent fevers . she had been well until 3 weeks before admission , when fever and fatigue developed . she had a history of cholecystectomy , spinal compression fracture , and an old cerebral infarction of the left middle cerebral artery . after the brain infarction , she developed aphasia and right hemiplegia and became dependent on a wheelchair . she showed paroxysmal atrial fibrillation , and warfarin was prescribed to prevent a second stroke . on examination , her blood pressure was 150/70 mm hg , her pulse 90 beats per minute , and her body temperature was 37.5c . there was a small decubitus ulcer on the sacrum and a nonpitting edema in both legs . her blood levels of lactate dehydrogenase ( ldh ) , c - reactive protein , and soluble interleukin-2 receptor ( sil-2r ) were high at 458 iu / l ( normal < 229 iu / l ) , 16.8 mg / dl ( normal < 0.8 mg / dl ) , and 3,458 u / ml ( normal < 515 u / ml ) , respectively . her blood levels of electrolytes , glucose , alkaline phosphatase , alanine aminotransferase , aspartate aminotransferase , amylase , brain natriuretic protein , and vitamin b1 were normal , as were her renal and thyroid function . lumbar puncture was performed ; there was no pleocytosis in the cerebrospinal fluid , but the protein and igg levels were increased to 85 mg / dl ( normal < 50 mg / dl ) and 17 mg / dl ( normal < 4 mg / dl ) , respectively . a contrast - enhanced ct of the chest , abdomen , and pelvis failed to reveal any abnormal lesions that could have caused the fever . a brain mri obtained 3 weeks after admission showed an old infarction but was otherwise normal . tests for antibodies to hepatitis b , hepatitis c , human immunodeficiency virus , human t - lymphotropic virus , and the treponema pallidum were negative . antibiotic treatments including ciprofloxacin at 600 mg / day , panipenem / betamipron at 1 g / day , and ceftazidime at 2 g / day combined with arbekacin at 200 mg / day were undertaken , but all were ineffective . the fever continued for more than 3 weeks and fulfilled the criteria for fuo . because the serum levels of ldh and sil-2r remained high , we suspected a hematogenous tumor such as myeloma , and bone marrow puncture was performed , but the result was normal . although there were no skin lesions , we strongly suspected ivl and thus performed a random skin biopsy . the biopsy was obtained from 1 lesion of the purpura on the abdomen and 2 regions of the skin with a normal appearance on the abdomen and left thigh . histological examination revealed atypical cells lodged in the intravascular lumens in the subcutaneous tissue of the normally appearing left thigh region ( fig . higher magnification revealed vessels filled with large malignant lymphoid cells and eosinophilic nucleoli ( fig . 1b ) ; the cells were stained with cd20 antibodies but not with cd3 ( fig . the patient was thus diagnosed with ivl ( intravascular large b - cell lymphoma ) . an mri obtained 7 weeks after admission showed a mass lesion involving the right basal ganglia , thalamus , corona radiata , uncus , and crus cerebri ( fig . 2 ) . the mass was isointense on a t1-weighted image , hyperintense on a t2-weighted image , and exhibited mild restricted diffusion on a diffusion - weighted image ( dwi ) . an mri obtained 9 weeks after admission showed an enlargement of the mass ( fig . ivl is an uncommon systemic disease in which malignant proliferation of lymphocytes occurs exclusively in vessels . studied 10 cases of ivl in a single institution and reported that fuo and a mental status change were the most common signs , being present in 60% of cases . they reported that the duration of fuo ranged from 2 to 6 months . in our patient , fuo had been present for 7 weeks until the diagnosis of ivl was made . in patients with long - standing fuo histological confirmation of the malignant proliferation of lymphocytes in vessels is required for the diagnosis of ivl . although the number of reported cases of ivl in which antemortem diagnosis was achieved by biopsy is small , such biopsies reportedly involved the brain , adrenal gland , kidney , liver , spleen , lung , bone marrow , muscles , and the skin . because dermatological manifestations including nodules , plaques , and macules are present in up to one third of patients with ivl , skin biopsies should be conducted when any skin lesions are found in patients in whom ivl is suspected . the involvement of clinically unaffected skin has been reported in autopsy findings , and this involvement serves as the basis for a random skin biopsy . in our case , we performed a random skin biopsy because of the strong suspicion of ivl based on the high serum levels of ldh and sil-2r . the mri findings of ivl have not been well characterized because the number of reported cases is relatively small . however , the most commonly reported mri findings are multifocal lesions that are hyperintense on t2-weighted images , mimicking small infarctions . baehring et al . recently evaluated 5 patients with ivl in whom serial diffusion - weighted mris were obtained . they reported that multifocal dwi lesions are the most common observations , suggesting the presence of small - vessel ischemia that is probably caused by the occlusion of vessels by malignant lymphomatous cells . a brain mass developed in the present patient . the mass was isointense on t1-weighted images and hyperintense on t2-weighted images and it showed a restricted diffusion on dwi and homogeneous gd enhancement . the differential diagnoses for a brain lesion appearing hyperintense on t2-weighted images with gd enhancement may include pcnsl , toxoplasmosis , glioblastoma multiforme , abscess , metastasis , tumefactive multiple sclerosis , and primary angiitis of the central nervous system ( pacns ) . of these etiologies , homogeneous gd enhancement and restricted diffusion on dwi make pcnsl most likely , and the serological findings suggesting a lymphomatous disease could have allowed for a diagnosis of pcnsl in the present case if the brain biopsy had not been performed . moreover , when the mass appeared , there were no definitive ischemic lesions , which are common radiological findings of ivl . antibiotic treatment was not effective and blood culture was negative in this case ; however , there was still a probability of developing a brain abscess after admission . despite this , the lack of a characteristic thick rim of contrast enhancement around the lesion was considered to make a brain abscess unlikely . pacns is a rare vasculitis of unknown etiology that exclusively involves the central nervous system . commonly reported mri findings of pacns are multifocal deep gray and subcortical hyperintensities on t2-weighted images . recently , some cases of pacns have been reported to present as brain masses , mimicking brain tumors . the low sensitivity of the characteristic angiographic signs and the lack of specific findings in general medical laboratory investigations make a brain biopsy necessary for the diagnosis of pacns . the findings in our case suggest that if pacns is suspected in a patient with a brain mass , a random skin biopsy prior to brain biopsy should be considered to allow for the avoidance of a more invasive brain biopsy . however , some authors have reported that extravasation of malignant lymphocytes can occur to some degree in the late stage of ivl [ 1 , 7 ] . to the best of our knowledge , there have been 4 cases of ivl in which postmortem examination revealed a brain mass and 5 cases of tissue - proven ivl in which mri showed a brain mass ( table 1 ) [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ] . our case is notable because it is the first description of dwi of a brain mass in a patient with ivl . dwi is a series of t2-weighted sequences that detect the movement of protons in water . the causes of restricted diffusion on dwi include acute ischemia , cerebral abscesses , diffuse axonal injury , active demyelination , and highly cellular tumors such as lymphoma . dwi change in acute ischemia is commonly known to occur , and marked restricted diffusion in acute ischemia generally remains for 35 days . in our case , the restricted diffusion enlarged over 2 weeks , supporting the high cellularity of the mass as the cause of restricted diffusion . although there are no pathognomonic presenting symptoms or signs in pcnsl , focal neurological deficits such as personal changes or cerebellar signs are reportedly rather common . patients with pcnsl may infrequently present with fuo as the initial clinical manifestation . the majority of patients with pcnsl reportedly develop a solitary supratentorial tumor , and the most common sites are the frontal lobe , temporal lobe , parietal lobe , deep nuclei , occipital lobe , cerebellum , or the brain stem . considering the fact that there are no specific symptoms or signs of pcnsl and that the brain mass noted in our case was a solitary mass located in the basal ganglia , which is a common site of pcnsl , the present case could have been misdiagnosed as pcnsl instead of ivl if the random biopsy had not been performed . a combination of cyclophosphamide , doxorubicin , vincristine , and prednisone with the recombinant anti - cd20 antibody rituximab ( r - chop ) is the most commonly employed treatment in patients with ivl . on the contrary , chop is either ineffective or toxic in the treatment of pcnsl , and methotrexate with brain radiation therapy is usually employed . if the skin biopsy had not been performed , this patient could have been treated by methotrexate , which is not effective against ivl . mri showed a brain mass mimicking pcnsl ; however , a random skin biopsy confirmed the diagnosis of ivl . although postmortem examination was not performed , the brain mass noted on mri was considered to be a collection of malignant lymphomatous cells invading from the vessels .
we herein report a 75-year - old female patient with intravascular lymphomatosis ( ivl ) who presented with fever of unknown origin . 
 examination , including contrast - enhanced ct and 67ga scintigraphy , failed to show any lesions . 
 her blood levels of lactate dehydrogenase and soluble interleukin-2 receptors were high , suggesting a lymphomatous tumor . 
 a bone marrow puncture was negative , and a random skin biopsy revealed a monoclonal proliferation of naked , large lymphocytes in the vascular space of the subcutaneous tissue , confirming the diagnosis of ivl . 
 mri , performed 7 weeks after admission , showed a brain mass mimicking primary central nervous system lymphoma . 
 the mass was considered to be a collection of malignant lymphocyte cells invading from the vessels . without the random skin biopsy , 
 this case may have been misdiagnosed as primary central nervous system lymphoma .