Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease
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, his symptoms were controlled with dehydration. During one episode on the day after admission, he developed transient headache, vomiting, and obnubilation. He developed seizures involving both hands and legs. He was treated with mannitol and dexamethasone intravenously. Anti-infection therapy including meropenem, itraconazole, voriconazole, and aciclovir was initiated; he recovered consciousness and headache disappeared on the following day.\nAt 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. Epstein-Barr virus (EBV)-encoded early RNA (EBER) was negative. Treatment consisted of non-Hodgkin's lymphoma-Berlin-Frankfurt-Milan-90 (NHL-BFM-90) protocol and rituximab. The patient completed chemotherapy on July 14, 2009. He continued to have persistent complete remission and was well on follow-up. 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. There was no family history of other cerebral vascular accidents or cerebral tumors.\nMagnetic resonance imaging (MRI) revealed multiple non-homogeneous, hypodense masses along the bilateral cortex, diffusing edema of the cerebral white matter, and demyelination (). The bone marrow showed normal presentation. Cerebrospinal fluid (CSF) was grey yellow, and laboratory examinations showed a slight decrease in glu (1.13 mmol/L, normal 2.5–4.5 mmol/L) and Cl (110.4 mmol/L, normal 120–130 mmol/L). In the CSF, protein levels were elevated (1,950 mg/L, normal 80–430 mg/L), and cell concentration was 6 × 106/L. Pandy test was positive. CSF pressure was normal. Evidence of tumor cells was absent on repeated examinations. CSF culture showed gram-positive bacteria; there was no evidence of the pathogens cryptococcosis, mycete, or mycobacterium. EBV-DNA copy number was 0. C-reactive protein (CRP) and procalcitonin (PCT) were normal.\nLumbar puncture was carried out in two weeks again after anti-infection therapy. CSF remained grey yellow. CSF smears showed many mature lymphocytes. CSF culture was negative. 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 mg/L). The patient's worsening mental and motor conditions were not resolved by two-week anti-infection therapy. He could not speak clearly or recognize his parents. The patient remained seizure-free. 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. These brain lesions were more severe than those revealed by prior MRI. His mental condition had not improved after 3 weeks of anti-infection therapy. Biopsy was performed on masses in the right cerebral front lobe to exclude Burkitt lymphoma relapse involving the central nervous system. Cerebral pathology revealed local pallium and white matter with a yellow appearance. Light microscopy revealed neurogliocyte and vessel hyperplasia accompanied by lymphocyte infiltration. 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 (). Special staining for Ag, periodic acid-schiff (PAS), and anti-acid was negative. There was no tumor in the brain. The biopsy tissue was cultured and no pathogen was found. Pathologic presentation coincided with chronic inflammatory changes, and pathologic diagnosis was cerebral vasculitis in the brain. On follow-up, the patient remains in a vegetative state.