EBV driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline

Abstract

Brain biopsy in patients presenting with subacute encephalopathyis never straightforward and only undertaken when a ‘treatable condition’ is a realistic possibility.This 63 year old right handed, immunocompetent Caucasian woman presented with an 8 month history of rapidly progressive right-sided hearing impairment, a 4 month history of intermittent headaches, tinnitus, ‘dizziness’, dysphagia, nausea and vomiting, with the subsequent evolution of progressive gait ataxia and a subacute global encephalopathy. The possibility of CJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. She died 9 days later and autopsy brain examination confirmed widespread subacute infarction due to an EBV positive atypical NK/T-cell infiltrate with positivity for CD3, CD56, granzyme B, perforin and EBER with absence of CD4, CD5 and CD8 expression. Molecular studies for T-cell clonality were attempted but failed due to insufficient DNA quality. Serology was consistent with past EBV infection (EBV VCA and EBNA IgG Positive). There was no evidence of disease outside the CNS. Primary central nervous system NK/T-cell lymphoma is extremely rare. The rare reported cases all present with a discrete intracranial mass, unlike the diffuse infiltrative pattern in this case. Whilst the diffuse interstitial pattern is reminiscent of chronic active EBV infection (CAEBV) seen in other organ systems such as the liver and bone marrow, the clinical presentation and epidemiologic profile are not typical for CAEBV.

Clinical analysis of patients with primary and secondary extranodal natural killer/T‐cell lymphoma of central nervous system

“…However, after the Kruskal–Wallis test, it was concluded that there were no statistical significance between NKPI, PINK‐E, and primary site on the prognosis of CNS NKTL patients ( p = 0.461, p = 0.091, p = 0.770). At present, the cause of CNS NKTL is not yet clear, and some studies believe that EBV infection may be the predisposing factor 21,22 . This is inconsistent with our conclusion.…”

“…At present, the cause of CNS NKTL is not yet clear, and some studies believe that EBV infection may be the predisposing factor. 21,22 This is inconsistent with our conclusion. A total of 13 patients had EBV quantitative examination results before and after the CNS involvement.…”

An Unusual Case of EBV-Negative Primary CNS Lymphoma of Natural Killer/T-Cell Lineage

“…The diagnoses were established either on biopsy or by the detection of malignant cells in the cerebrospinal fluid. 12 - 25 …”

“…The diagnoses were established either on biopsy or by the detection of malignant cells in the cerebrospinal fluid. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] A recent review reported a collection of 18 cases of primary CNS T-cell lymphomas. 26 Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma (ALCL), ALK-positive and 2 ALCL, ALK-negative.…”

Chronic Active Epstein-Barr Virus Infection With Central Nervous System Involvement in Children: A Clinical Study of 22 Cases

“…CAEBV with CNS involvement has a poor prognosis, and there may be permanent neurologic sequelae such as cognitive decline, ataxia, paralysis and so on. 4 However, because of scarcity of reports regarding CAEBV with CNS involvement, the clinical characteristics of those patients remain unclear.…”