Objective:

To report a rare case of systemic double-hit Diffuse Large B-Cell Lymphoma masquerading as autoimmune encephalopathy.

Background:

DLBCL is an aggressive lymphoma, particularly in double-hit cases (translocations involving c-MYC, BCL2, and/or BCL6). The incidence of secondary CNS involvement at diagnosis is 5%. Double-hit confers high risk of CNS involvement with 3-year incidence of 13%,. Recommended workup includes PET, excisional node biopsy, and CSF testing.

Design/Methods:

N/A

Results:

A 44-year-old woman experienced subacute onset of ataxia, dysarthria, hiccups, hypersomnia, and disinhibition. Exam revealed mild left-sided hemiparesis and hyperreflexia. MRI brain showed nodular enhancement with vascular and leptomeningeal involvement of bilateral frontal lobes (right-predominant). Days later, there was new involvement of bilateral basal ganglia, internal capsules, and cerebral peduncles extending to midbrain. CSF studies showed nonspecific lymphocytic pleocytosis. Autoimmune encephalitis was suspected and treated with steroids and IVIG with mild improvement. Autoantibody testing detected low-titer CSF GAD and IgLON5 antibodies, further anchoring the diagnosis of autoimmune encephalitis. Contrast CT of the chest, abdomen, and pelvis showed no lymphadenopathy.  PET scan was ordered due to worsening symptoms, and revealed retroperitoneal and cervical lymphadenopathy with tonsillar uptake; biopsy showed DLBCL ABC subtype positive for BCL2 and cMYC with negative FISH. She has shown improvement after starting a methotrexate-based treatment regimen (MR-CHOP).

Conclusions:

This case is unusual as the first manifestation of DLBCL was CNS-predominant without any systemic symptoms or radiographic findings. White matter changes and leptomeningeal enhancement distracted from covert malignancy not appreciated on CT.  While a positive IgLON5 antibody would support an autoimmune etiology of this constellation of symptoms, this was a red herring, as the initial CSF titer was low and repeat testing was negative. This case suggests that subacute progressive neurologic symptoms merit earlier PET imaging and workup of broad differentials.