Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. Although progressive lymphadenopathy is a typical feature, extranodal involvement may also occur, including the gastrointestinal tract, skin, bone, thyroid, and testes. Central nervous system invasion is rare, so differentiating it from diseases such as inflammatory demyelinating disorder or infection is essential. DLBCL is therefore a challenge to diagnose, especially when the first findings are neurological symptoms. We report an unusual case of DLBCL that presented as transverse myelitis.

Non-Hodgkin’s lymphoma (NHL) may initially present with atypical neurological manifestations, including paraneoplastic neurological syndromes. Herein, we report the case showing an initial manifestation of systemic NHL with paraneoplastic demyelination in the brain that initially mimicked the symptoms of stroke, seizure, and brain tumor. A high index of suspicion and timely diagnostic workup is required to prevent diagnostic delay and commence proper management of the condition. In this situation, a whole-body FDG PET/CT could be useful to screen for occult malignancy.