Paraneoplastic neurological syndromes associated with non-Hodgkin lymphoma: a case series.

Background: Paraneoplastic neurological syndromes (PNS) associated with lymphoma are rare diseases that usually have different peculiar features when compared to PNS associated with solid neoplasms.
Methods: We retrospectively identified patients with NHL-associated PNS. Clinical and demographic data are reported.
Results: We report two cases of NHL-associated PNS: a 72-years old female that presented with rapidly progressive cerebellar syndrome (RCPS) and a 65-years old male that presented with encephalomyelitis (confusion, sensory neuropathy, lower motor neuron involvement). Both PNS were associated with a NHL, small lymphocytic lymphoma and nodal marginal zone lymphoma respectively, and onconeural antibodies tested negative. All patients received first-line immunotherapy with absent or minimal benefit and died of intercurrent infection before cancer or immunosuppressive treatment.
Discussion: RCPS and encephalomyelitis rarely present in association with NHL. In our cases, those syndromes took place in the setting of non-aggressive advanced hematological disorders, had an unfavorable prognosis with minimal benefit from immunotherapy, and were seronegative for onconeural antibodies. Our patients fulfilled the criteria for "definite PNS" in the 2004 PNS criteria, but they would be classified as "probable", in the new 2021 PNS criteria. The newest criteria rely on onconeural antibodies testing and on the evidence of antigen expression in cancer cells, features that are usually absent in NHL-associated PNS. New antibodies are being discovered but are still not available to promptly test yet.
Conclusion: NHL-associated PNS are rare and bear unfavorable prognosis. The diagnosis should not be overlooked even in seronegative patients.
(© 2021. Fondazione Società Italiana di Neurologia.)