Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine
cancer with a high risk of recurrence and
metastasis. MCC is generally associated with advanced age, fair skin, sun exposure, immunosuppression, and in the majority of cases, the Merkel cell polyomavirus. Neuroendocrine
malignancies are associated with a variety of paraneoplastic neurological syndromes (PNS), characterized as autoimmune responses to
malignancy-associated expression of neural
antigens. Our literature review underscores previous case reports of MCC-associated PNS with voltage-gated
calcium channel (VGCC) and anti-Hu (or ANNA-1)
autoantibodies. We present the case of a 59-year-old male with regionally metastatic
Merkel cell carcinoma complicated by the paraneoplastic manifestation of anti-
N-methyl-D-aspartate receptor (NMDAR)
encephalitis. His primary lower neck subcutaneous MCC and
metastasis were initially treated with surgery. Additional recurrent
lymph node metastases were successfully treated with definitive intensity-modulated
radiation therapy. His PNS improved with
rituximab therapy. Although rare, this case highlights that in the setting of
seizures and prominent psychiatric symptoms accompanying an MCC diagnosis, evaluation for autoimmune paraneoplastic
encephalitis is warranted. Awareness and detection of preexisting PNS are crucial in the era of
immune checkpoint inhibitors (ICI) for advanced MCC, where treatment with ICI has the potential to exacerbate preexisting autoimmune PNS and lead to worsened or even lethal neurologic immune-related adverse events (nirAEs).