Regionally Metastatic Merkel Cell Carcinoma Associated withParaneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis

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