We present a patient with known Merkel cell carcinoma treated with immune checkpoint inhibitor therapy who developed progressive cranial neuropathies and was found to have Kelch-like protein 11 (KLHL11) antibody-associated rhombencephalitis.

The KLHL11 antibody was discovered in 2019 and has been linked to paraneoplastic rhombencephalitis. It is most commonly associated with testicular germ cell tumors and carries a poor prognosis.

An 84-year-old male with a 15-year history of metastatic squamous cell carcinoma, more recently diagnosed with Merkel cell carcinoma and treated with avelumab, developed progressive bilateral ophthalmoplegia, dysphagia, and dysarthria accompanied by gait ataxia. MRI showed T2 hyperintensity in the left dorsal pons. CSF studies revealed lymphocytic pleocytosis, elevated protein, increased IgG index, and 9 unique oligoclonal bands. Imaging, including a PET scan, CT of the chest, abdomen, and pelvis, and scrotal ultrasound were negative for malignancy. KLHL11 antibody was identified with titers of 1:64 in the CSF and 1:7680 in the serum.   

Initial treatment with 3 days of intravenous methylprednisolone and 5 days of intravenous immunoglobulin showed no improvement. Subsequently, a course of 5 additional days of intravenous methylprednisolone and 5 plasma exchange treatments (PLEX) resulted in partial improvement of the diplopia but no significant improvement in his other symptoms. The patient was then treated with intravenous cyclophosphamide and was discharged. Two weeks later, he developed a bowel obstruction requiring colectomy and died.

KLHL11-IgG rhombencephalitis is a rare paraneoplastic syndrome typically associated with testicular germ cell tumors. This case suggests a potential association with Merkel cell carcinoma and immune checkpoint inhibitor therapy, though confirmation is pending further tissue analysis, which may clarify the underlying etiology.