KLHL11 IgG+ PNS is a disabling syndrome often associated with younger patients with testicular germ cell tumor (TGCT). Recently other tumors and older patients have been reported.

Evaluate age-related differences in clinical characteristics and outcomes among patients with Kelch-like protein-11 Immunoglobulin G seropositive (KLHL11 IgG+) associated paraneoplastic neurologic syndrome (PNS).

Sixty patients (median age 45 years (IQR 24-73; 97% male) with a KLHL11 IgG+ PNS were identified, of which 23 were classed as older (>50).  Among older patients, 16/20 (median age 62, range 51-73, 9% females) had an underlying cancer (seminomatous TGCT n=11; 69%, non-testicular cancer (NTC) n=5, 31%). Presentation of TGCT was extragonadal in 4/11 (36%). NTCs included esophageal cancer, lung adenocarcinoma, B-cell lymphoma, chronic lymphocytic leukemia and Mullerian Cancer. Presenting features included ataxia (78%), diplopia (57%), vertigo (57%) and dysarthria/dysphagia (48%). MRI was abnormal in 14/21 (61%), with cerebellar atrophy (n=4) most common, and CSF had inflammatory changes in 15/19 (65%). Of the 19 patients treated with immunotherapy, six had improvement, eight had stabilization, and five had progression of their symptoms, with a median surveillance time of 24 months. Thirteen patients had an MRS >= 3 at last follow-up. Compared to the younger cohort NTC was more frequent in patients >50 years (p=0.004). There was no significant difference in clinical features, imaging abnormalities and outcomes in the total cohort or the paraneoplastic cohort

KLHL11 IgG+ PNS is infrequently linked to non-testicular cancer, and more often observed in individuals >50. Patients within this demographic presenting with signs indicative of rhombencephalitis should be carefully evaluated, as there is potential for improvement, although overall prognosis for this syndrome remains unfavorable.