To report the clinical and radiological associations and treatment outcomes of paraneoplastic neurologic disorders (PND) associated with squamous cell carcinomas

The data on PND associated with squamous cell carcinoma are largely confined to case reports and cohort studies are lacking.

It is a retrospective cohort study. Patients with PNS were identified using the hospital and neuroimmunology databases. Cases were included in the study if there were adequate demographic, clinical, radiological, treatment and outcome details. The updated 2021 paraneoplastic neurologic syndrome criteria were also applied.

Eleven patients were identified to have PNS. Rapidly progressive cerebellar syndrome was the most common PNS phenotype (5/11,46%), followed by longitudinally extensive or tract specific myelopathy, brainstem encephalitis and polyradiculoneuropathy – 2 patients each. All cases had the onset of neurological symptoms before the detection of cancer (median duration, 11 months (range 1-38)). Primary sites of squamous carcinomas were in decreasing order of frequency: lung (4/11, 37%), oropharynx (tonsil 2, tongue 1 (3/11, 28%)), metastatic squamous cell carcinoma with unknown primary (3/11, 28%).  All patients had an abnormal cerebrospinal fluid profile while abnormal magnetic resonance imaging was seen in 6 (55%) patients. High risk antibodies were seen in five patients (45%, ANNA1 IgG (n=1), CRMP5 IgG (n=2), Ma2 antibody (n=2). Immune therapy was instituted in 8/11 (73%) patients. The median duration of follow up was 15.5 months (range 3-114). Nine patients (9/11; ~ 82%) had either stabilization or improvement in their status. Only two patients met the 2021 PNS Care criteria. Four patients had a score ≤ 3 (36%).

PNSs in association with squamous cell carcinoma are rare. Future studies should evaluate expression of target neural antigen in tumor tissue.