TOPLINE: 

Among patients with testicular cancer and paraneoplastic neurologic syndromes (PNS), most developed the neurological symptoms — including ataxia, hearing loss, and vertigo — before their cancer diagnosis.

METHODOLOGY:

• PNS are known to affect men with testicular germ cell tumors. Timely detection and treatment of PNS may help mitigate long-term neurological disabilities.
• To describe the characteristics of patients with testicular cancer and PNS, researchers at the Mayo Clinic conducted a retrospective study of 49 patients treated at their center (median age, 41 years). All had testicular germ cell tumors, mostly seminomas (33 of 49; 67%); nine patients had nonseminomatous tumors, and seven had regressed tumors. Most patients (n = 45) had definite PNS, while four had probable cases.
• Serum and cerebrospinal fluid were tested for neural antibodies, including KLHL11-IgG, LUZP4-IgG, and Ma2-IgG.
• Patient records were reviewed for demographic, oncologic, and neurologic data, with a median follow-up of 33 months from cancer diagnosis to final assessment.

TAKEAWAY:

• Most patients (80%) developed neurologic symptoms before their cancer diagnosis. The most common presenting features were ataxia (63% of patients), diplopia (59%), sensorineural hearing loss (45%), and vertigo (41%). However, patients with nonseminomatous tumors usually presented with sleep disturbances and/or seizure.
• Neural autoantibodies were detected in 94% of patients. KLHL11‑IgG was the most frequent antibody, detected in 32 patients — 20 alone and 12 with LUZP4-IgG — followed by Ma2‑IgG in nine cases and LUZP4-IgG alone in five cases.
• KLHL11-IgG was significantly associated with seminomas (odds ratio [OR], 8.06; P = .02), whereas Ma2-IgG was significantly associated with nonseminomatous tumors (OR, 54.25; P < .001). Similarly, when it came to neurological symptoms, Ma2-IgG antibodies were strongly associated with sleep disturbance (OR, 43.17; P < .001) and seizures (OR, 11.33; P = .004); KLHL11-IgG antibodies were associated with hearing loss (OR, 12.5; P < .001) and tinnitus (OR, 12.44; P = .006).
• Despite favorable cancer outcomes, with 80% of patients achieving cure or remission, only 16% had an improvement in neurological symptoms. Another 43% experienced stabilization, while 41% worsened despite immunomodulatory therapy. Nine patients died, with six deaths attributed to PNS.

IN PRACTICE:

Signs of PNS in younger patients should alert clinicians to test for neural antibodies and search for “any underlying occult malignant entity, especially [testicular germ cell tumors],” the authors wrote. For patients with testicular cancer, they added, early diagnosis of PNS by oncologists — via testing for these antibodies — may reduce long-term neurological dysfunction, a major cause of morbidity and mortality in this patient population.

SOURCE:

The study, led by Ehab Harahsheh, MBBS, Mayo Clinic Arizona in Scottsdale, was published online in JAMA Network Open.

LIMITATIONS: 

Potential selection bias and referral bias could affect the generalizability of the findings.

DISCLOSURES:

The study received funding from the Department of Defense. Several authors reported receiving grants or personal fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.