Paraneoplastic Neurologic Syndromes Associated with Testicular Germ Cell Tumors: Clinical and Serological Characteristics
Ehab Harahsheh1, M Bakri Hammami2, Pranjal Gupta3, Brian A Costello4, John Cheville4, Anastasia Zekeridou5, Andrew McKeon4, Sean Pittock6, Divyanshu Dubey4
1Neurology, Mayo Clinic Arizona, 2Jacobi Medical Center, 3Wayne State University, 4Mayo Clinic, 5Neuroimmunology Laboratory, Mayo Clinic, 6Mayo Clinic Dept of Neuro
Objective:
To describe oncological, neurological and serological characteristics in patients with paraneoplastic neurological syndromes (PNS) and testicular germ cell tumors (TGCT).
Background:
TGCT are one of the most common malignancies affecting young patients. These tumors are associated with varied PNS and neural antibodies.
Design/Methods:
Patients evaluated at Mayo Clinic (January 1, 1990, to March 30, 2023) with histopathologically confirmed/regressed TGCT and PNS, were reviewed
Results:
Fifty patients (median age 41, IQR 33-46) with TGCT and PNS were identified. Thirty-three patients (66%) had seminomas, 10 (20%) had non-seminomatous GCT (NSGCT), and 7 (14%) had regressed TGCT. 74% of GCT were gonadal (n=37) and the rest were extra-gonadal (mediastinal (n=7) or retroperitoneal (n=6)). Eighty-percent of GCT were either stage 1 or 2 at the time of diagnosis. Eighty-percent (n=40) achieved cure or remission from their TGCT and only 12% (n=6) had relapses. Forty-seven patients (94%) with PNS tested positive for paraneoplastic antibodies, most commonly KLHL11 IgG (n=32, 64%, 11 with co-existing LUZP4-IgG) followed by LUZP4-IgG alone (n=18, 36%) and Ma2-IgG (n=9, 18%). The majority of KLHL11-IgG (n=24, 75%) and LUZP4-IgG (n=13, 72 %) seropositive cases had seminomas while most of Ma2-IgG (n=7, 77%) had NSGCT. The most common PNS phenotypes associated with seminomas were rhombencephalitis (64%), often presenting with ataxia (64%) and/or hearing loss (55%) whereas NSGCT more frequently had limbic encephalitis (60%), presenting with seizures (50%) and/or cognitive decline (40%). Only 15% of cases showed improvement in PNS despite treatment of cancer and/or immunotherapy. Nine patients died, 6 (67%) of which were related to PNS progression, and rest were unknown or non-cancer related reasons
Conclusions:
KLHL11-IgG with/without LUZP4-IgG is the most common autoantibody associated with TGCTs, especially seminomas. Predominant neural IgG specificities and clinical presentations differ based on the TGCT type. Most of these patients have favorable cancer outcomes, but they accrue significant long-term neurologic disability.