Abstract Details

Title Paraneoplastic Neurologic Syndromes Associated with Testicular Germ Cell Tumors: Clinical and Serological Characteristics

Topic Autoimmune Neurology

Presentation(s) S38 - Autoimmune Neurology: Peripheral Autoimmunity, Paraneoplastic Disease, Checkpoint Inhibitors, and Neurosarcoidosis (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Background TGCT are one of the most common malignancies affecting young patients. These tumors are associated with varied PNS and neural antibodies.

Objective To describe oncological, neurological and serological characteristics in patients with paraneoplastic neurological syndromes (PNS) and testicular germ cell tumors (TGCT).

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.

Authors/Disclosures
Ehab Y. Harahsheh, MBBS (Mayo Clinic College of Medicine) PRESENTER	Dr. Harahsheh has nothing to disclose.
M Bakri Hammami, MD (Jacobi Medical Center)	Dr. Hammami has received intellectual property interests from a discovery or technology relating to health care.
Pranjal Gupta, MD	Dr. Gupta has nothing to disclose.
Brian Costello (Mayo Clinic)	No disclosure on file
John Cheville	No disclosure on file
Anastasia Zekeridou, MD, PhD, FAAN (Neuroimmunology Laboratory, Mayo Clinic)	The institution of Dr. Zekeridou has received research support from Roche/Genentech. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care. Dr. Zekeridou has received intellectual property interests from a discovery or technology relating to health care.
Andrew McKeon, MD (Mayo Clinic)	The institution of Dr. McKeon has received research support from National Institutes of Health. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received intellectual property interests from a discovery or technology relating to health care. Dr. McKeon has received publishing royalties from a publication relating to health care.
Sean J. Pittock, MD (Mayo Clinic Dept of Neurology)	Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arialys. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received publishing royalties from a publication relating to health care.
Divyanshu Dubey, MD, FAAN (Mayo Clinic)	The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received research support from UCB. Dr. Dubey has received research support from David J. Tomassoni ALS Research Grant Program . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care.