Testicular Teratomas Are Definitively Associated with Autoimmune Encephalitis
Yes, testicular teratomas and seminomas are established causes of autoimmune encephalitis, particularly anti-Ma2 antibody-associated limbic encephalitis and anti-NMDAR encephalitis, and should be actively screened for in young and middle-aged males presenting with encephalitis. 1, 2, 3
Key Tumor-Encephalitis Associations
Testicular germ cell tumors cause paraneoplastic neurological syndromes through two main mechanisms:
- Anti-Ma2 antibody-mediated encephalitis is specifically associated with testicular tumors (both teratomas and seminomas) and presents with limbic encephalitis, brainstem symptoms, and ataxia 1, 4, 5
- Anti-NMDAR encephalitis occurs with testicular teratomas, though far less commonly than with ovarian teratomas 2, 6
- Testicular teratomas and seminomas are among the most common neoplasms associated with autoimmune encephalitis overall, alongside small cell lung cancer, thymic neoplasms, breast cancer, and ovarian teratomas 1, 3
Mandatory Screening Protocol
All young and middle-aged males with typical autoimmune encephalitis presentations require testicular ultrasound screening: 1, 2, 3
- Testicular ultrasound (7.5 MHz transducer) is the specific screening modality for detecting testicular teratomas in males with suspected NMDAR or Ma2 antibody encephalitis 1, 2
- Initial CT chest/abdomen/pelvis with contrast is reasonable for broader cancer screening but has low sensitivity for early testicular cancers 1, 2, 3
- FDG-PET should be considered when CT is negative but clinical suspicion remains high 2, 3
Clinical Presentation Patterns
Neurological symptoms often precede tumor diagnosis by months to years: 4, 7
- Limbic encephalitis symptoms include subacute cognitive impairment, seizures (partial and generalized), psychiatric disturbances, altered consciousness, and memory deficits 5, 7
- Brainstem involvement and cerebellar ataxia are particularly suggestive of Ma2 antibody-associated disease with testicular primary 1, 8
- MRI typically shows hyperintense lesions in medial temporal lobes on T2/FLAIR sequences 7
Critical Treatment Principle
Tumor removal is the most effective treatment for paraneoplastic limbic encephalitis and is essential for neurological recovery: 4, 5
- Radical inguinal orchiectomy should be performed for testicular primary tumors 1, 5
- Anti-Ma2 antibody-positive encephalitis associated with testicular tumors is an exception among paraneoplastic syndromes—it responds well to tumor treatment and immunotherapy, unlike most other onconeuronal antibody syndromes 4
- Immunosuppressive therapy (corticosteroids) should be combined with tumor resection 5, 6
- Retroperitoneal lymph node dissection may be required for metastatic disease 8
Important Clinical Pitfalls
"Burned out" testicular tumors can cause paraneoplastic syndromes despite minimal or absent testicular findings: 8
- Retroperitoneal metastases may be the only detectable disease when the primary testicular tumor has regressed 8
- FDG-PET can identify occult retroperitoneal disease when testicular ultrasound is negative 8
- Maintain high suspicion even with equivocal testicular imaging if paraneoplastic antibodies are positive 8
Annual tumor screening should continue for several years, particularly if treatment response is poor or relapses occur 2
Antibody Testing Strategy
Both serum and CSF should be tested for paraneoplastic antibodies: 1, 3
- Some antibodies are more sensitive in CSF (NMDAR, GFAP) while others are more sensitive in serum (onconeuronal antibodies including Ma2, LGI1) 1
- Antibodies against intracellular antigens (including Ma2) have stronger cancer associations 1, 3
- The implicated antibody is usually unknown at initial presentation, necessitating broad cancer screening 1