What is the approach to diagnosing teratomas, especially in the context of N-methyl-D-aspartate (NMDA) receptor encephalitis?

Diagnosing Teratomas in NMDA Receptor Encephalitis

All young and middle-aged adults with typical NMDA receptor encephalitis should be specifically screened for teratoma using transvaginal or transabdominal pelvic ultrasound in females (or testicular ultrasound in males), as 20-50% of female patients harbor an ovarian teratoma that requires surgical removal. 1

Initial Screening Approach

First-Line Imaging: CT Chest, Abdomen, and Pelvis

• CT with contrast of the chest, abdomen, and pelvis is the reasonable initial screening modality given its lower cost compared to FDG-PET and ability to provide structural details for surgical planning if a tumor is identified 1

• Major limitations include low sensitivity for early breast and testicular cancers, and CT is not preferred in children, pregnant women, or women of childbearing age for pelvic imaging 1

• CT contrast is relatively safer in pregnant women compared to MRI gadolinium-based contrast 1

Targeted Pelvic Imaging for NMDAR Encephalitis

• Transvaginal or transabdominal pelvic ultrasound is the specific screening tool for ovarian teratoma in female patients presenting with the typical clinical picture of NMDAR encephalitis 1

• In males with suspected NMDAR encephalitis, testicular ultrasound should be performed to screen for testicular teratoma 1

• Pelvic MRI should be obtained if ultrasound findings are equivocal 1

• Extraovarian and extratesticular germ cell tumors may be detected on CT-based or MRI-based general cancer screening 1

Additional Screening Modalities

Whole Body FDG-PET

• FDG-PET is more sensitive for early neoplasms when initial CT screening is negative or inconclusive and suspicion of cancer remains high 1

• FDG-PET can be used as the initial screening tool when there is a contraindication to high-resolution CT or iodine contrast 1

• Insurance coverage can be an obstacle, but insurers should consider fewer restrictions given the high likelihood of coexisting cancer in autoimmune encephalitis patients 1

Breast Cancer Screening

• Mammogram should be performed if the initial CT screen is negative, as breast cancer is a common source of paraneoplastic syndromes in females 1

• Patients with strong family history of breast cancer or those not up to date with regular mammograms warrant special attention 1

• Breast MRI may improve sensitivity if mammogram is negative but suspicion remains high 1

Tumor Prevalence and Demographics

Gender and Age Considerations

• In female patients with NMDAR encephalitis, 20-50% will have an associated tumor, which is almost always an ovarian teratoma 1

• In men and children, the rate of associated tumors is lower 1

• Up to 50% of women over age 18 with NMDAR encephalitis have ovarian teratomas 2, 3

• The median age at presentation of NMDAR encephalitis is 25 years with a male to female ratio of 1:2 1

Critical Clinical Pitfalls

Imaging-Negative Teratomas

• Teratomas can occasionally be found only on subsequent imaging long after initial presentation, or even at oophorectomy despite negative conventional imaging 4

• Very rarely, patients have undergone oophorectomy despite negative imaging, with pathology demonstrating teratoma and resulting in marked clinical improvement 4

• Teratomas can be found at multiple sites other than ovaries, including mediastinal and bilateral ovarian locations, so whole-body evaluation may be helpful 5

• Teratomas of the fallopian tube can cause anti-NMDAR encephalitis; imaging analysis and exploratory laparoscopies of the fallopian tube as well as the ovary should be considered 6

Ongoing Surveillance

• Tumor screening should be performed annually for several years, particularly if treatment response is poor or relapses occur 1

• This is critical because approximately 30% of patients with NMDAR encephalitis can relapse despite no evidence of tumor presence 1

Integration with Treatment

• Tumor removal (particularly ovarian teratoma) is a critical component of treatment, as the tumor often triggers the autoimmune response 2, 7, 8

• Removal of the teratoma is first-line therapy when detected on imaging 4

• Surgical removal of both fallopian tubes and ovaries with normal appearance should be considered for patients in whom immunotherapy is not effective 6

• The decision to pursue oophorectomy with negative imaging presents a major clinical challenge, requiring consideration of risks including sterilization and early menopause versus possibility of death without response to immunosuppression 4