When and how is it appropriate to search for an underlying tumor?

In seropositive autoimmune encephalitides, the probability and most common localization of an underlying tumor can be predicted regardless of the detected neuronal antibody (Table 1). Of course, risk factors (e.g. smoking history), age and gender should also be taken into account in these considerations. Tumor diagnostics should be graded (Table 2).

Tabelle 1: Association between cancer and the most common antineuronal antibodies. SCLC = Small cell lung cancer, LEMS = Lambert-Eaton myasthenic syndrome, DNER = Delta/notch-like epidermal growth factor-related receptor, *in some patients Ma antibodies coexist, meaning that brainstem syndromes and non-testicular tumors will predominate.

Antibody

Most common cancers

Antibodies against intracellular antigens (onconeural antigens). Cancer-related >95%

Anti-Hu (ANNA-1)

Lung cancer (85%), mostly SCLC, neuroblastoma, Merkel cell carcinoma, other tumors with neuroendocrine differentiation

Anti-Yo (PCA-1)

Ovarian cancer, breast cancer

Anti-CV2/CRMP5

SCLC, thymoma

Anti-Ta/Ma2*

Testicular tumor

Anti-Ri (ANNA-2)

Breast cancer, ovarian cancer, SCLC

Anti-amphiphysin

Breast cancer, SCLC

Anti-recoverin

SCLC

Anti-SOX-1 (AGNA)

SCLC (in LEMS)

Anti-Tr (PCA-Tr), DNER

Hodgkin's, non-Hodgkin's lymphoma

Anti-Zic4

SCLC (idiopathic forms known, cancer-related <90%)

Antibodies against synaptic antigens (neuronal surface antigens). Variable cancer relationship

Anti-NMDA receptor

Age and gender dependent. Women aged between 12-45 years in Germany
Ovarian teratomas (25%)

Anti-AMPA receptor

SCLC, thymoma, breast cancer (50%)

Anti-GABA(B) receptor

SCLC (50%)

Anti-LGI1

Thymoma (<5%)

Anti-CASPR2

Depending on the syndrome: Limbic encephalitis various tumors <5%; Morvan syndrome (40%)

Anti-mGluR5

Hodgkin’s lymphoma (approx. 50%)

Anti-DPPX

B cell neoplasms (<10%)

Anti-GABA(A) receptor

Thymoma (30%)

Anti-neurexin-3α

Not known

Anti-IgLON5

No known cancer relationship

Modified after the Practice Guideline on “Paraneoplastic Syndromes” issued by the German Neurological Society (DGN)

 

Table 2: Graded tumor diagnostics guided by the presumed localization for select tumors. Sensitivity in parentheses, if known. EB-US = Endobronchial ultrasound

Cancer Diagnostics
Primary Secondary Tertiary
Lung cancer Chest CT (80-85%),
Chest MRI
FDG-PET or FDG-PET/CT Bronchoscopy/EB-US and, if indicated, fine-needle aspiration
Mediastinoscopy, if indicated
Thymoma Chest CT (75-90%),
Chest MRI
FDG-PET or FDG-PET/CT  
Breast cancer Mammography (80%),
Ultrasound
Breast MRI  
Ovarian cancer Transvag. ultrasound (69-90%) + CA-125 Pelvic/abdominal CT FDG-PET or
FDG-PET/CT
Ovarian teratoma Transvag. ultrasound (69-90%) MRI (93-98%) Chest CT (extrapelvic teratomas)
Testicular tumors Ultrasound (72%) + β-HCG, AFP Pelvic/abdominal CT (76%),
abdominal MRI
If indicated FDG-PET or FDG-PET/CT (malignant teratomas)
Lymphoma Chest CT/abdominal ultrasound FDG-PET or FDG-PET/CT  
Skin cancer (Merkel cell carcinoma) Dermatological examination
Biopsy, if applicable

Modified after the Practice Guideline on “Paraneoplastic Syndromes” issued by the German Neurological Society (DGN)

 

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References

Brändle SM, Cerina M, Weber S et al. PNAS March 2, 2021 118 (9) e1916337118.

Dieses Paper wurde vom Research4Rare Verbund zum Paper of the Month gewählt und erscheint im April dieses Jahres im BMBF Newsletter!

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