23152 Paraneoplastic Autoantibody Evaluation, Serum (PAVAL)

​Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.

Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

2. This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.

​Negative results do not exclude cancer.​

Intravenous immunoglobulin treatment prior to the serum collection may cause a false-positive result.

This evaluation does not include Ma2 autoantibody (also known as ​MaTa). Ma2 autoantibody has been described in patients with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advisable in men who present with unexplained subacute encephalitis. N-methyl-D-aspartate receptor antibodies have been reported in women with paraneoplastic encephalitis related to ovarian teratoma.

Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer. The cancer may be new or recurrent, is usually limited in metastatic volume, and is often occult by standard imaging procedures. Autoantibodies specific for onconeural proteins found in the plasma membrane, cytoplasm, and nucleus of neurons, glia, or muscle are generated in this immune response and serve as serological markers of paraneoplastic autoimmunity. Cancers recognized in this context most commonly are small-cell lung carcinoma, thymoma, ovarian (or related Mullerian) carcinoma, breast carcinoma, and Hodgkin lymphoma. Pertinent childhood neoplasms recognized thus far include neuroblastoma, thymoma, Hodgkin lymphoma, and chondroblastoma. An individual patient's autoantibody profile can predict a specific neoplasm with 90% certainty but not the neurological syndrome.

Four classes of autoantibodies are recognized in this evaluation:

-Antineuronal nuclear antibodies (ANNA-1, ANNA-2, ANNA-3)

-Anti-glial/neuronal nuclear antibodies (AGNA-1; also known as Sox1)

-Neuronal and muscle cytoplasmic antibodies (Purkinje cytoplasmic antibody [PCA]-1, PCA-2, PCA-Tr, collapsin response-mediator protein [CRMP]-5, and amphiphysin)

-Plasma membrane cation channel, P/Q-type calcium channel, and dendrotoxin-sensitive potassium channels. These autoantibodies are potential effectors of neurological dysfunction.

Patients who are seropositive usually present with subacute neurological signs and symptoms, such as encephalopathy, cerebellar ataxia, myelopathy, radiculopathy, plexopathy, or sensory, sensorimotor, or autoimmune neuropathy, with or without a neuromuscular transmission disorder: Lambert-Eaton syndrome, myasthenia gravis, or neuromuscular hyperexcitability. Initial signs may be subtle, but a subacute multifocal and progressive syndrome usually evolves. Sensorimotor neuropathy and cerebellar ataxia are common presentations, but the clinical picture in some patients is dominated by striking gastrointestinal dysmotility, limbic encephalopathy, basal ganglionitis, or cranial neuropathy (especially loss of vision, hearing, smell, or taste).

Cancer risk factors include previous or family history of cancer, history of smoking, or social or environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less neurological morbidity and offer the best hope for survival.