title: Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies.
abstract: Type 1 antineuronal nuclear autoantibody (ANNA-1, also known as "anti-Hu") is a marker of neurologic autoimmunity that is highly associated with small-cell lung carcinoma (SCLC). To determine the spectrum of symptoms and signs as well as the frequency of cancer in adult patients who are seropositive for ANNA-1, we reviewed 162 sequential patients (67% female) identified as ANNA-1-positive in a comprehensive immunofluorescence screening test. In 21% of these patients, the antibody test requested by the physician was not ANNA-1. By the end of the follow-up period, cancer had been found in 142 patients (88%). Ten of these lacked evidence of SCLC (4 had prostate carcinoma, 3 breast carcinoma, 1 both prostate carcinoma and melanoma, 1 lymphoma, and 1 squamous-cell lung carcinoma). Of the 132 patients (81%) with proven SCLC, 17 had one or more coexisting malignant neoplasms (6 had renal carcinoma, 4 another lung primary carcinoma, 3 prostate carcinoma, 3 breast carcinoma, and 4 assorted neoplasms). The diagnosis of SCLC in 128 patients (97%) followed the onset of paraneoplastic symptoms. SCLC was identified in 10 patients by chest MRI after an equivocal chest radiograph or CT; in 28 by bronchoscopy, mediastinoscopy, or thoracotomy; and in 7 at autopsy. Neurologic signs in decreasing frequency were neuropathy (sensory > mixed somatic > autonomic > cranial [especially cranial nerve VIII] > motor), cerebellar ataxia, limbic encephalitis, polyradiculopathy, associated Lambert-Eaton myasthenic syndrome, myopathy, myelopathy, opsoclonus/myoclonus, motor neuronopathy, brachial plexopathy, and aphasia. Nineteen patients had a solely gastrointestinal initial presentation, including gastroparesis, pseudo-obstruction, esophageal achalasia, or other dysmotility. We conclude that seropositivity for ANNA-1 can expedite the diagnosis and treatment of otherwise occult cancer in patients, especially tobacco abusers, with varied neurologic and gastroenterologic presentations. The search for SCLC should not end on discovering a different neoplasm.
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: D W
authors.initials: DW
authors.lastname: Kimmel
authors.forename: V A
authors.initials: VA
authors.lastname: Lennon
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D018288:Carcinoma, Small Cell / Q000453:epidemiology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D051959:ELAV Proteins; D005260:Female; D005767:Gastrointestinal Diseases / Q000276:immunology; D005769:Gastrointestinal Motility; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D009419:Nerve Tissue Proteins; D009422:Nervous System Diseases / Q000276:immunology; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D002556:Cerebrospinal Fluid Proteins; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins