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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.
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“Seropositivity for any of the above-mentioned antibodies may therefore prompt further investigation for occult malignancy (e.g. whole-body fluorodeoxyglucose-positron emission tomography).”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [432]
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Metadata
- Authors
- Lucchinetti, C. F., Kimmel, D. W., & Lennon, V. A.
- Affiliations
- Mayo Clinic (US)
- Venue
- Neurology
- Published
- 1998-03
- Volume
- 50
- Issue
- 3
- Pages
- 652-657
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2130696458
- Cited by
- 499
- References
- 50
- Citations by year
- 2026: 10 · 2025: 1 · 2024: 19 · 2023: 13 · 2022: 11 · 2021: 25 · 2020: 20 · 2019: 19 · 2018: 11 · 2017: 18 · 2016: 22 · 2015: 16 · 2014: 12 · 2013: 23 · 2012: 22
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca037343-11)
- National Cancer Institute (CA-37343)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- anti-Hu antibodies, small cell lung cancer, paraneoplastic syndrome, multiple primary neoplasms, gastrointestinal motility disorders, Lambert-Eaton myasthenic syndrome, limbic encephalitis, opsoclonus-myoclonus syndrome, cancer screening, tobacco use, achalasia, gastroparesis
- MeSH terms
- Adult, Aged, Autoantibodies, Cerebrospinal Fluid Proteins, Female, Gastrointestinal Diseases, Gastrointestinal Motility, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasms, Nerve Tissue Proteins, Nervous System Diseases, Paraneoplastic Syndromes, Incidence, RNA-Binding Proteins, Carcinoma, Small Cell, ELAV Proteins
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