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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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