{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:40:21Z","timestamp":1777887621933,"version":"3.51.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thymoma is frequently associated with myasthenia gravis (MG), but the coexisting of stiff person syndrome (SPS) is exceedingly rare. This overlap syndrome poses diagnostic and therapeutic challenges, and its immunopathogenic basis is not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 55-year-old woman with thymoma-associated SPS and MG was evaluated using detailed clinical, electrophysiological, serological and radiologic investigations. In addition, a PubMed-based literature review of published cases of thymoma complicated by SPS with MG was conducted. Exploratory whole-exome sequencing (WES) with pathway analysis were performed on resected thymoma tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The index patient presented with progressive gait unsteadiness, painful axial and lower-limb stiffness, dysarthria and dysphagia. Examination revealed marked truncal rigidity and exaggerated startle responses. Serology demonstrated high-titer anti\u2013glutamic acid decarboxylase 65 (GAD65) and elevated acetylcholine receptor (AChR) antibodies. Chest computed tomography (CT) demonstrated an anterior mediastinal soft-tissue mass highly suggestive of thymoma. Treatment with immunotherapy, symptomatic agents and thymectomy resulted in substantial clinical improvement. The literature search identified seven additional patients with thymoma-associated SPS and MG, typically characterized by GAD65 positivity, World Health Organization (WHO) B1\/B2 mixed histology, and favorable outcomes after combined immunotherapy and surgical resection. WES of the thymoma revealed a somatic CACNA1A frameshift variant and variants in immune-signaling genes, with enrichment of pathways related to calcium channels, \u03b3-aminobutyric acidergic (GABAergic) synapses and immune regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Thymoma-associated SPS and MG constitute a rare but recognizable overlap syndrome. Integration of clinical, literature and exploratory genomic data supports a convergent mechanism involving thymic epithelial neoplasia, impaired inhibitory neurotransmission and neuromuscular junction autoimmunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1801960","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:18:56Z","timestamp":1777609136000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Thymoma-associated stiff person syndrome and myasthenia gravis: an index case with exploratory exome sequencing and review of reported cases"],"prefix":"10.3389","volume":"16","author":[{"given":"Lu","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Clinical Medicine, Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingbo","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kewei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Qiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, The First Hospital of Jilin University","place":["Changchun, China"]},{"name":"College of Clinical Medicine, Jilin University","place":["Changchun, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(21)00297-0","article-title":"Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders","volume":"21","author":"Punga","year":"2022","journal-title":"Lancet Neurol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"200394","DOI":"10.1183\/16000617.0394\u20132020","article-title":"Thymic tumours and their special features","volume":"30","author":"Basse","year":"2021","journal-title":"Eur Respir Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1186\/s12933-025-02984\u20132","article-title":"Elevated triglyceride-glucose index and risk of thymoma-associated myasthenia gravis: a prospective analysis from the UK Biobank","volume":"24","author":"Zhu","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2025.103875","article-title":"Myasthenia gravis with antibodies against the AChR, current knowledge on pathophysiology and an update on treatment strategies with special focus on targeting plasma cells","volume":"24","author":"Man\u00e9-Damas","year":"2025","journal-title":"Autoimmun Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/cmi.2010.74","article-title":"Thymoma and autoimmunity","volume":"8","author":"Shelly","year":"2011","journal-title":"Cell Mol Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12974-022-02448\u20134","article-title":"Independent risk factors for myasthenic crisis and disease exacerbation in a retrospective cohort of myasthenia gravis patients","volume":"19","author":"Nelke","year":"2022","journal-title":"J Neuroinflamm"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.2887","article-title":"Efficacy and safety of rituximab for new-onset generalized myasthenia gravis: the RINOMAX randomized clinical trial","volume":"79","author":"Piehl","year":"2022","journal-title":"JAMA Neurol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1038\/s41582-024-01012\u20133","article-title":"Stiff-person syndrome and related disorders - 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