ArticleFrontiers in oncology2026
Case Report: Thymoma-associated stiff person syndrome and myasthenia gravis: an index case with exploratory exome sequencing and review of reported cases.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Methods: 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. Results: 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-glutamic 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, γ-aminobutyric acidergic (GABAergic) synapses and immune regulation. Conclusion: 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.
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