ReviewEuropean respiratory review : an official journal of the European Respiratory Society2026
Thymic neuroendocrine tumours: molecular landscape, immune microenvironment and therapeutic perspectives.
Review in European respiratory review : an official journal of the European Respiratory Society, 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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4 authors.
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Abstract
backgroundThymic neuroendocrine tumours (T-NETs) are rare, aggressive malignancies with distinct biology and poor outcomes. Current management is extrapolated from other neuroendocrine tumours (NETs), highlighting a critical need for a synthesised understanding of their unique molecular and immune landscape.
methodsWe conducted a comprehensive narrative review (2000-2026) of T-NETs, interrogating PubMed, Embase, Web of Science and Scopus. Focus was placed on clinicopathology, molecular alterations, tumour immune microenvironment and therapeutic outcomes.
resultsT-NETs encompass a spectrum from well-differentiated carcinoids to high-grade carcinomas. Their molecular drivers are grade-specific, featuring TP53 (tumour protein p53)/RB1 (retinoblastoma 1) loss and chromosomal instability in high-grade tumours, alongside prevalent chromatin remodelling and PI3K (phosphatidylinositol 3-kinase)-mTOR (mechanistic target of rapamycin) dysregulation. The immune microenvironment is predominantly "inflamed", with heterogeneous PD-L1 (programmed death-ligand 1)/VISTA (V-domain Ig suppressor of T-cell activation) expression and T-cell infiltration that is often restrained by a myeloid-rich stroma. For clinical management, surgical resection is curative for localised disease. In advanced stages, therapy is extrapolated from other NETs and includes somatostatin analogues (for somatostatin receptor-positive tumours), everolimus, temozolomide-based regimens and, in selected cases, peptide receptor radionuclide therapy. Immunotherapy and novel combinations represent emerging investigational avenues.
conclusionT-NETs are biologically distinct thymic malignancies. Improved care will require thymus-specific molecular and immune profiling, standardised diagnostic criteria, and prospective collaborative studies to move beyond extrapolated treatment paradigms.
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