ArticleVirchows Archiv : an international journal of pathology2017
Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift.
Article in Virchows Archiv : an international journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 36 citations in OpenAlex.
- Concept of neuroendocrine neoplasms of all organs with a focus on grading, subtyping.Virchows Archiv : an international journal of pathology · 2026Review
- Rapid Evolution of Metastases in Patients with Treated G3 Neuroendocrine Tumors Associated with NEC-Like Transformation and TP53 Mutation.Endocrine pathology · 2024Article
- Diagnostic issues in neuroendocrine neoplasms of the lung.Pathologie (Heidelberg, Germany) · 2024Review
- The Ki-67 antigen in the new 2021 World Health Organization classification of lung neuroendocrine neoplasms.Pathologica · 2021Review
- A Subset of Large Cell Neuroendocrine Carcinomas in the Gastroenteropancreatic Tract May Evolve from Pre-existing Well-Differentiated Neuroendocrine Tumors.Endocrine pathology · 2021Article
- Genomics of High-Grade Neuroendocrine Neoplasms: Well-Differentiated Neuroendocrine Tumor with High-Grade Features (G3 NET) and Neuroendocrine Carcinomas (NEC) of Various Anatomic Sites.Endocrine pathology · 2021Review
- Molecular Pathology of Well-Differentiated Pulmonary and Thymic Neuroendocrine Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Morphologic and molecular classification of lung neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2021Review
- Molecular studies of lung neuroendocrine neoplasms uncover new concepts and entities.Translational lung cancer research · 2019Article
- Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.Nature communications · 2019Article
- Stage IV lung carcinoids: spectrum and evolution of proliferation rate, focusing on variants with elevated proliferation indices.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Large Cell Neuroendocrine Carcinoma of the Mediastinum Successfully Treated with Systemic Chemotherapy after Palliative Radiotherapy.Internal medicine (Tokyo, Japan) · 2019Article
- Most high-grade neuroendocrine tumours of the lung are likely to secondarily develop from pre-existing carcinoids: innovative findings skipping the current pathogenesis paradigm.Virchows Archiv : an international journal of pathology · 2018Article
- Pulmonary neuroendocrine carcinomas-evidence for a spectrum of differentiation.Virchows Archiv : an international journal of pathology · 2018Article
- Distinctive pathological and clinical features of lung carcinoids with high proliferation index.Virchows Archiv : an international journal of pathology · 2017Article
- Classification of pulmonary neuroendocrine tumors: new insights.Translational lung cancer research · 2017Review
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21 authors at 8 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1-retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.
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