Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease–Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms

IF 7.1 1区 医学 Q1 PATHOLOGY
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Abstract

The pathogenesis of neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) in the gastrointestinal tract remains poorly understood. This study aims to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared with a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation. Both groups exhibited a male predominance and similar age distribution. The NEC/MiNEN group was more likely to have a higher percentage of Crohn disease (9/18 vs 1/12; P = .024), occur in the rectum (9/18 vs 3/12) and small intestine (4/18 vs 0/12) (P < .01), be diagnosed on resection without a preceding biopsy (6/18 vs 0/12; P = .057), and have unidentifiable precursor lesions (10/18 vs 1/12; P = .018) than the control group. Synchronous carcinoma, advanced tumor stage (pT3 and pT4), and lymph node metastasis occurred at similar rates; however, the NEC/MiNEN group had a higher incidence of angiovascular invasion (14/18 vs 4/12; P = .024), distant metastasis (8/18 vs 1/12; P = .049), mortality (8/18 vs 2/12; P = .058), and worse survival (Kaplan–Meier; P = .023) than the control group. All tested cases were mismatch repair proficient. A Ki-67 proliferation index ranged from 25% to 100%. Next-generation sequencing in 11 NEC/MiNEN cases revealed low tumor mutational burdens but complex genetic abnormalities commonly involving TP53 (9/11; 82%), FBXW7 (4/11; 36%), and APC (3/11; 27%) genes, with the other genetic alterations randomly occurring in 1 or 2 cases. The neuroendocrine component, which shared similar molecular alterations as the nonneuroendocrine component, was subcategorized into intermediate (G3a) and high grade (G3b); the higher grade correlated with more genetic alterations. In conclusion, IBD-associated NEC/MiNEN shows diverse histologic features, variable precursor lesions, intricate genetic abnormalities, and aggressive biologic behavior. The classification and grading of gastrointestinal NEC/MiNEN may be refined for better clinical management.

炎症性肠病相关神经内分泌癌和神经内分泌-非神经内分泌混合肿瘤的临床病理和分子特征描述
人们对胃肠道神经内分泌癌(NEC)和神经内分泌-非神经内分泌混合瘤(MiNEN)的发病机制仍然知之甚少。本研究旨在描述炎症性肠病(IBD)患者 NEC/MiNEN 的临床病理和分子特征。研究人员从 6 个学术中心收集了 18 例手术切除的 IBD 相关肠癌,其中神经内分泌成分至少占 30%,并将其与对照组的 12 例无神经内分泌分化的 IBD 相关癌进行了比较。两组患者均以男性为主,年龄分布相似。NEC/MiNEN组患克罗恩病的比例更高(9/18对1/12,P=0.024),发生在直肠(9/18对3/12)和小肠(4/18对0/12)的可能性更大(P=0.024)。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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