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Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.
Liao, Xiaoyan; Schmidt, Alicia L; Zhang, Dongwei; Li, Peizi; Wang, Xintong; Ko, Huaibin M; Choi, Won-Tak; Alpert, Lindsay; Hao, Yansheng; Kovar-Peltz, Sierra; Polydorides, Alexandros D; Wanjari, Pankhuri; Mastro, Julius; Wang, Peng.
Afiliación
  • Liao X; Department of Pathology, University of Rochester Medical Center, Rochester, New York. Electronic address: xiaoyan_liao@urmc.rochester.edu.
  • Schmidt AL; Department of Pathology, University of Rochester Medical Center, Rochester, New York.
  • Zhang D; Department of Pathology, Indiana University, Indianapolis, Indiana.
  • Li P; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Wang X; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Ko HM; Department of Pathology, Columbia University, New York, New York.
  • Choi WT; Department of Pathology, University of California San Francisco, San Francisco, California.
  • Alpert L; Department of Pathology, University of Chicago, Chicago, Illinois.
  • Hao Y; Department of Pathology, University of Rochester Medical Center, Rochester, New York.
  • Kovar-Peltz S; Department of Pathology, University of Rochester Medical Center, Rochester, New York.
  • Polydorides AD; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
  • Wanjari P; Department of Pathology, University of Chicago, Chicago, Illinois.
  • Mastro J; Department of Pathology, University of Chicago, Chicago, Illinois.
  • Wang P; Department of Pathology, University of Chicago, Chicago, Illinois.
Mod Pathol ; 37(10): 100566, 2024 Jul 16.
Article en En | MEDLINE | ID: mdl-39025404
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mod Pathol Asunto de la revista: PATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mod Pathol Asunto de la revista: PATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos