Interlesional Genomic Heterogeneity in Small Bowel Adenocarcinoma: Evidence from Matched Primary and Peritoneal Metastatic Lesions - 26/03/26

Doi : 10.1016/j.clinre.2026.102815

Alessandro Vanoli ^1,^2,^{^{a
Co-first Authors}}, Paola Parente ^3,^{^{a
Co-first Authors}}, Giuseppe De Lisi ^1,^{^{a
Co-first Authors}}, Erica Travaglino ², Francesca Antoci ², Erica Quaquarini ⁴, Federica Grillo ^5,⁶, Tommaso Colella ¹, Caterina Antoniacomi ¹, Camilla Guerini ^1,⁷, Paola Alberizzi ², Chandra Bortolotto ^8,⁹, Marco Vincenzo Lenti ^10,¹¹, Paolo Pedrazzoli ^10,⁴, Matteo Fassan ^12,¹³, Marco Paulli ^1,², Antonio Di Sabatino ^10,^11,^{^{b
Co-last Authors}}, Salvatore Corallo ^10,^4,^{^{b
Co-last Authors},}^⁎

¹ Department of Molecular Medicine, University of Pavia, Pavia, Italy

² Unit of Anatomic Pathology, IRCCS San Matteo Hospital Foundation, Pavia, Italy

³ Pathology Unit, Azienda Ospedaliero Universitaria Policlinico Foggia, Foggia, Italy

⁴ Department of Oncology, Comprehensive Cancer Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

⁵ Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy

⁶ IRCCS Ospedale Policlinico San Martino, Genoa, Italy

⁷ Unit of Anatomic Pathology and Diagnostic Cytopathology, ASL Novara, Borgomanero, Italy

⁸ Diagnostic Imaging and Radiotherapy Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

⁹ Radiology Institute, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

¹⁰ Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

¹¹ First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

¹² Department of Medicine (DIMED), University of Padua, Padua, Italy

¹³ Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy

^⁎ Corresponding author: Salvatore Corallo, Department of Internal Medicine and Therapeutics University of Pavia, Address: Corso Strada Nuova, 65 – 27100 Pavia (Italy), Tel +39 0382501557. Department of Internal Medicine and Therapeutics University of Pavia Corso Strada Nuova, 65 – 27100 Pavia (Italy)

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Abstract

This study analyzed the spatiotemporal heterogeneity of metastatic small bowel adenocarcinoma (SBA) with peritoneal involvement by examining genomic profiles of six SBAs and their corresponding peritoneal metastases using next-generation sequencing. Four cases had synchronous peritoneal metastases, showing complete genomic concordance with the primary tumors. In contrast, one of the two cases with metachronous peritoneal metastases developed an additional KRAS mutation compared to the paired primary, shifted from moderately to poorly differentiated morphology, and exhibited mismatch-repair deficiency by immunohistochemistry, while remaining microsatellite stable by NGS. These findings suggest interlesional molecular heterogeneity in SBA and emphasize the need for re-biopsies in precision oncology for metachronous metastases.

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Keywords : small intestinal cancer, immune-mediated intestinal disorder, immunotherapy, microsatellite instability, molecular profiling