Other tumors of the digestive system
2026-05-06 Paola Dal Cin, PhD , Matteo Fassan, MD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.University of Padua (Italy)
Keywords
mucosal melanoma ; germ cell tumors;liver metastases, peritoneal metastases; metastases to other digestive system sites ;carcinoma of unknown primary (CUP).Classification
Definition
They include mucosal melanoma and germ cell tumors and digestive system metastases e.g. liver metastases, peritoneal metastases, metastases to other digestive system sites and carcinoma of unknown primary (CUP).
| Other primary tumors of the digestive system | Genetic events |
|---|---|
| Mucosal melanoma of the digestive system | Primary malignant melanocytic neoplasms are rare tumor typically arisi in the anorectal region, while those in the other organs are usually metastatic in nature. They do not have UV radiation signature, but several somatic mutations involving mainly the KIT followed by NRAS. Compared with cutaneous melanomas, BRAF mutations are less frequent in mucosal melanomas, with a relatively higher proportion of non-Val600 mutations. 1,2 |
| Germ cell tumors of the digestive system | Germ cell tumors rae rare tumors derived from extragonadal germ cells, and he presentation varies depending on the patient’s age. Rare cases with molecular data have been reported, but chromosome 12p amplification and isochromosome 12p have been detected. 3 |
| Metastases | |
| Liver metastases | Cases of liver metastases outnumber primary liver carcinomas due to the liver’s blood supply via the portal venous system. Most metastatic lesions are histologically similar to the primary tumor, although loss of differentiation or changes in differentiation can occur in metastases. Typical molecular alterations can also help in identifying the site of the primary tumor. |
| Peritoneal metastasis | |
| Metastatic non-appendiceal tumors | Peritoneal metastasis from metastatic non-appendiceal tumors can affect all sites of the peritoneal cavity according movement of the peritoneal fluid. 4 Staging, prognostic factors and molecular analysis for treatment selection depend on the primary site of malignancy. 5 |
| Metastatic appendiceal mucinous neoplasms | The majority of mucinous carcinoma peritonei (MCP) cases harbor KRAS and GNAS mutations, often co-occurring, while NRAS, TP53, and SMAD4 mutations are less common and typically found in high-grade tumors. About 10% of cases are wildtype for RAS, GNAS, and TP53 mutations. Mismatch repair deficiency or microsatellite instability is absent. 6-13 |
| Metastases to other digestive system sites | Metastatic tumors can affect any organ of the digestive tract, but the liver is by far the most commonly involved. Metastases in the small intestine are reported more frequently than in other sites. Primary breast and lung cancers most commonly metastasize to the stomach and small intestine, renal cell carcinoma to the pancreas, and melanoma, renal cell carcinoma, and colorectal cancer to the gallbladder. The pattern of metastatic spread within the GI tract depends on the type and location of the primary tumor. Like all metastatic lesions, they are histologically similar to the primary tumor, although loss or changes in differentiation can occur, particularly under therapeutic pressure or hypoxic conditions. 14,15 |
| Carcinoma of unknown primary | Carcinoma of unknown primary (CUP) refers to metastatic disease where no primary tumour has been identified after extensive investigations. The majority of CUP are unfavourable where optimal treatment is undefinedand. Comprehensive genomic profiling should be performed according to some international guidelines (e.g. ESMO) 16,17 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 31383963 | 2020 | Prognostic model for patient survival in primary anorectal mucosal melanoma: stage at presentation determines relevance of histopathologic features. | Nagarajan P et al |
| 2 | 31398831 | 2019 | Atypical BRAF and NRAS Mutations in Mucosal Melanoma. | Dumaz N et al |
| 3 | 20128038 | 2010 | Primary mixed germ cell tumor of the liver with sarcomatous components. | Xu AM et al |
| 4 | 31082158 | 2026 | Peritoneal Surface Malignancies. | Menon G et al |
| 5 | 36700339 | 2023 | The molecular biology of peritoneal metastatic disease. | Bootsma S et al |
| 6 | 24633196 | 2014 | Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. | Davison JM et al |
| 7 | 24821835 | 2014 | Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations. | Liu X et al |
| 8 | 25274248 | 2015 | Genomic profile of pseudomyxoma peritonei analyzed using next-generation sequencing and immunohistochemistry. | Nummela P et al |
| 9 | 26475379 | 2015 | Molecular profiles of high-grade and low-grade pseudomyxoma peritonei. | Noguchi R et al |
| 10 | 28263231 | 2018 | Appendix-derived Pseudomyxoma Peritonei (PMP): Molecular Profiling Toward Treatment of a Rare Malignancy. | Gleeson EM et al |
| 11 | 36493333 | 2023 | Molecular Classification of Appendiceal Adenocarcinoma. | Foote MB et al |
| 12 | 37314541 | 2023 | Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei). | Wald AI et al |
| 13 | 39435876 | 2024 | Targeted Genetic Sequencing Analysis of 223 Cases of Pseudomyxoma Peritonei Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Shows Survival Related to GNAS and KRAS Status. | Gibson J et al |
| 14 | 18517275 | 2008 | Metastatic patterns of cancers: results from a large autopsy study. | Disibio G et al |
| 15 | 27421135 | 2016 | Incidence and origin of histologically confirmed liver metastases: an explorative case-study of 23,154 patients. | de Ridder J et al |
| 16 | 39007224 | 2024 | The evolution of molecular management of carcinoma of unknown primary. | Sivakumaran T et al |
| 17 | 39096927 | 2024 | Molecular guided therapies: a practice-changing step forward in cancer of unknown primary management. | Rassy E et al |
Citation
Paola Dal Cin, PhD ; Matteo Fassan, MD
Other tumors of the digestive system
Atlas Genet Cytogenet Oncol Haematol. 2026-05-06
Online version: http://atlasgeneticsoncology.org/solid-tumor/209371
