Tumors of the jejunum and ileum

2026-06-02   Paola Dal Cin, PhD , Matteo Fassan, MD 

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2.University of Padua (Italy)

Keywords
Small bowel, jejunum, ileum, ademoma, dysplastic lesions, adenocarcinoma. adenoma-carcinoma pathway

Classification

Definition

Neoplasms are much less frequent in the small bowel and share many features with their colorectal counterparts. Metastatic tumors are the most encountered malignancies in the small bowel, whereas adenocarcinomas are frequently primary tumors. 1

Known risk factors for both small bowel polyps and adenocarcinomas are celiac disease, alcohol and smoking, as well as, familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, and Crohn’s disease. 2-4 Interestingly, in patients with Crohn’s disease, the tumor usually occurs in the ileum, where Crohn’s disease is prevalent.


Adenomas originating in the small bowel mucosa probably are premalignant lesions and many primary adenocarcinomas of the small intestine arise in adenomas.  Jejunal and ileal adenocarcinomas show adjacent residual adenoma in a quarter of cases, suggesting an adenoma–carcinoma pathway like in the colorectum. 5  Dysplastic lesions resembling inflammatory bowel disease–associated colorectal dysplasia are frequently found in ileal adenocarcinomas associated with Crohn disease. 6

Solitary Peutz-Jeghers polyps (PJP) can arise anywhere along the GI tract and occur in patients that are clinicopathologically distinct from patients with Peutz-Jeghers syndrome OMIM:175200. 7 


Tumors of the jejunum and ileum Genetic events
Benign epithelial tumours and precursors
Conventional jejunoileal adenomaJejunal and ileal adenomas are less common than their duodenal counterparts. Their molecular alterations are, therefore, essentially unknown, 8,9 and more likely to originate in a genetic syndrome e.g. Familial adenomatous polyposis (FAP) OMIM:175100, All jejunal and ileal adenomas reported to date are generally indistinguishable from their colorectal counterparts, where APC mutations , and less commonly KRAS mutations are the primary pathways to tumorigenesis. 9
Hamartomatous polyps: Peutz–Jeghers polypSolitary Peutz-Jeghers polyp (PJP) is more frequently diagnosed in the small bowel, when a single hamartomatous lesion is identified in the gastrointestinal tract of patients without mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome (PJS) or germaline STK11 mutations. 7,10 They occur in patients that are clinicopathologically distinct from patients with PJS. 11,12 However, rare patients with somatic STK11 mosaicism have been described.13
Malignant epithelial tumors
Jejunoileal adenocarcinoma TP53 , KRAS , APC , PIK3C , and SMAD4 are most commonly altered genes in small bowel adenocarciomas, amomg others, which were also observed in duodenal and colorectal adenocarcinomas. 14-16 A variable but relatively high proportion of mismatch repair (MMR) deficiency / microsatellite instability (MSI) has been reported, typically due to MLH1 promoter hypermethylation.17 IDH1 mutations , almost always the Arg132Cys variant, often also associated with MGMT methylation, were detected in ileal adenocarcinomas mainly associated with Crohn disease. 6,15,18 Conversely FGFR3, FGFR1 and KDR mutations have been associated with Lynch syndrome.15 MSI-immune subtype and the mesenchymal subtype have been associated with celiac disease (CD)–associated small bowel adenocarcinomas. 19
Risk of jejunoileal adenocarcinoma is associated in patients with Crohn disease or celisc disease , 2,4 less frequently in genetic syndrome as familial adenomatous polyposis, Lynch syndrome, and Peutz–Jeghers syndrome , as well as environmental factors. 3,20

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1308773302019Tumors of the jejunum and ileum: a pattern-based imaging approach on CT.Kim SW et al
2347041272022Small bowel adenocarcinoma in Crohn's disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes.Chin YH et al
3355653982022Epidemiology, Risk Factors and Diagnosis of Small Bowel Adenocarcinoma.Aparicio T et al
4396942142025High Risk of Digestive Cancers in Patients With Celiac Disease: A Nationwide Case-Control Cohort Study.Jannot AS et al
572489081981Adenomas of the small intestine: a clinicopathologic review of 51 cases and a study of their relationship to carcinoma.Perzin KH et al
6379882812024IDH1-mutated Crohn's disease-associated small bowel adenocarcinomas: Distinctive pathological features and association with MGMT methylation and serrated-type dysplasia.Guerini C et al
7377769582023Clinicopathologic comparison between sporadic and syndromic Peutz-Jeghers polyps.Liu BL et al
8313920542019Upper gastrointestinal neoplasia in familial adenomatous polyposis: prevalence, endoscopic features and management.Campos FG et al
9339223052021Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations.Vanoli A et al
10349550632022Solitary Peutz-Jeghers Type Polyp of Jejunum with Gastric Fundic and Antral Gland Lining Mucosa: A Case Report and Review of Literature.Liu BL et al
11315829722019Long-Term Outcome in Patients with a Solitary Peutz-Jeghers Polyp.Iwamuro M et al
12311077262019Clinical and Histologic Overlap and Distinction Among Various Hamartomatous Polyposis Syndromes.Gilad O et al
13325042102021Two cases of somatic STK11 mosaicism in Danish patients with Peutz-Jeghers syndrome.Jelsig AM et al
14357786982022Genetic analysis of Japanese patients with small bowel adenocarcinoma using next-generation sequencing.Tatsuguchi A et al
15387450882024Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases.Aparicio T et al
16380625622024Relationship Between Immunophenotypes, Genetic Profiles, and Clinicopathologic Characteristics in Small Bowel Adenocarcinoma.Hoshimoto A et al
17283332392017Small Bowel Carcinomas in Coeliac or Crohn's Disease: Clinico-pathological, Molecular, and Prognostic Features. A Study From the Small Bowel Cancer Italian Consortium.Vanoli A et al
18313886692020Clinicopathological and Molecular Characterisation of Crohn's Disease-associated Small Bowel Adenocarcinomas.Liao X et al
19316963602020Small-bowel carcinomas associated with celiac disease: transcriptomic profiling shows predominance of microsatellite instability-immune and mesenchymal subtypes.Rizzo F et al
20110758672000Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-center case-control study.Kaerlev L et al

Citation

Paola Dal Cin, PhD ; Matteo Fassan, MD

Tumors of the jejunum and ileum

Atlas Genet Cytogenet Oncol Haematol. 2026-06-02

Online version: http://atlasgeneticsoncology.org/solid-tumor/209374