Do serrated neoplasms of the small intestine represent a distinct entity? Pathological findings and molecular alterations in a series of 13 cases

Histopathology. 2015 Feb;66(3):333-42. doi: 10.1111/his.12469. Epub 2015 Jan 6.


Aims: To characterize pathological, immunohistochemical and molecular features of small intestinal serrated neoplasms.

Methods and results: We report 13 serrated neoplasms located predominantly in the duodenum (median age, 71 years; male to female ratio, 7:6). The serrated adenomas demonstrated prominent serration, ectopic crypt formations and cytological features reminiscent of colorectal traditional serrated adenomas. Almost half the serrated adenomas demonstrated high-grade dysplasia or were associated with an adenocarcinoma. Immunohistochemical and molecular analysis showed an intestinal (CDX2-positive) phenotype in all tumours, abnormal β-catenin staining in three cases (23%), abnormal p53 expression in four cases (31%), focal loss of MGMT expression in one case (8%), KRAS mutation in five cases (38%) and CpG island methylator phenotype in six cases (50%). A diffuse pattern of Ki67 expression was present in eight adenomas (62%) and was associated with high-grade dysplasia (P = 0.02). No BRAF(V600E) mutation or loss of MLH1 expression was observed.

Conclusions: To our knowledge, this is the first series reporting serrated adenoma in the small intestine, a rare subtype of adenomas resembling traditional serrated adenoma with aggressive morphological features. The absence of the BRAF(V600E) mutation does not support a role for the serrated neoplasia pathway in the development of these lesions, as in colorectal serrated polyps.

Keywords: BRAF; CIMP; KRAS; serrated adenocarcinoma; serrated adenoma; small intestine; traditional serrated adenoma.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenoma / genetics*
  • Adenoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / genetics*
  • Intestinal Neoplasms / pathology*
  • Intestine, Small / pathology
  • Male
  • Middle Aged


  • Biomarkers, Tumor