Endoscopy Challenge #4 - Jan '11
12-year-old female with intermittent blood in her stool
12-year-old female with no significant past medical history with 2 episodes separated by 9 months of passing small amounts of blood and blood clots in her stool. Each episode lasted 1 day, was not associated with abdominal pain, or a change in her bowel movements. She reports no history of constipation. Infectious stools studies were negative and she had a normal complete blood count and erythrocyte sedimentation rate. There was no significant family history.
Colonoscopy reveals the following finding:
Removal was complete. Polyp was retrieved and sent to pathology for examination. The rest of the colon and ileum were normal in appearance. Histologic findings include hyperplastic mucosa with slightly dilated small glandular tissue.
Adenomatous polyp arising from a juvenile inflammatory polyp.
Pathology showed a large polyp with mixed morphology. Some portions were juvenile polyp-like with glands and hyperplastic mucosa. A majority of the polyp had glands with crowded nuclei, low grade dysplasia and stained positive for p53, which was typical of a tubular adenoma.
Juvenile polyps account for 90% of polyps in children and are benign in nature. This case is unusual with the presence of a tubular adenoma arising from a juvenile polyp. The special stains help to highlight the abnormal looking tissue. As endoscopists, we often focus on appearance, anatomic location and clinical context for our diagnosis and the histology will either support this impression or provide alternative diagnoses. Adenomas are usually asymptomatic, by the 5th decade of life 12% of individuals can have them and local "environmental" factor seem to play a role in their development(1).
Inflammatory polyps on the other hand are defined as intraluminal projections formed on non-neoplastic tissue; a mixture of glandular, stromal tissue and inflammatory cells(1). Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of dysplasia and carcinomas. These mutations frequently result in intranuclear protein accumulation (the p53 protein from abnormal p53 genes has a longer half-life), which can be detected by immunohistochemistry and produces a nuclear signal or nuclear staining. Normal p53 protein has an extremely short half life and it is not detected by immunohistochemical stain with antibodies directed against the p53 protein. In theory, p53 overexpression, as a surrogate marker for p53 gene mutations, is an immunohistochemical test for dysplasia. However, the correlation between staining and gene abnormality is not precise (2).
Furthermore, differentiating benign adenomas from those harboring adenocarcinoma can be challenging. Antibodies against stromal proteins like p53, matrix metalloproteinase-1, E-cadadherin and collagen IV have been shown to be useful in detecting adenomas and adenocarcinoma compared with surrounding normal colonic mucosa(3). This is outside the clinical case here presented but the usefulness of these immuno-stains should be understood by pediatric endoscopists. This case highlights the value of understanding histologic technique and applying it in our daily clinical work.
Further diagnostic studies included upper gastrointestinal series with small bowel follow through which was normal. Video capsule and genetic testing for the FAP gene was also ordered and is pending.
- Brandy Lu MD
- Ian Jaffee MD*
- Maria Patino MD*
- J. Antonio Quiros MD
Department of Pediatric Gastroenterology and the Department of Surgical Pathology* California Pacific Medical Center.
- Abraham SC, Burgart L, "Polyps of the Large Intestine" from Surgical Patholgy. Odze R, Goldblum, Crawford J (Editors). pp 327-377.
- Krasinskas T, Goldsmith. Immunohistology of the gastrointestinal tract . Diagnostic Immunohistochemistry: theranostic and genomic applications. Third edition. Saunders Dabbs, D.J (Editor) pp 501
- Yantiss R, Bosenberg M, Antoniolli D. Utility of MMP-1, p53, E-Cadherin, and Collagen IV Immunohistochemical Stains in the Differential Diagnosis of Adenomas With Misplaced Epithelium versus Adenomas With Invasive Adenocarcinoma. Am J Surg Path, 2002; Vol 26: 206-215.