The polyp puzzle: multiple lesions, one diagnosis
Article information
Quiz
A 19-year-old female presented with hematochezia in March 2015. Colonoscopy performed at a local hospital revealed more than 100 colorectal polyps (Fig. 1). Biopsies were obtained from each polyp larger than 1 cm, and histological examination revealed tubular adenomas (TAs) with high-grade dysplasia (HGD) and low-grade dysplasia (LGD). Esophagogastroduodenoscopy (EGD) also revealed multiple gastric polyps.
Colonoscopic examination revealed more than 100 colorectal polyps throughout the entire colon.
Her medical history included hypothyroidism, for which she had been taking levothyroxine 100 µg daily for five years, and a past diagnosis of epilepsy. Her family exhibited a notable history of colon cancer (her mother had undergone surgery for colon cancer four years prior, followed by a Whipple procedure for ampulla of Vater [AoV] cancer two years ago), and among her three siblings, her younger brother also had multiple colonic polyps).
In May 2015, the patient was referred for colorectal surgery to address extensive polyposis and HGD. The patient underwent total proctocolectomy with ileal pouch-anal anastomosis and protective loop ileostomy. The surgical margins were dysplasia-free. Ileostomy reversal surgery was successfully performed in August 2015.
A follow-up EGD in September 2023 revealed an adenoma of the AoV (Fig. 2A), which was histologically confirmed to be TA with LGD. Multiple duodenal and gastric polyps were also identified via EGD (Fig. 2B, C). Histology revealed fundic glands and hyperplastic polyps in the stomach and TAs with LGD in the duodenum. In January 2024, the adenoma at the AoV was successfully treated with endoscopic papillectomy (Fig. 3).
Endoscopic findings. (A) The ampulla of Vater appears nodular. (B) Multiple polyps (<5 mm) were observed in the duodenum. (C) Multiple polyps (5–10 mm) were observed in the stomach.
Endoscopic findings during papillectomy. (A) Nodularity at the ampulla of Vater. (B) Endoscopic papillectomy performed using a snare. (C) Post-papillectomy view of the ampulla of Vater. (D) Multiple duodenal polyps observed in the duodenum.
Surveillance colonoscopy (Fig. 4) revealed multiple polyps in the ileal pouch mucosa and anal transitional zone. Biopsies of polyps >1 cm showed TAs with LGD upon histological examination.
Follow-up colonoscopy after total protocolectomy with ileal pouch-anal anastomosis. Multiple polyps were observed on the ileal pouch mucosa (A, B) and in the anal transitional zone (C).
What is the most likely diagnosis?
Answer
Based on clinical and familial history, familial adenomatous polyposis (FAP) was the most likely diagnosis for this patient. In this patient, genetic testing was conducted in April 2015, and a pathogenic mutation in the adenomatous polyposis coli (APC) gene was identified.
FAP is a hereditary disorder characterized by the development of hundreds of adenomatous polyps in the colon and rectum, with onset often in the teen years.1 Nearly all individuals with classic FAP will develop colorectal cancer (CRC), often by the age of 40.2 FAP accounts for approximately 1% of all CRCs and is typically diagnosed in adolescence or early adulthood.2 Clinical symptoms can include hematochezia, abdominal pain, and diarrhea. Some patients may be asymptomatic, and diagnosis may be made through routine surveillance of individuals with a family history of FAP.3
FAP results from a germline mutation in the APC gene, located on chromosome 5q21–22.4 The APC gene functions as a tumor suppressor, regulating cell growth and apoptosis.5 While most mutations in the APC gene are inherited, 15% to 30% arise de novo.6
Patients with FAP are also at increased risk of developing gastric and duodenal polyps. A prospective study from Nordic and Dutch polyposis registries found that approximately 90% of FAP patients had gastric or duodenal polyps by the age of 70 years, with a median age of diagnosis of 38 years.7 Approximately two-thirds of duodenal adenomas develop in the papilla or periampullary region.7 Risk factors for progression of duodenal adenomas to cancer include aging, stage IV Spigelman polyposis, HGD adenomas, and adenomas larger than 10 mm.7 A family history of colorectal or duodenal cancer is suggested to be a risk factor for duodenal cancer, but the evidence is limited.7
Gastric polyps, particularly fundic gland polyps (FGPs), are common in FAP, with an incidence of 26% to 61%, compared to only 0.8% to 1.9% in the general population.8 FAP patients tend to have a higher number of gastric polyps and develop them at a younger age compared to individuals with sporadic FGPs.8 While there may be an increased risk of gastric cancer in FAP patients with FGPs, the evidence remains limited.8
In addition to gastrointestinal polyps and tumors, FAP is associated with several extra-gastrointestinal manifestations,1 including desmoid tumors, papillary thyroid carcinoma, hepatoblastoma (primarily in children), and rarer tumors such as those found in the pancreatic, adrenal, and central nervous systems.9 Congenital hypertrophy of the retinal pigment epithelium is a non-neoplastic feature of FAP that is often identified during ophthalmologic examination.1,9
In summary, FAP is a hereditary disorder caused by mutations in the APC gene on chromosome 5q21–22. It is characterized by numerous colonic adenomas and an increased risk of CRC. Upper gastrointestinal polyps and cancers along with various extraintestinal manifestations are also commonly observed in patients with this syndrome.
Notes
Conflicts of Interest
Eunae Cho currently serves as a Publication Committee member for the journal Clinical Endoscopy. She was not involved in peer reviewer selection, evaluation, or the decision process regarding publication of this article.
Funding
None.