Rapid Rectal Polyposis Development in a Patient With Familial Adenomatous Polyposis

ABSTRACT

Familial adenomatous polyposis (FAP) is a well-described genetic condition that results in the development of multiple benign and malignant lesions throughout the gastrointestinal tract. The development of colorectal cancer is nearly universal in classic FAP, and total proctocolectomy after polyp development is recommended. We present a patient with FAP who was unable to undergo proctectomy. Despite careful removal of all rectal polyps before subtotal colectomy with ileorectal anastomosis, he developed 12 rectal polyps, including 4 advanced neoplastic lesions, within 73 days after initial endoscopic removal. This case highlights the rapid regrowth rate of colorectal adenomas in FAP.

INTRODUCTION

Familial adenomatous polyposis (FAP) is a cancer-predisposing condition that results from a mutation in the adenomatous polyposis coli (APC) gene, a tumor suppressor gene involved in cellular growth regulation.¹ It is most commonly inherited in an autosomal dominant manner with near-complete penetrance and is characterized by the development of thousands of synchronous colonic polyps.^1,2 Approximately 20%–25% of cases are associated with de novo mutations.² Untreated patients progress from polyp development at a median age of 17 to colorectal cancer (CRC) diagnosis at a median age of 40; almost all patients in the presurveillance era died of CRC between ages 40–50.³ We present the unique case of interendoscopic polyp regrowth in a 52-year-old patient with classical FAP who declined proctectomy to highlight the impressive rate of polyp growth that can occur in such patients.

CASE REPORT

A 52-year-old man with no history of smoking or diabetes and with family history of CRC in his mother and maternal uncle presented for direct access esophagoduodenoscopy and colonoscopy for iron deficiency anemia (hemoglobin 9.7 g/dL; mean corpuscular volume 69.1 fL; ferritin 8 ng/mL) without previous endoscopic evaluation. On esophagoduodenoscopy, he was noted to have ∼20 duodenal adenomas from the second and third portions of the duodenum and a 1.5 cm ampullary adenoma. On colonoscopy, he was noted to have innumerable colorectal polyps ranging in size from <5 mm to 10 cm in all segments of the colon (>1,000 polyps) with a ∼10 cm malignant-appearing cecal mass found to be moderately differentiated adenocarcinoma in a background of a tubulovillous adenoma with normal immunohistochemistry (Figure 1). The patient's carcinoembryonic antigen was 0.7 ng/mL. Thoracic, abdominal, and pelvic staging computed tomography and positron emission tomography/computed tomography scan were negative for metastatic disease. Genetic testing demonstrated a pathogenic variant at the 5′ end of the APC gene (NM_000038.6:c.487C > T heterozygous).

Figure 1.

Rectal polyposis pre-endoscopic resection in familial adenomatous polyposis patient.

Given documented malignancy, the patient was encouraged to undergo total proctocolectomy; however, the temporary ileostomy maintenance required was not compatible with the patient's employment.⁴ Endoscopy was performed to resect all rectal polyps and ensure no cancer was present 2 days before colectomy with ileorectal anastomosis (IRA). Seventy-one polyps ranging in size from <5 mm to 1.5 cm were removed with a combination of cold and hot (cautery) snare polypectomy techniques (Figure 2). The most distal area of the rectum to be retained was tattooed for surgical planning. Rectal polyp pathology ranged from tubular to tubulovillous adenomas with focally increased atypia. No features of high-grade dysplasia or cancer were seen. Total colectomy was performed and demonstrated innumerable polyploid masses ranging from < 0.1 cm to > 4 cm in diameter, the largest of which was found to be a pT3 pN0 adenocarcinoma with histological grade 2 invasion through the muscularis propria into the pericolonic tissue.

Figure 2.

Cleared rectum after endoscopic resection of 72 rectal polyps in a patient with familial adenomatous polyposis.

Short-term surveillance proctoscopy performed 73 days after the initial endoscopy showed that the retained 14-cm rectum had 12 rectal polyps ranging in size from 5 mm to 1.5 cm with pathology ranging from tubular to tubulovillous adenomas with focal high-grade dysplasia in regions previously cleared of all polyps (Figure 3). Given the number, size, and concerning histology of the recurrent rectal polyps, in combination with high duodenal polyposis burden with ampullary adenoma (Spigelman stage 4), the patient was referred for and agreeable to the removal of retained rectum and Whipple procedure and started on daily sulindac for chemoprevention. He is followed in genetics clinic for FAP-specific cancer surveillance, including annual thyroid ultrasounds. His 2 children were referred for endoscopic evaluation and genetic testing.

Figure 3.

After 73 days (A) recurrence of rectal polyposis after initial endoscopic resection of all rectal polyps and (B) histologic image of biopsied rectal segment after initial endoscopic resection, demonstrating tubulovillous adenoma with focal areas of high-grade dysplasia, demonstrated by fused glands with marked atypia and increased mitoses.

DISCUSSION

Previous studies have identified a median polyp progression rate of 25.4 polyps/year in adults with FAP.⁵ In our patient, a limited segment of the rectum developed 12 polyps within 73 days, equating to a growth rate of 60 polyps/y. This is approximately double the previously reported rate of polyp progression in patients with a codon mutation between codons 312 and 493 of the APC gene, as this patient had.⁵ Of note, this occurred over only a 14 cm segment of the rectum, and because polyps are pancolonically distributed in FAP, this likely corresponds to a dramatically increased overall polyp progression rate and correlates to the initial polyp burden of >1,000.⁶ Furthermore, interval development or regrowth of 4 adenomas with high-grade dysplasia reflects the heightened risk of postoperative colon cancer in patients undergoing IRA (12%–43% at 20 years) compared with other surgeries for FAP.⁷ Other contributing factors that are generally associated with a greater rate of polyp growth are mutation in codons 962–1,309, ≥100 polyps on initial colonoscopy, and patients not undergoing NSAID chemoprophylaxis; the presence of the latter 2 factors may contribute to the explanation of this patient's high polyp growth rate.⁵ Mutations in regions including codon 487 are also associated with congenital hypertrophy of the retinal pigment epithelium, although genotype-phenotype relationships between this codon and other extracolonic features of FAP such as osteomas and other malignancies have not been established.⁸

Beyond the high polyp growth rate seen in this patient, the case illustrates critical questions that arise in surgical planning for patients with FAP. The recommended surgical intervention for this patient with >1,000 colonic polyps, colorectal carcinoma, and pathogenic APC mutation was restorative proctocolectomy with ileal pouch-anal anastomosis (RPC-IPAA).⁴ Other reasons that may favor RPC-IPAA in patients in general include high-grade dysplasia, mutations in the 1,309 codon, or >20 rectal polyps.^5,9 IRA is preferred in patients with attenuated FAP, without CRC, or in patients prioritizing lower risk of sexual dysfunction.⁹ Although associated with reduced fecal incontinence and frequency, IRA requires rectal surveillance because of a 5% postoperative risk of rectal cancer.⁹ Recommended post-IRA surveillance is semiannual or annual endoscopy depending on polyp burden, whereas the recommended monitoring for patients with ileostomy is biennial.^4,7 The initial surgical decision for IRA vs RPC-IPAA included consideration of the patient's age, disease severity, and preferences. Although the most important factor in this patient's surgical choice was decided by employment factors, these factors affecting quality of life, such as risk of fecal incontinence and surveillance requirements, may also influence the patient's choice for or against IRA. This case demonstrates the aggressive polyp regrowth that can occur in patients declining proctectomy and the risk of neoplastic development in these patients. Careful consideration of disease- and patient-specific factors is critical to surgical decision-making for patients with FAP.

DISCLOSURES

Author contributions: All authors contributed equally to this manuscript. N. Khalaf is the article guarantor.

Financial disclosure: None to report.

Informed consent was obtained for this case report.