Gardner Variant of Familial Adenomatous Polyposis: From Extensive Skull Osteomatosis to Metastatic Rectal Remnant Cancer
Authors: Vincent Zimmer, Frank Lammert, Jochen Raedle
Journal: Clinical Gastroenterology and Hepatology (2009)

A 53-year-old man was referred because of recurrent emesis, abdominal pain, and severe weight loss. His medical history was significant for multiple protruding osseous lesions, especially involving the skull bones (Figures A and B). Pathologic evaluation of a surgical biopsy taken at the age of 21 was consistent with osteoma. At the age of 38, the patient reported rectal hemorrhage, and colonoscopy revealed more than 100 colorectal polyps consistent with familial adenomatous polyposis (FAP). The patient underwent subtotal colectomy with ileorectal anastomosis, and sporadic follow-up endoscopies at another institution documented no major rectal polyps. While family history was negative, genetic testing revealed a 2–base pair deletion in the APC gene (codon 1516, c.4547-4548delTA). On admission to our hospital, clinical examination in addition showed tooth abnormalities and cutaneous epidermoid cysts. Upper gastrointestinal endoscopy indicated advanced duodenal polyposis (Spigelman stage IV1Vasen H.F. Möslein G. Alonso A. et al.Guidelines for the clinical management of familial adenomatous polyposis (FAP).Gut. 2008; 57: 704-713Crossref PubMed Scopus (490) Google Scholar) and a severe external compression of the distal duodenum. An abdominal computed tomography scan revealed diffuse liver metastases and an obstructive mesenteric lesion, suspicious for a desmoid tumor. At lower gastrointestinal endoscopy the rectal remnant showed spontaneous hemorrhage and a slit-like narrowed lumen but no significant rectal polyposis. Biopsies from the rectum and a liver lesion confirmed metastatic rectal adenocarcinoma. The gastrointestinal passage was surgically restored, and palliative chemotherapy was scheduled. FAP is an autosomal-dominant colorectal cancer syndrome caused by APC mutations. The variant form with an extended, clinically prominent spectrum of extracolonic manifestations, including osteomas, dental abnormalities, and epidermoid cysts, traditionally is referred to as Gardner syndrome, possibly reflecting variable extracolonic penetrance of APC mutations.2Groen E.J. Roos A. Muntinghe F.L. et al.Extra-intestinal manifestations of familial adenomatous polyposis.Ann Surg Oncol. 2008; 15: 2439-2450Crossref PubMed Scopus (174) Google Scholar Because FAP features outside the colon often precede colorectal polyposis, their clinical recognition may be essential for early diagnosis, especially in the estimated 20% to 30% of patients with de novo mutations.3Galiatsatos P. Foulkes W.D. Familial adenomatous polyposis.Am J Gastroenterol. 2006; 101: 385-398Crossref PubMed Scopus (437) Google Scholar Despite the much pronounced, externally visible osteomatosis of the skull, underlying FAP only was recognized 16 years later after polyposis became symptomatic. At this late stage there is already a substantial risk for coincident colorectal cancer. With the widespread implementation of prophylactic surgery, prognosis in FAP nowadays rather depends on extracolonic complications, such as duodenal cancer and desmoid tumors. Nevertheless, clinicians should bear in mind that individuals with FAP in whom subtotal colectomy has been performed are at a relevant persistent cancer risk in the residual rectal mucosa. Tight endoscopic surveillance is recommended in these patients, and secondary proctocolectomy may become necessary.1Vasen H.F. Möslein G. Alonso A. et al.Guidelines for the clinical management of familial adenomatous polyposis (FAP).Gut. 2008; 57: 704-713Crossref PubMed Scopus (490) Google Scholar However, as illustrated by this case, rectal cancer also may develop without significant polyposis, which highlights the challenge and intricacy of endoscopic surveillance of the rectum.