TUMOURS OF THE SMALL INTESTINE
Benign Tumours of the small gut are uncommon, the most frequent being leiomyomas and lipomas. Malignant small intestinal Tumours are also rare, accounting for about 1 % of all intestinal neoplasms (incidence of 0.5 per 100,000 population in the UK). In order of decreasing frequency, these are adenocarcinomas, carcinoids, lymphomas, and leiomyosarcomas.
Gastric, duodenal, and jejunal adenomas have been reported in 8 %, 31 %, and 53 % of patients with familial adenomatous polyposis, respectively, and the total probability of adenomas developing in the duodenum in FAP is probably 50–90 %, with about 5 % risk of malignancy, and upper gastroenterological malignancy is the most common cause of death in individuals with familial adenomatous polyposis who have had a colectomy (Groves et al. 2002; Burt et al. 1994; De Pietri et al. 1995; Koornstra et al.
2008; Vasen et al. 2008; Bulow et al. 2004). Age is the most important risk factor; there is no clear association between mutation site and the development of duodenal polyposis. The severity of duodenal polyposis is assessed using the Spigelman classification, which classifies severity in five (0–IV) stages. Points are accumulated for number, size, histology, and severity of dysplasia of polyps. Stage I (1–4 points) indicates mild disease, whereas Stage III–IV (5–12 points) implies severe duodenal polyposis.
Approximately 80 % of patients with duodenal polyposis have Stage I–III disease, and 10–20 % have Stage IV disease (Spigelman et al. 1989). The risk of developing cancer appears to be related to the Spigelman stage. In one study, 2 of 27 patients with Stage IV disease at the first endoscopy developed cancer compared with 2 of 339 with Stage 0–III. The overall cumulative risk of duodenal cancer at age 57 was 4.5 % (Bulow et al. 2004) and has been estimated at between 7–36 % in individuals with Stage l–lV disease. The rate of progression from adenoma to carcinoma is slow, although it appears that recurrence of adenomas after initial detection and removal of duodenal adenomas is high.
Adenocarcinoma of the small bowel has been reported in families with Lynch syndrome, with a lifetime risk of about 4 % and a high relative risk (100–300) (Vasen et al. 1996), and individuals with Lynch syndrome present with small bowel cancer 10–20 years earlier than in the general population. Small bowel cancers may occur in individuals homozygous for MMR gene mutations (Herkert et al. 2011). A high proportion of small intestinal carcinomas (about 45 %) appear to demonstrate microsatellite instability in individuals with Lynch syndrome (Hibi et al. 1997). The cancers seem to be distributed evenly throughout the small bowel, and there is no clear genotype-phenotype correlation. Screening of the small bowel is not usually advocated in Lynch syndrome, but it has its advocates (Koornstra et al. 2008), and it is technically much easier to do this now that video capsule endoscopy is available. The rarity of small bowel cancer in Lynch families may, however, make this unfeasible in most centers.
Crohn’s disease is associated with an increased risk of small intestinal carcinoma, usually in chronic cases (Fresko et al. 1982). Crohn’s disease and ulcerative colitis are multifactorial conditions, but the familial contribution is becoming increasingly appreciated, with sibling relative risks of 30–40 for Crohn’s and 10–20 for ulcerative colitis, and with the identification of a susceptibility locus, NOD2/ CARD2, which is one of several susceptibility gene loci for this multifactorial condition (Mathew and Lewis 2004; Cooney et al. 2009).
Celiac disease in adults is associated with an increased risk of small bowel lymphoma and, less commonly, of carcinoma (Holmes et al. 1980). Small bowel lymphomas may develop as a complication of immune deficiency disorders.
Pancreatoduodenal endocrine Tumours may occur in MEN1 and these require aggressive management (Bartsch et al. 2000). Hamartomatous polyps occur in the small intestine in Peutz–Jeghers syndrome (PJS), and there is a significant risk of malignant degeneration in these polyps, resulting in a 2–13 % lifetime risk of colorectal cancer (CRC) in affected individuals (Jenne et al. 1998; van Lier et al. 2011). The relative risk of small bowel cancer in PJS has been estimated as 520 (220 to 1,306), with a lifetime risk of 13 %, mean age at diagnosis 41.7 years of age, and age range of 21–84 years of age (Giardiello et al. 2000).
Other small bowel Tumours are rare but may have genetic implications. Carcinoid Tumours are rarely syndromic, hamartomatous polyposis of the upper gastrointestinal tract has been reported in Gorlin syndrome, small intestinal neurofibroma may complicate NF1, and angiomas of the small gut occur in hereditary hemorrhagic telangiectasia. There have been rare reports of familial polyposis of the entire gastrointestinal tract, but these may be cases of FAP (Yonemoto et al. 1969). Gastrointestinal stromal Tumours (GIST), leiomyomas, and leiomyosarcomas may occur, and germline c-kit mutations have been described in individuals with familial GISTs and hyperpigmentation (Robson et al. 2004). Leiomyoma of the small intestine has been described in neurofibromatosis type 1, but is uncommon (Chu et al. 1999).
Upper gastrointestinal surveillance is advocated for individuals with FAP from the age of 25–30 years of age, the frequency depending on the Spigelman score (Vasen et al. 2008). Individuals with Peutz–Jeghers syndrome should be offered a baseline upper GI endoscopy at 8 years followed by 3-yearly video capsule endoscopy (VCE) from 18 years of age (Beggs et al. 2011; van Lier et al. 2011; Cairns et al. 2010). If polyps were detected at 8 years of age, VCE should be performed 3 yearly from that age. Magnetic resonance enterography (MRE) and barium follow-through (BaFT) are reasonable alternatives in adult patients, but BaFT is not favored in children due to radiation exposure. Colonoscopy is also advised every 2–3 years from 40 years of age in individuals with PJS (Giardiello et al. 2005; Giardiello and Trimbath 2006).