Major Genetic Syndromes
FAP patients with particularly severe duodenal polyposis, sometimes called dense polyposis, or with histologically advanced duodenal adenomas appear to be at the highest risk of developing duodenal adenocarcinoma.[16,70,78,79] Because the risk of duodenal adenocarcinoma is correlated with the number and size of polyps, and the severity of dysplasia of the polyps, a stratification system based on these features was developed in order to attempt to identify those individuals with FAP at highest risk of developing duodenal adenocarcinoma. According to this system, known as the Spigelman Classification (see Table 6), 36% of patients with the most advanced stage will develop carcinoma.
Table 6. Spigelman Classification
Stage I, 1-4 points; Stage II, 5-6 points; Stage III, 7-8 points; Stage IV, 9-12 points
|Points||Polyp Number||Polyp Size (mm)||Histology||Dysplasia|
A baseline upper endoscopy, including side-viewing duodenoscopy, should be performed between ages 25 and 30 years in FAP patients. The subsequent intervals between endoscopy vary according to the findings of the previous endoscopy, often, based on Spigelman stage. Recommended intervals are based on expert opinion although the relatively liberal intervals for stage 0-II disease are based in part on the natural history data generated by the Dutch/Scandinavian duodenal surveillance trial.
The main advantages of the Spigelman Classification are its long-standing familiarity to and usage by those in the field, which allows reasonable standardization of outcome comparisons across studies.[62,80] However, there are several limitations on attempted application of the Spigelman Classification:
- Most pathologists do not currently employ the term moderate dysplasia, preferring a simpler low- versus high-grade dysplasia system.
- Because of the villous nature of normal duodenal epithelium, pathologists commonly disagree over the classification of "tubular," "tubulovillous," and "villous."
- Spigelman staging requires biopsy, which is not always essential when only a few small plaques are present; conversely, for larger adenomas, sampling variation leads to understaging.[81,82]
Table 7. Recommended Screening Intervals by Spigelman Stage
CP = chemoprevention; ET = endoscopic therapy; GA = general anesthetic; NCCN = National Comprehensive Cancer Network.
Refer to the Interventions/FAP section in the Major Genetic Syndromes section of this summary for more information about chemoprevention.
Refer below for additional information about the use of surgical resection in Spigelman stage IV disease.
|Spigelman Stage ||NCCN ||Groves et al. |
|0 (no polyps) ||Endoscopy every 4 y ||Endoscopy every 5 y|
|I||Endoscopy every 2-3 y ||Endoscopy every 5 y|
|II||Endoscopy every 1-3 y ||Endoscopy every 3 y |
|CP + ET |
|III||Endoscopy every 6-12 mo ||Endoscopy every 1-2 y |
|CP + ET (+/- GA)|
|IV||Surgical referral||Surgical resection|
|Complete mucosectomy or duodenectomy or Whipple procedure if duodenal papilla is involved|
|Endoscopy every 3-6 mo ||Endoscopy every 1-2 y|
|CP + ET (+/- GA)|