Duodenal adenocarcinoma: why the extreme rarity of duodenal bulb primary tumors?

Adenocarcinoma of the small bowel accounts for only one per cent of all gastrointestinal malignancies. Duodenal adenocarcinoma accounts for half of all small bowel adenocarcinomas. The duodenum is divided into four segments: D1 (proximal horizontal 5 cm beginning with the 3-cm duodenal bulb), D2 (descending), D3 (distal horizontal), and D4 (ascending). The most common location of duodenal adenocarcinomas is the ampullary region of D2. Based on observational experience, our hypothesis was that primary adenocarcinomas arising from the mucosa of the duodenal bulb are extremely rare or possibly nonexistent. Our institutional cancer registry provided a list of patients for the years 1990 through 2012 who had small bowel cancers. Only those patients with primary adenocarcinomas of the duodenal mucosa were reviewed. Ampullary cancers arising from bile duct mucosa were specifically excluded. Medical records were abstracted to obtain patient age, sex, race, anatomic location of the tumor, disease stage (as per American Joint Committee on Cancer 7th edition staging guidelines), operation performed, and current vital status. A total of 30 patients with primary duodenal adenocarcinomas were identified. The mean age was 58 years and 17 (57%) patients were male. The tumor locations were: D2 in 26 (87%), D3 in two (7%), and D4 in two (7%). No tumors arose from D1. The patients presented with the following stages of disease: Stage 0is in three (10%), Stage I in three (10%), Stage II in five (17%), Stage III in 15 (50%), and Stage IV in four (13%). These findings combined with a diligent review of 724 reported cases in the English language literature yielded only five clearly defined cases of adenocarcinoma arising from the mucosa of the duodenal bulb. Although a 1991 published multicenter tumor registry series of 128 localized duodenal adenocarcinomas reported 29 D1 tumors, no anatomic distinction was made between duodenal bulb and more distal D1 tumors. Earlier reports used nonanatomic divisions of the duodenum or a simple breakdown into supra-ampullary, periampullary, and infra-ampullary portions. These data beg the question as to why primary duodenal bulb adenocarcinomas are so exceedingly rare. The obvious implication is that the duodenal bulb mucosa may be physiologically, immunologically, or otherwise uniquely privileged to virtually escape oncogenic transformation. The scientific challenge and opportunity is to explore and understand the important phenomena responsible for this finding.