Pathogenesis and Significance of Distended Glands

The pathogenesis and significance of the distended glands of the ampullary mucosa have not been clarified. One possible explanation that, however, does not apply to all cases is as follows: intrapapillary adenomyomatous or adenomatous/myomatous hyperplasia might oppress the duodenal mucosa, resulting in atrophy and desquamation of the latter near a portion of the outlet. Finally, the end-to-side, less acute and right-angled formation occurs and the distended glands begin to grow on the extension of Oddi's sphincter muscle. According to

Fig. 7. MUC5AC staining of the distended glands, the same case as in figure 5. The distended glands were selectively immunopositive for MUC5AC. X64. (Reproduced with permission from [8].)

Albores-Saavedra et al. [2], the ampullary region contains a transition from pancreaticobiliary to intestinal epithelium, and such areas of transition are inherently unstable. Although the evidence indicates that most ampullary carcinomas arise from adenomas, it is probable that some arise de novo or from nonpolypoid precursors. Extremely small invasive carcinomas have been found with no evidence of preexisting adenoma [2]. According to Klöppel [9], the ampulla of Vater harbors exophytic adenomas composed of tubular and/or villous epithelial proliferations that show an intestinal phenotype. Tumors revealing pancreaticobiliary differentiation are usually invasive and may be a carcinoma from the onset. Features of an intestinal origin are seen in the lesion arising in the ampullary region, at the interface between pancreaticobiliary epithelium and intestinal epithelium.

Table 2. Mucosal differences of the papilla of Vater

Item

Common channel Distended glands Duodenum valvules

Mucosal structure

CK20

CA19-9

MUCSAC

Ki67LI

papillary

about 10%

dilated/glandular glandular/tubulo-villous about 20%

about 20%

about 80%2

Not significant

'Mostly negative.

2So-called proliferative zone of the duodenal mucosa.

Furthermore, on autopsy, epithelial hyperplasia bordering on severe dysplasia has been observed in the ampullary epithelium in the absence of architectural features of adenoma [10]. Immunoreactivity against anti-CA19-9 in the distended glands is mostly different from that of the intrapapillary portion of the ampullary mucosa, especially in cases with a high proliferation index as mentioned above. However, it is similar or close to that for the duodenal mucosa, as shown in table 2. The distended glands are immunopositive for CK7 and selectively positive for MUC5AC, as mentioned above. Hence, the distended glands might not only maintain a pan-creaticobiliary phenotype but also acquire a gastric surface phenotype, resulting in a difference in character that leads to malignant change. Moreover, although most distended glands or so-called overreplacement are acquired, some can be found in infancy, similar to the findings of Kirk [6]. Therefore, such an occurrence might be related not only to malignant changes, but also to a kind of adaptive phenomenon against bile and pancreatic juice flow based on chronic inflammation.

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