Mural Intracholecystic Neoplasms Arising in Adenomyomatous Nodules of the Gallbladder: An Analysis of 19 Examples of a Clinicopathologically Distinct Entity

Abstract

Intracholecystic neoplasms (ICNs) (pyloric gland adenomas and intracholecystic papillary neoplasms, collectively also called intracholecystic papillary/tubular neoplasms) form multifocal, extensive proliferations on the gallbladder mucosa and have a high propensity for invasion (>50%). In this study, 19 examples of a poorly characterized phenomenon, mural papillary mucinous lesions that arise in adenomyomatous nodules and form localized ICNs, were analyzed. Two of these were identified in 1750 consecutive cholecystectomies reviewed specifically for this purpose, placing its incidence at 0.1%. Median age was 68 years. Unlike other gallbladder lesions, these were slightly more common in men (female/male=0.8), and 55% had documented cholelithiasis. All were characterized by a compact multilocular, demarcated, cystic lesion with papillary proliferations and mucinous epithelial lining. The lesions' architecture, distribution, location, and typical size were suggestive of evolution from an underlying adenomyomatous nodule. All had gastric/endocervical-like mucinous epithelium, but 5 also had a focal intestinal-like epithelium. Cytologic atypia was graded as 1 to 3 and defined as 1A: mucinous, without cytoarchitectural atypia (n=3), 1B: mild (n=7), 2: moderate (n=2), and 3: severe atypia (n=7, 3 of which also had invasive carcinoma, 16%). Background gallbladder mucosal involvement was absent in all but 2 cases, both of which had multifocal papillary mucosal nodules. In conclusion, these cases highlight a distinct clinicopathologic entity, that is, mural ICNs arising in adenomyomatous nodules, which, by essentially sparing the "main" mucosa, not displaying "field-effect/defect" phenomenon, and only rarely (16%) showing carcinomatous transformation, are analogous to pancreatic branch duct intraductal papillary mucinous neoplasms.

Figure 1.

AM-ICN, gastric-type, A) gross and B) microscopic view (hematoxylin-eosin, original magnification x20). Cystic and solid lesion grows beneath normal appearing gallbladder mucosa or as in this case papillary changes may be seen in the overlying mucosa.

Figure 2.

All cases arose within an adenomyoma and had at least some degree of cyst formation and papillae formation, hematoxylin-eosin, original magnification, x20.

Figure 3.

A-B) Florid papillary nodules that fill the cyst lumen, hematoxylin-eosin, original magnification x100). C-D) The mucosa of the cyst in the AM in all cases was composed predominantly of gastric/endocervical-like mucinous epithelium and focal pyloric gland features, with focal intestinal phenotype in some (B, upper right), hematoxylin-eosin, original magnification x200.

Figure 4.

Case of AM-ICN showing high grade dysplasia and intestinal-type epithelium, hematoxylin-eosin, original magnification x40 (A) and x400 (B).

Figure 5.

High grade dysplasia (“carcinoma in-situ”) arising in an AM-ICN. While most cases were exclusively mural lesions, confined to the wall, in three cases, one of which is illustrated here, the papillary proliferation protruded into the gallbladder lumen. However, even in these cases the normal mucosa on the edges of the lesion was noticeable, and the lesional tissue in fact stopped abruptly once it reached the surface mucosa, hematoxylin-eosin, original magnification x20.

Figure 6.

Invasive carcinoma arising in an AM-ICN. A) The intracholecystic (non-invasive) component is depicted on the right. On the left and in B, the invasive component is illustrated. It is composed of both large and small invasive glandular units as well as non-glandular poorly differentiated elements (circled), hematoxylin-eosin, original magnification x20 (A) and X400 (B).