Adenomyomas of the Gallbladder: An Analysis of Frequency, Clinicopathologic Associations, and Relationship to Carcinoma of a Malformative Lesion

Abstract

Context.—: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs.

Objective.—: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM.

Design.—: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM.

Results.—: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM).

Conclusions.—: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.

Figure 1.

Adenomyoma, distribution. Most adenomyomas are localized lesions that form nodules on the wall that are covered by mucosa and may not even be noticeable from the mucosal perspective. Many are round structures that appear to converge at a focus in the mucosa centrifugally, forming a reverse cup-shaped structure (A). Another common presentation is the plaque-like thickening of the gallbladder wall with the cut sections showing trabeculations due to the cystic glands intervened by hypertrophic stroma (B). In some adenomyomas there appears to be an occluded lumen in the center that closely resembles a duplication (C). Diffuse examples are much less common and typically appear as thickened wall with prominent trabeculations (D).

Figure 2.

Adenomyoma, spectrum of cystic and solid components macroscopically. In addition to the characteristic trabecular architecture that is the most common pattern (see Figure 1), adenomyomas also show a spectrum of cystic structures. Some appear like a submucosal multilocular cystic lesion (A), some as multinodular lesion with focal cystic change (B), and some others as an almost entirely solid nodule (C). Cystic structures may be impacted with bile and may occasionally reveal calculi (not shown).

Figure 3.

Centrifugal pattern of adenomyoma. Most adenomyomas have a round flasklike configuration with more cystic structures at the periphery appearing to point toward a central focus in the surface gallbladder mucosa, which may show a subtle dimple (A) or a slight invagination (B) at that location (hematoxylin-eosin, original magnifications ×10 [A] and ×100 [B]).

Figure 4.

In some adenomyomas, presumably also related to the plane of sectioning, the convergence phenomenon illustrated in Figure 3 is not evident, and instead the whole lesion appears as a separate gallbladder with a well-formed wall and layering (hematoxylin-eosin, original magnifications ×10 [A, B, and C]).

Figure 5.

In most adenomyomas, the glands or cysts tend to be larger at the periphery (also illustrated in Figure 3), and they often display substantially irregular contours. This zonation phenomenon is more striking in the rounder examples in which the muscle is also more abundant centrally (A). In those with more plaque-like growth (B), this zonation phenomeonon is not as evident (hematoxylin-eosin, original magnifications ×10 [A and B]).

Figure 6.

This actin stain shows the variable muscle distribution in adenomyomas. The tunica muscularis of the native gallbladder is somewhat disrupted in the area of adenomyoma. In the lesion itself, the muscle is more condensed in the central and superficial segments and decreases toward the serosa (actin, original magnification ×10).

Figure 7.

Peculiar stromal changes often accompany the glands of adenomyomas. Taken in isolation, this can be interpreted as “desmoplastic” stroma of an invasive process. In some cases the stroma adjacent to the glands or cysts is more cellular, creating a picture that has been mi-interpreted as ovarian stroma of mucinous cystic neoplasm (hematoxylin-eosin, original magnifications ×10 [A] and ×40 [B]).

Figure 8.

Microscopic invasion in adenomyoma (AM). The lesion at the figure has the characteristic features of AM as illustrated in Figures 1 through 6 including the zonal muscle distribution, dimple-like structure on the surface mucosa corresponding to the middle of the lesion, and dilated glands forming a mural nodule. In this AM, there was a microscopic focus of invasive carcinoma (inset) in addition to dysplastic changes in the glands of the AM. Although the invasion is very small, it had to be qualified as T2 just by default of its localization (hematoxylin-eosin, original magnifications ×10, inset ×400).