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Adenomyomatous hyperplasia is now recognized as a common condition of the gallbladder wall, occurring in up to 8.7% of cholecystectomy specimens.

This is the most confusing lesion within the gall bladder, which may simulate malignancy.

It is known by a variety of names including cholecystis glandularis proliferans, adenomyomatosis,  adenomyoma, diverticular disease, intramural diverticulosis  and cholecystitis cystica.

Adenomyomatous hyperplasia is more common in females and its incidence increases with age.

The majority of patients present with complaints of chronic right upper quadrant pain.

It may produce symptoms even in the absence of cholelithiasis and it usually occurs within the fundus. Cholelithiasis is present in 50% of cases.

The diagnosis may be made on cholecystography or ultrasound. 

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There are out-pouchings of the mucosa into the muscle coat, which is thickened up to 5 times normal. Some of these are dilated, the mucosa has papillary folds, smooth muscle hypertrophy may be seen in the neck of the gall bladder. This may occur secondary to muscle thickening or may be congenital. They are usually 1.5 cm in diameter.

There are three variants of adenomyomatous hyperplasia:

-localized (or fundal) : The localized variant is the most common and is also known as an adenomyoma. At gross examination, it is characterized by a well-formed mass in the gallbladder fundus. The mass may have a semilunar or crescent shape . Cut sections of the mass have a honeycombed appearance that is created by multiple, small cystic spaces . The cystic spaces represent prominent epithelial invaginations (Rokitansky-Aschoff sinuses or intramural diverticula).

- segmental :  The segmental variant is characterized by focal circumferential thickening in the gallbladder wall. The segmental variant is typically located in the body of the gallbladder, giving it an hourglass configuration at gross inspection.

- diffuse :  Diffuse adenomyomatous hyperplasia is characterized by diffuse gallbladder wall thickening with intramural diverticula that appear as cystic spaces within the wall.

Microscopic features:  Image Link

Adenomyomatous hyperplasia is histologically characterized by epithelial and smooth muscle proliferation.

Normal gallbladder epithelium lines the epithelial structures that may extend down into the subserosa and reach the serosa.

Hyperplastic smooth muscle cells accompany the epithelial invaginations that contain inspissated bile, mucus, or stones.

Inflammatory and fibrotic changes may be present as well as  metaplastic changes (intestinal metaplasia, pyloric gland metaplasia).

Dysplastic changes and in situ and invasive carcinomas may arise from the epithelium of adenomyomatous hyperplasia.

The development of carcinoma is related to the presence of stones, chronic inflammation, and metaplastic changes rather than adenomyomatous hyperplasia. Thus, adenomyomatous hyperplasia is   not considered a premalignant lesion.

Cases of segmental adenomyomatous hyperplasia of the gallbladder with perineural invasion have been reported. Perineural and intraneural invasion was noted in the subserosal layer.

The mechanism by which the epithelial structures "invaded" the perineural spaces and the nerves is unclear but it has been suggested by the authors that the migration of the benign glandlike structures into the nerves is related to the production of chemotactic factors or signaling substances and the activation of cell receptors.

Other authors have suggested that perineural invasion is due to extension and growth of epithelial ductal structures along tissue  planes of least resistance, such as the perineural space, and growth of hyperplastic  nerve trunks in close proximity to or within epithelial structures.

The pattern of perineural invasion in cases of adenomyomatous hyperplasia should not be confused with adenocarcinoma. Attention to the general architecture of the lesion and the bland cytologic features of the glands and ductal structures should prevent this misinterpretation.

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We report 9 examples of segmental adenomyomatous hyperplasia of the gallbladder with perineural invasion. Five patients were women and 4 men. Their ages ranged from 49 to 81 years (mean age 64 y). Eight patients had gallbladder calculi. The original pathologic diagnosis of adenocarcinoma was made in 5 patients and of "adenoma malignum" in one. Six patients are disease-free for 2 to 11 years following cholecystectomy, 1 patient died of unrelated causes and 2 were lost to follow-up. Histologically 2 types of adenomyomatous hyperplasia were recognized. The first one characterized by numerous Rokitansky-Aschoff sinuses (RASs) was accompanied by smooth muscle hyperplasia and an expanded subserosal layer containing numerous nerve trunks (6 cases). The second type was characterized by an extensively fibrotic gallbladder wall with numerous RASs but with few or no smooth muscle bundles and an expanded subserosal layer containing abundant nerve-trunks (3 cases). Perineural (7 cases) and intraneural invasion (2 cases) was identified only in the subserosal layer. The lack of p53 reactivity and the very low MIB-1-labeling index provide additional support to the non-neoplastic nature of the lesion. The pseudoinvasive pattern of the RASs, reactive epithelial atypia, and the perineural and intraneural invasion probably contributed to the erroneous diagnosis of adenocarcinoma or "adenoma malignum." The mechanism by which the epithelial structures "invaded" the perineural spaces and the nerves is unclear. We favor the hypothesis that the migration of the benign glandlike structures into the nerves is related to the production of chemotactic factors or signaling substances and the activation of cell receptors.

Combined segmental and focal adenomyomatosis involving the body of the gallbladder.J Clin Ultrasound. 2005 Jun;33(5):248-50.

Adenomyomatosis (adenomyomatous hyperplasia) of the gallbladder is a benign process of unknown origin that has been classified into three morphologic types: diffuse, segmental, and focal (fundal). Cases of combined (segmental and focal) forms involving the gallbladder body are very rare. We present the sonographic findings of a case having adenomyomatosis of the gallbladder body with focal as well as segmental forms of the disease.

Polypoid lesions of the gallbladder: report of 100 cases with special reference to operative indications.Surgery. 2000 Jun;127(6):622-7.

BACKGROUND: The nature of polypoid lesions of the gallbladder is difficult to define before operation, and surgical indications still remain controversial. The aim of this study was to identify characteristics of each type of polypoid lesion of the gallbladder and indications for surgery. METHODS: Clinical data were retrospectively correlated with the histopathologic characteristics of polypoid lesions in 100 patients who had cholecystectomy. RESULTS: There were 74 benign polypoid lesions, including 39 cholesterol polyps, 20 adenomas, and 15 with adenomyomatous hyperplasia and 26 malignant polypoid lesions. Twenty-seven percent of patients with benign polyps and 73 percent of patients with malignant polyps were over 60 years of age. Polypoid lesions of the gallbladder were diagnosed by preoperative ultrasonography in only 36 patients (36%). All types of polypoid lesions of the gallbladder, whether benign or malignant, were frequently solitary, and gallstones coexisted in the majority of patients with all polypoid lesions of the gallbladder except cholesterol polyps. The lesions were > 10 mm in 88% of the malignant polyps and in only 15% of the benign polyps. CONCLUSIONS: The risk factors for malignancy were the age of the patient ( >60 years), the coexistence of gallstones, and the size of the polypoid lesions (>10 mm in diameter). In asymptomatic patients, cholecystectomy can be justified if there are risk factors for malignancy.

Adenomyomatous hyperplasia of the human gallbladder. South Med J. 1982 May;75(5):533-5.

Adenomyomatous hyperplasia of the human gallbladder, an infrequently observed alteration, has a controversial pathogenesis and clinical significance. In the nine gallbladders and patient profiles discussed, the morphologic alterations and associated clinical phenomena are compared to other mucosal-stromal reactions of the gastrointestinal tract. It is suggested that adenomyomatous hyperplasia represents a reaction to injury that occurs after an initial structural degenerative process and is followed by a proliferative repair.

Adenomyomatous hyperplasia of the gallbladder with perineural invasion. Arch Pathol Lab Med. 1995 Dec;119(12): 1173-6.

We report three examples of either localized or segmental adenomyomatous hyperplasia of the gallbladder in association with cholelithiasis. Two patients were women, 58 and 81 years of age, and the third was a 62-year-old man. The finding of perineural invasion by epithelial ductal structures in two cases and of perineural and intraneural invasion in the third case led to initial diagnoses of well-differentiated adenocarcinoma. The presence of mucinous metaplasia in some of the cystically dilated ductal structures and the diffuse proliferation of pyloric-type glands probably contributed to the erroneous diagnosis of adenocarcinoma. Although the mechanism by which the epithelial structures invade perineural spaces is unknown, we offer two possible explanations: (1) extension and growth of epithelial ductal structures along tissue planes of least resistance, such as the perineural space, and (2) growth of hyperplastic nerve trunks in close proximity to or within epithelial structures. The pattern of perineural invasion in cases of adeno myomatous hyperplasia should not be confused with adenocarcinoma. Attention to the general architecture of the lesion and the bland cytologic features of the glands and ductal structures should prevent this misinterpretation. The gallbladder should be added to the list of organs in which perineural invasion by benign epithelial structures has been described.

Papillary mucinous adenoma arising in adeno myomatous hyperplasia of the gall bladder.J Clin Pathol. 1995 Oct;48(10):965-7.

A case of papillary mucinous adenoma arising in adeno myomatous hyperplasia (AMH) of the gall bladder is reported. The lesion was unsuspected and discovered by routine palpation of the gall bladder during laparotomy. The adenoma developed within fundal AMH and showed cytological atypia. This case illustrates that neoplastic proliferation is indeed possible in AMH and challenges the classical opinion that AMH is devoid of neoplastic potential.