Adenomyomatous Hyperplasia of the Gallbladder With Perineural Invasion

Abstract

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.

Mucin-containing Rokitansky-Aschoff Sinuses With Extracellular Mucin Deposits Simulating Mucinous Carcinoma of the Gallbladder

“…3,5,9,11,13,21 Adenomyomatous hyperplasia with perineural and intraneural invasion has been frequently confused with adenocarcinoma. 1,7 Pyloric gland metaplasia with perineural invasion has also been misinterpreted as adenocarcinoma. 2 The mechanism by which the epithelial structures ''invade'' the perineural spaces and nerves may be due to the production of chemotactic factors or signaling substances and the activation of cell receptors.…”

Gallbladder Sarcoma: A Clinicopathological Study of Seven Cases from the UK and Austria with Emphasis on Morphological Subtypes

“…It has been speculated that PGBS or sarcomatoid carcinoma (which was excluded from this study) of the gallbladder arise from totipotential stem cells [1,2], rest cells of mesoblasts that retain the capability of transformation, primitive undifferentiated mullerian stroma [2,16,17], or paramesonephric tissue [18], although cholelithiasis with accompanying cholecystitis (n = 12, in the current series) has been suggested as a promoting factor [1,2,16,17,[19][20][21]. Abnormal bile composition that causes stones, and subsequent chronic inflammatory changes and irritation, have been suggested as promoting factors in the pathogenesis.…”

“…Anomalies of the junction of the cystic duct and common bile duct have been observed frequently in patients with gallbladder carcinoma or even carcinosarcoma. Ethnicity may be a predisposing factor because gallbladder cancer is more common in Latin Americans and less in blacks [1,2,16,17,19,22,23].…”

Adenocarcinoma of the Gallbladder: Biology of Disease, Prognosticators, and Staging

“…The incidence ranged from 22 % to more than 50 % (Vadheim et al 1944;Kuwayti et al 1957;Fahim et al 1962;Ouchi et al 1987;Nagakawa et al 1993). Perineural cancer invasion has to be distinguished from perineural invasion observed in benign conditions, such as adenomyomatous hyperplasia (Albores-Saavedra et al 2007) and pyloric gland metaplasia (Albores-Saavedra and Henson 1999). There is a correlation between the prevalence of perineural invasion and higher histologic grade (Fahim et al 1962).…”