In 1753, Ferrein, a human anatomist, initially identified the presence of bile ducts within the left lateral or triangular ligament of the liver. These ducts were later described by Weber in 1842 as “aberrant biliary ducts” located outside the hepatic parenchyma.19
However, it was not until 1863 that Luschka described these ducts in detail as “slender bile ducts running along the gallbladder fossa, draining into the right hepatic duct or common duct,” and thus these ducts were designated as ducts of Luschka.11,19
The ducts of Luschka are also known as accessory biliary ducts, vasa aberrantia, subvesicular ducts, or supravesicular ducts.
The ducts of Luschka are small biliary ducts, measuring up to 2mm in diameter, and typically originate within the right hepatic lobe. Microscopic examination shows that they may occur as a single duct or a meshwork of ductules. The ductules are lined by flattened-to-columnar biliary epithelium and are classically surrounded by a fibrous collar.6
However, the concentric fibrosis, which surrounds larger ductules, may be absent around smaller ductules. They run an intermediate course along the gallbladder bed, usually reaching the adventitia of the gallbladder. Often, they drain into the right hepatic duct or subsegmental branch of segment 4 or 5.8,10,12
These ducts have blind distal ends, and thus, do not drain a particular region of the liver. The ducts are usually not accompanied by arteries and veins. Furthermore, portal triads are absent, distinguishing them from other bile ducts that drain the liver.13
Embryologically, ducts of Luschka are thought to arise from anomalous and autonomic proliferation of the most distal biliary ducts formed from the pars hepatica as it develops in the septum transversum. These biliary ducts may persist in certain zones where the liver parenchyma should regress secondarily during development.9
Their incidence is fairly common, and they are reported in up to 10% of cholecystectomy specimens.6,17
The clinical significance of these ducts lies in the fact that they are often unnoticed during cholecystectomy and may be injured. Therefore, injury to the ducts of Luschka is well known to surgeons as a frequent cause of bile leak and biliary peritonitis.12,18
Although the ducts of Luschka are appreciated clinically, pathologists should also be aware of this normal variant of biliary histology. Confusion with neoplastic conditions can occur, especially in cases of florid proliferation in the setting of marked reactive inflammatory atypia. The problem is compounded when only a small serosal biopsy of the gallbladder fossa is performed (as in case 1), which may not allow the pathologist to appreciate the lobular configuration of the glands and their relationship with the liver and gallbladder. In this setting, the irregular growth pattern and epithelial atypia, and also the absence of characteristic concentric fibrosis, may strongly suggest the diagnosis of metastatic adenocarcinoma involving the peritoneal cavity. Metastatic adenocarcinoma typically demonstrates greater cytologic atypia, more irregular growth pattern, mitotic activity, and lacks the typical concentric fibrous collar seen in reactive Luschka ducts. However, in some cases, this distinction may be difficult to make. We urge caution when evaluating peritoneal biopsies of the gallbladder fossa (particularly on frozen section), recognizing that this specific site is home to the cancer mimic we have illustrated herein. Indeed, 2 of our cases were originally considered to represent invasive adenocarcinoma. At times, when encountering a bland but irregular ductal proliferation in the gallbladder fossa, it may be appropriate to defer the frozen section diagnosis and request additional tissue sampling intraoperatively or wait until permanent sections are available.
A comparison of 21 cases of invasive well-to-moderately differentiated gallbladder adenocarcinoma in our study was helpful in delineating key histologic features that may aid in distinguishing florid ducts of Luschka from invasive adenocarcinoma (). In fact, in contrast to Luschka ducts, invasive adenocarcinoma was characterized by a haphazard infiltrative growth pattern, glands with incomplete lumen formation, and irregular fibrosis surrounding individual glands consistent with desmoplasia. In addition, Luschka ducts are limited to the gallbladder adventitia, whereas the majority of invasive adenocarcinomas involved the entire gallbladder wall. Numerous mitotic figures, marked nuclear variation within a single gland, vascular invasion, and perineural invasion were frequently found in cases of adenocarcinoma, but were absent in benign Luschka ducts. A lobular configuration, confinement to the gallbladder adventitia, and a fibrous collar associated with larger glands were never appreciated in invasive adenocarcinoma. However, in a few cases, probable cancerization of Luschka ducts was identified. This may cause added confusion and difficulty; however in all cases, where this occurred, smaller, angulated, and incomplete glands diagnostic for invasive adenocarcinoma were found nearby.
Immunohistochemical markers discriminating benign ducts of Luschka from malignancy would be extremely helpful. Previous studies have shown that a limited immunohistochemical panel consisting of markers such as, p53, DPC4, and a Ki-67 has been very useful in making the distinction between benign versus malignant biliary disease. The overexpression of p53, loss of DPC4, and demonstration of a high proliferation index by Ki-67 have been shown to be associated with malignancy. However, this panel has not been specifically applied to hyperplastic Luschka ducts. Owing to the limited material available, immunohistochemical studies could not be conducted systematically on all the cases of florid ducts of Luschka presented herein. Therefore, future studies to determine their utility in differential diagnosis are warranted. We do note that case 1 of our series demonstrated a low Ki-67 index, whereas case 2 demonstrated a high Ki-67 index, suggesting that this single marker may not discriminate reactive Luschka ducts, especially in the context of severe acute cholecystitis from adenocarcinoma.
Benign diagnoses are also in the differential diagnosis of florid ducts of Lushka. For instance, Rokitansky-Aschoff sinuses represent herniations of the mucosa into the lamina propria, muscularis, and/or even the subserosa.5,6
They display smooth, undulating contours and are lined by a single layer of epithelium. In contrast to the cuboidal-to-columnar lining of ducts of Luschka, the epithelium of Rokitansky-Aschoff sinuses is typically composed of a distinctly columnar biliary epithelium. Rokitansky-Aschoff sinuses may be associated with hyperplastic muscularis, and once present in the subserosa, result in the fibrous distortion of the surrounding connective tissue. Furthermore, they may be associated with an inflammatory background and demonstrate marked reactive atypia. Adenomyomatous hyperplasia is essentially an exaggerated proliferation of Rokitansky-Aschoff sinuses. Three types of adenomyomatous hyperplasia are recognized: the localized form, also known as adenomyoma, and the segmental and diffuse types. As with Rokitansky-Aschoff sinuses, these are characterized by smooth muscle hyperplasia. Over time, the wall of the gallbladder may become fibrotic and the hyperplastic smooth muscle bundles may no longer be visible.2,4
Unlike florid ducts of Luschka, Rokitansky-Aschoff sinuses and adenomyomatous hyperplasia communicate through the thickened gallbladder muscular wall with the gallbladder lumen and are not restricted to the gallbladder subserosa. Moreover, they may contain bile and lack the concentric fibrosis surrounding larger ductules, which is typical of Luschka ducts.
For completeness, it is important to note that neoplastic transformation has been described within ducts of Luschka, but only 2 cases have been reported in the literature.7,14
Both cases demonstrated gross thickening of the fundic portion of the gallbladder and the neoplasms formed solid, gray-colored masses. Histologically, the neoplasms were characterized by both an intraductal and invasive component intermingled between benign ducts of Luschka. However, the intraductal component differed between the cases. One case exhibited prominent arborizing papillary fronds containing fibrovascular cores,14
whereas the other displayed a solid epithelial growth pattern.7
The invasive adenocarcinoma in both cases was composed of a haphazard arrangement of irregular, small glands within a desmoplastic stroma. The glands were lined by a single layer of markedly atypical cuboidal epithelium. Mitotic figures were rare. Lymphovascular invasion was absent in both cases, but perineural invasion was identified in a single case.7
In conclusion, the distinction between ducts of Luschka and other non-neoplastic and neoplastic conditions can be diagnostically challenging, especially in cases of florid proliferation and marked reactive inflammatory atypia. Special attention to the anatomic location and key histologic features are essential to establish the correct diagnosis.