LETTER
Heterogeneity of Luschka Ducts of the Gallbladder To the Editor: The Luschka ducts (LDs) are well-known structures that were described in the 19th century, around the start of the microscope era. However, the recent review of Schnelldorfer et al1 suggests that information on the histologic descriptions are limited. In addition, the differential diagnosis with adenocarcinoma remains challenging as recently reported.2 Moreover, the immunohistochemical profile of LDs has not been reported to our knowledge. We recently observed such lesions in a gallbladder with lithiasic cholecystitis (2 cm calculus). The LD complexes (over 20 complexes, over a 2 cm length; gallbladder length, 9 cm) were situated as a rim in subserosal location, close to the point of adherence of the gallbladder to the liver (Fig. 1). The largest of the LD complexes measured 3.5 mm. Myofibroblasts (smooth muscle actin positive and desmin negative) were more abundant in this subserosal zone, with both concentric and rim-like disposition. The serosa was atrophic. The LDs were either made up of a central duct surrounded by smaller ductules or only of equally sized small ducts. Their form varied from round to collapsed with some angular lumens. The central duct was cystic (3 mm) in only one of these complexes. The epithelial layer was composed of cuboidal cells with regular nuclei. Rare ducts showed tall, col-
TO THE
EDITOR
umnar cells with supranuclear mucin, which was positive for Alcian blue. These structures were not connected to mucosa. At distance, on another slide, there was a 2.5 mm rim of hepatocytes (1 to 8 hepatocytes in height) and a detached fragment of 1 mm that did not show a biliary structure (the resected specimen was analyzed entirely microscopically). Immunohistochemical analysis revealed that the epithelial cells of LDs expressed cytokeratins 7 (membrane and/or cytoplasmic), 19 (membrane and/or cytoplasmic), and CD10 (membrane but negative in the cystic duct) and showed a more focal expression of CK20 (membrane and/or cytoplasmic), Cdx2 (nuclear and/or cytoplasmic), and progesterone receptor (nuclear and/or cytoplasmic) (Fig. 1). These cells were negative for CK5/6, calretinin, p63, and estrogen receptor. Herein, we report on morphologic and immunohistochemical heterogeneity of LDs. They may show focal mucinous metaplasia with cytoplasmic staining of mucins by Alcian blue. The majority of cuboidal epithelial cells with cytoplasmic mucin expression were also positive for CK7, CK19, and small intestinal marker CD10. The intestinal marker Cdx2 (caudal-related homeobox transcription factor) was also expressed focally in LD cells, either in sparse nuclei or in the cytoplasm.3 Of interest would be the expression of progesterone receptors, which are known to be positive in cholelithiasis.4 Rather than the inflammation accompanying lithiasis, it is more likely that this heterogeneity is due to abnormal endodermal development, as no intraluminal stones or inflammation was
observed at the LD subserosal level. Although the morphologic features of this presented case did not suggest a malignant tumor, the heterogenous morphophenotype and immunophenotype of such lesions should be acknowledged as it might be relevant in the differential diagnosis with welldifferentiated adenocarcinomas, including biliary or pancreatic carcinomas. Adriana Handra-Luca, MD, PhD*w Seung-Mo Hong, MD, PhDz *Service d’Anatomie pathologique APHP GHU Avicenne wUFR Me´decine, Universite´ Paris Nord Sorbonne Cite´, Bobigny, France zDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
ACKNOWLEDGMENTS The authors thank Dr Hanh Luong and Florence Bouchard, Virginie Akdim, Christine Van Vetteren, Leila Jovanov, Isabelle Pluchart, Fella Spindler, Nathalie Delva, Valerie Ipotesi, Nadine Jalem, Amelie Poirier, Julie Diallo, Valerie Moigne, and Laurent Lefebure. REFERENCES 1. Schnelldorfer T, Sarr MG, Adams DB. What is the duct of Luschka?: a systematic review. J Gastrointest Surg. 2012;16:656–662. 2. Singhi AD, Adsay NV, Swierczynski SL, et al. Hyperplastic Luschka ducts: a mimic of adenocarcinoma in the gallbladder fossa. Am J Surg Pathol. 2011;35:883–890. 3. Sakamoto H, Mutoh H, Ido K, et al. A close relationship between intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis. Hum Pathol. 2007;38:66–71. 4. Gupta P, Agarwal A, Gupta V, et al. Expression and clinicopathological significance of estrogen and progesterone receptors in gallbladder cancer. Gastrointest Cancer Res. 2012;5:41–47.
The authors declare no conflict of interest.
674 | www.appliedimmunohist.com
Appl Immunohistochem Mol Morphol
Volume 23, Number 9, October 2015
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Appl Immunohistochem Mol Morphol
Volume 23, Number 9, October 2015
Letter to the Editor
FIGURE 1. The gallbladder wall showing several Luschka duct complexes disposed as a rim in the subserosal tissue, without connection to the mucosa (A, C, D, D inset: arrows for the Luschka ducts). One of the ducts was cystic (A inset: star). Several cells showed abundant, cytoplasmic Alcian blue-positive mucin (B). Epithelial cells expressed cytokeratins 7, cytokeratin 19, and CD10 (C, D, D inset, respectively). Smooth muscle actin stained a rim of myofibroblasts disposed around the subserosal Luschka ducts, at distance of the gallbladder muscle wall (C inset, arrow). Cytokeratin 20 was expressed focally (E). Cdx2 was expressed in epithelial cell cytoplasm or nuclei (F, arrow). White star indicates gallbladder lumina (C, D); black star, cystic Luschka duct (A inset, E); (A, A inset), hematoxylin and eosin stain (original magnification, 2.5); (B), Alcian blue stain ( 20); (C), cytokeratin 7 ( 2.5); (C) inset, smooth muscle actin ( 2.5); (D), cytokeratin 19 ( 2.5); (D inset), CD10 ( 2.5); (E), cytokeratin 20 ( 20); (F), Cxd2 ( 40).
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.appliedimmunohist.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
675
Heterogeneity of Luschka Ducts of the Gallbladder To the Editor: The Luschka ducts (LDs) are well-known structures that were described in the 19th century, around the start of the microscope era. However, the recent review of Schnelldorfer et al1 suggests that information on the histologic descriptions are limited. In addition, the differential diagnosis with adenocarcinoma remains challenging as recently reported.2 Moreover, the immunohistochemical profile of LDs has not been reported to our knowledge. We recently observed such lesions in a gallbladder with lithiasic cholecystitis (2 cm calculus). The LD complexes (over 20 complexes, over a 2 cm length; gallbladder length, 9 cm) were situated as a rim in subserosal location, close to the point of adherence of the gallbladder to the liver (Fig. 1). The largest of the LD complexes measured 3.5 mm. Myofibroblasts (smooth muscle actin positive and desmin negative) were more abundant in this subserosal zone, with both concentric and rim-like disposition. The serosa was atrophic. The LDs were either made up of a central duct surrounded by smaller ductules or only of equally sized small ducts. Their form varied from round to collapsed with some angular lumens. The central duct was cystic (3 mm) in only one of these complexes. The epithelial layer was composed of cuboidal cells with regular nuclei. Rare ducts showed tall, col-
TO THE
EDITOR
umnar cells with supranuclear mucin, which was positive for Alcian blue. These structures were not connected to mucosa. At distance, on another slide, there was a 2.5 mm rim of hepatocytes (1 to 8 hepatocytes in height) and a detached fragment of 1 mm that did not show a biliary structure (the resected specimen was analyzed entirely microscopically). Immunohistochemical analysis revealed that the epithelial cells of LDs expressed cytokeratins 7 (membrane and/or cytoplasmic), 19 (membrane and/or cytoplasmic), and CD10 (membrane but negative in the cystic duct) and showed a more focal expression of CK20 (membrane and/or cytoplasmic), Cdx2 (nuclear and/or cytoplasmic), and progesterone receptor (nuclear and/or cytoplasmic) (Fig. 1). These cells were negative for CK5/6, calretinin, p63, and estrogen receptor. Herein, we report on morphologic and immunohistochemical heterogeneity of LDs. They may show focal mucinous metaplasia with cytoplasmic staining of mucins by Alcian blue. The majority of cuboidal epithelial cells with cytoplasmic mucin expression were also positive for CK7, CK19, and small intestinal marker CD10. The intestinal marker Cdx2 (caudal-related homeobox transcription factor) was also expressed focally in LD cells, either in sparse nuclei or in the cytoplasm.3 Of interest would be the expression of progesterone receptors, which are known to be positive in cholelithiasis.4 Rather than the inflammation accompanying lithiasis, it is more likely that this heterogeneity is due to abnormal endodermal development, as no intraluminal stones or inflammation was
observed at the LD subserosal level. Although the morphologic features of this presented case did not suggest a malignant tumor, the heterogenous morphophenotype and immunophenotype of such lesions should be acknowledged as it might be relevant in the differential diagnosis with welldifferentiated adenocarcinomas, including biliary or pancreatic carcinomas. Adriana Handra-Luca, MD, PhD*w Seung-Mo Hong, MD, PhDz *Service d’Anatomie pathologique APHP GHU Avicenne wUFR Me´decine, Universite´ Paris Nord Sorbonne Cite´, Bobigny, France zDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
ACKNOWLEDGMENTS The authors thank Dr Hanh Luong and Florence Bouchard, Virginie Akdim, Christine Van Vetteren, Leila Jovanov, Isabelle Pluchart, Fella Spindler, Nathalie Delva, Valerie Ipotesi, Nadine Jalem, Amelie Poirier, Julie Diallo, Valerie Moigne, and Laurent Lefebure. REFERENCES 1. Schnelldorfer T, Sarr MG, Adams DB. What is the duct of Luschka?: a systematic review. J Gastrointest Surg. 2012;16:656–662. 2. Singhi AD, Adsay NV, Swierczynski SL, et al. Hyperplastic Luschka ducts: a mimic of adenocarcinoma in the gallbladder fossa. Am J Surg Pathol. 2011;35:883–890. 3. Sakamoto H, Mutoh H, Ido K, et al. A close relationship between intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis. Hum Pathol. 2007;38:66–71. 4. Gupta P, Agarwal A, Gupta V, et al. Expression and clinicopathological significance of estrogen and progesterone receptors in gallbladder cancer. Gastrointest Cancer Res. 2012;5:41–47.
The authors declare no conflict of interest.
674 | www.appliedimmunohist.com
Appl Immunohistochem Mol Morphol
Volume 23, Number 9, October 2015
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Appl Immunohistochem Mol Morphol
Volume 23, Number 9, October 2015
Letter to the Editor
FIGURE 1. The gallbladder wall showing several Luschka duct complexes disposed as a rim in the subserosal tissue, without connection to the mucosa (A, C, D, D inset: arrows for the Luschka ducts). One of the ducts was cystic (A inset: star). Several cells showed abundant, cytoplasmic Alcian blue-positive mucin (B). Epithelial cells expressed cytokeratins 7, cytokeratin 19, and CD10 (C, D, D inset, respectively). Smooth muscle actin stained a rim of myofibroblasts disposed around the subserosal Luschka ducts, at distance of the gallbladder muscle wall (C inset, arrow). Cytokeratin 20 was expressed focally (E). Cdx2 was expressed in epithelial cell cytoplasm or nuclei (F, arrow). White star indicates gallbladder lumina (C, D); black star, cystic Luschka duct (A inset, E); (A, A inset), hematoxylin and eosin stain (original magnification, 2.5); (B), Alcian blue stain ( 20); (C), cytokeratin 7 ( 2.5); (C) inset, smooth muscle actin ( 2.5); (D), cytokeratin 19 ( 2.5); (D inset), CD10 ( 2.5); (E), cytokeratin 20 ( 20); (F), Cxd2 ( 40).
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.appliedimmunohist.com |
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
675
