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Alramadhan HJ, Lim SY, Jeong HJ, Jeon HJ, Chae H, Yoon SJ, Shin SH, Han IW, Heo JS, Kim H. Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer. Cancers (Basel) 2023; 15:5166. [PMID: 37958339 PMCID: PMC10650487 DOI: 10.3390/cancers15215166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 10/19/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR.
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Affiliation(s)
| | - Soo-Yeun Lim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Hye-Jeong Jeong
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Hyun-Jeong Jeon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Hochang Chae
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - So-Jeong Yoon
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Sang-Hyun Shin
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - In-Woong Han
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Jin-Seok Heo
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
| | - Hongbeom Kim
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea; (S.-Y.L.); (H.-J.J.); (H.-J.J.); (H.C.); (S.-J.Y.); (S.-H.S.); (I.-W.H.); (J.-S.H.)
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Xue Y, Basturk O. Intraductal neoplasms of the pancreatobiliary tract: navigating the alphabet. Histopathology 2023; 83:499-508. [PMID: 37455382 DOI: 10.1111/his.15003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 06/02/2023] [Accepted: 06/19/2023] [Indexed: 07/18/2023]
Abstract
Cancers of the pancreatobiliary tract are diseases with unfavourable prognoses. In the last couple of decades, two types of lesions have been described as precursors that precede pancreatobiliary cancers. These include incidental microscopic (flat) lesions known as pancreatic intra-epithelial neoplasia and biliary intra-epithelial neoplasia, and grossly visible, mass-forming lesions (tumoral intra-epithelial neoplasia) including intraductal papillary mucinous neoplasms, intraductal oncocytic papillary neoplasms, intraductal tubulopapillary neoplasms, intraductal papillary neoplasms of the bile duct and intracholecystic papillary neoplasms. Early detection and adequate treatment of these precursor lesions, especially the second group, have the potential to prevent pancreatobiliary cancer or at least improve its prognosis. In this review, we discuss their histopathology and recent updates on molecular profiling of these intraductal neoplasms of the pancreatobiliary tract.
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Affiliation(s)
- Yue Xue
- Department of Pathology and Laboratory Medicine, Northwestern University, Chicago, IL, USA
| | - Olca Basturk
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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Desjonqueres E, Campani C, Marra F, Zucman-Rossi J, Nault JC. Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice. Liver Int 2022; 42:492-506. [PMID: 34982503 DOI: 10.1111/liv.15152] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/20/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver cancers, accounting for approximately 80% and 15%, respectively. HCC carcinogenesis occurs mostly in cirrhosis and is a complex multi-step process, from precancerous lesions (low-grade and high-grade dysplastic nodules) to progressed HCC. During the different stages of liver carcinogenesis, there is an accumulation of pathological, genetic and epigenetic changes leading to initiation, malignant transformation and finally tumour progression. In contrast, a small subset of HCC occurs in normal liver from the transformation of hepatocellular adenoma (HCA), a benign hepatocellular tumour. The recent molecular classification enables to stratify HCAs according to their risk of complication, in particular malignant transformation, associated with mutations in exon 3 of the catenin beta 1 (CTNNB1) gene. Cholangiocarcinoma (CCA) derives from the multistep malignant transformation of preneoplastic lesions, like biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB), for which a pre-operative diagnosis remains difficult. Different genetic alterations are involved in BilIN and IPNB progression, leading to the development of tubular or intestinal adenocarcinoma. The aims of this review are to describe the main clinical and molecular features of preneoplastic lesions leading to the development of HCC and CCA, their implications in clinical practice and the perspectives for future research.
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Affiliation(s)
- Elvire Desjonqueres
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Claudia Campani
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Jessica Zucman-Rossi
- Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.,Hôpital Européen Georges Pompidou, APHP, Paris, France
| | - Jean-Charles Nault
- Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France.,Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Paris, France.,Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
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Sarcognato S, Sacchi D, Fassan M, Fabris L, Cadamuro M, Zanus G, Cataldo I, Covelli C, Capelli P, Furlanetto A, Guido M. Benign biliary neoplasms and biliary tumor precursors. Pathologica 2021; 113:147-157. [PMID: 34294933 PMCID: PMC8299320 DOI: 10.32074/1591-951x-251] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 01/04/2021] [Indexed: 12/21/2022] Open
Abstract
Benign biliary tumor are common lesions that are often an incidental finding in subjects who undergo medical imaging tests for other conditions. Most are true neoplasms while few result from reactive or malformative proliferation. Benign tumors have no clinical consequences, although the premalignant nature or potential for malignant transformation is of concern in some cases. The main practical problem for pathologists is the need to differentiate them from malignant biliary tumours, which is not always straightforward. Premalignant lesions of the bile duct have been described, although their incidence has been poorly characterized. These lesions include biliary mucinous cystic neoplasms, intraductal papillary neoplasms of the bile duct, and biliary intraepithelial neoplasia. In this article, histopathology of benign biliary tumors and biliary tumor precursors is discussed, with a focus on the main diagnostic criteria.
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Affiliation(s)
| | - Diana Sacchi
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Matteo Fassan
- Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Luca Fabris
- Department of Molecular Medicine - DMM, University of Padova, Padova, Italy
| | | | - Giacomo Zanus
- 4 Surgery Unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Surgery, Oncology and Gastroenterology - DISCOG, University of Padova, Padova, Italy
| | - Ivana Cataldo
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Claudia Covelli
- Pathology Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza”, San GiovanniRotondo, Italy
| | - Paola Capelli
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | | | - Maria Guido
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Medicine - DIMED, University of Padova, Padova, Italy
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Ramachandran A, Srivastava DN, Madhusudhan KS. Gallbladder cancer revisited: the evolving role of a radiologist. Br J Radiol 2020; 94:20200726. [PMID: 33090880 DOI: 10.1259/bjr.20200726] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Gallbladder cancer is the most common malignancy of the biliary tract. It is also the most aggressive biliary tumor with the shortest median survival duration. Complete surgical resection, the only potentially curative treatment, can be accomplished only in those patients who are diagnosed at an early stage of the disease. Majority (90%) of the patients present at an advanced stage and the management involves a multidisciplinary approach. The role of imaging in gallbladder cancer cannot be overemphasized. Imaging is crucial not only in detecting, staging, and planning management but also in guiding radiological interventions. This article discusses the role of a radiologist in the diagnosis and management of gallbladder cancer.
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Affiliation(s)
- Anupama Ramachandran
- Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
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Impact of Remnant Carcinoma in Situ at the Ductal Stump on Long-Term Outcomes in Patients with Distal Cholangiocarcinoma. World J Surg 2020; 45:291-301. [PMID: 32989580 DOI: 10.1007/s00268-020-05799-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND The management of positive ductal margins with carcinoma in situ (R1-CIS) after resection is controversial. The aim of this study was to evaluate the impact of R1-CIS on survival in patients who underwent resection for distal cholangiocarcinoma. METHODS We enrolled 121 consecutive patients with distal cholangiocarcinoma. Poor prognostic factors were investigated by multivariable analysis, and we performed a stratified analysis to evaluate the impact of R1-CIS on survival in patients with or without prognostic factors. RESULTS Multivariable analysis identified node-positive status as the prognostic factor (P = 0.003). Stratified by lymph node status, overall survival (OS) in the R0 group was significantly better than that in the R1-CIS group in node-negative patients (57.1% vs 30.0%; P < 0.050). Although OS was comparable between the two groups in node-positive patients (5-year OS: 22.2% vs 20.0%, respectively; P = not significant). Furthermore, OS in patients in whom R0 was achieved by additional resection was significantly better than that in patients with R1-CIS (5-year OS: 66.7% vs 30.0%, respectively; P < 0.050). CONCLUSIONS Remnant CIS is associated with a poor prognosis in patients with node-negative distal cholangiocarcinoma. Every effort should be made to achieve negative bile duct margins.
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Shin D, Lee S, Lee JH, Hong SM, Park SY, Yoo C, Lee W, Song KB, Hwang DW, Kim SC. Prognostic implication of high grade biliary intraepithelial neoplasia in bile duct resection margins in patients with resected perihilar cholangiocarcinoma. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:604-613. [PMID: 32639085 DOI: 10.1002/jhbp.800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/21/2020] [Accepted: 06/28/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND In surgery for perihilar cholangiocarcinoma (PHCC), it is still controversial as to whether additional resection of the bile duct is needed on high grade (HG) biliary intraepithelial neoplasia (BilIN) margin. METHODS Patients who underwent surgery for PHCC with curative intent between 2001 and 2015 were stratified by resection margin, and were analyzed comparing the clinical outcomes. RESULTS Of the 306 study participants, 217 patients had negative margins (R0), 18 patients had HG BilIN, and 71 patients had positive margins (R1). The median overall survival was 36.0 months in the R0 group, 41.0 months in the HG BilIN group, and 25.0 months in the R1 group while overall survival rates at 5 years were 34.5% in the R0 group, 44.4% in the HG BilIN group, and 21.0% in the R1 group. The median disease-free survival was 15.0 months in the R0 group, 16.5 months in the HG BilIN group, and 12.0 months in the R1 group. CONCLUSIONS Although the HG BilIN group had neoplasia with malignant potential, survival and recurrence outcomes were comparable to those of the R0 group, which suggests that no additional resection is needed when the maximal bile duct margin in PHCC surgery contains HG BilIN.
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Affiliation(s)
- Dakyum Shin
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sojung Lee
- Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seo Young Park
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Prevalence and Clinical Significance of Biliary Intraepithelial Neoplasia (BilIN) in Cholangiocarcinoma. Indian J Surg 2020. [DOI: 10.1007/s12262-019-01930-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Geramizadeh B. Precursor Lesions of Cholangiocarcinoma: A Clinicopathologic Review. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2020; 13:2632010X20925045. [PMID: 32596664 PMCID: PMC7297471 DOI: 10.1177/2632010x20925045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 04/18/2020] [Indexed: 12/12/2022]
Abstract
Cholangiocarcinoma (CCA) develops through multistep carcinogenesis. During the past decades, 2 precursors have been proved to evolve to CCA. The 2 main precursor lesions of CCA are biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. It is an interesting and relatively novel entity for the hepatobiliary surgeons, radiologists, oncologists, and pathologists. It worth being familiar with these 2 entities for better communication between pathologists, oncologists, and surgeons to improve the treatment and follow-up of these lesions, which can definitely decrease their evolvement to CCA as an aggressive, poor prognostic, and life-threatening cancer. In this narrative review, I collected and discussed all published studies about these 2 precursor lesions of CCA including radiologic, clinical, and pathological manifestation.
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Affiliation(s)
- Bita Geramizadeh
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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10
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Abstract
Cancers of the biliary tract include intra- and extrahepatic cholangiocarcinomas and gallbladder cancer. Biliary tract cancers are diseases with unfavorable prognoses. In recent years, several lesions have been described as precursors that precede biliary cancers. They include flat and microscopic lesions known as biliary intraepithelial neoplasia, macroscopic and tumor-forming intraductal papillary biliary neoplasia, intraductal tubular neoplasia, and mucinous cystic neoplasm of the bile duct. These conditions are rarely diagnosed, while their natural history and progression to cancer have yet to be adequately characterized. This review examines the epidemiology, pathology, molecular biology, diagnosis, and therapy of these various precursors. Further research is required if we are to better understand this evolving field and improve the prevention and early detection of bile duct cancer.
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Yoshida N, Aoyagi T, Kimura Y, Naito Y, Izuwa A, Mizoguchi K, Ishii K, Tanaka Y, Ohnishi E, Miura S, Shimamura S, Shirahama N, Kaneshiro K, Saruwatari A, Iwanaga A, Sadakari Y, Hirokata G, Ogata T, Taniguchi M. A rare case of symptomatic grossly-visible biliary intraepithelial neoplasia mimicking cholangiocarcinoma. World J Surg Oncol 2019; 17:191. [PMID: 31711502 PMCID: PMC6849222 DOI: 10.1186/s12957-019-1737-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 10/29/2019] [Indexed: 11/25/2022] Open
Abstract
Background Biliary intraepithelial neoplasia (BilIN) is often distinguished by what it is not: the precancerous lesions are not mass-forming, are not the cause of bile duct obstruction, and are small enough (less than 5 mm long) to evade detection by the naked eye. Here, we describe an atypical case of BilIN resembling cholangiocarcinoma (CC) that was large enough to be identified by diagnostic imaging and presented with obstructive jaundice caused by a hematoma in the common bile duct (CBD). Case presentation A 64-year-old man presented to our hospital with upper abdominal pain and anorexia. Initial laboratory examinations revealed increased total bilirubin and a computed tomography (CT) scan revealed a dilated CBD. Gastroenterologists performed an endoscopic sphincterotomy (EST), which revealed that the cause of obstructive jaundice was a hematoma in the CBD. Enhanced CT scan and magnetic resonance cholangiopancreatography (MRCP) performed after the hematoma was drained showed improved dilation of the CBD and an enhanced wall thickness of bile duct measuring 25 × 10 mm at the union of the cystic and common hepatic ducts. A cholangioscope detected an elevated tumor covered by sludge in the CBD, and we performed an extrahepatic bile duct resection and cholecystectomy. The postoperative course was uneventful and the pathological examination of the resected tumor revealed that although the ulcerated lesion had inflammatory granulation tissue, it did not contain the components of invasive carcinoma. Many consecutive intraepithelial micropapillary lesions spread around the ulcerated lesion, and the epithelial cells showed an increased nucleus-to-cytoplasm ratio, nuclear hyperchromasia, and architectural atypia. The pathological diagnosis was BilIN-1 to -2. Immunohistochemical staining showed that S100P was slightly expressed and MUC5AC was positive, while MUC1 was negative and p53 was not overexpressed. Conclusion We experienced an atypical case of BilIN mimicking CC that presented with obstructive jaundice caused by a hematoma in the CBD. Our case suggested that the occurrence of BilIN can be triggered by factors other than inflammation, and can grow to a size large enough to be detected by image analyses.
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Affiliation(s)
- Naohiro Yoshida
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan.
| | - Takeshi Aoyagi
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Yoshizo Kimura
- Department of Pathology and Cytology, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Yoshiki Naito
- Department of Pathology, Kurume University School of Medicine, Asahi-machi 67, Kurume-shi, Fukuoka, 8300011, Japan
| | - Aya Izuwa
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Kimihisa Mizoguchi
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Kota Ishii
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Yu Tanaka
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Emi Ohnishi
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Shun Miura
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Satoshi Shimamura
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Nobuhisa Shirahama
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Kazuhisa Kaneshiro
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Akihiro Saruwatari
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Ayako Iwanaga
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Yoshihiko Sadakari
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Gentaro Hirokata
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Toshiro Ogata
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
| | - Masahiko Taniguchi
- Department of Surgery, St. Mary's Hospital, Tsubukuhon-machi 422, Kurume-shi, Fukuoka, 8308543, Japan
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Zaccari P, Cardinale V, Severi C, Pedica F, Carpino G, Gaudio E, Doglioni C, Petrone MC, Alvaro D, Arcidiacono PG, Capurso G. Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas. World J Gastroenterol 2019; 25:4343-4359. [PMID: 31496617 PMCID: PMC6710182 DOI: 10.3748/wjg.v25.i31.4343] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 07/13/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.
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Affiliation(s)
- Piera Zaccari
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00161 Rome, Italy
| | - Carola Severi
- Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Sapienza University of Rome, Rome 00161, Italy
| | - Federica Pedica
- Pathology Department, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Guido Carpino
- Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome "Foro Italico", Rome 00161, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Division of Human Anatomy, Sapienza University of Rome, Rome 00161, Italy
| | - Claudio Doglioni
- Pathology Department, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Maria Chiara Petrone
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Domenico Alvaro
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome 00161, Italy
| | - Paolo Giorgio Arcidiacono
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
| | - Gabriele Capurso
- PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan 20132, Italy
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Yoon KC, Yu YD, Kang WH, Jo HS, Kim DS, Kim JY. Prevalence and Clinical Significance of Biliary Intraepithelial Neoplasia (BilIN) in Cholangiocarcinoma. Am Surg 2019. [DOI: 10.1177/000313481908500529] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Biliary intraepithelial neoplasia (BilIN) is the most common noninvasive precursor lesion which progresses to cholangiocarcinoma (CC) and is often found synchronously adjacent to the tumor or at the surgical resection margin. The aim of this study was to elucidate the prevalence and prognostic effect of BilIN on survival after resection for CC. We retrospectively analyzed the database of patients with CC who underwent surgery performed at our institution from 2010 to 2017. There were 142 patients who underwent surgery for CC. BilIN was detected in 42 patients (29.5%). On univariate analysis, extrahepatic CC (ExtraH CC) patients with BilIN lesions significantly showed better disease-free survival ( P = 0.05). Also, although not statistically significant, ExtraH CC patients with BilIN lesions revealed better overall survival (OS) ( P = 0.09). On multivariate analysis, presence of BilIN lesion, irrespective of location, was significantly associated with better disease-free survival (HR = 2.059, 95% confidence interval (CI): 1.057–4.432, P = 0.041) and OS (HR = 1.831, 95% CI: 1.149–3.534, P = 0.044) in ExtraH CC patients. The presence of BilIN lesions was not uncommon in CC patients and was significantly associated with better disease-free survival and OS in ExtraH CC patients. However, larger studies with longer follow-up are needed to accurately determine its clinical significance.
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Affiliation(s)
- Kyung-Chul Yoon
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea; and
| | - Young-Dong Yu
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea; and
| | - Woo-Hyung Kang
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea; and
| | - Hye-Sung Jo
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea; and
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea; and
| | - Joo-Young Kim
- Department of Pathology, Eulji Medical Center, Seoul, Korea
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Higaki T, Yamazaki S, Sugitani M, Takayama T. Biliary intraepithelial neoplasia in liver parenchyma of the caudate lobe: honeycomb appearance. Eur Surg 2019; 51:66-70. [DOI: 10.1007/s10353-018-0550-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 07/07/2018] [Indexed: 11/26/2022]
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15
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Wakai T, Sakata J, Katada T, Hirose Y, Soma D, Prasoon P, Miura K, Kobayashi T. Surgical management of carcinoma in situ at ductal resection margins in patients with extrahepatic cholangiocarcinoma. Ann Gastroenterol Surg 2018; 2:359-366. [PMID: 30238077 PMCID: PMC6139714 DOI: 10.1002/ags3.12196] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 06/12/2018] [Accepted: 06/24/2018] [Indexed: 12/13/2022] Open
Abstract
Recent advances in dimensional imaging, surgical technique, and perioperative patient care have resulted in increased rates of complete resection with histopathologically negative margins and improved surgical outcomes in patients with extrahepatic cholangiocarcinoma. However, achieving cancer-free resection margins at ductal stumps in surgery for this disease remains challenging because of longitudinal extension, which is one of the hallmarks of extrahepatic cholangiocarcinoma. When the ductal resection margins are shown to be positive on examination of frozen sections, discrimination between carcinoma in situ and invasive carcinoma is clinically important because residual carcinoma in situ may lead to late local recurrence whereas residual invasive carcinoma is associated with early local recurrence. Residual invasive carcinoma at the ductal margins should be avoided whenever technically feasible. Residual "carcinoma in situ" at the ductal margins appears to be allowed in resection for the advanced disease because it has less effect on survival than other adverse prognostic factors (pN1 and/ or pM1). However, in surgery for early-stage (pTis-2N0M0) extrahepatic cholangiocarcinoma, residual carcinoma in situ at the ductal margins may have an adverse effect on long-term survival, so should be avoided whenever possible. In this review, we focus on the histopathological term "carcinoma in situ," the biological behavior of residual carcinoma in situ at ductal resection margins, intraoperative histological examination of the ductal resection margins, outcome of additional resection for positive ductal margins, and adjuvant therapy for patients with positive margins.
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Affiliation(s)
- Toshifumi Wakai
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Jun Sakata
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Tomohiro Katada
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Yuki Hirose
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Daiki Soma
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Pankaj Prasoon
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Kohei Miura
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
| | - Takashi Kobayashi
- Division of Digestive and General SurgeryNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
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Jiang K, Al-Diffhala S, Centeno BA. Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk Stratification. Cancer Control 2018; 25:1073274817744625. [PMID: 29350068 PMCID: PMC5933592 DOI: 10.1177/1073274817744625] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors. The histomorphology of normal liver, preinvasive precursors, primary malignancies, and morphological variants, and the utilization of ancillary tests for the pathological diagnosis are described. Dysplastic nodules are the preinvasive precursors of HCC, and intraductal papillary neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive precursors of CC. Benign liver nodules including focal nodular hyperplasia and adenomas are included in this review, since some forms of adenomas progress to HCC and often they have to be differentiated from well-differentiated HCC. A number of morphological variants of HCC have been described in the literature, and it is necessary to be aware of them in order to render the correct diagnosis. Risk stratification is still dependent on the AJCC staging system. The diagnosis of primary liver carcinomas is usually straightforward. Application of the appropriate ancillary studies aids in the differential diagnosis of difficult cases. The understanding of the carcinogenesis of these malignancies has improved with the standardization of the pathological classification of preinvasive precursors and studies of the molecular pathogenesis. Risk stratification still depends on pathological staging.
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Affiliation(s)
- Kun Jiang
- 1 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.,2 Department of Oncologic Sciences, Morsani College of Medicine at University of South Florida, Tampa, FL, USA
| | - Sameer Al-Diffhala
- 3 Division of Anatomic Pathology, Department of Pathology, University of Alabama School of Medicine, Birmingham, AL, USA
| | - Barbara A Centeno
- 1 Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.,2 Department of Oncologic Sciences, Morsani College of Medicine at University of South Florida, Tampa, FL, USA
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17
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18
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Ainechi S, Lee H. Updates on Precancerous Lesions of the Biliary Tract: Biliary Precancerous Lesion. Arch Pathol Lab Med 2016; 140:1285-1289. [DOI: 10.5858/arpa.2015-0396-rs] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Precursor lesions of invasive adenocarcinoma of the bile duct (cholangiocarcinoma) have been increasingly recognized during the past decade because of the results of multiple studies on the carcinogenesis of cholangiocarcinoma, technologic advancements in diagnostic imaging modalities, and an increase in the volume of elective procedures. The two main precursor lesions of cholangiocarcinoma that have evolved are biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. These lesions demonstrate histomorphologic similarities to pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm of the pancreas, respectively, whereas mechanisms of carcinogenesis and risk of progressive disease appear distinct. An enhanced understanding of the clinical presentation and pathologic features of precursor lesions of the biliary tract and use of the correct terminology will facilitate efficient communication between surgeons, oncologists, and pathologists and improve quality of patient care.
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Affiliation(s)
- Sanaz Ainechi
- From the Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York
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Nakanuma Y, Uchida T, Sato Y, Uesaka K. An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma. Hum Pathol 2016; 60:46-57. [PMID: 27984121 DOI: 10.1016/j.humpath.2016.10.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Revised: 10/08/2016] [Accepted: 10/14/2016] [Indexed: 12/21/2022]
Abstract
Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs.
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Affiliation(s)
- Yasuni Nakanuma
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan.
| | - Tsuneyuki Uchida
- Department of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan; Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan
| | - Katsuhiko Uesaka
- Department of Hepatobiliary Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, 411-8777, Japan
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20
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Ettel M, Eze O, Xu R. Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma. World J Hepatol 2015; 7:2563-2570. [PMID: 26557948 PMCID: PMC4635141 DOI: 10.4254/wjh.v7.i25.2563] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/10/2015] [Accepted: 10/19/2015] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis.
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