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Memis B, Saka B, Pehlivanoglu B, Kim G, Balci S, Tajiri T, Ohike N, Bagci P, Akar KE, Muraki T, Jang KT, Maithel SK, Sarmiento J, Kooby DA, Esmer R, Tarcan ZC, Goodman M, Xue Y, Krasinskas A, Reid M, Basturk O, Adsay V. Comparison of Ampullary and Pancreatic Adenocarcinomas: Smaller Invasion, Common Adenomatous Components, Resectability, and Histology are Factors for Improved Survival for Patients with Ampullary Adenocarcinoma. Ann Surg Oncol 2025; 32:1858-1868. [PMID: 39402320 DOI: 10.1245/s10434-024-16355-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 09/29/2024] [Indexed: 02/12/2025]
Abstract
BACKGROUND The information on the clinicopathologic/outcome differences between ampullary adenocarcinoma (AC) and pancreatic adenocarcinoma (PC) has been conflicting to the extent that it still is questioned whether ACs need to be recognized separately from PCs. METHODS The characteristics of 413 ACs were compared with those of 547 PCs. RESULTS The ACs had a better prognosis than the PCs (5-year survival, 57 % vs 23 %; p < 0.001). Even the pancreatobiliary (PB)-type ACs had a better prognosis (5-year survival, 46 % vs 23 %; p < 0.001). Several differences also were identified as contributing factors: (1) the preinvasive adenomatous component often constituted a significant proportion of the mass in ACs (>50 % of the tumor in 16 % vs 1.5 %; p < 0.001); (2) the mean size of the carcinoma was smaller in ACs (2.5 vs 3.2 cm; p < 0.001): when matched for invasion size, the survival advantage of AC was minimized, and when matched for invasion size larger than 2 cm, the survival advantage of AC lost its statistical significance; (3) lymph node (LN) metastases were less common in ACs (49 % vs 71 %; p < 0.001); (4) the definitive R1 rate was lower in ACs (4 % vs 23.5 %; p < 0.001); and (5) non-PB and non-tubular adenocarcinoma types were more common in ACs (17 % vs 3 %; p < 0.001). CONCLUSIONS Comparatively, ACs have better clinical survival than PCs. Potential contributing factors are the relative abundance of the preinvasive component, smaller invasion, lower LN metastasis rate, higher resectability, and common occurrence of less aggressive histologic phenotypes (intestinal, medullary, mucinous). However, this survival advantage is sustained even in PB-type ACs, highlighting the importance of accurately determining the site of origin.
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Affiliation(s)
- Bahar Memis
- Department of Pathology, School of Medicine, Kocaeli University, Kocaeli, Turkey
| | - Burcu Saka
- Department of Pathology, School of Medicine, Koc University, Istanbul, Turkey
| | - Burcin Pehlivanoglu
- Department of Pathology, School of Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Grace Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Serdar Balci
- Department of Pathology, Memorial Health Group, Istanbul, Turkey
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Pelin Bagci
- Department of Pathology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Kadriye Ebru Akar
- Department of Pathology, School of Medicine, Marmara University, Istanbul, Turkey
| | - Takashi Muraki
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, USA
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Shishir K Maithel
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, USA
| | - Juan Sarmiento
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, USA
| | - David A Kooby
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, USA
| | - Rohat Esmer
- School of Medicine, Koc University, Istanbul, Turkey
| | - Zeynep Cagla Tarcan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael Goodman
- Department of Epidemiology, Emory University, Atlanta, GA, USA
| | - Yue Xue
- Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
| | - Alyssa Krasinskas
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, USA
| | - Michelle Reid
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, USA
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Volkan Adsay
- Department of Pathology, School of Medicine, Koc University, Istanbul, Turkey.
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Krasinskas AM. Diagnostic Pearls and Pitfalls in the Evaluation of Small Biopsies From the Bile Duct and Ampulla. Arch Pathol Lab Med 2025; 149:e47-e53. [PMID: 39603257 DOI: 10.5858/arpa.2024-0160-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/14/2024] [Indexed: 11/29/2024]
Abstract
CONTEXT.— Histopathologic evaluation of bile duct and ampullary biopsies can be challenging. Biopsies from these sites are often tiny, scant, and/or fragmented. When assessing these biopsies, there is significant overlap between reactive atypia and malignancy, in situ precursor lesions can be misinterpreted as malignancy, and nonprimary tumors can mimic primary disease. OBJECTIVE.— To provide diagnostic pearls and pitfalls in the evaluation of small biopsies from the biliary tract. DATA SOURCES.— Literature review of published studies and the author's own observations. CONCLUSIONS.— Because the procedures for obtaining specimens from the bile duct and ampulla are invasive, pathologists need to try to make definitive diagnoses. Diagnostic clues/pearls, ancillary studies, and recognition of various pitfalls can assist in providing accurate and confident diagnoses.
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Affiliation(s)
- Alyssa M Krasinskas
- From the Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia
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3
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Paolino G, Basturk O, Esposito I, Hong SM, Brosens LA, Tarcan Z, Wood LD, Gkountakos A, Omori Y, Mattiolo P, Ciulla C, Marchegiani G, Pea A, Bevere M, De Robertis R, D'Onofrio M, Salvia R, Cheng L, Furukawa T, Scarpa A, Adsay V, Luchini C. Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review. Mod Pathol 2024; 37:100554. [PMID: 38950698 DOI: 10.1016/j.modpat.2024.100554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 05/23/2024] [Accepted: 06/20/2024] [Indexed: 07/03/2024]
Abstract
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathologic, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) The male-to-female ratio was 1.5:1. Pancreatic head was the most common site (131/237; 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1 out of 5 cases (49/237; 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1 or pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and molecular features were as follows. The most commonly expressed mucins were MUC5AC (110/112; 98.2%) and MUC6 (78/84; 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (P < .01). Moreover, fusions involving PRKACA or PRKACB gene were detected in all of the 68 cases examined, with PRKACB::ATP1B1 being the most common (27/68 cases; 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (P < .01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathologic and molecular features. Considering the clinical or prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.
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Affiliation(s)
- Gaetano Paolino
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; Pathology Unit, Azienda Socio Sanitaria Territoriale Spedali Civili Di Brescia, Brescia, Italy
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Irene Esposito
- Institute of Pathology, University Hospital of Duesseldorf, Duesseldorf, Germany
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Lodewijk A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Zeynep Tarcan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Anastasios Gkountakos
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Yuko Omori
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Paola Mattiolo
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Calogero Ciulla
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Giovanni Marchegiani
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Antonio Pea
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Michele Bevere
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Riccardo De Robertis
- Section of Radiology, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy
| | - Mirko D'Onofrio
- Section of Radiology, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, The Warren Albert Medical School of Brown University, Lifespan Academic Medical Center, and the Legorreta Cancer Center at Brown University, Providence, Rhode Island
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Aldo Scarpa
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; ARC-Net Research Center, University of Verona, Verona, Italy
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Claudio Luchini
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; ARC-Net Research Center, University of Verona, Verona, Italy.
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Tarcan ZC, Esmer R, Akar KE, Bagci P, Bozkurtlar E, Saka B, Armutlu A, Sahin Ozkan H, Ozcan K, Taskin OC, Kapran Y, Aydin Mericoz C, Balci S, Yilmaz S, Cengiz D, Gurses B, Alper E, Tellioglu G, Bozkurt E, Bilge O, Cheng JD, Basturk O, Adsay NV. Intra-ampullary Papillary Tubular Neoplasm (IAPN): Clinicopathologic Analysis of 72 Cases Highlights the Distinctive Characteristics of a Poorly Recognized Entity. Am J Surg Pathol 2024; 48:1093-1107. [PMID: 38938087 DOI: 10.1097/pas.0000000000002275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
Abstract
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
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Affiliation(s)
- Zeynep C Tarcan
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | | | | | - Kerem Ozcan
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | - Serdar Balci
- Department of Pathology, Memorial Hospitals Group
| | | | | | | | | | | | | | - Orhan Bilge
- Department of Surgery, American Hospital, Istanbul, Turkey
| | | | - Olca Basturk
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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5
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Basturk O, Adsay NV. Early Cancerous Lesions of the Pancreas and Ampulla: Current Concepts and Challenges. Gastroenterol Clin North Am 2024; 53:57-84. [PMID: 38280751 PMCID: PMC10823180 DOI: 10.1016/j.gtc.2023.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2024]
Abstract
Owing to the increased use of advanced imaging techniques, mass-forming (cystic/intraductal) preinvasive neoplasms are being detected much more frequently and they have rapidly become one of the main focuses of interests in medical field. These neoplasms have very distinctive clinical and radiographic findings, exhibit a spectrum of dysplastic transformation, from low-grade dysplasia to high-grade dysplasia, and may be associated with an invasive carcinoma. Accounting for about 5% to 10% of pancreatic ductal adenocarcinomas, they provide a curable target subset in an otherwise biologically dismal pancreas cancer category.
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Affiliation(s)
- Olca Basturk
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
| | - N Volkan Adsay
- Department of Pathology, Koc University School of Medicine, Davutpaşa Cd. No:4, Zeytinburnu, Istanbul 34010, Turkey.
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6
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Kwon CH, Ahn JH, Seo HI, Kim DU, Han SY, Kim S, Lee NK, Hong SB, Park YM, Noh BG. Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining. World J Surg Oncol 2024; 22:5. [PMID: 38167037 PMCID: PMC10763163 DOI: 10.1186/s12957-023-03289-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/26/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.
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Affiliation(s)
- Chae Hwa Kwon
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Ji Hyun Ahn
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Pathology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Hyung Il Seo
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea.
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea.
| | - Dong Uk Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Sung Yong Han
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Suk Kim
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Nam Kyung Lee
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Seung Baek Hong
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Radiology, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Young Mok Park
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea
| | - Byeong Gwan Noh
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
- Department of Surgery, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, 179 Gudeok-Ro, Seo-Gu, Busan, 49241, South Korea
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Tejaswi S, Parikh M, Fananapazir G, Olson K, Gui D. Intra-ampullary papillary-tubular neoplasm. VIDEOGIE : AN OFFICIAL VIDEO JOURNAL OF THE AMERICAN SOCIETY FOR GASTROINTESTINAL ENDOSCOPY 2023; 8:277-282. [PMID: 37456221 PMCID: PMC10338961 DOI: 10.1016/j.vgie.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
Video 1Cholangioscopic examination of the ampullary channel and extrahepatic bile duct.
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Affiliation(s)
- Sooraj Tejaswi
- Division of Gastroenterology & Hepatology, University of California, Davis School of Medicine, Sacramento, California
| | - Mili Parikh
- Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, California
| | - Ghaneh Fananapazir
- Department of Radiology, University of California, Davis School of Medicine, Sacramento, California
| | - Kristin Olson
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, California
| | - Dorina Gui
- Department of Pathology and Laboratory Medicine, University of California, Davis School of Medicine, Sacramento, California
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Intraductal tubulopapillary neoplasms of the bile ducts: identity, clinicopathologic characteristics, and differential diagnosis of a distinct entity among intraductal tumors. Hum Pathol 2023; 132:12-19. [PMID: 35934108 DOI: 10.1016/j.humpath.2022.07.019] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023]
Abstract
Among the mass-forming preinvasive (tumoral intraepithelial) neoplasms of the biliary tract, intraductal tubulopapillary neoplasms (ITPN-Bs) are increasingly being recognized as a separate category. By being intramucosal polypoid proliferations of dysplastic/neoplastic cells, they are highly similar to other members of the "intraductal neoplasms (IDNs)" category (namely, intraductal papillary neoplasms [IPNBs], and intraductal oncocytic papillary neoplasms [IOPNs]); however, they are distinguished by MUC6-expressing nonmucinous cells that lack intestinal differentiation and form striking tubular configuration. Their molecular/genetic profile is also proving to be different with frequent alterations in cell cycle and chromatin remodeling genes, which are quite uncommon in other IDNs and cholangiocarcinomas. Despite the conceptual overlaps, they are also very different from intracholecystic nonmucinous tubular neoplasms (ICTN) of the gallbladder with the latter being associated with Wnt/beta-catenin pathway alterations, and almost never invasive. In contrast, ITPN-Bs are invasive in an estimated 80% of the cases, although even invasive examples often exhibit a protracted course. Invasive carcinomas arising from ITPN-Bs are overall similar to cholangiocarcinomas (including small duct and large duct patterns) but also often have peculiar characteristics such as more nodular-compact (blunt invasion) pattern. Like other IDNs, the ITPN-Bs have also been classified in the past as intraductal-spreading type of cholangiocarcinomas (and they are still regarded as such in some publications). In small biopsies, they are prone to be mistaken as ordinary adenocarcinomas because of their tubular pattern and pancreatobiliary cytology although their relatively monotonous cytology and zones of back-to-back tubule formation can help in their correct identification. Clinical presentation of ITPN-Bs is generally similar to other intraductal neoplasms; however, in the intrahepatic component, they tend to be more nodular than cystic, and their snake-like intraductal growth pattern is often more striking. In the management (diagnosis and treatment) of these tumors that are in essence adenoma-carcinoma sequence, the invasive and noninvasive components ought to be evaluated separately. Minimally invasive examples are commonly curable, and even those more extensively invasive may have a surprisingly good prognosis. In summary, biliary ITPNs form a distinct category not only clinicopathologically, immunophenotypically, and molecular-wise but regarding their biological behavior as well.
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Xue Y, Balci S, Pehlivanoglu B, Muraki T, Memis B, Saka B, Kim G, Bandyopadhyay S, Knight J, El-Rayes B, Kooby D, Maithel SK, Sarmiento J, Basturk O, Reid MD, Adsay V. Medullary carcinoma of the ampulla has distinct clinicopathologic characteristics including common association with microsatellite instability and PD-L1 expression. Hum Pathol 2023; 131:38-46. [PMID: 36502926 DOI: 10.1016/j.humpath.2022.12.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 11/13/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022]
Abstract
Medullary carcinomas have not yet been fully characterized in the ampulla. Here, 359 ampullary carcinomas (ACs) were reviewed and 11 medullary-type carcinomas (3%) were found and analyzed. In addition to the diagnostic medullary pattern, 6 showed focal mucinous and 8 had focal abortive gland-like formations. They occurred in younger patients (57 versus 65 y; P = .02), had larger invasion size (mean, 3.2 versus 1.9 cm; P = .01), formed nodular polypoid or plaque-like tumors, and often lacked preinvasive component. In addition to the lymphoplasmacytic infiltrates, they also had prominent eosinophils in 5 of 11 cases. Eight were papilla Vateri-NOS (not otherwise specified) tumors, 2 were ampullary-duodenal origin, 1 had a minor intra-ampullary papillary tubular neoplasm component, and none were ampullary-ductal. Although they had pushing-border infiltration, perineural and vascular invasion was common. They were strongly associated with DNA mismatch repair (MMR) protein deficient (7/11, 64%). The 5-yr survival rate (53%) appeared to be comparable with, and perhaps even better than that of nonmedullary ACs (47%), although this did not reach statistical significance (P = .47). Programmed cell death ligand-1 (PD-L1) expression levels were assessed in 8, and all 4 that were MMR deficient were positive both by combined positive score (CPS) ≥1 and tumor proportion score (TPS) ≥1, and of the 4 MMR proficient cases, 3 were positive by CPS; 2 by TPS. Overall, only 1 of the 8 available for analysis failed to show PD-L1 positivity by CPS. In contrast, nonmedullary MMR-deficient carcinomas expressed PD-L1 in only 33% of tumors by CPS, and none by TPS. One medullary carcinoma was also EBV associated. Unlike 'medullary carcinomas' of the kidney, INI1 was retained in all 8 cases tested. In conclusion, medullary carcinomas are 3% of ACs, have a strong association with MMR-D, and may be less aggressive despite their larger size. PD-L1 expression appears to be closely associated with medullary ACs regardless of MMR status, and thus targeted therapies can be considered for all medullary carcinomas of this site.
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Affiliation(s)
- Yue Xue
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Serdar Balci
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Burcin Pehlivanoglu
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Takashi Muraki
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Bahar Memis
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Burcu Saka
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Grace Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA
| | | | - Jessica Knight
- Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA, 30606, USA
| | - Bassel El-Rayes
- Department of Hematology and Medical Oncology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - David Kooby
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Shishir K Maithel
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Juan Sarmiento
- Department of Surgery, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, 10065, USA
| | - Michelle D Reid
- Department of Pathology, School of Medicine, Emory University, Atlanta, GA, 30322, USA
| | - Volkan Adsay
- Department of Pathology, Koc University Hospital, Davutpasa Caddesi No. 4, 34010 Topkapi, Istanbul, Turkey.
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10
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Slack JC, Bründler MA, Box A, Koro K. A Subset of Pancreatoblastomas May Arise From an Adenomatous Precursor: An Ampullary Pancreatoblastoma and Adjacent Adenoma With a Shared Molecular Phenotype in an Adult Patient. Pancreas 2022; 51:1455-1460. [PMID: 37099791 DOI: 10.1097/mpa.0000000000002189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
ABSTRACT Pancreatoblastomas are rare pediatric tumors. In adults, they are exceedingly rare and seem to have a worse prognosis. Most are sporadic, though rare, cases occur in patients with familial adenomatous polyposis. Unlike pancreatic ductal adenocarcinomas, pancreatoblastomas are not believed to arise from dysplastic precursor lesions. Clinical history, along with endoscopic, pathological, and molecular findings, was reviewed for a 57-year-old male patient with an ampullary mass who presented with obstructive jaundice. Microscopic examination showed a pancreatoblastoma subjacent to an adenomatous polyp with intestinal differentiation and low-grade dysplasia. Both tumors had abnormal p53 (complete loss) and nuclear β-catenin immunostaining. Mutational panel analysis showed an identical CTNNB1 (p.S45P) mutation in both. This case adds to our understanding of the pathogenesis of these rare tumors and suggests that a subset may arise from an adenomatous precursor. In addition, this case is just the second pancreatoblastoma to originate in the duodenal ampulla, and the preceding case suggests that an ampullary location leads to earlier diagnosis. Moreover, this case highlights the difficulty in diagnosing pancreatoblastoma on limited tissue specimens and illustrates the need to include pancreatoblastoma in the differential diagnosis in all tumors in and around the pancreas, including those in adult patients.
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Affiliation(s)
| | | | - Adrian Box
- From the Departments of Pathology and Laboratory Medicine
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11
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Zulfiqar M, Chatterjee D, Yoneda N, Hoegger MJ, Ronot M, Hecht EM, Bastati N, Ba-Ssalamah A, Bashir MR, Fowler K. Imaging Features of Premalignant Biliary Lesions and Predisposing Conditions with Pathologic Correlation. Radiographics 2022; 42:1320-1337. [PMID: 35930475 DOI: 10.1148/rg.210194] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Biliary malignancies include those arising from the intrahepatic and extrahepatic bile ducts as well as the gallbladder and hepatopancreatic ampulla of Vater. The majority of intrahepatic and extrahepatic malignancies are cholangiocarcinomas (CCAs). They arise owing to a complex interplay between the patient-specific genetic background and multiple risk factors and may occur in the liver (intrahepatic CCA), hilum (perihilar CCA), or extrahepatic bile ducts (distal CCA). Biliary-type adenocarcinoma constitutes the most common histologic type of ampullary and gallbladder malignancies. Its prognosis is poor and surgical resection is considered curative, so early detection is key, with multimodality imaging playing a central role in making the diagnosis. There are several risk factors for biliary malignancy as well as predisposing conditions that increase the risk; this review highlights the pertinent imaging features of these entities with histopathologic correlation. The predisposing factors are broken down into three major categories: (a) congenital malformations such as choledochal cyst and pancreaticobiliary maljunction; (b) infectious or inflammatory conditions such as parasitic infections, hepatolithiasis, primary sclerosing cholangitis, and porcelain gallbladder; and (c) preinvasive epithelial neoplasms such as biliary intraepithelial neoplasm, intraductal papillary neoplasm of the bile duct, intra-ampullary papillary tubular neoplasm, and intracholecystic papillary neoplasm of the gallbladder. Recognizing the baseline features of these premalignant biliary entities and changes in their appearance over time that indicate the advent of malignancy in high-risk patients can lead to early diagnosis and potentially curative management. An invited commentary by Volpacchio is available online. Online supplemental material is available for this article. ©RSNA, 2022.
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Affiliation(s)
- Maria Zulfiqar
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Deyali Chatterjee
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Norihide Yoneda
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Mark J Hoegger
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Maxime Ronot
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Elizabeth M Hecht
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Nina Bastati
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Ahmed Ba-Ssalamah
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Mustafa R Bashir
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
| | - Kathryn Fowler
- From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, St Louis, MO 63110 (M.Z., M.J.H.); Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Tex (D.C.); Department of Radiology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan (N.Y.); Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy & Université de Paris, Paris, France (M.R.); Department of Radiology, Weill Cornell Medicine, New York, NY (E.M.H.); Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Vienna, Austria (N.B., A.B.S.); Departments of Radiology and Medicine, Duke University Medical Center, Durham, NC (M.R.B.); and Department of Radiology, UC San Diego School of Medicine, San Diego, Calif (K.F.)
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12
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Zavrtanik H, Luzar B, Tomažič A. Intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma: A case report. World J Clin Cases 2022; 10:8045-8053. [PMID: 36158500 PMCID: PMC9372858 DOI: 10.12998/wjcc.v10.i22.8045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/03/2022] [Accepted: 06/26/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The ampulla of Vater is an anatomically and histologically complex region giving rise to a heterogenous group of tumors. This is, to the best of our knowledge, the first case of intra-ampullary papillary-tubular neoplasm combined with ampullary neuroendocrine carcinoma reported in the literature.
CASE SUMMARY A 61-year-old woman presented to the emergency department for evaluation of painless jaundice. Contrast-enhanced computed tomography (CT) of the abdomen and chest showed a periampullary tumor mass measuring 15 mm × 12 mm × 14 mm, with no evidence of locoregional and distant metastases, for which she underwent pancreatoduodenectomy. Histopathologic examination of a resected specimen revealed an intra-ampullary papillary tubular neoplasm with high-grade dysplasia in combination with poorly differentiated grade 3 neuroendocrine carcinoma with a mitotic count of more than 20 mitoses per 10 high power fields and Ki-67 index of 100%. No positive lymph nodes were identified. Her postoperative course was uneventful. Postoperatively, she remained under close surveillance. Multiple liver metastases were observed on follow-up CT 8 mo after the surgery, so systemic therapy with cisplatin and etoposide was initiated.
CONCLUSION The simultaneous occurrence of neuroendocrine and non-neuroendocrine tumors in the ampulla of Vater is rare and the pathogenesis of such tumors is largely unknown. Due to unpredictable clinical behavior and lack of solid evidence on optimal treatment strategy, close patient surveillance is advised after radical resection of the primary tumor.
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Affiliation(s)
- Hana Zavrtanik
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
| | - Boštjan Luzar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
| | - Aleš Tomažič
- Department of Abdominal Surgery, University Medical Centre Ljubljana, Ljubljana 1000, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia
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13
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Lv Y, Wang P, Chen J, Zhao L, Chen L, Zhuang Y, Wang L, Zou X. Indicative value of pathological classification of duodenal papillary adenomas in clinical diagnosis and treatment. Surg Endosc 2022; 36:5183-5197. [PMID: 35286472 DOI: 10.1007/s00464-021-08894-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 11/16/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVES The relationship between the pathological classification and recurrence of duodenal papillary adenomas (DPAs) has not been elucidated. We studied the clinicopathological characteristics of DPAs with different pathological types and conducted long-term follow-up to explore its prognosis and identify methods for appropriate clinical management of DPAs. METHODS In total, 95 DPA cases confirmed by postoperative pathology were enrolled, of which 58 underwent endoscopic papillectomy (EP) and 37 underwent pancreatoduodenectomy (PD). The cases were classified into three anatomical and two histomorphological types according to the histopathology and location of endoscopic features. We analyzed the clinicopathological characteristics of DPAs with different pathological types and investigated the factors associated with recurrence in the EP subgroup. RESULTS Although EP was associated with fewer adverse events, the complete resection rate was significantly lower (72.4% vs. 100.0%, p < 0.001) and the recurrence rate significantly higher than with PD (16.3% vs. 0.0%, p < 0.001). Among eight EP cases with recurrence, six had intra-DPA (75%). A positive resection margin (HR 23.67, 95% CI 6.42-87.27; p < 0.001) and MUC2-negative status (HR 3.47, 95% CI 1.16-10.40; p = 0.026) were independent risk factors for recurrence after EP. CONCLUSION We identified different pathological types within DPAs, which presented varying clinicopathological features. The majority of peri-DPAs and mixed-DPAs were of the intestinal type histologically and EP is the primary recommendation. However, intra-DPA was mainly of the pancreaticobiliary type, which tends to get positive resection margins; thus, surgical resection is more suitable.
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Affiliation(s)
- Ying Lv
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Pin Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Jun Chen
- Department of Pathology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Li Zhao
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Lingyan Chen
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Yingjia Zhuang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lei Wang
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
| | - Xiaoping Zou
- Department of Gastroenterology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
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14
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Pradhan S, Adhikari KM, Dahal R, Pradhan S, Bhandari RS. Transduodenal surgical ampullectomy for intra-ampullary papillary tubular neoplasm (IAPN): A case report. Int J Surg Case Rep 2021; 86:106253. [PMID: 34388591 PMCID: PMC8363816 DOI: 10.1016/j.ijscr.2021.106253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/16/2021] [Accepted: 07/27/2021] [Indexed: 11/26/2022] Open
Abstract
Introduction and importance Intra-ampullary papillary tubular neoplasms (IAPNs) are relatively rare kind of neoplasms occurring in the region of the papilla which exhibit significant malignant transformation. The patient was concerned about his pain and the possibility of malignancy. Case presentation We report a case of a 47-year-old male who presented with persistent upper abdomen pain. Following detail investigations, he was diagnosed as IAPN and managed by transduonal ampullectomy (TDA). Clinical discussion The insidious onset of IAPN along with its high risk of malignancy makes it mandatory for its proper treatment. Although, endoscopic approach is advantageous for initial therapy, it has some technical difficulties. Hence TDA forms the cornerstone in the management of IAPN with good prognosis. Conclusion Transduodenal ampullectomy is a safe and feasible option for IAPN. It can be the first choice of treatment in selected cases where endoscopic papillectomy is not available.
Intra-ampullary papillary tubular neoplasms (IAPNs) are unusual neoplasms capable of potential malignant progression. We report a rare case of IAPN which was treated through transduonal ampullectomy (TDA). TDA can be adopted as an alternative treatment approach to manage IAPNs with great efficacy and fair long-term results.
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Affiliation(s)
- Susan Pradhan
- Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Kathmandu, Nepal.
| | - Krishna Mohan Adhikari
- Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Kathmandu, Nepal
| | - Romi Dahal
- Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Kathmandu, Nepal
| | - Sumita Pradhan
- Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Kathmandu, Nepal
| | - Ramesh Singh Bhandari
- Department of GI and General Surgery, Tribhuvan University Teaching Hospital, Institute of Kathmandu, Nepal
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15
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Gonzalez RS, Raza A, Propst R, Adeyi O, Bateman J, Sopha SC, Shaw J, Auerbach A. Recent Advances in Digestive Tract Tumors: Updates From the 5th Edition of the World Health Organization "Blue Book". Arch Pathol Lab Med 2021; 145:607-626. [PMID: 32886739 DOI: 10.5858/arpa.2020-0047-ra] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/12/2020] [Indexed: 11/06/2022]
Abstract
CONTEXT.— The World Health Organization Classification of Tumours: Digestive System Tumors, 5th edition, was published in 2019 and shows several impactful changes as compared with the 4th edition published in 2010. Changes include a revised nomenclature of serrated lesions and revamping the classification of neuroendocrine neoplasms. Appendiceal goblet cell adenocarcinoma is heavily revised, and intrahepatic cholangiocarcinoma is split into 2 subtypes. New subtypes of colorectal carcinoma and hepatocellular carcinoma are described. Precursor lesions are emphasized with their own entries, and both dysplastic and invasive lesions are generally recommended to be graded using a 2-tier system. Hematolymphoid tumors, mesenchymal tumors, and genetic tumor syndromes each have their own sections in the 5th edition. New hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma; duodenal-type follicular lymphoma; intestinal T-cell lymphoma, not otherwise specified; and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. This paper will provide an in-depth look at the changes in the 5th edition as compared with the 4th edition. OBJECTIVE.— To provide a comprehensive, in-depth update on the World Health Organization classification of digestive tumors, including changes to nomenclature, updated diagnostic criteria, and newly described entities. DATA SOURCES.— The 5th edition of the World Health Organization Classification of Tumours: Digestive System Tumours, as well as the 4th edition. CONCLUSIONS.— The World Health Organization has made many key changes in its newest update on tumors of the digestive system. Pathologists should be aware of these changes and incorporate them into their practice as able or necessary.
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Affiliation(s)
- Raul S Gonzalez
- The Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (Gonzalez)
| | - Anwar Raza
- The Department of Pathology and Human Anatomy, Loma Linda University, Loma Linda, California (Raza, Propst)
| | - Robert Propst
- The Department of Pathology and Human Anatomy, Loma Linda University, Loma Linda, California (Raza, Propst)
| | - Oyedele Adeyi
- The Department of Pathology, University of Minnesota, Minneapolis (Adeyi, Bateman)
| | - Justin Bateman
- The Department of Pathology, University of Minnesota, Minneapolis (Adeyi, Bateman)
| | - Sabrina C Sopha
- The Department of Pathology, University of Maryland Baltimore Washington Medical Center, Glen Burnie (Sopha)
| | - Janet Shaw
- The Joint Pathology Center, Silver Spring, Maryland (Shaw, Auerbach)
| | - Aaron Auerbach
- The Joint Pathology Center, Silver Spring, Maryland (Shaw, Auerbach)
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16
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Roa JC, Basturk O, Adsay V. Dysplasia and carcinoma of the gallbladder: pathological evaluation, sampling, differential diagnosis and clinical implications. Histopathology 2021; 79:2-19. [PMID: 33629395 DOI: 10.1111/his.14360] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 02/09/2021] [Accepted: 02/23/2021] [Indexed: 12/22/2022]
Abstract
Pathological evaluation of gallbladder neoplasia remains a challenge. A significant proportion of cases presents as clinically and grossly inapparent lesions, and grossing protocols are not well established. Among epithelial alterations, pseudo-pyloric gland metaplasia is ubiquitous and of no apparent consequence, whereas goblet cell metaplasia and a foveolar change in surface cells require closer attention. Low-grade dysplasia is difficult to objectively define and appears to be clinically inconsequential by itself; however, extra sampling is required to exclude the possibility of accompanying more significant lesions. For high-grade dysplasia ('high-grade BilIN', also known as 'carcinoma in situ'), a complete sampling is necessary to rule out invasion. Designating in-situ or minimally invasive carcinomas limited to muscularis or above as early gallbladder carcinoma (EGBC) helps to alleviate the major geographical differences (West/East) in the criteria for 'invasiveness' to assign a case to pTis or pT1. Total sampling is crucial in proper diagnosis of such cases. A subset of invasive GBCs (5-10%) arise from the intracholecystic neoplasm (ICN, 'adenoma-carcinoma sequence') category. Approximately two-thirds of ICNs have invasive carcinoma. However, this propensity differs by subtype. True 'pyloric gland adenomas' (> 1 cm) are uncommon and scarcely associated with invasive carcinoma. A distinct subtype of ICN composed of tubular, non-mucinous MUC6+ glands [intracholecystic tubular non-mucinous neoplasm (ICTN)] forms a localised pedunculated polyp. Although it is morphologically complex and high-grade, it appears to be invasion-resistant. Some of the invasive carcinoma types in the gallbladder have been better characterised recently with adenosquamous, neuroendocrine, poorly cohesive and mucinous carcinomas often being more advanced and aggressive.
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Affiliation(s)
- Juan C Roa
- Department of Pathology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.,European-Latin American ESCALON Consortium, EU Horizon 2020, Rotterdam, the Netherlands
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
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17
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Kang JS, Lee KB, Choi YJ, Byun Y, Han Y, Kim H, Kwon W, Jang JY. A comparison of outcomes in patients with intracholecystic papillary neoplasms or conventional adenocarcinomas of the gallbladder. HPB (Oxford) 2021; 23:746-752. [PMID: 33092965 DOI: 10.1016/j.hpb.2020.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 09/14/2020] [Accepted: 09/16/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intracholecystic papillary neoplasm (ICPN) of the gallbladder (GB) is an exophytic intraepithelial neoplasm. This study aimed to investigate clinicopathologic findings, prognosis and recurrence patterns of patients with ICPN as compared to those patients with conventional adenocarcinoma of the gallbladder (GBC). METHODS Patients who underwent surgical resection for suspected GB cancer between 2000 and 2018 were included. ICPN was defined as an exophytic papillary mass within the GB lumen with a size ≥1.0 cm. RESULTS Of 607 patients, 241 patients (40%) were pathologically diagnosed with ICPN. Of the 241 patients with ICPNs, 110 (46%) were T1 or less. Following T stage-matched analysis, the rate of lymph node metastases were comparable (50 [52%] vs. 37 [49%], P = 0.581). The five-year survival rate was higher in ICPN, but after T stage-matching, they were comparable (69.1 vs. 63.2%, P = 0.171). Overall recurrence rates were also comparable, with the exception of lower peritoneal seeding in patients with ICPN. CONCLUSION Patients with ICPN who underwent resection were more likely to have an earlier T stage. There was no significant difference in prognosis and recurrence between ICPN and conventional GBC after stage matching. Therefore, the treatment strategy for ICPN should follow the same protocols used for conventional GBC.
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Affiliation(s)
- Jae Seung Kang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoo Jin Choi
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yoonhyeong Byun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Youngmin Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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18
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Vanoli A, Grillo F, Furlan D, Arpa G, Grami O, Guerini C, Riboni R, Mastracci L, Di Sabatino A. Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations. Int J Mol Sci 2021; 22:ijms22094388. [PMID: 33922305 PMCID: PMC8122855 DOI: 10.3390/ijms22094388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/18/2021] [Accepted: 04/20/2021] [Indexed: 12/15/2022] Open
Abstract
The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.
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Affiliation(s)
- Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
- Correspondence: ; Tel.: +39-0382503612
| | - Federica Grillo
- Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, 16132 Genoa, Liguria, Italy; (F.G.); (L.M.)
| | - Daniela Furlan
- Pathology Unit, Department of Medicine and Surgery, University of Insubria, 21100 Varese, Lombardy, Italy;
| | - Giovanni Arpa
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Oneda Grami
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Camilla Guerini
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Roberta Riboni
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy; (G.A.); (O.G.); (C.G.); (R.R.)
| | - Luca Mastracci
- Pathology Unit, Department of Surgical and Diagnostic Sciences, University of Genoa and Ospedale Policlinico San Martino University Hospital, 16132 Genoa, Liguria, Italy; (F.G.); (L.M.)
| | - Antonio Di Sabatino
- Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, 27100 Pavia, Lombardy, Italy;
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19
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Noguchi H, Higashi M, Idichi T, Kurahara H, Mataki Y, Tasaki T, Kitazono I, Ohtsuka T, Tanimoto A. Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report. World J Clin Cases 2021; 9:2671-2678. [PMID: 33889635 PMCID: PMC8040169 DOI: 10.12998/wjcc.v9.i11.2671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/18/2021] [Accepted: 02/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm, and the most common histological type is adenocarcinoma with a tubular growth pattern. Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis. IMPC was first described as a histological subtype of breast cancer; however, IMPC of the ampulla of Vater is extremely rare, with only three articles reported in the English literature.
CASE SUMMARY We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man. Microscopically, the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm, and the deep invasive front area exhibited a pattern of IMPC. The carcinoma showed lymphatic invasion and extensive lymph node metastasis. The immunohistochemical study revealed mixed intestinal and gastric/pan-creatobiliary phenotypes.
CONCLUSION This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.
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Affiliation(s)
- Hirotsugu Noguchi
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Michiyo Higashi
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Tetsuya Idichi
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Hiroshi Kurahara
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Yuko Mataki
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Takashi Tasaki
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Ikumi Kitazono
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
| | - Akihide Tanimoto
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan
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20
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Fujita H, Ishido K, Kimura N, Wakiya T, Nagase H, Yoshizawa T, Haga T, Goto S, Kijima H, Hakamada K. A case report of mucinous adenocarcinoma derived from intra-ampullary papillary-tubular neoplasm with a malignant course. Surg Case Rep 2021; 7:25. [PMID: 33452648 PMCID: PMC7810803 DOI: 10.1186/s40792-020-01045-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 10/09/2020] [Indexed: 11/30/2022] Open
Abstract
Background Intra-ampullary papillary-tubular neoplasm (IAPN) has been classified as a Vater papillary tumor. The prognosis of IAPN is generally relatively good. Here, we describe a patient with a mucinous adenocarcinoma cluster in the Vater papilla of IAPN origin. Clinical presentation The patient was a 66-year-old man who was admitted to our hospital after a diagnosis of pancreatic head carcinoma based on a pancreatic duct dilatation found on abdominal ultrasound. CT showed a 40 mm lesion in the pancreatic head and expansion of the main pancreatic duct to a maximum diameter of 9 mm on the caudal side of the lesion. The extrahepatic bile duct had also expanded to a maximum diameter of 8 mm. PET/CT showed fluorodeoxyglucose (FDG) accumulation of SUVmax 6.02 that corresponded to the tumor in the pancreatic head, though it did not suggest distant metastasis. The patient was diagnosed with pancreatic head carcinoma T3 N0 M0 Stage IIA and underwent a pancreaticoduodenectomy. Pathology indicated that the tumor in the pancreatic head was a benign inflammatory lesion. On the other hand, the papillotubular tumor pervading the lumen in the duodenal papillary common channel met the criteria for IAPN, and a mucinous adenocarcinoma cluster found in the surrounding stroma suggested malignant transformation of IAPN. No metastasis to lymph nodes was demonstrated. With regard to the mucus phenotype of each lesion, the IAPN was MUC2 and MUC5AC positive, while the mucinous adenocarcinoma was MUC2-positive and MUC5AC-negative. In addition, CD10 was negative in both lesions, suggesting that mucus transformation from the gastric type to the intestinal type was a key element. A blood test 10 months after surgery showed increased CA19-9 (105 U/mL) and CEA (7.1 ng/mL). Abdominal CT showed multiple cystoid nodes in the liver, which were diagnosed as multiple liver metastases of mucinous adenocarcinoma transformed from the IAPN. Conclusions We reported a case with IAPN that developed in the Vater papilla, which took an extremely malignant course. IAPN generally has a good prognosis, but it is important to understand that a malignant course may occur.
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Affiliation(s)
- Hiroaki Fujita
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Keinosuke Ishido
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Norihisa Kimura
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Taiichi Wakiya
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hayato Nagase
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tadashi Yoshizawa
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Toshihiro Haga
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shintaro Goto
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hiroshi Kijima
- Department of Pathology and Bioscience, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
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21
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Rowan DJ, Pehlivanoglu B, Memis B, Bagci P, Erbarut I, Dursun N, Jang KT, Sarmiento J, Mucientes F, Cheng JD, Roa JC, Araya JC, Bellolio E, Losada H, Jang JY, Koshiol J, Reid MD, Basturk O, Adsay V. Mural Intracholecystic Neoplasms Arising in Adenomyomatous Nodules of the Gallbladder: An Analysis of 19 Examples of a Clinicopathologically Distinct Entity. Am J Surg Pathol 2020; 44:1649-1657. [PMID: 33060404 PMCID: PMC7658044 DOI: 10.1097/pas.0000000000001603] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Intracholecystic neoplasms (ICNs) (pyloric gland adenomas and intracholecystic papillary neoplasms, collectively also called intracholecystic papillary/tubular neoplasms) form multifocal, extensive proliferations on the gallbladder mucosa and have a high propensity for invasion (>50%). In this study, 19 examples of a poorly characterized phenomenon, mural papillary mucinous lesions that arise in adenomyomatous nodules and form localized ICNs, were analyzed. Two of these were identified in 1750 consecutive cholecystectomies reviewed specifically for this purpose, placing its incidence at 0.1%. Median age was 68 years. Unlike other gallbladder lesions, these were slightly more common in men (female/male=0.8), and 55% had documented cholelithiasis. All were characterized by a compact multilocular, demarcated, cystic lesion with papillary proliferations and mucinous epithelial lining. The lesions' architecture, distribution, location, and typical size were suggestive of evolution from an underlying adenomyomatous nodule. All had gastric/endocervical-like mucinous epithelium, but 5 also had a focal intestinal-like epithelium. Cytologic atypia was graded as 1 to 3 and defined as 1A: mucinous, without cytoarchitectural atypia (n=3), 1B: mild (n=7), 2: moderate (n=2), and 3: severe atypia (n=7, 3 of which also had invasive carcinoma, 16%). Background gallbladder mucosal involvement was absent in all but 2 cases, both of which had multifocal papillary mucosal nodules. In conclusion, these cases highlight a distinct clinicopathologic entity, that is, mural ICNs arising in adenomyomatous nodules, which, by essentially sparing the "main" mucosa, not displaying "field-effect/defect" phenomenon, and only rarely (16%) showing carcinomatous transformation, are analogous to pancreatic branch duct intraductal papillary mucinous neoplasms.
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Affiliation(s)
- Daniel J. Rowan
- Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Burcin Pehlivanoglu
- Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Bahar Memis
- Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Pelin Bagci
- Department of Pathology, Marmara University School of Medicine, İstanbul, Turkey
| | - Ipek Erbarut
- Department of Pathology, Marmara University School of Medicine, İstanbul, Turkey
| | - Nevra Dursun
- Department of Pathology, University of Health Sciences, Istanbul Education and Research Hospital, Istanbul, Turkey
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Juan Sarmiento
- Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
| | | | | | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Catolica de Chile, Chile
| | - Juan Carlos Araya
- Hospital Dr. Hernan Henriquez Aravena, Department of Pathology, Temuco, Chile
| | | | - Hector Losada
- Department of Surgery and Traumatology, Universidad de La Frontera, Chile
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jill Koshiol
- National Cancer Institute, Division of Cancer Epidemiology & Genetics, Infections and Immunoepidemiology Branch, NCI, NIH, Rockville, MD, USA
| | - Michelle D. Reid
- Department of Pathology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY USA
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
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22
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Palmeri M, Funel N, Franco GD, Furbetta N, Gianardi D, Guadagni S, Bianchini M, Pollina LE, Ricci C, Chiaro MD, Candio GD, Morelli L. Tissue microarray-chip featuring computerized immunophenotypical characterization more accurately subtypes ampullary adenocarcinoma than routine histology. World J Gastroenterol 2020; 26:6822-6836. [PMID: 33268964 PMCID: PMC7684454 DOI: 10.3748/wjg.v26.i43.6822] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/24/2020] [Accepted: 08/27/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Ampullary adenocarcinomas (AACs) are heterogeneous tumors currently classified into three important sub-classes (SC): Intestinal (INT), Pancreato-Biliary (PB) and Mixed-Type (MT). The different subgroups have similar clinical presentation and are treated by pancreatoduodenectomy with curative intent. However, they respond differently to chemotherapy and have different prognostic outcomes. The SC are often difficult to identify with conventional histology alone. The clinical outcome of all three remains unclear, particularly for MT.
AIM To identify two main subtypes of AACs, using an immunohistochemical (IHC) score based on CDX2, CK7 and CK20.
METHODS Tissue samples from 21 patients who had undergone resection of AAC were classified by HE histology and IHC expression of CDX2, CK7 and CK 20. An IHC score was obtained for each marker by counting the number of positive cells (0 = no stained cells; 1 < 25%; 2 < 50% and 3 > 50%) and their intensity (1 = weak; 2 = moderate and 3 = strong). A global score (GS) was then obtained by summation of the IHC scores of each marker. The MT tumors were grouped either with the INT or PB group based on the predominant immuno-molecular phenotype, obtaining only two AACs subtypes. The overall survival in INT and PB patients was obtained by Kaplan-Meier methods.
RESULTS Histological parameters defined the AACs subtypes as follows: 15% INT, 45% PB and 40% MT. Using IHC expression and the GS, 75% and 25% of MT samples were assigned to either the INT or the PB group. The mean value of the GS was 9.5 (range 4-16). All INT samples had a GS above the average, distinct from the PB samples which had a GS score significantly below the average (P = 0.0011). The INT samples were identified by high expression of CDX2 and CK20, whereas PB samples exhibited high expression of CK7 and no expression of CK20 (P = 0.0008). The INT group had a statistically significant higher overall survival than in the PB group (85.7 mo vs 20.3 mo, HR: 8.39; 95%CI: 1.38 to 18.90; P = 0.0152).
CONCLUSION The combination of histopathological and molecular criteria enables the classification of AACs into two clinically relevant histo-molecular phenotypes, which appear to represent distinct disorders with potentially significant changes to the current therapeutic strategies.
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Affiliation(s)
- Matteo Palmeri
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Niccola Funel
- Division of Surgical Pathology, University-Hospital of Pisa, Pisa 56124, Italy
| | - Gregorio Di Franco
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Niccolò Furbetta
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Desirée Gianardi
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Simone Guadagni
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Matteo Bianchini
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Luca E Pollina
- Division of Surgical Pathology, University-Hospital of Pisa, Pisa 56124, Italy
| | - Claudio Ricci
- Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa 56124, Italy
| | - Marco Del Chiaro
- Department of Surgery, University of Colorado, Denver, CO 80045, United States
| | - Giulio Di Candio
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
| | - Luca Morelli
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56124, Italy
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23
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Kim H, Jang JY, Chang J, Kim H, Byun Y, Kim JR, Kwon W, Kim SW, Lee KB. Clinical meaning of the World Health Organization morphologic classification (flat vs. tumoral) of gallbladder intraepithelial neoplasm as a prognostic factor in gallbladder cancer. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1413. [PMID: 33313158 PMCID: PMC7723553 DOI: 10.21037/atm-20-432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background In the World Health Organization (WHO) classification, gallbladder (GB) intraepithelial lesions are grouped as flat or tumoral, according to their morphological features. The purpose of this study was to investigate the relationship between the morphologies and clinical features of GB cancer (GBC) and to examine the feasibility of using morphologic classification as a prognostic factor. Methods From January 2000 to December 2012, the available pathologic slide reviews of 381 patients were analyzed at the Seoul National University Hospital. All pathologic slides were evaluated by two pancreato-biliary tract pathology experts. GBCs were categorized into eight groups (Flat: F1-2, Borderline, Tumoral: Tu1-5), according to the thickness of the mucosal lesion, histologic patterns of the mucosa under microscopy, invasion extent, and patient history of premalignant lesions. According to the morphologic classification, clinical features were compared and survival analysis was performed. Results In three groups, flat lesions comprised 179 (46.9%) cases and borderline and tumoral comprised 97 (25.4%) and 105 (27.5%) cases, respectively. More favorable pathologic and clinical results were found within the tumoral group. The borderline group had an intermediate tendency between flat and intraluminal in clinicopathologic parameters. In the curative resected T2 stage group, the borderline group demonstrated an intermediate trend compared to that of the flat and tumoral groups, but this was statistically insignificant (P=0.08). Conclusions Flat type GBCs show worse prognosis than tumoral GBCs. The morphological classifications between flat and tumoral on the basis of 1 cm and by papillary feature is feasible. Tumor morphology can be used as a reference while deciding the treatment plan, especially in T2 GBC.
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Affiliation(s)
- Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jihoon Chang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoonhyeong Byun
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Ri Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sun-Whe Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Kyoung-Bun Lee
- Department of Pathology, Seoul National University College of Medicine, Seoul, Korea
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24
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Han S, Jang KT, Choi DW, Choi SH, Heo JS, Han IW, Park D, Ryu Y. Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma. Dig Surg 2020; 37:505-514. [PMID: 33080609 DOI: 10.1159/000510961] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 08/17/2020] [Indexed: 12/10/2022]
Abstract
BACKGROUND The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). METHODS From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. RESULTS The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (p = 0.002), nodal involvement (p < 0.001), poor differentiation (p < 0.001), perineural and lymphovascular invasion (p < 0.001), and pancreatobiliary or mixed subtype (p < 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (p = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (p < 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; p < 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. CONCLUSION FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.
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Affiliation(s)
- Sunjong Han
- Department of Surgery, Chungnam National University Sejong Hospital, Sejong, Republic of Korea
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea,
| | - Seong Ho Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jin Seok Heo
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - In Woong Han
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - DaeJoon Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Youngju Ryu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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25
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Taskin OC, Basturk O, Reid MD, Dursun N, Bagci P, Saka B, Balci S, Memis B, Bellolio E, Araya JC, Roa JC, Tapia O, Losada H, Sarmiento J, Jang KT, Jang JY, Pehlivanoglu B, Erkan M, Adsay V. Gallbladder polyps: Correlation of size and clinicopathologic characteristics based on updated definitions. PLoS One 2020; 15:e0237979. [PMID: 32915805 PMCID: PMC7485812 DOI: 10.1371/journal.pone.0237979] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 08/06/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Different perspectives exist regarding the clinicopathologic characteristics, biology and management of gallbladder polyps. Size is often used as the surrogate evidence of polyp behavior and size of ≥1cm is widely used as cholecystectomy indication. Most studies on this issue are based on the pathologic correlation of polyps clinically selected for resection, whereas, the data regarding the nature of polypoid lesions from pathology perspective -regardless of the cholecystectomy indication- is highly limited. METHODS In this study, 4231 gallbladders -606 of which had gallbladder carcinoma- were reviewed carefully pathologically by the authors for polyps (defined as ≥2 mm). Separately, the cases that were diagnosed as "gallbladder polyps" in the surgical pathology databases were retrieved. RESULTS 643 polyps identified accordingly were re-evaluated histopathologically. Mean age of all patients was 55 years (range: 20-94); mean polyp size was 9 mm. Among these 643 polyps, 223 (34.6%) were neoplastic: I. Non-neoplastic polyps (n = 420; 65.4%) were smaller (mean: 4.1 mm), occurred in younger patients (mean: 52 years). This group consisted of fibromyoglandular polyps (n = 196) per the updated classification, cholesterol polyps (n = 166), polypoid pyloric gland metaplasia (n = 41) and inflammatory polyps (n = 17). II. Neoplastic polyps were larger (mean: 21 mm), detected in older patients (mean: 61 years) and consisted of intra-cholecystic neoplasms (WHO's "adenomas" and "intracholecystic papillary neoplasms", ≥1 cm; n = 120), their "incipient" version (<1 cm) (n = 44), polypoid invasive carcinomas (n = 26) and non-neoplastic polyps with incidental dysplastic changes (n = 33). In terms of size cut-off correlations, overall, only 27% of polyps were ≥1 cm, 90% of which were neoplastic. All (except for one) ≥2 cm were neoplastic. However, 14% of polyps <1 cm were also neoplastic. Positive predictive value of ≥1 cm cut-off -which is widely used for cholecystectomy indication-, was 94.3% and negative predictive value was 85%. CONCLUSIONS Approximately a third of polypoid lesions in the cholecystectomies (regardless of the indication) prove to be neoplastic. The vast majority of (90%) of polyps ≥1 cm and virtually all of those ≥2 cm are neoplastic confirming the current impression that polyps ≥1 cm ought to be removed. However, this study also illustrates that 30% of the neoplastic polyps are <1 cm and therefore small polyps should also be closely watched, especially in older patients.
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Affiliation(s)
- Orhun C. Taskin
- Department of Pathology and Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey
| | - Olca Basturk
- Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY, United States of America
| | - Michelle D. Reid
- Department of Pathology, Emory University, Atlanta, GA, United States of America
| | - Nevra Dursun
- Department of Pathology, Istanbul Research and Training Hospital, Istanbul, Turkey
| | - Pelin Bagci
- Department of Pathology, Marmara University Pendik Research and Training Hospital, Istanbul, Turkey
| | - Burcu Saka
- Department of Pathology, Medipol University, Istanbul, Turkey
| | - Serdar Balci
- Department of Pathology, Emory University, Atlanta, GA, United States of America
| | - Bahar Memis
- Department of Pathology, Şişli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
| | - Enrique Bellolio
- Anatomic Pathology Department, Universidad de La Frontera, Temuco, Chile
| | - Juan Carlos Araya
- Department of Pathology, Hospital Dr. Hernan Henriquez Aravena, Temuco, Chile
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Oscar Tapia
- Department of Pathology, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Hector Losada
- Department of Surgery and Traumatology, Universidad de La Frontera, Temuco, Chile
| | - Juan Sarmiento
- Department of Surgery, Emory University, Atlanta, GA, United States of America
| | - Kee-Taek Jang
- Department of Pathology, Emory University, Atlanta, GA, United States of America
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Burcin Pehlivanoglu
- Department of Pathology, Adiyaman Training and Research Hospital, Adiyaman, Turkey
| | - Mert Erkan
- Department of Surgery and Research Center for Translational Medicine (KUTTAM), Koç University Hospital, Istanbul, Turkey
| | - Volkan Adsay
- Department of Pathology and Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey
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Xue Y, Balci S, Aydin Mericoz C, Taskin OC, Jiang H, Pehlivanoglu B, Muraki T, Memis B, Saka B, Kim GE, Bandopadhyay S, Knight J, El-Rayes BF, Sarmiento J, Reid MD, Erkan M, Basturk O, Adsay V. Frequency and clinicopathologic associations of DNA mismatch repair protein deficiency in ampullary carcinoma: Routine testing is indicated. Cancer 2020; 126:4788-4799. [PMID: 32857459 DOI: 10.1002/cncr.33135] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 06/09/2020] [Accepted: 07/06/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established. METHODS In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically. RESULTS MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method. CONCLUSIONS In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.
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Affiliation(s)
- Yue Xue
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Serdar Balci
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Cisel Aydin Mericoz
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Orhun C Taskin
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey
| | - Hongmei Jiang
- Department of Statistics, Northwestern University, Evanston, Illinois
| | | | - Takashi Muraki
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Bahar Memis
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Burcu Saka
- Department of Pathology, Emory University, Atlanta, Georgia
| | - Grace E Kim
- Department of Pathology, University of California San Francisco, San Francisco, California
| | | | - Jessica Knight
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia
| | - Juan Sarmiento
- Department of Surgery, School of Medicine, Emory University, Atlanta, Georgia
| | | | - Mert Erkan
- Department of Surgery, Koç University School of Medicine, Istanbul, Turkey
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Volkan Adsay
- Department of Pathology, Koç University School of Medicine, Istanbul, Turkey.,Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
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Abstract
The ampulla of Vater gives rise to a versatile group of cancers of mixed/hybrid histologic phenotype. Ampullary carcinomas (ACs) are most frequently intestinal or pancreatobiliary adenocarcinomas but other subtypes, such as medullary, mucinous, or signet ring/poorly cohesive cell carcinoma, may be encountered. Ampullary cancer can also be subclassified based on immunohistochemical features, however these classification systems fail to show robust prognostic reliability. More recently, the molecular landscape of AC has been uncovered, and has been shown to have prognostic and predictive significance. In this article, the site-specific, histologic, and genetic characteristics of ampullary carcinoma and its precursor lesions are discussed.
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Affiliation(s)
- Yue Xue
- Department of Pathology and Laboratory Medicine, Northwestern University, 251 East Huron Street, Room 7332, Chicago, IL 60611, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University Hospital, 1364 Clifton Road Northeast, Room H 180A, Atlanta, GA 30322, USA.
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Hollenbach M, Ali EA, Auriemma F, Gulla A, Heise C, Regnér S, Gaujoux S. Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm-A Pancreas2000/EPC Study. Front Med (Lausanne) 2020; 7:152. [PMID: 32435644 PMCID: PMC7218136 DOI: 10.3389/fmed.2020.00152] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 04/07/2020] [Indexed: 12/17/2022] Open
Abstract
Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions.
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Affiliation(s)
- Marcus Hollenbach
- Medical Department II—Gastroenterology, Hepatology, Infectious Diseases, Pulmonology, University of Leipzig Medical Center, Leipzig, Germany
| | - Einas Abou Ali
- Department of Gastroenterology, Digestive Oncology and Endoscopy, Cochin Hospital, Paris Descartes University, Paris, France
| | - Francesco Auriemma
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Hospital, Rozzano, Italy
| | - Aiste Gulla
- Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
- Center of Abdominal Surgery, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
- Department of Surgery, Georgetown University University Hospital, Washington, DC, United States
| | - Christian Heise
- Department of Medicine I—Gastroenterology, Pulmonology, Martin-Luther University Halle-Wittenberg, Halle, Germany
| | - Sara Regnér
- Section for Surgery, Department of Clinical Sciences Malmö, Lund University, Skane University Hospital, Malmö, Sweden
| | - Sébastien Gaujoux
- Department of Digestive, Hepatobiliary and Endocrine Surgery, Paris Descartes University, Cochin Hospital, Paris, France
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Taggart MW, Foo WC, Lee SM. Tumors of the Gastrointestinal System Including the Pancreas. ONCOLOGICAL SURGICAL PATHOLOGY 2020:691-870. [DOI: 10.1007/978-3-319-96681-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Miyabe K, Notohara K, Asano G, Kachi K, Kato A, Natsume M, Jinno N, Hori Y, Yoshida M, Naitoh I, Hayashi K, Ohara H, Takahashi S, Kataoka H. Laterally Spreading Adenocarcinoma Involving the Lower Bile Duct and Duodenum Expressing Heterogeneous Immunohistochemical Phenotypes. Intern Med 2019; 58:3087-3092. [PMID: 31292382 PMCID: PMC6875461 DOI: 10.2169/internalmedicine.2801-19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
A 70-year-old man was admitted to our hospital due to elevated levels of hepatobiliary and pancreatic enzymes. Computed tomography showed contrast-enhanced mucosal hypertrophy from the duodenal papilla to the distal bile duct. Endoscopic examinations revealed a laterally spreading granular tumor and ampullary swelling. After surgical resection, an examination revealed well-differentiated adenocarcinoma of the ampulla with tubular adenoma spreading from the distal common bile duct to the second part of the duodenum showing both bile duct and duodenal phenotypes. To our knowledge, this is the first case of a tumor spreading from the bile duct to the duodenum that exhibited multiple phenotypes.
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Affiliation(s)
- Katsuyuki Miyabe
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Japan
| | - Go Asano
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Kenta Kachi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Akihisa Kato
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Makoto Natsume
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Naruomi Jinno
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Yasuki Hori
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Michihiro Yoshida
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Kazuki Hayashi
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Hirotaka Ohara
- Department of Community-based Medical Education, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Japan
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Shi J, Wan X, Xie Y, Lin J, Long J, Xu W, Liang Z, Sang X, Zhao H. CK20 and lymph node involvement predict adverse outcome of malignant intraductal papillary neoplasm of the bile duct. Histol Histopathol 2019; 35:449-456. [PMID: 31657857 DOI: 10.14670/hh-18-179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES To identify prognostic factors of malignant intraductal papillary neoplasm of the bile duct (m-IPNB). MATERIALS AND METHODS We included 38 consecutive cases which underwent surgical resection and diagnosed as IPNB with malignant component from January 2003 to January 2017. Clinicopathological variables were collected to conduct survival analysis and identify prognostic factors. RESULTS The median overall survival (OS) of m-IPNB was 76.0 months, with 1-, 3-, and 5-year survival rates of 97.2%, 73.5%, and 59.8%, respectively. The median RFS was 48.0 months with 1-, 3-, and 5-year recurrence-free survival (RFS) rate was 83.2%, 59.8%, and 44.6%, respectively. Univariate analysis showed that elevation of carcinoembryonic antigen CEA, lymph node involvement, resection margin status, degree of periductal invasion, and positive expression of CK20 were associated with both OS and RFS of m-IPNB. After multivariate Cox models analysis, lymph node involvement and positive expression of CK20 were identified as independent prognostic factors for OS, while lymph node involvement and resection margin status were independent prognostic factors for RFS. The median OS of patients with m-IPNB involving lymphatic metastases and positive expression of CK20 was 27.0±8.8 months and 51.0±12.4 months, respectively. The median RFS of cases with lymph node involvement and R1 resection was 10.0±3.3 months and 25.0±6.9 months, respectively. However, there was no significant difference in OS or RFS between cases of pancreaticobiliary and intestinal subtype. CONCLUSIONS Lymph node involvement and positive expression of CK20 are independent prognostic factors for shorter OS of m-IPNB, while patients with lymph node involvement and positive resection margin are at higher risk of tumor recurrence.
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Affiliation(s)
- Jie Shi
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xueshuai Wan
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuan Xie
- Department of Hepatobiliary Surgery II, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Jianzhen Lin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Junyu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiyu Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiyong Liang
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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Tuncel D, Basturk O, Bradley KT, Kim GE, Xue Y, Reid MD, Balci S, Erbarut I, Adsay V. Poorly Cohesive (Signet Ring Cell) Carcinoma of the Ampulla of Vater. Int J Surg Pathol 2019; 28:236-244. [PMID: 31612756 DOI: 10.1177/1066896919880968] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
In the ampulla of Vater, carcinomas with "diffuse-infiltrative"/"signet ring cell" morphology, designated as "poorly cohesive carcinoma" (PCC) in the WHO classification, are very rare and poorly characterized. Nine cases with a classical PCC morphology constituting >50% of the tumor were identified. Mean age was 64.8 years (vs 64.6 in ampullary carcinomas [ACs]) and 6 were males, 3 females. The mean invasive tumor size was 2.5 cm (vs 1.9 in ACs). Other morphologic patterns displayed included cord-like infiltration (n=2), plasmacytoid cells (n=2), and microglandular component (n=4), including goblet cell adenocarcinoma-like foci. None of the cases were associated with dysplasia. By immunohistochemistry, the carcinomas did not show intestinal differentiation (CDX2 0/9, CK20 1/9, MUC2 3/9), MUC1 was positive in 4/9, MUC5AC was positive in 7/8. E-cadherin loss was noted in 4/9. All cases were advanced stage (6/9-pT3, 3/9-pT4) (vs 43% in ACs). Lymph node metastases were identified in 44% (vs 45% in AC). Six patients (67%) died of disease at a median of 25 months, 3 were alive at 13, 15, and 60 months. Overall median survival was significantly worse than that of intestinal-type ACs (26 vs 122 months, P = .006) and trended toward worse than pancreatobiliary type (26 vs 42 months, P = .1). In conclusion, PCCs constitute 2.45% of all ACs. These present as advanced tumors and express upper-gastrointestinal immunoprofile with frequent MUC5AC labeling, which may be helpful in identifying subtle infiltration in the surface mucosa since MUC5AC is not expressed in the ampullary mucosa. Patients have poor prognosis.
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Affiliation(s)
| | - Olca Basturk
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Grace E Kim
- University of California San Francisco, CA, USA
| | - Yue Xue
- Emory University, Atlanta, GA, USA
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Harthimmer MR, Stolborg U, Pfeiffer P, Mortensen MB, Fristrup C, Detlefsen S. Mutational profiling and immunohistochemical analysis of a surgical series of ampullary carcinomas. J Clin Pathol 2019; 72:762-770. [DOI: 10.1136/jclinpath-2019-205912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 06/08/2019] [Accepted: 06/10/2019] [Indexed: 12/20/2022]
Abstract
AimsKnowledge regarding the genetic features of ampullary carcinoma (AC) in European patients is limited. The utility of tumour markers for the establishment of a malignant diagnosis in biopsies from the ampullary region has not been fully elucidated. We aimed to describe the clinical, pathological, immunohistochemical (IHC) and genetic features of a Danish series of surgically resected ACs.MethodsSurgically resected ACs (n=59) were examined regarding (1) clinicopathological features, (2) histological subtypes, (3) expression of IMP3, maspin, MUC5AC and S100P and (4) next-generation sequencing using a hybrid capture-based platform (Illumina HiSeq2500), including 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. Tumour mutational burden (TMB) and microsatellite instability (MSI) were also evaluated.ResultsPancreatobiliary adenocarcinomas (PB-AC), intestinal adenocarcinomas (INT-AC), other ampullary tumours and mixed adenocarcinomas represented 45.8%, 23.7%, 16.9% and 13.6%. The proportion of IHC-positive ACs (score ≥2) was: Maspin (94.9%), IMP3 (67.8%), S100P (39.0%) and MUC5AC (18.6%). Most frequently altered genes were TP53 (59.3%), KRAS (40.7%), APC (27.8%), SMAD4 (20.4%), CDKN2A (16.7%) and ARID2/PIK3CA (each 11.1%). MUC5AC and S100P were frequently expressed in PB-AC, APC alterations frequent in INT-AC, SOX9 alterations were exclusive in INT-AC and MDM2 and FRS2 alterations in PB-AC. Four of 49 ACs (8.2%) were TMB-high/MSI-high and showed loss of MLH1 and PMS2.ConclusionsPB-AC was the most frequent histological subtype of AC. Maspin and IMP3 were the IHC tumour markers with the highest sensitivity. Adenocarcinoma subtypes differed regarding several genetic alterations, whose predictive value remains to be evaluated.
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Intracholecystic papillary-tubular neoplasms of the gallbladder – A clinicopathological study of 36 cases. Ann Diagn Pathol 2019; 40:88-93. [DOI: 10.1016/j.anndiagpath.2019.04.014] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/19/2019] [Accepted: 04/28/2019] [Indexed: 02/04/2023]
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da Silveira Santos JPL, Machado CJ, Junior EP, Rodrigues JBSR, Vidigal PT, Resende V. Immunohistochemical Predictors for Intestinal and Pancreatobiliary Types of Adenocarcinoma of The Ampulla of Vater. J Gastrointest Surg 2018; 22:1171-1178. [PMID: 29736668 DOI: 10.1007/s11605-018-3797-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 04/24/2018] [Indexed: 01/31/2023]
Abstract
OBJECTIVES To investigate immunohistochemical predictors for intestinal and pancreatobiliary types of adenocarcinoma of ampulla of Vater and identify clinicopathological characteristics associated with the histological types and patient survival. METHODS Immunohistochemical markers included MUC1, MUC2, MUC5AC, CDX2, CK7, and CK20. The data were analyzed by univariate and multivariate methods. The two-step cluster method was used to determine the best immunohistochemical markers to discriminate the intestinal from the pancreatobiliary type. RESULTS This study identified 9 (33.3%) intestinal and 21 (66.7%) pancreatobiliary tumors. CK7 and CDX2 achieved the highest value (= 1) as predictor markers, while CK20, MUC1, and MUC2 showed degrees of importance equal to 0.77, 0.71, and 0.68, respectively. MUC5AC did not reach 0.50 of importance. In the univariate analysis, lymph node involvement, staging (TNM), and angiolymphatic and perineural invasions were associated with histological types. The independent clinicopathological variable in the multivariate model to predict the histological type was angiolymphatic invasion (p = 0.005), OR = 17 (95% CI 2.33 to 123.83). The final model showed positive nodes (N1) associated with shorter survival (HR = 9.5; p = 0.006). Overall survival at 12, 36, and 60 months was 88.5, 67.0, and 47.6%, respectively. CONCLUSIONS CDX2 and CK7 were the immunohistochemical markers that best discriminated the intestinal from the pancreatobiliary type. Lymph node involvement had a high impact on survival and proved to be more frequent in the pancreatobiliary type.
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Affiliation(s)
- João Paulo Lemos da Silveira Santos
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil
| | - Carla Jorge Machado
- Department of Epidemiology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Eduardo Paulino Junior
- Department of Histopathology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - João Bernardo Sancio Rocha Rodrigues
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil
| | - Paula Teixeira Vidigal
- Department of Histopathology, Medical School, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Vivian Resende
- Department of Surgery, Medical School, UFMG, Belo Horizonte, Rua Sergipe, 67 apto 2401, Bairro Funcionários, Belo Horizonte, CEP 30130 170, Brazil.
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Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and Highlights MUC5AC as a Strong Prognosticator. Am J Surg Pathol 2017; 41:865-876. [PMID: 28505002 DOI: 10.1097/pas.0000000000000863] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large "ambiguous" group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were "unclassifiable." The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas.
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Sauvanet A, Dokmak S, Cros J, Cazals-Hatem D, Ponsot P, Palazzo M. Surgical Ampullectomy with Complete Resection of the Common Bile Duct: a New Procedure for Radical Resection of Non-invasive Ampulloma with Biliary Extension. J Gastrointest Surg 2017; 21:1533-1539. [PMID: 28560704 DOI: 10.1007/s11605-017-3457-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 05/15/2017] [Indexed: 01/31/2023]
Abstract
Extension of ampulloma into the lower common bile duct (CBD) is observed in up to 30% of cases. This biliary extension can prevent complete tumor resection thus is considered as a contraindication for endoscopic and even surgical ampullectomy. For ampullomas associated with a prolonged biliary extension, a pancreaticoduodenectomy is associated with a high morbidity and can be considered as an overtreatment for a benign neoplasm. The present study describes a new surgical approach including ampullectomy with complete resection of the intrapancreatic CBD and restoration of both biliary and pancreatic flow by two separate anastomoses. This procedure was performed in seven patients for a non-invasive ampulloma with a 25- to 70-mm CBD involvement. No patients died and three developed postoperative complications. Resection was R0 in all patients but one. With a 24-month median follow-up (range = 3-84), no patients developed pancreatic insufficiency or tumor recurrence.
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Affiliation(s)
- Alain Sauvanet
- Department of Hepatic and Pancreatic Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD) Hospital Beaujon, AP-HP, University Paris Diderot, 100 Boulevard du Général Leclerc, 92110, Clichy, France.
| | - Safi Dokmak
- Department of Hepatic and Pancreatic Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD) Hospital Beaujon, AP-HP, University Paris Diderot, 100 Boulevard du Général Leclerc, 92110, Clichy, France
| | - Jérôme Cros
- Department of Pathology, Hospital Beaujon, AP-HP, University Paris Diderot, 92110, Clichy, France
| | - Dominique Cazals-Hatem
- Department of Pathology, Hospital Beaujon, AP-HP, University Paris Diderot, 92110, Clichy, France
| | - Philippe Ponsot
- Department of Endoscopy, Pôle des Maladies de l'Appareil Digestif (PMAD) Hospital Beaujon, AP-HP, University Paris Diderot, 92110, Clichy, France
| | - Maxime Palazzo
- Department of Endoscopy, Pôle des Maladies de l'Appareil Digestif (PMAD) Hospital Beaujon, AP-HP, University Paris Diderot, 92110, Clichy, France
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Xue Y, Vanoli A, Balci S, Reid MM, Saka B, Bagci P, Memis B, Choi H, Ohike N, Tajiri T, Muraki T, Quigley B, El-Rayes BF, Shaib W, Kooby D, Sarmiento J, Maithel SK, Knight JH, Goodman M, Krasinskas AM, Adsay V. Non-ampullary-duodenal carcinomas: clinicopathologic analysis of 47 cases and comparison with ampullary and pancreatic adenocarcinomas. Mod Pathol 2017; 30:255-266. [PMID: 27739441 DOI: 10.1038/modpathol.2016.174] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 08/28/2016] [Accepted: 08/31/2016] [Indexed: 02/07/2023]
Abstract
Literature on non-ampullary-duodenal carcinomas is limited. We analyzed 47 resected non-ampullary-duodenal carcinomas. Histologically, 78% were tubular-type adenocarcinomas mostly gastro-pancreatobiliary type and only 19% pure intestinal. Immunohistochemistry (n=38) revealed commonness of 'gastro-pancreatobiliary markers' (CK7 55, MUC1 50, MUC5AC 50, and MUC6 34%), whereas 'intestinal markers' were relatively less common (MUC2 36, CK20 42, and CDX2 44%). Squamous and mucinous differentiation were rare (in five each); previously, unrecognized adenocarcinoma patterns were noted (three microcystic/vacuolated, two cribriform, one of comedo-like, oncocytic papillary, and goblet-cell-carcinoid-like). An adenoma component common in ampullary-duodenal cancers was noted in only about a third. Most had plaque-like or ulcerating growth. Mismatch repair protein alterations were detected in 13% (all with plaque-like growth and pushing-border infiltration). When compared with ampullary (n=355) and pancreatic ductal (n=227) carcinomas, non-ampullary-duodenal carcinomas had intermediary pathologic features with mean invasive size of 2.9 cm (vs 1.9, and 3.3) and 59% nodal metastasis (vs 45, and 77%). Its survival (3-, 5-year rates of 57 and 57%) was similar to that of ampullary-duodenal carcinomas (59 and 52%; P=0.78), but was significantly better than the ampullary ductal (41 and 29%, P<0.001) and pancreatic (28 and 18%, P<0.001) carcinomas. In conclusion, non-ampullary-duodenal carcinomas are more histologically heterogeneous than previously appreciated. Their morphologic versatility (commonly showing gastro-pancreatobiliary lineage and hitherto unrecognized patterns), frequent plaque-like growth minus an adenoma component, and frequent expression of gastro-pancreatobiliary markers suggest that many non-ampullary-duodenal carcinomas may arise from Brunner glands or gastric metaplasia or heterotopic pancreatobiliary epithelium. The clinical behavior of non-ampullary-duodenal carcinoma is closer to that of ampullary-duodenal subset of ampullary carcinomas, but is significantly better than that of ampullary ductal and pancreatic cancers. The frequency of mismatch repair protein alterations suggest that routine testing should be considered, especially in the non-ampullary-duodenal carcinomas with plaque-like growth and pushing-border infiltration.
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Affiliation(s)
- Yue Xue
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Alessandro Vanoli
- Department of Molecular Medicine, San Matteo Hospital, University of Pavia, Pavia, Italy
| | - Serdar Balci
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Michelle M Reid
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Burcu Saka
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Pelin Bagci
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Bahar Memis
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Hyejeong Choi
- Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
| | - Nobuyike Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Takashi Muraki
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Brian Quigley
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
| | - Walid Shaib
- Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
| | - David Kooby
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Juan Sarmiento
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Jessica H Knight
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA
| | - Michael Goodman
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA
| | - Alyssa M Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Volkan Adsay
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
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Reid MD, Lewis MM, Willingham FF, Adsay NV. The Evolving Role of Pathology in New Developments, Classification, Terminology, and Diagnosis of Pancreatobiliary Neoplasms. Arch Pathol Lab Med 2017; 141:366-380. [PMID: 28055239 DOI: 10.5858/arpa.2016-0262-sa] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Pancreatobiliary tract lesions are increasingly being discovered because of more sensitive imaging modalities. Magnetic resonance imaging has identified incidental pancreatic cysts in 13.5% of patients of progressively increasing age. Pancreatobiliary tissue is more accessible through endoscopic ultrasound and magnetic resonance imaging-guided biopsy procedures, and is now an integral part of pathologists' routine practice. Accordingly, several new tumor categories have been recently recognized, including intraductal tubulopapillary neoplasm, a new addition to tumoral intraepithelial neoplasms. Other entities have been reclassified, including the recent transition to 2-tiered grading of preinvasive neoplasms, as well as new perspectives on the distinctive biologic behavior of oncocytic intraductal papillary mucinous neoplasms (IPMNs) compared with other IPMN subtypes. This has led to proposals for revised staging of virtually every segment of the pancreatobiliary tree, with theranostic markers becoming an integral part of workup. Ki-67 is now an integral part of the classification of neuroendocrine tumors, with new definitions of "high-grade neuroendocrine carcinoma." Although bile duct brushings have opened new avenues for diagnosis, their sensitivity remains low and often requires concomitant fluorescent in situ hybridization to better define ambiguous cases. Various molecular pathways have been elucidated for pancreatic cysts, including KRAS for ductal neoplasia, GNAS for intestinal IPMNs, RNF3 for mucinous cysts, and VHL for serous cystic neoplasms, all key players in diagnostic workup. Integration of these updates into our understanding of pancreatobiliary disease requires active engagement of pathologists for appropriate specimen triage, judicious interpretation of results, and incorporation into reporting and staging. They also provide exciting opportunities for targeted therapy.
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Affiliation(s)
| | | | | | - N Volkan Adsay
- From the Departments of Pathology (Drs Reid, Lewis, and Adsay) and Digestive Diseases (Dr Willingham), Emory University School of Medicine, Atlanta, Georgia
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40
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Do SI, Lee HW, Sohn JH, Kim K. Clinicopathologic characteristics of young patients with gallbladder cancer. Pathol Res Pract 2016; 213:189-193. [PMID: 28216138 DOI: 10.1016/j.prp.2016.12.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Revised: 12/26/2016] [Accepted: 12/26/2016] [Indexed: 10/20/2022]
Abstract
Gallbladder cancer is the most common biliary tract cancer and the fifth most common cancer of the digestive system. However, the clinicopathologic features of gallbladder cancer in young Korean patients have not been studied. This study included 101 consecutive cases of gallbladder cancer that underwent cholecystectomy at Kangbuk Samsung Hospital from December 1990 to March 2011. The patients were divided into two groups by age at initial diagnosis of gallbladder cancer: a young patient group aged less than 45 years and an old patient group aged 45 or older. The young patient group included 10 patients with mean age of 38 (range, 29-44 years). Compared with the old patient group, the young patient group showed polypoid tumor appearance (p=0.014), lower pT stage (p=0.023), more frequent adenoma background (p=0.009), and less frequent dysplasia in remaining mucosa (p=0.001). The disease-related survival rate after 13.5 months was significantly more favorable for the young patients. Gallbladder cancers in young Korean patients have distinct clinicopathologic features of a high frequency of cancer arising in adenoma, rare association with intestinal metaplasia and dysplasia, and a favorable patient's prognosis. These findings suggest that the adenoma-carcinoma pathway could contribute more to gallbladder cancer carcinogenesis in young Korean patients than the metaplasia-dysplasia-carcinoma pathway.
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Affiliation(s)
- Sung-Im Do
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hyoun Wook Lee
- Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
| | - Jin Hee Sohn
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Kyungeun Kim
- Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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41
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Reid MD, Balci S, Ohike N, Xue Y, Kim GE, Tajiri T, Memis B, Coban I, Dolgun A, Krasinskas AM, Basturk O, Kooby DA, Sarmiento JM, Maithel SK, El-Rayes BF, Adsay V. Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases. Mod Pathol 2016; 29:1575-1585. [PMID: 27586202 DOI: 10.1038/modpathol.2016.124] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Revised: 06/03/2016] [Accepted: 06/03/2016] [Indexed: 12/13/2022]
Abstract
Histologic classification of ampullary carcinomas as intestinal versus pancreatobiliary is rapidly becoming a part of management algorithms, with immunohistochemical classification schemes also being devised using this classification scheme as their basis. However, data on the reproducibility and prognostic relevance of this classification system are limited. In this study, five observers independently evaluated 232 resected ampullary carcinomas with invasive component >3 mm. Overall interobserver agreement was 'fair' (κ 0.39; P<0.001) with complete agreement in 23%. Using agreement by 3/5 observers as 'consensus' 40% of cases were classified as 'mixed' pancreatobiliary and intestinal. When observers were asked to provide a final diagnosis based on the predominant pattern in cases initially classified as mixed, there was 'moderate' agreement (κ 0.44; P<0.0001) with 5/5 agreeing in 35%. Cases classified as pancreatobiliary by consensus (including those with pure-pancreatobiliary or mixed-predominantly pancreatobiliary features) had shorter overall (median 41 months) and 5-year survival (38%) than those classified as pure-intestinal/mixed-predominantly intestinal (80 months and 57%, respectively; P=0.026); however, on multivariate analysis this was not independent of established prognostic parameters. Interestingly, when compared with 476 cases of pancreatic ductal adenocarcinomas, the pancreatobiliary-type ampullary carcinomas had better survival (16 versus 41 months, P<0.001), even when matched by size and node status. In conclusion, presumably because of the various cell types comprising the region, ampullary carcinomas frequently show mixed phenotypes and intratumoral heterogeneity, which should be considered when devising management protocols. Caution is especially warranted when applying this histologic classification to biopsies and tissue microarrays. While ampullary carcinomas with more pancreatobiliary morphology have a worse prognosis than intestinal ones this does not appear to be an independent prognostic factor. However, pancreatobiliary-type ampullary carcinomas have a much better prognosis than their pancreatic counterparts.
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Affiliation(s)
- Michelle D Reid
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Serdar Balci
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Yue Xue
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Grace E Kim
- Department of Pathology, University of California, San Francisco, San Francisco, CA, USA
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Bahar Memis
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Ipek Coban
- Department of Pathology, Istanbul Bilim University, Florence Nightingale Hospital, Istanbul, Turkey
| | - Anil Dolgun
- Department of Biostatistics, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Alyssa M Krasinskas
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
| | - Olca Basturk
- Department of Pathology, Wayne State University, Detroit, MI, USA
| | - David A Kooby
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Juan M Sarmiento
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Shishir K Maithel
- Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Bassel F El-Rayes
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
| | - Volkan Adsay
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA
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MDCT and MRI of the ampulla of Vater. Part I: technique optimization, normal anatomy, and epithelial neoplasms. ACTA ACUST UNITED AC 2016; 40:3274-91. [PMID: 26306515 DOI: 10.1007/s00261-015-0528-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The purpose of this two-part article is to review the cross-sectional anatomy of the ampulla and periampullary region, to propose novel and optimized MDCT and MRI techniques that allow accurate evaluation of the ampulla of Vater, and to summarize the cross-sectional imaging features of benign and malignant ampullary conditions. In this first part, we will review the normal anatomy of the ampullary region, provide suggestions on how to optimize evaluation of the ampullary region by MDCT and MRI, and review the imaging features of select epithelial neoplasms of the ampulla. Familiarity with the normal ampullary anatomy and the pathologic conditions involving the ampulla, as well as the use of optimized MDCT and MRI techniques, may improve the diagnostic accuracy of radiologists facing ampullary abnormalities.
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43
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Jang KT, Ahn S. Tumoral Versus Flat Intraepithelial Neoplasia of Pancreatobiliary Tract, Gallbladder, and Ampulla of Vater. Arch Pathol Lab Med 2016; 140:429-36. [DOI: 10.5858/arpa.2015-0319-ra] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Context.—The identification of a precursor lesion is important to understanding the histopathologic and genetic alterations in carcinogenesis. There are a plethora of terminologies that describe precursor lesions of the pancreatobiliary tract, ampulla of Vater, and gallbladder. The current terminologies for precursor lesions may make it difficult to understand the tumor biology. Here, we propose the concept of tumoral and flat intraepithelial neoplasia to improve our understanding of precursor lesions of many epithelial organs, including the pancreatobiliary tract, ampulla of Vater, and gallbladder.
Objective.—To understand the dichotomous pattern of tumoral and flat intraepithelial neoplasia in carcinogenesis of pancreatobiliary tract, ampulla of Vater, and gallbladder.
Data Sources.—Review of relevant literatures indexed in PubMed.
Conclusions.—Tumoral intraepithelial neoplasia presents as an intraluminal or intraductal, mass-forming, polypoid lesion or a macroscopic, visible, cystic lesion without intracystic papillae. Microscopically, tumoral intraepithelial neoplasia shows various proportions of papillary and tubular architecture, often with a mixed pattern, such as papillary, tubular, and papillary-tubular. The malignant potential depends on the degree of dysplasia and the cell phenotype of the epithelium. Flat intraepithelial neoplasia presents as a flat or superficial, spreading, mucosal lesion that is frequently accompanied by an invasive carcinoma. Tumoral and flat intraepithelial neoplasias are not homogeneous entities and may exhibit histopathologic spectrum changes and different genetic profiles. Although intraepithelial neoplasia showed a dichotomous pattern in the tumoral versus flat types, they can coexist. Tumoral and flat intraepithelial neoplasia can be interpreted as part of a spectrum of changes in the carcinogenesis pathway of each organ.
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Affiliation(s)
| | - Sangjeong Ahn
- From the Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (Dr Jang); and the Department of Pathology, Pusan National University Hospital and the Pusan National University School of Medicine, and the Biomedical Research Institute, Pusan National University Hospital, Pusan, Korea (Dr Ahn)
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44
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Papillary adenoma of the common bile duct: infrequent pathology, novel endoscopic resolution, rare complication. A case report. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2016. [DOI: 10.1016/j.rgmxen.2016.04.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
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45
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Curvale C, Guidi M, Málaga I, Hwang HJ, Matanó R. Papillary adenoma of the common bile duct: Infrequent pathology, novel endoscopic resolution, rare complication. A case report. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2016; 81:109-11. [PMID: 26993161 DOI: 10.1016/j.rgmx.2015.07.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/01/2015] [Accepted: 07/28/2015] [Indexed: 10/22/2022]
Affiliation(s)
- C Curvale
- Servicio de Gastroenterología, Hospital de Alta Complejidad en Red «El Cruce»-Néstor Carlos Kirchner, Buenos Aires, República Argentina.
| | - M Guidi
- Servicio de Gastroenterología, Hospital de Alta Complejidad en Red «El Cruce»-Néstor Carlos Kirchner, Buenos Aires, República Argentina
| | - I Málaga
- Servicio de Gastroenterología, Hospital de Alta Complejidad en Red «El Cruce»-Néstor Carlos Kirchner, Buenos Aires, República Argentina
| | - H J Hwang
- Servicio de Gastroenterología, Hospital de Alta Complejidad en Red «El Cruce»-Néstor Carlos Kirchner, Buenos Aires, República Argentina
| | - R Matanó
- Servicio de Gastroenterología, Hospital de Alta Complejidad en Red «El Cruce»-Néstor Carlos Kirchner, Buenos Aires, República Argentina
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46
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Lai ZW, Bolm L, Fuellgraf H, Biniossek ML, Makowiec F, Hopt UT, Werner M, Keck T, Bausch D, Sorio C, Scarpa A, Schilling O, Bronsert P, Wellner UF. Characterization of various cell lines from different ampullary cancer subtypes and cancer associated fibroblast-mediated responses. BMC Cancer 2016; 16:195. [PMID: 26951071 PMCID: PMC4782372 DOI: 10.1186/s12885-016-2193-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 02/17/2016] [Indexed: 12/20/2022] Open
Abstract
Background Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. Methods We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). Results On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. Conclusion Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2193-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Zon Weng Lai
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany
| | - Louisa Bolm
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Hannah Fuellgraf
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany
| | - Martin L Biniossek
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany
| | - Frank Makowiec
- Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany
| | - Ulrich Theodor Hopt
- Clinic for General and Visceral Surgery, University Medical Center Freiburg, Freiburg, Germany.,Klinik für Chirurgie, Ratzeburger Allee 160, 23562, Lübeck, Germany
| | - Martin Werner
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany
| | - Tobias Keck
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Dirk Bausch
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany
| | - Claudio Sorio
- Dipartimento di Patologia, Universita di Verona, Verona, Italy
| | - Aldo Scarpa
- Dipartimento di Patologia, Universita di Verona, Verona, Italy
| | - Oliver Schilling
- Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany. .,BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany. .,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.
| | - Peter Bronsert
- Department of Pathology, University Medical Center Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany
| | - Ulrich Friedrich Wellner
- Clinic for Surgery, UKSH Campus Lübeck, Lübeck, Germany.,Comprehensive Cancer Center Freiburg, Freiburg, Germany.,Klinik für Chirurgie, Ratzeburger Allee 160, 23562, Lübeck, Germany
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47
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Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, Bassi C, Salvia R, Malleo G, Paiella S, Wolfgang CL, Matthaei H, Offerhaus GJ, Adham M, Bruno MJ, Reid M, Krasinskas A, Klöppel G, Ohike N, Tajiri T, Jang KT, Roa JC, Allen P, Castillo CFD, Jang JY, Klimstra DS, Hruban RH. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. Ann Surg 2016; 263:162-77. [PMID: 25775066 PMCID: PMC4568174 DOI: 10.1097/sla.0000000000001173] [Citation(s) in RCA: 167] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.
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Affiliation(s)
- Volkan Adsay
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Toru Furukawa
- Department of Pathology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | | | - Claudio Bassi
- Department of Surgery, University of Verona, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, University of Verona, Verona, Italy
| | | | | | - Christopher L. Wolfgang
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Hanno Matthaei
- Department of Surgery, University of Bonn, Bonn, Germany
| | - G. Johan Offerhaus
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Mustapha Adham
- Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Michelle Reid
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Alyssa Krasinskas
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Günter Klöppel
- Department of Pathology, Technical University, München, Germany
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Católica de Chile, Chile
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | - Jin-Young Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - David S. Klimstra
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Ralph H. Hruban
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
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48
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Balci S, Basturk O, Saka B, Bagci P, Postlewait LM, Tajiri T, Jang KT, Ohike N, Kim GE, Krasinskas A, Choi H, Sarmiento JM, Kooby DA, El-Rayes BF, Knight JH, Goodman M, Akkas G, Reid MD, Maithel SK, Adsay V. Substaging Nodal Status in Ampullary Carcinomas has Significant Prognostic Value: Proposed Revised Staging Based on an Analysis of 313 Well-Characterized Cases. Ann Surg Oncol 2015; 22:4392-401. [PMID: 25783680 PMCID: PMC4575255 DOI: 10.1245/s10434-015-4499-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND Current nodal staging (N-staging) of ampullary carcinoma in the TNM staging system distinguishes between node-negative (N0) and node-positive (N1) disease but does not consider the metastatic lymph node (LN) number. METHODS Overall, 313 patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma were categorized as N0, N1 (1-2 metastatic LNs), or N2 (≥3 metastatic LNs), as proposed by Kang et al. Clinicopathological features and overall survival (OS) of the three groups were compared. RESULTS The median number of LNs examined was 11, and LN metastasis was present in 142 cases (45 %). When LN-positive cases were re-classified according to the proposed staging system, 82 were N1 (26 %) and 60 were N2 (19 %). There was a significant correlation between proposed N-stage and lymphovascular invasion, perineural invasion, increased tumor size (each p < 0.001), and surgical margin positivity (p = 0.001). The median OS in LN-negative cases was significantly longer than that in LN-positive cases (107.5 vs. 32 months; p < 0.001). Patients with N1 and N2 disease had median survivals of 40 and 24.5 months, respectively (p < 0.0001). In addition, 1-, 3-, and 5-year survivals were 88, 76, 62 %, respectively, for N0; 90, 55, 31.5 %, respectively, for N1; and 68, 34, 30 %, respectively for N2 (p < 0.001). Even with multivariate modeling, the association between higher proposed N stage and shorter survival persisted (hazard ratio 1.6 for N1 and 1.9 for N2; p = 0.018). CONCLUSIONS Classification of nodal status in ampullary carcinomas based on the number of metastatic LNs has a significant prognostic value. A revised N-staging classification system should be incorporated into the TNM staging of ampullary cancers.
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Affiliation(s)
- Serdar Balci
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Olca Basturk
- Department of Pathology, New York University, New York, NY, USA
| | - Burcu Saka
- Department of Pathology, İstanbul Medipol University, İstanbul, Turkey
| | - Pelin Bagci
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachiouji Hospital, Tokyo, Japan
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Tokyo, Japan
| | - Grace E Kim
- Department of Pathology, University of California San Francisco, San Francisco, CA, USA
| | - Alyssa Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Hyejeong Choi
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Juan M Sarmiento
- Division of General and Gastrointstinal Surgery, Emory University, Atlanta, GA, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | | | | | - Michael Goodman
- Department of Epidemiology, Emory University, Atlanta, GA, USA
| | - Gizem Akkas
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Michelle D Reid
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, GA, USA
| | - Volkan Adsay
- Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
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49
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Bledsoe JR, Shinagare SA, Deshpande V. Difficult Diagnostic Problems in Pancreatobiliary Neoplasia. Arch Pathol Lab Med 2015; 139:848-57. [PMID: 26125425 DOI: 10.5858/arpa.2014-0205-ra] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
CONTEXT Many common diagnostic dilemmas are encountered in pancreatobiliary pathology, frequently resulting in uncertainty on behalf of the pathologist and referral for a second opinion. OBJECTIVES To review 4 common diagnostic dilemmas encountered in the practice of pancreatobiliary pathology: (1) pancreatic ductal adenocarcinoma versus chronic pancreatitis; (2) pancreatic ductal carcinoma versus adenocarcinomas arising in the ampulla and intrapancreatic common bile duct; (3) the distinction of uncommon intraductal neoplasms--intraductal oncocytic papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal acinar cell carcinoma; and (4) intrahepatic cholangiocarcinoma versus metastatic carcinoma. DATA SOURCES A review of pertinent literature, along with the authors' personal experience, based on institutional and consultation materials. CONCLUSIONS Important diagnostic features for a few challenging problems in pancreatobiliary pathology are reviewed. Careful study of the microscopic features along with awareness of differential diagnoses and diagnostic pitfalls generally allows distinction of these entities. We also highlight established and novel ancillary studies that help to arrive at an accurate diagnosis.
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Affiliation(s)
| | | | - Vikram Deshpande
- From the Department of Pathology, Massachusetts General Hospital, Boston (Drs Bledsoe and Deshpande); and the Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston (Dr Shinagare)
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50
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Intraductal tubulopapillary neoplasms of the bile ducts: clinicopathologic, immunohistochemical, and molecular analysis of 20 cases. Mod Pathol 2015; 28:1249-64. [PMID: 26111977 DOI: 10.1038/modpathol.2015.61] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2015] [Revised: 04/28/2015] [Accepted: 04/29/2015] [Indexed: 02/08/2023]
Abstract
Intraductal tubulopapillary neoplasm is a well-established entity in the pancreas. A similar, if not identical, tumor occurs also in the biliary tract. We conducted a multicenter study of 20 such lesions, focusing on their clinicopathologic characteristics and molecular profile. Biliary intraductal tubulopapillary neoplasms were seen in patients in their 60s (mean 62 years). The tumors were intrahepatic 70%, extrahepatic 10%, and perihilar 20%; mean tumor size was 6.9 cm. Histologically, all intraductal tubulopapillary neoplasms showed, in addition to their typical tubular pattern, solid areas (70%) or abortive papillae (50%). Necrosis was common (85%), predominantly focal (40%), and with 'comedocarcinoma-like pattern' in 40%. Immunohistochemically, these neoplasms were characterized by the expression of MUC1 (80%) and MUC6 (30%) and by the absence of MUC2 and MUC5AC. Associated invasive carcinomas were present in 16 (80%), mainly conventional tubular adenocarcinoma (50%). The molecular alterations observed included CDKN2A/p16 (intraductal components 44%, invasive 33%) and TP53 (intraductal components 17%, invasive 9%). Mutations in KRAS (intraductal 6%, invasive 0%), PIK3CA (intraductal 6%, invasive 0%), and loss of SMAD4/DPC4 (intraductal 7%, invasive 0%) were rare. No alterations/mutations were identified in IDH1/2, BRAF, GNAS, EGFR, HER2, and β-catenin. Follow-up information was available for 17 patients (85%) with mean follow-up 44 months. Overall combined survival rates showed favorable prognosis: 1 year 100%, 3 years 90%, and 5 years 90%. In conclusion, despite the relatively high incidence of invasive carcinoma (80%), available follow-up suggests that biliary intraductal tubulopapillary neoplasms have an indolent behavior. Molecular analyses highlight the low prevalence of alterations of common oncogenic signaling pathways in intraductal tubulopapillary neoplasm. Further studies using whole-exome sequencing are required to discover yet unknown molecular changes and to understand the carcinogenesis of intraductal tubulopapillary neoplasms.
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