Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Pancreatic Neoplasms: HELP
Articles by Dr. G Klöppel
Based on 68 articles published since 2010
(Why 68 articles?)

Between 2010 and 2020, G. Klöppel wrote the following 68 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors. 2016

Falconi, M / Eriksson, B / Kaltsas, G / Bartsch, D K / Capdevila, J / Caplin, M / Kos-Kudla, B / Kwekkeboom, D / Rindi, G / Klöppel, G / Reed, N / Kianmanesh, R / Jensen, R T / Anonymous1140854. · ·Neuroendocrinology · Pubmed #26742109.

ABSTRACT: -- No abstract --

2 Guideline 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. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6721124. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

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.

3 Guideline European experts consensus statement on cystic tumours of the pancreas. 2013

Del Chiaro, Marco / Verbeke, Caroline / Salvia, Roberto / Klöppel, Gunter / Werner, Jens / McKay, Colin / Friess, Helmut / Manfredi, Riccardo / Van Cutsem, Eric / Löhr, Matthias / Segersvärd, Ralf / Anonymous3160750. ·Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. Electronic address: marco.del-chiaro@karolinska.se. ·Dig Liver Dis · Pubmed #23415799.

ABSTRACT: Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.

4 Editorial The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. 2010

Klöppel, Günter / Rindi, Guido / Perren, Aurel / Komminoth, Paul / Klimstra, David S. · ·Virchows Arch · Pubmed #20422210.

ABSTRACT: -- No abstract --

5 Review Unmet Needs in Functional and Nonfunctional Pancreatic Neuroendocrine Neoplasms. 2019

Jensen, Robert T / Bodei, Lisa / Capdevila, Jaume / Couvelard, Anne / Falconi, Massimo / Glasberg, Simona / Kloppel, Günter / Lamberts, Steven / Peeters, Marc / Rindi, Guido / Rinke, Anja / Rothmund, Mathias / Sundin, Anders / Welin, Staffan / Fazio, Nicola / Anonymous1371017 / Anonymous1381017. ·Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland, USArobertj@bdg10.niddk.nih.gov. · Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Medical Oncology, Vall d'Hebron University Hospital, Vall Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain. · Service de Pathologie, Hôpital Bichat, Paris, France. · Chirurgia del Pancreas, Università Vita e Salute, San Raffaele Hospital IRCCS, Milan, Italy. · Neuroendocrine Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. · Institute of Pathology, Technische Universität München, Munich, Germany. · Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Oncology, Antwerp University Hospital, Edegem, Belgium. · Institute of Anatomic Pathology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy. · Department of Gastroenterology, UKGM Marburg and Philipps University, Marburg, Germany. · Department of Surgery, Philipps University, Marburg, Germany. · Department of Radiology, Institute of Surgical Sciences, Uppsala University, Uppsala, Sweden. · Endocrine Oncology Unit, Department of Medical Sciences, University Hospital, Uppsala, Sweden. · Gastrointestinal and Neuroendocrine Oncology Unit, European Institute of Oncology (IEO), Milan, Italy. ·Neuroendocrinology · Pubmed #30282083.

ABSTRACT: Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.

6 Review Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. 2018

Klöppel, Günter / La Rosa, Stefano. ·Institute of Pathology, Consultation Center for Pancreatic and Endocrine Tumors, Technical University of Munich, Trogerstr. 18, 81675, Munich, Germany. guenter.kloeppel@tum.de. · Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland. ·Virchows Arch · Pubmed #29134440.

ABSTRACT: In 1983, a monoclonal antibody, Ki67, was generated, that labeled the nuclei of proliferating non-neoplastic and neoplastic cells. The name Ki67 derived from the city of Kiel (Ki) where the antibody was produced in the university department of pathology and refers to the number of the original clone (67). Systematic assessment of the proliferative activity of tumors using Ki67 started in the 1990s, when Ki67, which only worked on frozen tissue, was complemented by the antibody MIB-1 that also worked in formalin-fixed tissues. Pancreatic neuroendocrine neoplasms (PanNENs) were the first endocrine tumors whose proliferative activity was assessed with Ki67. This approach was so successful that Ki67 was included as prognostic marker in the 2000 and 2004 WHO classifications of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In 2010, the WHO classification of GEP-NENs introduced a three-tiered grading, originally proposed by ENETS in 2006 that was mainly based on the Ki67 index. As it has subsequently been shown that the Ki67 index is the most reliable factor in the prognostic evaluation of GEP-NENs, especially of PanNENs, the 2017 WHO classification of PanNENs requires its use and strongly recommends exact assessment of the proportion Ki67-labeled cells as basis for the calculation of the Ki67 index. Problems in assessing the Ki67 index include intertumoral and intratumoral staining heterogeneity and counting methods. Despite such problems, the Ki67 index has emerged as indispensable for the prognostic and therapeutic stratification of the majority of GEP-NENs and can barely be replaced by counting mitoses. In future, however, it can be anticipated that the Ki67 cut-offs experience refinement in relation to the type of tumor, its location, and its response to therapy. It is also possible that the prognostic risk of an individual tumor is calculated for each Ki67 unit and not for an "a priori" fixed Ki67 class.

7 Review Mixed acinar-neuroendocrine carcinoma of the pancreas: a case report and a review. 2016

Jakobsen, Mark / Klöppel, Günter / Detlefsen, Sönke. ·Department of Pathology, Odense University Hospital, Odense, Denmark. · Department of Pathology, Technical University of Munich, Munich, Germany. · Department of Pathology, Odense University Hospital, Odense, Denmark. Sonke.Detlefsen@rsyd.dk. ·Histol Histopathol · Pubmed #27081013.

ABSTRACT: A 62-year-old woman presented with abdominal discomfort. Imaging studies showed a tumor in the pancreatic tail. At contrast-enhanced CT and macroscopy, the tumor showed cystic, solid and hemorrhagic areas. Histologically, the tumor was well-circumscribed and entirely encapsulated. Some of the tumor cells in the cystic areas were reminiscent of acinar cells, and the majority was arranged in a solid growth pattern. Immunohistochemistry revealed >30% positivity for chymotrypsin, chromogranin A, synaptophysin, and CD56. The diagnosis of a mixed acinar-neuroendocrine carcinoma (MAEC) was made. Review of the English-language literature revealed 44 previously published cases of resected MAECs. We found that, compared to pure acinar cell carcinoma, patients with MAEC have a slightly higher age and are less frequently males, as the male / female ratio was almost equal. The histogenesis of MAEC is still controversial. Due to the small number of cases it is at present not possible to define an evidence-based optimal treatment strategy for these patients.

8 Review Pathology, genetics and precursors of human and experimental pancreatic neoplasms: An update. 2015

Esposito, Irene / Segler, Angela / Steiger, Katja / Klöppel, Günter. ·Institute of Pathology, Heinrich-Heine-University of Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany. Electronic address: Irene.Esposito@med.uni-duesseldorf.de. · Institute of Pathology, Technische Universität München, Ismaningerstr. 22, 81675, Munich, Germany. ·Pancreatology · Pubmed #26365060.

ABSTRACT: Over the past decade, there have been substantial improvements in our knowledge of pancreatic neoplasms and their precursor lesions. Extensive genetic analyses, recently using high-throughput molecular techniques and next-generation sequencing methodologies, and the development of sophisticated genetically engineered mouse models closely recapitulating human disease, have improved our understanding of the genetic basis of pancreatic neoplasms. These advances are paving the way for refined, molecular-based classifications of pancreatic neoplasms with the potential to better predict prognosis and, possibly, response to therapy. Another major development resides in the identification of subsets of pancreatic exocrine and endocrine neoplasms which occur in the context of hereditary syndromes and whose genetic basis and tumor development have been at least partially defined. However, despite all molecular progress, correct and careful morphological characterization of tissue specimens both in the context of experimental and routine diagnostic pathology represents the basis for any further genetic investigation or clinical decision. This review focuses on the current and new concepts of classification and on the current models of tumor development, both in the field of exocrine and endocrine neoplasms, and underscores the importance of applying standardized terminology to allow adequate data interpretation and promote scientific exchange in the field of pancreas research.

9 Review [Classification and malignant potential of pancreatic cystic tumors]. 2015

Esposito, I / Schlitter, A M / Sipos, B / Klöppel, G. ·Institut für Pathologie und Pathologische Anatomie, Technische Universität München, Ismaningerstr. 22, 81675, München, Deutschland, esposito@lrz.tum.de. ·Pathologe · Pubmed #25663186.

ABSTRACT: Cystic lesions of the pancreas are increasingly diagnosed with a reported prevalence of 10 % in 70-year-old individuals. Despite their broad spectrum, most resected cystic lesions can be attributed to one of the following entities: intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN), neuroendocrine cystic tumors (NECT), and solid pseudopapillary neoplasms (SPN). Among them, IPMN and MCN represent precursors of ductal adenocarcinoma, NECT and SPN are low-grade, potentially malignant lesions, and SCN are usually benign. Due to the not negligible morbidity and mortality rates in pancreatic surgery, even in highly specialized centers, an interdisciplinary preoperative stratification of pancreatic cystic lesions into high- and low-risk tumors is necessary in order to accurately select those cases that need to undergo immediate resection. The role of the pathologist is fundamental in both the preoperative assessment and in the postoperative classification, which determines prognosis, further treatment, and follow-up.

10 Review Pathology of pancreatic ductal adenocarcinoma: facts, challenges and future developments. 2014

Esposito, Irene / Konukiewitz, Björn / Schlitter, Anna Melissa / Klöppel, Günter. ·Irene Esposito, Björn Konukiewitz, Anna Melissa Schlitter, Günter Klöppel, Institute of Pathology, Technische Universität München, 81675 Munich, Germany. ·World J Gastroenterol · Pubmed #25320520.

ABSTRACT: Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.

11 Review Intraductal neoplasms of the pancreas. 2014

Klöppel, Günter / Basturk, Olca / Schlitter, Anna Melissa / Konukiewitz, Björn / Esposito, Irene. ·Institute of Pathology, Technische Universität München, Munich, Germany. Electronic address: guenter.kloeppel@lrz.tum.de. · Memorial Sloan-Kettering Cancer Center, New York, New York. · Institute of Pathology, Technische Universität München, Munich, Germany. ·Semin Diagn Pathol · Pubmed #25282472.

ABSTRACT: There are three types of pancreatic neoplasms that predominantly have an intraductal growth pattern: the common, usually cystic, intraductal papillary mucinous neoplasms (IPMNs); the rare, usually solid intraductal tubulopapillary neoplasms (ITPNs); and the rare intraductal tubular pyloric gland-type adenoma. In addition to these three tumor types, pancreatic neoplasms with a usually solid growth pattern such as acinar cell carcinomas, neuroendocrine tumors, and undifferentiated carcinomas may present, though very rarely, as predominantly intraductally growing neoplasms. IPMNs can be subclassified into main duct and branch duct tumors; into low- and high-grade dysplasia groups; and into tumors with intestinal, pancreatobiliary, oncocytic, or gastric cellular differentiation. The intestinal-, pancreatobiliary-, and oncocytic-type IPMNs occur predominantly in the main duct of the head of the pancreas and more commonly progress to invasive adenocarcinomas. The gastric-type IPMNs are frequently multifocal, occur predominantly in the branch ducts of the uncinate process, and have a low risk of progressing to invasive carcinoma. The prognosis for patients with an IPMN depends largely on the subtype and the presence and the stage of an invasive carcinoma. ITPNs are nodular tumors, often in the pancreatic head, and composed of densely packed tubular glands. Molecular genetics reveal KRAS, GNAS, and RNF43 as the most frequently mutated genes in IPMNs, while ITPNs show wild-type KRAS. Recent progress in genetic sequencing of pancreatic neoplasms and the identification of specific genetic mutations also holds promise for the future development of novel gene-based diagnostic tests in intraductal neoplasms of the pancreas that might even be used in preoperative conditions.

12 Review Hyperplasia to neoplasia sequence of duodenal and pancreatic neuroendocrine diseases and pseudohyperplasia of the PP-cells in the pancreas. 2014

Klöppel, Günter / Anlauf, Martin / Perren, Aurel / Sipos, Bence. ·Department of Pathology, Technical University, Ismaningerstr. 22, 81675, München, Germany, guenter.kloeppel@alumni.uni-kiel.de. ·Endocr Pathol · Pubmed #24718881.

ABSTRACT: Hyperplastic changes of the neuroendocrine cell system may have the potential to evolve into neoplastic diseases. This is particularly the case in the setting of genetically determined and hereditary neuroendocrine tumor syndromes such as MEN1. The review discusses the MEN1-associated hyperplasia-neoplasia sequence in the development of gastrinomas in the duodenum and glucagon-producing tumors in the pancreas. It also presents other newly described diseases (e.g., glucagon cell adenomatosis and insulinomatosis) in which the tumors are (or most likely) also preceded by islet cell hyperplasia. Finally, the pseudohyperplasia of PP-rich islets in the pancreatic head is defined as a physiologic condition clearly differing from other hyperplastic-neoplastic neuroendocrine diseases.

13 Review [Intraductal papillary neoplasms of the bile duct (IPNB). Diagnostic criteria, carcinogenesis and differential diagnostics]. 2013

Schlitter, A M / Klöppel, G / Esposito, I. ·Institut für Allgemeine Pathologie und pathologische Anatomie, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, München, Deutschland. ·Pathologe · Pubmed #24196621.

ABSTRACT: Intraductal papillary neoplasms of the bile duct (IPNB) are rare precursor lesions of intrahepatic and extrahepatic cholangiocarcinoma that follow an adenoma-carcinoma sequence. According to the histomorphology and the distinct immunohistochemical mucin pattern, four different subtypes are recognized: pancreatobiliary, intestinal, gastric and oncocytic. Differential diagnoses include micropapillary lesions (biliary intraepithelial neoplasms), papillary cystic lesions (intraductal tubulopapillary neoplasms) and cystic lesions (mucinous cystic neoplasms).

14 Review [New insights into the origin of pancreatic cancer. Role of atypical flat lesions in pancreatic carcinogenesis]. 2012

Esposito, I / Konukiewitz, B / Schlitter, A M / Klöppel, G. ·Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Trogerstr. 18, 81675 München. Esposito@lrz.tum.de ·Pathologe · Pubmed #23011021.

ABSTRACT: The identification and characterization of precursor lesions is fundamental to develop screening programs for early diagnosis and treatment, aiming at reducing cancer-related mortality. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that becomes clinical apparent only in advanced stages. In order to enable screening procedures for early detection of PDAC, an exact characterization of precursor lesions is of utmost importance. Pancreatic intraepithelial neoplasias (PanIN) are the most frequent and best characterized precursors of PDAC and are lesions with a ductal phenotype thus indicating a ductal cell origin of PDAC. However, evidence from genetically engineered mouse models suggests that tubular complexes (TC) originating through a process of acinar-ductal metaplasia (ADM) form atypical flat lesions (AFL) that may represent an alternative pathway of pancreatic carcinogenesis. Based on a thorough morphological and genetic analysis of murine TC, AFL and PanIN and their human counterparts, a new dual model of pancreatic carcinogenesis is proposed taking into account the role of AFL as possible new precursors of PDAC.

15 Review Classification and pathology of gastroenteropancreatic neuroendocrine neoplasms. 2011

Klöppel, Günter. ·Department of Pathology, Technical University of München, Ismaninger Strasse 22, 81675 München, Germany. guenter.kloeppel@alumni.uni-kiel.de ·Endocr Relat Cancer · Pubmed #22005112.

ABSTRACT: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are composed of cells with a neuroendocrine phenotype. The old and the new WHO classifications distinguish between well-differentiated and poorly differentiated neoplasms. All well-differentiated neoplasms, regardless of whether they behave benignly or develop metastases, will be called neuroendocrine tumours (NETs), and graded G1 (Ki67 <2%) or G2 (Ki67 2-20%). All poorly differentiated neoplasms will be termed neuroendocrine carcinomas (NECs) and graded G3 (Ki67 >20%). To stratify the GEP-NETs and GEP-NECs regarding their prognosis, they are now further classified according to TNM-stage systems that were recently proposed by the European Neuroendocrine Tumour Society (ENETS) and the AJCC/UICC. In the light of these criteria the pathology and biology of the various NETs and NECs of the gastrointestinal tract (including the oesophagus) and the pancreas are reviewed.

16 Review Intraductal papillary mucinous tumors of the pancreas: biology, diagnosis, and treatment. 2010

Grützmann, Robert / Niedergethmann, Marco / Pilarsky, Christian / Klöppel, Günter / Saeger, Hans D. ·University Hospital Carl Gustav Carus, Department of General, Vascular, and Thoracic Surgery, Dresden, Germany. Robert.Gruetzmann@uniklinikum-dresden.de ·Oncologist · Pubmed #21147870.

ABSTRACT: Pancreatic intraductal papillary mucinous neoplasms (IPMNs) rank among the most common cystic tumors of the pancreas. For a long time they were misdiagnosed as mucinous cystadenocarcinoma, ductal adenocarcinoma in situ, or chronic pancreatitis. Only in recent years have IPMNs been fully recognized as clinical and pathological entities, although their origin and molecular pathogenesis remain poorly understood. IPMNs are precursors of invasive carcinomas. When resected in a preinvasive state patient prognosis is excellent, and even when they are already invasive, patient prognosis is more favorable than with ductal adenocarcinomas. Subdivision into macroscopic and microscopic subtypes facilitates further patient risk stratification and directly impacts treatment. There are main duct and branch duct IPMNs, with the main duct type including the intestinal, pancreatobiliary, and oncocytic types and the branch duct type solely harboring the gastric type. Whereas main duct IPMNs have a high risk for malignant progression, demanding their resection, branch duct IPMNs have a much lower risk for harboring malignancy. Patients with small branch duct/gastric-type IPMNs (<2 cm) without symptoms or mural nodules can be managed by periodic surveillance.

17 Clinical Trial Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer. 2012

Harder, J / Ihorst, G / Heinemann, V / Hofheinz, R / Moehler, M / Buechler, P / Kloeppel, G / Röcken, C / Bitzer, M / Boeck, S / Endlicher, E / Reinacher-Schick, A / Schmoor, C / Geissler, M. ·Medizinische Klinik II, Hegau- Bodensee Klinikum, Virchowstraße 10, D-78224 Singen, Germany. jan.harder@hbh-kliniken.de ·Br J Cancer · Pubmed #22374460.

ABSTRACT: BACKGROUND: New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined with capecitabine in the patients with pancreatic cancer and HER2 overexpression. METHODS: Primary endpoint was progression-free survival (PFS) after 12 weeks. A total of 212 patients were screened for HER2 expression. RESULTS: Immunohistochemical (IHC) HER2 expression was: 83 (40%) grade 0, 71 (34%) grade 1, 31 (15%) grade 2, 22 (11%) grade 3. A total of 17 patients with IHC +3 HER2 expression or gene amplification could be assessed for the treatment response. Grade 3/4 treatment toxicities were: each 7% leucopenia, diarrhoea, nausea and hand-foot syndrome. Progression-free survival after 12 weeks was 23.5%, median overall survival (OS) 6.9 months. CONCLUSION: This study demonstrates +3 HER2 expression or gene amplification in 11% of patients. Contrary to breast and gastric cancer, only 7 out of 11 (64%) patients with IHC +3 HER2 expression showed gene amplification. Although the therapy was well tolerated, PFS and OS did not perform favourably compared with standard chemotherapy. Together, we do not recommend further evaluation of anti-HER2 treatment in patients with metastatic pancreatic cancer.

18 Article A semicentennial of pancreatic pathology: the genetic revolution is here, but don't throw the baby out with the bath water! 2020

Hruban, Ralph H / Klimstra, David S / Zamboni, Giuseppe / Klöppel, Günter. ·The Sol Goldman Pancreatic Cancer Research Center, Departments of Pathology and Oncology, the Johns Hopkins University School of Medicine, Baltimore, 21287, MD, USA. Electronic address: rhruban@jhmi.edu. · The Department of Pathology, Memorial Sloan Kettering Cancer Center, NY, USA. · Sacro Cuore Don Calabria Hospital, Italy. · Technical University of Munich, Munich, Germany. ·Hum Pathol · Pubmed #31521627.

ABSTRACT: The last 50 years have witnessed an explosion in our understanding of the pathology of pancreatic diseases. Entities known to exist 50 years ago have been defined more precisely and are now better classified. New entities, previously not recognized, have been discovered and can now be treated. Importantly, new tools have been developed that have unraveled the fundamental biological drivers of a number of pancreatic diseases. Many of these same tools have also been applied clinically, supplementing the tried and true hematoxylin and eosin stained slide with a plethora of new, highly sensitive and specific tests that improve diagnostic accuracy and delineate best treatments. As exciting as these many advances are, our knowledge of pancreatic pathology remains incomplete, and there is much to be learned.

19 Article [Neuroendocrine neoplasms : Two families with distinct features unified in one classification (German version)]. 2019

Klöppel, G. ·Institut für Pathologie, Konsultationszentrum für Pankreas und Endokrine Tumoren, Technische Universität München, Trogerstr 18, 81675, München, Deutschland. guenter.kloeppel@tum.de. ·Pathologe · Pubmed #30969346.

ABSTRACT: All neuroendocrine neoplasms (NENs) are characterized by the expression of synaptophysin and chromogranin A (or B). Yet, they are not a homogeneous group of tumors. Paradigmatic for these tumors are the NENs of the gastroenteropancreatic (GEP) system. Two NEN families can be distinguished: predominantly well differentiated and low-proliferative NENs, called neuroendocrine tumors (NET), and poorly differentiated and high-proliferative NENs, called neuroendocrine carcinomas (NECs). Based on their proliferative activity, GEP NETs are further classified into G1, G2, and G3 tumors. NECs are per definition G3 carcinomas. The morphological NEN dichotomy is supported by differences in epidemiology, genetics, clinics, and prognosis, and potentially has its cause originating from different progenitor cells. Genetically, NECs are distinguished by TP53 and RB1 alterations, which are lacking in NETs and are helpful in the distinction of NETs from NECs. Comparison of the GEP NEN WHO classification with extragastroenteropancreatic NEN classifications commonly reveal differences in terminology and categorization. In addition, they lack a grading system. However, common to all NEN classifications is the recognition of two tumor families differing in histological differentiation and prognosis. This allows the construction of a uniform classification frame for all NENs.

20 Article Molecular alterations associated with metastases of solid pseudopapillary neoplasms of the pancreas. 2019

Amato, Eliana / Mafficini, Andrea / Hirabayashi, Kenichi / Lawlor, Rita T / Fassan, Matteo / Vicentini, Caterina / Barbi, Stefano / Delfino, Pietro / Sikora, Katarzyna / Rusev, Borislav / Simbolo, Michele / Esposito, Irene / Antonello, Davide / Pea, Antonio / Sereni, Elisabetta / Ballotta, Maria / Maggino, Laura / Marchegiani, Giovanni / Ohike, Nobuyuki / Wood, Laura D / Salvia, Roberto / Klöppel, Günter / Zamboni, Giuseppe / Scarpa, Aldo / Corbo, Vincenzo. ·ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, Tokai University School of Medicine, Isehara, Japan. · Institute of Pathology, Heinrich-Heine-University and University Hospital of Düsseldorf, Düsseldorf, Germany. · Department of Surgery, General Surgery B, University of Verona, Verona, Italy. · Section of Anatomic Pathology, Azienda Ospedaliera Rovigo, Rovigo, Italy. · Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Technical University Munich, Munich, Germany. · Division of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·J Pathol · Pubmed #30306561.

ABSTRACT: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare, low-grade malignant neoplasms that metastasise to the liver or peritoneum in 10-15% of cases. They almost invariably present somatic activating mutations of CTNNB1. No comprehensive molecular characterisation of metastatic disease has been conducted to date. We performed whole-exome sequencing and copy-number variation (CNV) analysis of 10 primary SPN and comparative sequencing of five matched primary/metastatic tumour specimens by high-coverage targeted sequencing of 409 genes. In addition to CTNNB1-activating mutations, we found inactivating mutations of epigenetic regulators (KDM6A, TET1, BAP1) associated with metastatic disease. Most of these alterations were shared between primary and metastatic lesions, suggesting that they occurred before dissemination. Differently from mutations, the majority of CNVs were not shared among lesions from the same patients and affected genes involved in metabolic and pro-proliferative pathways. Immunostaining of 27 SPNs showed that loss or reduction of KDM6A and BAP1 expression was significantly enriched in metastatic SPNs. Consistent with an increased transcriptional response to hypoxia in pancreatic adenocarcinomas bearing KDM6A inactivation, we showed that mutation or reduced KDM6A expression in SPNs is associated with increased expression of the HIF1α-regulated protein GLUT1 at both primary and metastatic sites. Our results suggest that BAP1 and KDM6A function is a barrier to the development of metastasis in a subset of SPNs, which might open novel avenues for the treatment of this disease. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

21 Article Incidentally detected pancreatic neuroendocrine microadenoma with lymph node metastasis. 2018

Kwon, Jeong-Hwa / Kim, Hyoung Jung / Park, Do Hyun / Lee, Young-Joo / Heaphy, Christopher M / Klöppel, Günter / Hruban, Ralph H / Hong, Seung-Mo. ·Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. · Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. · Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. · Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. · Departments of Pathology and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Technical University Munich, Munich, Germany. · Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. smhong28@gmail.com. ·Virchows Arch · Pubmed #30003325.

ABSTRACT: Pancreatic neuroendocrine microadenomas (NEMAs) are non-functioning neuroendocrine tumors < 0.5 cm with a low proliferation rate and are considered benign. We report on a pancreatic NEMA with lymph node metastasis. A male in his 70s had pylorus-preserving pancreaticoduodenectomy for a distal bile duct carcinoma, which was a 2.1 cm well-differentiated-infiltrating adenocarcinoma with invasion limited to the bile duct wall. An incidental separate 0.4 cm well-differentiated NEMA was found in the pancreatic head with metastatic well-differentiated neuroendocrine tumor in one peripancreatic lymph node. Both neuroendocrine tumors in the pancreatic head and in the lymph node were composed of nests of uniform neoplastic cells with a fine chromatin pattern. The Ki-67 labeling index of NEMA was 0.85%. The neoplastic neuroendocrine cells in both the pancreas and node were diffusely positive for synaptophysin, chromogranin, and insulin. Therefore, this unusual case provides an exception to the current classification system which regards NEMAs as benign lesions.

22 Article Pancreatic neuroendocrine carcinomas reveal a closer relationship to ductal adenocarcinomas than to neuroendocrine tumors G3. 2018

Konukiewitz, Björn / Jesinghaus, Moritz / Steiger, Katja / Schlitter, Anna Melissa / Kasajima, Atsuko / Sipos, Bence / Zamboni, Giuseppe / Weichert, Wilko / Pfarr, Nicole / Klöppel, Günter. ·Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: b.konukiewitz@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: moritz.jesinghaus@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: katja.steiger@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: melissa.schlitter@web.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: atsuko.kasajima@tum.de. · Institute of Pathology, University Hospital of Tuebingen, 72076 Tuebingen, Germany. Electronic address: Bence.Sipos@med.uni-tuebingen.de. · Institute of Pathology, Sacro Cuore Don Calabria Hospital, 37024 Negrar, Verona, Italy. Electronic address: giuseppe.zamboni@sacrocuore.it. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: wilko.weichert@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: nicole.pfarr@tum.de. · Institute of Pathology, Technical University of Munich, 81675 Munich, Germany. Electronic address: guenter.kloeppel@alumni.uni-kiel.de. ·Hum Pathol · Pubmed #29596894.

ABSTRACT: Pancreatic neuroendocrine carcinoma is a rare aggressive tumor commonly harboring TP53 and RB1 alterations and lacking neuroendocrine-related genetic changes such as mutations in MEN1 and ATRX/DAXX. Little is known about its genetic profile with regard to that of pancreatic ductal adenocarcinoma. We therefore conducted a detailed genetic study in 12 pancreatic neuroendocrine carcinomas of large cell (n = 9) and small cell type (n = 3) using massive parallel sequencing applying a 409-gene panel on an Ion Torrent system. The genetic data were compared with known data of pancreatic ductal adenocarcinoma and correlated with exocrine lineage marker expression. A similar analysis was performed in 11 pancreatic neuroendocrine tumors G3. Neuroendocrine carcinomas harbored 63 somatic mutations in 45 different genes, affecting most commonly TP53 (8/12 cases), KRAS (5/12 cases), and RB1 (loss of expression with or without deletion in 4/12 cases). Five carcinomas had both TP53 and KRAS mutations. Neuroendocrine tumors G3 only shared singular mutations in 5 different genes with neuroendocrine carcinomas, including TP53, CDKN2A, ARID1A, LRP1B, and APC, affecting 5 different cases. Most KRAS-positive neuroendocrine carcinomas also expressed MUC1 (4/5) and carcinoembryonic antigen (3/5) as markers of ductal differentiation. Our data indicate that almost half of the pancreatic neuroendocrine carcinomas are genetically and phenotypically related to pancreatic ductal adenocarcinoma, and might therefore respond to chemotherapies targeting the latter carcinomas.

23 Article Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes. 2018

Mueller, Sebastian / Engleitner, Thomas / Maresch, Roman / Zukowska, Magdalena / Lange, Sebastian / Kaltenbacher, Thorsten / Konukiewitz, Björn / Öllinger, Rupert / Zwiebel, Maximilian / Strong, Alex / Yen, Hsi-Yu / Banerjee, Ruby / Louzada, Sandra / Fu, Beiyuan / Seidler, Barbara / Götzfried, Juliana / Schuck, Kathleen / Hassan, Zonera / Arbeiter, Andreas / Schönhuber, Nina / Klein, Sabine / Veltkamp, Christian / Friedrich, Mathias / Rad, Lena / Barenboim, Maxim / Ziegenhain, Christoph / Hess, Julia / Dovey, Oliver M / Eser, Stefan / Parekh, Swati / Constantino-Casas, Fernando / de la Rosa, Jorge / Sierra, Marta I / Fraga, Mario / Mayerle, Julia / Klöppel, Günter / Cadiñanos, Juan / Liu, Pentao / Vassiliou, George / Weichert, Wilko / Steiger, Katja / Enard, Wolfgang / Schmid, Roland M / Yang, Fengtang / Unger, Kristian / Schneider, Günter / Varela, Ignacio / Bradley, Allan / Saur, Dieter / Rad, Roland. ·Center for Translational Cancer Research (TranslaTUM), Technische Universität München, 81675 Munich, Germany. · Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. · Institute of Pathology, Technische Universität München, 81675 Munich, Germany. · The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK. · Comparative Experimental Pathology, Technische Universität München, 81675 Munich, Germany. · Anthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians Universität, 82152 Martinsried, Germany. · Helmholtz Zentrum München, Research Unit Radiation Cytogenetics, 85764 Neuherberg, Germany. · Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK. · Instituto de Medicina Oncológica y Molecular de Asturias (IMOMA), 33193 Oviedo, Spain. · Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain. · Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, 33011 Oviedo, Spain. · Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, 33940 El Entrego, Spain. · Medizinische Klinik und Poliklinik II, Klinikum der LMU München-Grosshadern, 81377 Munich, Germany. · Instituto de Biomedicina y Biotecnología de Cantabria (UC-CSIC), 39012 Santander, Spain. ·Nature · Pubmed #29364867.

ABSTRACT: The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest Kras

24 Article None 2018

Iacovazzo, Donato / Flanagan, Sarah E / Walker, Emily / Quezado, Rosana / de Sousa Barros, Fernando Antonio / Caswell, Richard / Johnson, Matthew B / Wakeling, Matthew / Brändle, Michael / Guo, Min / Dang, Mary N / Gabrovska, Plamena / Niederle, Bruno / Christ, Emanuel / Jenni, Stefan / Sipos, Bence / Nieser, Maike / Frilling, Andrea / Dhatariya, Ketan / Chanson, Philippe / de Herder, Wouter W / Konukiewitz, Björn / Klöppel, Günter / Stein, Roland / Korbonits, Márta / Ellard, Sian. ·Centre for Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, United Kingdom. · Institute of Biomedical and Clinical Science, University of Exeter Medical School, EX2 5DW Exeter, United Kingdom. · Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232. · Serviço de Endocrinologia e Diabetes, Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, 60430-372 Fortaleza, Brazil. · Division of Endocrinology and Diabetes, Department of Internal Medicine, Kantonsspital St. Gallen, CH-9007 St. Gallen, Switzerland. · Section of Endocrine Surgery, Division of General Surgery, Department of Surgery, University of Vienna, A-1090 Vienna, Austria. · Division of Diabetes, Endocrinology and Metabolism, University Hospital of Basel, CH-4031 Basel, Switzerland. · Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland. · Department of Pathology, University of Tübingen, 72076 Tübingen, Germany. · Department of Surgery and Cancer, Imperial College London, W12 0HS London, United Kingdom. · Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, NR4 7UY Norwich, United Kingdom. · Service d'Endocrinologie et des Maladies de la Reproduction, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, F-94275 Le Kremlin-Bicêtre, France. · INSERM 1185, Faculté de Médicine Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, France. · Department of Internal Medicine, Sector of Endocrinology, ENETS Centre of Excellence for Neuroendocrine Tumors, Erasmus MC, 3015 Rotterdam, The Netherlands. · Department of Pathology, Consultation Center for Pancreatic and Endocrine Tumors, Technical University of Munich, 81675 Munich, Germany. · Centre for Endocrinology, Barts and The London School of Medicine, Queen Mary University of London, EC1M 6BQ London, United Kingdom; m.korbonits@qmul.ac.uk. ·Proc Natl Acad Sci U S A · Pubmed #29339498.

ABSTRACT: The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing

25 Article Pancreatic Ductal Adenocarcinoma Subtyping Using the Biomarkers Hepatocyte Nuclear Factor-1A and Cytokeratin-81 Correlates with Outcome and Treatment Response. 2018

Muckenhuber, Alexander / Berger, Anne Katrin / Schlitter, Anna Melissa / Steiger, Katja / Konukiewitz, Björn / Trumpp, Andreas / Eils, Roland / Werner, Jens / Friess, Helmut / Esposito, Irene / Klöppel, Günter / Ceyhan, Güralp O / Jesinghaus, Moritz / Denkert, Carsten / Bahra, Marcus / Stenzinger, Albrecht / Sprick, Martin R / Jäger, Dirk / Springfeld, Christoph / Weichert, Wilko. ·Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. · Department of Medical Oncology, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany. · Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany. · Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH, Heidelberg, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Theoretical Bioinformatics and Heidelberg Center for Personalised Oncology (DKFZ-HIPO), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany. · Department of Surgery, University Hospital of the Ludwig-Maximilian University, Munich, Germany. · Department of Surgery, University Hospital of the Technical University Munich, Munich, Germany. · Institute of Pathology, University Hospital Düsseldorf, Düsseldorf, Germany. · Institute of Pathology, Charité University Medicine Berlin and German Cancer Consortium (DKTK; partner site Berlin), Berlin, Germany. · Department of Surgery, Charité University Medicine Berlin, Berlin, Germany. · Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany. · Institute of Pathology, Technical University Munich and German Cancer Consortium (DKTK; partner site Munich), Munich, Germany. wilko.weichert@tum.de. ·Clin Cancer Res · Pubmed #29101303.