BACKGROUND: In Germany pancreas transplants are performed in only a few selected and specialized centres, usually combined with a kidney transplant. Knowlegde of the indications for and techniques of transplantation as w...BACKGROUND: In Germany pancreas transplants are performed in only a few selected and specialized centres, usually combined with a kidney transplant. Knowlegde of the indications for and techniques of transplantation as well as of the histopathological assessment for rejection in pancreas and duodenal biopsies is not very widespread. AIM: To give an overview of the development and status quo in pancreas-kidney-transplantation in Germany summarizing the experience of the largest German pancreas transplant centre and to give a résumé of the results of histological diagnoses of biopsy specimens submitted between 06/2017 and 12/2020. Moreover, a detailed description and illustration of histological findings is included. MATERIAL AND METHODS: A thorough literature search for aspects of the history, technique and indication for pancreas transplantation was performed and discussed in the context of the local experience and technical particularities specific for the transplant centre in Bochum. The occurrence of complications was compared with international reports. Results of pancreas and duodenal biopsies submitted to Erlangen between 06/2017 and 12/2020 for histological evaluation, which were evaluated according to the Banff classification, were summarized. For a better understanding key histological findings of pancreas rejection and differential diagnoses were illustrated and discussed. RESULTS: A total of 93 pancreas transplant specimens and 3 duodenal biopsies were included. 34.4% of pancreas specimens did not contain representative material for a diagnosis. In the remaining 61 biopsies 24.6% showed no rejection, 62.3% were diagnosed with acute T-cell mediated rejection (TCMR) and 8.2% with signs suspicious of antibody-mediated rejection (ABMR). Acute acinary epithelial injury was seen in 59%, pancreatitis in 8.2% and allograft fibrosis was reported in as many as 54.1%. Calcineurin-inhibitor toxicity was discussed in only 4.9%. CONCLUSION: Pancreas-kidney-transplantation and standardized histological assessment of the transplanted pancreas or rarely duodenum with reporting according to the updated Banff classification of pancreas transplants or previous reports of duodenal rejection are important mainstays in the management of patients with diabetes.
Beyond pancreatic ductal adenocarcinoma, which is by far the most frequent pancreatic neoplasm, a great variety of tumors occur in the pancreas. They include solid and cystic masses and epithelial and nonepithelial neopl...Beyond pancreatic ductal adenocarcinoma, which is by far the most frequent pancreatic neoplasm, a great variety of tumors occur in the pancreas. They include solid and cystic masses and epithelial and nonepithelial neoplasms, and they show a great diversity in their biological behavior, ranging from benign tumors to highly aggressive neoplasms. As examples of rare pancreatic tumors, clinical, morphological, and molecular aspects of acinar cell carcinoma, pancreatoblastoma, solid pseudopapillary neoplasm, and serous cystic neoplasms are presented and discussed.
The latest WHO classification of tumors of the digestive system (2019) has introduced new concepts for the stratification of intraductal neoplasms of the pancreas, mostly based on molecular genetics and malignant potenti...The latest WHO classification of tumors of the digestive system (2019) has introduced new concepts for the stratification of intraductal neoplasms of the pancreas, mostly based on molecular genetics and malignant potential. Among them, pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms (IPMN) are both precursors of pancreatic ductal adenocarcinoma, whereas intraductal oncocytic papillary neoplasms (IOPN) and intraductal tubulopapillary neoplasms (ITPN) are usually associated with less aggressive subtypes of pancreatic cancer and therefore have a much better prognosis. Hence, it is of utmost importance to correctly classify these lesions and to distinguish them from each other as well as from other nonductal types of neoplasms, which can rarely display an intraductal growth, such as neuroendocrine tumors and acinar cell carcinomas. PanIN are microscopic lesions with limited clinical significance. In contrast, all other intraductal neoplasms can be identified as cystic processes and/or solid tumors by means of imaging, thereby setting an indication for a potential surgical resection. This review presents diagnostically relevant aspects of intraductal neoplasms of the pancreas, which are instrumental for the discussion within interdisciplinary tumor boards (resection vs. watch-and-wait strategies) as well as to determine the extent of resection intraoperatively.
Ductal adenocarcinoma is the most common tumor of the pancreas. Although relatively rare, it poses one of the greatest oncological challenges because of its poor prognosis, which has so far only slightly improved. Progre...Ductal adenocarcinoma is the most common tumor of the pancreas. Although relatively rare, it poses one of the greatest oncological challenges because of its poor prognosis, which has so far only slightly improved. Progress has been made in the more precise classification and standardization of the morphological assessment. In the current WHO classification, prognostically relevant subtypes are clearly delimited among themselves and from ductal adenocarcinoma not otherwise specified (NOS). In the recent TNM classification, a size-based T‑category was introduced. Diagnostically, the histological assessment of the resection specimen is relatively easy; on the other hand, assessment of the fine-needle biopsy from the primary tumor or a liver metastasis is still difficult. The molecular stratification of ductal adenocarcinoma and the other pancreatic neoplasms has made great progress. This not only defined the genetics of tumor entities, but also identified the prognosis and biology of tumor groups on the basis of RNA expression patterns. The range of treatment could be expanded by targeted molecular therapies (especially for patients with BRCA1/2 germline mutations, NTRK- or NRG1-fusions, or oncogenic BRAF and PIK3CA mutations as well as tumors with microsatellite instability (MSI)), even if targeted therapies are currently only available for a minority of patients (<10%).
Most pancreatic ductal adenocarcinomas are localized in the pancreatic head. Due to the complex anatomic relationships with the surrounding organs and vascular structures in the retroperitoneal space and to the presence...Most pancreatic ductal adenocarcinomas are localized in the pancreatic head. Due to the complex anatomic relationships with the surrounding organs and vascular structures in the retroperitoneal space and to the presence of numerous transection margins and dissection planes, pancreatic head resections belong to the most complex specimens concerning grossing and sampling for histopathologic analysis.Here we discuss current guidelines for standardized grossing and reporting of pancreatic cancer, with special reference to the assessment of the resection margin status. The importance of standardized reporting for the sake of completeness, comprehensibility, comparability, and quality control as well as for the integration of pathology reports in interdisciplinary digital workflows and artificial intelligence applications will be emphasized.
While patients with clinico-radiologically diagnosed resectable pancreatic cancer usually undergo surgery without preoperative cytological or histopathological diagnostics, patients with inoperable tumors or ambiguous fi...While patients with clinico-radiologically diagnosed resectable pancreatic cancer usually undergo surgery without preoperative cytological or histopathological diagnostics, patients with inoperable tumors or ambiguous findings in imaging often undergo EUS-FNA or EUS-FNB (endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound-guided fine-needle biopsy). In many cases, this concerns pancreatic cystic lesions, which can range from benign inflammatory pseudocysts to invasive pancreatic cancer emerging from intraductal papillary mucinous neoplasms (IPMNs) or mucinous cystic neoplasms (MCNs). However, the evaluation of EUS-FNA material can be especially hampered by contamination with gastric or enteric cells or mucin, degenerative changes, or low or even no cellularity of the sample. Next-generation-sequencing-based molecular analyses, especially of cystic lesions, can significantly increase the accuracy of EUS-FNA diagnostics of the pancreas. Interpretation of morphological and molecular data considering each case's clinico-radiological context is crucial. While reliable molecular markers for the detection of mucinous and specific nonmucinous pancreatic neoplasms already exist, establishing valid markers for the detection of high-grade lesions is an urgent future goal.
Pancreatitis harbors a spectrum of different inflammatory changes of the pancreas of variable etiology and histopathology. In this context, common variants have to be distinguished from rare variants to optimize therapy....Pancreatitis harbors a spectrum of different inflammatory changes of the pancreas of variable etiology and histopathology. In this context, common variants have to be distinguished from rare variants to optimize therapy. Each type of pancreatitis has characteristic features such as the age of patients and clinical presentation as well as the composition of the inflammatory infiltrates and histological changes.
In the past 25 years, treatment of metastatic colorectal cancer (mCRC) has undergone profound changes. The approval of newer chemotherapeutics such as irinotecan and oxaliplatin was followed in 2005 by the first targeted...In the past 25 years, treatment of metastatic colorectal cancer (mCRC) has undergone profound changes. The approval of newer chemotherapeutics such as irinotecan and oxaliplatin was followed in 2005 by the first targeted therapies, for example, monoclonal antibodies directed against the epidermal growth factor receptor (EGFR), as cetuximab and panitumumab, or the angiogenesis inhibitors bevacizumab, ramucirumab, and aflibercept. With the rapidly progressing molecular characterization of mCRC in the last 10 years and the classification of the disease in four consensus subtypes, further changes are emerging, which will promote, among other things, the introduction of protein-kinase inhibitors developed for specific molecular aberrations as well as immune checkpoint inhibitors into the treatment algorithm.Thorough molecular pathologic testing is indispensable today for guideline-compliant treatment of mCRC patients. In addition to RAS testing as a precondition for the therapy decision with regard to cetuximab and panitumumab, BRAF testing is of considerable relevance to allow decision making with regard to the newly approved chemotherapy-free combination of the BRAF inhibitor encorafenib and cetuximab in cases where a BRAF-V600E mutation is detected. Additional diagnostic tests should also include genome instability (microsatellite instability). Overall, more and more molecular alterations need to be investigated simultaneously, so that the use of focused next-generation sequencing is increasingly recommended.This overview describes the prognostic relevance of BRAF testing in the context of molecular pathologic diagnostics of mCRC, presents new treatment options for BRAF-mutated mCRC patients, and explains which modern DNA analytical and immunohistochemical methods are available to detect BRAF mutations in mCRC patients.
The comprehensive investigation of the excellently preserved mummy of Ötzi, the Iceman, and his equipment over the last 30 years has provided a wealth of information about the life and disease of this late Neolithic indi...The comprehensive investigation of the excellently preserved mummy of Ötzi, the Iceman, and his equipment over the last 30 years has provided a wealth of information about the life and disease of this late Neolithic individual. This research has indicated that his origin was from a local southern Alpine population, that he grew up in the valleys of the Southern Alps, and that he had considerable local mobility. He had well-balanced nutrition with a mixed vegetable and animal diet. He was very mobile in the alpine terrain and of athletic constitution. The Iceman suffered from mild to moderate degenerative joint disease primarily of the right hip joint, slight spondylosis of the cervical and lumbar spine, a minor focal (premature) arteriosclerosis, lung anthracosis and possibly silicosis, previous pleuritic inflammation (possibly of post-specific origin), intestinal infections of the stomach by Helicobacter pylori and Trichuris trichiura worm infestation in the intestines, a mild osteomalacia of cancellous bone, and diverse pathologies of his teeth with dental caries and periodontitis, as well as hair anomalies. The presence of borreliosis is still under debate. As potential remedies, the Iceman carried some anthelmintic substances with him: a birch polypore and an anthelmintic fern. The numerous tattoos may also have had therapeutic effects. Finally, the last days of Ötzi could be reconstructed quite precisely: his gastrointestinal content indicates that the Iceman moved from Alpine heights to a lower location and then again up to the glacier region where he died. During this journey he encountered two attacks: the first, several days before his death, lead to a stabbing wound in his right hand; the second was an arrow hit that wounded the Iceman lethally at his left axilla by laceration of the subclavian artery.
Paraffin histology is one of the most important and commonly-used laboratory techniques in diagnostic histopathology. The discovery of paraffin embedding is often attributed to the pathologist Edwin Klebs. Klebs was foll...Paraffin histology is one of the most important and commonly-used laboratory techniques in diagnostic histopathology. The discovery of paraffin embedding is often attributed to the pathologist Edwin Klebs. Klebs was following the lead of Stricker, who embedded embryos in a mixture of hot stearin and white beeswax. We show that Klebs experimented with paraffin wax for embedding tumour tissue. But he quickly rejected it as unsuitable because paraffin wax did not infiltrate the tissue. One of Klebs' correspondents, embryologist Wilhelm His, Sr., learned of Klebs' experiments and decided to try paraffin embedding. His dehydrated chicken embryos in alcohol, cleared them in lavender oil, and dripped hot paraffin wax onto them. This process allowed His to cut good sections. Here, we have replicated His's paraffin embedding protocol in order to determine whether His had indeed made the landmark discovery of infiltration embedding with paraffin wax. We followed the protocol that he gives in his 1868 monograph on the early development of the chicken. The protocol described by His failed, in our hands, to yield sections of the quality that he illustrates in his monograph. Typically, the tissue disintegrated when sectioned due to poor infiltration of the wax. Usable sections could only be obtained if His's protocol was modified by melting the embedded embryos in fresh paraffin wax. One explanation for our findings is that we failed to faithfully replicate His's protocol. Another is that his protocol was incomplete. We suggest that His is likely to have discovered and perfected infiltration embedding with paraffin wax but did not publish a complete protocol.