[Fine-needle aspiration (FNA) of the thyroid gland : Analysis of discrepancies between cytological and histological diagnoses]. / Feinnadelaspiration (FNA) der Schilddrüse : Analyse diskrepanter zytologischer und histologischer Diagnosen.

BACKGROUND: Diagnostic problems of thyroid cytology are frequently discussed, but relevance and causes of discrepant cytological and histological diagnoses are rarely studied in detail. OBJECTIVES: Investigation of causes and relevance of discrepant diagnoses. MATERIALS AND METHOD: The analysis includes 297 patients who had thyroid resection after prior fine needle aspiration (FNA) and is based on the cytological and histological reports. In special cases, cytological and histological specimens were re-examined. RESULTS: Malignant tumors were found in 45 patients (15.1 %). In 5 patients the cytological diagnosis was "false negative". Three of these 5 tumors were papillary carcinomas (PTC) of ≤10 mm, one an obviously nonmalignant papillary proliferation of the thyroidal epithelium and one a malignant lymphoma complicating autoimmune thyreoiditis (AIT). In 11 of the 35 patients with a FNA diagnosis "suspicious of malignancy" or "malignant," 1 AIT, 4 goiter nodules, and 6 adenomas were diagnosed histologically. However, since distinct nuclear atypia was found in three of five false positive diagnoses, there still remains doubt in their benignity. CONCLUSIONS: Carcinomas of ≤10 mm incidentally detected in the resected thyroid tissue may not be relevant to the patient and do not reduce the high negative predictive value of FNA. The final diagnosis on the resected tissue should include the cytological findings. Discrepant findings should be commented in the report to the clinician.

[Update of the S3 guidelines for pancreatic cancer. What is new for pathologists?]. / Update der S3-Leitlinie für das Pankreaskarzinom. Was ist neu für Pathologen?

The S3 guidelines for pancreatic cancer were revised in 2013. Besides the oncological and palliative therapy modalities and surgical therapy, the guidelines for pathologists in topic 3 were updated. The modifications essentially concern the histopathological assessment of surgical specimens and in particular the circumferential resection margin and the R classification. In addition, the current recommendations were amended by recommendations concerning the pathohistological records, which should include the lymph node ratio in the future.

New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel.

Although the treatment of pancreatic ductal adenocarcinoma (PDAC) remains a huge challenge, it is entering a new era with the development of new strategies and trial designs. Because there is an increasing number of novel therapeutic agents and potential combinations available to test in patients with PDAC, the identification of robust prognostic and predictive markers and of new targets and relevant pathways is a top priority as well as the design of adequate trials incorporating molecular-driven hypothesis. We presently report a consensus strategy for research in pancreatic cancer that was developed by a multidisciplinary panel of experts from different European institutions and collaborative groups involved in pancreatic cancer. The expert panel embraces the concept of exploratory early proof of concept studies, based on the prediction of response to novel agents and combinations, and randomised phase II studies permitting the selection of the best therapeutic approach to go forward into phase III, where the recommended primary end point remains overall survival. Trials should contain as many translational components as possible, relying on standardised tissue and blood processing and robust biobanking, and including dynamic imaging. Attention should not only be paid to the pancreatic cancer cells but also to microenvironmental factors and stem/stellate cells.

[What's new? The 2010 WHO classification for tumours of the pancreas]. / Was ist neu? Die WHO-Klassifikation 2010 für Tumoren des Pankreas.

The new WHO classification of tumours of the pancreas logically includes both exocrine and neuroendocrine neoplasms in one volume, thus differing from all previous editions. Ductal adenocarcinoma is still the most frequent and clinically the most relevant malignant tumour. Its subtypes and variants are described in detail, as are mixed tumours. Other ductal tumours [mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPNM)] are classified as neoplasms with various grades of dysplasia up to invasive carcinoma. A new subtype of IPNM, intraductal tubulopapillary neoplasm (ITPN), has been characterized and newly added to the IPMN group. Serous and acinar tumours are classified as neoplasms with varying grades of dysplasia. Solid pseudopapillary neoplasm (SPN) is regarded as malignant (low grade) as a matter of principle because of its inherent potential to metastasize. Neuroendocrine neoplasms are characterized as G1 or G2 neuroendocrine tumours (NET) and neuroendocrine carcinomas (NEC, highly malignant). Syndromatic NETs are described and named according to their hormone expression pattern. The problems of staging when applying either the TNM or AJCC/UICC (American Joint Committee on Cancer/Union Internationale Contre le Cancer) classifications, which apply equally to endocrine and exocrine tumors, are discussed.

[Histopathological diagnosis and differential diagnosis of colorectal serrated polys: findings of a consensus conference of the working group "gastroenterological pathology of the German Society of Pathology"]. / Histopathologische Diagnostik und Differenzialdiagnostik serratierter Polypen im Kolorektum : Ergebnisse einer Konsensuskonferenz der AG "Gastroenterologische Pathologie der DGP"

Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas - because of their cytological atypia - were recognized as precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression, mainly because hyperplastic polyps lack cytological atypia. Meanwhile, it is evident that the lesions formerly classified as hyperplastic represent a heterogeneous group of polyps, some of which exhibit a significant risk of neoplastic progression. These lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CIMP pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas (SSA), traditional serrated adenomas (TSA) and mixed polyps, showing serrated and "classical" adenomatous features. In a consensus conference of the working group of gastroenterological pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.

Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry.

BACKGROUND: Worldwide survival data for ductal adenocarcinoma of the pancreas are the lowest among the 60 most frequent types of organ cancers. Hence published data on long time survivors of this disease are controversial. We performed a nationwide study comprising all Finnish patients diagnosed with pancreatic cancer in the period 1990-1996 who survived for at least five years after diagnosis. METHODS: Data on patients registered as five year survivors of pancreatic cancer were obtained from the Finnish Cancer Registry and Statistics Finland. Slides or paraffin blocks were collected from patients recorded as having histologically proven pancreatic ductal adenocarcinoma (PDAC) and were re-evaluated in a double blind fashion by three pathologists with special expertise in pancreatic pathology. RESULTS: Between 1990 and 1996, the Finnish Cancer Registry recorded 4922 pancreatic cancer patients, 89 of whom survived for at least five years. Reviewing this series of patients revealed 45 (49%) non-PDACs and 18 cases without histological verification. In 26 patients recorded as having histologically proven PDAC, re-evaluation of histological specimens confirmed PDAC in only 10 patients. CONCLUSIONS: This study indicates that (1) the prognosis of PDAC remains poor and (2) careful histopathological review of all patients with pancreatic cancer is mandatory if survival data are to be meaningful.

[Pancreatic ductal adenocarcinoma and its precursors]. / Das duktale Pankreaskarzinom und seine Vorläufer.

Pancreatic ductal adenocarcinoma is the most frequent malignant pancreatic tumor. It is one of the tumors that has a particularly poor prognosis. Its morphological characteristics are: preferential localization in the head of the pancreas, ductal-glandular tumor structures combined with marked desmoplasia and CEA and MUC1 positivity. Variants of this carcinoma include adenosquamous carcinomas, undifferentiated pleomorphic carcinomas and mixed ductal-endocrine tumors. With the definition of ductal lesions as pancreatic intraepithelial neoplasia, a progression model for pancreatic ductal carcinoma has been developed and corresponding gene alterations have been detected.

[Intraductal neoplasms of the pancreas: cystic and common]. / Intraduktale Pankreasneoplasien. Zystisch und häufig.

The most important of the generally rare intraductal tumors of the pancreas is the intraductal papillary-mucinous neoplasm (IPMN). In recent years this tumor type has been described in detail, and it was included in the WHO classification of 1996. IPMNs typically grow for a long time within the ducts, before approximately 50% of them eventually become invasive. Because of this feature the IPMNs are clearly distinct from ductal adenocarcinomas. Currently, IPMNs have advanced to the most commonly resected cystic tumor of the pancreas. Recent studies have shown that IPMNs may be distinguished into different types showing a different biology according to their mucin pattern.

[Spectrum of chronic pancreatitis. On the way to etiological classification]. / Das Spektrum der chronischen Pankreatitis. Auf dem Weg zur ätiologischen Klassifikation.

Chronic pancreatitis is a fibroinflammatory disease that is induced by injuries to the interstitial, ductal, and/or acinar cells. The most important causes are alcohol abuse, gene mutations, autoimmune processes, special anatomic changes, and obstructive duct lesions. The morphologic spectrum of the various types of chronic pancreatitis related to the above causes shows features that increasingly allow an etiological distinction and categorization to be made. A catalog of five criteria is presented for distinguishing chronic pancreatitis from ductal adenocarcinoma of the pancreas.

[Cystic pancreas tumors and their classification: features old and new]. / Zystische Pankreastumoren und ihre Klassifikation. Alte und neue Gesichter.

Cystic tumors and tumor-like lesions of the pancreas are rare, but have attracted a great deal of attention because they are easily recognized with new imaging methods and, in contrast to ductal adenocarcinoma, they can usually be cured surgically. The increasing resection rate in recent years has also increased our knowledge of cystic pancreatic tumors by conspicuously enlarging their morphological spectrum. Known entities have been better characterized (i.e. solid pseudopapillary neoplasm, intraductal papillary mucinous neoplasm) and new ones described (serous oligocystic adenoma, mucinous non-neoplastic cyst, acinar cell cystadenoma and cystic hamartoma). This review discusses the most important cystic tumors and tumor-like lesions, presents a new classification, and summarizes the immunohistochemical differential diagnosis.

[Solid pseudopapillary neoplasms. Enigmatic entity with female preponderance]. / Solid-pseudopapilläre Neoplasien. Weiblich orientiert und rätselhaft.

Solid pseudopapillary neoplasms (SPN) of the pancreas represent a special tumor entity, both morphologically and biologically. They form large solitary tumors that occur predominantly in young women. Histologically, they show solid, pseudopapillary, and pseudocystic patterns. The tumor cells are monomorphous and typically express vimentin, neuron-specific enolase, nuclear beta-catenin, and the progesterone receptor. Complete resection cures the tumor in about 90% of the cases. However, because recurrences and even metastases may occur in a small number of cases, SPN are classified as low-grade malignant tumors. Predicting malignancy histologically is not yet possible. The most important differential diagnosis to consider is neuroendocrine tumor of the pancreas. The etiology and pathogenesis of SPN are obscure.

Cystic neoplasms of the pancreas and tumor-like lesions with cystic features: a review of 418 cases and a classification proposal.

Although cystic neoplasms and lesions of the pancreas are rare, they have attracted a great deal of attention because of their potential curability. Since, in recent years, several new entities have been identified, the relative frequency of the tumors and their classification need to be reevaluated. In a series of 1454 tumorous lesions of the pancreas collected between 1971 and 2003 in our surgical pathology files and consultation files, all cystic pancreatic neoplasms and tumor-like lesions were identified and typed both histologically and immunohistochemically. There were 418 cases (29%) showing cysts with a diameter ranging between 0.5 cm and 27 cm. Most common were solid pseudopapillary neoplasms (21%) and intraductal papillary-mucinous neoplasms (18%). When only the cystic neoplasms and lesions that had been resected in a single institution were considered, intraductal papillary mucinous neoplasms were the most frequent cystic neoplasms, while solid pseudopapillary neoplasms took fifth place behind ductal adenocarcinomas with cystic features, serous cystic neoplasms and mucinous cystic neoplasms. The most frequent cystic tumor-like lesions were pancreatitis-associated pseudocysts. New and rare entities that have recently been identified are mucinous nonneoplastic cysts, acinar cell cystadenomas and cystic hamartomas. Bearing in mind that figures from referral centers such as ours may be biased regarding the relative frequency of lesions, we concluded from our data that intraductal papillary-mucinous neoplasms are the most frequently occurring pancreatic cystic neoplasms, rather than solid pseudopapillary neoplasms. It was possible to classify all cystic lesions encountered in our files or described in the literature in a new system that distinguishes between neoplastic and nonneoplastic lesions, with further subdivisions into epithelial (adenomas, borderline neoplasms and carcinomas) and nonepithelial tumors. This classification is easy to handle and enables a distinction on the basis of clinical behavior and prognosis.

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma.

Gene expression profiling revealed ADAM9 to be distinctly overexpressed in pancreatic ductal adenocarcinoma (PDAC). We examined the relevance of ADAM9 expression in PDAC diagnosis and prognosis. A total of 59 infiltrating PDACs, 32 specimens from patients with chronic pancreatitis, 11 endocrine tumours and 24 acinar cell carcinomas were immunohistochemically analysed for ADAM9 expression. Staining for ADAM9 was detected in 58 out of 59 (98.3%) PDACs and in two out of 24 (8.3%) acinar cell carcinomas, but not in endocrine tumours. In the non-neoplastic pancreas, whether normal or chronically inflamed, ADAM9 was expressed in centroacinar and intralobular duct cells, but not in interlobular duct cells and their hyperplastic lesions. Pancreatic ductal adenocarcinomas showing cytoplasmic ADAM9 expression correlated with poor tumour differentiation and also with shorter overall survival than in cases showing only an apical membranous staining pattern (P=0.001). Multivariate analysis identified cytoplasmic ADAM9 expression as an independent marker of shortened survival in a set of 42 curatively (R0) resected PDAC (P<0.05, hazard ratio 2.85, 95% confidence interval: 1.21-6.71). The results show that ADAM9 expression distinguishes PDACs from other solid pancreatic tumours. In addition, cytoplasmic ADAM9 overexpression is associated with poor differentiation and shortened survival. Therefore, ADAM9 overexpression might contribute to the aggressiveness of PDACs.

Lichenoid reactions of murine mucosa associated with amalgam.

BACKGROUND: In 97% of all patients with oral lichenoid reactions (OLR) associated with dental amalgam a removal of the fillings leads to a decline of the lesions, as a minimum. OBJECTIVES: The aim of this study was to determine if contact allergic or local toxic effects or both may contribute to OLR using an animal model with mercury-sensitive and non-sensitive rats. METHODS: Twenty Brown Norway rats, which have a genetic predisposition for an autoimmune syndrome after exposure to mercury and 20 Lewis rats, not mercury sensitive, were treated as follows: 10 animals of each group were sensitized with a low dose of mercuric chloride. Half of all animals received local exposure of the right buccal mucosa to amalgam (left: control), the others to amalgam alloy free of mercury. All rats were patch tested with an amalgam series. RESULTS: After 20 days of exposure 96% of all animals showed white mucosal lesions restricted to the contact zone of the alloy on the treated side, but only up to 25% had a positive patch test reaction to amalgam or inorganic mercury (INM). The lesions showed no relation to species, alloy, sensitization or patch test reaction. CONCLUSIONS: While allergic mechanisms may contribute to mucosal contact lesions in Brown Norway rats, this is less probable in Lewis rats. Mercury in general appears to be irrelevant in the development of ORL in this study. If this holds true for humans as well, patch testing with an amalgam series may be helpful in a minor fraction of all patients with OLR.

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001]. / Histopathologische Diagnostik der Barrett-Schleimhaut und ihrer Neoplasien. Ergebnisse einer Konsensus-Konferenz der Arbeitsgemeinschaft "Gastroenterologische Pathologie der Deutschen Gesellschaft für Pathologie" am 22. September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas.

Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile. To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas. The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.

Primary squamous cell carcinoma of the stomach. Report of a case and review of literature.

Primary squamous cell carcinomas of the stomach represent a rare entity. Since the first report in 1895 by Rörig et al. (1) only 80 cases have been published. These reports show a peak incidence in the sixth decade of life and preference of male gender (5:1). We report the case of a 61-year-old patient who presented with anemia and weight loss due to a large tumor of the gastric wall with adhesion to the pancreatic tail. After radical regional "en bloc" gastrectomy, splenectomy and pancreatic tail resection, the diagnosis of primary gastric squamous cell carcinoma could be confirmed, since the esophageal wall and the pancreatic tail were not infiltrated and extragastric squamous cell primaries could be excluded. After postoperative irradiation of the upper abdominal area, the patient developed a single liver metastasis in the left hepatic lobe that decreased with polychemotherapy. It was resected half a year later. Due mainly to advanced tumor stages, survival after surgical resection is poor. However, adjuvant radio and chemotherapy have resulted in survival rates of more than 3 years in reported cases, as in the present case. Five years after the diagnosis was established the patient is free of recurrence and without any complaint. Pathophysiological features, therapy and outcome are discussed by reviewing the cases reported in world literature.