[Pathohistology of polyps of the gastrointestinal tract]. / Pathohistologie von Polypen des Gastrointestinaltrakts.

Polyps of the gastrointestinal tract encompass a variety of epithelial and non-epithelial tumour-like conditions. The most common polyps are epithelial lesions. In the upper gastrointestinal tract, reactive inflammatory changes and hyperplastic polyps dominate, whereas true neoplastic polyps, like adenomas, are much more common in the colorectum. In addition to neoplasias such as adenomas, non-neoplastic polyps such as hyperplastic polyps of the stomach may also be associated with an increased risk of malignancy. The risk of malignancy is determined by the histological subtype of polyp, as well as the size, presence and degree of dysplasia. The term "dysplasia" has been reintroduced for adenomas in the current 2019 World Health Organization (WHO) classification and replaces "intraepithelial neoplasia". A further change is the term "sessile serrated lesion" with and without dysplasia, which was formerly known as sessile serrated adenoma.

[The German Mesothelioma Register : Current pathological diagnostics and services]. / Das Deutsche Mesotheliomregister : Aktuelle pathologische Diagnostik und Leistungen.

BACKGROUND: In Germany, asbestos-related diseases (asbestosis, lung cancer, mesothelioma) are recognised and compensated occupational diseases. The histologic diagnosis of mesothelioma is sometimes a challenge; additional immunohistochemical and molecular methods are needed. With lung dust analysis, the current asbestos fibre burden of the lung is measured (biomonitoring). Identification of grade I asbestosis (minimal asbestosis) requires directed histological examinations with up to 400-fold magnification, additional iron staining and possibly in connection with a lung dust analysis. OBJECTIVES: Demonstration of current pathologic diagnostics in association with mesothelioma and lung dust analysis. MATERIALS AND METHODS: Analysis of routine data from the German Mesothelioma Register. RESULTS: Contrary to reactive mesothelial hyperplasia, malignant mesotheliomas have a nuclear BAP1 loss-of-expression in up to 66% of cases. For differential diagnosis between reactive versus malignant, a p16-FISH test may be helpful. BAP1 loss-of-expression and p16-deletion are independent markers. Evaluation of the dataset of the German Mesothelioma Register of patients with repeated tissue sampling proves the detection of asbestos fibres at the same level even after 40 years. The asbestos fibre burden in the human lung remains stable over this long period of time. In the electron microscopic analysis, white asbestos was predominantly found. CONCLUSIONS: The well-known and industrially appreciated characteristics of asbestos fibres (in ancient ἄσßεστος asbestos "imperishable") as biopersistent have also been experimentally confirmed in human lungs.

[Mesothelioma]. / Mesotheliom.

Malignant mesotheliomas are rare and aggressive tumours arising from mesothelial cells of the pleura and peritoneum. Infrequent sites of origin are the pericardium and tunica vaginalis testis. More than 80% of mesotheliomas are localized in the pleura. Men are more frequently affected than women. The median age is >60 years. Asbestos exposure is the best known aetilogical risk factor and is reported in 54-90% of patients. In Germany, malignant mesotheliomas caused by occupational asbestos exposure are compensated as occupational disease since 1977. Several neoplastic and non-neoplastic lesions like metastasis, sarcomas, lymphomas or pleuritis with reactive mesothelial proliferation have to be distinguished from malignant mesotheliomas. Especially, the pathohistological differentiation between atypical reactive mesothelial proliferation from malignant mesothelioma is a diagnostic challenge.

[Lymphoma of the ocular adnexa]. / Lymphome der okulären Adnexe.

BACKGROUND: Lymphomas of the ocular adnexa are heterogeneous and demonstrate a wide range of clinical, histological, immunohistochemical and molecular genetic characteristics. AIM: The aim of this article is to give an overview of the interdisciplinary diagnostics and individually adapted lymphoma subtype-based therapy. DIAGNOSTICS: Depending on the lymphoma localisation, i.e. whether in the eyelid, the conjunctiva or in the orbit, a photograph or a radiological scan is required to record the tumor extent. Visual function is more likely to be impacted when the lymphoma arises in the posterior orbit, close to the optic nerve and imaging diagnostics are therefore necessary. Histological investigations are essential for confirming the lymphoma diagnosis and give information about the particular subtype, which in turn will determine subsequent patient management, Clinical staging investigations for determining the systemic extent of the lymphoma manifestation (e.g. imaging, blood analyses as well as bone marrow biopsy) are mandatory. THERAPY: External beam radiation, local and systemic chemotherapy or in some cases antibiotics are treatment options after surgical excision in isolated ocular adnexal lymphoma. The TNM classification of the American Joint Committee on Cancer or the Ann Arbor staging system, as well as the guidelines of the German Society of Hematology and Medical Oncology are all tools to aid the choice of the appropriate individually adapted therapy for systemic disease, which includes psycho-oncological care.

[Loss of appetite, night sweats, eczema, and axillary and inguinal lymph node swelling in a 28-year-old man]. / Inappetenz, Nachtschweiß, chronisches Ekzem und inguinale sowie axilläre Lymphknotenpakete bei einem 28-jährigen Patienten.

A 28-year-old man presented with loss of appetite, night sweats, eczema, and axillary and inguinal lymph node swelling. The tentative diagnosis of malignant lymphoma was made. To confirm the diagnosis, extirpation of a lymph node and a skin biopsy were performed. Systemic treatment with methylprednisolone resulted in an improvement of eczema and lymph node swelling. Because of the histological findings and clinical course, we diagnosed dermatopathic lymphadenopathy, also known as Pautrier-Woringer syndrome.

[Precancerous colorectal tumors]. / Präkanzerosen im Kolon.

Preneoplastic lesions of colorectal carcinoma can be divided in non-serrated and serrated lesions. Non-serrated lesions include conventional adenomas (tubular, tubulovillous and villous) and dysplasias associated with inflammatory bowel disease like flat intraepithelial neoplasia, dysplasia-associated lesions or masses (DALM) and adenoma-like masses (ALM). Conventional adenomas are mostly sporadic, but also found in hereditary adenomatous-polyposis syndromes. Hamartous polyposis syndromes are also associated with colorectal cancer. Serrated lesions include hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. Based on these precancerous colorectal lesions different molecular subtypes were identified. Histological subtype, size and grade of dysplasia of polyps are essential for risk assessment of colorectal cancer.

[Regression grading in gastrointestinal tumors]. / Regressionsgrading bei gastrointestinalen Tumoren.

Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification.

[Chemotherapy-associated steatohepatitis in patients with colorectal cancer and surgery on hepatic metastasis: clinical validation of a histopathological scoring system and preoperative risk assessment]. / Chemotherapieassoziierte Leberveränderungen bei Patienten mit kolorektalem Karzinom und operativer Entfernung von Lebermetastasen: Evaluierung eines histopathologischen Scores und Erhebung präoperativer Risikofaktoren.

Colorectal cancer (CRC) can only be cured by complete resection of the tumour. Primarily unresectable metastases of the liver are treated by chemotherapy to achieve down-sizing of metastasis and curative resection. Chemotherapy can affect tumour-free healthy liver tissue and lead to histopathological and functional changes summarised as "chemotherapy-associated steatohepatitis" (CASH). We have evaluated a histopathological scoring system for CASH and searched for preoperative risk factors for the development of CASH. Liver alterations such as CASH were more pronounced when patients received chemotherapy, especially when treated with oxaliplatin. A higher BMI, male sex and elevated serum transaminases were risk factors for the development of CASH. Patients with a higher CASH score, reflecting more advanced changes in liver tissue, had a higher serum peak bilirubin level postoperatively. We did not find a higher morbidity or mortality in patients with a more severe liver damage measured by the CASH score.

[Epigenetic alterations in colorectal carcinomas and precancerous lesions]. / Die Rolle epigenetischer Veränderungen in kolorektalen Karzinomen und ihren Vorläuferläsionen.

Colorectal carcinomas are the third most common malignant tumours worldwide with an incidence of 570,000 per year. According to their molecular mechanisms, sporadic colorectal carcinomas can be divided into two different phenotypes. The genetic phenotype, 50 to 70 % of all sporadic colorectal carcinomas, is characterised by a chromosomal instability (CIN) with the classical adenoma-carcinoma sequence due to alteration of the APC-betacatenin pathway with p53 mutations, SMAD alterations and LOH (loss of heterozygositiy) of 5q, 17 p 18q. On the other, the CpG island methylator phenotype (CIMP+) was described with an epigenetic inactivation of tumour suppressor genes that are typically inactivated by germline mutations in familiar cancer syndromes, e. g., Rb, VHL, hMLH1, p16 or BRCA. Colorectal carcinomas of the CIMP+ type often show a high microsatellite instability (MSI+) caused by aberrant promoter methylation of the missmatch repair gene hMLH1. Further CIMP+ are located in the proximal right-side colon and show a poor grading with mucinous or signet-cell differentiation.

[Pathologic and anatomic evidence of peritoneal metastases]. / Peritonealmetastasen in der pathologisch-anatomischen Befundung.

Peritoneal metastases are secondary tumours of the peritoneum and the most common tumours at this location. Ovarian carcinoma, colorectal cancer, and gastric cancer are the most frequent ones that show peritoneal involvement, along with carcinomas of the pancreas, gallbladder, uterus, and lung. Primary tumours originating in the peritoneum such as malignant peritoneal mesothelioma, primary peritoneal carcinoma, and benign peritoneal tumours along with inflammatory and reactive lesions must be differentiated from peritoneal metastases. Especially in cancer of unknown primary tumour, the discrimination between primary peritoneal tumours and peritoneal metastases is difficult and often requires immunohistochemical identification.

[Hepatocellular carcinoma and cholangiocarcinoma--different prognosis, pathogenesis and therapy]. / Hepatozelluläres Karzinom und Cholangiokarzinom--Unterschiedliche Prognose, Pathogenese und Therapie.

Primary liver cancer is one of the most common cancer worldwide. Beside hepatocellular carcinoma (HCC), accounting for more than 80%, cholangiocarcinoma (CC) is the second most frequent primary malignant epithelial liver tumor. Combined hepatocellular-cholangiocarcinoma (HCC/CC) is a rare form of liver cancer with a frequency of 1%. Both, hepatocellular carcinoma and cholangiocarcinoma, show a wide geographical variation with low-incidence areas in North America and Europe and high incidence areas in Africa and Asia. Whereas hepatocellular carcinomas develop by malignant transformation of hepatocytes, cholangiocarcinomas arise from the small intrahepatic bile duct epithelium. The UICC-TNM classification of malignant liver tumors is applied for both tumor entities. 70-80% of hepatocellular carcinoma occur in cirrhotic liver. In high incidence areas, such as Asia and Africa, HCC is strongly associated with chronic viral hepatitis B and C and liver cirrhosis. Nutritional factors, toxins and metabolic diseases contribute also to hepatocarcinogenesis. The etiology of cholangiocarcinoma remains unclear, most occur in absence of known etiological factors. But several risk factors including hepatolithiasis, liver fluke infection, and anatomical abnormalities associated with inflammation of the biliary tract have been described.

Methylation of SOCS-3 and SOCS-1 in the carcinogenesis of Barrett's adenocarcinoma.

BACKGROUND: The suppressors of cytokine signalling (SOCS) are inhibitors of cytokine signalling; methylation of SOCS-3 has been implicated in the tumorigenesis of liver as well as head and neck cancer. AIMS: This study was performed to elucidate the role of SOCS-1 and SOCS-3 in Barrett's adenocarcinoma and its precursor lesions. METHODS: DNA of specimens from 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias (n = 29 low grade and n = 27 high grade), 30 Barrett's mucosa without neoplasia, 20 samples of normal squamous and gastric epithelium and four cell lines were studied using methylation specific PCR for the SOCS-1 and SOCS-3 promoter following microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real time PCR, and the SOCS-3 protein was analysed immunohistochemically. RESULTS: In normal squamous epithelium and normal gastric mucosa, neither SOCS-3 nor SOCS-1 methylation was observed. In Barrett's mucosa without intraepithelial neoplasia, SOCS-3 methylation occurred in 4/30 cases (13%) whereas SOCS-1 was unmethylated. A hypermethylated SOCS-3 promoter was found in 14/19 Barrett's adenocarcinomas (74%) and in 20/29 high and 6/27 low grade intraepithelial neoplasias (69% and 22%, respectively). SOCS-1 promoter hypermethylation occurred in 8/19 adenocarcinomas (42%) and in 6/29 high grade and 1/27 low grade intraepithelial neoplasias (21% and 4%, respectively). Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumours and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased after treatment with the demethylation compound 5-aza-2-deoxycytidine. CONCLUSIONS: These data indicate that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of Barrett's adenocarcinoma.

[Role of epigenetics in the carcinogenesis of head and neck carcinomas - possible new targeted therapy?]. / Epigenetik in der Entstehung von Plattenenepithelkarzinomen des Kopf-Halses - mögliche neue Therapieoption?

In search of new targeted therapies for squamous cell carcinoma of the head neck (HNSCC), a better understanding of the carcinogenesis is of outmost importance. Recent studies show that not only genetic but also epigenetic alterations initiate the multistep process of tumordevelopment. Epigenetic changes lead to altered gene expression without alterations of the DNA sequence. The best characterized epigenetic change is the methylation of the promoter region of genes, especially of tumorsuppressor genes. The methylation of the promoter region blocks the promoter and therefore represses transcription. The loss of the gene products of tumorsuppressor genes leads to increased proliferation and decreased apoptosis. Methylation of tumorsuppressor genes was shown in precancerous lesions of HNSCC, which emphasizes the importance of methylation as an early biomarker. Several studies of tumor cell cultures show reactivated expression of proteins and as a result reduction of proliferation and induction of apoptosis after treatment with demethylating agentens. This presents a very promising new option for a targeted therapy.

[Histopathological faults and their importance for staging and therapy]. / Kolorektales Karzinom: Histopathologische Fehler -- Welche Bedeutung haben sie für die Stadieneinteilung und Therapie?

There is a variety of mistake sources of histopathological workup of biopsies and resection specimen. Among those are the incorrect or missing transmission of clinical findings and data. The most critical opportunities for producing mistakes are the histopathological examination, diagnosis and classifications. Many of these mistakes bear the potential to induce a wrong therapy. Generally, the use of forms, check lists and standardized diagnosis sheets may help to reduce the mistake rates. Comparison of own data with quality indicators enables pathologists to validate their own findings.

[Tumor classifications]. / Tumorklassifikationen. Aktuelle Aspekte und Probleme der Anwendung.

The correct use of tumor classifications is one of the key elements of adequate oncological treatment. Tumor classifications comprise: localization, typing, grading staging and stage grouping, classification after neoadjuvant radio(chemo)therapy, TNM classification and R classification. For easier identification and better documentation it is advisable to have a summary of tumor classifications at the end of each tumor concerning pathology report. Experience in clinical use has shown that classification may be incomplete or inadequately used. Not infrequently they are reported in a way which is open for misinterpretation. Some possible mistakes and misuse of tumor classifications are discussed. Users, among which are clinicians and pathologists, have to bear in mind the limitations of tumor classifications. These are for example reflected by the difficulty to classify single tumor entities in a correct way.