[Breast cancer: current recommendations for pathologists on the basis of the S3 guidelines]. / Mammakarzinom: aktuelle Empfehlungen für Pathologen auf Basis der S3-Leitlinie.

Optimal management of breast cancer patients is based on efficient multidisciplinary cooperation. The role of pathologists is to survey those parameters that are crucial for the individually adopted therapy. Thereby, distinct quality criteria have to be considered concerning the handling of the tissue samples, including preparation and examination, as well as the analytical methods used. The interdisciplinary S3 guideline "Diagnosis, therapy and follow-up of breast cancer" includes recommendations concerning these aspects based on current evidence. Its third edition was published in July 2012. In this article an overview of the topics relevant for pathologists that have been modified in the latest edition is provided.

[Her2 testing in gastric cancer. What is different in comparison to breast cancer?]. / Her2-Diagnostik beim Magenkarzinom. Was ist anders im Vergleich zum Mammakarzinom?

Based on data from a large multicenter phase III trial (ToGA study) trastuzumab has very recently been approved by the EMEA for metastatic gastric cancer and adenocarcinoma of the gastro-esophageal junction. Only patients with tumors which over express Her2 as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, determined by an accurate and validated assay are eligible for trastuzumab therapy. However, testing of Her2 status by immunohistochemistry (IHC) differs from breast cancer in core aspects: 1. IHC2+/3+ is scored even though membranous staining is incomplete if membrane staining is clearly detectable even at low magnification (2.5x/5x, 3+) or medium magnification (10x/20x, 2+). 2. Additionally, membrane staining at the appropriate intensity found in at least 10% of tumor cells is restricted to resection specimens. Evaluation of Her2 in situ hybridization (ISH) is similar to breast cancer with ratio values of > or =2.0 indicating Her2 gene amplification. Taking these modifications into account and defining the HER2 positive subgroup as IHC 3+ and IHC2+/FISH+, approximately 16% of gastric cancers are considered Her2 positive, affecting mainly tumor regions with intestinal (gland forming) type carcinoma. In contrast to breast cancer, up to one-third of gastric cancers show a heterogeneous Her2 status both at IHC and ISH levels which favors bright field ISH over FISH.

TNF-alpha antibody treatment in refractory collagenous sprue: report of a case and review of the literature.

Collagenous sprue (CS) is a rare disease characterized by celiac type small bowel malabsorption that is resistant to gluten free diet (GFD) and is associated with a poor prognosis. Our aim was to assess the properties of the monoclonal TNF-alpha antibody infliximab in a patient with high-dose steroid refractory CS. A 27-year-old man developed watery diarrhea with weight loss and abdominal pain. Duodenal biopsies showed a subtotal villous atrophy with an extensive subepithelial layer of collagenous fibers. An apparent GFD did not reduce symptoms. High dose steroid treatment (75 mg prednisone) in combination with azathioprine (150 mg) reduced diarrhea but did not induce complete remission. Based on strongly elevated mucosal TNF-alpha transcript concentrations we introduced infliximab (5 mg/kg body weight) into therapy. After two applications the patient's symptoms quickly improved. During the following year no recurrence of diarrhea has been observed. This case suggests that infliximab is an effective treatment in complicated cases of collagenous sprue.

[Guideline for the Early Detection of Breast Cancer in Germany 2008. Recommendations from the short version]. / Stufe-3-Leitlinie Brustkrebs-Früherkennung in Deutschland 2008 : Auszug aus der Kurzfassung: Handlungsempfehlungen.

The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

[Study of efficiancy of teleconsultation: the Telepathology Consultation Service of the Professional Assoziation of German Pathologists for the screening program of breast carcinoma]. / Studie zur Effektivität der Telekonsultation: Der Telepathologie-konsultationsservice des Berufsverbandes Deutscher Pathologen im Rahmen des Mamma-Screening-Programms.

AIMS: In the autumn a German screening program was started for detecting breast cancer in the population of women fifty and above. For the first time in this program, quality assurance rules were established: All statements of the radiologists and pathologists have to be confirmed by a second opinion. This improvement in quality is combined with a delay in time and additional expence. A new Telepathology Consultation Service was developed based on the experiences of the Telepathology Consultation Center of the UICC to speed up the second opinion process. METHODS AND MATERIAL: The complete web-based service is operated under MS Windows 2003 Server, as web server the Internet Information Server, and the SQL-Server (both Microsoft) as the database. The websites, forms and control mechanism have been coded in by ASP scripts and JavaScript. A study to evaluate the effectiveness of telepathological consultation in comparison to conventional consultation has been carried out. Pathologists of the Professional Association of German Pathologists took part as well as requesting pathologists and as consultants for other participants. RESULTS AND CONCLUSION: The quality of telepathological diagnosis was comparable to the conventional diagnosis. Telepathology allows a faster respond of 1 to 2 day (conventional postal delay). The time to prepare a telepathology request is about twice as conventional. This ratio may be inverted by an interface between the Pathology Information System and the Telepathology Server and the use of virtual microscopy. The Telepathology Consultation Service of the Professional Association of German Pathologists is a fast and effective German-language, internet-based service for obtaining a second opinion.

[Granulomatous orchitis]. / Orchitis Granulomatosa.

Five cases of granulomatous orchitis are reported and the literature is reviewed. The clinical features, pathology and treatment of this rare disease are discussed. In four cases the clinical features were chronic, while one patient had an acute course. The average age of the five patients was 31 years. In all cases we found only one testes was affected. In two cases the affected testis was removed, and in the remaining three cases only partial orchiectomy was performed.

[Jakob-Creutzfeld disease--intra vitam diagnosis?]. / Jakob-Creutzfeldt-Krankheit--Diagnose intra vitam?

The diagnosis of Jakob-Creutzfeld disease was made in two women (aged 59 and 76 years) whose course was marked by rapidly progressing signs of dementia, myoclonus and rhythmic bi- and tri-phasic steep waves in the EEG. The diagnoses were confirmed neuropathologically at autopsy. Since the disease is transmissible, precautions must be taken if the disease is suspected: wearing of disposable gloves, disinfection of instruments by one-hour autoclaving at 121 degrees C, disinfection of potentially contaminated surfaces with 5% sodium hypochlorite, and avoidance of skin cuts or punctures by instruments or syringes.

[Clinical observations in vascular occlusion of kidney tumors by absolute alcohol]. / Klinische Beobachtungen bei dem Gefässverschluss des Nierentumors durch absoluten Alkohol.

The results of the occlusion of renal tumors by two different materials-Ethibloc (n = 26) and absolute alcohol (n = 72) are being compared. The kidneys were occluded under equal clinical conditions. The clinical symptoms following embolisation are fewer in the group of alcohol embolized patients than in the group with Ethibloc. On the capillary level, the histological reaction to alcohol corresponds to a histotoxic alteration. This reaction goes beyond the reactive inflammation of the tissue observed after Ethibloc. This intensified reaction of the tissue after alcohol application partially explains the advantage of a fractionated application of alcohol during tumor embolisation.

[Histoautoradiographic studies of Billroth I-operated rat stomachs in relation to the postoperative interval. I. Proliferation kinetics in the area of the gastroenterostomy]. / Histoautoradiographische Untersuchungen im Billroth-I-operierten Rattenmagen in Abhängigkeit vom postoperativen Intervall. I. Die Proliferationskinetik im Bereich der Gastro-Enterostomie.

Nowadays the resected stomach is considered to be in a precancerous state in the broader sense. Until now there have been no systematic, histoautoradiographic investigations concerning the proliferative kinetics of the resected stomach in the region of anastomosed mucosa sections. Histoautoradiographic investigations should give an answer to the following questions: 1. In which way do the proliferative kinetics of gastric mucosa in the part of the anastomosis change with increasing postoperative interval? 2. Is there a result of variations in the proliferative kinetics of the anastomotic distant mucosa of the fundus? To find an answer to these questions, 75 Wistar-rats out of 231 operated rats (Billroth's 1st principle) were selected for histoautographic analysis. The laboratory animals were killed at fixed points of time in a postoperative interval of 104 weeks of experiment and the gastrointestinal preparations were worked up and interpreted for the histoautographic analysis. During the postoperative period the 3H-labelling-indices showed a characteristic course in the part of the gastric anastomosis. After a continuous increase of the 3H-labelling indices up to the fourfold of standard values two years after the operation there was a slight decrease of the proliferative activity. But it still remained twice the normal value. In addition, extended displacements and decompositions of gastric anastomosis mucosa could be observed. However, the proliferative activity in the anastomotid distant mucosa remained unchanged. A cell proliferation of gastric anastomosis increasing considerably and demonstrated in our experiment has to be considered as promotion factor of cancer development. Anastomotic carcinomas developing during the total experiment give evidence for this.

[Histoautoradiographic studies of Billroth I-operated rat stomachs in relation to the postoperative interval. II. Histologic changes in the area of the anastomosis and its proliferation-kinetic behavior]. / Histoautoradiographische Untersuchungen im Billroth-I-operierten Rattenmagen in Abhängigkeit vom postoperativen Intervall. II. Histologische Veränderungen im Bereich der Anastomose und ihr proliferationskinetisches Verhalten.

In a postoperative interval of 104 weeks' experience with 75 Wistar rats resected according to Billroth's 1st principle, the fourfold of standard of proliferative activity in addition to extended displacements and decompositions could be demonstrated. During 104 weeks of experience 8 animals developed in the anastomosed mucosa section adenomatous cystic glandular proliferations, 5 animals anastomotic polypi, 16 animals dysplastic gland areas and 10 animals showed anastomotic carcinomas. For these pathologic-anatomically outlined changes cellular proliferation was analysed by histoautoradiographic methods in parts of highest mitotic activity. The results were interpreted in dependence on their postoperative interval. In all pathologic-anatomical changes sources of strongest labelling could be found in the periphery. As most serious complication rats in experiment developed carcinoma in the anastomosed parts of mucosa. The peripheral sections of the carcinoma, so-called "front of invasion", showed regions of highest mitotic activity. Analysis of histoautoradiographic investigation in pathologic-anatomical change revealed modified proliferation kinetics in the sense of highly increased cell proliferation rates, which refer to the important role of the anastomotic region in the resected stomach.

[Absolute alcohol, an adjustable embolization material in kidney tumors]. / Der absolute Alkohol, ein "steuerbares Embolisationsmaterial" bei Nierentumoren.

Fourty-four patients with angiographically verified malignant renal tumors underwent a complete or selective embolisation of the affected kidney with absolute alcohol. The occlusion is effected by slow infusion of absolute alcohol. The technique is supported by animal experiments. The quantity of alcohol applied is measured by its intracorporal spread. The method of slow infusion is compared to other published embolisation techniques using absolute alcohol. This method allows an individual application of the vascular occlusion of the tumor supplying and the normal tissue supplying vessels, depending on size and localisation of the tumor, and further clinical data.

Biologic characterization of human bone tumors. III. Giant cell tumor of bone. A combined electron microscopical, histochemical, and autoradiographical study.

The cytogenesis of giant cell tumors of bone was studied in 6 cases by combined electron microscopical, histochemical and autoradiographical investigations. Electron microscopy identified two different types of mononuclear stromal cells: fibroblast-like cells with spindly shape and numerous membranes of the granular ER occur together with macrophages bearing many large lysosomes and a prominent Golgi apparatus. Enzyme histochemical results reflect the same diversity: One portion of mononuclear cells exhibits strong alpha-naphthyl acetate esterase (ANAE) activity, known as a marker for cells of the mononuclear phagocyte system, while the other, fibroblast-like cell type is ANAE negative. Tumor giant cells contain numerous membranes of granular ER, mitochondria, and a few isolated lysosomes. They lack the typical brush border of osteoclasts. Moderate to strong ANAE activity of these giant cells reflects their belonging to the mononuclear phagocyte system. Consequently, the giant cell tumor of bone consists of two different cell types, i.e. fibroblast-like cells and cells of the mononuclear phagocyte system, and so is appraised as a fibrohistiocytic tumor. A new inference from our autoradiographic findings is that tritiated thymidine is incorporated only by mononuclear cells, but not by giant cells. Electron microscopical autoradiography demonstrated that among the mononuclear cells, only fibroblasts are found to proliferate, but not macrophages. Thus, the giant cell tumor of bone is seen as a neoplasm of fibroblastic cells with a strong reactive infiltration of cells from the mononuclear phagocyte system.

Congenital muscular dystrophy, brain malformation and ocular problems (muscle, eye and brain disease) in two German families.

We report on two brothers and an unrelated girl with congenital muscular dystrophy (CMD), brain malformation and ocular changes (strabismus, myopia, glaucoma, cataracts, retinal dystrophy). Correlations with the inherited autosomal recessive syndromes of CMD, including the Fukuyama-type CMD with CNS malformation, and the Muscle, Eye and Brain Disease published by Santavuori are discussed.

Combined ultrastructural, histochemical, and autoradiographic study of osteosarcoma after preoperative chemotherapy according to the COSS 80 protocol.

Twelve osteosarcomas treated according to the COSS 80 protocol (preoperative chemotherapy, resection) were studied by light and electron microscopic, histochemical, and autoradiographic methods. Evidence of regressive and necrotic changes was found in many tumor cells, but the alterations were unspecific. Viable tumor cells of high malignancy were also observed regularly, often at the S phase. As the tumor regression continued, a strong reaction of the mononuclear phagocyte system was manifested by the presence of macrophages and giant cells.

[In vitro studies of cells in histiocytosis X]. / In-vitro-Untersuchungen an Zellen von Histiocytosis X.

In a female patient with histiologically ensured histiocytosis X, cell cultures modified according to NEZELOF were performed in methylcellulosis and Eagle's medium. From the 5th to the 15th day of incubation the cells were daily observed natively through a normal microscope and taken for histochemical examinations and for checking their capacity of phagocytosis. Two cell types could be distinguished: spindle-shaped fibroblasts as well as round cells of changing form and size, the alpha-naphthylacetate esterase response of which proved to be positive. The round cells can partly be regarded as HK cells, whereas giant cells could be predominantly observed during the second week. A phagocytosis of iron chips and human erythrocytes loaded with antibodies could be revealed in both types. HK cells represented mature macrophages, from which giant cells developed under in vitro conditions. There is still not explanation as to the local and immunological factors characterizing the clinical picture of histiocytosis X.

Histological classification of gastric cancer from initial to advanced stages.

An ideal classification of malignant tumors should imply not only the histogenesis of the tumor and adequate reproducibility of its specific characteristics by other investigators, but also an exact definition of the stages of tumor development to facilitate prognostic prediction. The present paper proposes a classification of gastric carcinoma with emphasis on the initial stages of malignant transformation. The classification is based on the analysis of early invasive gastric cancer observed in biopsy material from the Institute of Pathology of Münster University. Since 1974, all cases of severe dysplasia or early gastric cancer were selected from a total of 200,000 gastric biopsies and more than 1500 gastric resections, and subjected to special work-up. In analogy to Clark's classification of malignant melanoma (Clark et al., 1969) the proposed classification defines consecutive stages of development in gastric carcinoma with special regard on the maximum depth of invasion and vertical thickness of the tumor, together with its histologic type and the predominant direction of tumor spread.