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Die Abgrenzung reaktiver Mesothellasionen gegenuber neoplastischen Prozessen des Mesothels innerhalb einer Hydrocele testis kann diagnostische Schwierigkeiten bereiten. Die immunhistochemische Analyse allein ist hier haufig nicht richtungsweisend, jedoch ist fur die Kombination der immunhistochemischen Bestimmung von BAP1 und der FISH-Analyse von CDKN2A> eine hohe Spezifitat und Sensitivitat bezuglich dieser Differenzialdiagnose dokumentiert. Eine weitere wichtige Hilfestellung ist die Anamnese von Risikofaktoren wie Asbestbelastung und zuruckliegende Traumata. Entscheidend fur die korrekte Diagnosestellung einer reaktiven Mesothellasion ist der Ausschluss von Invasivitat anhand ausgedehnter Gewebeaufarbeitung.

More than 20% of soft-tissue tumors belong to the group of adipocytic neoplasms. Difficulties may occur in the differential diagnosis of lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas, in the distinction of dedifferentiated liposarcomas from other soft-tissue sarcoma entities and in the detailed subtyping of liposarcomas. Especially in biopsies, the correct diagnosis and grading may be hampered due to limited tissue. Because of the ever-increasing molecular-pathological knowledge of soft-tissue tumors and the rising distribution of molecular diagnostic assays in institutes of pathology, differential diagnosis has been facilitated, as more than 90% of adipocytic tumors carry more or less specific genomic alterations. In the following, the most important subtypes of adipocytic tumors are described morphologically and genomically.

Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.

More than 20% of soft-tissue tumors belong to the group of adipocytic neoplasms. Difficulties may occur in the differential diagnosis of lipomas versus atypical lipomatous tumors/well-differentiated liposarcomas, in the distinction of dedifferentiated liposarcomas from other soft-tissue sarcoma entities and in the detailed subtyping of liposarcomas. Especially in biopsies, the correct diagnosis and grading may be hampered due to limited tissue. Because of the ever-increasing molecular-pathological knowledge of soft-tissue tumors and the rising distribution of molecular diagnostic assays in institutes of pathology, differential diagnosis has been facilitated, as more than 90% of adipocytic tumors carry more or less specific genomic alterations. In the following, the most important subtypes of adipocytic tumors are described morphologically and genomically.

Das Malignitatsgrading stellt einen wesentlichen Baustein bei der Klassifikation von Sarkomen dar. Es korreliert mit der Prognose der Erkrankung und dem Risiko einer Metastasierung. Der Artikel prasentiert die Gradierungsschemata von Sarkomen der Weichteile, des Knochens und des Kindesalters. Die histomorphologischen Kriterien des FNCLCC-Systems (Federation Nationale des Centres de Lutte Contre le Cancer) und der Pediatric Oncology Group werden ebenso vorgestellt wie das Grading von Knochentumoren nach dem System des College of American Pathologists (CAP). Des Weiteren wird aufgezeigt, inwieweit Genexpressionssignaturen („complexity index in sarcoma“, CINSARC) und einzelne genetische Veranderungen (p53, MDM2, p16, SWI/SNF, EWSR1-Fusionen, PAX3/PAX7-FOXO1-Fusionen) fur die Prognoseeinschatzung von Sarkomen von Bedeutung sein konnen.

Die Obduktion eines Fetus der 23. Schwangerschaftswoche ergab den Befund eines partiellen Perikarddefektes mit einem hernierten Anteil des linken Ventrikels. Mikroskopisch war das Bild bei taillenformigen Einschnurungen des Myokards gepragt durch Zeichen rezidivierend abgelaufener hypoxischer Schadigungen des Myokards mit Nekrosen, scholligen Verkalkungen, Fibrosen und Eisenspeicherungen wie nach abgelaufenen Mikroinfarkten.

Invasion and metastatic dissemination of tumor cells defines prognosis not only in patients with epithelial, but also mesenchymal neoplasms. Early and clinically inapparent micrometastases occur in many patients, and the risk for metastasis correlates with the tumor subtype and histologic tumor grade. In recent years and analogous to the situation in epithelial tumors, mechanisms of tumor cell dissemination in soft tissue tumors have been increasingly understood, and it has been shown that reorganization of the actin cytoskeleton plays a key role in these processes. This review summarizes current knowledge on the mechanisms of progression and metastasis of soft tissue tumors and points out possible targets for novel anti-invasive and anti-metastatic therapies.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract although they are much less frequent than epithelial tumors. In more than 60% of cases they occur in the stomach. Especially small lesions measuring ≤1 cm in diameter, so-called microscopic GIST can occur multifocally, frequently in the proximal stomach wall and sometimes as an incidental finding in a gastrectomy specimen resected for gastric cancer. The multicentricity of GIST alone is not proof of a metastatic behavior or a syndromal or hereditary disease. Multiple sporadic synchronous and metachronous GIST are characterized by different primary mutations mostly in the KIT or PDGFRA genes and are often less aggressive. It is speculative whether a field effect is responsible or whether still unknown GIST-promoting factors may facilitate the development of several independent lesions. If KIT or PDGFRA mutations are lacking, a succinate dehydrogenase (SDH) deficient GIST has to be considered, either hereditary as Carney-Stratakis syndrome or syndromal as part of a Carney triad.

The autopsy of a fetus at 23 weeks gestational age revealed a partial pericardial defect with subsequent herniation of parts of the left ventricle. The myocard was impinged by the fibrous rim of the residual pericardium. Microscopic examination showed signs of recurrent myocardial infarctions with necrosis, calcification, fibrosis and prominent deposition of iron.Partial pericardial defects result from incomplete fusion of the pleuropericardial membrane and may lead to myocardial infarction via compression of the coronary arteries.

Malignancy grading is an essential element in the classification of sarcomas. It correlates with the prognosis of the disease and the risk of metastasis. This article presents the grading schemes for soft tissue, bone and pediatric sarcomas. It summarizes the histological criteria of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system and the Pediatric Oncology Group as well as the grading of bone tumors by the College of American Pathologists (CAP). Furthermore, the potential relevance of gene expression signatures, the complexity index in sarcoma (CINSARC) and single genetic alterations (p53, MDM2, p16, SWI/SNF, EWSR1 fusions and PAX3/PAX7-FOXO1 fusions) for the prognosis of sarcomas are discussed.

Durch extremen Zigarettenkonsum bestimmter Tabake konnen GIP-ahnliche („giant cell interstitial pneumonia“) Lungenveranderungen als Sonderform einer Kondensatpneumopathie resultieren, die zur Fallstrickdiagnose einer Sideropneumokoniose oder einer Hartmetalllunge verleiten. Genaue Angaben zur Berufs- und Raucheranamnese insbesondere bzgl. der Herkunft der Zigaretten fuhren zur korrekten Einordnung des Krankheitsbildes.

Due to their rarity and multiple subtypes, there is scant experience with sarcomas. Any effective targeted therapy depends on precise diagnosis of the tumor group using molecular markers and, increasingly, mutation testing. The necessary histopathological expertise and molecular diagnostic tools are usually only found at specialized centers. Using the Bonner GIST register as an example, the advantages of this kind of register from a diagnostic and therapeutic perspective will be discussed. Material submitted for gastrointestinal stromal tumors and other mesenchymal tumors, as well as the supervision of pathological referencing for national and international studies have made accurate diagnosis and appropriate therapy strategies ever more possible. The introduction of epidemiological as well as interdisciplinary sarcoma registers is a prerequisite for the improvement of sarcoma diagnostics and therapy.

The use of modern molecular techniques has gained importance in the diagnosis of sarcomas in recent years. Each of the analytical methods discussed here has its unique advantages and specific requirements. Cytogenetic screening methods which provide genome-wide information depend on the availability of fresh tissue. With the aid of fluorescence in situ hybridization and RT-polymerase chain reaction, specific events such as translocations in Ewing sarcoma, synovial sarcoma or alveolar rhabdomyosarcoma, as well as gene amplifications in well-differentiated and dedifferentiated liposarcoma or radiation-induced angiosarcoma and deletions in rhabdoid tumors or well-differentiated spindle cell liposarcoma can be detected in fresh and formalin fixed tissues. Molecular methods including Sanger sequencing, pyrosequencing and high resolution melting provide information about specific molecular aberrations on gene level. Here we review the most important molecular techniques currently used in sarcoma diagnosis, describe their relevance for differential diagnosis and point out specific examples.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the gastrointestinal tract. Two thirds of them are located in the stomach, another 30% occur in the small bowel, while the remaining tumors occur in the rectum or more rarely in the oesophagus. GIST most commonly grow from the smooth muscular layer towards the serosal surface whereas development towards to the mucosal layer is less frequent. In the latter case ulceration may occur, leading to gastrointestinal bleeding as the main symptom. However, the majority of GIST of the stomach are asymptomatic, resulting in large tumors on initial diagnosis. Most gastric GIST are not visible on endoscopy but may be diagnosed by endosonography. Due to their location in the outer layers of the tubular gastrointestinal tract biopsy is often hindered of even impossible. GIST of the stomach differ from tumors in other locations with regard to their morphology, molecular pathology and prognosis. This present article provides an overview of these differences also with regard to possible therapeutic consequences.

Inflammatorische fibroide Polypen (IFP) wurden vor 60 Jahren von Vaněk erstmals als „submukoses Granulom mit eosinophiler Infiltration“ beschrieben. IFP stellen polypose Spindelzellproliferate in der Submukosa und Mukosa von Magen, Dunndarm und Kolon mit entzundlicher Infiltration dar. Die Lasion ist bislang als entzundlich-reaktiv angesehen worden. Neuere Daten zeigen, dass die lasionalen Spindelzellen den PDGFRA exprimieren, in der Mehrzahl der Falle sind aktivierende PDGFRA-Mutationen nachweisbar. IFP sind also echte benigne mesenchymale Tumoren des Gastrointestinaltrakts.

Hintergrund Inflammatorische fibroide Polypen (IFP) sind Proliferationen CD34-positiver Spindelzellen vor einem inflammatorischen Hintergrund in der Submukosa und Mukosa des Gastrointestinaltrakts. IFP kommen vor allem im Magen, aber auch im Dunndarm, Kolon und Osophagus vor. Atiologie und Pathogenese sind bislang unklar.

Echte biphasische epithelial-mesenchymal differenzierte Tumoren der Harnblase sind auserordentlich selten. Bislang wurden nur 2 Adenosarkome in dieser Lokalisation publiziert, die auf dem Boden einer Endometriose entstanden waren. Im Gefolge einer malignen Transformation einer vesikalen Endometriose entstehen vorrangig endometrioide oder klarzellige Adenokarzinome. Wir berichten uber den ungewohnlichen und offenbar ersten Fall eines malignen Muller-Mischtumors mit heterologer rhabdomyoblastarer Differenzierung, der in der Blase einer postmenopausalen Frau entstanden war.

Invasion and metastatic dissemination of tumor cells defines prognosis not only in patients with epithelial, but also mesenchymal neoplasms. Early and clinically inapparent micrometastases occur in many patients, and the risk for metastasis correlates with the tumor subtype and histologic tumor grade. In recent years and analogous to the situation in epithelial tumors, mechanisms of tumor cell dissemination in soft tissue tumors have been increasingly understood, and it has been shown that reorganization of the actin cytoskeleton plays a key role in these processes. This review summarizes current knowledge on the mechanisms of progression and metastasis of soft tissue tumors and points out possible targets for novel anti-invasive and anti-metastatic therapies.

Ein massives Ovarialodem ist eine seltene benigne Erkrankung junger Frauen, die aufgrund einer teilweisen oder intermittierenden Torsion oder sekundar aufgrund einer vorbestehenden Ovarlasion entsteht. Wir berichten uber ein 13-jahriges Madchen mit einem 16 cm messenden Ovarialtumor und einer leichten CA-125-Erhohung im Serum. Aufgrund dieser Laborwerte wurde eine Adnektomie durchgefuhrt. Die histopathologische Untersuchung zeigte ein massives Ovarialodem mit multiplen venosen Thrombosen. Die korrekte Diagnose des Ovarialodems in Abgrenzung zu einem malignen Ovarialtumor ist insbesondere im Hinblick auf den Erhalt der Fertilitat entscheidend.

Giant cell interstitial pneumonia (GIP)-like pulmonary alterations as a special form of condensate pneumopathy may result following inhalation of certain types of tobacco smoke which can cause a pitfall diagnosis of sideropneumoconiosis or hard metal lung disease. Exact information regarding the patient occupation and smoking history and especially regarding the origin of the cigarettes helps to clarify the findings.

Massive ovarian edema is a rare tumor-like condition found in young women resulting from accumulation of fluid mostly due to partial or intermittent torsion of the ovary or secondary, to a preexisting ovarian lesion. We report a case of a 13-year-old girl presenting with an ovarian mass measuring 16 cm. CA-12-5 levels were slightly elevated. Concerns regarding underlying malignancy led to salpingo-oophorectomy. Pathological evaluation revealed a massive ovarian edema and multiple thromboses of ovarian veins. Differentiating massive ovarian edema from malignant ovarian tumor is crucial to prevent patients from undergoing unnecessary surgery.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the digestive tract. In up to 90% of cases, they are characterized by activating mutations in the KIT or the PDGFRA gene. GIST represent a paradigm for successful targeted treatment with tyrosine kinase inhibitors (TKI). Since the approval of the TKI imatinib in 2002 the survival of patients with metastatic GIST has tripled. The next logical step was the concept of using imatinib in an adjuvant approach, which was recently shown to increase overall survival significantly. In both settings, the mutational status has high predictive implications. In detail, GIST with KIT exon 11 mutations show the best response rates with partial remission rates of up to 80%. In KIT exon 9 mutations, a doubled daily dose of 800 mg imatinib is now standard. The PDGFRA exon 18 mutation D842V has been shown to lead to primary resistance. The treatment strategy in GIST is driven by their molecular characterisation. Further research has increased our knowledge on resistance mechanisms in solid tumors against TKI. The number of patients with secondary resistance due to acquired KIT mutations is increasing with treatment duration. Strategies to address this situation are the introduction of novel pathway inhibitors targeting different levels of signal transduction pathways, such as the mTOR/Akt pathway, the RAS/RAF pathway, histone deacetylation, among others. Among the GIST without mutations in the common hot spot regions of KIT and PDGFRA, the so-called wildtype GIST, further genomic subgroups have been identified. One such subgroup carries inactivating germline mutations in the genes encoding succinate dehydrogenase B, C, or D. They are associated with the occurrence of paragangliomas, so-called Carney-Stratakis syndrome. Most frequently, these GIST are located in the stomach, showing an epithelioid phenotype and a multinodular growth pattern. They preferentially occur in young females and often show lymph node metastases, the latter being very unusual in sporadic GIST. In sporadic Carney's triad additional pulmonary chondromas are observed and there are no SDH mutations. Another small subgroup of sporadic GIST present with BRAF mutations as an alternative genomic event. Finally, very rare kindreds with germline mutations in either KIT or PDGFRA have been described who develop multiple GIST and depending on the mutational subtype mastocytosis, hyperpigmentation and/or dysphagia. In summary, the molecular characterisation of GIST has revolutionized their treatment due to increasing knowledge about the high relevance of predictive molecular typing in solid tumors.

Due to their rarity and multiple subtypes, there is scant experience with sarcomas. Any effective targeted therapy depends on precise diagnosis of the tumor group using molecular markers and, increasingly, mutation testing. The necessary histopathological expertise and molecular diagnostic tools are usually only found at specialized centers. Using the Bonner GIST register as an example, the advantages of this kind of register from a diagnostic and therapeutic perspective will be discussed. Material submitted for gastrointestinal stromal tumors and other mesenchymal tumors, as well as the supervision of pathological referencing for national and international studies have made accurate diagnosis and appropriate therapy strategies ever more possible. The introduction of epidemiological as well as interdisciplinary sarcoma registers is a prerequisite for the improvement of sarcoma diagnostics and therapy.

The use of modern molecular techniques has gained importance in the diagnosis of sarcomas in recent years. Each of the analytical methods discussed here has its unique advantages and specific requirements. Cytogenetic screening methods which provide genome-wide information depend on the availability of fresh tissue. With the aid of fluorescence in situ hybridization and RT-polymerase chain reaction, specific events such as translocations in Ewing sarcoma, synovial sarcoma or alveolar rhabdomyosarcoma, as well as gene amplifications in well-differentiated and dedifferentiated liposarcoma or radiation-induced angiosarcoma and deletions in rhabdoid tumors or well-differentiated spindle cell liposarcoma can be detected in fresh and formalin fixed tissues. Molecular methods including Sanger sequencing, pyrosequencing and high resolution melting provide information about specific molecular aberrations on gene level. Here we review the most important molecular techniques currently used in sarcoma diagnosis, describe their relevance for differential diagnosis and point out specific examples.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

Inflammatory fibroid polyps (IFP) were described by Vanek 60 years ago as "submucosal granuloma with eosinophilic infiltration". IFP represent polypous proliferations of spindle cells in the submucosa and mucosa of the stomach, small bowel and colon with inflammatory infiltration. The lesions have been regarded as inflammatory and reactive. Recent data show that the spindle cells express PDGFRA, and the majority of IFP harbour activating PDGFRA mutations. Therefore, IFP represent true benign mesenchymal tumors of the gastrointestinal tract.

Inflammatory fibroid polyps (IFP) are proliferations of CD34-positive spindle cells in the submucosa and mucosa of the gastrointestinal tract with an inflammatory infiltrate. IFP occur in the stomach, small bowel, colon and esophagus. To date, etiology and pathogenesis are unclear.A total of 29 IFP originating in the stomach, small bowel and colon were examined immunohistochemically, and mutational analyses of PDGFRA exons 10, 12, 14 and 18 were conducted.Activating mutations in PDGFRA exons 12 and 18 were found in 20 cases (69%). The mutational types are related to mutations known from gastrointestinal stromal tumors (GIST). D842V was the most frequent mutation. No activating mutations were found in exons 10 and 14.The majority of IFP reveal activating PDGFRA mutations. Our data indicate that IFP are true neoplasms (true benign tumors) and not reactive lesions. In terms of pathogenesis, the relationship between PDGFRA-mutant GISTs and IFP remains to be determined.

True mixed epithelial-mesenchymal tumors of the urinary bladder are exceedingly rare, and only two vesical adenosarcomas have been reported to date. These tumors originated from bladder endometriosis, and malignant transformation of endometriosis has been described, with endometrioid and clear-cell carcinomas being the most common malignancies. We report an unusual case of a malignant mixed Müllerian tumor with heterologous rhabdomyoblastic differentiation, which originated in the urinary bladder of a postmenopausal woman. To the best of our knowledge, such a neoplasm has not yet been reported in the literature.