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Cytokines possess discrepant effects on tumour cells varying from anti- to proapoptotic activities. We recently reported that testicular germ cell tumours (TGCT) express a functional form of the proinflammatory cytokine interferon-gamma (IFNgamma). The present study asked whether TGCT-derived IFNgamma influences survival or death of neoplastic germ cells. Analysis of TGCT cell lines demonstrated that they expressed and secreted IFNgamma, but were resistant to the endogenous IFNgamma since neutralisation of IFNgamma by a specific blocking antibody had no influence on the proliferation and/or the degree of apoptosis of tumour cells. To study mechanisms providing tumour resistance to endogenous IFNgamma, we analysed primary TGCT and two human TGCT cell lines (NTERA and NCCIT) for the expression of IFNgamma receptor and for the level of phosphorylation of the signal transducer and activator of transcription (STAT)-1. In situ hybridisation, immunocytochemistry, Western blot analysis and flow cytometry indicated that primary TGCT as well as NCCIT and NTERA cell lines expressed the heterodimeric cell surface IFNgamma receptor which consists of both 90-kDa alpha- and the 85-kDa beta-chains. However, the downstream transcription factor STAT-1 was not phosphorylated constitutively, indicating that STAT-1 is not activated by the endogenous IFNgamma. Upon application of recombinant human IFNgamma in excess, however, STAT-1 was phosphorylated and the interferon regulatory factor-1 (IRF-1) was induced, suggesting that both IFNgammaR and STAT-1 are functionally intact in TGCT. Altogether our results suggest that despite secreting biologically active IFNgamma, the concentration of the endogenous IFNgamma is too low to stimulate the IFNgammaR/STAT signalling pathway in TGCT in an autocrine and/or paracrine manner. [ABSTRACT FROM AUTHOR]

Gout tophi are characterised by foreign body granulomas consisting of mono- and multinucleated macrophages surrounding deposits of monosodium urate microcrystals. After primary formation, granulomas grow associated with degradation of the extracellular matrix. Based on this background, we have sought (1) to investigate whether during granuloma's growth new macrophages are recruited into the tophi, (2) to find in situ evidence for macrophages' active role in matrix degradation and (3) to examine whether shrunk cells seen within gout tophi are apoptotic. Immunohistochemistry showed that perivascular localised mononuclear cells are CD68+, S100A8+, S100A9+, 25F9-, representing freshly migrated monocytes/macrophages. In contrast, almost all CD68+ mono- and multinucleated cells arranged within granulomas were S100A8-, S100A9-, 25F9+, representing mature (non-migrating) macrophages. Serial sections revealed that macrophages co-express tumour necrosis factor (TNF)-alpha and matrix metalloproteinases (MMPs) 2 and 9. In situ end-labelling of fragmented DNA demonstrated that CD68+ macrophages undergo apoptosis within gout tophi. Our data show that macrophages are continuously recruited into the gout tophi. These macrophages co-produce the proinflammatory cytokine TNF-alpha and two TNF-alpha inducible lytic enzymes, MMP-2 and MMP-9, suggesting that TNF-alpha may induce MMP production followed by matrix degradation within foreign body granulomas. In parallel, macrophages undergo apoptosis, a phenomenon that may restrict the destructive potential of inflammatory macrophages. [ABSTRACT FROM AUTHOR]

Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335

Abstract Background Pulmonary carcinosarcoma is a biphasic tumour with an unfavourable prognosis. The differential diagnosis includes pulmonary blastoma and is often challenging. Case presentation We here describe a case of blastomatoid pulmonary carcinosarcoma in a 58-year-old patient, who underwent surgical resection. Histopathological examination revealed immature glandular epithelium resembling high-grade fetal adenocarcinoma expressing epithelial markers and membranous beta-catenin, and blastomatoid spindle cells with partial rhabdomyosarcoma-like differentiation. Both elements expressed p53, MDM2, and cyclin-dependent kinase 4 (CDK4), but not thyroid-transcription factor 1 (TTF-1). Mutation analysis of KRAS, EGFR, and beta-catenin revealed no mutations. Comparative genomic hybridization detected +1q, +6p, +6q24qter, +8q, +11q12q14, +11q23qter, +12q12q21, +12q24qter, +17q, +20q, -5q14q23, -9p13pter, -13q21q21, and amplifications at 12q14q21, 15q24qter, 20q11q12. Conclusion The observed molecular and cytogenetic findings may provide additional tools for the differential diagnosis of biphasic pulmonary neoplasms. Furthermore, TP53, MDM2, CDK4, and PTPN1 may be involved in tumourigenesis.