RESUMEN
Burkitt lymphoma (BL) is a B cell lymphoma composed of monomorphic medium-sized blastic cells with basophilic cytoplasm and a high proliferation index. BL has a characteristic immunophenotype of CD10 and BCL6 positive and BCL2 negative and harbours MYC gene rearrangements (MYCR) in >90% of the cases. Owing to its highly aggressive nature, intensified chemotherapy regimens are usually administered, requiring an exact diagnosis. Since the diagnosis usually warrants an integration of morphologic, immunophenotypic and genetic findings and because there is a morphologic overlap with the new WHO category of high-grade B cell lymphoma, not otherwise specified (HGBL, NOS) and some cases of diffuse large B cell lymphoma (DLBCL), we wanted to test the distinctiveness of the CD10+, BCL6+, BCL2- and MYCR positive immunopheno-genotype in a large cohort of >1000 DLBCL and HGBL. Only 9/982 DLBCL classified by an expert panel of haematopathologists (0.9%) displayed a single MYCR and were CD10+, BCL6+ and BCL2-. In a similar fashion, only one out of 32 HGBL, NOS (3%) displayed the "Burkitt-like" genetic/immunophenotypic constitution. The samples of non-BL showing the BL-typic immunopheno-genotype, interestingly, harboured higher copy number variations (CNV) by OncoScan analysis (mean 7.3 CNVs/sample; range: 2-13 vs. 2.4; range 0-6) and were also distinct from pleomorphic BL cases regarding their mutational spectrum by NGS analysis. This implies that the characteristic immunophenotype of BL, in concert with a single MYCR, is uncommon in these aggressive lymphomas, and that this constellation favours BL.
Asunto(s)
Biomarcadores de Tumor , Linfoma de Burkitt/genética , Linfoma de Burkitt/inmunología , Variaciones en el Número de Copia de ADN , Dosificación de Gen , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Mutación , Antígenos CD20/análisis , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Linfoma de Burkitt/patología , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/patología , Clasificación del Tumor , Neprilisina/análisis , Fenotipo , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6/análisis , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-myc/genética , Estudios RetrospectivosRESUMEN
Mixed adenoneuroendocrine carcinomas are rare and usually occur in the gastrointestinal tract. Although there have been several investigations regarding their developmental mechanism, the molecular origin of these tumors remains unclear. In this article, we present an exceedingly rare case of a mixed tumor of the urinary bladder with an adenocarcinomatous and a neuroendocrine component and a concomitant urothelial carcinoma in situ (CIS). Due to this extraordinary combination of tumor components, our goal was to extensively examine the 3 tumor components with regard to a representable common origin. Therefore, a comprehensive immunohistochemical analysis and review of the literature was performed. Besides expected outcome, our examination also revealed surprising staining results. Urothelial CIS, like the adenocarcinomatous component, showed strong staining for CDX2. In addition, parts of the adenocarcinoma were positive for synaptophysin like the neuroendocrine tumor component. All 3 components showed a significant overexpression of p53 and a moderate to strong membranous and cytoplasmatic staining for ß-catenin. To our knowledge, we are the first to describe a case of a mixed tumor of the urinary bladder with an adenocarcinomatous and a neuroendocrine component and a concomitant CIS. The components share striking molecular features that argue for a common clonal origin and a development of the invasive tumor via the urothelial precursor lesion.
