Diagnosis of Burkitt's lymphoma in due time: a practical approach

Aims: The quick diagnosis of Burkitt's lymphoma (BL) and its clear-cut differentiation from diffuse large B-cell lymphoma (DLBCL) is of great clinical importance since treatment for these two disease entities differ markedly and should promptly be initiated in BL. However, these two tumours are difficult to distinguish using the current WHO classification, particularly in regard to BL variants, i.e., BL with plasmacytoid differentiation and atypical Burkitt's/Burkitt's-like lymphomas. Methods: We studied 39 cases of highly proliferative blastic B-cell lymphoma (HPBCL) to establish a practical differential-diagnostic algorithm. Characteristics set for BL were a typical morphology, a mature B-cell phenotype of CD10+, Bcl-6+ and Bcl-2- tumour cells, a proliferation rate of >95%, and the presence of C-MYC rearrangements in the absence of t(14;18)(q32;q21). All cases were selectively negative for cyclin D-1, CD5, CD23, LMP-EBV, CD34 and TdT, and there were no cases of endemic or immunodeficiency-associated Burkitt's lymphoma. Results: Altogether the set BL characteristics were found in only 5/39 cases (12.8%), whereas the majority of tumours revealed mosaic features (87.2%). In a second attempt, we followed a pragmatic stepwise approach for a classification algorithm that includes the assessment of C-MYC status to stratify HPBCL into four predefined diagnostic categories (DC), namely DC I (5/39, 12.8%): "classical BL", corresponding to the classical variant of sporadic BL in the WHO classification; DC II (11/39, 28.2%): "atypical BL", corresponding to the atypical Burkitt's/Burkitt's-like variants of sporadic BL in the WHO classification; DC III (9/39, 23.1%): "C-MYC+ DLBCL"; and DC IV (14/39, 35.9%): "C-MYC- HPBCL". Conclusion: This proposal may serve as a robust and objective operational basis for therapeutic decisions for HPBCL within one week and is applicable to be evaluated for its prognostic relevance in prospective clinical trials

Seltene Variante eines low-grade Osteosarkoms des Sinus sphenoidalis

Einleitung: Osteosarkome im HNO-Bereich sind eine Seltenheit. Von 2-3 Fällen pro 1 Mio. Einwohner pro Jahr sind weniger als 7% im kraniofazialen Bereich lokalisiert. Ein Auftreten im Bereich der Schädelbasis ist eine Rarität. In unserer Poliklinik stellte sich eine Patientin mit gelegentlicher Epistaxis nasi links als einzigem Symptom vor. Methoden: Endonasal zeigte sich eine kugelige Raumforderung an der Concha nasalis media links. Im MRT mit CISS-Sequenz war diese tumorsuspekt im Sinne eines Plattenepithelcarcinoms, da sie das Os sphenoidale, den linken Processus pterygoideus und die Seitenwand des Sinus sphenoidalis links destruierte. Da der Prozess kaum Größenprogress zeigte, wurde von einem niedrig malignen Tumor ausgegangen. Ergebnisse: Eine initiale Biopsie ergab einen riesenzellhaltigen, myxoiden Tumor ohne Malignität. Bei klinisch suspektem Bild mit ossärer Destruktion wurde das Gewebe abgetragen, histologisch zeigte es einen Chondromyxoidfibrom-artigen Tumor mit irregulärer Osteoidbildung. In der Integration mit der Bildgebung bei lokaler Aggressivität wurde der Tumor als seltene Variante eines niedrig malignen Chondromyxoidfibrom-artigen Osteosarkoms eingestuft. Nach Ausschluss von Metastasen erfolgte gemäß Beschluss der interdisziplinären Tumorkonferenz die endonasale Nachresektion in der Keilbeinhöhle links (R0). Die Patientin war in der regelmäßigen Nachsorge beschwerdefrei. Schlussfolgerungen: Da kraniofaziale Osteosarkome extrem seltene Tumore sind, gibt es kein standardisiertes therapeutisches Vorgehen. Literaturdaten legen nahe, dass diese grundsätzlich eine benignere Biologie als konventionelle Osteosarkome haben. Ein möglicher Nutzen für das krankheitsfreie und das Gesamtüberleben durch eine adjuvante Radiatio oder Chemotherapie ist nicht gesichert.Der Erstautor gibt keinen Interessenkonflikt an

LDHA in neuroblastoma is associated with poor outcome and its depletion decreases neuroblastoma growth independent of aerobic glycolysis

© 2018 American Association for Cancer Research. Purpose: To investigate whether lactate dehydrogenase A (LDHA), an important component of the LDH tetramer crucial for aerobic glycolysis, is associated with patient outcome and constitutes a therapeutic target in neuroblastoma (NB). Experimental Design: Expression of LDHA mRNA and protein was determined in 709 and 110 NB patient samples, respectively, and correlated with survival and risk factors. LDHA and LDHB were depleted in human NB cell lines by CRISPR/Cas9 and shRNA, respectively, and aerobic glycolysis, clonogenicity, and tumorigenicity were determined. Expression of LDHA in relation to MYCN was measured in NB cell lines and in the TH-MYCN NB mouse model. Results: Expression of LDHA, both on the mRNA and the protein level, was significantly and independently associated with decreased patient survival. Predominant cytoplasmic localization of LDHA protein was associated with poor outcome. Amplification and expression of MYCN did not correlate with expression of LDHA in NB cell lines or TH-MYCN mice, respectively. Knockout of LDHA inhibited clonogenicity, tumorigenicity, and tumor growth without abolishing LDH activity or significantly decreasing aerobic glycolysis. Concomitant depletion of LDHA and the isoform LDHB ablated clonogenicity while not abrogating LDH activity or decreasing aerobic glycolysis. The isoform LDHC was not expressed. Conclusions: High expression of LDHA is independently associated with outcome of NB, and NB cells can be inhibited by depletion of LDHA or LDHB. This inhibition appears to be unrelated to LDH activity and aerobic glycolysis. Thus, investigations of inhibitory mechanisms beyond attenuation of aerobic glycolysis are warranted, both in NB and normal cells

Significance of complete 1p/19q co-deletion, IDH1 mutation and MGMT promoter methylation in gliomas: use with caution

Item does not contain fulltextThe histopathological diagnosis of diffuse gliomas often lacks the precision that is needed for tailored treatment of individual patients. Assessment of the molecular aberrations will probably allow more robust and prognostically relevant classification of these tumors. Markers that have gained a lot of interest in this respect are co-deletion of complete chromosome arms 1p and 19q, (hyper)methylation of the MGMT promoter and IDH1 mutations. The aim of this study was to assess the prognostic significance of complete 1p/19q co-deletion, MGMT promoter methylation and IDH1 mutations in patients suffering from diffuse gliomas. The presence of these molecular aberrations was investigated in a series of 561 diffuse astrocytic and oligodendroglial tumors (low grade n=110, anaplastic n=118 and glioblastoma n=333) and correlated with age at diagnosis and overall survival. Complete 1p/19q co-deletion, MGMT promoter methylation and/or IDH1 mutation generally signified a better prognosis for patients with a diffuse glioma including glioblastoma. However, in all 10 patients with a histopathological diagnosis of glioblastoma included in this study complete 1p/19q co-deletion was not associated with improved survival. Furthermore, in glioblastoma patients >50 years of age the favorable prognostic significance of IDH1 mutation and MGMT promoter methylation was absent. In conclusion, molecular diagnostics is a powerful tool to obtain prognostically relevant information for glioma patients. However, for individual patients the molecular information should be interpreted with caution and weighed in the context of parameters such as age and histopathological diagnosis