Introducing Mediterranean Journal of Hematology and Infectious Diseases

Mediterranean Journal of Hematology and Infectious Diseases (MJHID) is a new open access, peer-reviewed, online journal, which encompasses different aspects of clinical and translational research providing an insight into the relationship between acute and chronic infections and hematological diseases. MJHID will be a topical journal on subjects of current importance in clinical haematology and infectious diseases. Every issue should have, beside the editor in chief, a guest editor. Both editor in chief and guest editor provide to invite experts in the selected topic to performe a complete update of the arguments readily available for practising phisicians. The journal will have also a section devoted to original papers, case reports and letters to editor and Editorial comment mostly focusing on the arguments treated in the previous topical issues

Combined Modality Treatment Including Methotrexate-Based Chemotherapy For Primary CENTRAL Nervous System Lymphoma: A Single Institution Experience

Chemotherapy including high-dose methotrexate (HD-MTX), with or without radiotherapy, is standard treatment for primary central nervous system lymphoma (PCNSL). It remains controversial whether addition of other drugs will add to therapeutic efficacy. We report here on 41 patients with PCNSL treated using a combined treatment modality, including HD-MTX (3.5 g/m2 for 2 cycles) prior to whole brain radiotherapy (WBRT). In 22 patients, the chemotherapy was intensified by adding high-dose cytosine arabinoside (HD-AraC) (2g/m2 for 4 doses for 2 cycles). Complete remission at the end of the combined treatment was obtained in 23 of 34 assessable patients (67%), and the predicted 5-year overall and disease-free survival rates were 24% and 46%, respectively, without differences between treatment groups. The addition of HD-AraC was complicated by severe infections in 17/22 (77%) patients, resulting in 3 toxic deaths. Our study indicates that addition of HD-AraC may not improve clinical outcome in PCNSL, while it increases toxicity. More targeted and less toxic therapies are warranted

Epstein-Barr Virus (EBV)-Associated Haemophagocytic Syndrome

We describe the case of a 17- year old female who developed fatal haemophagocytic syndrome (HPS) one month following acute infection caused by Epstein-Barr virus (EBV). Despite initiation of treatment and reduction of EBV load, laboratory signs of HPS as severe cytopenia, hypofibrinogenemia, hyperferritinemia and hypertriglyceridemia persisted, and the patient died of multiorgan failure. HPS is a rare, but life-threatening complication of EBV infection

Humoral immune response after anti-SARS-CoV-2 vaccine “booster” dose in patients with monoclonal gammopathy of undetermined significance (MGUS)

Not Applicable

Relevance of rosette patterns in variants of papillary thyroid carcinoma

IntroductionThe detection of rosette‐like clusters (RLC) of follicular cells in thyroid carcinoma has been reported mostly in the columnar cell variant of papillary thyroid carcinoma (PTC). Despite the fact that diagnosing variants of PTC is no longer encouraged by The Bethesda System for Reporting Thyroid Cytopathology, the identification of cytomorphological features such as RLC linked with these tumours might help reduce possible misinterpretation in thyroid fine needle aspiration (FNA) cytology. We accordingly investigated the potential correlation of architectural patterns including RLC with PTC variants.MethodsWe analysed 225 thyroid FNA cytology cases diagnosed as suspicious for malignancy (SFM) and positive for malignancy (M) over a 1‐year time where all samples had corresponding histology. We also included 150 benign lesions from the same period. The presence of RLC vs similar appearing solid clusters, papillary structures and microfollicles were evaluated. We also performed immunocytochemistry and molecular testing for BRAFV600E.ResultsWe included 100 (44.4%) SFM favouring PTC and 125 (55.6%) M cases with cyto‐histological correlation. On histology, all SFM and M cases showed malignancy including 140 (62.2%) classic PTC and 85 (37.8%) PTC variants. The cytomorphological patterns in all FNA samples included solid (74%), papillary (89%), microfollicular (70%), and pseudo‐RLC morphology (25.7%). We identified only pseudo‐RLC in 33 FNA specimens from PTC variant cases that included tall cell variant (42.4%), hobnail variant (21.2%) and miscellaneous variants (36.3%) of PTC. No definitive RLC were detected in our series. Immunocytochemistry and BRAFV600E were not specifically linked with an RLC pattern.ConclusionsThese findings demonstrate that in our dataset the architectural pattern of RLC was not recognised within PTC variants. However, we did identify a pseudo‐RLC pattern that was observed in association with tall cell variant and hobnail variant cases of PTC.The findings discussed in the present study demonstrate that certain architectural patterns such as rosette‐like clusters (RLC) may be recognized more frequently in specific PTC variants that may be helpful in reducing their misinterpretation. In the series presented, RLCs were observed mostly in association with tall cell and hobnail variants of PTC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163372/2/cyt12885_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163372/1/cyt12885.pd

Levetiracetam enhances the temozolomide effect on glioblastoma stem cell proliferation and apoptosis

Abstract BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor in which cancer cells with stem cell-like features, called cancer stem cells (CSCs), were identified. Two CSC populations have been previously identified in GBM, one derived from the GBM area called enhanced lesion (GCSCs) and the other one from the brain area adjacent to the tumor margin (PCSCs) that greatly differ in their growth properties and tumor-initiating ability. To date the most effective chemotherapy to treat GBM is represented by alkylating agents such as temozolomide (TMZ), whose activity can be regulated by histone deacetylases (HDACs) inhibitors through the modulation of O6-methylguanine-DNA methyltransferase (MGMT) expression. Levetiracetam (LEV), a relatively new antiepileptic drug, modulates HDAC levels ultimately silencing MGMT, thus increasing TMZ effectiveness. However, an improvement in the therapeutic efficacy of TMZ is needed. METHODS: Cell proliferation was investigated by BrdU cell proliferation assay and by Western Blot analysis of PCNA expression. Apoptosis was evaluated by Western Blot and Immunofluorescence analysis of the cleaved Caspase-3 expression. MGMT and HDAC4 expression was analyzed by Western Blotting and Immunofluorescence. Statistical analysis was performed using the Student's t test and Mann-Whitney test. RESULTS: Here we evaluated the effect of TMZ on the proliferation rate of the IDH-wildtype GCSCs and PCSCs derived from six patients, in comparison with the effects of other drugs such as etoposide, irinotecan and carboplatin. Our results demonstrated that TMZ was less effective compared to the other agents; hence, we verified the possibility to increase the effect of TMZ by combining it with LEV. Here we show that LEV enhances the effect of TMZ on GCSCs proliferation (being less effective on PCSCs) by decreasing MGMT expression, promoting HDAC4 nuclear translocation and activating apoptotic pathway. CONCLUSIONS: Although further studies are needed to determine the exact mechanism by which LEV makes GBM stem cells more sensitive to TMZ, these results suggest that the clinical therapeutic efficacy of TMZ in GBM might be enhanced by the combined treatment with LEV

Soft tissue non-Hodgkin lymphoma of shoulder in a HIV patient: a report of a case and review of the literature

The risk of developing lymphoma is greatly increased in HIV infection. Musculoskeletal manifestations of the human immunodeficiency virus (HIV) are common and are sometimes the initial presentation of the disease. Muscle, bone, and joints are involved by septic arthritis, myopathies and neoplasms. HIV-related neoplastic processes that affect the musculoskeletal system include Kaposi's sarcoma and non-Hodgkin's lymphoma, the latter being mainly localized at lower extremities, spine and skull

Glioblastoma endothelium drives bevacizumab-induced infiltrative growth via modulation of PLXDC1

Bevacizumab, a VEGF-targeting monoclonal antibody, may trigger an infiltrative growth pattern in glioblastoma. We investigated this pattern using both a human specimen and rat models. In the human specimen, a substantial fraction of infiltrating tumor cells were located along perivascular spaces in close relationship with endothelial cells. Brain xenografts of U87MG cells treated with bevacizumab were smaller than controls (p = 0.0055; Student t-test), however, bands of tumor cells spread through the brain farther than controls (p < 0.001; Student t-test). Infiltrating tumor Cells exhibited tropism for vascular structures and propensity to form tubules and niches with endothelial cells. Molecularly, bevacizumab triggered an epithelial to mesenchymal transition with over-expression of the receptor Plexin Domain Containing 1 (PLXDC1). These results were validated using brain xenografts of patient-derived glioma stem-like cells. Enforced expression of PLXDC1 in U87MG cells promoted brain infiltration along perivascular spaces. Importantly, PLXDC1 inhibition prevented perivascular infiltration and significantly increased the survival of bevacizumab-treated rats. Our study indicates that bevacizumab-induced brain infiltration is driven by vascular endothelium and depends on PLXDC1 activation of tumor cells

Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction

Life expectancy of patients affected by glioblastoma multiforme is extremely low. The therapeutic use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed to treat this disease based on its ability to kill glioma cell lines in vitro and in vivo. Here, we show that, differently from glioma cell lines, glioblastoma multiforme tumors were resistant to TRAIL stimulation because they expressed low levels of caspase-8 and high levels of the death receptor inhibitor PED/PEA-15. Inhibition of methyltransferases by decitabine resulted in considerable up-regulation of TRAIL receptor-1 and caspase-8, down-regulation of PED/PEA-15, inhibition of cell growth, and sensitization of primary glioblastoma cells to TRAIL-induced apoptosis. Exogenous caspase-8 expression was the main event able to restore TRAIL sensitivity in primary glioblastoma cells. The antitumor activity of decitabine and TRAIL was confirmed in vivo in a mouse model of glioblastoma multiforme. Evaluation of tumor size, apoptosis, and caspase activation in nude mouse glioblastoma multiforme xenografts showed dramatic synergy of decitabine and TRAIL in the treatment of glioblastoma, whereas the single agents were scarcely effective in terms of reduction of tumor mass, apoptosis induction, and caspase activation. Thus, the combination of TRAIL and demethylating agents may provide a key tool to overcome glioblastoma resistance to therapeutic treatments. ©2005 American Association for Cancer Research