Background:Chronic lymphocytic leukemia (CLL) is a genetically heterogeneous disease in which chromosomal and genomic aberrations are found in more than 80% of patients. The complex karyotype (CK) in CLL is defined as the presence of >3 structural or numerical aberrations in the same clone of CLL malignant cell.

No abstract

Introduction. Primary central nervous system lymphoma is a rare entity mostly presenting with non-GCB diffuse large B-cell lymphoma, being confined to the brain, spinal cord, meninges, and eyes. Diagnosis. The diagnosis is frequently established by stereotactic or open the brain biopsy, but in some cases with isolated leptomeningeal involvement, the only way is to identify atypical/monoclonal lymphocytes in cerebrospinal fluid. By workup, we aim to define the extent of disease in the central nervous system and to exclude systemic involvement. Treatment. Treatment is tailored according to the patient?s age, fitness, vital organ function, comorbidities, and available therapy. The backbone of induction treatment is high-dose methotrexate, usually within polychemotherapy. Consolidation phase is a matter of debate between two approaches: 1. high dose chemotherapy with autologous stem cell transplantation, which appears to be the preferable option for young fit patients, and 2. whole brain radiotherapy, preserved for transplant-ineligible ones. Whole brain radiotherapy has been raising concerns because of frequent cognitive impairment, which has been significantly diminished by reducing the irradiation dose. Despite a comprehensive treatment approach, many patients relapse, and since the prognosis of relapsed/refractory disease is devastating, there is a sense of urgency for novel treatment strategies. Several targeted agents and immunomodulatory drugs have been investigated in the settings of both relapsed/refractory and initial therapy, but with limited success. Ibrutinib monotherapy can induce durable remissions in the first line, but in relapse/refractory settings, the results are controversial. Conclusion. Adequate patient selection and new prospective trials should improve survival and preserve the patient?s neurological status.

Diffuse large B-cell lymphoma, not otherwise specified, is the most common type of non-Hodgkin lymphoma worldwide, accounting for 30-40% of all lymphomas. It represents a collection of morphologically, genetically and clinically different diseases. Therefore, it can be subdivided into morphological variants, phenotypic subtypes, and molecular or genetic categories. More recently, diffuse large B-cell lymphoma has witnessed advances in molecular profiling and treatment of patients with refractory and relapsed disease. The optimal management requires integrated morphological and immunophenotypic analysis of cell and tissue, along with chromosome and molecular analyses. Double-expressor lymphoma, defined as overexpression of MYC and BCL2 proteins not related to underlying chromosomal rearrangements, accounts for 20% to 30% of Diffuse large B-cell lymphoma cases. In the latest, 5th edition of the World Health Organization Classification of Hematolymphoid Tumors-lymphoid neoplasms, double-expressor lymphoma is not defined as an independent entity, but it has been proven to be a marker for poor outcome in diffuse large B-cell lymphoma. However, the degree of adverse prognosis is lesser than in double-hit lymphomas. Although double-expressor lymphoma feature is confirmed as adverse prognostic marker for diffuse large B-cell lymphoma patients, currently no sufficient data is available to support treatment intensification over standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone regimen. Well-designed randomized clinical trials are mandatory in order to properly respond to this substantial clinical dispute.

The long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) dysregulated expression and prognostic significance have been reported in a variety of cancers, including hematological malignancies, but have been poorly investigated in chronic lymphocytic leukemia (CLL). Acting through regulation of gene expression at transcriptional and post-transcriptional level, lncRNA MALAT1 is involved in many cellular processes such as proliferation, apoptosis, migration and drug resistance. However, its role as either an oncogene or a tumor-supressor is still controversial, and clearly tumor type-dependent.