Heterogeneity among diffuse large B-cell lymphoma: new entities in WHO classification, a first step in personalized therapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma, being part of mature B-cell neoplasm according to the 2016 World Health Organization (WHO) Classification of lymphoid tumors. This type of non-Hodgkin's lymphoma (NHL) can develop in the lymph nodes in most cases, or in extranodal sites (the most frequent involvement being the digestive tract, but also the thyroid, central nervous system, testes, etc.). Despite being an aggressive lymphoma, DLBCL benefits of potentially curable therapy. The addition of monoclonal antibodies to standard chemotherapy in the therapeutic approach of DLBCL leads to some net superior results to those obtained by chemotherapy alone. Despite the fact that the aggressive therapy is very efficient, 10% of patients remain refractory to it, 30-40% of them after obtaining a complete response (CR) will relapse, and 90% of refractory DLBCL have poor survival rates. Based on these findings, an explanation for the differences in clinical outcome and therapy response was attempted. The important progresses made in the understanding of DLBCL heterogeneity were based on molecular biology studies and showed differences in chromosomal alterations and in signaling pathways activation. These findings have paved the way for new therapeutic targets in order to improve therapy response. The large heterogeneity of DLBCL is acknowledged by the 2016 WHO Classification of lymphoid neoplasms, with 17 DLBCL subtypes, some of them as new varieties, compared to the 2008 Classification, and others introduced as provisional entities.

Correlations between clinical and placental histopathological and immunohistochemical features in women with and without hereditary thrombophilia.

AIM: The primary objective of this study was to correlate hereditary thrombophilia (high- or low-risk) with specific placental histopathological (HP) and∕or immunohistochemical (IHC) changes, for confirming∕ruling out a possible linkage between these two biological parameters. PATIENTS, MATERIALS AND METHODS: We present a 3-year prospective study conducted between 2016 and 2019 that enrolled 90 women registered in two Clinics of Obstetrics and Gynecology in Craiova, Romania, with personal thrombotic and/or pathological obstetrical history. The HP and IHC analysis of the placenta was performed using monoclonal anti-cluster of differentiation 34 (CD34) antibody, anti-hypoxia-inducible factor-1 alpha (HIF-1α) and anti-endothelial nitric oxide synthase (eNOS) antibody. RESULTS: There was a high incidence of all thrombophilia (TPh) mutations in Caucasian women with thrombotic and obstetrical complications. Among them, both HP and IHC examination revealed significant changes. These were more severe in the placentas of patients with homozygous Factor V Leiden (FVL) gene mutation and double heterozygous FVL∕PII gene mutation. Multiple placental infarctions with massive fibrinoid necrosis and an increase in syncytial knots are common findings. In the same group, we found by means of IHC examination - intense positive HIF-1α and eNOS immunoexpression, and low positive CD34 expression, especially in fibrinoid necrosis and thrombosis areas. We found no correlation between clinical, HP and IHC changes in patients with low-risk TPh or without TPh. CONCLUSIONS: Among patients with obstetric and thrombotic complications, there is a high prevalence of TPh. It appears that hypercoagulability reported in high-risk thrombophilia (HR-TPh) has major effects on placental tissue (fibrinoid necrosis, multiple thromboses, hypoxia and oxidative stress). Significant placental changes were found predominantly in women with HR-TPh. Strategies for TPh screening based on HP/IHC pattern would be, most probably, more cost-effective compared with the extended TPh testing offered in large populations. This way, a smaller number of patients will be tested and in this group a higher proportion of patients will be found as having HR-TPh mutations.

Primary diffuse large B-cell lymphoma of the testis.

Non-Hodgkin's lymphomas are chronic lymphoproliferative disorders, with nodal or extranodal onset, most of which being digestive tract lymphomas. Testicular primitive lymphoma generally affects men; it is rare but aggressive type of lymphoma. We present the case of the only patient diagnosed with testicular lymphoma in Hematology Clinic of Craiova, Romania, in the last 20 years. Histopathological and immunohistochemical exams confirmed the diagnosis of diffuse large B-cell lymphoma, and the stage was IIB. According to International Prognostic Index (IPI) score, the patient was classified as low risk. He received combined treatment consisting of surgery, chemotherapy, central nervous system prophylaxis and radiotherapy. The outcome was very good, the patient achieving complete remission. After 36 months, he is still in complete remission with clinical and biological evaluation performed every three month, and computerized tomography once a year.

The prognostic role of Bcl-2, Ki67, c-MYC and p53 in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphoid malignancies, which counts for more than a third of non-Hodgkin's lymphoma cases. The aim of the current study is to evaluate the prognostic role of several immunohistochemical (IHC) markers involved in the pathological process of DLBCL. This is a retrospective analysis of the 97 de novo DLBCL patients admitted between January 2007 and December 2016 in the Department of Hematology, "Filantropia" Municipal Hospital, Craiova, Romania. The expression of Bcl-2, Ki67, c-MYC and p53 was assessed by immunohistochemistry. A significant level of association was observed between high prognostic index values and Bcl-2, Ki67, c-MYC and p53 positive cases. Moreover, overall survival and disease-free survival were higher in patients with negative expression for these markers. Bcl-2, Ki67, c-MYC and p53 could make important diagnostic and therapeutic targets; therefore, their routine assessment should be mandatory.