FOXO1 is a TXN- and p300-dependent sensor and effector of oxidative stress in diffuse large B-cell lymphomas characterized by increased oxidative metabolism.

Molecular profiling has led to identification of subtypes of diffuse large B-cell lymphomas (DLBCLs) differing in terms of oncogenic signaling and metabolic programs. The OxPhos-DLBCL subtype is characterized by enhanced mitochondrial oxidative phosphorylation. As increased oxidative metabolism leads to overproduction of potentially toxic reactive oxygen species (ROS), we sought to identify mechanisms responsible for adaptation of OxPhos cells to these conditions. Herein, we describe a mechanism involving the FOXO1-TXN-p300 redox-dependent circuit protecting OxPhos-DLBCL cells from ROS toxicity. We identify a BCL6-dependent transcriptional mechanism leading to relative TXN overexpression in OxPhos cells. We found that OxPhos cells lacking TXN were uniformly more sensitive to ROS and doxorubicin than control cells. Consistent with this, the overall survival of patients with high TXN mRNA expression, treated with doxorubicin-containing regimens, is significantly shorter than of those with low TXN mRNA expression. TXN overexpression curtails p300-mediated FOXO1 acetylation and its nuclear translocation in response to oxidative stress, thus attenuating FOXO1 transcriptional activity toward genes involved in apoptosis and cell cycle inhibition. We also demonstrate that FOXO1 knockdown in cells with silenced TXN expression markedly reduces ROS-induced apoptosis, indicating that FOXO1 is the major sensor and effector of oxidative stress in OxPhos-DLBCLs. These data highlight dynamic, context-dependent modulation of FOXO1 tumor-suppressor functions via acetylation and reveal potentially targetable vulnerabilities in these DLBCLs.

Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally advanced myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The use of preoperative hypofractionated radiotherapy 5 × 5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced STS showed a good local control rate. The main objective of our work was to assess the efficacy of hypofractionated radiotherapy in preoperative setting in patients with locally advanced primary MLPS. METHODS: From February 1999 to March 2014, 32 patients with primary MLPS were treated with preoperative hypofractionated radiotherapy for 5 consecutive days followed by immediate surgery (median dose 5 × 5 Gy). Median size of the tumor 10.5 cm. In one patient the tumor was located on the upper extremity, the other (31 patients) had their tumors located on the lower extremity. RESULTS: In 90% patients histologically negative surgical margins (R0) were obtained. 34% patients had distant recurrence of the disease, local recurrence was found in 9.3% of the patients. 5-year local relapse-free survival rate was 90% and overall survival was 68%. In all analyzed surgical specimens the radiotherapy response features (hyalinization, fibrosis, paucicelularity, hemorrhages, dilatation of vessels) were detected. We have not found statistically significant differences in terms of OS and LRFS for RCC component, tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy specimens significantly higher positivity of TP53 expression was detected as compared to primary biopsies. CONCLUSION: Combined therapy with hypofractionated radiotherapy followed by immediate surgery seems to be effective therapy in MLPS demonstrating good local control and pathological response to therapy.

Distribution of lymphomas in Poland according to World Health Organization classification: analysis of 11718 cases from National Histopathological Lymphoma Register project - the Polish Lymphoma Research Group study.

Most national lymphoma registers rely on broad classifications which include Hodgkin and non-Hodgkin lymphomas (NHL), multiple myeloma and leukaemia. In Poland the National Histopathological Lymphoma Register project (NHLR) was implemented by hematopathologists in accordance with the 2008 WHO classification into haematopoietic and lymphoid tissues. We present the NHLR data and compare lymphoma distribution in Poland, Europe, as well as in North Central and South America. Records of 11718 patients diagnosed in 24 pathology departments from all over the country were retrieved and reclassified into indolent and aggressive lymphomas according to the 2008 revised WHO classification system. DLBCL (32.9%; 2587), CLL/SLL (31.84%; 2504) and MCL (9.04%; 711) were the three most frequent NHL. The ratio of indolent to aggressive NHL was 1.72; 63.25% (4809) to 36.25% (2794) of cases respectively. Multiple myeloma was less frequent as compared to the data from population-based national cancer register (13.32% vs. 28.94%). Major differences between NHLR and European and American data on NHL subtypes concered: higher incidence of aggressive B-cell lymphomas including DLBCL, lower FL and MALT incidence rate. The percentage of unclassified lymphomas in the study was minimal due to participation of hematopathologists.

Vascular patterns in superficial lymphomatous lymph nodes: A detailed sonographic analysis().

PURPOSE: To identify the vascular patterns found in superficial lymph nodes with histologically confirmed lymphomatous involvement and to determine their value in the sonographic diagnosis of lymphadenopathy. METHODS AND MATERIALS: The study involved the prospective classification of vascular patterns observed during power Doppler and/or color Doppler studies of superficial lymph nodes scheduled for resection. Forty patients (27 men and 13 women, aged 22-84 years; mean age: 58 years) with pathologically proven lymphoma were selected for this study (26 cervical, 13 axillary and 1 inguinal). RESULTS: A longitudinal vessel with or without branches (pattern I) was found in 14 lymphomatous nodes. Six contained short vessel segments distributed in the hilum area or centrally (pattern II), five had multiple vessels, partially branching, entering the node in a few rows from its longitudinal side (pattern III), seven presented multiple vessels that branched irregularly or chaotically with avascular areas (pattern IV), and eight had a peripheral vessel distribution (pattern V). Therefore, 50% of the lymphomatous nodes had vascular patterns regarded as characteristic of reactive lymph nodes (patterns I and II), and 37.5% had patterns normally described in lymph nodes with metastatic involvement (patterns IV and V); other lymphomatous lymph nodes had ambiguous vascular patterns that have not been previously classified (pattern III). CONCLUSION: The angioarchitecture of superficial lymphomatous lymph nodes varies widely and is difficult to classify. It may resemble that reported in normal or reactive lymph nodes or patterns that are associated with metastases. The finding of a normal or benign vascular pattern in a lymph node with suspected lymphomatous involvement does not eliminate the need for a diagnostic biopsy.

3D ultrasound examination of the superficial lymph nodes--does it provide additional information?

PURPOSE: To compare the appearance of superficial lymph nodes on standard two-dimensional (2D) ultrasound examination and on three-dimensional (3D) ultrasound examination. MATERIALS AND METHODS: Fifty two lymph nodes (35 cervical, 16 axillary, 1 inguinal) in 52 patients were examined with ultrasound in 3D mode. In standard 2D grey-scale examination and on a C-plane of 3D mode (parallel to the surface of the probe), the shape of a lymph node and its hilum were assessed. Final histopathological diagnoses included 36 lymphomas, 11 reactive or inflammatory lymph nodes, 3 metastases and 2 plasmocytoma infiltrations. RESULTS: The appearance of hilums and lymph nodes as a whole changed on a C-plane of 3D mode (as compared with 2D presentation) in 28 % and 37 %, respectively. The differences in lymph node shape on 2D and 3D ultrasound were apparent in a comparable percentage of reactive lymph nodes (45 %) and lymphomatous lymph nodes (39 %). The differences in lymph node hilum shape on 2D and 3D ultrasound applied to 56 % of reactive lymph nodes and 20 % of lymphomatous lymph nodes. CONCLUSION: Three-dimensional imaging on a C-plane (parallel to the surface of the probe) may supply the examiner with different information concerning the shape of the lymph node and its hilum in comparison to standard 2D ultrasound. Changes in the shapes of hilum and lymph node occurred in reactive or inflamed lymph nodes as well as in lymphomas. Clinical significance of this fact demands further investigation.

Primary splenic B-cell lymphoma (marginal zone lymphoma). Clinicopathological evaluation of 10 cases.

SMZL has been included in the REAL classification of lymphoid neoplasms (1994) as an entity. It affects middle aged adults presenting with splenomegaly, mild lymphocytosis and in 40% of cases with the presence of monoclonal paraprotein. Our material includes 10 patients (6 women + 4 men). In all patients bone marrow biopsy was the initial material for histopathological examination. With characteristic intertrabecular nodular interstitial infiltrates of CD20+ small lymphocytes and corresponding clinical data (splenomegaly, lymphocytosis in peripheral blood and sporadic elevation of IgM levels) it was very suggestive of SMZL diagnosis. Splenectomy was the treatment of choice. The spleen showed micronodular white foci in all cases. Morphologically the pattern of white pulp involvement was observed with lymphoma infiltrates as well as small foci in the red pulp. The white pulp showed follicles surrounded by a wide marginal zone, resembling reactive splenic follicles. A corona-like rim consisted of medium size cells with abundant clear cytoplasm, resembling monocytoid B cells, often with plasmacytoid differentiation, or centrocyte-like cells. Smaller aggregates of these cells were present in the red pulp. Lymphoma cells were CD20+, bcl-2 and IgM+. In all cases monoclonal kappa light chains were found. Although SMZL is a disseminated lymphoma at diagnosis, its course is indolent and splenectomy is the treatment of choice. Clinical and histopathological differential diagnoses include hairy cell leukemia and secondary involvement of the spleen by infiltrates of nodal B-cell lymphomas.

[Hemangioma of bone and soft tissue in the midfoot--case report]. / Naczyniak kosci miekkich sródstopia--opis przypadku.

A case of in isolated arterovenous developmental disorder in 23 years old female is described. Bony changes were at the beginning obscured by skin and soft tissue changes. The diagnosis has been established on the basis of histopathological evaluation of the II metatarsal bone and soft tissue vascular changes removed at the operation.