Key Points• PD-L1 expression is associated with poor prognosis in DLBCL.• The double-staining technique is a useful method for identifying and distinguishing PD-L1 1 DLBCL.Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1 1 DLBCL. (P 5 .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1

Histology, EBV positivity, and monoclonality of IGH are useful for predicting clinical outcomes in patients with RA-LPD.

1 Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co-localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P. with mRNA for the prostaglandin E receptor subtypes (EPI, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively. 2 IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes. 3 IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe. 4 IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small-and large-sized neurones were labelled but no labelling was found in the glia. Expression of PPTA mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor-positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41 % and 24% of the IP receptor-positive neurones co-expressed the EP1, EP3 and EP4 receptor, respectively.5 These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.

Methotrexate (MTX) carries a risk of lymphoproliferative disorders (LPDs), but MTX-associated LPDs (MTX-LPDs) can resolve spontaneously after MTX withdrawal. However, the precise clinicopathologic features of MTX-LPD remain unclear. We aimed to investigate the clinicopathologic characteristics, outcomes, and prognostic factors for histologic types of MTX-LPD. Paraffin-embedded tissue samples of 219 patients with MTX-LPD were analyzed. In total, 30,33,106, and 26 had reactive lymphoid hyperplasia (RH), polymorphic-LPD (Poly-LPD), diffuse large B-cell lymphomas (DLBCLs), and classic Hodgkin lymphoma (CHL), respectively. The clinicopathologic features of RH, Poly-LPD, DLBCLs, and CHL were as follows: extranodal involvement: 13.8% (4/29), 36.4% (12/33), 69.5% (73/105), and 15.4% (4/26); Epstein-Barr virus encoded RNA positivity: 55.2% (16/29), 71.9% (23/32), 45.3% (48/106), and 76.9% (20/26); necrosis: 0% (0/29), 51.5% (17/33), 34.3% (36/105), and 12.0% (3/25); and Hodgkin Reed-Sternberg-like cells: 17.2% (5/29), 50% (14/28), and 19.8% (21/106). The median duration from MTX withdrawal to the time of disease regression was 10.4, 3.0, 4.2, and 2.7 months for RH, Poly-LPD, DLBCLs, and CHL. After MTX withdrawal, progression-free survival was the greatest for RH, followed by for Poly-LPD, DLBCL, and CHL (all P<0.05). Overall survival did not differ significantly between the groups. On univariate analysis, the predictive factors for progression-free survival included plasma cell infiltrate for CHL, eosinophil infiltrate, age above 70 years, and extensive necrosis for Poly-LPD, while they were Epstein-Barr virus encoded RNA positivity and International Prognostic Index risk for DLBCL on multivariate analysis. In conclusion, histologic categorization and histology-specific factors could be useful for predicting MTX-LPD progression after MTX withdrawal.

No abstract

Composite lymphomas (CLs) have been reported in 1-4.7% of all lymphomas, however, CLs containing both T- and B-cell lymphomas (CTBLs) are very rare. Here, we examined the clinical and pathological features of 29 CTBLs. These CTBLs included 21 patients with angioimmunoblastic T-cell lymphoma (AITL) and diffuse large B-cell lymphoma (DLBCL), two with adult T-cell leukemia/lymphoma and DLBCL, one with AITL and Follicular lymphoma, one with Lennert lymphoma and DLBCL, one with subcutaneous panniculitis-like T-cell lymphoma and DLBCL, one with peripheral T-cell lymphoma (PTCL) and DLBCL, one with cutaneous T-cell lymphoma and DLBCL, and one with PTCL and chronic lymphocytic leukemia. Eighteen of 27 patients (67%) were shown to be Epstein-Barr virus (EBV)-encoded RNA-positive in their B-cell lymphoma component. T-cell and B-cell clonality were confirmed by flow cytometry, Southern blot analysis, and/or polymerase chain reaction (PCR). Using Southern blot analysis, clonal immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) rearrangements were detected in 11 of 21 and 15 of 24 cases, respectively. Using PCR analysis, clonal IgH and TCR rearrangements were detected in 7 of 8 and 7 of 7 Southern blot-negative cases, respectively. Our results suggested that PCR analysis was useful in diagnosing CTBL.

No abstract

Whether and how left ventricular (LV) strain and strain rate correlate with wall stress is not known. Furthermore, it is not determined whether strain or strain rate is less dependent on the afterload. In 41 healthy young adults, LV global peak strain and systolic peak strain rate in the longitudinal direction (LS and LSR, respectively) and circumferential direction (CS and CSR, respectively) were measured layer-specifically using speckle tracking echocardiography (STE) before and during a handgrip exercise. Among all the points before and during the exercise, all the STE parameters significantly correlated linearly with wall stress (LS: r = -0.53, p < 0.01, LSR: r = -0.28, p < 0.05, CS in the inner layer: r = -0.72, p < 0.01, CSR in the inner layer: r = -0.47, p < 0.01). Strain more strongly correlated with wall stress than strain rate (r = -0.53 for LS vs. r = -0.28 for LSR, p < 0.05; r = -0.72 for CS vs. r = -0.47 for CSR in the inner layer, p < 0.05), whereas the interobserver variability was similar between strain and strain rate (longitudinal 6.2 vs. 5.2 %, inner circumferential 4.8 vs. 4.7 %, mid-circumferential 7.9 vs. 6.9 %, outer circumferential 10.4 vs. 9.7 %), indicating that the differences in correlation coefficients reflect those in afterload dependency. It was thus concluded that LV strain and strain rate linearly and inversely correlated with wall stress in the longitudinal and circumferential directions, and strain more strongly depended on afterload than did strain rate. Myocardial shortening should be evaluated based on the relationships between these parameters and wall stress.