The Ring Study: an international comparison of PD-L1 diagnostic assays and their interpretation in non-small cell lung cancer, head and neck squamous cell cancer and urothelial cancer.

PD-L1 immunohistochemistry has been approved as a diagnostic assay for immunotherapy. However, an international comparison across multiple cancers is lacking. This study aimed to assess the performance of PD-L1 diagnostic assays in non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC) and urothelial cancer (UC).

Immune pathway upregulation and lower genomic instability distinguish EBV-positive nodal T/NK-cell lymphoma from ENKTL and PTCL-NOS.

Primary Epstein-Barr virus (EBV)-positive nodal T/NK-cell lymphoma (PTCL-EBV) is a poorly understood disease which shows features resembling extranodal NK/T-cell lymphoma (ENKTL) and is currently not recognized as a distinct entity but categorized as a variant of primary T-cell lymphoma not otherwise specified (PTCL-NOS). Herein, we analyzed copynumber aberrations (n=77) with a focus on global measures of genomic instability and homologous recombination deficiency and performed gene expression (n=84) and EBV miRNA expression (n=24) profiling as well as targeted mutational analysis (n=16) to further characterize PTCL-EBV in relation to ENKTL and PTCL-NOS. Multivariate analysis revealed that patients with PTCL-EBV had a significantly worse outcome compared to patients with PTCL-NOS (P=0.

MYC single-hit large B-cell lymphoma: clinicopathologic difference from MYC-negative large B-cell lymphoma and MYC double-hit/triple-hit lymphoma.

MYC-rearranged large B-cell lymphoma with BCL2 and/or BCL6 rearrangement, double-hit (DH) or triple-hit (TH) lymphoma, is associated with poor survival after standard treatment. To investigate the clinical impact of single-hit (SH) MYC rearrangement, we analyzed 241 cases of diffuse large B-cell lymphoma (DLBCL) for MYC, BCL2, and BCL6 rearrangement by fluorescence in situ hybridization. Fifty-five of 241 (22.

Integrative genomic analysis of salivary duct carcinoma.

Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type.

Epstein-Barr virus NK and T cell lymphoproliferative disease: report of a 2018 international meeting.

Epstein-Barr virus (EBV) normally infects B cells, but in some persons the virus infects T or NK cells. Infection of B cells can result in infectious mononucleosis, and the virus is associated with several B cell malignancies including Hodgkin lymphoma, Burkitt lymphoma, and diffuse large B cell lymphoma. Infection of T or NK cells with EBV is associated with extranodal NK/T cell lymphoma, aggressive NK-cell leukemia, systemic EBV-associated T-cell lymphoma, and chronic active EBV disease, which in some cases can include hydroa vacciniforme-like lymphoproliferative disease and severe mosquito bite allergy.

Incidence and outcomes of rare T cell lymphomas from the T Cell Project: hepatosplenic, enteropathy associated and peripheral gamma delta T cell lymphomas.

The T Cell Project was the largest prospective trial to explore the incidence, treatment patterns, and outcomes for T cell lymphomas. The rare subtypes of T cell lymphomas, including hepatosplenic T cell lymphoma (HSTCL), enteropathy associated T cell lymphoma (EATL), and peripheral gamma delta T cell lymphomas (PGDTCLs) are poorly represented in most studies and there is little data regarding treatment patterns. We report results from 115 patients with hepatosplenic (n = 31), enteropathy associated (n = 65), and PGDTCLs (n = 19).

Primary cutaneous peripheral T-cell lymphoma with a late relapse solely in the ileum mimicking monomorphic epitheliotropic intestinal T-cell lymphoma.

Background: Primary cutaneous peripheral T-cell lymphomas (PC-PTCLs) are classified into mycosis fungoides (MF) and other rare specific types; and those do not fit into any specific entities are designated as PTCL, not otherwise specified (NOS), an aggressive neoplasm. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive primary intestinal T-cell lymphoma with enteropathy in the non-neoplastic mucosa. We report a rare case of PC-PTCL-NOS with a late relapse solely in the ileum after complete remission.

Treatment outcomes in metastatic and localized high-grade salivary gland cancer: high chance of cure with surgery and post-operative radiation in T1-2 N0 high-grade salivary gland cancer.

Background: High-grade salivary gland cancer is a distinct clinical entity that has aggressive disease progression and early systemic spread. However, because of the rarity of the disease, the clinical outcomes, prognostic factors and clinical decision on the optimal treatments have not been fully understood.

Methods: In this study, we retrospectively analyzed the clinical data of 124 patients with high-grade salivary gland cancers and performed multivariate survival analyses to evaluate the clinico-pathological factors affecting the treatment outcomes.

Targeted deep sequencing of gastric marginal zone lymphoma identified alterations of TRAF3 and TNFAIP3 that were mutually exclusive for MALT1 rearrangement.

Gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is a distinct entity in that Helicobacter pylori infection plays the most important causative role in the development of the disease. To investigate the genomic alteration in gastric marginal zone lymphoma that was resistant to the H. pylori eradication therapy, we analyzed 19 cases of the gastric marginal zone lymphoma using fluorescence in situ hybridization for MALT1, BCL10 rearrangement, and targeted sequencing using an Illumina platform.

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS). A new prognostic model developed by the International T cell Project Network.

Different models to investigate the prognosis of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) have been developed by means of retrospective analyses. Here we report on a new model designed on data from the prospective T Cell Project. Twelve covariates collected by the T Cell Project were analysed and a new model (T cell score), based on four covariates (serum albumin, performance status, stage and absolute neutrophil count) that maintained their prognostic value in multiple Cox proportional hazards regression analysis was proposed.

Significance of circulating Epstein-Barr virus DNA monitoring after remission in patients with extranodal natural killer T cell lymphoma.

Circulating Epstein-Barr virus (EBV)-DNA has been established as a useful parameter for diagnosis and predicting prognosis in patients with extranodal natural killer T cell lymphoma (ENKTL); however, the role of monitoring of circulating EBV-DNA after complete remission (CR) is not well established. From January 2008 to August 2016, 328 ENKTL patents were enrolled in 2 lymphoma cohorts. Of 171 patients achieved a CR, 81 had available monitoring data for circulating EBV-DNA with negative post-treatment EBV-DNA.

The outcome of peripheral T-cell lymphoma patients failing first-line therapy: a report from the prospective, International T-Cell Project.

This analysis explored factors influencing survival of patients with primary refractory and relapsed peripheral T-cell lymphomas enrolled in the prospective International T-cell Project. We analyzed data from 1020 patients with newly diagnosed disease, enrolled between September 2006 and December 2015. Out of 937 patients who received first-line treatment, 436 (47%) were identified as refractory and 197 (21%) as relapsed.

Correlation of Expression: Clinical implication in Ovarian Carcinomas.

: ALDH1 is a putative cancer stem cell marker, while the Notch signaling pathway is involved in regulation of cancer stem cell (CSC)s. This study aims to determine the expression of Notch signaling genes in ovarian CSCs, and to assess the clinical impact of expression of and Notch signaling genes in ovarian cancers. : We examined expression of Notch signaling genes in FACS-sorted ALDH1(+) putative ovarian CSCs and expression of and Notch signaling genes in 86 ovarian epithelial tumors and various ovarian cancer cell lines by real-time RT-PCR, including Notch receptors (), Notch ligands (), and the downstream molecule, .

Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes.

The molecular biology of primary nodal T- and NK-cell lymphoma and its relationship with extranodal NK/T-cell lymphoma, nasal type is poorly understood. In this study, we assessed the relationship between nodal and extranodal Epstein-Barr virus-positive T/NK-cell lymphomas using gene expression profiling and copy number aberration analyses. We performed gene expression profiling and copy number aberration analysis on 66 cases of Epstein-Barr virus-associated T/NK-cell lymphoma from nodal and extranodal sites, and correlated the molecular signatures with clinicopathological features.

Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests.

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS.

Molecular Testing of Lymphoproliferative Disorders: Current Status and Perspectives.

Molecular pathologic testing plays an important role for the diagnosis, prognostication and decision of treatment strategy in lymphoproliferative disease. Here, we briefly review the molecular tests currently used for lymphoproliferative disease and those which will be implicated in clinical practice in the near future. Specifically, this guideline addresses the clonality test for B- and T-cell proliferative lesions, molecular cytogenetic tests for malignant lymphoma, determination of cell-of-origin in diffuse large B-cell lymphoma, and molecular genetic alterations incorporated in the 2016 revision of the World Health Organization classification of lymphoid neoplasms.

Axl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma.

Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT.

Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.

Low-Grade Salivary Gland Cancers: Treatment Outcomes, Extent of Surgery and Indications for Postoperative Adjuvant Radiation Therapy.

Background: Histologic grade of tumor is one of the major prognostic predictors for patients with salivary gland cancer. Because of disease rarity, little is known about the optimal treatment modalities and outcomes in low-grade salivary gland cancers (LGSGC). We tried to identify prognostic factors, and the adequate treatment modalities and outcomes in pathologically confirmed LGSGC patients.