Analysis of MUM1/IRF4 Protein Expression Using Tissue Microarrays and Immunohistochemistry

n/

Co-expression of CD56 and CD30 in lymphomas with primary presentation in the skin: clinicopathologic, immunohistochemical and molecular analyses of seven cases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74772/1/j.1600-0560.2000.027008392.x.pd

LymphoML: An interpretable artificial intelligence-based method identifies morphologic features that correlate with lymphoma subtype

The accurate classification of lymphoma subtypes using hematoxylin and eosin (H&E)-stained tissue is complicated by the wide range of morphological features these cancers can exhibit. We present LymphoML - an interpretable machine learning method that identifies morphologic features that correlate with lymphoma subtypes. Our method applies steps to process H&E-stained tissue microarray cores, segment nuclei and cells, compute features encompassing morphology, texture, and architecture, and train gradient-boosted models to make diagnostic predictions. LymphoML's interpretable models, developed on a limited volume of H&E-stained tissue, achieve non-inferior diagnostic accuracy to pathologists using whole-slide images and outperform black box deep-learning on a dataset of 670 cases from Guatemala spanning 8 lymphoma subtypes. Using SHapley Additive exPlanation (SHAP) analysis, we assess the impact of each feature on model prediction and find that nuclear shape features are most discriminative for DLBCL (F1-score: 78.7%) and classical Hodgkin lymphoma (F1-score: 74.5%). Finally, we provide the first demonstration that a model combining features from H&E-stained tissue with features from a standardized panel of 6 immunostains results in a similar diagnostic accuracy (85.3%) to a 46-stain panel (86.1%).Comment: To be published in Proceedings of the 3rd Machine Learning for Health symposium, Proceedings of Machine Learning Research (PMLR

CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas Diagnostic and Therapeutic Implications

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy

Lmo2 expression defines tumor cell identity during T-cell leukemogenesis

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL. In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL. The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL. We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.J.H. has been supported by the German Cancer Aid (Project 110997 and Translational Oncology Program 70112951), the German Jose Carreras Leukemia Foundation (DJCLS 02R/2016), Deutsches Konsortium für Translationale Krebsforschung (DKTK), Joint funding (Targeting MYC L*10), the Kinderkrebsstiftung (2016/17), and the “Elterninitiative Kinderkrebsklinik e.V. Düsseldorf”. SG has been supported by a scholarship of the Hochschule Bonn-Rhein-Sieg. AB has been supported by the German Children's Cancer Foundation and the Federal Ministry of Education and Research, Bonn, Germany. Research in ISG group is partially supported by FEDER and by MINECO (SAF2012-32810, SAF2015-64420-R, and Red de Excelencia Consolider OncoBIO SAF2014-57791-REDC), Instituto de Salud Carlos III (PIE14/00066), ISCIII- Plan de Ayudas IBSAL 2015 Proyectos Integrados (IBY15/00003), by Junta de Castilla y León (BIO/SA51/15, CSI001U14, UIC-017, and CSI001U16), Fundacion Inocente Inocente, and by the ARIMMORA project (European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282891). ISG Lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. AB and ISG have been supported by the German Carreras Foundation (DJCLS R13/26). IGR was supported by BES-Ministerio de Economía y Competitividad (BES-2013-063789). AML and GRH were supported by FSE-Conserjería de Educación de la Junta de Castilla y León (CSI001-13, CSI001-15). Research in CVD group is partially supported by FEDER, “Miguel Servet” Grant (CP14/00082—AES 2013-2016) from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), “Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III” (PI17/00167), and by the Lady Tata International Award for Research in Leukaemia 2016–2017

Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type

Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression

Correction. "The 5th edition of The World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms" Leukemia. 2022 Jul;36(7):1720-1748

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms

On the Shoulders of a Giant: Contributions of Thomas Grogan, MD to Hematopathology

The story of Thomas Grogan, MD is one of the most compelling narratives in the modern history of pathology. Progressing from a quintessential academic pathologist to an entrepreneur and a renowned inventor, his remarkable journey is one of creativity, courage, and a keen focus on improving the care of cancer patients. By enabling precision health and empowering the pathologist in that mission, he transformed the landscape of diagnostic pathology. In this review, we describe some of his salient contributions and how his vision has shaped and continues to shape hematopathology today

HGAL Protein Expression Persists in Disorders of Germinal Center Dissolution

Human Germinal Center-associated Lymphoma (HGAL) is a germinal center (GC) B-cell marker associated with a favorable outcome in diffuse large B-cell and classic Hodgkin lymphomas (CHL). To test its potential role in GC function, 75 cases involving GC disruption including 23 progressive transformation of germinal centers (PTGC), 25 follicle lysis and 27 Castleman disease (CD) were studied. HGAL protein expression uniformly correlated with GC B-cells in all except a subset of hyaline-vascular CD that showed severe regression of GCs. HGAL staining highlighted dismantled GCs in PTGC, in contrast to weak or absent CD10 and BCL6 staining. In follicle lysis, HGAL staining was comparable to that of CD10, BCL6, and CD21 in highlighting lysed follicles. Our findings show that HGAL protein expression effectively discriminates clusters of GC B-cells in disrupted follicles. Its persistence in disrupted GCs, suggests that it may be necessary for GC maintenance and supports its proposed role of confining B-cells to the GC microenvironment