Lymphoma

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain en-hancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2 , CBP/ CREBBP , p300/ EP300 , and HIST1H1 in > 95% of cases. B-cells "arrested" in germinal centers acquire dozens of additional genetic aberrations that influence key pathways controlling their physiological development including B Cell Receptor (BCR) signaling, PI3K/AKT, TLR, mTOR, NF-κB, JAK/STAT, MAPK, CD40/CD40L, chemokine, and interleukin signaling. Additionally, most cases of FL do not result from linear accumulation of ge-nomic aberrations, but rather evolve from a common progenitor cell population by diverse evolution, creating multiple FL subclones in one patient. Moreover, one of the subclones might acquire a combination of aberrations involving genes controlling cell survival and proliferation including MDM2, CDKN2A/B, BCL6, MYC, TP53, β2M, FOXO1, MYD88, STAT3, or miR-17-92 , and this can lead to the transformation of an initially indolent FL to an aggressive lymphoma (2%-3% risk per year). The complexity of the disease is also underscored by the importance of its interactions with the microenvironment that can substantially influence disease development and prognosis. Interpreting individual aberrations in relation to their impact on normal processes, their frequency, position in the disease evolution, and the consequences of their (co)occurrence, are the basis for understanding FL pathogenesis. This is necessary for the identification of patients with risk of early progression or transformation, for the development of novel targeted therapies, and for personalized treatment approaches. In this review, we summarize recent knowledge of molecular pathways and microenvironmental components involved in FL biology, and discuss them in the context of physiological B-cell development, FL evolution, and targeted therapies.

... The role of major histocompatibility complex class I antigens in tumorigenesis: future applications in cancer therapy. Auteur(s) / Author(s). NAPOLITANO L. (1) ; VOGEL J. ; JAY G. ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). ... Tumor. ; Antígeno histocompatibilidad clase ...

A new generation of novel, effective targeted drugs and cellular therapies include monoclonal antibodies directed at the cell surface, such as the anti-CD-19 tafasitamab which, combined with lenalidomide, is the first therapy approved by the Food and Drug Administration for second-line treatment of diffuse large B-cell lymphoma. Other agents interfere with pro-survival intracellular signaling pathways including drugs that inhibit Bruton tyrosine kinase, phosphatidylinositol-3 kinase (PI3-kinase), and bcl-2. An increasing number of therapies impact the microenvironment, notably checkpoint inhibitors and bispecific antibodies. Chimeric antigen receptor-T cell therapy has improved the outcome of patients with a variety of histologies of lymphoma. Whereas in the past, such therapies would be used inrelapsed and refractory settings, they are now being evaluated as initial treatment in selected patients. With an improved ability to individualize treatment approaches, chemo-free will be a reality for lymphoma patients.

OBJECTIVE To evaluate the importance of inter-institutional second opinion surgical pathology review of lymphoma, and identify the lymphoma pathologic mimics. METHODS The surgical pathology material of patients referred to 2 tertiary care hospitals in the western region of Saudi Arabia (King Faisal Specialist Hospital and Research Centre and King Abdulaziz University Hospital, Jeddah, Saudi Arabia), for evaluation or therapy for lymphoma over a 10-year period (August 2001 to August 2011), were reviewed. This study included only cases in which the patient referred with a diagnosis previously made at the primary institution. RESULTS Of 560 cases, the second opinion diagnosis differed significantly from the initial diagnosis in 39 cases (7%). These include changing the diagnoses from lymphoma to non-lymphoma lesions, change the type of lymphoma with major clinical impact, and change from reactive/non-diagnostic to lymphoma. CONCLUSION Second opinion surgical pathology for lymphomas can...

The techniques of flow cytometry are becoming more and more important for the clinical hematology laboratory. No longer a novelty confined to a few specialized institutions as it was 10 years ago, flow cytometry has blossomed into a mature discipline. The methodology is well-known, the mechanical apparatus is readily available, and the role it plays in clinical hematology is increasingly appreciated. The burgeoning number of scientific articles devoted to this topic attests to the interest it has aroused as a tool for both medical research and patient care. In fact, more than a thousand such papers are now published each year and it would be impossible to deal with all the methodologies and applications of FCM currently utilized or under development. Throughout this paper four relevant hematologic fields are briefly discussed, in which FCM appears to be of great help at present: the immunophenotyping of leukemias and lymphomas, the measurement of proliferative activity and DNA ploid...

The interplay between tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Thus, the fact that a strong infiltration of memory T cells with a Th1 and cytotoxic pattern is the strongest predictor for recurrence and metastasis is exemplified in colorectal cancer in which intratumoral chemokines shape an efficient immune reaction. Based on these data, we propose an immune score that predicts recurrence in early stage (UICC-TNM stage I-II) cancers. Studies on non-small lung cancers have confirmed findings of colorectal cancers and have addressed the question of the sites where antitumor immune reactions may take place. ...

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type...

Cutaneous or subcutaneous lymphoma is one of the four different forms appearing in the horse. This type of equine lymphoma is usually lymphohistiocytic with a T, B or mixed-cell immunophenotype and with a prevalence of less than 3% among skin neoplasms. This is all about a 9-year old Warmblood mare admitted with a 5-month history of multiple cutaneous masses spreading to many parts of the body. Apart from the multiple subcutaneous nodules and plaques, which did not provide discomfort to the horse, no other abnormalities were found either in clinical or laboratory examination. Lesional histopathology and immunohistochemistry revealed a lymphohistiocytic T-cell lymphoma, which most likely was primary. The owner elected not to have her horse treated, but readmitted it for euthanasia 5 months later, because of the worsening of skin lymphoma and the appearance of general and systemic clinical signs. The ensuing postmortem was suggestive of distant metastatic disease (liver, mediastinal l...

The implementation of new techniques of imaging in the daily practice of the radiation oncologist is a major advance in these last 10 years. This allows optimizing the therapeutic intervals and locoregional control of the disease while limiting side effects. Among them, positron emission tomography (PET) offers an opportunity to the clinician to obtain data relative to the tumoral biological mechanisms, while benefiting from the morphological images of the computed tomography (CT) scan. Recently hybrid PET/CT has been developed and numerous studies aimed at optimizing its use in the planning, the evaluation of the treatment response and the prognostic value. The choice of the radiotracer (according to the type of cancer and to the studied biological mechanism) and the various methods of tumoral delineation, require a regular update to optimize the practices. We propose throughout this article, an exhaustive review of the published researches (and in process of publication) until Dec...

Non IgM-Lymphoplasmacytic Lymphoma (LPL) is a rare chronic lymph proliferative disorder with worse outcome with respect to classical LPL and Waldenstrom Macroglobulinemia. Therapeutic options are limited and differently from other indolent lymphomas no specific approved therapies are available. Here we present the case of a IgA-secreting LPL previously treated with 6 lines of therapies including immuno-chemotherapy, proteasome inhibitor and radiotherapy. At the last relapse this patient was successfully treated with zanubrutinib monotherapy within the BGB-311-AU-003 trial. Treatment with this BTK inhibitor showed to be well tolerated and led to a rapid and still ongoing response at 4 years follow up.

Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous.
Gene-expression profiling has identified subgroups of DLBCL (activated
B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according
to cell of origin that are associated with a differential response to chemotherapy
and targeted agents. We sought to extend these findings by identifying genetic
subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic
vulnerabilities based on tumor genetics.

Evidence suggests a growing number of youth soccer players in the U.S. have been diagnosed with cancer (over 60 percent of which are goalkeepers). Claims have been made that the increase may be due to the crumb rubber turf and the toxic chemicals which are linked with the materials used to make the fields. This paper investigates an alternate hypothesis that the increased cancers by athletes on artificial turf fields are due to repeated electrostatic charge buildup and electrical discharge due to triboelectric effects from the crumb rubber turf and plastic blades of grass in contact with player's skin and jerseys. INTRODUCTION A soccer coach at the University of Washington [1] has developed a list of athletes with cancer who have played on synthetic turf which now stands at/above 200 athletes, 158 of whom are soccer players. Of those soccer players, 101 are goalkeepers. Eighty of the athletes on the list have some form of lymphoma.

The World Health Organization (WHO) classification of lymphomas updated in 2008 represents an international consensus for diagnosis of lymphoid neoplasms based on the recognition of distinct disease entities by applying a constellation of clinical and laboratory features. The 2008 classification has refined and clarified the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. Rather than being a theoretical scheme this classification has used data from published literature. Recent knowledge of molecular pathways has led to identification and development of new diagnostic tools, like gene expression profiling, which could complement existing technologies. However, some questions remain unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors. In general, practical considerations and economics preclude a heavily molecular and genetic ...