Lymphoma Classification.

Twenty-five years after the Revised European American Classification of Lymphoid Neoplasms classification was published, its principle of an integrative approach to disease definition based on several parameters still prevails and has been adopted and expanded in the following World Health Organization classifications of tumors of the hematopoietic organs. The latest World Health Organization classification revised in 2017 comprises more than 80 entities of mature lymphoid neoplasms (B-cell, T-cell, and Hodgkin lymphomas), which are defined according to their morphology, immunophenotype, genetic lesions and molecular profiles, clinical features, and cellular derivation. The classification also recognizes both incipient and indolent lymphoid neoplasms with a low potential of progression. In this review, we highlight some of the new data and recent modifications introduced in the 2017 classification

Pathobiology of nodal peripheral T-cell lymphomas: current understanding and future directions.

Predominantly nodal is the most common clinical presentation of peripheral T- (and NK-) cell lymphomas (PTCL), which comprise three main groups of diseases: (i) systemic anaplastic large cell lymphomas (ALCL), whether positive or negative for anaplastic lymphoma kinase (ALK); (ii) follicular helper T-cell lymphomas (TFHL); and (iii) PTCL, not otherwise specified (NOS). Recent advances in the genomic and molecular characterization of PTCL, with enhanced understanding of pathobiology, have translated into significant updates in the latest 2022 classifications of lymphomas. ALK-negative ALCL is now recognized to be genetically heterogeneous, with identification of DUSP22 rearrangements in approximately 20-30% of cases, correlated with distinctive pathological and biological features. The notion of cell-of-origin as an important determinant of the classification of nodal PTCL is best exemplified by TFHL, considered as one disease or a group of related entities, sharing oncogenic pathways with frequent recurrent epigenetic mutations as well as a relationship to clonal hematopoiesis. Data are emerging to support that a similar cell-of-origin concept might be relevant to characterize meaningful subgroups within PTCL, NOS, based on cytotoxic and/or Th1 versus Th2 signatures. The small group of primary nodal Epstein-Barr virus-positive lymphomas of T- or NK-cell derivation, formerly considered PTCL, NOS, is now classified separately, due to distinctive features, and notably an aggressive course. This review summarizes current knowledge of the pathology and biology of nodal-based PTCL entities, with an emphasis on recent findings and underlying oncogenic mechanisms

Successful salvage therapy for refractory primary cutaneous gamma-delta T-cell lymphoma with a combination of brentuximab vedotin and gemcitabine.

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very rare lymphoma with an aggressive clinical course and a dismal outcome. The prognosis is linked to a pronounced resistance to chemotherapy and radiotherapy. No standard treatment approach is defined due to the low frequency of the disease and lack of prospective studies. CD30 is expressed in almost half of the cases of PCGD-TCL, which offers a potential therapeutic option. We report the successful treatment of a 68-year-old man who suffered PCGD-TCL with a combination of Brentuximab Vedotin and Gemcitabine after the failure of two lines of previous chemotherapy. CD30 expression was only partial. The treatment was very well tolerated and allowed the patient to benefit from allogeneic hematopoietic stem cell transplantation

Recent advances upper gastrointestinal lymphomas: molecular updates and diagnostic implications.

Approximately one-third of extranodal non-Hodgkin lymphomas involve the gastrointestinal (GI) tract, with the vast majority being diagnosed in the stomach, duodenum, or proximal small intestine. A few entities, especially diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, represent the majority of cases. In addition, there are diseases specific to or characteristic of the GI tract, and any type of systemic lymphoma can present in or disseminate to these organs. The recent advances in the genetic and molecular characterisation of lymphoid neoplasms have translated into notable changes in the classification of primary GI T-cell neoplasms and the recommended diagnostic approach to aggressive B-cell tumours. In many instances, diagnoses rely on morphology and immunophenotype, but there is an increasing need to incorporate molecular genetic markers. Moreover, it is also important to take into consideration the endoscopic and clinical presentations. This review gives an update on the most recent developments in the pathology and molecular pathology of upper GI lymphoproliferative diseases

Lymph node involvement by enteropathy-like indolent NK-cell proliferation.

Natural killer (NK)-cell enteropathy (NKCE) and lymphomatoid gastropathy (LG) are closely related lymphoproliferative disorders (LPDs) composed of mature and Epstein-Barr virus (EBV)-negative NK-cells. Although these uncommon and indolent lymphoid proliferations mostly arise within the gastrointestinal (GI) tract as their designations implies, a few cases have been reported outside the GI tract. We hereby describe a unique case of lymph node infiltration by such EBV-negative NK-cell proliferation fortuitously found during routine examination of a gallbladder resected for biliary lithiasis. The histologic, phenotypic, and molecular features of this NK-cell proliferation, which were very similar if not identical to those previously reported in NKCE or LG, suggest that similar indolent EBV-negative NK-cell LPDs may also occasionally involve lymph nodes

Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned.

The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and laboratory suites require same day consolidation of all procedures. With laboratory medicine absorbed by the need to deploy large scale COVID-testing, the availability of routine molecular tests is affected. Finally, we are increasingly faced with the challenge of making complex treatment decisions in SARS-CoV-2 positive patients with aggressive but potentially curable blood cancers. When to treat, how to treat, when to wait, how long to wait, how to predict and manage toxicities, and how to avoid compromising cure rates remains unknown. We present an outline of the scientific, medical, and operational challenges posed by the COVID-19 pandemic at selected American and European institutions and offer our current view of the key elements of a response. While the peak of the pandemic may be past us, in the absence of a vaccine risks remain, and our alertness and response to future challenges need to be refined and consolidated

Daratumumab and venetoclax in combination with chemotherapy provide sustained molecular remission in relapsed/refractory CD19, CD20, and CD22 negative acute B lymphoblastic leukemia with KMT2A-AFF1 transcript.

Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) has a very poor prognosis with a median overall survival of four to nine months. Achieving a complete molecular response is most often required to obtain a sustained leukemia-free survival after allogeneic hematopoietic stem cell transplantation. Immunotherapies targeting CD19, CD20, or CD22 are very efficient in achieving this goal. However, in the absence of the expression of these immunotherapeutic targets by lymphoblasts, treatment options are extremely scarce. We report the successful treatment of a 26-year-old man who suffered R/R, CD19, CD20, and CD22 negative B-ALL targeting Bcl-2 and CD38 by combining venetoclax and daratumumab with chemotherapy