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20 pages, 1875 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Burkitt Lymphoma Incidence in Five Continents

by Sam M. Mbulaiteye and Susan S. Devesa

Hemato 2022, 3(3), 434-453; https://doi.org/10.3390/hemato3030030 - 13 Jul 2022

Cited by 9 | Viewed by 5255

Burkitt lymphoma (BL) is a rare non-Hodgkin lymphoma first described in 1958 by Denis Burkitt in African children. BL occurs as three types, endemic, which occurs in Africa and is causally attributed to Epstein-Barr virus and P. falciparum infections; sporadic, which occurs in [...] Read more.

Burkitt lymphoma (BL) is a rare non-Hodgkin lymphoma first described in 1958 by Denis Burkitt in African children. BL occurs as three types, endemic, which occurs in Africa and is causally attributed to Epstein-Barr virus and P. falciparum infections; sporadic, which occurs in temperate areas, but the cause is obscure; and immunodeficiency-type, which is associated with immunosuppression. All BL cases carry IG∷MYC chromosomal translocations, which are necessary but insufficient to cause BL. We report a comprehensive study of the geographic, sex, and age-specific patterns of BL among 15,122 cases from Cancer Incidence in Five Continents Volume XI for 2008–2012 and the African Cancer Registry Network for 2018. Age-standardized BL rates were high (>4 cases per million people) in Uganda in Africa, and Switzerland and Estonia in Europe. Rates were intermediate (2–3.9) in the remaining countries in Europe, North America, and Oceania, and low (<2) in Asia. Rates in India were 1/20th those in Uganda. BL rates varied within and between regions, without showing a threshold to define BL as endemic or sporadic. BL rates were twice as high among males as females and showed a bimodal age pattern with pediatric and elderly peaks in all regions. Multi-regional transdisciplinary research is needed to elucidate the epidemiological patterns of BL. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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Review

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16 pages, 8790 KiB

Open AccessFeature PaperReview

B Lymphoproliferative Neoplasms of Uncertain Biological Significance: Report from the IV Workshop of the Italian Group of Hematopathology and Review of the Literature

by Gioia Di Stefano, Francesca Magnoli, Massimo Granai, Federico Vittone, Raffaella Santi, Domenico Ferrara, Emanuela Boveri, Ada M. Florena, Falko Fend, Elena Sabattini, Marco Paulli, Maurilio Ponzoni, Stefano Lazzi, Stefano A. Pileri, Lorenzo Leoncini and the Italian Group of Hematopathology

Hemato 2022, 3(4), 634-649; https://doi.org/10.3390/hemato3040043 - 03 Oct 2022

Cited by 1 | Viewed by 2023

Abstract

Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues [...] Read more.

Lymphoproliferative neoplasms of uncertain biological significance are increasingly encountered due to widespread usage of immunophenotypic and molecular techniques. Considering that clearer biological criteria and patient management have been established for B-cell lymphoproliferative diseases of undetermined significance occurring in the peripheral blood, many issues are still obscure for early lesions detected in lymphoid tissues. Regardless that some categories of lymphoproliferative neoplasms of uncertain biological significance have been recognized by the 4th edition of the WHO, other anecdotal early lymphoproliferative lesions still remain fully undefined. Some early lesions frequently originate from the germinal center, including atypical germinal centers BCL2-negative, an early pattern of large B-cell lymphoma with IRF4 rearrangement, and “in situ” high-grade B lymphomas. Moreover, other early lymphoproliferative lesions arise outside the germinal center and include those developing within the setting of monocytoid B-cell hyperplasia, but they also can be directly or indirectly associated with chronic inflammations. This review aims to summarize the concepts discussed during the IV Workshop organized by the Italian Group of Hematopathology, focus on the state-of-the-art on B-cell lymphoproliferative neoplasms of uncertain biological significance, and offer operative insights to pathologists and clinicians in routine diagnostics. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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19 pages, 928 KiB

Open AccessReview

Genetics of Transformed Follicular Lymphoma

by Miguel Alcoceba, María García-Álvarez, Jessica Okosun, Simone Ferrero, Marco Ladetto, Jude Fitzgibbon and Ramón García-Sanz

Hemato 2022, 3(4), 615-633; https://doi.org/10.3390/hemato3040042 - 01 Oct 2022

Viewed by 2731

Abstract

Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have [...] Read more.

Histological transformation (HT) to a more aggressive disease–mostly diffuse large B-cell lymphoma–is considered one of the most dismal events in the clinical course of follicular lymphoma (FL). Current knowledge has not found a single biological event specific for HT, although different studies have highlighted common genetic alterations, such as TP53 and CDKN2A/B loss, and MYC translocations, among others. Together, they increase genomic complexity and mutational burden at HT. A better knowledge of HT pathogenesis would presumably help to find diagnostic biomarkers allowing the identification of patients at high-risk of transformation, as well as the discrimination from patients with FL recurrence, and those who remain in remission. This would also help to identify new drug targets and the design of clinical trials for the treatment of transformation. In the present review we provide a comprehensive overview of the genetic events frequently identified in transformed FL contributing to the switch towards aggressive behaviour, and we will discuss current open questions in the field of HT. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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20 pages, 2042 KiB

Open AccessFeature PaperReview

Molecular Pathogenesis of Follicular Lymphoma: From Genetics to Clinical Practice

by Cristina López, Pablo Mozas, Armando López-Guillermo and Sílvia Beà

Hemato 2022, 3(4), 595-614; https://doi.org/10.3390/hemato3040041 - 26 Sep 2022

Cited by 5 | Viewed by 4184

Abstract

Follicular lymphoma (FL), a generally indolent disease that derives from germinal center (GC) B cells, represents around 20–25% of all new lymphomas diagnosed in Western countries. The characteristic t(14;18)(q32;q21) translocation that places the BCL2 oncogene under control of the immunoglobulin heavy-chain enhancer occurs [...] Read more.

Follicular lymphoma (FL), a generally indolent disease that derives from germinal center (GC) B cells, represents around 20–25% of all new lymphomas diagnosed in Western countries. The characteristic t(14;18)(q32;q21) translocation that places the BCL2 oncogene under control of the immunoglobulin heavy-chain enhancer occurs in pro- or pre-B cells. However, additional secondary alterations are required for the development of overt FL, which mainly affects genes involved in epigenetic and transcriptional regulation, signaling and B cell differentiation, the BCR/NF-κB pathway, and proliferation/apoptosis. On the other hand, new insights into the FL pathogenesis suggest that FL lacking the BCL2 translocation might be a distinct biological entity with genomic features different from the classical FL. Although FL is considered an indolent disease, around 10–20% of cases eventually transform to an aggressive lymphoma, usually a diffuse large B cell lymphoma, generally by a divergent evolution process from a common altered precursor cell acquiring genomic alterations involved in the cell cycle and DNA damage responses. Importantly, FL tumor cells require interaction with the microenvironment, which sustains cell survival and proliferation. Although the use of rituximab has improved the outlook of most FL patients, further genomic studies are needed to identify those of high risk who can benefit from innovative therapies. This review provides an updated synopsis of FL, including the molecular and cellular pathogenesis, key events of transformation, and targeted treatments. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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16 pages, 36252 KiB

Open AccessReview

Lymphomas in People Living with HIV

by Emanuela Vaccher, Annunziata Gloghini, Chiara C. Volpi and Antonino Carbone

Hemato 2022, 3(3), 527-542; https://doi.org/10.3390/hemato3030037 - 06 Sep 2022

Cited by 1 | Viewed by 2287

Abstract

Lymphomas in people living with HIV (PLWH) are associated with Epstein Barr virus (EBV) and Kaposi-sarcoma-associated herpesvirus (KSHV). They include primary effusion lymphoma, large B-cell lymphoma arising in multicentric Castleman disease, plasmablastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma (HL). [...] Read more.

Lymphomas in people living with HIV (PLWH) are associated with Epstein Barr virus (EBV) and Kaposi-sarcoma-associated herpesvirus (KSHV). They include primary effusion lymphoma, large B-cell lymphoma arising in multicentric Castleman disease, plasmablastic lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, and Hodgkin lymphoma (HL). Inclusion of these lymphomas in the WHO classification of tumors of hematopoietic and lymphoid tissues and the increasing recognition of these disorders have resulted in established clinical management that has led to improved outcomes. In this review, we report on the current management in lymphomas occurring in PLWH with an emphasis on KSHV-associated disorders and EBV-related HL. We also report on the simultaneous occurrence of KSHV- and EBV-associated disorders and highlight preventive measures that have been planned for tumor prevention in PLWH. In conclusion, it is recommended that treatment choice for PLWH affected by lymphoma, and receiving effective combined antiretroviral therapy (cART), should not be influenced by HIV status. Moreover, there is an urgent need (1) to reduce the current large disparities in health care between HIV-infected and HIV-uninfected populations, (2) to disseminate effective treatment, and (3) to implement preventive strategies for PLWH. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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10 pages, 1322 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Clinical Impact of Precisely Defining Mantle Cell Lymphoma: Contributions of Elaine Jaffe

by Mark Roschewski and Dan L. Longo

Hemato 2022, 3(3), 508-517; https://doi.org/10.3390/hemato3030035 - 16 Aug 2022

Viewed by 1656

Abstract

Mantle cell lymphoma (MCL) is an aggressive yet incurable B-cell lymphoma that was only first recognized as a distinct subtype in 1992, with early reports suggesting a poor median survival. Elaine Jaffe is a renowned hematopathologist and scientist from the National Cancer Institute [...] Read more.

Mantle cell lymphoma (MCL) is an aggressive yet incurable B-cell lymphoma that was only first recognized as a distinct subtype in 1992, with early reports suggesting a poor median survival. Elaine Jaffe is a renowned hematopathologist and scientist from the National Cancer Institute who was instrumental in many of the early descriptions of MCL that distinguished it from other B-cell lymphomas. Further, she has led multiple international collaborations that have harmonized the lymphoma classification systems that are currently in use today. The early morphologic descriptions of MCL along with the contributions of immunologic and genetic techniques have confirmed MCL as a distinct entity with unique biology and clinical behavior. Importantly, these scientific discoveries laid the foundation for unprecedented therapeutic breakthroughs that have led to significant improvements in overall survival. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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23 pages, 1270 KiB

Open AccessReview

The Era of Genomic Research for Lymphoma: Looking Back and Forward

by Wing C. Chan and Javeed Iqbal

Hemato 2022, 3(3), 485-507; https://doi.org/10.3390/hemato3030034 - 15 Aug 2022

Viewed by 2283

Abstract

Technological and informatics advances as well as the availability of well-annotated and reliable genomic data have ushered in the era of genomics research. We describe in this brief review how the genomics approach has impacted lymphoma research in the understanding of the pathogenesis [...] Read more.

Technological and informatics advances as well as the availability of well-annotated and reliable genomic data have ushered in the era of genomics research. We describe in this brief review how the genomics approach has impacted lymphoma research in the understanding of the pathogenesis and biology of lymphoma, in lymphoma diagnosis and in targeted therapy. Some exciting directions that could be explored in the future are also discussed. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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9 pages, 2702 KiB

Open AccessEditor’s ChoiceReview

Evolution in the Definition of Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: A Model for the Future of Personalized Medicine

by Elaine S. Jaffe and Antonino Carbone

Hemato 2022, 3(3), 466-474; https://doi.org/10.3390/hemato3030032 - 21 Jul 2022

Cited by 2 | Viewed by 4867

Abstract

The definitions of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are evolving in the era of personalized medicine. Early stages of the evolution of FL have been recognized. Two histological manifestations of early lesions are in situ follicular neoplasia and duodenal [...] Read more.

The definitions of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are evolving in the era of personalized medicine. Early stages of the evolution of FL have been recognized. Two histological manifestations of early lesions are in situ follicular neoplasia and duodenal type FL. Additionally, FL frequently undergoes histological transformation, the most common form being DLBCL. High-grade B-cell lymphoma with double hit, with translocations involving BCL2 and MYC are important clinically. Rarer forms of transformation include classic Hodgkin lymphoma (CHL) and histiocytic sarcoma. In addition to conventional FL associated with the BCL2 translocation, alternative forms of BCL2-negative FL have been observed. These are heterogenous clinically and genetically. A distinctive group of B-cell lymphomas of follicle cell derivation arise in young patients and include pediatric type FL, testicular FL and a large B-cell lymphoma with IRF4 rearrangement. Historically DLBCL was separated into only two histological variants, centroblastic and immunoblastic. In 2017 the WHO classification recommended (1) the segregation of activated B cell and germinal center B cell derived DLBCL, (2) the identification of high-grade B-cell lymphoma with double hit, and (3) the recognition of an aggressive lymphoma that may resemble Burkitt lymphoma, currently designated in the International Consensus Classification as Large B-cell lymphoma with 11q aberration. Today we appreciate greater genomic complexity among aggressive B-cell lymphomas. Recent studies with NGS and mutational profiling have identified clinically significant genetic subgroups. It is hoped that these data ultimately will lead to targeted therapy based on the genetic profile. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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23 pages, 5309 KiB

Open AccessReview

Primary Cutaneous B-Cell Lymphoma: An Update on Pathologic and Molecular Features

by Marco Lucioni, Sara Fraticelli, Giuseppe Neri, Monica Feltri, Giuseppina Ferrario, Roberta Riboni and Marco Paulli

Hemato 2022, 3(2), 318-340; https://doi.org/10.3390/hemato3020023 - 29 May 2022

Cited by 6 | Viewed by 4662

Abstract

Primary cutaneous B-cell lymphomas (PCBCLs) account for 25% of all primary cutaneous lymphomas. Three major types are currently recognized by the WHO classification: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) (both considered indolent lymphomas) and primary cutaneous [...] Read more.

Primary cutaneous B-cell lymphomas (PCBCLs) account for 25% of all primary cutaneous lymphomas. Three major types are currently recognized by the WHO classification: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) (both considered indolent lymphomas) and primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT), which is, instead, a very aggressive disease. Nowadays, the PCBCL’s category also includes some rare entities such as intravascular B-cell lymphoma (IVBL) and the EBV+ mucocutaneous ulcer (EBVMCU). Furthermore, controversies still exist concerning the category of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), because some cases may present with clinical and histological features between PCFCL and PCDLBCL-LT. Therefore, some authors proposed introducing another category called PCDLBCL, not otherwise specified (NOS). Regardless, PCBCLs exhibit distinct features and differ in prognosis and treatment from their nodal/systemic counterparts. Therefore, clinicopathologic analysis is a key diagnostic element in the work-up of these lymphomas. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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19 pages, 7580 KiB

Open AccessEditor’s ChoiceReview

Peripheral T-Cell Lymphomas of the T Follicular Helper Type: Clinical, Pathological, and Genetic Attributes

by Karthik A. Ganapathi, Kristin H. Karner and Madhu P. Menon

Hemato 2022, 3(1), 268-286; https://doi.org/10.3390/hemato3010020 - 21 Mar 2022

Viewed by 9398

Abstract

Follicular helper T-cell (TFH) lymphomas comprise a unique group of T-cell lymphomas that represent neoplastic proliferations of follicular helper T-cells and share genetic, immunophenotypic, morphologic, and clinical features. Angioimmunoblastic T-cell lymphoma (AITL) is the prototypical TFH lymphoma; in addition, the 2017 revised World [...] Read more.

Follicular helper T-cell (TFH) lymphomas comprise a unique group of T-cell lymphomas that represent neoplastic proliferations of follicular helper T-cells and share genetic, immunophenotypic, morphologic, and clinical features. Angioimmunoblastic T-cell lymphoma (AITL) is the prototypical TFH lymphoma; in addition, the 2017 revised World Health Organization (WHO) 4th edition recognizes two other unique subtypes: follicular T-cell lymphoma (FTCL) and nodal peripheral T-cell lymphoma with the T follicular helper phenotype (PTCL-TFH). This review discusses the morphologic spectrum, immunophenotype, diagnostic mimics/pitfalls, and unique genetic attributes of this category of T-cell lymphomas. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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13 pages, 25015 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Indolent T- and NK-Cell Lymphoproliferative Disorders of the Gastrointestinal Tract: Current Understanding and Outstanding Questions

by Craig R. Soderquist and Govind Bhagat

Hemato 2022, 3(1), 219-231; https://doi.org/10.3390/hemato3010018 - 10 Mar 2022

Cited by 2 | Viewed by 3658

Abstract

Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract are uncommon clonal neoplasms that have a protracted clinical course and limited response to therapy. In recent years, advances in the immunophenotypic, genetic, and clinical characterization of these disorders have led to increased [...] Read more.

Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract are uncommon clonal neoplasms that have a protracted clinical course and limited response to therapy. In recent years, advances in the immunophenotypic, genetic, and clinical characterization of these disorders have led to increased awareness and a better understanding of disease pathogenesis. However, many questions remain unanswered, including those concerning the cell(s) of origin, inciting immune or environmental factors, and the molecular pathways underlying disease progression and transformation. In this review, we discuss recent findings regarding the immunophenotypic and genomic spectrum of these lymphoproliferative disorders and highlight unresolved issues. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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14 pages, 289 KiB

Open AccessReview

Epigenetic Modifications in Lymphoma and Their Role in the Classification of Lymphomas

by Sean Harrop, Costas Kleanthes Yannakou, Carrie Van Der Weyden and Henry Miles Prince

Hemato 2022, 3(1), 174-187; https://doi.org/10.3390/hemato3010015 - 21 Feb 2022

Viewed by 3112

Abstract

The characterisation of the lymphoma epigenome has provided insight into mechanisms involved in lymphomagenesis. Multiple lymphoma subtypes demonstrate recurrent mutations in key epigenetic regulators that have been utilised to define clinicogenetic groups that can predict clinical behaviour in these heterogenous entities. The high [...] Read more.

The characterisation of the lymphoma epigenome has provided insight into mechanisms involved in lymphomagenesis. Multiple lymphoma subtypes demonstrate recurrent mutations in key epigenetic regulators that have been utilised to define clinicogenetic groups that can predict clinical behaviour in these heterogenous entities. The high frequency of mutations in epigenetic regulators provides rationale to incorporate these in the classification of some subtypes of lymphoma. In addition, their recurrent nature provides a rationale to target such mutations, or the relevant pathway, for treatment. In this review, we summarised the available literature on epigenetic dysregulation in lymphoma and how it has been utilised in diagnosis and classification. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

11 pages, 2342 KiB

Open AccessEditor’s ChoiceReview

Cold Agglutinin Disease: A Distinct Clonal B-Cell Lymphoproliferative Disorder of the Bone Marrow

by Fina Climent, Joan Cid and Anna Sureda

Hemato 2022, 3(1), 163-173; https://doi.org/10.3390/hemato3010014 - 13 Feb 2022

Cited by 2 | Viewed by 9166

Abstract

Cold agglutinin disease (CAD) is a distinct clinicopathologic entity characterized by clonal B-cell lymphoproliferative disorder in the bone marrow. B-cell gene mutations affect NF-ΚB as well as chromatin modification and remodeling pathways. Clonal immunoglobulins produced by B cells bind to red cells (RBCs) [...] Read more.

Cold agglutinin disease (CAD) is a distinct clinicopathologic entity characterized by clonal B-cell lymphoproliferative disorder in the bone marrow. B-cell gene mutations affect NF-ΚB as well as chromatin modification and remodeling pathways. Clonal immunoglobulins produced by B cells bind to red cells (RBCs) at cold temperatures causing RBC aggregation, complement cascade activation and cold-autoantibody autoimmune hemolytic anemia (cAIHA). The clinical picture shows cold-induced symptoms and cAIHA. Therapeutic options include “wait and watch”, rituximab-based regimens, and complement-directed therapies. Steroids must not be used for treating CAD. New targeted therapies are possibly identified after recent molecular studies. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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9 pages, 903 KiB

Open AccessEditor’s ChoiceReview

The NKL- and TALE-Codes Represent Hematopoietic Gene Signatures to Evaluate Deregulated Homeobox Genes in Hodgkin Lymphoma

by Stefan Nagel

Hemato 2022, 3(1), 122-130; https://doi.org/10.3390/hemato3010011 - 02 Feb 2022

Cited by 2 | Viewed by 1958

Abstract

Homeobox genes encode transcription factors which control basic processes in development and differentiation. Concerning the sequence conservation in their homeobox, these genes are arranged into particular groups sharing evolutionary ancestry and resembling in function. We have recently described the physiological expression patterns of [...] Read more.

Homeobox genes encode transcription factors which control basic processes in development and differentiation. Concerning the sequence conservation in their homeobox, these genes are arranged into particular groups sharing evolutionary ancestry and resembling in function. We have recently described the physiological expression patterns of two homeobox gene groups, NKL and TALE, in early hematopoiesis and subsequent lymphopoiesis. The hematopoietic activities of eleven NKL and nine TALE homeobox genes have been termed as NKL- and TALE-codes, respectively. Due to the developmental impact of homeobox genes, these expression data indicate a key role for their activity in normal hematopoietic differentiation processes, including B-cell development. On the other hand, aberrant expression of NKL- and TALE-code members or ectopic activation of non-code members have been frequently reported in lymphoid malignancies, demonstrating their oncogenic potential in the hematopoietic compartment. Here, we provide an overview of the established NKL- and TALE-codes in normal lymphopoiesis and of deregulated homeobox genes in Hodgkin lymphoma, demonstrating the capability of gene codes to identify homeo-oncogenes in lymphoid malignancies. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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10 pages, 2739 KiB

Open AccessReview

KSHV/HHV8-Associated Lymphoproliferative Disorders: Lessons Learnt from People Living with HIV

by Mark Bower and Antonino Carbone

Hemato 2021, 2(4), 703-712; https://doi.org/10.3390/hemato2040047 - 24 Nov 2021

Cited by 5 | Viewed by 2501

Abstract

In 1992, Kaposi sarcoma herpesvirus (KSHV/HHV8) was discovered and identified as the causative agent for Kaposi sarcoma. Subsequently, the presence of this virus has been detected in a number of lymphoproliferative disorders in people living with HIV (PLWH), including: KSHV-associated multicentric Castleman disease, [...] Read more.

In 1992, Kaposi sarcoma herpesvirus (KSHV/HHV8) was discovered and identified as the causative agent for Kaposi sarcoma. Subsequently, the presence of this virus has been detected in a number of lymphoproliferative disorders in people living with HIV (PLWH), including: KSHV-associated multicentric Castleman disease, primary effusion lymphoma, KSHV-positive diffuse large B-cell lymphoma, and germinotropic lymphoproliferative disorder. Each of these rare entities has subsequently been diagnosed in HIV-negative individuals. The recognition of some of these KSHV/HHV8-associated lymphoproliferative disorders has led to their inclusion in the WHO classification of lymphomas in 2008 and the revision of 2016; however, further revision is under way to update the classification. The relatively recent recognition of these lymphoproliferative disorders and their low incidence, particularly in the HIV-negative population, means that there is little published evidence and consensus on their clinical features and management. The publication of a new WHO classification of lymphomas should yield diagnostic clarity, providing an impetus for retrospective case series and prospective clinical trials in these KSHV/HHV8-associated lymphoproliferative disorders. Full article

(This article belongs to the Special Issue Classification of Lymphomas and Hematological Neoplasia in the Era of Genomic Research: A Themed Issue in Honor of Dr. Elaine S. Jaffe)

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