Pub Date : 2021-06-01Epub Date: 2021-06-30DOI: 10.21037/aol-20-52
Simone Krebs, Julia G Barasch, Robert J Young, Christian Grommes, Heiko Schöder
This review addresses the challenges of primary central nervous system (CNS) lymphoma diagnosis, assessment of treatment response, and detection of recurrence. Primary CNS lymphoma is a rare form of extra-nodal non-Hodgkin lymphoma that can involve brain, spinal cord, leptomeninges, and eyes. Primary CNS lymphoma lesions are most commonly confined to the white matter or deep cerebral structures such as basal ganglia and deep periventricular regions. Contrast-enhanced magnetic resonance imaging (MRI) is the standard diagnostic modality employed by neuro-oncologists. MRI often shows common morphological features such as a single or multiple uniformly well-enhancing lesions without necrosis but with moderate surrounding edema. Other brain tumors or inflammatory processes can show similar radiological patterns, making differential diagnosis difficult. [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) has selected utility in cerebral lymphoma, especially in diagnosis. Primary CNS lymphoma can sometimes present with atypical findings on MRI and FDG PET, such as disseminated disease, non-enhancing or ring-like enhancing lesions. The complementary strengths of PET and MRI have led to the development of combined PET-MR systems, which in some cases may improve lesion characterization and detection. By highlighting active developments in this field, including advanced MRI sequences, novel radiotracers, and potential imaging biomarkers, we aim to spur interest in sophisticated imaging approaches.
{"title":"Positron emission tomography and magnetic resonance imaging in primary central nervous system lymphoma-a narrative review.","authors":"Simone Krebs, Julia G Barasch, Robert J Young, Christian Grommes, Heiko Schöder","doi":"10.21037/aol-20-52","DOIUrl":"10.21037/aol-20-52","url":null,"abstract":"<p><p>This review addresses the challenges of primary central nervous system (CNS) lymphoma diagnosis, assessment of treatment response, and detection of recurrence. Primary CNS lymphoma is a rare form of extra-nodal non-Hodgkin lymphoma that can involve brain, spinal cord, leptomeninges, and eyes. Primary CNS lymphoma lesions are most commonly confined to the white matter or deep cerebral structures such as basal ganglia and deep periventricular regions. Contrast-enhanced magnetic resonance imaging (MRI) is the standard diagnostic modality employed by neuro-oncologists. MRI often shows common morphological features such as a single or multiple uniformly well-enhancing lesions without necrosis but with moderate surrounding edema. Other brain tumors or inflammatory processes can show similar radiological patterns, making differential diagnosis difficult. [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) has selected utility in cerebral lymphoma, especially in diagnosis. Primary CNS lymphoma can sometimes present with atypical findings on MRI and FDG PET, such as disseminated disease, non-enhancing or ring-like enhancing lesions. The complementary strengths of PET and MRI have led to the development of combined PET-MR systems, which in some cases may improve lesion characterization and detection. By highlighting active developments in this field, including advanced MRI sequences, novel radiotracers, and potential imaging biomarkers, we aim to spur interest in sophisticated imaging approaches.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/55/nihms-1715614.PMC8248935.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39158050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Primary central nervous system lymphoma (PCNSL) arises in the central nervous system and remains confined into the brain, an organ with singular biological and immunological characteristics, where the structured lymphoid tissue is not normally present. Early diagnosis represents one of the main tasks for clinicians approaching PCNSL patients, because it would allow both a reduction of the risk of cerebral damage due to the presence of lymphomatous tissue and a limited time of use of steroid therapy, that raises a higher risk of immunosuppression. To date, diagnostic stereotactic biopsy is required in the most of the cases with suspicious PCNSL, however the use of less invasive and alternative diagnostic procedures would limit the surgery related-risks and morbidities, that are described in 8% of the cases. The PCNSL molecular profile and biological characteristics are poorly known, and the researchers’ efforts have been focused on studying these aspects only in the last years. In particular, the progressive knowledge on the genomic and molecular profile of lymphomatous cells and their microenvironment have helped to better characterize the pathophysiology of PCNSL. However, their diagnostic predictive and prognostic roles still remain unclear and have not yet been applied into the clinical practice. In this review we have reported the important advances on the knowledge of the main biomarkers detectable on biological fluids [blood, cerebrospinal fluid (CSF) and vitreous humor] that include genomic fragments, cytokines and their receptors, surface molecules. These biomarkers demonstrated a potential role in the early diagnosis of PCNSL, particularly when they are detected in combination, and some of them showed to have a prognostic value and a role in monitoring
{"title":"Narrative review: biomarkers, a hope towards early diagnosis in primary CNS lymphoma","authors":"S. Steffanoni, T. Calimeri","doi":"10.21037/AOL-20-56","DOIUrl":"https://doi.org/10.21037/AOL-20-56","url":null,"abstract":"Primary central nervous system lymphoma (PCNSL) arises in the central nervous system and remains confined into the brain, an organ with singular biological and immunological characteristics, where the structured lymphoid tissue is not normally present. Early diagnosis represents one of the main tasks for clinicians approaching PCNSL patients, because it would allow both a reduction of the risk of cerebral damage due to the presence of lymphomatous tissue and a limited time of use of steroid therapy, that raises a higher risk of immunosuppression. To date, diagnostic stereotactic biopsy is required in the most of the cases with suspicious PCNSL, however the use of less invasive and alternative diagnostic procedures would limit the surgery related-risks and morbidities, that are described in 8% of the cases. The PCNSL molecular profile and biological characteristics are poorly known, and the researchers’ efforts have been focused on studying these aspects only in the last years. In particular, the progressive knowledge on the genomic and molecular profile of lymphomatous cells and their microenvironment have helped to better characterize the pathophysiology of PCNSL. However, their diagnostic predictive and prognostic roles still remain unclear and have not yet been applied into the clinical practice. In this review we have reported the important advances on the knowledge of the main biomarkers detectable on biological fluids [blood, cerebrospinal fluid (CSF) and vitreous humor] that include genomic fragments, cytokines and their receptors, surface molecules. These biomarkers demonstrated a potential role in the early diagnosis of PCNSL, particularly when they are detected in combination, and some of them showed to have a prognostic value and a role in monitoring","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85427713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: The genetic underpinnings of follicular lymphoma (FL) are now better understood through sequencing efforts of the last decade. Epigenetic deregulation, particularly through mutations in chromatin-modifying enzymes, is recognised as a pivotal hallmark that occurs alongside the t(14;18) chromosomal translocation, together with mutations in genes that affect a number of secondary biological pathways including mTORC1, JAK-STAT, NF-kB signalling and immune evasion. In recent years, the functional relevance of these genetic aberrations has been independently deciphered. The protracted nature of FL has provided an excellent model to chart the heterogeneity and evolution of the genetic features of the lymphomas both temporally and spatially. These studies have pointed to the early and late genetic drivers of the disease and the existence of a putative reservoir population that is difficult to eradicate with conventional treatment and most likely contributes to the relapsing-remitting nature of FL. Additionally, these sequencing studies have identified similarities and distinct differences in the genetic profiles of FL compared to related histological entities. In this review, we aim to summarise the current state of our understanding of the genetic landscape and heterogeneity, its contribution to the spectrum of clinical phenotypes in FL and related entities and finally, the ongoing efforts to utilise biology to provide lines of sight to the clinic.
{"title":"Genetic heterogeneity in follicular lymphoma","authors":"Megan Perrett, J. Okosun","doi":"10.21037/AOL-21-5","DOIUrl":"https://doi.org/10.21037/AOL-21-5","url":null,"abstract":": The genetic underpinnings of follicular lymphoma (FL) are now better understood through sequencing efforts of the last decade. Epigenetic deregulation, particularly through mutations in chromatin-modifying enzymes, is recognised as a pivotal hallmark that occurs alongside the t(14;18) chromosomal translocation, together with mutations in genes that affect a number of secondary biological pathways including mTORC1, JAK-STAT, NF-kB signalling and immune evasion. In recent years, the functional relevance of these genetic aberrations has been independently deciphered. The protracted nature of FL has provided an excellent model to chart the heterogeneity and evolution of the genetic features of the lymphomas both temporally and spatially. These studies have pointed to the early and late genetic drivers of the disease and the existence of a putative reservoir population that is difficult to eradicate with conventional treatment and most likely contributes to the relapsing-remitting nature of FL. Additionally, these sequencing studies have identified similarities and distinct differences in the genetic profiles of FL compared to related histological entities. In this review, we aim to summarise the current state of our understanding of the genetic landscape and heterogeneity, its contribution to the spectrum of clinical phenotypes in FL and related entities and finally, the ongoing efforts to utilise biology to provide lines of sight to the clinic.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84216812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that can affect any component of the central nervous system: brain, eyes and/or spinal cord. While it is a rare entity, the incidence has been rising since the 1960s with an increase in incidence in the 1990s that coincided with the human immunodeficiency virus (HIV) pandemic. More recently in the last two decades, incidence has been rising in the elderly population. PCNSL can have a wide range of presentations given possible involvement of any part of the nervous system, which can often lead to a delay in the diagnosis and treatment. Depending on the location involved, PCNSL can present with a variety of symptoms. Intracranial lesions are the most common manifestation of PCNSL and the majority present with focal neurologic symptoms, but nonspecific non-specific neuropsychiatric symptoms are also common. Primary leptomeningeal involvement is rare and can manifest with cranial neuropathies. Primary vitreoretinal lymphoma can present with blurred vision and symptoms mimicking uveitis. Spinal cord involvement can present with subacute myelopathy and peripheral nerve involvement or neurolymphomatosis can present with focal sensory and motor involvement. Given the wide range of clinical presentation, an understanding of the variable clinical manifestations of PCNSL is important for prompt diagnosis and treatment.
{"title":"Primary central nervous system lymphoma: epidemiology and clinical presentation","authors":"Kun Song, S. Issa, T. Batchelor","doi":"10.21037/AOL-20-50","DOIUrl":"https://doi.org/10.21037/AOL-20-50","url":null,"abstract":"Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that can affect any component of the central nervous system: brain, eyes and/or spinal cord. While it is a rare entity, the incidence has been rising since the 1960s with an increase in incidence in the 1990s that coincided with the human immunodeficiency virus (HIV) pandemic. More recently in the last two decades, incidence has been rising in the elderly population. PCNSL can have a wide range of presentations given possible involvement of any part of the nervous system, which can often lead to a delay in the diagnosis and treatment. Depending on the location involved, PCNSL can present with a variety of symptoms. Intracranial lesions are the most common manifestation of PCNSL and the majority present with focal neurologic symptoms, but nonspecific non-specific neuropsychiatric symptoms are also common. Primary leptomeningeal involvement is rare and can manifest with cranial neuropathies. Primary vitreoretinal lymphoma can present with blurred vision and symptoms mimicking uveitis. Spinal cord involvement can present with subacute myelopathy and peripheral nerve involvement or neurolymphomatosis can present with focal sensory and motor involvement. Given the wide range of clinical presentation, an understanding of the variable clinical manifestations of PCNSL is important for prompt diagnosis and treatment.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88780809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Secondary central nervous system (CNS) lymphomas (SCNSL) include the systemic lymphoproliferative diseases with CNS involvement at presentation or at relapse or at both stages of disease. Potentially all lymphoproliferative diseases can present or relapse in the CNS, although with a different incidence. While for some of these the management of CNS localization can be considered standard for others a worldwide consensus on the management and treatment lacks. The incidence of CNS relapse in diffuse large B-cell lymphoma (DLBCL) is about 5%, and it is possibly slightly reduced over the last decades. Two possible reasons of this reduction are: (I) the improvement of systemic disease control obtained with the addition of rituximab to the chemotherapy; (II) the advances in identifying patients at high risk of CNS relapse and the application of prophylaxis. However, many unanswered questions remain and there is not a worldwide consensus on the criteria identifying patients at high risk of CNS and on the standard prophylaxis therapy. Patients who develop SCNSL have a poor prognosis, and the optimal treatment is unknown, and indeed often unsatisfactory. In this manuscript we report the important advances of the knowledge of this rare and fatal disease, obtained in the last years, thanks to the development of multicenter collaborations. However, this disease remains still highly fatal and the discovery of more and more efficient therapy strategies is becoming a priority. New therapeutic strategies alternative to or in combination with chemotherapy such as target and immunomodulatory therapy are being addressed in future trials. In this regard, a more accurate knowledge of the molecular and biological characteristics of this malignancy is becoming a priority for the development of innovative therapies that will be firstly investigated in refractory/ relapsing patients and, if efficient, successively incorporated as part of first-line treatment.
{"title":"Narrative review: secondary central nervous system lymphoma","authors":"S. Steffanoni, Jeanette Karin Doorduijin","doi":"10.21037/AOL-20-39","DOIUrl":"https://doi.org/10.21037/AOL-20-39","url":null,"abstract":": Secondary central nervous system (CNS) lymphomas (SCNSL) include the systemic lymphoproliferative diseases with CNS involvement at presentation or at relapse or at both stages of disease. Potentially all lymphoproliferative diseases can present or relapse in the CNS, although with a different incidence. While for some of these the management of CNS localization can be considered standard for others a worldwide consensus on the management and treatment lacks. The incidence of CNS relapse in diffuse large B-cell lymphoma (DLBCL) is about 5%, and it is possibly slightly reduced over the last decades. Two possible reasons of this reduction are: (I) the improvement of systemic disease control obtained with the addition of rituximab to the chemotherapy; (II) the advances in identifying patients at high risk of CNS relapse and the application of prophylaxis. However, many unanswered questions remain and there is not a worldwide consensus on the criteria identifying patients at high risk of CNS and on the standard prophylaxis therapy. Patients who develop SCNSL have a poor prognosis, and the optimal treatment is unknown, and indeed often unsatisfactory. In this manuscript we report the important advances of the knowledge of this rare and fatal disease, obtained in the last years, thanks to the development of multicenter collaborations. However, this disease remains still highly fatal and the discovery of more and more efficient therapy strategies is becoming a priority. New therapeutic strategies alternative to or in combination with chemotherapy such as target and immunomodulatory therapy are being addressed in future trials. In this regard, a more accurate knowledge of the molecular and biological characteristics of this malignancy is becoming a priority for the development of innovative therapies that will be firstly investigated in refractory/ relapsing patients and, if efficient, successively incorporated as part of first-line treatment.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85486745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Follicular lymphoma (FL) represents a group of B-cell neoplasms derived from germinal center (GC) B cells. A better understanding of the pathogenic mechanisms of FL is important for developing innovative therapies. The most common form of FL is primarily nodal and associated with the t(14;18). Recent advances obtained via genomic profiling have provided unprecedented insights into the pathogenesis of FL. Conventional FL evolves through multiple independent or convergent genetic pathways. The classical pathogenesis of t(14;18)-positive FL is a multi-stage and multi-hit process escalating along accumulation of genetic and epigenetic alterations, which starts from FL-like B cells, through premalignant lesions, into full-blown malignancy. Early precursor lesions have been recognized in the form of FL-like B cells in normal peripheral blood, and both in-situ follicular neoplasia (ISFN) and duodenal-type FL. In comparison, t(14;18)-negative FL is much more heterogeneous at the molecular level, and the underlying mechanisms are less well understood. Some variants of FL, while lacking upregulation of BCL2, share a common mutational profile with conventional FL, including mutations in epigenetic modifiers. These cases also show some clinical overlap with BCL2-positive FL, including mainly nodal involvement. Other forms of FL show more profound differences, both clinically and biologically. These emerge more clearly as separate entities and include FL, grade 3B, testicular FL (TFL), pediatric-type FL (PTFL), and primary cutaneous follicle center lymphoma (PCFCL). Mutations in epigenetic regulators and 1p36/ TNFRSF14 abnormalities are highly recurrent and are seen across different subtypes of FL. Genetic profiling has offered important new insights, and will continue to impact the diagnostic approach, with changes in future classification schemes.
{"title":"Molecular insights into the pathogenesis of follicular lymphoma","authors":"Ting Zhou, S. Pittaluga, E. Jaffe","doi":"10.21037/AOL-20-49","DOIUrl":"https://doi.org/10.21037/AOL-20-49","url":null,"abstract":": Follicular lymphoma (FL) represents a group of B-cell neoplasms derived from germinal center (GC) B cells. A better understanding of the pathogenic mechanisms of FL is important for developing innovative therapies. The most common form of FL is primarily nodal and associated with the t(14;18). Recent advances obtained via genomic profiling have provided unprecedented insights into the pathogenesis of FL. Conventional FL evolves through multiple independent or convergent genetic pathways. The classical pathogenesis of t(14;18)-positive FL is a multi-stage and multi-hit process escalating along accumulation of genetic and epigenetic alterations, which starts from FL-like B cells, through premalignant lesions, into full-blown malignancy. Early precursor lesions have been recognized in the form of FL-like B cells in normal peripheral blood, and both in-situ follicular neoplasia (ISFN) and duodenal-type FL. In comparison, t(14;18)-negative FL is much more heterogeneous at the molecular level, and the underlying mechanisms are less well understood. Some variants of FL, while lacking upregulation of BCL2, share a common mutational profile with conventional FL, including mutations in epigenetic modifiers. These cases also show some clinical overlap with BCL2-positive FL, including mainly nodal involvement. Other forms of FL show more profound differences, both clinically and biologically. These emerge more clearly as separate entities and include FL, grade 3B, testicular FL (TFL), pediatric-type FL (PTFL), and primary cutaneous follicle center lymphoma (PCFCL). Mutations in epigenetic regulators and 1p36/ TNFRSF14 abnormalities are highly recurrent and are seen across different subtypes of FL. Genetic profiling has offered important new insights, and will continue to impact the diagnostic approach, with changes in future classification schemes.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"15 12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86972908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-01Epub Date: 2021-03-30DOI: 10.21037/aol-20-28
James R Cerhan, Thomas M Habermann
In 2016 there were an estimated 7,460 newly diagnosed patients with marginal zone lymphoma (MZL) in the US, which comprised 7% of all mature non-Hodgkin lymphomas (NHL). Based on data from the US SEER-18 program from 2001-2017, the age-standardized incidence rate for MZL was 19.6 per 1,000,000 person-years; 9% of MZL cases were splenic MZL (SMZL), 30% nodal MZL (NMZL), and 61% extranodal MZL (EMZL) of mucusa-associated lymphoid tissue (MALT). Incidence rates were slightly higher in men for SMZL and NMZL, but similar for EMZL, and increased steeply with age for all MZL subtypes. The incidence (age-standardized per 1,000,000) of MZL was highest among non-Hispanic whites (20.7), followed by Hispanics of all races (17.6), non-Hispanic blacks (15.4), and Asian/Pacific islanders (15.0). The incidence of MZL increased +1.0% per year in the US from 2001-2017, with increases reported in other countries during this timeframe. The 5-year relative survival rate for MZL in the US was 89.8% and was similar across racial/ethnic groups and by sex; survival rates have been increasing in the US and other countries. Established risk factors for MZL (or MZL subtypes) include family history of NHL, genetic loci in the HLA region, Helicobacter pylori infection (gastric MALT lymphoma), and several autoimmune diseases (Sjögren syndrome, systemic lupus erythematosus and Hashimoto thyroiditis), with strong (but not definitive) evidence for Chlamydia psittaci (ocular adnexal MALT lymphoma), Borrelia burgdorferi (cutaneous MZL), hepatitis C virus, human immunodeficiency virus, and solid organ transplantation. Promising risk factors that require additional study include other infections, other autoimmune conditions, trichloroethylene exposure, certain occupations, hair dye, cigarette smoking, sun exposure (protective), and alcohol use (protective). MZL is a model of an antigen-driven malignancy, where epidemiologic risk factors, tissue-specific factors, and host immune response (including the impact of chronic inflammation and immunosuppression) drive lymphomagenesis with implications for prevention.
{"title":"Epidemiology of Marginal Zone Lymphoma.","authors":"James R Cerhan, Thomas M Habermann","doi":"10.21037/aol-20-28","DOIUrl":"https://doi.org/10.21037/aol-20-28","url":null,"abstract":"<p><p>In 2016 there were an estimated 7,460 newly diagnosed patients with marginal zone lymphoma (MZL) in the US, which comprised 7% of all mature non-Hodgkin lymphomas (NHL). Based on data from the US SEER-18 program from 2001-2017, the age-standardized incidence rate for MZL was 19.6 per 1,000,000 person-years; 9% of MZL cases were splenic MZL (SMZL), 30% nodal MZL (NMZL), and 61% extranodal MZL (EMZL) of mucusa-associated lymphoid tissue (MALT). Incidence rates were slightly higher in men for SMZL and NMZL, but similar for EMZL, and increased steeply with age for all MZL subtypes. The incidence (age-standardized per 1,000,000) of MZL was highest among non-Hispanic whites (20.7), followed by Hispanics of all races (17.6), non-Hispanic blacks (15.4), and Asian/Pacific islanders (15.0). The incidence of MZL increased +1.0% per year in the US from 2001-2017, with increases reported in other countries during this timeframe. The 5-year relative survival rate for MZL in the US was 89.8% and was similar across racial/ethnic groups and by sex; survival rates have been increasing in the US and other countries. Established risk factors for MZL (or MZL subtypes) include family history of NHL, genetic loci in the HLA region, <i>Helicobacter pylori</i> infection (gastric MALT lymphoma), and several autoimmune diseases (Sjögren syndrome, systemic lupus erythematosus and Hashimoto thyroiditis), with strong (but not definitive) evidence for <i>Chlamydia psittaci</i> (ocular adnexal MALT lymphoma), <i>Borrelia burgdorferi</i> (cutaneous MZL), hepatitis C virus, human immunodeficiency virus, and solid organ transplantation. Promising risk factors that require additional study include other infections, other autoimmune conditions, trichloroethylene exposure, certain occupations, hair dye, cigarette smoking, sun exposure (protective), and alcohol use (protective). MZL is a model of an antigen-driven malignancy, where epidemiologic risk factors, tissue-specific factors, and host immune response (including the impact of chronic inflammation and immunosuppression) drive lymphomagenesis with implications for prevention.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020862/pdf/nihms-1670831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25586091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lauren R Schaff, Prakash Ambady, Nancy D Doolittle, Christian Grommes
Primary central nervous system lymphoma (PCNSL) is a rare disease of the brain, spine, cerebrospinal fluid (CSF) and/or vitreoretinal space. PCNSL is chemo and radiosensitive but relapse is common even years after initial treatment. Outside of consensus regarding the use of high-dose methotrexate (HD-MTX) for first line treatment, there is little uniformity in the management of newly diagnosed or relapsed PCNSL. The lack of consensus is driven by a paucity of randomized trials in this disease. Prospective studies are troubled by low enrollment, the lack of a standard induction regimen, and a varied approach to consolidation strategies. Moreover, the PCNSL patient population is heterogeneous and includes a high proportion of elderly or frail patients and consists of patients manifesting disease in varied compartments of the central nervous system (CNS). As a result, current treatment strategies vary widely and are often dictated by physician and institutional preference or regional practice. This review provides an overview of recently completed and ongoing therapeutic studies for patients with newly diagnosed and recurrent or refractory PCNSL. It discusses the existing evidence behind common approaches to induction and consolidation or maintenance regimens as well as the recent data regarding management of recurrent disease. Finally, it highlights the complexity of trial design in this disease and provides a framework for the design of future studies, which are needed to identify patient populations likely to benefit from specific induction, consolidation, or maintenance therapies.
{"title":"Primary central nervous system lymphoma: a narrative review of ongoing clinical trials and goals for future studies.","authors":"Lauren R Schaff, Prakash Ambady, Nancy D Doolittle, Christian Grommes","doi":"10.21037/aol-20-47","DOIUrl":"https://doi.org/10.21037/aol-20-47","url":null,"abstract":"<p><p>Primary central nervous system lymphoma (PCNSL) is a rare disease of the brain, spine, cerebrospinal fluid (CSF) and/or vitreoretinal space. PCNSL is chemo and radiosensitive but relapse is common even years after initial treatment. Outside of consensus regarding the use of high-dose methotrexate (HD-MTX) for first line treatment, there is little uniformity in the management of newly diagnosed or relapsed PCNSL. The lack of consensus is driven by a paucity of randomized trials in this disease. Prospective studies are troubled by low enrollment, the lack of a standard induction regimen, and a varied approach to consolidation strategies. Moreover, the PCNSL patient population is heterogeneous and includes a high proportion of elderly or frail patients and consists of patients manifesting disease in varied compartments of the central nervous system (CNS). As a result, current treatment strategies vary widely and are often dictated by physician and institutional preference or regional practice. This review provides an overview of recently completed and ongoing therapeutic studies for patients with newly diagnosed and recurrent or refractory PCNSL. It discusses the existing evidence behind common approaches to induction and consolidation or maintenance regimens as well as the recent data regarding management of recurrent disease. Finally, it highlights the complexity of trial design in this disease and provides a framework for the design of future studies, which are needed to identify patient populations likely to benefit from specific induction, consolidation, or maintenance therapies.</p>","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/81/31/nihms-1690102.PMC8078860.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38919526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The association between human immunodeficiency virus (HIV) and lymphoma was observed early in the HIV epidemic in the 1980s. Lymphoma incidence remains significantly higher than in the general population. Previously people living with HIV (PLWH) had advanced immune suppression, organ dysfunction and consequently poor performance status (PS). The advent of combination antiretroviral therapy (ART) has led to improved immune reconstitution and significantly enhanced the outlook of PLWH, influenced the incidence of lymphoma subtypes and improved tolerability of treatment. However lymphoma still remains the most common cause of cancer related death. We describe the multidisciplinary management of HIV-associated lymphomas and outline recent advances. Challenges include the advanced stage at presentation, propensity for extranodal sites including the central nervous system (CNS), potential drug interactions and increased incidence of opportunistic infections (OIs). Overall management now focusses less on HIV-related factors and more on lymphoma characteristics, with favourable outcomes. Representation in lymphoma clinical trials however is lacking, as a positive serostatus is an exclusion criterion for the majority. Data is scant for the rarer subtypes. A number of small phase I/II trials have successfully recruited patients living with HIV. Immunotherapy trial and safety data will be essential in understanding toxicity and efficacy of this promising targeted treatment. We welcome the recent more permissive inclusion criteria for clinical trials and support the expansion of understudied targeted therapies particularly for rarer subtypes. Broadening access will provide better equity for those living with HIV.
{"title":"HIV-associated lymphoma—advances in clinical management","authors":"J. Khwaja, J. E. Burns, N. Ahmed, K. Cwynarski","doi":"10.21037/aol-21-16","DOIUrl":"https://doi.org/10.21037/aol-21-16","url":null,"abstract":"The association between human immunodeficiency virus (HIV) and lymphoma was observed early in the HIV epidemic in the 1980s. Lymphoma incidence remains significantly higher than in the general population. Previously people living with HIV (PLWH) had advanced immune suppression, organ dysfunction and consequently poor performance status (PS). The advent of combination antiretroviral therapy (ART) has led to improved immune reconstitution and significantly enhanced the outlook of PLWH, influenced the incidence of lymphoma subtypes and improved tolerability of treatment. However lymphoma still remains the most common cause of cancer related death. We describe the multidisciplinary management of HIV-associated lymphomas and outline recent advances. Challenges include the advanced stage at presentation, propensity for extranodal sites including the central nervous system (CNS), potential drug interactions and increased incidence of opportunistic infections (OIs). Overall management now focusses less on HIV-related factors and more on lymphoma characteristics, with favourable outcomes. Representation in lymphoma clinical trials however is lacking, as a positive serostatus is an exclusion criterion for the majority. Data is scant for the rarer subtypes. A number of small phase I/II trials have successfully recruited patients living with HIV. Immunotherapy trial and safety data will be essential in understanding toxicity and efficacy of this promising targeted treatment. We welcome the recent more permissive inclusion criteria for clinical trials and support the expansion of understudied targeted therapies particularly for rarer subtypes. Broadening access will provide better equity for those living with HIV.","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75043960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
: Hodgkin lymphoma (HL) exists in two major forms, the so-called classical type (cHL) and the nodular lymphocyte predominant type (NLPHL). Since NLPHL is considered to be an EBV-negative entity, this review focusses only on the cHL form. Although cHL is a curable disease in many cases, we still lack an understanding of its pathogenesis that could lead to kinder treatments for patients, and also to more effective therapies for the smaller subset of patients who are destined to die of their disease. One approach might be to therapeutically target the Epstein-Barr virus (EBV), which is present in up to one-half of cases in resource rich nations, and in almost all cases in some resource-poor countries. However, it has been suggested that EBV might be simply a silent passenger in cHL. In this review, we present evidence in support of a crucial role for EBV in virus-positive cHL. In particular, we highlight important epidemiological differences between EBV-positive and EBV-negative cHL that suggest different aetiologies, as well as genetic differences, including a different profile of somatic mutations pointing to a distinct contribution for EBV in substituting for cellular genetic changes that are required for disease development when the virus is absent. We also focus attention on important roles for the individual latent virus genes in the pathogenesis of cHL. Overall, this review suggests that a better understanding of how EBV contributes to the pathogenesis of cHL may eventually lead to improved stratification of patients and to the development of therapies that specifically target EBV or its latent genes. 13
{"title":"The contribution of ebv to the pathogenesis of classical hodgkin lymphoma","authors":"K. Vrzalikova, M. Pugh, L. Mundo, P. Murray","doi":"10.21037/AOL-21-8","DOIUrl":"https://doi.org/10.21037/AOL-21-8","url":null,"abstract":": Hodgkin lymphoma (HL) exists in two major forms, the so-called classical type (cHL) and the nodular lymphocyte predominant type (NLPHL). Since NLPHL is considered to be an EBV-negative entity, this review focusses only on the cHL form. Although cHL is a curable disease in many cases, we still lack an understanding of its pathogenesis that could lead to kinder treatments for patients, and also to more effective therapies for the smaller subset of patients who are destined to die of their disease. One approach might be to therapeutically target the Epstein-Barr virus (EBV), which is present in up to one-half of cases in resource rich nations, and in almost all cases in some resource-poor countries. However, it has been suggested that EBV might be simply a silent passenger in cHL. In this review, we present evidence in support of a crucial role for EBV in virus-positive cHL. In particular, we highlight important epidemiological differences between EBV-positive and EBV-negative cHL that suggest different aetiologies, as well as genetic differences, including a different profile of somatic mutations pointing to a distinct contribution for EBV in substituting for cellular genetic changes that are required for disease development when the virus is absent. We also focus attention on important roles for the individual latent virus genes in the pathogenesis of cHL. Overall, this review suggests that a better understanding of how EBV contributes to the pathogenesis of cHL may eventually lead to improved stratification of patients and to the development of therapies that specifically target EBV or its latent genes. 13","PeriodicalId":72224,"journal":{"name":"Annals of lymphoma","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82984516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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