As the world turns, evolving lymphoma classifications-past, present and future.

The last century and a half has seen first the recognition of lymphomas, and then the publication of one lymphoma classification after another often together with highly critical comments about preceding classifications or a welcome that was less than warm. The introduction of HUMAN PATHOLOGY in 1970 came just before one of the very acrimonious periods in lymphoma classification, as we were learning more about the normal immune system and with the proposed functional lymphoma classifications of Lukes/Collins and Kiel in 1974 relating the lymphomas to their normal B-cell or T-cell 'counterparts'. Those difficult times were followed by the regressive strictly morphologic NCI Working Formulation in 1982, with the REAL classification in 1994 putting us back on a rational path, once again grouping the lymphoid neoplasms first into those of B-cell and T- and putative NK-cell origin, and then using multiple parameters to define specific entities. Planning for the first modern WHO lymphoma classification began soon afterward, with concordance and collegiality leading to the 2001 WHO classification, which then evolved with publication of the 2008 and 2016 WHO classifications. While this review looks at these important past developments which have gotten us to where we are today, it also concentrates on where we are now, what has been learned since the most recent WHO classification and 'Blue Book' were published and on some of the unanswered questions that remain as we look to the future.

Primary renal lymphoma: A population-based analysis using the SEER program (1973-2015).

OBJECTIVE: Primary renal lymphoma (PRL) is defined as a non-Hodgkin lymphoma (NHL) restricted to kidneys without extensive nodal disease. The literature on epidemiology and outcome in PRL is limited to case reports and small case series. METHODS: We utilized Surveillance, Epidemiology, and End Result database (1984-2015) to study the demographic, clinical, and pathological characteristics of PRL. We conducted analysis to assess factors associated with overall survival (OS) and cause-specific survival (CSS). RESULTS: A total of 599 (0.17% of all NHL) patients were eligible for the study. The age-adjusted incidence was 0.035/100,000 population and is increasing. The median age was 72 years, and most of the patients were Caucasians and were males. Most of the patients had unilateral tumors, and diffuse large B-cell lymphoma (DLBCL) was the most common histologic type. The median OS was 112 months, while median CSS was not reached. Age ≥ 60 years was the strongest independent risk factor for worse OS and CSS, while non-DLBCL histology was associated with better OS and CSS. DISCUSSION: Primary renal lymphoma is a rare lymphoma with increasing incidence in more recent years. In this study, we describe demographic, clinical, and pathological characteristics of PRL and factors affecting survival among these patients.

[Hodgkin and the classification of malignant lymphomas: how the British physician also became associated with later discovered lymphomas]. / Hodgkin en de classificatie van maligne lymfomen.

Thomas Hodgkin was the first to describe a malignant lymphoma, which would later carry his name. Over the course of time, other lymphoid malignancies were recognised that showed no similarity with Hodgkin's disease. They were subsequently named after the - at that time - applicable morphological nomenclature of the associated cells. Later, nomenclature also took immunological features into consideration. However, we still describe the group of lymphomas recognised after Hodgkin's discovery as 'not being Hodgkin's disease', i.e. non-Hodgkin lymphoma. We feel it is unjust that not many people know about the man behind this prominent disease. In this article, an historic overview is given of Thomas Hodgkin, 'his' lymphoma and the other malignant lymphomas.

Increasing incidence of primary central nervous system lymphoma but no improvement in survival in Sweden 2000-2013.

OBJECTIVES: This study aims to characterize the epidemiology of immunocompetent Primary central nervous system lymphoma (PCNSL) diagnosed 2000-2013 in Sweden. METHODS: Cases were identified in the population-based Swedish Lymphoma Register. Incidence per 100 000 person-years and 95% confidence intervals (CI) were calculated, and PCNSL-specific survival was estimated using relative survival. Tests for temporal trends were performed using Poisson regression. Population incidence of all brain tumors was retrieved for comparison. RESULTS: With 359 identified PCNSL cases (median age 66 years), overall incidence was 0.26 (95% CI: 0.24-0.29) and the average annual increase 4% (P = .002). The increasing trend was primarily observed among elderly individuals (70+ years). Similarly, an increase in incidence of all brain tumors was noted only among the elderly. There was no significant improvement in relative survival across the study period although, among fit patients (with Eastern Cooperative Oncology Group, EGOC 0), survival plateaued 6 years after diagnosis. CONCLUSION: The increasing PCNSL incidence in the elderly was consistent with an increasing incidence of brain tumors of any type and may in part be attributable to improved diagnostics and reporting in this group. New treatment options have not yet translated into general survival improvements in a population-based setting, although the presence of long-term survivors among fit patients is encouraging.

A Bacterial Cause of Cancer: An Historical Essay.

This article reviews the history of the discovery of microbes that increase the risk of cancer of some tissues with a special emphasis on the bacterium Helicobacter pylori and the role played by two Australian physicians, neither schooled in research, who had open minds about the shibboleth that mycobacteria (acid-fast organisms) can survive the acid environment of the stomach, but that other pathogenic bacteria cannot. They discovered one of the most important human pathogens, Helicobacter pylori, and showed it capable of inducing severe gastric inflammatory disease. Subsequently, others built on their observations and showed it capable of inducing two gastric neoplasms: carcinoma and lymphoma. The Oncologist 2017;22:542-548.

Historique de l'immunothérapie. Changement de paradigme ?

HISTORY OF IMMUNOTHERAPY. PARADIGM CHANGE?: Born at the dawn of the 20th century with W.B. Coley's intratumoral injections of bacteria, cancer immunotherapy was built on the corpus of the immune surveillance theory in 1957, modified by R.D. Schreiber in 2004. Scientific knowledge and technological advances have allowed it to become efficacious and to expand in the 21st century as the 4th and most important pillar of cancer treatment.

Population mixing for leukaemia, lymphoma and CNS tumours in teenagers and young adults in England, 1996-2005.

BACKGROUND: Little aetiological epidemiological research has been undertaken for major cancers occurring in teenagers and young adults (TYA). Population mixing, as a possible proxy for infectious exposure, has been well researched for childhood malignancies. We aimed to investigate effects of population mixing in this older age group using an English national cancer dataset. METHODS: Cases of leukaemia, lymphoma and central nervous system (CNS) tumours amongst 15-24 year olds in England (diagnosed 1996-2005) were included in the study. Data were obtained by ward of diagnosis and linked to 1991 census variables including population mixing (Shannon index); data on person-weighted population density and deprivation (Townsend score) were also used and considered as explanatory variables. Associations between TYA cancer incidence and census variables were investigated using negative binomial regression, and results presented as incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: A total of 6251 cases of leukaemia (21%), lymphoma (49%) and CNS tumours (30%) were analysed. Higher levels of population mixing were associated with a significant decrease in the incidence of CNS tumours (IRR=0.83, 95% CI=0.75-0.91), accounted for by astrocytomas and 'other CNS tumours'; however, there was no association with leukaemia or lymphoma. Incidence of CNS tumours and lymphoma was 3% lower in more deprived areas (IRR=0.97, 95% CI=0.96-0.99 and IRR=0.97, 95% CI=.96-0.98 respectively). Population density was not associated with the incidence of leukaemia, lymphoma or CNS tumours. CONCLUSIONS: Our results suggest a possible role for environmental risk factors with population correlates in the aetiology of CNS tumours amongst TYAs. Unlike studies of childhood cancer, associations between population mixing and the incidence of leukaemia and lymphoma were not observed.

High-dose therapy with autologous stem cell support for lymphoma--from experimental to standard treatment.

High-dose therapy with autologous stem cell support (HDT) has been a therapeutic option for lymphomas in Norway since as far back as 1987. By restoring bone marrow function through reinfusion of the patient's own stem cells, it is possible to administer cancer treatment in higher and otherwise lethal doses, and thereby achieve better treatment results. Originally stem cells were harvested from bone marrow and the high-dose therapy included total body irradiation, but since the mid 1990s stem cells have been harvested by apheresis and the high-dose therapy has consisted of chemotherapy alone (BEAM chemotherapy). In 1995 the treatment was regionalised and since then it has been performed in all health regions. The HDT procedure was introduced as an experimental treatment in clinical studies with international collaboration. The indications have changed over time, and this is now established treatment for a number of types of lymphoma.

Evolution of the techniques of radiation therapy in the management of lymphoma.

Radiation techniques for the treatment of Hodgkin's disease have evolved dramatically in the past century. Shortly after the discovery of X-rays, the lymphomas in general, and Hodgkin's disease in particular, were noted to be radiosensitive. However, equipment limitations restricted the ability to administer sufficient doses to adequate depth to ensure long-term control. This situation improved sequentially with the development of the Coolidge tube, (60)Co machine, and medical linear accelerators. With megavoltage radiation it was possible to demonstrate cures of stage I-II disease with high-dose extended-field irradiation. When combined modality therapy programs were introduced, this permitted restriction of radiation fields and doses in order to decrease toxicity. Innovative advanced technologies such as PET simulation, 3-D treatment planning, intensity-modulated radiotherapy, active breathing control, and proton therapy have further improved the outcomes for patients treated with irradiation.

Classifications of lymphoma; reflections of time and technology.

'Nowhere in pathology has a chaos of names so clouded clear concepts as in the subject lymphoid tumors'. R.A. Willis. In 1858, Rudolf Virchow, with a primitive microscope and limited experiential base, recognized 'at least three different conditions here, hyperinosis, leucocytosis and leukemia….'. One hundred and fifty years later, the World Health Organization (WHO 2008), with a much more extensive armamentarium of tools, and a wealth of diverse experience, promulgated criteria distinguishing more than 100 types of 'Tumors of the Hematopoietic and Lymphoid Tissues'. From three to one hundred and three; this is progress! And this is history! Our goal is to examine the course and causes of this history; how we moved from three entities to a hundred and three, what we have learned from it, and how we may use the insights that we have gained to anticipate 'future histories' in this marvelously dynamic area of biology and disease.