Lymphoma: History and Discovery

The story of lymphoma is a nearly two-hundred-year detective trail that runs from a quiet museum curator dissecting seven bodies in 1832 to the molecular classification of the 21st century. It is a history of careful looking: of pathologists arguing over a single strange giant cell, of a surgeon coining a word, of an Irish missionary doctor noticing a jaw tumour in African children and, with it, opening the entire field of cancer-causing viruses. Throughout, the names attached to the disease — Hodgkin, Reed-Sternberg, Burkitt — mark not single moments of genius but a slow accumulation of evidence by many hands. This page traces who saw what, and when, with care to separate the first description of a disease from the later attachment of a person's name to it, and to mark hypotheses as hypotheses.

Table of Contents

  1. Thomas Hodgkin and the Seven Cases of 1832
  2. Samuel Wilks and the Naming of Hodgkin's Disease (1865)
  3. The Reed-Sternberg Cell: Sternberg (1898) and Reed (1902)
  4. Virchow, Billroth, and the Birth of the Word "Lymphoma"
  5. The Non-Hodgkin Lymphomas Take Shape
  6. Denis Burkitt, the African Lymphoma, and Epstein-Barr Virus
  7. A Century of Classification: From Rappaport to the WHO
  8. From Incurable to Curable: Radiotherapy and MOPP
  9. B Cells, T Cells, and the Molecular Era
  10. Research Papers and References
  11. Connections

Thomas Hodgkin and the Seven Cases of 1832

The recorded history of lymphoma as a distinct disease begins with Thomas Hodgkin (1798–1866), an English physician and pathologist at Guy's Hospital in London. Hodgkin had joined Guy's as a curator of its anatomical museum in 1826, a role that made him, in effect, a full-time student of diseased tissue at a time when most physicians studied the living patient and rarely the corpse. Working alongside his celebrated contemporaries Richard Bright and Thomas Addison — together the so-called "three great men of Guy's" — Hodgkin had an unusually disciplined eye for the gross (naked-eye) appearance of organs at autopsy.

In January 1832 his paper "On Some Morbid Appearances of the Absorbent Glands and Spleen" was read to the Medical and Chirurgical Society of London. In it Hodgkin described seven cases in which the "absorbent glands" (the period term for lymph nodes) and the spleen were progressively and massively enlarged in a way he believed was a primary disease of those organs themselves — not a secondary inflammation or a spread from elsewhere. This insight, that the lymphatic system could be the seat of its own malignancy, is what makes the paper a landmark. It is worth being candid about the limits of his evidence: working only with the naked eye, decades before reliable microscopy of tissue, Hodgkin could not have known that some of his seven cases were almost certainly other diseases, such as tuberculosis, rather than what we now call Hodgkin lymphoma. Modern re-examination of the surviving specimens suggests only a portion were true cases.

Hodgkin's report attracted little attention in his lifetime. He left Guy's after being passed over for a senior post, devoted much of his later life to humanitarian causes, and died of dysentery in 1866 while accompanying the philanthropist Sir Moses Montefiore on a journey to the Middle East. His foundational paper was, for more than three decades, very nearly forgotten.

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Samuel Wilks and the Naming of Hodgkin's Disease (1865)

The eponym "Hodgkin's disease" did not come from Hodgkin and did not appear in 1832. It was the gift of a successor at the same hospital, Sir Samuel Wilks (1824–1911), a physician, pathologist, and biographer of Guy's. Wilks independently encountered a series of patients with the same pattern of enlarged lymph nodes and spleen. He published an initial account in 1856 — at first unaware that anyone had described the condition before him.

On learning that Thomas Hodgkin had documented the same disease a generation earlier, Wilks did something that has made the episode a small classic of scientific generosity: rather than claim the territory, he credited his predecessor. In 1865 he published a larger series of fifteen cases under a title naming the condition "Cases of Enlargement of the Lymphatic Glands and Spleen (or, Hodgkin's Disease)", lamenting that "Dr. Hodgkin did not affix a distinct name to the disease." It is largely thanks to Wilks that Hodgkin — whose own obituary did not even mention the paper — is remembered in medicine at all.

This is the central distinction to keep straight: the first description was Hodgkin's, in 1832; the eponym was coined by Wilks, in 1865. The disease and the name therefore have different fathers and different dates, a pattern that recurs throughout the history of lymphoma.

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The Reed-Sternberg Cell: Sternberg (1898) and Reed (1902)

For most of the 19th century, Hodgkin's disease was a diagnosis made by gross appearance and clinical course. What transformed it into a disease defined under the microscope was the recognition of a peculiar giant cell — large, often two-lobed or multinucleated, with prominent "owl-eye" nucleoli — that became the histological signature of the condition. Two pathologists, working a few years and an ocean apart, are jointly credited with its definitive description.

The Austrian pathologist Carl Sternberg published his account in 1898, including descriptions and illustrations of the characteristic cells. Notably — and this is a historically important caveat — Sternberg interpreted the disease as a peculiar form of tuberculosis, a reasonable hypothesis at the time given how often TB and lymphoma could coexist or mimic one another. That interpretation was wrong, but his morphological description was sound. Four years later, the American physician Dorothy Reed (later Dorothy Reed Mendenhall) published, in 1902, her paper "On the Pathological Changes in Hodgkin's Disease, with Especial Reference to its Relation to Tuberculosis," giving an exceptionally clear, well-illustrated description of the same cells and arguing — correctly — that the disease was not tuberculosis.

Their two names were joined into the Reed-Sternberg cell, the hallmark whose presence still defines classic Hodgkin lymphoma today. (By convention, the multinucleated form is the Reed-Sternberg cell and a mononuclear variant is called the Hodgkin cell.) As with the disease's name, the eponym papers over a genuine priority debate — earlier observers, including Greenfield, had drawn similar cells — but the descriptions of Sternberg and Reed are the ones accepted as foundational.

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Virchow, Billroth, and the Birth of the Word "Lymphoma"

While Hodgkin's disease was acquiring its name and its signature cell, the broader vocabulary of lymphatic cancer was being assembled by the founders of modern pathology in continental Europe. The towering figure here is the German pathologist Rudolf Virchow (1821–1902), the architect of cellular pathology. Virchow introduced the term "leukemia" in 1845 (independently and in the same year as the Scottish physician John Hugh Bennett), and in 1863 he used the term "lymphosarcoma" for malignant solid tumours arising in lymphoid tissue. Virchow's framework began the long, difficult work of distinguishing the leukaemias (cancers spilling into the blood) from the lymphomas (solid tumours of lymphoid organs) — a distinction that turned out to be far blurrier than anyone first supposed, since many lymphomas can circulate and many leukaemias arise from lymphocytes.

The word from which the whole category takes its modern name was coined by the great Viennese surgeon Theodor Billroth, who is generally credited with introducing the term "malignant lymphoma" around 1871 to describe these solid lymphoid tumours. The terminology remained unsettled for decades: in 1893 the Austrian physician Hans Kundrat reintroduced and sharpened "lymphosarcoma" for a generalized, uniformly fatal disease of the lymphatic system, so much so that non-Hodgkin lymphomas were for a time called Kundrat's disease. The modern, broad umbrella term "lymphoma" — covering every malignancy of the lymphocyte — is thus a composite inheritance from Virchow, Billroth, Kundrat, and many others across the later 19th and 20th centuries, not the invention of any one person on any one date.

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The Non-Hodgkin Lymphomas Take Shape

Once Hodgkin's disease had a defining cell, everything that looked like a lymphatic cancer but lacked the Reed-Sternberg cell came to be lumped together as a residual category. The phrase "non-Hodgkin lymphoma" (NHL) is therefore historically backwards: it is defined by what a tumour is not, a linguistic fossil of the fact that Hodgkin's was the first lymphoma to be cleanly recognized. The category is enormous and biologically diverse, encompassing dozens of distinct diseases that share only an origin in the lymphocyte.

Through the late 19th and early 20th centuries, pathologists worked to carve order out of this mass. Kundrat's lymphosarcoma, the "giant follicular lymphoma" that Brill and colleagues and later Symmers described in the 1920s and 1930s (giving the historical name Brill-Symmers disease to what is now follicular lymphoma), and a growing list of named entities accumulated faster than any unifying theory could organize them. Without the microscope's later companions — immunology and genetics — these early classifiers could rely only on what cells looked like, and morphology alone repeatedly proved an unreliable guide to how a given lymphoma would behave.

The result, by the mid-20th century, was a confusing thicket of competing names for overlapping diseases. Imposing rational order on the non-Hodgkin lymphomas would occupy pathologists for the rest of the century and is taken up in the classification section below.

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Denis Burkitt, the African Lymphoma, and Epstein-Barr Virus

One of the most consequential chapters in lymphoma's history did not begin in a European autopsy room but in East Africa. Denis Burkitt, an Irish surgeon working in Uganda, reported in 1958 a distinctive, fast-growing cancer that struck the jaw and abdomen of young children across a broad belt of central Africa. The aggressive tumour — a B-cell lymphoma — was soon named after him, Burkitt lymphoma. What made Burkitt's work revolutionary was not only the description but the epidemiology: he mapped the tumour's distribution and found it tracked geography, altitude, temperature, and rainfall in a way that matched the range of a mosquito-borne infection. This led him to a bold hypothesis — explicitly a hypothesis, and a contested one at the time — that an infectious agent might cause a human cancer.

That idea, then close to heresy, set off one of the great chases in cancer biology. After hearing Burkitt lecture in London in 1961, the pathologist Michael Anthony Epstein, working with Bert Achong and the PhD student Yvonne Barr, obtained tumour samples flown from Uganda. In 1964 the team, using electron microscopy of a cell line grown from the tumour, identified a previously unknown herpes-type virus — the Epstein-Barr virus (EBV), the first virus ever convincingly linked to a human cancer. EBV is now understood to be a contributing factor in (especially the endemic African form of) Burkitt lymphoma and in a subset of Hodgkin lymphomas and other cancers, though it is one element among several — including chronic malaria and a characteristic MYC gene translocation — rather than a sole cause. Burkitt's insight opened the entire field of tumour virology, which would later illuminate the roles of viruses in cervical, liver, and other cancers.

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A Century of Classification: From Rappaport to the WHO

The history of lymphoma in the 20th century is, in large part, the history of arguments over how to classify it — a problem with direct stakes for patients, because how a tumour is named determines how it is treated. The first widely adopted modern scheme was the Rappaport classification, developed by Henry Rappaport and finalized in a U.S. Armed Forces Institute of Pathology fascicle in 1966. Rappaport sorted non-Hodgkin lymphomas chiefly by architecture — nodular (better prognosis) versus diffuse (worse) — and by cell size. It was clinically useful and dominated practice for years, even though some of its underlying biological assumptions were later shown to be incorrect.

The 1970s brought the immunological revolution: the discovery that lymphocytes come in B-cell and T-cell lineages reframed every lymphoma as a cancer of a specific cell type frozen at a specific stage of development. Two rival schemes embraced this idea — the European Kiel classification (Karl Lennert and colleagues) and the American Lukes-Collins classification, both published around 1974. The proliferation of competing systems became so unworkable that the U.S. National Cancer Institute sponsored a compromise "Working Formulation" in 1982, intended as a translation table between the others.

The decisive modern breakthrough was the Revised European-American Lymphoma (REAL) classification, proposed in 1994 by the International Lymphoma Study Group (with Nancy Lee Harris and Elaine Jaffe among the leaders). REAL abandoned the search for one perfect organizing principle and instead defined each lymphoma as a real biological entity using everything available at once: appearance, immunophenotype, genetics, and clinical behaviour. This pragmatic, multi-parameter approach became the foundation of the World Health Organization (WHO) classification of lymphoid neoplasms, first published in 2001 and revised in subsequent editions (2008, 2017, and the 2022 update). The WHO system, the global standard today, is the direct descendant of every classifier from Kundrat onward.

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From Incurable to Curable: Radiotherapy and MOPP

For most of its documented history, lymphoma — and Hodgkin's disease in particular — was regarded as inexorably fatal. The transformation of Hodgkin lymphoma from a death sentence into one of the most curable of all cancers is itself a milestone in the broader history of oncology, and it unfolded along two fronts in the 20th century.

The first was radiation. The Canadian radiation oncologist Vera Peters demonstrated, in landmark work published from 1950 onward, that localized (early-stage) Hodgkin's disease could be cured — not merely palliated — by carefully delivered extended-field radiotherapy, overturning the prevailing assumption of incurability. Peters also pioneered the concept of clinical staging, the still-essential practice of defining how far a lymphoma has spread before deciding on treatment.

The second front was chemotherapy. At the U.S. National Cancer Institute in the mid-1960s, Vincent T. DeVita Jr. and colleagues showed that combining several drugs at once could cure even advanced Hodgkin's disease that radiation alone could not reach. Their regimen, the four-drug MOPP combination (mechlorethamine, Oncovin/vincristine, procarbazine, and prednisone), produced lasting complete remissions in a large fraction of patients; the pivotal results were published in 1970. MOPP is widely cited as the first demonstration that combination chemotherapy could cure a non-leukaemic cancer in adults, a proof of principle whose influence extended far beyond lymphoma. Later regimens such as ABVD reduced toxicity, and modern targeted and immunotherapeutic agents have continued the trajectory — but the historical pivot from "incurable" to "curable" was the work of Peters and DeVita.

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B Cells, T Cells, and the Molecular Era

The thread that ties two centuries of lymphoma history together is a steadily deepening answer to one question: what cell is this, and what went wrong inside it? Hodgkin could answer only at the level of the organ; Reed and Sternberg pushed the answer down to a single distinctive cell; the immunologists of the 1970s identified that cell's lineage as B or T; and the molecular biologists of recent decades have read the answer in the genome itself.

The recognition that the great majority of lymphomas (including, it eventually emerged, the strange Reed-Sternberg cell of Hodgkin lymphoma) arise from B lymphocytes, with a smaller share from T lymphocytes and natural-killer cells, gave classification a biological backbone. Landmark molecular findings followed: the MYC translocation that defines Burkitt lymphoma; the BCL2 rearrangement (the t(14;18) translocation) characteristic of follicular lymphoma; and the gene-expression profiling that, around the year 2000, split diffuse large B-cell lymphoma into distinct subtypes with different outcomes. These discoveries did not rename the old diseases so much as explain them, finally supplying the mechanistic "why" beneath the descriptive names left by Hodgkin, Kundrat, and Burkitt.

Seen whole, the history of lymphoma is a model of how medical knowledge actually grows: not by a single revelation but by generations of observers — a London curator, a generous Guy's physician, two pathologists arguing over a giant cell, a German father of cellular pathology, a Viennese surgeon, an Irish surgeon in Uganda, and the classifiers and oncologists who followed — each adding a layer, correcting a predecessor, and handing the question forward. The detailed clinical picture, subtypes, staging, and modern treatment are covered on the main Lymphoma page.

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Research Papers and References

The references below combine landmark historical papers and modern historical reviews with curated PubMed topic-search links into the history of lymphoma. Several entries are the original primary publications (Hodgkin 1832, Reed 1902, the 1964 EBV discovery, the 1970 MOPP trial); others are scholarly histories. Where a stable identifier is available it is linked directly; otherwise a PubMed topic search is provided. All external links open in a new tab.

  1. Hodgkin T. On some morbid appearances of the absorbent glands and spleen. Medico-Chirurgical Transactions. 1832;17:68–114. (Classics-in-oncology reprint, National Library of Medicine.) — PubMed: Hodgkin 1832 (classics in oncology reprint)
  2. Reed DM. On the pathological changes in Hodgkin's disease, with especial reference to its relation to tuberculosis. Johns Hopkins Hospital Reports. 1902;10:133–196. — PubMed: Dorothy Reed 1902 Hodgkin disease
  3. Stone MJ. Thomas Hodgkin: medical immortal and uncompromising idealist. Proc (Bayl Univ Med Cent). 2005;18(4):368–375. — PMC: Thomas Hodgkin biography
  4. Hellman S. Brief consideration of Thomas Hodgkin and his times. — PubMed: Hodgkin, Wilks, and the eponym
  5. Reed-Sternberg cells — history and pathology (StatPearls, National Library of Medicine). — NCBI Bookshelf: Reed-Sternberg cells
  6. A historical tale of two lymphomas. Part II: non-Hodgkin lymphoma. Ann Diagn Pathol / historical review. — PMC: A Historical Tale of Two Lymphomas (Part II)
  7. Burkitt D. A sarcoma involving the jaws in African children. Br J Surg. 1958;46(197):218–223. — PubMed: Burkitt 1958 African jaw sarcoma
  8. Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964;1(7335):702–703. — doi:10.1016/S0140-6736(64)91524-7
  9. Magrath I. Denis Burkitt and the African lymphoma. ecancermedicalscience. 2009;3:159. — PMC: Denis Burkitt and the African lymphoma
  10. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms (REAL): a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–1392. — PubMed: REAL classification 1994
  11. Rappaport H. Tumors of the hematopoietic system (Rappaport classification). AFIP Atlas of Tumor Pathology. 1966. — PubMed: Rappaport classification history
  12. DeVita VT, Serpick AA, Carbone PP. Combination chemotherapy (MOPP) in the treatment of advanced Hodgkin's disease. Ann Intern Med. 1970;73(6):881–895. — PubMed: DeVita MOPP 1970
  13. Cox MC, et al. Vera Peters and the curability of Hodgkin disease. — PMC: Vera Peters and the curability of Hodgkin disease
  14. History and evolution of lymphoma classification (Kiel, Lukes-Collins, Working Formulation, REAL, WHO). — PubMed: history of lymphoma classification

External Authoritative Resources

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Connections

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