There seems to be something a bit ironic about a history major being diagnosed with a type of cancer with as long and as interesting a history as Hodgkin’s Disease. Being a history buff afflicted with this particular malignancy, I thought it might be interesting to give … drum roll … a brief history of both Dr. Hodgkin and his horrible disease.
Dr. Thomas Hodgkin
Hodgkin’s Disease is one of the best known medical eponyms. The fellow who’s name got attached to this relatively rare cancer was named Thomas Hodgkin. Hodgkin was born in to a Quaker family in Middlesex, England on August 17, 1798. In 1819, he entered medical school at St. Thomas’s and Guy’s Medical School (affiliated today with King’s College in London). In 1823, he earned his M.D. Two years later, Dr. Hodgkin was appointed lecturer in morbid anatomy and curator of the Pathology Museum at Guy’s Hospital Medical School. (Morbid anatomy?!? Doesn’t sound pleasant does it??)
Physically, Hodgkin was dark haired, with a slight and wiry build. He was reputed to have a hot temper, but was also greatly appreciated as a lecturer. Hodgkin’s passion seems to have been pathology. In 1829, Hodgkin published a work that became a classic in pathology, The Morbid Anatomy of Serous and Mucous Membranes. This work focused on unexpected intra-thoracic and intra-abdominal tumors and how these tumors spread.
In 1832, Dr. Hodgkin described the disease that now bears his name in a paper entitled On Some Morbid Appearances of the Absorbent Glands and Spleen. The paper was published in the journal of the Medical and Chirurgical Society in London. The disease would be rediscovered in 1865 — right as the American Civil War ended — by Dr. Samuel Wilks who recognized Hodgkin’s work and named the disease after him in a paper entitled Cases of enlargement of the lymphatic glands and spleen, (or, Hodgkin’s disease) with remarks.
Hodgkin was one of the early advocates of preventive medicine, publishing On the Means of Promoting and Preserving Health in 1841.
Although the most brilliant pathologist of his day, Hodgkin was an abject failure in business. After staying up all night caring for a very rich patient, Hodgkin received a blank check for his work. He filled in the blank with 10 pounds, then added insult to injury by saying that the patient didn’t seem to be able to afford more. Many of his friends were reluctant to ask him to consult on their cases because he would refuse to charge them.
Hodgkin was a social progressive. He opposed slavery, advocated for reforms in medical education, and founded the the British and Foreign Aborigines Protection Society. His liberal views along with his hot temper made him enemies in the medical profession.
Dr. Hodgkin died of a terrible illness — dysentery — on April 5, 1866 in Jaffa, Palestine. His grave reads: “Here rests the body of Thomas Hodgkin M.D. of Bedford Square, London. A man distinguished alike for scientific attainments, medical skills and self-sacrificing philanthropy.”
Hodgkin’s Disease – The Early Years
Dr. Hodgkin was the first to note that Hodgkin’s Disease seemed to form in the intra-thoracic region and would spread through contiguous lymph node chains. He also noted that involvement of the spleen seemed a symptom of advanced disease.
Dr. Hodgkin also recognized that the “father of microscopical anatomy,” Marcelle Malpighi published the first actual recorded description of Hodgkin’s disease in his paper De viscerum structuru exercitatio anatomica in the year 1666. Hodgkin’s Disease was not the first cancer discovered, but it was among the first and one of the first to be accurately described.
(Cancer is an ancient disease. Bone remains of mummies have revealed growths suggestive of bone cancer. The Edwin Smith Papyrus found in Egypt that dates back to 1600 BC actually describes 8 cases of tumors or ulcers of the breast that were treated by cauterization, with a tool called “the fire drill.” The writing explains that there was, “no treatment.” Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. He used the word that referred to a crab because crab the disease often presented with finger-like spreading projections from a cancer called to mind the shape of a crab.)
Hodgkin only examined his disease grossly; he did not undertake to use the primitive microscopes of the day to explore the tissue further. As previously mentioned, a year before his death, Dr. Wilks assigned Hodgkin’s name to the disease. Hodgkin’s Disease proved to be interesting because it was difficult to classify — was it an infection? a cancer? an inflammatory process? The disease additionally attracted much attention and infamy due to it’s frequency in young adults.
Several pathologists who followed Hodgkin and Wilks did examine biopsies of Hodgkin’s Disease under the microscope, but it was Dorthy Reed (1874-1964), a fellow at Johns Hopkins, who first classified the unusual giant cells unique to Hodgkin’s Disease. Dr. Reed failed to recognize that they represented a neoplasm, however, thinking they were inflammatory. The unique giant cells that make up Hodgkin’s Disease are today known as Reed-Sternberg cells (Dr. Carl Sternberg (1872-1935) had also done work describing them independently in Germany in 1898).
Pathologists were eventually able to tie the giant Reed-Sternberg cells to the malignant process. Hodgkin’s Disease is a cancer, sometimes called Hodgkin’s Lymphoma. ((A lymphoma is a cancer of the lymphatic system, a set of interconnected organs and tissues that helps the body fight diseases and infections. There are two major types, the much more common Non-Hodgkin’s Lymphomas and Hodgkin’s Disease. Connected along the thin network of vessels of the lymph system are groups of small, bean shaped and sized organs called lymph nodes. Lymph nodes are found in the neck, chest, armpits, abdomen, and groin. The lymphatic system also includes the tonsils, thymus, spleen, and bone marrow.))
Reed-Sternberg cells are interesting because they only make up 1 to 2% of a Hodgkin’s Disease tumor. Hodgkin’s Disease is the only malignancy where the size of the masses aren’t a result of the number of cancerous cells. ((Most of the Hodgkin’s Disease mass consists of benign inflammatory cells including small T lymphocytes, histiocytes, plasma cells, eosinophils, and neutrophils. The inflammation is produced by cytokines which are in turn produced by the tumor cells.)) (This is one reason why there is so much inflammation with Hodgkin’s Disease and often scar tissue).
In 1925, Hodgkin’s Disease, Non-Hodgkin’s Lymphoma, and the leukemias were finally differentiated officially as different diseases.
Hodgkin’s Disease: The First Curable Cancer
Although early pathologists did not recognize that Hodgkin’s Disease was a malignancy, it’s ability to kill was well known. Ninety percent of people with Hodgkin’s Disease would die within three years time; almost all would die within five years.
Through the early 20th century, doctors experimented with using radiation to try and control Hodgkin’s Disease. They had limited success. They began to then experiment with nitrogen mustard. Now my military readers are probably asking mustard? Isn’t that the stuff that was so terrible and killed so many in WWI? Yes. Ironically, the development of the nitrogen mustard drug used in Hodgkin’s disease stemmed from the use of mustard compounds during World War I and from a terrible explosion during World War II in Bari, Italy that exposed servicemen to toxic effects. The Bari incident showed that nitrogen mustard could cause suppression of the bone marrow and of the lymphatic system. By the mid-1940s, doctors were beginning to control Hodgkin’s Disease and shrink the tumors.
The big breakthrough came in the middle 1960s. By 1964, doctors had come up with a combination chemotherapy regimen that utilized the mustard known as MOPP. MOPP consists of cyclophosphamide, vincristine, methotrexate, and prednisone.
The current staging system was also set up by the mid-1960s. The Ann Arbor Staging for Lymphomas also applies to Hodgkin’s Disease. Stage is closely associated with prognosis. The stages for lymphoma are:
- Stage I indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
- Stage II indicates that the cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas are confined to one side of the diaphragm – that is, both are above the diaphragm, or both are below the diaphragm.
- Stage III indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
- Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs, including any involvement of the liver, bone marrow, or nodular involvement of the lungs.
To this letters are often appended:
- A or B: the absence of constitutional (B-type) symptoms is denoted by adding an “A” to the stage; the presence is denoted by adding a “B” to the stage. The B symptoms include night sweats, fevers, and weight loss of 10% of more. Many symptoms associated with Hodgkin’s Disease (itching, pain on drinking alcohol) are not official B-symptoms.
- E: is used if the disease is “extranodal” or has spread from lymph nodes to adjacent tissue.
- X: is used if the largest deposit is >10 cm large (“bulky disease”), or whether the mediastinum is wider than 1/3 of the chest on x-ray.
- S: is used if the disease has spread to the spleen.
(So if you assigned your author all the different letters that applied to her case, she would have Stage III-AEXS Hodgkin’s Disease.)
By the way there are also four known sub-types of Classical Hodgkin’s Disease:
- lymphocyte predominance (approximately 5% of cases)
- nodular sclerosis (approximately 70%)
- mixed cellularity (approximately 20%)
- lymphocyte depletion (5%)
(Your author had the NS sub-type.)
By 1967, the results from MOPP were coming in and they were astounding: an 81% complete remission rate. In 1968, Adriamycin ((Adriamycin is the red drug. It is used for many different kinds of cancers. It’s generic name is doxorubicin. Adriamycin is in the class of chemo drugs known as Anthracyclines.)) became available for the first-time and in 1972 Dacarbazine ((Dacarbazine is also known by it’s brand name, DTIC. Dacarbazine is an alkylating antineoplastic agent. It is used mainly now for Hodgkin’s Disease and for certain kinds of melanoma.)) was approved for use. Because MOPP caused severe side effects (including sterility and severe suppression of the bone marrow leading to secondary leukemias), in 1972-73 a group from Italy led by Bonadonna came up with the current “gold standard” for Hodgkin’s Disease: ABVD Chemotherapy. ABVD combined a vinca-alkaloid known as Vinblastine ((Vinblastine is a mitotic inhibitor. It derives from the perwinkle plant.)) (similar to Vincristine in MOPP), an anti-tumor antibiotic called Bleomycin, and Adriamycin, and Dacarbazine. In head to head trials, ABVD proved not only less toxic, but also provided superior rates of cure.
The last major step in treating Hodgkin’s Disease came in 1992 when a German group came up with a new regimen for highest risk patients known as BEACOPP. Along with the Stanford V regimen (a combination chemotherapy and radiation regimen), these two treatments are now sometimes used in place of ABVD in advanced disease.
With modern chemotherapy, sometimes combined with radiation to areas of disease, about 80% of patients with Hodgkin’s Disease can today be cured.
As you would expect, Hodgkin’s Disease is still an evolving field, especially in terms of treating patients who have relapsed disease. Much of the work currently involves effective treatments for Hodgkin’s Disease that reoccurs despite first-line therapies. Also, there has been focus on trying to predict which patients are most likely to relapse. The use of radiation remains an issue as does attempting to lessen the toxicities from chemotherapy.
A Few Famous Hodgkin’s Disease Survivors You’ve Probably heard of
- Paul Allen
- Mario Lemieux
- Arlen Specter
- and a host of wonderful people you’ve never heard of, but are just as important, and just as valuable
So there you have it — a brief history of Dr. Hodgkin and his disease.
(The World Health Organization in 2001 tried to officially name Hodgkin’s Disease, Hodgkin’s Lymphoma. Personally, I think Hodgkin’s Disease sounds better and my doc uses the term “Disease”, so I am going to keep referring to it as Hodgkin’s Disease. It’s your disease, and you can call it whatever YOU prefer!)