Hodgkin's lymphoma
Encyclopedia
Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma
, which is a cancer
originating from white blood cell
s called lymphocyte
s. It was named after Thomas Hodgkin
, who first described abnormalities in the lymph system in 1832.
Hodgkin's lymphoma is characterized by the orderly spread of disease from one lymph node
group to another and by the development of systemic symptoms
with advanced disease. When Hodgkins cells are examined microscopically, multinucleated Reed-Sternberg cell
s (RS cells) are the characteristic histopathologic
finding. Hodgkin's lymphoma may be treated with radiation therapy
, chemotherapy
or hematopoietic stem cell transplantation, the choice of treatment depending on the age and sex of the patient and the stage, bulk and histological subtype of the disease.
The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and the second in those over 55 years old.
The 10-year overall survival rate is more than 90% for any stage, though early diagnosis may help. Since many patients are young, they often live 40 years or more after treatment. However, few studies follow patients as long as 25 years, and those studies are of older treatments with more life-threatening adverse effects, so it is impossible to predict long-term outcomes of newer, less harmful treatments. Radiation treatments, and some chemotherapy drugs, pose a risk of causing potentially fatal secondary cancers, heart disease, and lung disease 40 or more years later. Modern treatments greatly minimize the chances of these late effects.
Patients with a history of infectious mononucleosis
due to Epstein-Barr virus
may have an increased risk of HL, but the precise contribution of Epstein-Barr virus
remains largely unknown.
) can be subclassified into 4 pathologic
subtypes based upon Reed-Sternberg cell morphology
and the composition of the reactive cell infiltrate
seen in the lymph node
biopsy
specimen (the cell composition around the Reed-Sternberg cell(s)).
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Nodular lymphocyte predominant Hodgkin's lymphoma
expresses CD20
, and is not currently considered a form of classical Hodgkin's.
For the other forms, although the traditional B cell
markers (such as CD20
) are not expressed on all cells, Reed-Sternberg cells are usually of B cell origin. Although Hodgkin's is now frequently grouped with other B cell
malignancies, some T cell
markers (such as CD2
and CD4
) are occasionally expressed. However, this may be an artifact of the ambiguity inherent in the diagnosis.
Hodgkin's cells produce Interleukin-21 (IL-21), which was once thought to be exclusive to T cell
s. This feature may explain the behavior of classical Hodgkin's lymphoma, including clusters of other immune cells gathered around HL cells (infiltrate) in cultures.
After Hodgkin's lymphoma is diagnosed, a patient will be staged
: that is, they will undergo a series of tests and procedures that will determine what areas of the body are affected. These procedures will include documentation of their histology, a physical examination, blood tests, chest X-ray
radiographs, computed tomography
(CT) scans or magnetic resonance imaging
(MRI) scans of the chest, abdomen and pelvis, and a bone marrow biopsy. Positron emission tomography
(PET) scan is now used instead of the gallium scan
for staging. In the past, a lymphangiogram or surgical laparotomy
(which involves opening the abdominal cavity and visually inspecting for tumors) were performed. Lymphangiograms or laparotomies are very rarely performed, having been supplanted by improvements in imaging with the CT scan and PET scan.
On the basis of this staging, the patient will be classified according to a staging classification (the Ann Arbor staging classification scheme is a common one):
The absence of systemic symptoms is signified by adding 'A' to the stage; the presence of systemic symptoms is signified by adding 'B' to the stage. For localized extranodal extension from mass of nodes that does not advance the stage, subscript 'E' is added.
is something that statistically increases one's chance of contracting a disease or condition. Risk factors for Hodgkin's lymphoma include:
(usually excisional biopsy with microscopic examination). Blood test
s are also performed to assess function of major organs and to assess safety for chemotherapy
. Positron emission tomography
(PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium Scan may be used instead of a PET scan.
Affected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis
) a nodular aspect may appear.
A fibrin ring granuloma
may be seen.
Microscopy
Microscopic examination of the lymph node biopsy reveals complete or partial effacement of the lymph node architecture by scattered large malignant cells known as Reed-Sternberg cells (RSC) (typical and variants) admixed within a reactive cell infiltrate composed of variable proportions of lymphocytes, histiocytes, eosinophils, and plasma cells. The Reed-Sternberg cells are identified as large often bi-nucleated cells with prominent nucleoli and an unusual CD45
-, CD30
+, CD15
+/- immunophenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus
.
Characteristics of classic Reed-Sternberg cells include large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin
is distributed at the cell periphery).
Variants:
Hodgkin's lymphoma can be sub-classified by histological type. The cell histology in Hodgkin's lymphoma is not as important as it is in non-Hodgkin's lymphoma: the treatment and prognosis in classic Hodgkin's lymphoma usually depends on the stage of disease rather than the histotype.
or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.
It should be noted that the common non-Hodgkin's treatment, rituximab
(which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin's lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been reviewed recently.
Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.
For Hodgkin's lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called a linear accelerator. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each, every day but Saturday and Sunday.
For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient's body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest and/or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen and/or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.
The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemia
s, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.
In 1998, an international effort identified seven prognostic factors that accurately predict the success rate of conventional treatment in patients with locally extensive or advanced stage Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years was directly related to the number of factors present in a patient. The 5-year FFP for patients with zero factors is 84%. Each additional factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for a patient with 5 or more factors is 42%.
The adverse prognostic factors identified in the international study are:
Other studies have reported the following to be the most important adverse prognostic factors: mixed-cellularity or lymphocyte-depleted histologies, male sex, large number of involved nodal sites, advanced stage, age of 40 years or more, the presence of B symptoms, high erythrocyte sedimentation rate
, and bulky disease (widening of the mediastinum
by more than one third, or the presence of a nodal mass measuring more than 10 cm in any dimension.)
, whose incidence
increases with age, Hodgkin's lymphoma has a bimodal
incidence curve; that is, it occurs most frequently in two separate age groups, the first being young adulthood (age 15–35) and the second being in those over 55 years old although these peaks may vary slightly with nationality. Overall, it is more common in males, except for the nodular sclerosis
variant, which is slightly more common in females. The annual incidence of Hodgkin's lymphoma is about 1 in 25,000 people, and the disease accounts for slightly less than 1% of all cancers worldwide.
The incidence of Hodgkin's lymphoma is increased in patients with HIV
infection. In contrast to many other lymphomas associated with HIV infection it occurs most commonly in patients with higher CD4
T cell counts.
, although Hodgkin noted that perhaps the earliest reference to the condition was provided by Marcello Malpighi
in 1666. While occupied as museum curator at Guy's Hospital
, Hodgkin studied seven patients with painless lymph node enlargement. Of the seven cases, two were patients of Richard Bright
, one was of Thomas Addison
, and one was of Robert Carswell. Carswell's report of this seventh patient was accompanied by numerous illustrations that aided early descriptions of the disease.
Hodgkin's report on these seven patients, entitled "On some morbid appearances of the absorbent glands and spleen", was presented to the Medical and Chirurgical Society in London in January 1832 and was subsequently published in the society's journal, Medical-Chirurgical Society Transactions. Hodgkin's paper went largely unnoticed, however, even despite Bright highlighting it in an 1838 publication. Indeed, Hodgkin himself did not view his contribution as particularly significant.
In 1856, Samuel Wilks
independently reported on a series of patients with the same disease that Hodgkin had previously described. Wilks, a successor to Hodgkin at Guy's Hospital, was unaware of Hodgkin's prior work on the subject. Bright made Wilks aware of Hodgkin's contribution and in 1865, Wilks published a second paper, entitled "Cases of enlargement of the lymphatic glands and spleen", in which he called the disease "Hodgkin's disease" in honor of his predecessor.
Theodor Langhans
and WS Greenfield first described the microscopic characteristics of Hodgkin's lymphoma in 1872 and 1878, respectively. In 1898 and 1902, respectively, Carl Sternberg and Dorothy Reed independently described the cytogenetic features of the malignant cells of Hodgkin's lymphoma, now called Reed-Sternberg cell
s.
Tissue specimens from Hodgkin's seven patients remained at Guy's Hospital for a number of years. Nearly 100 years after Hodgkin's initial publication, histopathologic
reexamination confirmed Hodgkin's lymphoma in only three of seven of these patients. The remaining cases included non-Hodgkin lymphoma
, tuberculosis
, and syphilis
.
Hodgkin's lymphoma was one of the first cancers which could be treated using radiation therapy
and, later, it was one of the first to be treated by combination chemotherapy.
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
, which is a cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
originating from white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s called lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s. It was named after Thomas Hodgkin
Thomas Hodgkin
Thomas Hodgkin was a British physician, considered one of the most prominent pathologists of his time and a pioneer in preventive medicine. He is now best known for the first account of Hodgkin's disease, a form of lymphoma and blood disease, in 1832...
, who first described abnormalities in the lymph system in 1832.
Hodgkin's lymphoma is characterized by the orderly spread of disease from one lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
group to another and by the development of systemic symptoms
B symptoms
B symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma...
with advanced disease. When Hodgkins cells are examined microscopically, multinucleated Reed-Sternberg cell
Reed-Sternberg cell
Reed–Sternberg cells are different giant cells found with light microscopy in biopsies from individuals with Hodgkin's lymphoma primarily due to EBV, and certain other disorders...
s (RS cells) are the characteristic histopathologic
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
finding. Hodgkin's lymphoma may be treated with radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
or hematopoietic stem cell transplantation, the choice of treatment depending on the age and sex of the patient and the stage, bulk and histological subtype of the disease.
The disease occurrence shows two peaks: the first in young adulthood (age 15–35) and the second in those over 55 years old.
The 10-year overall survival rate is more than 90% for any stage, though early diagnosis may help. Since many patients are young, they often live 40 years or more after treatment. However, few studies follow patients as long as 25 years, and those studies are of older treatments with more life-threatening adverse effects, so it is impossible to predict long-term outcomes of newer, less harmful treatments. Radiation treatments, and some chemotherapy drugs, pose a risk of causing potentially fatal secondary cancers, heart disease, and lung disease 40 or more years later. Modern treatments greatly minimize the chances of these late effects.
Patients with a history of infectious mononucleosis
Infectious mononucleosis
Infectious mononucleosis is an infectious, widespread viral...
due to Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
may have an increased risk of HL, but the precise contribution of Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
remains largely unknown.
Types
Classical Hodgkin's lymphoma (excluding nodular lymphocyte predominant Hodgkin's lymphomaNodular lymphocyte predominant Hodgkin's lymphoma
Nodular lymphocyte predominant Hodgkin's lymphoma is a form of lymphoma.It is no longer classified as a form of classic Hodgkin's lymphoma...
) can be subclassified into 4 pathologic
Anatomical pathology
Anatomical pathology or Anatomic pathology is a medical specialty that is concerned with the diagnosis of disease based on the gross, microscopic, chemical, immunologic and molecular examination of organs, tissues, and whole bodies...
subtypes based upon Reed-Sternberg cell morphology
Morphology (biology)
In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....
and the composition of the reactive cell infiltrate
Infiltration (medical)
Infiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is called infiltrate.-Classification:...
seen in the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
specimen (the cell composition around the Reed-Sternberg cell(s)).
| Name | Description | ICD-10 ICD-10 The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the... |
ICD-O >- | Nodular sclerosing HL |
Is the most common subtype and is composed of large tumor Tumor A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer... nodules showing scattered lacunar classical RS cells set in a background of reactive lymphocytes, eosinophils and plasma cells with varying degrees of collagen fibrosis/sclerosis. |
>- | Is a common subtype and is composed of numerous classic RS cells admixed with numerous inflammatory cells including lymphocytes, histiocytes, eosinophils, and plasma cells without sclerosis. This type is most often associated with EBV Epstein-Barr virus The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis... infection and may be confused with the early, so-called 'cellular' phase of nodular sclerosing CHL. |
>- | Is a rare subtype, show many features which may cause diagnostic confusion with nodular lymphocyte predominant B-cell Non-Hodgkin's Lymphoma (B-NHL). This form also has the most favorable prognosis. | >- | Is a rare subtype, composed of large numbers of often pleomorphic RS cells with only few reactive lymphocytes which may easily be confused with diffuse large cell lymphoma. Many cases previously classified within this category would now be reclassified under anaplastic large cell lymphoma Anaplastic large cell lymphoma Anaplastic large-cell lymphoma is a type of non-Hodgkin lymphoma that features in the World Health Organisation classification of lymphomas.Its name derives from anaplasia and large-cell lymphoma.-Signs and symptoms:... . |
>- |
Nodular lymphocyte predominant Hodgkin's lymphoma
Nodular lymphocyte predominant Hodgkin's lymphoma is a form of lymphoma.It is no longer classified as a form of classic Hodgkin's lymphoma...
expresses CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
, and is not currently considered a form of classical Hodgkin's.
For the other forms, although the traditional B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
markers (such as CD20
CD20
B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
) are not expressed on all cells, Reed-Sternberg cells are usually of B cell origin. Although Hodgkin's is now frequently grouped with other B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
malignancies, some T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
markers (such as CD2
CD2
CD2 is a cell adhesion molecule found on the surface of T cells and natural killer cells.It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor....
and CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
) are occasionally expressed. However, this may be an artifact of the ambiguity inherent in the diagnosis.
Hodgkin's cells produce Interleukin-21 (IL-21), which was once thought to be exclusive to T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s. This feature may explain the behavior of classical Hodgkin's lymphoma, including clusters of other immune cells gathered around HL cells (infiltrate) in cultures.
Staging
The staging is the same for both Hodgkin's as well as non-Hodgkin's lymphomas.After Hodgkin's lymphoma is diagnosed, a patient will be staged
Cancer staging
The stage of a cancer is a description of the extent the cancer has spread. The stage often takes into account the size of a tumor, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized to , and whether it has spread to distant organs...
: that is, they will undergo a series of tests and procedures that will determine what areas of the body are affected. These procedures will include documentation of their histology, a physical examination, blood tests, chest X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
radiographs, computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
(CT) scans or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) scans of the chest, abdomen and pelvis, and a bone marrow biopsy. Positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) scan is now used instead of the gallium scan
Gallium scan
A gallium scan or gallium 67 scan is a type of nuclear medicine study that uses a radioactive tracer to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate are used. The form of salt is not important, since it is the freely...
for staging. In the past, a lymphangiogram or surgical laparotomy
Laparotomy
A laparotomy is a surgical procedure involving a large incision through the abdominal wall to gain access into the abdominal cavity. It is also known as coeliotomy.- Terminology :...
(which involves opening the abdominal cavity and visually inspecting for tumors) were performed. Lymphangiograms or laparotomies are very rarely performed, having been supplanted by improvements in imaging with the CT scan and PET scan.
On the basis of this staging, the patient will be classified according to a staging classification (the Ann Arbor staging classification scheme is a common one):
- Stage I is involvement of a single lymph node region (I) (mostly the cervical region) or single extralymphatic site (Ie);
- Stage II is involvement of two or more lymph node regions on the same side of the diaphragm (II) or of one lymph node region and a contiguous extralymphatic site (IIe);
- Stage III is involvement of lymph node regions on both sides of the diaphragm, which may include the spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
(IIIs) and/or limited contiguous extralymphatic organ or site (IIIe, IIIes); - Stage IV is disseminated involvement of one or more extralymphatic organs.
The absence of systemic symptoms is signified by adding 'A' to the stage; the presence of systemic symptoms is signified by adding 'B' to the stage. For localized extranodal extension from mass of nodes that does not advance the stage, subscript 'E' is added.
Signs and symptoms
Patients with Hodgkin's lymphoma may present with the following symptoms:- Itchy Skin
- Night sweatsSleep hyperhidrosisSleep hyperhidrosis, more commonly known as the night sweats, is the occurrence of excessive sweating during sleep. The sufferer may or may not also suffer from excessive perspiration while awake....
- Unexplained weight loss
- Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervicalCervical lymph nodesCervical lymph nodes are lymph nodes found in the neck.-Classification:There are approximately 300 lymph nodes in the neck, and they can be classified in many different ways.Henri Rouvière produced an influential classification in 1938...
and supraclavicularSupraclavicular lymph nodesSupraclavicular lymph nodes are lymph nodes found superior to the clavicle, palpable in the supraclavicular fossa.The most notable supraclavicular lymph node is Virchow's node.-External links:* * http://www.med.mun.ca/anatomyts/head/hnl3a.htm...
) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph. - SplenomegalySplenomegalySplenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
: enlargement of the spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive and the size of the spleen may fluctuate during the course of treatment. - HepatomegalyHepatomegalyHepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
: enlargement of the liverLiverThe liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, due to liver involvement, is present in about 5% of cases. - HepatosplenomegalyHepatosplenomegalyHepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
: the enlargement of both the liver and spleen caused by the same disease. - Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon, occurring in only two to three percent of people with Hodgkin's lymphoma, thus having a low sensitivitySensitivity and specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
. On the other hand, its specificitySensitivity and specificitySensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
is high enough for it to be regarded as a pathognomonicPathognomonicPathognomonic is a term, often used in medicine, that means characteristic for a particular disease. A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt...
sign of Hodgkin's lymphoma. The pain typically has an onset within minutes after ingesting alcohol, and is usually felt as coming from the vicinity where there is an involved lymph node. The pain has been described as either sharp and stabbing or dull and aching. - Back painBack painBack pain is pain felt in the back that usually originates from the muscles, nerves, bones, joints or other structures in the spine.The pain can often be divided into neck pain, upper back pain, lower back pain or tailbone pain...
: nonspecific back pain (pain that cannot be localized or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin's lymphoma. The lower back is most often affected. - Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc. – i.e. decreased production, increased removal)
- Systemic symptoms: about one-third of patients with Hodgkin's disease may also present with systemic symptoms, including low-grade feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
; night sweats; unexplained weight loss of at least 10% of the patient's total body mass in six months or less, itchy skin (pruritusItchItch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...
) due to increased levels of eosinophils in the bloodstream; or fatigueFatigue (physical)Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
(lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptomsB symptomsB symptoms refer to systemic symptoms of fever, night sweats, and weight loss which can be associated with both Hodgkin's lymphoma and non-Hodgkin's lymphoma...
; thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, for example, 2B instead of 2A. - Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein feverPel-Ebstein feverPel-Ebstein fever is a rarely seen condition noted in patients with Hodgkin's lymphoma in which the patient experiences fevers which cyclicly increase then decrease over an average period of one or two weeks...
, or more simply "P-E fever". However, there is debate as to whether or not the P-E fever truly exists.
Cause
There are no guidelines for preventing Hodgkin's lymphoma; this is because the cause is unknown or multifactorial. A risk factorRisk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
is something that statistically increases one's chance of contracting a disease or condition. Risk factors for Hodgkin's lymphoma include:
- Sex: maleManThe term man is used for an adult human male . However, man is sometimes used to refer to humanity as a whole...
- Ages: 15–40 and over 55
- Family history
- History of infectious mononucleosisInfectious mononucleosisInfectious mononucleosis is an infectious, widespread viral...
or infection with Epstein-Barr virusEpstein-Barr virusThe Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, a causative agent of mononucleosis - Weakened immune system, including infection with HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
or the presence of AIDSAIDSAcquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus... - Prolonged use of human growth hormone
- Exposure to exotoxins, such as Agent OrangeAgent OrangeAgent Orange is the code name for one of the herbicides and defoliants used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. Vietnam estimates 400,000 people were killed or maimed, and 500,000 children born with birth...
Diagnosis
Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(usually excisional biopsy with microscopic examination). Blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s are also performed to assess function of major organs and to assess safety for chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
. Positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium Scan may be used instead of a PET scan.
Pathology
MacroscopyAffected lymph nodes (most often, laterocervical lymph nodes) are enlarged, but their shape is preserved because the capsule is not invaded. Usually, the cut surface is white-grey and uniform; in some histological subtypes (e.g. nodular sclerosis
Nodular sclerosis
Nodular sclerosis is a form of Hodgkin's lymphoma that is the most common subtype of HL in developed countries. It affects females and males equally and has a median age of onset at ~28 years...
) a nodular aspect may appear.
A fibrin ring granuloma
Fibrin ring granuloma
A fibrin ring granuloma is a histopathological finding that is characteristic of Q fever. On hematoxylin-eosin staining, the fibrin ring granuloma consists of a central lipid vacuole surrounded by a dense red fibrin ring and epithelioid macrophages...
may be seen.
Microscopy
CD45
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen , which was originally called leukocyte common antigen.- Function :The protein encoded by this gene is a member of the protein tyrosine...
-, CD30
CD30
CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and tumor marker.This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the...
+, CD15
CD15
CD15 is a cluster of differentiation antigen - an immunologically significant molecule. CD15 is a carbohydrate adhesion molecule that can be expressed on glycoproteins, glycolipids and proteoglycans.- Function :...
+/- immunophenotype. In approximately 50% of cases, the Reed-Sternberg cells are infected by the Epstein-Barr virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
.
Characteristics of classic Reed-Sternberg cells include large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane (chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
is distributed at the cell periphery).
Variants:
- Hodgkin cell (atypical mononuclear RSC) is a variant of RS cell, which has the same characteristics, but is mononucleated.
- Lacunar RSC is large, with a single hyperlobated nucleus, multiple, small nucleoli and eosinophilic cytoplasm which is retracted around the nucleus, creating an empty space ("lacunae").
- Pleomorphic RSC has multiple irregular nuclei.
- "Popcorn" RSC (lympho-histiocytic variant) is a small cell, with a very lobulated nucleus, small nucleoli.
- "Mummy" RSC has a compact nucleus, no nucleolus and basophilic cytoplasm.
Hodgkin's lymphoma can be sub-classified by histological type. The cell histology in Hodgkin's lymphoma is not as important as it is in non-Hodgkin's lymphoma: the treatment and prognosis in classic Hodgkin's lymphoma usually depends on the stage of disease rather than the histotype.
Management
Patients with early stage disease (IA or IIA) are effectively treated with radiation therapyRadiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.
| ABVD ABVD ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, supplanting the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:*Adriamycin *bleomycin... |
Stanford V Stanford V Stanford V is a chemotherapy regimen intended as a first line treatment for Hodgkin's lymphoma... |
BEACOPP |
|---|---|---|
| Currently, the ABVD ABVD ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, supplanting the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:*Adriamycin *bleomycin... chemotherapy regimen is the standard treatment of Hodgkin's disease in the US. The abbreviation stands for the four drugs Adriamycin, bleomycin Bleomycin Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA... , vinblastine Vinblastine Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis.... , and dacarbazine Dacarbazine Dacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl... . Developed in Italy in the 1970s, the ABVD treatment typically takes between six and eight months, although longer treatments may be required. |
The newer Stanford V Stanford V Stanford V is a chemotherapy regimen intended as a first line treatment for Hodgkin's lymphoma... regimen is typically only half as long as the ABVD but involves a more intensive chemotherapy schedule and incorporates radiation therapy. In a randomized controlled study in Italy, Stanford V was inferior to ABVD. |
BEACOPP is a form of treatment for stages > II mainly used in Europe. The cure rate with the BEACOPP esc. regimen is approximately 10–15% higher than with standard ABVD in advanced stages. This was shown in a paper in The New England Journal of Medicine (Diehl et al.), but US physicians still favor ABVD, maybe because some physicians think that BEACOPP induces more secondary leukemia. However, this seems negligible compared to the higher cure rates. BEACOPP is more expensive because of the requirement for concurrent treatment with GCSF to increase production of white blood cells. Currently, the German Hodgkin Study Group tests 8 cycles (8x) BEACOPP esc vs. 6x BEACOPP esc vs. 8x BEACOPP-14 baseline (HD15-trial). |
| Doxorubicin Doxorubicin Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA.... |
Doxorubicin Doxorubicin Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA.... |
Doxorubicin Doxorubicin Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA.... |
| Bleomycin Bleomycin Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA... |
Bleomycin Bleomycin Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA... |
Bleomycin Bleomycin Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA... |
| Vinblastine Vinblastine Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis.... |
Vinblastine Vinblastine Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis.... , Vincristine Vincristine Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to... |
Vincristine Vincristine Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to... |
| Dacarbazine Dacarbazine Dacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl... |
Mechlorethamine | Cyclophosphamide Cyclophosphamide Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group.... , Procarbazine Procarbazine Procarbazine Procarbazine Procarbazine (Matulane (US), Natulan (Canada), Indicarb (India) is an antineoplastic chemotherapy drug for the treatment of Hodgkin's lymphoma and certain brain cancers (such as Glioblastoma multiforme). It is a member of a group of medicines called alkylating agents. It... |
| Etoposide Etoposide Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting... |
Etoposide Etoposide Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting... |
|
| Prednisone Prednisone Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects... |
Prednisone Prednisone Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects... |
It should be noted that the common non-Hodgkin's treatment, rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
(which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin's lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been reviewed recently.
Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.
For Hodgkin's lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called a linear accelerator. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each, every day but Saturday and Sunday.
For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient's body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest and/or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen and/or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.
The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
s, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.
Prognosis
Treatment of Hodgkin's disease has been improving over the past few decades. Recent trials that have made use of new types of chemotherapy have indicated higher survival rates than have previously been seen. In one recent European trial, the 5-year survival rate for those patients with a favorable prognosis was 98%, while that for patients with worse outlooks was at least 85%.In 1998, an international effort identified seven prognostic factors that accurately predict the success rate of conventional treatment in patients with locally extensive or advanced stage Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years was directly related to the number of factors present in a patient. The 5-year FFP for patients with zero factors is 84%. Each additional factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for a patient with 5 or more factors is 42%.
The adverse prognostic factors identified in the international study are:
- Age ≥ 45 years
- Stage IV disease
- HemoglobinHemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
< 10.5 g/dl - Lymphocyte count < 600/µl or < 8%
- MaleMaleMale refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
- AlbuminAlbuminAlbumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
< 4.0 g/dl - White blood count ≥ 15,000/µl
Other studies have reported the following to be the most important adverse prognostic factors: mixed-cellularity or lymphocyte-depleted histologies, male sex, large number of involved nodal sites, advanced stage, age of 40 years or more, the presence of B symptoms, high erythrocyte sedimentation rate
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
, and bulky disease (widening of the mediastinum
Mediastinum
The mediastinum is a non-delineated group of structures in the thorax, surrounded by loose connective tissue. It is the central compartment of the thoracic cavity...
by more than one third, or the presence of a nodal mass measuring more than 10 cm in any dimension.)
Epidemiology
Unlike some other lymphomasNon-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
, whose incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
increases with age, Hodgkin's lymphoma has a bimodal
Bimodal distribution
In statistics, a bimodal distribution is a continuous probability distribution with two different modes. These appear as distinct peaks in the probability density function, as shown in Figure 1....
incidence curve; that is, it occurs most frequently in two separate age groups, the first being young adulthood (age 15–35) and the second being in those over 55 years old although these peaks may vary slightly with nationality. Overall, it is more common in males, except for the nodular sclerosis
Nodular sclerosis
Nodular sclerosis is a form of Hodgkin's lymphoma that is the most common subtype of HL in developed countries. It affects females and males equally and has a median age of onset at ~28 years...
variant, which is slightly more common in females. The annual incidence of Hodgkin's lymphoma is about 1 in 25,000 people, and the disease accounts for slightly less than 1% of all cancers worldwide.
The incidence of Hodgkin's lymphoma is increased in patients with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection. In contrast to many other lymphomas associated with HIV infection it occurs most commonly in patients with higher CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
T cell counts.
History
Hodgkin's lymphoma was first described in an 1832 report by Thomas HodgkinThomas Hodgkin
Thomas Hodgkin was a British physician, considered one of the most prominent pathologists of his time and a pioneer in preventive medicine. He is now best known for the first account of Hodgkin's disease, a form of lymphoma and blood disease, in 1832...
, although Hodgkin noted that perhaps the earliest reference to the condition was provided by Marcello Malpighi
Marcello Malpighi
Marcello Malpighi was an Italian doctor, who gave his name to several physiological features, like the Malpighian tubule system.-Early years:...
in 1666. While occupied as museum curator at Guy's Hospital
Guy's Hospital
Guy's Hospital is a large NHS hospital in the borough of Southwark in south east London, England. It is administratively a part of Guy's and St Thomas' NHS Foundation Trust. It is a large teaching hospital and is home to the King's College London School of Medicine...
, Hodgkin studied seven patients with painless lymph node enlargement. Of the seven cases, two were patients of Richard Bright
Richard Bright (physician)
Richard Bright was an English physician and early pioneer in the research of kidney disease.He was born in Bristol, Gloucestershire, the third son of Sarah and Richard Bright Sr., a wealthy merchant and banker. Bright Sr. shared his interest in science with his son,encouraging him to consider it...
, one was of Thomas Addison
Thomas Addison
Thomas Addison was a renowned 19th-century English physician and scientist. He is traditionally regarded as one of the "great men" of Guy's Hospital in London....
, and one was of Robert Carswell. Carswell's report of this seventh patient was accompanied by numerous illustrations that aided early descriptions of the disease.
Hodgkin's report on these seven patients, entitled "On some morbid appearances of the absorbent glands and spleen", was presented to the Medical and Chirurgical Society in London in January 1832 and was subsequently published in the society's journal, Medical-Chirurgical Society Transactions. Hodgkin's paper went largely unnoticed, however, even despite Bright highlighting it in an 1838 publication. Indeed, Hodgkin himself did not view his contribution as particularly significant.
In 1856, Samuel Wilks
Samuel Wilks
Sir Samuel Wilks, 1st Baronet , was a British physician and biographer.-Early life:Samuel Wilks was born on 2 June 1824 in Camberwell, London, the second son of Joseph Barber Wilks, a cashier at the East India House...
independently reported on a series of patients with the same disease that Hodgkin had previously described. Wilks, a successor to Hodgkin at Guy's Hospital, was unaware of Hodgkin's prior work on the subject. Bright made Wilks aware of Hodgkin's contribution and in 1865, Wilks published a second paper, entitled "Cases of enlargement of the lymphatic glands and spleen", in which he called the disease "Hodgkin's disease" in honor of his predecessor.
Theodor Langhans
Theodor Langhans
Theodor Langhans was a German pathologist who was a native of Usingen, Duchy of Nassau. He studied medicine at the University of Heidelberg, and at the University of Göttingen under Friedrich Gustav Jakob Henle , at Berlin under Rudolf Virchow and in Würzburg, where he became an assistant to...
and WS Greenfield first described the microscopic characteristics of Hodgkin's lymphoma in 1872 and 1878, respectively. In 1898 and 1902, respectively, Carl Sternberg and Dorothy Reed independently described the cytogenetic features of the malignant cells of Hodgkin's lymphoma, now called Reed-Sternberg cell
Reed-Sternberg cell
Reed–Sternberg cells are different giant cells found with light microscopy in biopsies from individuals with Hodgkin's lymphoma primarily due to EBV, and certain other disorders...
s.
Tissue specimens from Hodgkin's seven patients remained at Guy's Hospital for a number of years. Nearly 100 years after Hodgkin's initial publication, histopathologic
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
reexamination confirmed Hodgkin's lymphoma in only three of seven of these patients. The remaining cases included non-Hodgkin lymphoma
Non-Hodgkin lymphoma
The non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
, tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, and syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
.
Hodgkin's lymphoma was one of the first cancers which could be treated using radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
and, later, it was one of the first to be treated by combination chemotherapy.
Notable cases
- Don CohanDon CohanDonald Smith "Don" Cohan is one of the leading yachtsmen in the U.S. He was the first Jew to compete at the highest levels of world yachting competitions and at the time of his active career, the only Jew to win an Olympic medal in yachting.He won a bronze medal at the 1972 Munich Olympics, at...
, oldest U.S. Olympic bronze medalist at the age of 42, diagnosed with stage IVB Hodgkins disease, defeated it twice, and then won a U.S. championship in sailing at the age of 72. - Howard CarterHoward CarterHoward Carter may refer to:* Howard Carter , English archaeologist who discovered Tutankhamun's tomb* Howard Carter , American basketball player...
, Egyptologist and discoverer of the Tomb of Tutankhamum, died in 1939 from Hodgkin's disease - Jörg KühnJörg KühnJörg Kühn was a Swiss artist, naturalist and scientific illustrator who specialized in animal and bird paintings and drawings. He was also a children's book illustrator...
, Swiss artist, naturalist and scientific illustrator who specialized in animal, bird and medical paintings died age 24 years old in 1964. - Prithviraj KapoorPrithviraj KapoorPrithviraj Kapoor , 3 November 1906 – 29 May 1972) was a pioneer of Indian theatre and of the Hindi film industry, who started his career as an actor, in the silent era of Hindi cinema, associated with IPTA and who founded Prithvi Theatres, a travelling theatre company based in Mumbai, in...
, a noted pioneer of Indian theatre and of the Hindi film industry died of Hodgkin's disease in 1972. - Paul AllenPaul AllenPaul Gardner Allen is an American business magnate, investor, and philanthropist. Allen co-founded Microsoft with Bill Gates...
, Microsoft co-founder, was diagnosed and treated for Hodgkin's lymphoma in 1983. He subsequently developed non-Hodgkin's lymphoma in November 2009 - DJ Qualls was diagnosed with Hodgkin's lymphoma at age 14, and after two years of treatment, his cancer was said to be in remission.
- Alese CocoAlese CocoAlese Kristine Coco – American woman who became face and voice of Hodgkin’s lymphoma was a strong advocate for research and clinical trials. She was diagnosed with Hodgkin’s in 2001 at the age of 17....
(1984–2007). American woman who founded the non-profit organization Fight 2 Win Campaign to raise money for Hodgkin’s research and awareness. - Lynden David HallLynden David HallLynden David Hall was a singer, songwriter, arranger, and producer.- Life and career :Born in Wandsworth, South London, he won the 'best newcomer' accolade at the 1998 MOBO Awards....
died of Hodgkin's lymphoma in 2006. - Delta GoodremDelta GoodremDelta Lea Goodrem is an Australian singer-songwriter, pianist, and actress. Signed to Sony at the age of 15, Goodrem rose to prominence in 2002, starring in the Australian soap opera Neighbours as Nina Tucker. Goodrem has achieved eight number-one singles and three number-one albums in her home...
, Australian singer, was diagnosed with Hodgkin's lymphoma in July 2003 - Freida J. RileyFreida J. RileyFreida Joy Riley was an American science and math teacher. She taught at Big Creek High School in War, West Virginia during the late 1950s and early 1960s while suffering from Hodgkin's disease.-Life:...
, teacher, influential in early career of Homer HickamHomer HickamHomer Hadley Hickam, Jr. is an American author, Vietnam veteran, and a former NASA engineer. His autobiographical novel Rocket Boys: A Memoir, was a #1 New York Times Best Seller, is studied in many American and international school systems, and was the basis for the popular film October Sky...
, featured in October SkyOctober SkyOctober Sky is a 1999 American biographical film directed by Joe Johnston, starring Jake Gyllenhaal, Chris Cooper and Laura Dern. It is based on the true story of Homer Hickam, a coal miner's son who was inspired by the launch of Sputnik 1 to take up rocketry against his father's wishes, and who...
, died aged 31. - Richard HarrisRichard HarrisRichard St John Harris was an Irish actor, singer-songwriter, theatrical producer, film director and writer....
, Irish actor, died from the condition in 2002 - Dinu LipattiDinu LipattiDinu Lipatti was a Romanian classical pianist and composer whose career was cut short by his death from Hodgkin's disease at age 33. He was elected posthumously to the Romanian Academy.-Biography:...
, the Romanian pianist, died of Hodgkin's disease in 1950, aged 33 - Craig WedrenCraig WedrenCraig Wedren is the former lead singer of Shudder to Think and now the lead for the newer pop-mash project, "BABY".Wedren has also contributed vocals to the musical act Tweaker with Chris Vrenna, formerly of Nine Inch Nails, The Verve Pipe's self-titled album, the musical act Cex, The Dead...
, lead singer of Shudder to ThinkShudder to ThinkShudder to Think is an American indie rock group. Formed in 1986, they released three albums on the Washington, D.C.-based label Dischord Records and were a post-hardcore band, although they drew upon a wide range of stylistic influences, including pop....
and the lead for the newer pop-mash project, "BABY". In remission. - Mario LemieuxMario LemieuxMario Lemieux, OC, CQ is a Canadian former professional ice hockey player. He is acknowledged to be one of the best players of all time. He played 17 seasons as a forward for the Pittsburgh Penguins of the National Hockey League between 1984 and 2006...
, National Hockey League forward, was diagnosed with Hodgkin's lymphoma in 1993 - Luke Menard, a finalist on the seventh season of American IdolAmerican IdolAmerican Idol, titled American Idol: The Search for a Superstar for the first season, is a reality television singing competition created by Simon Fuller and produced by FremantleMedia North America and 19 Entertainment...
, was diagnosed with the disease after being voted off the show. - Starchild Abraham CherrixVirginia v. CherrixVirginia v. Cherrix is a court case in which the Commonwealth of Virginia sued to force Starchild Abraham Cherrix , aged 16 at the time of the court case, to undergo further conventional medical treatment for a highly treatable form of cancer, Hodgkin disease.Cherrix was diagnosed with the blood...
, a teenager whose refusal to undergo further conventional treatment after relapsing resulted in a court battle and a change to Virginia laws about medical neglect. - Big John StuddBig John StuddJohn William Minton was an American professional wrestler and actor who was born and raised in Butler, Pennsylvania, better known by his ring name, Big John Studd.-Career:...
, Wrestler John William Minton, died from the disease in 1995 - Emma LazarusEmma LazarusLazarus began to be more interested in her Jewish ancestry after reading the George Eliot novel, Daniel Deronda, and as she heard of the Russian pogroms in the early 1880s. This led Lazarus to write articles on the subject. She also began translating the works of Jewish poets into English...
, Jewish-American poet and author of "The New ColossusThe New Colossus"The New Colossus" is a sonnet by Emma Lazarus , written in 1883 and, in 1903, engraved on a bronze plaque and mounted inside the Statue of Liberty.- History of the poem :...
," the poem at the base of the Statue of LibertyStatue of LibertyThe Statue of Liberty is a colossal neoclassical sculpture on Liberty Island in New York Harbor, designed by Frédéric Bartholdi and dedicated on October 28, 1886...
, died from the disease in 1887 - Brandon TartikoffBrandon TartikoffBrandon Tartikoff was a television executive who was credited with turning around NBC's low prime time reputation with such hit series as Hill Street Blues, L.A. Law, ALF, Family Ties, The Cosby Show, Cheers, Seinfeld, Miami Vice, The Golden Girls, Knight Rider, The A-Team, St...
, American television executive, died from the disease in 1997. - Ethan ZohnEthan ZohnEthan Zohn is an American reality television series contestant who won $1,000,000 on Survivor: Africa, the third season of the reality TV series Survivor. He also appeared on the All-Stars edition of the show. After winning Survivor he co-founded Grassroot Soccer, which uses soccer to raise money...
, Won Survivor: AfricaSurvivor: AfricaSurvivor: Africa is the third season of the United States reality show Survivor. It was filmed during 2001 and aired from October 11, 2001 - January 10, 2002 on CBS. It was set in Kenya's Shaba National Reserve on the African continent.... - Daniel Hauser, whose mother fled with him in order to prevent him from undergoing chemotherapy.
- Michael C. HallMichael C. HallMichael Carlyle Hall is an American actor whose television roles include David Fisher on the HBO drama series Six Feet Under and Dexter Morgan on the Showtime series Dexter. In 2009, Hall won a Golden Globe award and a Screen Actors Guild Award for his role in Dexter.-Early life:Hall was born in...
, American actor (DexterDexter (TV series)Dexter is an American television drama series, which debuted on Showtime on October 1, 2006. The sixth season premiered on October 2, 2011. The series centers on Dexter Morgan , a bloodstain pattern analyst for the Miami Metro Police Department who moonlights as a serial killer...
, Six Feet Under), in remission as of April 2010. - Wesley CoeWesley CoeWesley Coe was an American athlete who competed mainly in the shot put.He competed for the United States in the 1904 Summer Olympics held in St Louis, United States in the shot put where he won the silver medal between fellow Americans winner Ralph Rose and bronze medal winner Lawrence...
, American silver medalist in the 1904 Olympics, died of Hodgkin's lymphoma. - Mamta MohandasMamta MohandasMamta Mohandas is an Indian film actress and playback singer. She has mainly acted in Malayalam films, besides few Telugu and Tamil productions and one Kannada film...
, Indian actress, survived the disease in November 2010. - Martyn BennettMartyn BennettMartyn Bennett was a Scottish musician who was born in St. John's, Newfoundland and Labrador, Canada...
, renowned Scottish musician died from the disease in 2005. - Alisa KleybanovaAlisa KleybanovaAlisa Mikhaelovna Kleybanova is a Russian professional tennis player. Her highest WTA world ranking to date is No. 20, achieved on February 21, 2010...
, Professional WTA tennis player, was diagnosed on 14 July 2011. Currently undergoing treatment in Italy. - Lawrence SummersLawrence SummersLawrence Henry Summers is an American economist. He served as the 71st United States Secretary of the Treasury from 1999 to 2001 under President Bill Clinton. He was Director of the White House United States National Economic Council for President Barack Obama until November 2010.Summers is the...
, Harvard Economist, Former President of Harvard University, Former Secretary of the Treasury, Former Chair of National Economics Council. - Facundo AranaFacundo AranaJorge Facundo Arana Tagle is an Argentine actor. He has participated in more than twenty telenovelas.-Biography:...
, Argentine actor, was diagnosed with Hodgkin's disease. Arana received treatment for much of 1989 and underwent regular testing until 1994, when he was finally declared cancer-free. - Richard Patteson, Carribeanist and literary commentator on Robert AntoniRobert AntoniRobert Antoni is a West Indian writer who was awarded the 1999 Aga Khan Prize for Fiction by The Paris Review for "My Grandmother's Tale of How Crab-o Lost His Head".- Background :...
, June 2010 - Gerald FinziGerald FinziGerald Raphael Finzi was a British composer. Finzi is best known as a song-writer, but also wrote in other genres...
, English composer, died 1956 after complications
See also
- ABVDABVDABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, supplanting the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:*Adriamycin *bleomycin...
- Ann Arbor stagingAnn Arbor stagingAnn Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma and Non-Hodgkin lymphoma . It was initially developed for Hodgkin's, but has some use in NHL...
- List of hematologic conditions
- LymphadenopathyLymphadenopathyLymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
- Non-Hodgkin lymphomaNon-Hodgkin lymphomaThe non-Hodgkin lymphomas are a diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from indolent to very aggressive....
, an outdated classification scheme for lymphomas - Progressive transformation of germinal centresProgressive transformation of germinal centresProgressive transformation of germinal centres, abbreviated PTGCs and also progressive transformation of germinal centers, is a reactive lymph node process of undetermined etiology.-Symptoms:...
Further reading
- Charlotte DeCroes Jacobs. Henry Kaplan and the Story of Hodgkin's Disease (Stanford University PressStanford University PressThe Stanford University Press is the publishing house of Stanford University. In 1892, an independent publishing company was established at the university. The first use of the name "Stanford University Press" in a book's imprinting occurred in 1895...
; 2010) 456 pages; combines a biography of the American radiation oncologist (1918–84) with a history of the lymphatic cancer whose treatment he helped to transform.
External links
- Hodgkin Disease at American Cancer SocietyAmerican Cancer SocietyThe American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
- Hodgkin's Lymphoma at the American National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
- Clinically reviewed Hodgkin's lymphoma information for patients, from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- UK Hodgkin's lymphoma statistics from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- Information from the German Hodgkin Studygroup (English version)
- Timeline of discovery and treatment of Hodgkin's Lymphoma at hodgkinshistory.com
- Video and information booklet on Hodgkins Lymphoma
- Information on Hodgkins Lymphoma from Lymphoma Research Foundation
- Lymphoma Association – Specialist UK charity providing free information and support to patients, their families, friends and carers
- Hodgkin Lymphoma - Diagnosis by Radiology, CT and MR Medical Image Database