Throughout history, cancer diagnosis has never been good news. In ancient Egypt, a diagnosis of a breast lump with arm swelling -a sign of cancer invasion- meant certain death in the near future. Advances in medicine, however, have made many cancers potentially curable and many surgeries more successful and less debilitating for patients. Hodgkin’s lymphoma is one of the few success stories that have been achieved thanks to new therapies and intensive clinical research.
What is Hodgkin’s lymphoma and how does it happen?
Hodgkin’s lymphoma is a cancer originating from a type of white blood cells called lymphocytes. Such cells are not only found in blood, but also in lymph nodes, the spleen, the liver and even the skin. They play an essential role in maintaining our immunity and -ironically- protect us against cancers and autoimmune conditions. Lymphocytes are of 2 main types: B and T lymphocytes. B lymphocytes originate in the bone marrow and that is where they mature, while T lymphocytes also originate in the bone marrow but mature in a small gland found in our chest in front of our hearts called the thymus.
Like many cancers, the exact cause of Hodgkin’s lymphoma is not one but the correlation of many different risk factors. One important risk factor found in about half Hodgkin’s lymphoma patients is infection with Epstein-Barr virus. This virus causes a condition called infectious mononucleosis especially in children and can affect lymphocytes in a way so as to trigger their conversion to cancer cells. This doesn’t mean that a large number of Epstein-Barr virus patients will develop Hodgkin’s since only 1 in 1000 cases develop the condition. Other risk factors include family history of lymphomas and infection with HIV.
What age does lymphoma affect?
Lymphoma has what we call a bimodal peak, which means that 2 distinct age groups have the highest incidence of occurrence of Hodgkin’s, the first age group is 15-25 years old and the second one is by 55 years old. Hodgkin’s lymphoma is generally more common in males, but one type -nodular sclerosing- is more common in females. Lymphoma affects roughly 3 individuals in 100,000 in most populations.
Types of Hodgkin’s lymphoma
Hodgkin’s lymphoma is classified into two broad types:
1) Classical Hodgkin’s lymphoma which is thought to be mostly related to Epstein-Barr virus infection and is subdivided into 4 types:
- Nodular sclerosing
- Lymphocyte depleted
- Lymphocyte rich
- Mixed cellularity
2) Non classical Hodgkin’s which is also called lymphocyte predominant Hodgkin lymphoma.
Those types are classified according to the appearance of cells under the microscope and generally speaking, types with more lymphocytes than cancer cells tend to have better outcomes than those with low lymphocyte content.
Symptoms of Hodgkin’s lymphoma
Hodgkin’s lymphoma has a variety of clinical presentations that depend on the lymph nodes affected and the severity of the condition. The most common symptoms include:
1) Painless swelling of the lymph nodes
Discrete groups of lymph nodes are the main site of cancer cells in Hodgkin’s lymphoma especially those in the upper body. Painless swellings can be found as a sole symptom in most lymphoma patients.
2) B symptoms of lymphoma
They are also called constitutional symptoms and they occur in a minority of cases. They are the same as those occurring in leukemia and are usually attributed to an inflammatory reaction resulting from the destruction of cancer cells or due to a variety of chemical substances released from cancer cells. They include:
- Night sweating, which tends to be so sever that the patient wakes from their sleep drenched in sweat.
- Unexplained weight loss of more than 10% of body weight in the past 6 months. Other causes of weight loss have to be excluded before judging it as unexplained. Weight loss in cancers reflects the great demands of cancer cells for energy and their deprivation of other parts of the body from it.
- Fever: There are varieties of fever patterns in lymphoma, but the most common in Hodgkin’s lymphoma is what we call Pel-Epstein fever which is a period of fever exceeding 38 Celsius (100.4F) for about one week followed by another week without fever and then the fever returns again for another week and so on. Fever reflects the increased rate of metabolism of the body resulting from the rapid uncontrolled division of cancer cells.
3) Enlargement of the liver and spleen
Both the liver and spleen are a part of the reticuloendothelial system which is responsible for the destruction of aged cells and -in some cases- the formation of new cells for the blood if the conditions demand. In lymphomas, they may also enlarge since some lymphoma cells can filter through them or some lymphocytes within their tissue may become malignant since they are exposed to the same stimuli as lymph nodes.
4) Paraneoplastic syndrome
Paraneoplastic syndrome is a group of clinical signs and symptoms that aren’t directly related to the cancer itself, but a result of the chemical substances released from it. Symptoms may vary according to the type of cancer but in Hodgkin’s lymphoma, it usually presents with neurological manifestations in the form of paralysis especially in an ascending manner (Guillain Barre) or as cerebellar problems affecting balance and coordination.
5) Pain
One of the classical tests for detecting lymphoma was advising the patient to drink alcohol, and if pain occurs minutes afterwards at the sites of suspicious swellings, then they are diagnosed with lymphoma. This sign can only be demonstrated in 10% of cases, however.
Diagnosing Hodgkin’s lymphoma
Even if all the mentioned clinical signs and symptoms are present, the diagnosis of Hodgkin’s lymphoma remains unsure unless a confirmatory test is done. Some conditions may still resemble Hodgkin’s lymphoma such as:
♦ Viral infections like cytomegalovirus and Epstein-Barr virus, both of which can cause enlarged lymph nodes and spleen.
♦ Tuberculosis: It can also cause enlarged painless lymph nodes with enlarged spleen in some cases. Tuberculosis can also cause night sweating and fever.
♦ Non–Hodgkin’s lymphoma: Although they may have similar names, but the outcome and clinical presentation of each condition varies greatly. Non-Hodgkin’s tends to occur at an older age and has a greater percentage of affecting the spleen as well as other sites of lymphoid tissue outside the lymph nodes.
♦ Other cancers: Other solid cancers can send metastases to their neighboring or even distant lymph nodes and cause a similar clinical presentation to Hodgkin’s lymphoma. A notable similar cancer is small cell lung cancer which is considered occult, which means that it usually presents by lymph node involvement and paraneoplastic syndrome.
To differentiate Hodgkin’s lymphoma from these conditions, a battery of laboratory investigations and imaging modalities are available. Not only do they confirm the diagnosis, but also help predict the outcome of the condition. Lab studies include:
- Complete blood count: Although the blood picture isn’t conclusive for diagnosing lymphoma, but some cases with anemia and decreased white blood count could mean an advanced stage with bone marrow involvement.
- Liver function tests: Again, they detect the extent of the disease and liver involvement.
- Lactate dehydrogenase: Lactate dehydrogenase is an enzyme found inside many cells and is essential for energy production. It is not specific for cancer cells, but an excess in its level could indicate an increased cellular destruction and points towards a large tumor load.
General lab studies can’t confirm the diagnosis of lymphoma since no specific marker is secreted by cancerous lymphocytes, but it can help assess the severity of the condition and give a rough estimation of cancer load.
Imaging modalities
The role of imaging in most cancers is confirming the diagnosis of cancer or an invasive condition, and more importantly the staging of the disease. Staging means the degree of spread of a certain cancer and it is essential for planning treatment and determine the outcome. In Hodgkin’s lymphoma, the most important findings by imaging include the number of lymph nodes affected, their side in relation to the diaphragm and involvement of the spleen or liver.
Imaging studies commonly used in Hodgkin’s include CT scan and PET scan. CT scan is better for the detection of liver or splenic involvement, while PET scan is better for detecting the overall condition of areas affected by lymphoma since it depends on the activity of such cells. It can also be used to detect response to treatment.
Biopsy
Biopsy remains the gold standard for confirming cancer diagnosis and Hodgkin’s is no different. Biopsy is usually taken from lymph nodes proven to be affected either by clinical examination or after performing an ultrasonography.
The lymph node has to be completely excised and the doctor may advise you to perform a fine needle aspiration first to confirm the lymph node involvement. The specimen is then sent to the pathology lab and examined under the microscope, such examination will determine the histological type of Hodgkin’s lymphoma which is essential for planning treatment and determining outcome.
Treatment
As mentioned above, tailoring therapy for Hodgkin’s lymphoma is no easy task and several factors play a role in determining the best line of therapy for a particular patient. Some of those factors include:
- Histological type
- Stage and extent of the disease especially involvement of the spleen and liver
- Age of the patient
- Affection of the central nervous system
- Some lab markers like severe anemia and elevated ESR
- The presence or absence of B symptoms of lymphoma
Several scoring systems are present for assessing the patient based on these criteria to offer the best care and avoid side effects as much as possible.
Most cancer therapies aim towards what we call a complete remission, which is the complete disappearance of all signs of cancer including signs and symptoms, any radiological evidence or lab markers. In Hodgkin’s lymphoma, it can be achieved in about three fourths of all patients, but the ratio varies according to the criteria mentioned above.
If complete remission can’t be achieved, therapy aims towards achieving partial remission or at least preventing the disease from involving the bone marrow which has a detrimental effect on survival. To achieve these goals, several therapies are available including:
1) Chemotherapy
Chemotherapy is largely considered the standard of care for induction of complete remission, many combinations of chemotherapeutic agents exist and they can differ between countries and cancer centres, but the most commonly used is a combination between Adriamycin, Bleomycin, Vinblastine and These drugs affect cell division of cancer cells by targeting their DNA or their apparatus responsible for cell division. They are given for at least 6 months in the form of cycles, a cycle every 4 weeks.
After the 6 months pass and even before, some investigations are carried out to assess the response to therapy including CT scanning and PET scan, if response to primary therapy fails, then another method of chemotherapy is done called salvage chemotherapy. Salvage therapy can include single drugs or combinations.
2) Radiotherapy
Chemotherapy is rarely used alone and can be used with doses of radiotherapy to help control the tumor with lower doses of both therapies. Radiotherapy is, however, notorious of having many side effects and even causing some types of cancers if used injudiciously, so balancing benefits and risks is essential when considering radiotherapy dose and mode of administration.
3) Stem cell transplantation
Stem cell transplantation is considered a feasible option in many conditions involving the bone marrow both cancerous and non-cancerous. It has 2 main types which are autologous and allogenic stem cell transplantation. In the autologous type, stem cells are harvested from the same patient after a dose of chemotherapy to ensure that they are as free as possible from cancer cells, while in the allogenic type, cells are harvested from donor, preferably first degree relatives of the patient.
The bone marrow may need to be ablated before infusing the bone marrow, and this is usually done via high doses of chemotherapy, following transplantation, we may also need to administer a dose of chemotherapy to eliminate any remaining cancer cells. Bone marrow transplantation especially of the allogenic type carries the risk of rejection because of the difference in the genetic composition between the transfused bone marrow and cells of the recipient body. This condition is called graft-versus-host-disease and can be life-threatening in many cases.
Long-term monitoring following complete remission
Cancers are genetic disorders that rarely go away completely, the genetic defect still remains even in a minority of cells and cancer recurrence is not uncommon. In most cases, cancer recurrence tends to have worse outcome than the primary condition, but its monitoring remains essential to catch it in an early stage. The risk of recurrence is usually highest in the first 2-3 years following remission and follow-up has to be extensive during this period.
For the first 2 years, follow up is done every 2-4 months via clinical examination, blood tests including hormonal levels and sometimes, radiological investigations. The period is extended to 6 months for the next 3 years and then every 1 year afterwards. An additional concern, however, is the increased risk of developing cancer after such high exposure to radiation either for therapeutic or monitoring purposes which also indicates running some tests to check for cancers that may result from radiation after 10 years of complete remission from Hodgkin’s.