Lymphoma results from malignant proliferation of cells derived from lymphocyte lineage or histiocyte lineage. Lymphocyte and histiocytes are cells found in the body that primarily function in the defense against infections and exposure to toxins. The lymphocytes are found in blood and in organized structure called lymph nodes. They can also be found in the spleen, thymus and bone marrow. Histiocytes tend to have the same distribution as lymphocytes. Lymph nodes are generally very small structures located where groups of lymphatic vessels meet. They are usually arranged in groups. Groups of lymph nodes include those found:
- around the neck (cervical lymph nodes)
- below the jaw (submandibular lymph nodes)
- in the arm pit (axillary lymph nodes)
- above the clavicle (supraclavicular lymph nodes)
- around the windpipe(trachea), next to the lungs (mediastinal lymph nodes)
- around stomach (celiac nodes)
- behind the organs within the abdomen (retroperitoneal lymph nodes)
- Within the pelvis (pelvic nodes)
- in the groin (Inguinal lymph nodes).
There are many other groups of lymph nodes found all over the body. These groups of nodes become enlarged when there is infection or inflammation in that area of the body. It is not unusual to have swollen groin nodes because of constant cuts and bruises of the legs. Likewise, neck nodes may become swollen when a child has throat infection or ear infection. Following the infection, the size of the node generally reduces. Enlarged lymph nodes become significant when there is no evidence of associated infection or other diseases and they are over a certain size (2 cm X 2 cm).
Lymphoma in childhood can be divided into Hodgkin's disease (lymphoma) and Non-Hodgkin's lymphoma.
Hodgkin's disease presents as progressive, painless swelling of lymph nodes. The cause is unknown. The annual incidence is about 1 - 10/ 100,000 population. There are two peak ages of presentation, between the ages of 15 - 35 years and above the age of 50 years. Hence most children with Hodgkin's disease are in the adolescent age group. It is slightly more common in males than females. Hodgkin's disease is sometimes associated with other medical conditions e.g. rheumatoid arthritis, systemic lupus erythematosus (lupus), and ataxia telangiectasia.
Hodgkin's disease usually presents with progressive, painless swelling of one or more groups of lymph nodes. The enlarged nodes are discrete (i.e. not matted with another node), rubbery and are usually painless. The nodes around the neck (cervical nodes) are the most commonly affected. In up to 60% of cases there is associated mediastinal lymph node enlargement. This may result in associated shortness of breath or a persistent non-productive cough. Occasionally, this result in obstruction of the venous drainage from the neck. The child then develops enlargement of the vessels of the neck, hoarse voice, rapid and shallow breathing and difficulty in swallowing. This is called "superior vena cava syndrome".
In Hodgkin's disease, enlargement of the spleen is often found. This does not necessarily mean that there are malignant cells in the spleen. Occasionally there is associated liver enlargement, which may not necessarily be because of malignant cells lodging and proliferating with the liver.
The lymphoma cell in Hodgkin's disease makes and secretes various substances. Secretion of some of these substances into the blood stream results in intermittent fever, poor appetite, nausea, weight loss, weakness, night sweats and excessive itching. Some people experience pain in affected lymph nodes affected when they drink alcohol.
The lymphoma cell also spread into the bone marrow via the blood stream. These could result in decreased production of mature blood cells (red blood cells, white blood cells and platelets). Thus the child may have mild anemia, increased tendency for infection and increased bleeding tendency.
Lymphoma cells can also invade the nervous system either via the blood stream or via the lymphatic system. Involvement of the nervous system occurs late in the disease. Symptoms seen when this occurs include:
- Early morning headaches and vomiting which signify increased pressure within the brain.
- Sensory deficits.
- Weakness in arms and legs limited to one side of the body (hemiparesis).
Lymphoma cells can also lodge with the lungs and bones. Involvement of the lungs results in fluid accumulation within the chest and shortness of breath. This is rare. It is seen only in about 17% of cases. If the bones are involved, it is usually the bone of the spine and this is very rare. However when this occurs it may result in spinal cord compression and the child will have problems with bladder control, constipation, and weakness or complete paralysis of the legs.
- Blood count
- Blood chemistry especially tests to study liver and kidney function.
- Lymphocyte counts. Tests for Band T lymphocyte function.
- CT scans of neck, chest, abdomen and pelvis. This will identify the different groups of lymph nodes that are enlarged and help in clinical staging of the disease.
- MRI of the bone. This helps to identify areas of bone involvement.
- Ultrasound of the abdomen with particular attention to liver and spleen.
Investigations are primarily done to confirm the diagnosis and to find the extent of spread. In most cases a lymph node that is enlarged and easily assessable is biopsied and reviewed by the pathologist. If the pathologic diagnosis is Hodgkin's disease then other studies are done to help stage the disease. The staging indicates the degree of spread and organ involvement. There are 6 clinical stages. These are I, II, III-1, III-2, III-3 and IV. The stage of the disease is determined by the number and location of lymph node regions affected, and involvement of other areas such as liver, spleen, bone marrow, bone, and lungs. There are two ways of staging the disease. These are clinical staging and surgical staging. Clinical staging is done using CT scan and nuclear studies. Surgical staging involves removal of the spleen, biopsy of the liver, biopsy of various groups of enlarged lymph nodes and bone marrow aspirate and biopsy. Both may need to be done to adequately define the extent of spread since this determines the type of treatment given and it also affects the prognosis. The need for accurate staging is also guided by the type of therapy been considered. If radiotherapy is going to be the only treatment offered then surgical staging is required. If both radiotherapy and chemotherapy will be used then clinical staging is sufficient.
The type of treatment offered is determined by the age of the child, the stage of the disease and extent of lymph node enlargement (moderately enlarged versus bulky nodes. also referred to as tumor burden).
The modalities of treatment are:
- Radiation therapy (radiotherapy).
- Bone marrow transplant. A combination of both is commonly used to treat children below the age of 14 years. The radiotherapy is given only to the affected lymph node group.
This consists of 4 to 6 cycles of a combination of chemotherapy drugs. Each cycle is about 28 days. There are different chemotherapy regimens (schedule) and some oncologist combine two schedule, alternating one schedule with the other.
In children older than 14 years of age who have stage I disease or stage II disease (with no history of fever, weight loss or night sweat at the time of presentation), full dose radiotherapy to the involved area is the only treatment given, Additional chemotherapy is not given. For all other stages, low dose radiotherapy is given in addition to chemotherapy.
Bone marrow transplant
Bone marrow transplant is reserved for children that present with relapsed Hodgkin's disease within a year of completion of treatment. It is also indicated in children who do not respond to standard treatment or those who have involvement of many organs (stage IV). It is an autologous transplant, meaning that the bone marrow is obtained from the child, stored and then re-infused into the child following a course of very high dose chemotherapy.
Clinical parameters that have been identified to predict prognosis include:
- Age: Survival is better in younger patients compared with elderly patients.
- Presentation with history of intermittent fever, weight loss and night sweats is associated with a poorer outcome.
- Response to treatment: Survival is better in children that have complete response to treatment (complete remission) compared to those that have partial or no response.
- Stage: Children that present with localized disease have better outcome than those that have evidence of involvement of multiple organs at the time of diagnosis.
- Histopathology: This refers to the microscopic appearance of the tumor. There are four distinct types based on the predominance or absence of lymphocytes (different from the tumor cells), the presence of nodules, the presence or absence of scarring and the presence of other types of cells. The prognosis tends to be better if there is a predominance of lymphocytes versus absence of lymphocytes.