Lymphomas are a heterogeneous group of cancers that develop in the lymph nodes and lymphoid tissues present throughout the body.
There are two general types of lymphoma: Hodgkinís disease (HD) and non-Hodgkinís lymphoma (NHL). HD has four subtypes, of which nodular sclerosing in the most common. It accounts for two-thirds of cases.
There are over 25 subtypes of NHL, but the two most common (diffuse large B-cell and follicular) account for over 50% of cases. Almost all subtypes of both HD and NHL present with swollen lymph nodes (termed lymphadenopathy).
Lymphadenopathy due to lymphoma can occur almost anywhere in the body. In addition, unlike lymph nodes that are swollen due to infection, lymphoma lymphadenopathy is generally hard to the touch, fixed in place, and usually painless.
The other important collection of symptoms that can be caused by lymphomas are so-called B symptoms. These are an important part of lymphoma staging, and their presence tends to indicate more extensive disease. There are three recognized B symptoms:
Drenching night sweats (e.g., the patient must change clothes and bed linens)
Fever greater than 38 degrees Celsius (100.4 degrees Fahrenheit)
Unintentional weight loss of more than 10% within 6 months of diagnosis
Common Signs and Symptoms
As discussed, lymphadenopathy is by far the most common presenting symptom of lymphoma and can occur almost anywhere. Although not 100% predictive, the location of lymphadenopathy often indicates if the lymphoma is HD or NHL. HD tends to present centrally in the thoracic cavity.
In contrast, NHL tends to present peripherally in the lymph nodes under the arms and/or in the abdominal cavity. The lymphadenopathy associated with indolent NHL may wax and wane over time, while that associated with HD and aggressive NHL progresses rapidly. B symptoms as described above are present in about 25% of lymphoma patients at the time of diagnosis.
Although lymphadenopathy indicates where the disease starts, from there, it can spread to extranodal sites. This includes the liver, spleen, bone marrow, gastrointestinal tract, skin, and central nervous system (CNS). NHL tends to spread to extranodal sites more often than HD, and in 25% of NHL patients, the disease is present only in extranodal sites (e.g., no detectable lymphadenopathy).
Other Signs and Symptoms
Symptoms associated with lymphadenopathy are dependent upon location and vary widely from patient to patient. For example, bulky lymphadenopathy in the thoracic cavity will often cause shortness of breath and chest pain. Lymphadenopathy in the pelvis may obstruct the ureters and cause renal failure.
Extranodal involvement of the liver and/or spleen may cause abdominal pain and distension. Likewise, patients with CNS lymphoma may have headaches, seizures, and/or stroke-like symptoms, such as weakness on one side of the body. Finally, patients with cutaneous involvement of lymphoma may report patches or plaques of tumor with redness and itching.
It is important to point out the particular signs and symptoms when lymphoma involves the bone marrow. This is a common site of extranodal spread, especially with indolent NHL. Any patient with lymphoma involving the bone marrow may have significant cytopenias due to decreased normal blood cell production.
Neutropenia is decreased white blood cell count and may lead to recurrent infections. Thrombocytopenia refers to low platelet count. This may lead to easy bruising, nose bleeds, and petechiae. Finally, anemia due to decreased red blood cell production often leads to fatigue and shortness of breath, especially on exertion.
Associated Disorders
Hypercalcemia is commonly associated with solid cancers such as multiple myeloma and breast cancer, but it may occur with lymphoma as well. As the serum calcium level increases, it leads to renal failure, constipation, and nausea/vomiting. In advanced stages, hypercalcemia causes cardiac arrhythmias and coma.
Temporary treatment is accomplished with aggressive intravenous fluids and drugs such as pamidronate or zoledronic acid. Long-term, control of hypercalcemia is only achieved by control of the underlying lymphoma.
Tumor lysis syndrome is a worrisome complication of initial treatment of advanced or bulky aggressive lymphomas. Because the lymphoma cells are so sensitive to radiation and chemotherapy, they may die quickly when treatment begins.
This leads to a rapid increase of intracellular contents in the blood, most notably potassium, phosphates, and uric acid (a breakdown product of DNA). Renal failure and cardiac arrhythmias are potentially fatal complications. Prevention is key, and most patients with aggressive lymphomas will receive their first treatment or two in the hospital.
There, they can receive aggressive intravenous fluids and drugs such as allopurinol. Note that Burkittís lymphoma is the fastest growing cancer known. It can present with tumor lysis syndrome even before treatment is initiated.
Superior vena cava syndrome can occur with any malignancy that presents in the right upper portion of the chest cavity. This is where the superior vena cava (SVC) enters into the right atrium of the heart.
Compression of the SVC leads to swelling of the head and neck and potentially respiratory compromise. Since up to two-thirds of patients with HD will have thoracic involvement at the time of diagnosis, SVC syndrome is more common in HD versus NHL. Treatment consists of systemic chemotherapy and corticosteroids, as well as localized radiation therapy to the mass compressing the SVC.
