Non-Hodgkin’s lymphomas are solid tumors in lymph tissues and other organs which result from clonal proliferation of lymphoid cells. Most cases are B-cell malignancies with follicular (small-cell) and diffuse large cell disease being by far the most common types encountered. Classification is based on the type of lymphocyte involved (B vs T cell), the cell size (large vs small), whether the cells display a tendency to form nodules (nodular/follicular vs diffuse), and the lymphocyte morphology (well-differentiated vs poorly differentiated). Risk factors for non-Hodgkin’s lymphoma development include HIV infection (usually with CD4 counts < 200cells/mm3), solid organ transplantation, T-cell depleted bone marrow transplantation, Hodgkin’s disease, Sjogren's syndrome, methotrexate therapy, and exposure to pesticides or black hair dye. In cases of gastric mucosa-associated lymphoid tissue lymphoma (MALToma), infection with Helicobacter pylori is considered an underlying risk factor.
Symptoms of lymphoma are nonspecific and include fever, night sweats, weight loss and painless lymphadenopathy. However, some or all of the symptoms may be lacking. Laboratory abnormalities are also nonspecific but the diagnosis should be considered when analysis reveals malignant cells on peripheral blood smear, an elevated LDH, and an elevated ESR. However, the diagnosis can not be exclude based on laboratory testing. Sometimes the diagnosis is first entertained when radiographs reveal enlarged lymph nodes or masses.
The diagnosis is established by tissue biopsy, preferably by excisional biopsy. Mediastinoscopy and laparascopy may be used to obtain tissue for mediastinal and abdominal disease, respectively. Following tissue diagnosis, bone marrow biopsy along with CT scanning of the chest, abdomen, and pelvis are performed for staging purposes. Gallium scanning may be useful after treatment to evaluate if masses noted on repeat CT scanning represent scar tissue (does not take up gallium) or lymphoma (takes up gallium).
Prognosis is dependant on several factors. A more favorable prognosis is expected: in patients less than 60 years of age, when the serum LDH is normal, with stage I or II disease, and when extranodal involvement is limited to one or less sites. As stated above, the majority of cases are either follicular (small-cell) or diffuse large B-cell disease. Follicular lymphoma patients generally survive for prolonged periods and often initially do not require therapy. However,even though this disease does respond to various therapies once symptoms necessitate treatment, it is incurable. Conversely, large cell disease is considered curable but if therapy does not induce remission the one year survival rate is poor. Therefore, once large cell disease has been diagnosed, even if only in a single small lymph node, chemotherapy should be strongly considered.
Chemotherapy is with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) although other regimens exist. CHOP is repeated every 21 days and restaging occurs after the fourth cycle. Therapy is then continued for an additional two cycles after complete remission has been induced.
If relapse occurs in patients with diffuse large-cell disease, treatment should include salvage DHAP (dexamethasone, cytarabine and cisplatin) chemotherapy followed by stem-cell transplantation. Once DHAP induces greater than a 50% reduction in disease, autologous bone marrow transplantation is performed using either bone marrow or peripheral blood stem cells.
Rituximab is a chimeric mouse-human anti-CD20 monoclonal antibody that has been approved for use in follicular lymphomas. Further studies regarding its efficacy are underway.
Other forms of lymphomas of interest:
HAIRY CELL LEUKEMIA
This uncommon form of disease is characterized by the proliferation of hairy cells (B-lymphoid cells with long thin cytoplasmic projections) in the spleen and bone marrow. This is generally a disease of middle-aged males and presents as fatigue, weakness, and weight loss. Physical exam often reveals splenomegaly and less commonly hepatomegaly and lymphadenopathy. Pancytopenia is a common laboratory manifestation of this disease. Hairy cells contain an enzyme, tartrate-resistant acid phosphatase (TRAP) that can be detected by appropriate testing.
This form of disease occurs secondary to infiltration of the skin by malignant lymphocytes and manifests as cutaneous erythema, thickening and scaling. This is a T-cell form of lymphoma. Eventually, malignant cells spread to lymphoid and other tissues.
This is another cutaneous T-cell lymphoma. Clinically it presents as patches of scaly nodular and ulcerative lesions with a purplish coloration. Like Sezary syndrome, this form of disease eventually spread to invade lymph and other organ tissues.
This form of disease occurs in the gastric mucosa-associated lymph tissues. Helicobacter pylori infection is an underlying risk factor for this form of lymphoma.