Surgery alone, without the addition of chemotherapy or radiation therapy, is sometimes used to treat lymphomas of extranodal internal organs such as thyroid, salivary glands, or stomach that are still confined to the organs where they started. Radiation therapy and/or chemotherapy are also options for these patients. When extranodal lymphomas have spread beyond the organ where they developed, treatment involves chemotherapy, with or without radiation therapy. The choice of chemotherapy drugs and doses depends on whether these extranodal lymphomas are low grade or high grade types.

Gastric (stomach) Lymphoma

Some lymphomas of the stomach appear to be caused by infection with Helicobacter pylori. Infection with this bacterium appears to stimulate an abnormal immune system response by lymphocytes in the stomach, which eventually develop into lymphoma. Remarkably, even after some of these lymphomas in the stomach are fully developed, treating the infection with antibiotics can cause the lymphoma to shrink or even completely disappear. Often, however, these lymphomas will recur after apparently successful antibiotic treatment, and chemotherapy or radiation therapy is then needed. Prognosis and choice of chemotherapy versus radiation therapy depend on whether the cancer is a low grade mucosa-associated lymphoid tissue (MALT) lymphoma or a high grade lymphoma.

Central Nervous System (CNS) Lymphoma

Lymphomas beginning in the brain and spinal cord are called primary CNS lymphomas. These lymphomas usually develop in people with immune system problems due to AIDS or to side effects of drugs given to prevent rejection of transplanted organs. They often respond temporarily to prednisone or to radiation therapy but recurrence within a year or two is common. Use of chemotherapy drugs such as methotrexate or cytosine arabinoside is being studied. The prognosis is affected by the patient's general condition and seriousness of the underlying immune system problems, and is usually poor.

Cutaneous Lymphoma

Lymphoma that starts in the skin is called primary cutaneous (skin) lymphoma. Most of these lymphomas are the T-cell type and are called cutaneous T-cell lymphoma (CTCL). Mycosis fungoides and Sezary's syndrome are other names for CTCL. Diagnosis, staging, and treatment of cutaneous lymphoma is not the same as that for NHL that starts in lymph nodes and other organs.

Patients with CTCL may have localized or extensive skin thickening and/or redness. They may develop nodules (lumps) of the skin. A skin biopsy is needed to diagnose CTCL. Some cases of CTCL may be very difficult to recognize under a microscope, and special studies of the biopsy sample, such as flow cytometry or molecular genetic analysis, are often helpful. Skin involvement may be treated by topical chemotherapy (chemotherapy drugs applied directly to the skin). Other options include electron beam radiation therapy (a type of radiation that can kill cancer cells in the skin without much damage to deeper tissues), cis-retinoic acid (a drug chemically related to vitamin A), and psoralen with ultraviolet light (combination of a drug and "sun-lamp" that may help kill CTCL cells).

Once CTCL has spread to lymph nodes or other organs, chemotherapy is usually needed. Drugs used include Adriamycin, cyclophosphamide, methotrexate, bleomycin, and prednisone (alone or in combination). Nucleoside analogs (Pentostatin, 2-CDA or fludarabine) and interferon are sometimes used. Investigational biological therapies using monoclonal antibodies are being studied in clinical trials.