The possibility of the malignant lymphomas must always be kept in mind in clinical situations involving obscure lymphadenopathy, fever of unknown origin, blood dyscrasias, or any of the extremely varied manifestations just described.

Biopsy And Microscopic Examination

Biopsy and microscopic examination of a lymph node is essential for definitive proof of diagnosis.

1. Choose a small or medium-sized node that seems representative of the type of lymphadenopathy present.

2. Excise the node in toto if at all possible. Partial biopsies are best avoided.

3. Avoid the inguinal areas in particular, since nodes in such areas often reflect chronic inflammation and are notoriously difficult to interpret.

4. Do not hesitate to repeat the node biopsy if the first specimen is interpreted as nonspecific lymphadenitis or is equivocal-and clinical suspicion persists. Occasionally several biopsies are required before a definitive diagnosis can be rendered. Usually, however, one suffices.

5. Use partial biopsy or punch or aspiration biopsy of lesions only under special conditions that preclude excisional biopsy.

6. Do a scalene node biopsy in cases of obscure mediastinal or other intrathoracic disease.

Blood Studies

These are seldom of diagnostic help except for the role they play in ruling out the presence of leukemia. They may be of major importance in determining the extent and degree of lymphomatous involvement as well as in selecting and following therapy, however.

1. Hemoglobin and/or hematocrit determination. Usually a mild or moderate anemia is present, and this becomes more definite and marked as the disease advances. Occasionally anemias may not be noted until quite late.

2. White blood count and differential. A mild or moderate leukocytosis is often noted, although a normal count or leukopenia may occasionally be present. There may be a relative or absolute granulocytosis with a shift to the left and a corresponding lymphopenia. Eosinophilia is sometimes noted, especially in Hodgkin's disease.

3. Platelets. Normal, elevated, or depressed platelet counts may be encountered. Moderate thrombocytopenia is fairly common and tends to become more marked as time goes on.

4. Other findings. There may be elevation of the following blood elements:

(a) Globulin

(b) Uric acid

(c) Alkaline phosphatase

It should be remembered that a substantial percentage of patients with lymphosarcoma, especially children, will eventually develop clinical and hematologic evidence of lymphatic leukemia.

Also, a hemolytic anemia may be added to the picture of the malignant lymphomas.

Bone Marrow

It is always helpful but seldom essential to have knowledge of the status of the bone marrow in order to make the diagnosis of one of the malignant lymphomas. Specific lymphoma cells are not commonly found in the marrow aspirate. More often the changes are nonspecific and parallel or anticipate those noted in the peripheral blood.

X-Ray Studies

In the presence of the malignant lymphomas, radiographic examination of virtually any region, system, or organ in the body may be indicated. The most common are as follows:

1. X-ray film of the chest. This may show evidence of mediastinal widening, pulmonary parenchymal involvement, pleural effusion, etc.

2. X-ray films of the bones. These may demonstrate the effects of lymphomatous involvement of the ribs, vertebrae, pelvis, etc.

3. Gastrointestinal series or barium enema is occasionally called for, and diffuse or localized infiltration of the intestinal tract, especially the stomach, ileum, or colon may be demonstrable. Or evidence of extrinsic pressure on the bowel by masses of lymphomatous nodes may be noted. 4. An intravenous pyelogram may reveal urinary tract obstruction due to large masses of lymphomatous tissue surrounding and occasionally infiltrating the kidneys and ureters or due to pressure caused by enlarged periaortic or other lymph nodes.

Thoracotomy, Laparotomy, Or Other Diagnostic Surgery

Any of these may be required to establish the diagnosis. When all other measures fail, the physician should not hesitate to urge the direct surgical approach in the case of obscure, undiagnosed disease in the chest, abdomen, or elsewhere. The tissue diagnosis obtained in this manner is essential for rational radiation therapy or chemotherapy. Moreover, the findings at operation may sometimes dictate definitive-and curative-surgical treatment, e.g., of malignant lymphoma confined to a resectable portion of the stomach or intestine.