These signs and symptoms may be the early presenting features of the malignant lymphomas or may not appear until later. At one time or another they will usually be found in almost all patients with nonlocalized malignant lymphomas. They include the following:

1. Fever. Usually, but not always, low-grade; may be persistent or intermittent. The so-called "classical" Pel-Ebstein fever is relatively uncommon. This is characterized by a stepwise climb of temperature to a moderately elevated plateau, where it remains for several days and then declines gradually to normal levels. This cycle may be repeated many times.

2. Pruritus. Generalized itching without evidence of skin abnormality is a characteristic and troublesome manifestation, especially in Hodgkin's disease.

3. Perspiration. This may occur at anytime, but night sweats, often of the drenching variety encountered in patients with tuberculosis, may be noted.

4. Other symptoms. These include weight loss, tachycardia, weakness, anorexia, and lassitude.

5. Pallor. This is secondary to the anemia, produced singly or in combination by the following:

(a) Bone marrow depression

(b) Hemorrhagic phenomena

(c) Hemolysis

6. Hemorrhagic phenomena. These may be due to multiple factors, the most important of which is usually the thrombocytopenia secondary to bone marrow depression.

7. Infections. These may be of any type, ranging from superficial cellulitis to pneumonia or septicemia. This lack of resistance is thought to be a consequence of abnormal numbers and types of white cells and diminished or altered immunologic responses.

Regional Manifestations

As noted previously, the malignant lymphomas may involve virtually any body tissue or organ with resulting signs and symptoms appropriate to that site. Some of the more commonly involved areas include the following:

1. Peripheral lymph nodes. Cervical lymphadenopathy is one of the commoner presenting features of the lymphomas, but supraclavicular, axillary, inguinal, and other node enlargement may be noted, singly or in various combinations. The nodes may be symmetrical or asymmetrical, small or large, hard or soft, discrete or ill-defined, mobile or fixed. They are almost always painless. On the basis of the character of the nodes it may be possible to make an educated guess as to the precise type of malignant lymphoma present, and much space could be devoted to such clinical differentiation-but the wisest course is to rely on the pathologist's report of the biopsy.

2. Deeper lymph nodes:

(a) Mediastinal lymphadenopathy. This may present as respiratory symptoms of cough, dyspnea, chest discomfort, etc., or the signs and symptoms of the superior vena caval syndrome may be noted, or the sole abnormality may be mediastinal widening noted on a routine chest x-ray film (Fig. 82).

(b) Para-aortic or retroperitoneal adenopathy, manifested by nonspecific abdominal complaints plus evidence of a palpable mass or masses.

3. Spleen. Splenomegaly of at least moderate degree is a common finding. This occasionally may be painful, with left lower chest and shoulder radiation, especially in the case of splenic infarction. Perisplenitis with an associated audible and palpable friction rub may be noted. Sensations of left upper quadrant and abdominal fullness, distention, and dragging, as well as bowel dysfunction, may occur if the spleen achieves real bulk.

4. Liver. Involvement of this organ less commonly gives rise to palpable enlargement than is the case with the spleen. Jaundice of the intrahepatic or extrahepatic type may occur.

5. Lungs. Involvement of the pulmonary parenchyma may be evidenced by the presence of diffuse or localized infiltration, nodular densities, atelectasis, etc. The pleura is commonly involved also, and pleural effusion may be demonstrable.

6. Heart. Pericardial invasion, with or without effusion and occasionally accompanied by cardiac arrhythmias, may also occur.

7. Gastrointestinal tract. Virtually any part of the alimentary tract may be involved. By way of emphasis, it should be recalled that primary malignant lymphomas make up about 5% of all stomach cancer and that in the small intestines they are as common as adenocarcinomas. They may also exert their effect on the gastrointestinal tract by invasion or extrinsic pressure from masses of lymphomatous tissue (e.g., retroperitoneal nodes). The symptoms and signs resulting from involvement of the gastrointestinal tract by malignant lymphomas are extremely varied and depend entirely on the nature and location of the lesion.

8. Bones. The lesions are usually osteolytic but may be osteoblastic. They most commonly occur in the pelvis, ribs, vertebrae, and femurs. Usually such osseous lesions are associated with disease elsewhere in the body, but occasionally an apparently solitary primary bone lesion is encountered. Frequently bone pain precedes by weeks or months any x-ray evidence of bone involvement. Pathologic fractures may occur.

9. Urinary tract. Occasionally the renal parenchyma is directly involved, but more often large aggregates of lymphomatous tissue surround and compress the kidneys and ureters, producing obstruction, infection, etc.

10. Nervous system. Portions of the central or peripheral nervous system are often involved at some time during the course of the malignant lymphomas. This is apparently not due to invasion of the nervous tissue itself but rather the consequence of secondary pressure phenomena. For example:

(a) Central nervous system symptoms and signs are usually due to meningeal involvement with secondary pressure effects.

(b) Manifestations of impending or actual paraplegia are due to spinal cord compression by lymphomatous involvement of the epidural space or vertebral collapse secondary to invasion of a vertebra.

(c) Other evidence of nervous system involvement depends on the area concerned (e.g., neuropathies relating to the individual cranial or peripheral nerves, Horner's syndrome secondary to cervical sympathetic palsy, and vocal cord paralysis resulting from compression of the recurrent laryngeal nerve).

(d) Herpes zoster is a relatively frequent and distressing complication, particularly in Hodgkin's disease.

11. Pruritus has already been mentioned as a manifestation of the malignant lymphomas. This is usually diffuse and unaccompanied by any visible skin lesions. More specific skin abnormalities include the following:

(a) Cutaneous or subcutaneous nodules. Most commonly encountered on the scalp and face of patients with lymphosarcoma and reticulum cell sarcoma. These nodules are usually reddish or purplish and tend to be small, discrete, and nontender.

(b) A variety of other skin lesions may occur, including the various eczemas, erythemas, and pyodermas, as well as erythema nodosum, Kaposi's hemorrhagic sarcoma, mycosis fungoides, etc.