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Chapter: Medical Immunology: Malignancies of the Immune System

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Leukemias and Lymphomas

The malignant proliferation of leukocytes can be classified by a variety of criteria. One first important distinction is made between leukemia and lymphoma.

LEUKEMIAS AND LYMPHOMAS

A. Nomenclature

The malignant proliferation of leukocytes can be classified by a variety of criteria. One first important distinction is made between leukemia and lymphoma.

Leukemia refers to any malignant proliferation of leukocytes in which the abnormal cell population can be easily detected in the peripheral blood and in the bone marrow. Leukemias may involve any type of hematopoietic cell, including granulocytes, red cells, and platelets. Leukemias are often classified as acute or chronic, based on their clinical evo-lution and morphological characteristics that are closely related.

Acute leukemias follow a very rapid progression towards death if left untreated. Many immature and atypical cells can be seen in the peripheral blood of patients with acute leukemias. Chronic leukemias have a more protracted evolution; differentiated cells pre-dominate in the peripheral blood of patients with chronic leukemia.

Leukemic states may evolve from a chronic form to an acute disease, and the type of proliferating cell may also change during the course of the disease. For example, transition from a chronic granulocytic stage to an acute and very often fatal lymphoblastic leukemia is characteristic of chronic myelocytic leukemia.

Lymphoma refers to localized lymphocyte malignancies, often forming solid tumors, predominantly affecting the lymph nodes and other lymphoid organs. Lymphomas are al-ways lymphocytic malignancies.

B. Classification

All malignant proliferations of cells identifiable as lymphocytes are classified as either T-or B-cell malignancies, based on a variety of characteristics:

·              Identification of the malignant cells as immunoglobulin-producing cells allows their classification as B-cell malignancies.

·              Cell membrane markers are widely used to classify malignant lymphocyte prolifera-tions.

·              Molecular genetic procedures may be used to determine whether the heavy-chain genes or the T-cell-receptor genes are rearranged in a malignant lymphocyte population.

Case 27.2

A 48-year-old black male who worked as a graphic designer emigrated from Jamaica 33 years ago. He was referred to the dermatology clinic of the university hospital for investi-gation of an atypical dermatitis, fever, and nonproductive cough. His main complaint was of a progressive skin rash that his family doctor did not know how to manage. The patient claimed that he noticed the first skin lesions 3 months earlier and started coughing more than usual 2 weeks prior to the time he sought medical attention. He also referred a weight loss of 19 lb. in 2 months. The erythematous lesions initially were very small and barely no-ticeable but had been spreading very fast during the last 2 weeks. Physical examination showed an underweight male in no acute distress. Blood pressure was 136/65, pulse 98/min., respiration 30/min., temperature 101.9°F (38.3°C). A generalized skin rash spar-ing very few areas of the body was seen. The skin was red, thickened, and infiltrated, feel-ing like cardboard at the touch. In addition, two skin ulcers were seen. One, on the fore-arm, had an approximate diameter of 1 inch and the second, on the lateral aspect of his right thigh, was larger, with a diameter of 2.5 inches. During physical examination, it was noted that pressure of the sixth and seventh ribs, on the right side, caused severe pain. On questioning about the chest pain, the patient referred that it had started suddenly 2 days earlier, when he was trying to lift a suitcase. He also noticed that after that, coughing caused pain. Two lymph nodes the size of a cherry were felt on the right side of the neck, four lymph nodes were felt in the left axilla (the largest about 1 inch in diameter), and three smaller nodes were felt in the right axilla. All nodes were firm, smooth, nontender, and mo-bile under the skin. Diffuse rhonchi were audible in both lungs. The liver was nontender and palpated 3 inches below the costal margin. The rest of the examination was normal. A chest x-ray showed bilateral diffuse interstitial infiltrates, severe osteoporosis of the ribs and vertebrae, and a fracture of the 6th and 7th ribs on the right. A CBC and differential revealed (normal values in parentheses) RBC = 2.9×106 / µL (4.4–5.5×106µL), hemoglobin of 7.3 g/dL (13.3–16.0 g/dL), WBC of 23,000 µL (4.0–10.5 103µL) with 37% lymphocytes (20–45%). Lymphocyte subpopulations were as follows: CD3+ : 86% (60 ±10%); CD4+ : 88% (40±10%); CD8+ : 12% (15±10%); CD1+ : 0% (0%); Tdt+ : 0% (0%); CD25+ : 28% ( <1%); CD4, CD25+ : 26% ( <1%). Serum calcium was 2.2 mg/dL (8.5–10.6 mg/dL). Serum immunoglobulins: IgG: 500 mg/dL (600 –1300); IgA: 48 mg/dL (60 –300); IgM: 21 mg/dL (30–150).

This case raises several questions:

What is the most likely diagnosis?

What test should be done to confirm the most likely diagnosis? What is the nature of the patient’s skin rash?

Why did the patient develop rib fractures with minimal trauma? What is the meaning of the large percentage of CD25+ cells?

What is the meaning of the bilateral diffuse interstitial infiltrates seen on the chest x-ray?

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