Occurrence of leukemia and lymphoma in patients with agammaglobulinemia.

This white male child was normal until the age of 6 months when he began to have recurrent upper respiratory and gastrointestinal infections. When he was 18 months old, he developed poliomyelitis and was left with some residual weakness of the legs. A few months later a diagnosis of dermatomyositis was made on the basis of generalized muscle weakness, induration of the skin, and chronic inflammatory changes in skin and muscle biopsy tissue. The child continued to have recurrent bouts of bacterial infection, including episodes of pharyngitis, otitis media, pneumonia, and meningitis. Serum electrophoresis was done for the first time when the patient was 3, and revealed absence of the gamma globulin fraction. Blood isoagglutinins were absent, zinc turbidity’ was 0.1 unit, and the gamma globulin concentration by a sensitive immunochemical method2 was 16 mg. per cent. These studies and the history of repeated bacterial infection established this as a case of congenital agammaglobulinemia. At about this same time, hepatomegaly and large, matted axillary and inguinal lymph nodes were noted. Studies of the bone marrow and peripheral blood revealed normal findings, except for toxic granulation of the neutrophil series. A lymph node biopsy showed only benign hyperplasia. After the child was started on gamma globulin replacement therapy ( 0.6 cc./Kg./month), the number of infections decreased. However, the dermatomyositis progressed, with increased induration of skin and muscles and development of contractures. At the age of 4, he had several generalized convulsions. Skull x-rays and a pneumoencephalogram showed no abnormalities, and the seizures did not recur. Steroid therapy was instituted for a period of several months without significant change in the dermatomyositis. During this period the patient suffered a fracture of the left femur that occurred without significant trauma. At the age of 4 years, 8 months, he suffered a short febrile illness and died in respiratory distress. Figure 1 is a photograph of this child during his last illness. It shows the wasting of the muscles, enlarged abdomen, tight shiny skin, and contractures of the hips, knees, and ankles. There was marked growth failure; when he died, the child weighed only 35 pounds and was 35 inches tall. The autopsy revealed pulmonary congestion and edema, as well as ascites ( about 600 cc. of straw-colored fluid in the peritoneal sac ) . The liver was enlarged, weighing 800 Gm., as were the kidneys: 160 and 170 Gm. The spleen was normal in size. The bone marrow was normal. Microscopic examination of liver tissue revealed extensive mononuclear cell infiltration of the portal triads with some extension into the sinusoids. These cells had large immature nuclei with only a small cytoplasmic rim ( fig. 2 ) . The kidneys showed