Seizures after infusion of factor VIII.
Authors: M Small, W F Durward, C D Forbes
Journal: BMJ (1983)

Angiotensin converting enzyme: a tumour marker in malignant histiocytosisAngiotensin converting enzyme is present in vascular endothelial cells and in cells of the monocyte macrophage series.Serum activities of the enzyme may be raised in active sarcoidosis, Gaucher's disease, leprosy, asbestosis, and silicosis,' in hyperthyroidism,2 and in alcoholic liver disease and diabetes mellitus with severe retinopathy.3Low serum activities of the enzyme have been reported in lung cancer, malignant lymphoma, leukaemia, and multiple myeloma.4We report raised activities of the enzyme in two patients with malignant histiocytosis (histiocytic medullary reticulosis).5Case reports Case 1-A 52 year old man was referred to our hospital because of sustained fever, weight loss, progressive hepatosplenomegaly, and jaundice.Laboratory values were haemoglobin concentration 4-8 mmol/l (7.7 g/dl), platelet count 60x 109/1, serum bilirubin concentration 166 tcmol/l (9 7 mg/100 ml), serum alkaline phosphatase activity 147 U/1, serum aspartate aminotransferase activity 162 U/1, serum alanine aminotransferase activity 7-7 U/1, and serum lactate dehydrogenase activity 1656 U/I.Bone marrow and liver biopsy showed infiltration with atypical, x-naphthylacetate esterase positive histiocytes and occasional erythrophagocytosis, which was also seen in a spleen biopsy specimen.The malignant histiocytes in the spleen showed ultrastructural characteristics of histiocytes-namely, abundant cytoplasm with small electrodense granules, large reniform nuclei with a moderate degree of nuclear chromatin condensation, and prominent nucleoli.Activity of serum angiotensin converting enzyme was greatly increased (167 U/1; normal 15-45).The patient died suddenly before treatment.Case 2-A 27 year old man presented in September 1981 with fever, malaise, sweating, and weight loss.Spleen and liver were palpable 6 and 3 cm below the costal margins.Peripheral, intrathoracic, and abdominal lymph nodes were not enlarged.Laboratory measurements showed moderate pancytopenia and raised serum lactate dehydrogenase activity (928 U/1); serum values of urea, creatinine, bilirubin, alkaline phosphatase, aspartate and alanine transferases, and y-glutamyltransferase were normal.Bone marrow biopsy showed increased cellularity and infiltration with atypical histiocytes, dispersed and in small foci.These cells showed phagocytosis of erythrocytes and granulocytes.The histiocytes were myeloperoxidase and periodic acid Schiff negative, acid phosphatase diffusely positive with inhibition by tartaric acid, and a-naphthylacetate esterase strongly positive, consistent with malignant histiocytosis.He was given combination chemo- therapy with CHOP (1250 mg cyclophosphamide, 100 mg doxorubicin, and 2 mg vincristine intravenously on day 1, and prednisone 100 mg/day on days 1-5).Three courses of chemotherapy were unsuccessful but after removal of the still enlarging spleen peripheral blood values returned to normal.Further courses of chemotherapy failed because of intercurrent infections and lack of cooperation, but reinstitution of regular CHOP then resulted in good clinical remission.The malignant histiocytes, however, did not disappear completely from the bone marrow.Serum activity of angiotensin converting enzyme was measured at regular intervals (figure) and values fell to normal during initial chemotherapy, concomitantly with subjective improvement.,,