Philadelphia chromosome-negative acute hematopoietic malignancy: ultrastructural, cytochemical and immunocytochemical evidence of mast cell and basophil differentiation.
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Biomedical subjects
Publications and source records attributed to J Mezger.
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Ascitic fluid concentrations of fibronectin, cholesterol and protein were determined in 95 patients: 38 with cirrhosis of the liver, 10 with miscellaneous nonmalignant diseases, 43 with peritoneal carcinomatosis and 4 with liver metastases or hepatocellular carcinoma. Fibronectin, cholesterol and protein at discrimination values of 7.5 mg/100 ml, 45 mg/100 ml and 3.0 g/100 ml, respectively, separated patients with peritoneal carcinomatosis from patients with cirrhosis with an efficiency of 94%, 90% and 85%, respectively. Thus, ascitic fluid determinations of fibronectin and cholesterol offer good discrimination of cirrhotic ascites from ascites related to peritoneal carcinomatosis, superior to the conventional protein determination. However, the failure of all parameters to distinguish ascites caused by miscellaneous nonmalignant diseases from malignancy-related ascites underscores the importance of highly specific methods to confirm a suspected diagnosis of malignancy-related ascites.
The histologic and cytologic distinction of malignant mesothelioma from carcinomas metastatic to the pleura or peritoneum is often problematic. For this reason immunologic methods are being increasingly used as diagnostic adjuncts. This review summarizes 40 studies on the expression of carcinoembryonic antigen in mesotheliomas and in lung and other carcinomas involving the pleura or peritoneum. Carcinoembryonic antigen was identified immunohistochemically in 11% of mesotheliomas and in 84% of carcinomas examined and immunocytochemically (in serous effusions) in 4% and 58%, respectively. In serum and in pleural or ascitic fluid, significantly elevated levels of carcinoembryonic antigen are commonly associated with (lung) carcinomas but rarely with mesotheliomas. Thus, together with identification of the antigen in serum, pleural fluid, or ascitic fluid, immunohistochemical and immunocytochemical techniques for detecting carcinoembryonic antigen provide a valuable aid for distinguishing malignant mesothelioma from metastatic carcinomas.
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Patients with benign pleurafibromas should undergo surgery as suspect thoracic tumors have the potential to become malignant. In benign cases diagnosis can easily be made during the operation. In such a case the prognosis is good and it is seldom necessary to undergo repeated surgery due to recurrence. In the case of malignant pleuramesothelioma the preoperative diagnosis with an exact staging of the tumor is very important to determine an adequate therapeutic regimen. X-ray, CT-scanning, tapping of the pleura fluid and biopsy of the pleura are together insufficient to diagnose a pleuramesothelioma correctly. Since it is not always possible to diagnose a malignant pleuramesothelioma even at thoracoscopy, one should not hesitate to perform an open lung biopsy in order to obtain enough material under adequate vision.
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A 42-year-old man was admitted to hospital with, previously wrongly diagnosed, fulminant falciparum malaria, 14 days after a two-week trip to Kenya. He had a high fever and was jaundiced, with severe anaemia and thrombocytopenia. He was given quinine intravenously and pyrimethamine/sulfadoxine (Fansidar) by mouth. He developed acute renal failure and increasingly severe cerebral symptoms, at times coma. An exchange transfusion and several plasmaphereses were, therefore, performed. The cerebral symptoms quickly abated during the exchange transfusion, but renal function failed to improve. Because of continuing fever, mefloquin (Lariam) and doxy-cycline (Vibramycin) were also administered. After several dialysis periods the patient improved gradually and was discharged after three weeks in generally good condition with normal renal function.
The use of tumour associated antigens in the diagnosis of serous effusions was studied in 76 patients with benign and 200 patients with malignant disease. Tissue polypeptide antigen (TPA), alpha fetoprotein, and CA 125 were found to be of little value. At cut off points of 3 ng/ml, 10 U/ml, and 30 U/ml, respectively, carcinoembryonic antigen (CEA), biliary glycoprotein I (BGP I), and CA 19-9 discriminated between benign and malignant serous effusions with a sensitivity of between 24% and 67%. The immunocytochemical staining for these markers resulted in malignant cells being detected in 18% to 33% of cases. Various combinations of conventional cytological examination, effusion fluid tumour marker determination, and immunocytochemical analysis identified malignant cells in serous effusions in up to 72% of cases; conventional cytology alone detected tumour cells in only 30%.
The tumor-associated antigen CA 125 is widely used in monitoring of ovarian carcinomas. As this determinant is also expressed in proliferating mesothelia, we studied CA 125 levels in serum and effusion fluid of patients with ascitic and pleural effusions. Patients with benign and malignant disease were included. There was no statistically significant or diagnostically useful difference between 26 benign and 44 malignant cases in the CA 125 levels in effusions or sera. In 77% of benign cases, serum levels exceeding 105 U/ml (3 times the recommended upper limit of normal values) were found. Thus, in patients with serous effusions, elevated serum CA 125 values alone do not provide evidence for the presence of an (ovarian) malignancy, but may also indicate a proliferation of mesothelium due to benign disease.
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In 26 patients with benign and 44 patients with malignant ascites or pleural effusion the levels of the tumour marker Ca 125 were determined in the effusion and in the serum. No significant differences between both groups were seen. Values exceeding the tenfold level of the upper standard limit were often found even in patients with benign and non-carcinomatous malignant diseases. This is probably due to a production of the antigen even in benign proliferating cells of the mesothelium. Enhanced Ca 125 serum levels cannot therefore be interpreted as indicating the presence of an (ovarian) carcinoma if there is an ascites or pleural effusion; they can also be an expression of a proliferation of the mesothelium in benign processes of other organs.
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Two patients with metastatic sweat gland carcinoma were treated with a combination chemotherapy consisting of adriamycin, cyclophosphamide, vincristine and bleomycin. In one patient, a complete remission of two years' duration, and in the other a partial remission (4 + months) were achieved. A review of the literature about chemotherapy in metastatic sweat gland carcinoma is given.
The identification of carcinoma cells in ascitic and pleural effusions by the detection of tumor markers was studied using an indirect immunoperoxidase method. Punctates from 56 patients with carcinomas, 18 with other malignant diseases and 10 with benign diseases were examined. In 35% of carcinomatous punctates tumor cells were stained by a CEA antiserum. No positive cells were found, however, in non-carcinomatous benign or malignant effusions. The immunocytochemical staining of CEA could detect tumor cells in 36% of carcinoma cases classified suspicious or negative using conventional cytology only. A TPA antiserum as well as the monoclonal antibody OC 125 stained cells in carcinomatous as well as in non-carcinomatous malignant and in benign punctates.
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Sixteen patients in chronic myeloid leukemia blast crisis entered a phase II trial with vindesine and prednisone. Median duration of the chronic phase was 29 months in 13 patients, one previously had polycythemia vera, and two presented with a primary blast crisis. Eleven patients had myeloblastic features, as evidenced by morphology, cytochemistry, and cell surface antigens; three had a mixture of myeloid and lymphoid blast cells with lymphoblastic predominance; one had blast cells which displayed lymphoid characteristics; and one was classified as undifferentiated. Three patients had complete remissions lasting 1 month (myeloid), 3 months (mixed), and 5 months (lymphoid). Eleven patients had minor responses, with a median duration of 3 weeks (eight with myeloid, two with mixed, and one with undifferentiated). Two patients did not respond to vindesine. Leukopenia and thrombocytopenia were severe and prolonged independent of their morphologic or immunologic phenotype.
16 patients with CML-BC were treated with vindesine/prednisone. Complete remissions were achieved in 3 cases which lasted 1 month (myeloid), 3 months (mixed) and 5 months (lymphoid). Minor responses, including less than 50% reduction of absolute blast counts and marked regression of organomegaly with a median duration of 3 weeks, occurred in 11 patients. Two patients did not respond to VDS. Leukopenia and thrombocytopenia were severe and prolonged, independent of their phenotype.