Pleomorphic large cell hemato-lymphoma (the so-called "malignant histiocytosis"): clinicopathological and immunophenotypic studies in 35 cases.

Thirty-five patients diagnosed with "malignant histiocytosis" from 1984 to 1989 were studied for clinical, laboratory, histopathological features as well as survival and response to therapy, Immunocytochemistry and immunophenotypic studies were performed in 12 cases using the paraffin immunoperoxidase method. The staining included alpha-1 antichymotrypsin, muramidase, immunoglobulins and monoclonal antibodies specific for T, B lymphocytes and macrophage. From the clinical features, responsiveness to therapy and survival, the patients were divided into 2 groups: the non-responders (25 cases) and responders (10 cases) groups. Very short median survival of 1.25 months was found in the non-responders, whereas, longer median survival of 14.15 months was found in the responder group. Important different clinical and laboratory features were observed among these two groups. Unresponsiveness to treatment; rapidly progressive pancytopenia, increased hemophagocytosis, presentation of immature cells in blood with extensive infiltration of malignant cells in the bone marrow; severe jaundice and deterioration of hepatic function accompanied by early extranodal involvement were almost exclusively observed initially in the non-responder group. Satisfactory response to treatment was observed only in the responder group. Similarity of histopathology, cytology and immunophenotype was observed in these two groups. The immunophenotypic study in 12 cases showed 5 cases of B-cell lymphoma, 3 cases of T-cell (with 1 Ki-1 -positive) lymphoma; 1 case of Ki-1 positive non-T, non-B anaplastic large cell lymphoma; and 3 cases of undetermined cell lineage. From this study, so-called "malignant histiocytosis" appears to be a disorder of heterogeneity. The immunophenotypes of malignant cells indicated that their origin belonged mostly to lymphoid cell lineage. Based on their clinical feature of the early hematogenous spread along with the distinct histopathological and immunophenotypic findings, the term "pleomorphic large cell hematolymphoma" is proposed to be used instead of the old misnomer, "malignant histiocytosis" (MH).

Pulmonary thromboembolism in thalassemic patients.

Chronic pulmonary thromboembolism plays an important role in cardiac failure which is a major cause of death in thalassemic patients over 20 years of age. This report is a study of autopsy lung tissue from 58 patients with beta-thalassemia/hemoglobin E disease (beta-thal/HbE), including whole lungs from five, 13 patients with hemoglobin H disease (HbH), and eight patients with beta-thalassemia major (beta-thal) including whole lung from one. Pulmonary thromboembolic lesions were found in 24 of 58 (41%) patients with beta-thal/HbE, of which 21 of 39 (54%) were splenectomized patients and 3 of 19 (16%) were nonsplenectomized patients, with the incidence increasing with age. Lung maps showed the greatest number of lesions in the lingula, right middle lobe, and anterior segments of both upper lobes. Pulmonary thromboembolic lesions were also found in one of 13 HbH patients and one of 8 beta-thal patients, both splenectomized. Eight of the 27 patients with these lesions had right ventricular and 14 biventricular hypertrophy, reflecting the deleterious effect of such lesions. Possible causative factors are discussed.

Pulmonary microthromboemboli in thalassemic cases.

Lung specimens obtained from wet materials were reviewed for detection of microthrombi. Multiple microthrombi, which were composed mainly of platelets, were seen in the pulmonary arteriole and microcirculation in two autopsy cases with splenectomized thalassemic disease. These findings provide a rational explanation for the increased spontaneous platelet aggregation in the whole blood, and may be an additional factor to the progress of pulmonary dysfunction and hypoxemia seen in splenectomized thalassemic patients.

Hypoxemia in thalassemia.

Data are reviewed describing hypoxemia, a newly identified feature in thalassemia. Evidence indicates platelet aggregation in the pulmonary circulation as being a key factor leading to hypoxemia and cor-pulmonale with right heart failure.

Brain pathology in 6 fatal cases of post-transfusion hypertension, convulsion and cerebral hemorrhage syndrome.

Six fatal cases of post-transfusion hypertension, convulsions and cerebral hemorrhage syndrome were found in a series of 76 autopsies of thalassemic patients. Five of these cases were hypertensive. At autopsy the brains were all markedly edematous and congested. Visible cerebral hemorrhages were found in 3 patients. Microscopically all cases showed small focal or perivascular hemorrhages and 1 patient had extensive arterial type hemorrhage. Microdissecting aneurysms characteristic of hypertensive cerebral hemorrhage were found in two. No underlying vascular disease was found in these 6 patients. A correlation was attempted between possible causes of post-transfusion hypertension and convulsions and anatomical findings.

Niemann-Pick disease: a case report.

The second case of infantile Niemann-Pick disease was reported in a Thai newborn baby who presented with respiratory distress and hepatosplenomegaly from birth and who succumbed from bronchopneumonia 20 days later. Autopsy examination showed generalized accumulation of foam cells in reticuloendothelial organs. The parenchymal cells of visceral organs as well as neurones in the central nervous system also showed cytoplasmic vacuolization. Electron microscopic study demonstrated characteristic intracytoplasmic electron-lucent membrane-bound bodies. The histologic and ultrastructural findings were similar to those described in the literature.

Immunoperoxidase study on paraffin sections of gastrointestinal lymphoreticular lesions.

Seventy-five cases of lymphoreticular lesions of the gastrointestinal tract were studied by the immunoperoxidase method on paraffin sections which demonstrated cytoplasmic markers, in particular immunoglobulin (Ig) in B-lymphocytes and alpha-1-antichymotrypsin in histiocytes. There were 4 cases of benign immunoproliferative disease (IPD), 1 in the stomach, 3 in the small intestine; their reactions were polyclonal. Large cell non-Hodgkin's lymphoma was subdivided into 21 cases with IPD ("Mediterranean Abdominal Lymphoma") and 29 cases without. Eight cases of lymphoma with IPD were gastric and 13 intestinal; 7 gastric and 12 intestinal lymphomas were of B-cell origin; 1 gastric tumour was histiocytic; 1 intestinal neoplasm had no detectable marker. Sixteen cases of lymphoma without IPD were gastric and 13 intestinal; 4 gastric and 4 intestinal lymphomas were of B-cell type; 3 gastric and 2 intestinal neoplasms were histiocytic; 1 intestinal tumour was a composite of B-cells and histiocytes, in separate but contiguous foci; 9 gastric and 4 intestinal lymphomas had no identifiable marker. One of 18 cases of mixed and small cell lymphoma was accompanied by IPD. In these types of lymphoma Ig was found only in 10-30% of cells, mainly with plasmacytoid differentiation.

Cardiac pathology in 47 patients with beta thalassaemia/haemoglobin E.

Autopsy protocols and heart slides of 47 patients with beta thalassaemia/haemoglobin E disease were reviewed. All but 1 patient had cardiac hypertrophy, accompanied by dilatation in 17; 5 of 9 patients (56%) with right ventricular and 11 of 22 patients (50%) with biventricular hypertrophy had chronic pulmonary thromboembolism. Cardiac iron deposition while present in 15 patients (32%) was very slight, in contrast to the amount of iron in their liver and pancreas. Four patients had fibrinous pericarditis, 2 with rheumatic heart disease. Twelve patients had chronic pericardial changes, 7 with adhesive pericarditis. The effects of cardiac pathology on the morbidity and mortality of patients with beta thalassaemia/haemoglobin E disease were discussed.

Pulmonary artery obstruction in thalassaemia.

A new feature has been encountered in review of a large species of autopsy materials of beta-thalassaemia/Hb E disease. Among 43 patients pulmonary arterial obstructive lesions were found in 19 (44%), of which 17 were splenectomised cases. The pulmonary arterial thromboembolism may have been due to circulating platelet aggregates. This newly discovered pathology may be an additional factor contributing toward dyspnoea and heart failure in thalassaemia besides anaemia and cardiac iron deposition. If it is proven that this pulmonary arterial thromboembolism is indeed due to circulating platelet aggregates, preventive measure by administration of drugs reducing platelet aggregation such as aspirin and Persantin may be indicated, especially after splenectomy.

Immunoproliferative disease of the gastrointestinal tract: a report of five cases.

Five patients with immunoproliferative disease of the gastrointestinal tract are presented. The main pathological feature was dense diffuse lymphoplasmacytic and immunoblastic infiltration of the mucosa and submucosa, of the proximal small bowel in 3 cases and the stomach in 2. Four of the five patients had concomitant immunoblastic sarcoma. The clinical presentation and pathological findings are compared and contrasted with those of "Mediterranean abdominal lymphoma" and alpha chain disease, and the possible role of ethnogeographical and environmental factors in the pathogenesis are discussed.

Hepatic carcinoma with opisthorchiasis.

Eighty-seven cases of primary hepatic carcinoma associated with opisthorchiasis were reviewed. The prevalence of liver carcinoma among 154 cases of liver fluke infection was 56.6%. The tumours were classified histologically as cholangiocarcinoma in 67 cases (77%), hepatocellular carcinoma in 9 (10.3%), mixed hepatocholangiocarcinoma in 4, squamous carcinoma in 2, and undifferentiated carcinoma in 5. Metastases, found in 71 cases, occurred most frequently in the regional lymph nodes and lungs. There were numerous or moderate numbers of liver flukes in most of these cases.

Pathological findings in four cases of human angiostrongyliasis.

Three adults and a 3 1/2-year-old child presented with eosinophilic meningitis. A history of consumption of raw snails was elicited in 2; evidence of a constant diet of raw food, in the form of opisthorchiasis and taeniasis, as well as angiostrongyliasis, was present in the third; no history of raw food ingestion was obtained in the fourth, the child. Pathologic changes were similar in all 4 cases. There was infiltration of the meninges and around intracerebral vessels by varying proportions of lymphocytes, plasma cells and eosinophils. Numerous tracks and microcavities were found in the brains, and in the spinal cords in 2 cases, varying in size from 0.1 to 2 mm, and in age, with older tracks containing debris and gitter cells, newer tracks showing disruption of brain tissue, with and without haemorrhage. Numerous 4th and 5th stage Angiostrongylus larvae, alive and dead, were found in the meninges and brain tissue, sometimes in blood vessels or perivascular spaces, in 3 cases; in the fourth case a 5th stage larva was found on the surface of the right frontal lobe. In one case a degenerating larva was found in a pulmonary vessel. Cellular reaction was more often associated with dead larvae.