Human immunodeficiency virus-associated Hodgkin's disease contains latent, not replicative, Epstein-Barr virus.

Severe immunodeficiency is associated with reactivation of latent Epstein-Barr virus (EBV) that is manifested by virus replication. It is unknown whether EBV replication also occurs in the Hodgkin's disease (HD) tissue of patients infected with the human immunodeficiency virus (HIV). Therefore, we studied paraffin-embedded lymph nodes from 13 cases of HIV-associated HD to determine the latent or replicative state of EBV infection. All patients were seropositive HIV-infected men; additional clinical information was available for 12 patients. The risk factor(s) for HIV infection were homosexuality (n = 7), intravenous drug abuse (n = 2), homosexuality and intravenous drug abuse (n = 1), sexual promiscuity (n = 1), or hemophilia (n = 1). Advanced clinical stage and B symptoms were common at the time of initial diagnosis of HD. The histological subtype of Hodgkin's disease was universally mixed cellularity, except for a single case classified as nodular sclerosis. Seven cases exhibited foci of relative lymphoid depletion. Five cases contained foci of necrosis. Reed-Sternberg (RS) cells and RS cell variants were positive for CD30/BerH2 and negative for CD45/LCA, CD45RO/UCHL1, and CD20/L26 in all cases. Tumor cells were positive for CD15/LeuM1 in seven cases. In all 13 cases, RS cells and RS cell variants were infected by latent EBV as shown by in situ hybridization to EBV-encoded ribonucleic acid (EBER1). In 12 of 13 cases neoplastic cells coexpressed EBV latent membrane protein 1 (LMP1). EBV replication was examined by two different methods: immunohistochemistry to identify EBV-encoded BZLF1 protein and in situ hybridization to detect EBV BHLF1 transcripts. No positivity in RS or RS cell variants was detected with either assay of EBV replication (95% confidence interval [CI] = 0% to 23%). The findings confirm that EBV is detected more frequently in HIV-associated HD when compared with immunocompetent patients with HD. The findings also suggest that EBV is tightly latent within RS and RS cell variants of HIV-associated HD. It appears that factors other than host immune status are important in maintaining EBV latency in HIV-associated HD.

Treatment of human immunodeficiency virus-associated Hodgkin disease. Is there a clue regarding the cause of Hodgkin disease?

BACKGROUND: The occurrence of human immunodeficiency virus (HIV)-associated Hodgkin disease (HD) offers a unique opportunity to study the cause of HD and compare HIV-HD with the well-characterized HIV-non-Hodgkin lymphoma (NHL). METHODS: Eight patients with HIV-HD and 17 with HIV-NHL were treated. RESULTS: The complete remission (CR) rate in HIV-HD was 100% with mechlorethamine, vincristine, procarbazine, and prednisone or doxorubicin, bleomycin, vinblastine, and dacarbazine (median survival, > 38.0 months). HIV-NHL patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CR, 80%; median survival, 13.0 +/- 1.3 months). Durable CR was achieved with one to six cycles of chemotherapy (median, 4). There were no late relapses. The difference between the survival rate associated with chemotherapy-treated HIV-HD and chemotherapy-treated HIV-NHL approached statistical significance (P = 0.06). Analysis indicated that all patients with HIV-HD (n = 8) may have acquired HIV through intravenous drug abuse (IVDA) compared with 1 of 17 patients with HIV-NHL (P = 0.0001). A combined analysis (metaanalysis) of 157 patients with chemotherapy-treated HIV-NHL and 51 with chemotherapy-treated HIV-HD confirmed the significantly better survival of those with HIV-HD (P < 0.0001). CONCLUSIONS: Standard combination chemotherapy, truncated as necessary, offers survival outcomes that are at least equivalent and, perhaps, superior to previously published experimental approaches for HIV-NHL and HIV-HD. HIV-HD has a significantly better prognosis than HIV-NHL and is associated with IVDA. These data suggest that the etiologic agents of HIV-HD and HIV-NHL may be transmissible, identifiable, and unique.

Malignant lymphoma of the urinary bladder. A case with signet-ring cells simulating urachal adenocarcinoma.

We describe a malignant lymphoma involving the dome and anterior wall of the urinary bladder in an elderly woman. The initial biopsy showed a malignant neoplasm of uncertain cell type. Because the clinical presentation was most compatible with urachal adenocarcinoma, an extensive resection was performed. Microscopically, the excised tumor was composed of large lymphoid cells with isolated and clustered signet-ring cells. Immunohistochemical analysis established the B-cell phenotype of the neoplasm, and electron microscopy of the signet-ring cells revealed endoplasmic reticulum-bound inclusions consistent with immunoglobulin. Primary malignant lymphomas of the urinary bladder are rare, and, to our knowledge, we report the first example with signet-ring cells. We emphasize this histopathologic finding because of the potential for confusion with urachal adenocarcinoma.

Autotransfusion from experimental hemothorax: levels of coagulation factors.

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

Myelodysplasia progressing to acute myeloblastic leukemia in an HTLV-III virus-positive homosexual man with AIDS-related complex.

Myelodysplastic changes have recently been described in patients with the acquired immunodeficiency syndrome (AIDS). The authors report a patient with AIDS-related complex and myelodysplasia who rapidly progressed to acute myeloblastic leukemia. Infection with human T-cell lymphotropic virus type III (HTLV-III) was documented by culture and by serology. Chromosome studies showed monosomy of chromosome 7 and structural abnormality of the long arm of chromosome 3. The association of HTLV-III infection with myelodysplasia and acute myeloblastic leukemia may have been coincidental in this reported case, but it is also possible that the leukemia was secondary to the HTLV-III infection. Further investigation appears justified.

Hemoglobin H disease with hemoglobin Constant Spring in a child of Laotian extraction.

In alpha-thalassemia, deletion or inactivation of one, two, three, or all four alpha-genes causes, respectively, silent carrier state (-alpha/alpha alpha); alpha-thalassemia trait (--/alpha alpha in Orientals, and -alpha/-alpha in blacks); Hb H disease (--/-alpha); and Hb Bart's hydrops fetalis (--/--). We have described a case of Hb H disease with Hb Constant Spring (--/alpha alpha cs) in a Laotian child whose father had alpha-thalassemia trait and whose mother was a carrier of Hb CS, a mutant hemoglobin produced in minimal amounts. Since alpha-thalassemia is highly prevalent in Southeast Asia, physicians should become alert to the potential occurrence of Hb H disease and Hb Bart's hydrops fetalis in the new Oriental immigrants and their progeny.

Fluorometric assay of antithrombin III. Diagnostic value in 112 patients with abnormal hemostasis.

The authors assessed the diagnostic value of the plasma anti-thrombin III (AT III) assay in 112 adult hospitalized patients with abnormal hemostatic parameters, using the Protopath procedure. In 100 patients tested only once, low AT III was observed in 25 of 29 cases of acute disseminated intravascular coagulation (DIC); 7 of 10 with infections; 8 of 11 with acute liver disease; 19 of 20 with chronic liver disease; and 16 of 30 with other illnesses. The authors conclude that the assay cannot distinguish among disease categories, although it is a sensitive index of DIC. AT III was also repeatedly measured at various time intervals in 12 additional patients. The results suggest enhancement of the diagnostic and prognostic value of the assay with serial testing.

Exsanguination from esophageal rupture of an atherosclerotic aortic aneurysm in a patient with treated tuberculosis.

An elderly man with previous tuberculosis exsanguinated from esophageal rupture of an atherosclerotic thoracic aneurysm. Because the patient refused angiography, the source of bleeding was discovered only at autopsy. Selected clinical and pathologic aspects of the case are discussed in relation to the different causes of thoracic aortic aneurysms. Because these lesions have a grave prognosis, the need for timely diagnostic evaluation and aggressive surgical management is emphasized.

Hepatoblastoma in infant sister and brother.

Two infants, a sister with motor retardation and brother with slight microcephaly and an undescended testis, died of hepatoblastoma. Only another documented familial occurrence of this tumor, affecting siblings of the same sex, can be found in the literature. The two patients described in this paper exhibited high platelet counts prior to liver resection. Although iron deficiency may have contributed to the thrombocytosis, the finding of many megakariocytes within the hepatoblastomas suggests an intra-tumoral production of platelets. An epidemiological investigation of the family under study failed to yield conclusive data. Hepatoblastoma is a rare tumor, but it may affect more than one sibling. Therefore, periodic clinical and laboratory evaluations of the siblings at risk appear to be justified.

Malignant lymphoma of thenasopharyns in waldenström's macroglobulinemia: report of a case with severe epistaxis.

An elderly woman with Waldenström's macroglobulinemia of four years' duration developed repeated severe epistaxis. This led to the discovery of a large malignant lymphoma of the nasopharynx. The clinical features of this rare case are discussed in relation to our present understanding of WM. Epistaxis in macroglobulinemic patients may be associated with anatomic lesions of the nasopharynx.

Pancytopenia associated with a granulosa-cell tumor of the ovary. Report of a case.

An unusual case of pancytopenia associated with a granulosa-cell tumor of the ovary in a 44-year-old woman is reported. Initially the patient was thought to have the rare, but well recognized, syndrome of hemolytic anemia complicating an ovarian tumor. However, laboratory studies and clinical follow-up ruled out hyperhemolysis and documented a condition of bone-marrow failure. Excision of the massive tumor was followed by hematologic recovery, which has now lasted more than a year and a half.