Primary central nervous system (CNS) lymphoma is one of the clinical presentations of the acquired immune deficiency syndrome (AIDS). Ten patients had biopsy-proven high-grade lymphomas that were confirmed by further staging as limited to the CNS. All ten patients received cranial irradiation (total dose, 2200 to 5000 cGy). Six patients demonstrated complete response (CR) of the intracranial masses at the time of repeat computed tomography (CT) scan, whereas one attained a partial response (PR). Two of the CR patients died of multiple opportunistic infections, two experienced relapse of lymphoma, and died at 7 and 16 months from diagnosis, and two were alive without evidence of disease at 8 and 14 months from diagnosis. The median survival of the whole group was 5.5 months (range, 2 to 16 months). Patients with AIDS-related primary CNS lymphoma may respond to radiation treatment; however, response duration is usually short, and survival is influenced by refractory disease or systemic opportunistic infections.

Twenty-four patients with acquired immunodeficiency syndrome (AIDS) received 80 courses of radiation therapy for Kaposi's sarcoma (KS). Pain and other symptoms due to mass effects were well controlled, but KS lesions often persisted in irradiated sites. Acute radiation toxicity to doses of approximately 2,000 cGy in ten fractions to the oral cavity and/or the foot were significant and may limit the dose and the efficacy of radiotherapy in patients with the epidemic form of KS.

Autopsies in 20 patients with the acquired immune deficiency syndrome (AIDS)-related lymphoma were studied retrospectively to ascertain the precise cause of death and the extent of lymphomatous disease. Eight patients had primary central nervous system (CNS) lymphoma: two of them were diagnosed antemortem; CNS lymphoma was suspected in three others by computerized tomographic (CT) scan and was confirmed at autopsy. The remaining three were diagnosed incidentally at autopsy. All had concurrent infections at autopsy, including opportunistic infection in six and pyogenic infections in two. Opportunistic infections at autopsy in these patients outnumbered those diagnosed clinically. Twelve patients had systemic lymphoma. Three were diagnosed only at autopsy, two of whom had extensive Kaposi's sarcoma (KS) as well. Eight patients were treated with chemotherapy, but died with disseminated disease. Opportunistic infections were found at autopsy in five patients. Secondary involvement of the CNS by lymphoma was frequent (66%) and was not related to previous bone marrow involvement. The authors conclude that the incidence of lymphoma occurring in AIDS may be more frequent than diagnosed clinically. Similarly, multiple opportunistic infections occur in these patients which are not diagnosed premortem and may contribute to early death.

Two monoclonal antibodies (LN-4, LN-5) reactive to human macrophages in B5 formalin-fixed, paraffin-embedded tissue sections have been produced by using deparaffinized cell extracts of peripheral blood mononuclear cells. Both monoclonal antibodies were initially identified on paraffin- embedded sections of hyperplastic lymph nodes by using the immunoperoxidase staining procedure. Specificity screens on normal human tissues show that LN-4 and LN-5 stain the cytoplasm of macrophages and histiocytes in hematopoietic organs including Kupffer's cells of the liver and Langerhans' cells of the skin. LN-4 also showed strong positivity with acini of the stomach, whereas LN-5 was positive with mantle zone B lymphocytes of the lymph node and spleen, spermatogonia, and chief cells of the stomach. Both antibodies were strongly reactive with cases of true histiocytic lymphoma but, except for infiltrating macrophages, were entirely negative in Hodgkin's disease and non-Hodgkin's lymphomas. In all cases of nodular sclerosis Hodgkin's disease, LN-4 was positive in macrophagelike cells present in the collagen bands surrounding the Hodgkin's lesions. Both monoclonal antibodies were also positive in macrophages and histiocytes present in a variety of benign lymphoid lesions including persistent generalized lymphadenopathy, Gaucher's disease, sinus histiocytosis, and dermatopathic lymphadenopathy. Because of their specificity for human macrophages, and their ability to stain B5-fixed, paraffin-embedded tissues, LN-4 and LN-5 are important new reagents for the diagnosis and classification of malignant and benign histiocytic lesions.

Data on 54 persons who died of acquired immunodeficiency syndrome were reviewed for lesions of the heart. These persons met the criteria of the Centers for Disease Control (Atlanta) for acquired immunodeficiency syndrome. Pathologic changes were seen in 30 patients (55%). Changes were seen in the endocardium (17%), myocardium (83%), and epicardium (3%). The most frequent finding was lymphocytic myocarditis. Six of these were due to Toxoplasma myocarditis. Only one patient succumbed to cardiac arrest.

The immunohistochemical localizations of 53 monoclonal antibodies with specificities expressed in human lymphoid tissue were investigated on lymph node tissues from Macaca mulatta, M. speciosa, and M. fascicularis using immunoperoxidase techniques. Thirty antibodies showed comparative cross-reactivity. The micro-anatomic distribution of these antigens was closely homologous to that observed in man and antigen densities appeared to be similar. A useful monoclonal antibody panel for immunopathological investigations in macaques was, thereby, defined. Of several pan-T antibodies studied, only OKT11(CD2) showed cross-reactivity. A detailed analysis of the immunocyto-architecture of five rhesus lymph nodes was undertaken. Automated flow cytometry of M. mulatta and M. speciosa peripheral blood showed a broadly similar pattern to man.

Using a quantitative classification, we evaluated serial lymph node biopsies in 20 homosexual men with Persistent Generalized Lymphadenopathy (PGL), and correlated the results with peripheral blood lymphocyte counts and clinical findings. In a median follow-up interval of 19 months, ten patients (50%) had progression from one histologic subtype of this disorder to another. Lymph nodes from the other 10 patients also demonstrated decreased numbers of organized follicles in the most recent specimens, in addition to progressive abnormalities of other histologic parameters and peripheral blood T4 counts. This suggests that these patients do not have stable disease. However, in a median follow-up interval of 19 months, only one (5%) of the patients had developed AIDS. We conclude that progressive lymph node histopathologic subtypes do not correlate well with decreased T4 lymphocyte counts or clinical course over a short time interval.

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.

Malignant lymphoma rarely involves the heart at initial presentation. We have cared for nine cases in the past 8 years. The median age was 45 years (range, 27 to 68). Initial presenting symptoms included chest pain in four, gastrointestinal (GI) symptoms in three, and constitutional "B" symptoms in two. Echocardiography was the most useful noninvasive procedure, and was abnormal in the eight cases studied. Echocardiographic findings included pericardial effusion in six, and mass lesions within the heart in five. Morphologically, the lymphoma was high-grade small noncleaved in four, immunoblastic sarcoma in one, and diffuse large-cell type in four. Clinical staging workup revealed widely disseminated disease in seven. In spite of multiagent chemotherapy, survival was short (median, 1.5 months). Interestingly, four of these patients were homosexual or bisexual men, who fulfill the criteria for acquired immune deficiency syndrome (AIDS).

Immunohistologic analysis of cellular changes in serial lymph node biopsies of eight patients with persistent generalized lymphadenopathy (PGL) syndrome was performed and correlated with clinical and laboratory findings to better determine the natural history of human immunodeficiency virus (HIV) infection. The authors observed decreased follicle size and area in the second biopsies of six of the eight patients, associated in some with increased numbers of B-cells in medullary regions (four of eight) and more involuted follicles (four of eight). Five cases showed progressively increased paracortical areas in the second biopsies, with increased numbers of T-cytotoxic/suppressor cells and decreased T-helper cells. Seven of the patients also had a progressive loss of T-helper cells in the peripheral blood. These findings provide tissue and peripheral blood evidence for progressive immunologic deterioration in some patients with PGL.

The medical and laboratory records were reviewed in 37 acquired immunodeficiency syndrome (AIDS) patients with cryptococcal infections. In 24 patients with the presentation of cryptococcal meningitis, the initial cerebrospinal fluid (CSF) culture was positive. The initial India ink mount demonstrated organisms in 79% of culture positive CSF specimens. After therapy the subsequent India ink mounts demonstrated 84% sensitivity and 53% specificity with respect to culture outcome. Cultures of blood, bronchoalveolar lavage fluid, and brain were more likely to be positive than cultures from other sites. The initial blood cultures were positive in eight of eight patients at presentation of cryptococcal meningitis. When the initial CSF titer was greater than 1:2, the corresponding CSF culture was always positive. A negative culture during therapy did not necessarily indicate eradication of infection. The initial cerebrospinal fluid and serum cryptococcal antigen titers varied significantly and could not be correlated with survival. In three instances when the CSF cryptococcal antigen titers and cultures were negative, a positive serum cryptococcal antigen greater than 1:8 suggested disseminated infection.

It has been shown previously that dendritic reticulum cells (DRC) in human secondary lymphoid follicles possess an immunoreactive acid cysteine-proteinase inhibitor (ACPI). In the present study, lymph nodes from 12 patients with AIDS-related persistent generalized lymphadenopathy (PGL) were investigated in order to detect whether or not any alterations occur in ACPI-immunoreactive DRC in this disorder. In the majority of PGL cases, profound alterations were found, the main characteristics of which were erosion, partial or total disruption of lymphoid follicles. However, similar though much less marked alterations were also found in some control cases. It is concluded that this type of follicular damage is a common and characteristic feature in PGL. It is not specific to PGL, however, but represents rather a special type of reaction in lymphatic tissue. The advantage of ACPI immunohistology for demonstrating the DRC pattern is that it can be performed on routinely fixed and paraffin-embedded tissues.

Blood and bone marrow samples from 20 individuals with reactive conditions and 26 cases of acute and chronic myeloid leukemias were tested for the presence of lysozyme, alpha-1-antitrypsin (alpha-1-AT), and alpha-1-antichymotrypsin (alpha-1-ACT). We compared the reactivity of samples in smears, cytocentrifuge preparations, and paraffin sections. Lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were found only in polymorphonuclear leukocytes and monocytes and their precursors. Lymphocytes, E-rosetting cells, Con A-activated lymphocytes, natural killer (NK) cells, red blood cells, erythroblasts, and megakaryocytes were consistently negative. Leukemic myeloblasts showed definite reactivity for both alpha-1-antitrypsin and alpha-1-ACT, but not for lysozyme. By contrast, lysozyme was present in poorly differentiated leukemic monoblasts, while alpha-1-antitrypsin and alpha-1-antichymotrypsin showed only weak reactivity. More mature myeloid and moncytic cells showed positive staining for all three antigens tested with differences in staining distribution and intensity. In four cases of chronic myeloid leukemia (CML), circulating mature polymorphonuclear leukocytes were deficient in both lysozymne and alpha-1-antitrypsin. The use of lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin identifies normal and leukemic cells of the myeloid-monocytic series at all stages of maturation and is applicable to a variety of sample preparations.

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.

Acute lymphocytic leukemia (ALL) is a heterogeneous group of disorders, clinically, immunologically, and pathologically. ALL of a B cell phenotype (B-ALL) is the least common. We have studied ten adult patients with B-ALL, none of whom had a tumor mass. The median age was 56 years (range, 30 to 90). A history of an altered immune state was noted in four cases: a distant history of Hashimoto's thyroiditis in one, pregnancy in one, and acquired immunodeficiency syndrome in two. Two patients presented with CNS involvement, and in two additional patients CNS leukemia developed during the course of disease. By the French-American-British (FAB) classification system, L3 leukemic morphology was present in nine, whereas L2 was present in one. Circulating leukemic blasts varied from less than 500/dL to greater than 15,000/dL. Eight patients were thrombocytopenic, and eight were anemic at presentation. Immunologic marker studies on leukemic blasts revealed monoclonal kappa light chain marking in nine and monoclonal lambda in one. Following chemotherapy, complete remission was achieved in three patients, two of whom experienced relapse within 9 months. The median survival for the group was 3 months, and only one patient experienced long-term, disease-free survival. We conclude that B-ALL in the adult presents with the classic L3 morphologic picture in the majority and is associated with extremely short survival.

Blast cells from ten patients (seven adults, three children) with acute lymphoblastic leukemias (ALL) contained immunoreactive cytoplasmic alpha-1-anti-trypsin (alpha-1-AT) and alpha-1-antichymotrypsin (alpha-1-ACT). Cytochemically positive reactions for block-like periodic acid-Schiff and a localized acid phosphatase suggested that the cells were of lymphoid origin rather than myeloid origin: negative for sudan black-B, nonspecific esterase, chloroacetate esterase, and myeloperoxidase. By surface phenotype, the leukemia showed positive reactions for both lymphoid (common acute lymphoblastic leukemia antigen, Ia, OKT-10) and myeloid (OKM-1, Leu M-1) antigens. Three of three patients tested portrayed the Philadelphia chromosome. Nine patients were Mexican-American and one was Japanese: all were of Asian ethnic derivation. Both myeloid and lymphoid treatment regimens were employed, with survival less than expected. Early granulocytic differentiation detectable by cytoplasmic alpha-1-AT and alpha-1-ACT in lymphoid blasts is discussed.

Eleven heterosexual patients (nine women, two men) without classic risk factors for development of acquired immunodeficiency syndrome (AIDS) were seen between March 1983, and April 1985, and diagnosed as having AIDS (four), persistent, generalized lymphadenopathy (PGL) (four), or asymptomatic human T-cell lymphotropic virus type III (HTLV-III) carrier state (three). The clinical presentations and course of those with AIDS or PGL were similar to those reported in homosexual men with AIDS or PGL, with reversed T4/T8 ratio, and the presence of antibody to HTLV-III. Asymptomatic carriers had normal T4/T8 ratios, had an absence of HTLV-III antibodies, but had HTLV-III virus cultured from blood. We conclude that the heterosexual population, with or without history of sexual exposure to individuals at risk for AIDS, may develop a wide range of clinical manifestations secondary to HTLV-III, varying from AIDS to the asymptomatic carrier state.

We performed some preliminary experiments to show that urease at room temperature and the concentration used would not be capable of degrading the urea in a sample containing 15-50 mmol (90-360 mg/ 100 ml) urea. We were also able to show that urease can function in the presence of 3-6 g/l formaldehyde at 56°C, these being the conditions in the peroxidase fixation bath. Working alkaline peroxidase diluent containing urease has been used in this laboratory for the past six months without any apparent adverse effects on the Technicon H6010C. Addition of the urease has doubled the cost of alkaline peroxidase diluent and added an additional 0005 Australian dollars (0-5 cents) to the cost of processing each sample when the Technical methods

Lymphoma of the rectum is a rare tumor and in most studies is not separated from other lymphomas of the large intestine. We have recently examined four homosexual men with lymphoma presenting in the rectum. Symptoms included rectal bleeding in three, pain on defecation in two, and mucoid rectal discharge in two. Systemic "B" symptoms (ie, fever, night sweats, and/or weight loss), as well as a rectal mass, were present in all four. All were high-grade tumors, with B-cell immunoblastic sarcoma in two and small noncleaved Burkitt-like lymphoma in two. Intracytoplasmic immunoperoxidase staining revealed monoclonal kappa light chains in three tumors, whereas the fourth was nonstaining. Immunologic abnormalities were similar to those reported in patients with acquired immunodeficiency syndrome. Antibodies to human T-cell lymphotropic virus type III were found in the three cases tested, and retrovirus was cultured from lymphomatous tissue in one. Despite multiagent chemotherapy, two patients died within six months of diagnosis and a third has recently suffered relapse within the central nervous system.