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A neuropathologically verified case of histiocytosis-X in a 21-year-old man with endocrine symptoms is presented. The granulomas were confined to the central nervous system and occupied mainly the pituitary stalk and hypothalamus, thus giving us the opportunity to observe the endocrine symptoms caused by such localized lesions. Diabetes insipidus was one cardinal endocrine symptom and is considered to be caused by a hypothalamic lesion in the supraoptic nuclei or the pathways to the posterior pituitary. In this case the anterior pituitary was not involved by granulomas, but the posterior lobe was atrophic. Severe hypogonadism and probably also a growth hormone defect were present, probably resulting from pituitary insufficiency secondary to the hypothalamic lesions. Hypothyroidism was another symptom but in this case was probably due to thyroiditis. Such a finding has previously been observed by two other authors and may therefore be pathologically connected to histiocytosis-X even though no granulomas were present in the thyroid gland. Repeated X-ray investigations from 9 years of age showed that the development of the sella turcica ceased about the same time as the patient got signs of diabetes insipidus. Increase in sellar volume normally reflects pituitary growth. The lesions in the pituitary stalk or the hypothalamus must therefore have been present from the time when diabetes insipidus started.

A thymolipoma in an 8-year-old boy is reported. The tumour had appeared on a routine chest X-ray as a broadened heart shadow and a peculiar right heart contour. Cardiac hypertrophy was suspected primarily. At thoracotomy a thymic tumour was found.

In accordance with the long-range goal to demonstrate the direct derivation of blood monocytes from promyelocytes in human bone marrow, the promyelocytic cell line HL-60 in the present study was differently stimulated with various inducers for the purpose of documenting its capability to evolve into granulocytes or monocytes-macrophages. Each differentiation line was monitored with the use of marker enzymes, antigens, and cell-specific monoclonal antibodies. In addition, studies were done on normal human bone marrow and leukemias. The results provided strong evidence for the close cytogeneic relationship of granulocytes and monocytes and for a common progenitor at the maturation stage of promyelocytes-myelocytes for both cell lineages.

Langerhans cells were enriched from epidermal cell suspensions by a monolayer technique based on the association of Langerhans cells with solid matrix-bound anti-Ia antibodies or by flow cytometry sorting of fluorescein-isothiocyanate labeled anti-Ia reactive cells. The monolayer technique gave a moderate enrichment (15-37%) whereas considerably higher purity (73-87%) was obtained by flow cytometry sorting. The identity of the enriched anti-Ia reactive cells as Langerhans cells was established by histochemical techniques or electron microscopy. The monolayer-enriched Langerhans cells could function as stimulating cells in the mixed leukocyte culture reaction and as antigen-presenting cells.

A case of thymic carcinoid appearing in a 56-year-old man is presented. No endocrine disturbances were apparent. Mediastinal lymph node metastases were found at operation. The tumour was positive with Grimelius argyrophil silver stain. Ultrastructurally neurosecretory granules were seen.

Twenty-three human haematopoietic cell lines, normal and mitogen stimulated peripheral blood lymphocytes and tumour material from fresh leukaemias, myelomas and lymphomas were investigated with a panel of cytochemical reactions. Normal and mitogen stimulated lymphocytes, non-neoplastic lymphoblastoid cell lines (LCL), lymphoma lines with B-lymphocyte characteristics, chronic lymphocytic leukaemia and fresh lymphocytic lymphomas reacted weakly or negatively with all stains. T-lymphocyte acute leukaemia lines were PAS and alpha-naphtyl acetate esterase positive. Myeloma lines and fresh myelomas were strongly beta-glucoronidase positive. A histiocytic lymphoma cell line was strongly esterase positive with naphtol AS-D acetate esterase inhibited by NaF. The three fresh histiocytic lymphomas, however, reacted as the lymphocytic lymphomas suggesting a lymphoid origin. A myeloid leukaemia line was strongly positive for acid phsophatase. No major disagreement was noted between the reactivity of established neoplastic lines and the corresponding fresh biopsy cells indicating an unaltered qualitative expression of enzyme production after prolonged in vitro culture.

The differential diagnosis between lymphocytic lymphoma of the B-CLL type and immunocytoma (IC) can be difficult when it is based only upon morphological criteria. With the aim of improving the distinction between these subgroups, frozen sections of lymph nodes or other biopsied tissues from 14 cases of B-CLL and 16 cases of IC were investigated according to immunophenotype. A panel of 13 B cell-associated and 2 T cell-associated monoclonal antibodies was used. All but one of the B-CLL cases were FMC7-, while 14/16 IC cases were FMC7+ (p less than 0.001). The two negative IC cases were both of the lymphoplasmacytic type, claimed to be "more differentiated" than the lymphoplasmacytoid type. We suggest that the cells in these cases are mature enough to have lost their FMC7 positivity, similar to plasma cells. There was also a statistically significant (p less than 0.01) difference, although not as pronounced, for the anti-CD38 antibody (Leu-17, B-CLL: 3/14, IC: 10/16 positive). No significant difference in expression of determinants was found for any of the other antibodies.

We describe an 8-year-old girl who presented a massive mediastinal tumour of thymic origin. Surgical excision was unsuccessful. Irradiation treatment (4,500 rad) together with intensive combination chemotherapy resulted in regression of the tumour. After three months, an increase of blasts was observed in the peripheral blood and bone marrow. The terminal phase was characterized by acute leukaemia, which did not respond to chemotherapy. Despite the thymic origin of this malignancy, the blast cells contained non-specific esterase activity as determined by naphthol-AS-acetate as substrate. The NaF-sensitive form of this enzyme is a characteristic of monocytes-macrophages. Other monocyte-macrophage markers were, however, negative. We conclude that the NaF-sensitive naphthol-AS-acetate esterase is not limited to tumours of the monocyte-macrophage system.

Spontaneous rosetting with mouse red blood cells (MRBC) seems to be a marker for a subpopulation of B-lymphocytes. We investigated the capacity of different hematopoietic cell lines to form rosettes with MRBC. The cell lines represent different hematopoietic malignancies and the results with these lines were compared with those obtained with non-malignant EBV carrying lymphoblastoid cell lines (LCL). Among tumor cell lines only exceptional lines, 1 myeloma and 2 leukemia lines, showed rosetting capacity with MRBC. Most LCL, however, bound MRBC. These results indicate that only 1 category of established hematopoietic cell line, the LCL, has MRBC receptors and that thus a further subset of B-lymphocyte, the one represented by LCL, has the capacity for rosetting with MRBC. This MRBC rosetting of LCL is, however, not restricted to those lines with S-IgM. Tumor lines of hematopoietic origin seem, however, in general to lack MRBC receptors, even such lines that are derived from malignant lymphomas which express other B-lymphocyte characteristics.

The surface glycoprotein patterns of leukaemic B lymphocytes from 20 patients with clinically progressive or non-progressive chronic lymphocytic leukaemia (CLL) were investigated. Cells were labelled by the neuraminidase-galactose oxidase-tritiated sodium borohydride technique and the radioactive proteins were separated by polyacrylamide slab gel electrophoresis and visualized by fluorography. A total of 13 to 16 bands were detected. A common surface glycoprotein pattern for CLL cells was seen in all patients consisting of 7 proteins with the apparent molecular weights of 210, 200, 185, 150, 135, 110 and 90 kilodaltons, respectively. Interesting differences were, however, observed as cells from patients with progressive CLL in general lacked the glycoproteins 120, 72 and 67 K, which were found on cells from inactive CLL. The possible biological and clinical significance of these findings is discussed.

53 patients with the myelodysplastic syndromes (MDS) were classified according to the proposals of the FAB cooperative group 1982. 29 patients had refractory anaemia (RA), 10 refractory anaemia with excess of blasts ( RAEB ), 5 RAEB in transformation, 7 RA with ringed sideroblasts and 2 chronic myelomonocytic leukaemia ( CMML ). Counting blast cells type I and II involved no difficulties. 4 of 15 patients who developed acute myeloid leukaemia (AML) according to the FAB classification of 1976 did not fulfill the new 1982 criteria for AML. A redefinition of the blast cell type II to include a more granulated blast cells, without the characteristics of promyelocytes, would solve this problem. We conclude that a redefinition of the blast cell type II might turn out to be useful.

The expression of complement receptors, of Fc receptors, of SRBC receptors and of S-Ig was investigated on human haematopoietic cell lines of proved malignant derivation. According to their origin and to a panel of phenotypic markers these lines have been classified into lymphoma lines, myeloma lines and leukemia lines. Results were compared with those obtained on non-malignant EBV carrying lymphoblastoid cell lines (LCL). Among the lymphoid cell lines the LCL showed a pattern of B-lymphocyte surface markers, i.e. surface immunoglobulins, C3 receptors but low density of Fc receptors. The non-Burkitt lymphoma lines bore in varying degree these B-lymphocyte markers. The lines U-698 M and DG-75 were exceptional in having only surface immunoglobulin. The Burkitt lymphoma lines had all B-lymphocyte markers. The myeloma lines differed from the lymphoid lines in lacking C3 and Fc receptors and showed only trace amounts of surface immunoglobulins. In contrast to lymphoid and myeloma lines, the leukaemia lines were completely lacking surface immunoglobulins, but showed C3 and Fc receptors in variable densities. On line, the ALL derived line MOLT-3 showed the capacity to spontaneous rosette formation with SRBC. The findings that LCL presented a homogeneous pattern of B-lymphocyte surface markers may be of value in order to discriminate between these lines and lines derived from haematopoietic malignancies other than Burkitt lymphomas.

Fresh neoplastic B cells from 14 untreated patients with naturally occurring B-cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non-cultured, neoplastic B cells was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non-progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK-susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re-emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor-enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B-cell leukemias was the presence of significantly lower NK effector-cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.

Human monocytes and ascites macrophages from cirrhotic patients were isolated in Percoll-gradient and cultured with and without silica. Similar experiments were carried out also with cultured malignant human histiocytes and transformed mouse macrophages. The fibrogenic activity of the culture media was tested by measuring the incorporation of [3H]proline and [3H]thymidine into cultured rat granuloma and human synovial cells. Media from silica-treated monocytes, ascites macrophages and certain histiocyte and mouse macrophage lines caused an increase in the incorporation of both [3H]proline and [3H]thymidine into collagen and DNA, respectively, in both cell systems. Alkaline RNase activities were decreased markedly in the media from silica-treated ascites macrophages but not in the media of the monocytes or histiocytes.

A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a "true" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.

The croton oil-derived tumour-promoting agent 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) exerts pleiotropic effects on the differentiation and proliferation of both normal and malignant animal and human cells in vitro. TPA is mitogenic in nanomolar concentration to chickens embryo fibroblasts and human T lymphocytes and inhibits the terminal differentiation of various committed embryonic cells and mouse Friend erythroleukaemia or myeloid leukaemia cells. TPA induces a terminal cell differentiation in some murine and human myeloid leukaemia and histiocytic lymphoma cells. We report here the effect of TPA on chronic lymphocytic leukaemia (CLL) biopsy cells in vitro. In four out of five CLL patients studied, TPA induced the appearance of 90-100% of lymphoblastoid and plasmacytoid cells after 4 days of culture. Under the influence of TPA, 86-97% of the cells expressed with time increasing amounts of intracytoplasmic immunoglobulin (C-Ig) of the same phenotype as that detected on the surface (S-Ig) of fresh, non-induced CLL cells. A parallel decrease in both monoclonal S-Ig density and DNA synthesis of the CLL cells was observed. Electron microscopic studies showed a muturation towards plasma cells. We therefore conclude that TPA is capable of inducing differentiation of CLL cells in vitro.

The results of treatment in 175 consecutive patients with nonHodgkin lymphoma (NHL) clinical stage I treated between 1969 and 1984 were analysed according to different pretreatment prognostic variables. Treatment consisted of radiotherapy in 166 of the 175 patients. The estimated 5 and 10-year disease-free survival rates (DFS) were 63% and 60% and the survival rates at 5 and 10 years 82% and 76% respectively. Lymphomas arising from gut-associated lymphoid tissue, i.e. Waldeyer's ring, the thyroid and the gastrointestinal tract had a more favourable clinical course (10-year projected DFS 83%) than nodal (50%) and other extranodal lymphomas. Although the number of patients with other extranodal sites was small, sites such as testis, nasal cavity, paranasal sinus and extradural space seemed to have a high relapse rate. Unfavourable clinical courses were also observed among nodal high-grade NHL if the lymph nodes were larger than 5 cm in diameter. Chemotherapy before radiotherapy may be recommended in NHL subgroups with a high relapse rate and which today are potentially curable with chemotherapy, i.e. highgrade NHL. This study indicates that large nodal lymphomas and some extranodal sites belong to this group.

Three exceptional cell lines have been tested for the presence of the Epstein-Barr virus genome by nucleic acid hybridization (complementary RNA.DNA) and Epstein-Barr virus-determined nuclear antigen tests. Two lines were derived from Swedish lymphoma cases and one from an African Burkitt-like lymphoma biopsy that was negative for Epstein-Barr virus DNA and the virus-determined nuclear antigen. All three lines apparently lacked the viral genome. Two of the three lines clearly had characteristics of B-cells (bone-marrow-derived).

Excision biopsy of the spleen was performed in 32 patients, using a recently invented instrument, which consists of a spring-trigger system for firing the two parts of a Tru-Cut needle. The biopsies were carried out under the guidance of an ultrasonic scanner. This technique yields sufficient material of high quality for a proper evaluation both of individual cells and the internal structure of the spleen. Eight patients had parenchymal abnormalities found by ultrasonic scanning: five had multiple abnormalities whereas three had a single abnormal area. Seven of these eight patients had a pathological spleen biopsy, consisting of Hodgkin's disease (four patients), "high-grade" malignant non-Hodgkin's lymphoma (two patients) or tuberculosis (one patient). In the other 24 patients with a normal ultrasonic picture of the splenic parenchyma five biopsies were pathological (3 cases of hairy-cell leukaemia, 1 of Gaucher's disease and 1 of Hodgkin's disease). Side-effects were: slight to moderate pain (16/32 patients) and bleeding requiring transfusion (4/32 patients). In one of these patients splenectomy was performed because of the bleeding. Two of the patients with bleeding complications suffered from hairy-cell leukaemia. It is concluded from this study that excision biopsy of the spleen is a diagnostic method which in some patients can replace splenectomy. The method seems to be valuable especially in patients with parenchymal abnormalities shown by ultrasonic scanning.

An unusual case of IgE-producing non-Hodgkin lymphoma (NHL) is presented. The patient's history included a 6-year period of increasing IgE level before a low grade NHL was diagnosed. The patient developed lymph node, skin, bone marrow and lung infiltrations. With a cytostatic combination therapy a temporary improvement was achieved, but the patient died from progressive disease after 2 yr. The morphological appearance of the tumour varied between that of LP immunocytoma and a centrocytic lymphoma. Immunophenotype studies showed intracytoplasmic IgE lambda in tumour cells and B-cell surface phenotype (BB-1 pos; OKT 10 pos; PCA weakly pos and SIgE lambda).

Enlarged mediastinal, retroperitoneal and pelvic lymph nodes are often difficult to differentiate from vascular structures. Contrast medium is therefore used to help to discriminate arteries and veins from lymph nodes. This study was undertaken to investigate the degree to which pathologic lymph nodes become enhanced after an intravenous bolus injection of contrast medium. Computed tomography was performed in 25 patients with enlargement of retroperitoneal lymph nodes due to primary lympho-proliferative disease or metastases. A dynamic sequence of a well delineated lymph node was obtained over a period of two minutes. Contrast enhancement was seen in all lymph nodes, but of varying degree. The enhancement was correlated to that observed in the inferior vena cava. Most examined lymph nodes showed slight or moderate enhancement, but in five instances strong enhancement, more than 75 per cent of that of the vena cava, was found. These nodes could possibly have been misinterpreted as blood vessels.

This paper presents a study on the structure and function of Kupffer cells (KC) and liver endothelial cells (LEC) isolated by a simple and rapid technique involving 1) perfusion of the liver with collagenase; 2) cell separation by means of density centrifugation in Percoll; and 3) cell culture, taking advantage of the fact that KC and LEC differ in their preferences for growth substrate. The KC, which attach and spread under serum-free conditions on surfaces of glass or plastic during the first 15 min in culture exhibit a typical macrophage-like morphology including membrane ruffling and a heterogenous content of vacuoles. Moreover, these cells express (a) Fc receptors (FcR) for binding and phagocytosis of erythrocytes covered with immune globulin G (E-IgG), and (b) complement receptors (CR) for binding and serum dependent phagocytosis of erythrocytes covered with either human C3b or mouse inactivated C3b (iC3b). The cells also bind fluid phase fluoresceinated C3b. Approximately 30% of the KC express immune response-associated (Ia)-antigens. The LEC attach and spread on fibronectin coated surfaces, but not on glass or plastic surfaces, during the first two hours in culture with or without serum, and are morphologically distinct from KC. Cultured LEC are well spread out with no membrane ruffling and with numerous large vesicles surrounding the regularly shaped nucleus. These cells bind, but do not ingest E-IgG via the FcR, but no binding of fluid phase C3b or particle fixed C3b or iC3b can be observed. Incubation of LEC with fluorescein amine conjugates of ovalbumin or formaldehyde treated serum albumin, but not with fluoresceinated native serum albumin, results in accumulation of fluorescence specifically localized in the large perinuclear vesicles. Neither KC nor any other cell types tested have the ability to accumulate fluorescence upon incubation with these compounds. Ia-antigens are not present on the LEC. Cytochemical demonstration of unspecific esterase, acid phosphatase, and peroxidase reveals different patterns and intensities of staining in KC as compared to LEC.

One hundred and thirty-three consecutive cases originally classified either as a lymphocytic lymphoma of the B-CLL type or as an immunocytic (IC) lymphoma could be reclassified morphologically and analyzed for the presence of cytoplasmic immunoglobulins (cIg) with the PAP-technique. The morphologic reclassification confirmed the initial diagnosis in most cases, whereas after staining for cIg, the diagnosis was changed in a large number of cases, i.e. from B-CLL to IC, or the reverse, or from IC of the polymorphic subtype (ICp) to 'high-grade' non-Hodgkin lymphoma (NHL). Cases classified as IC were often localized (stage I+II: 22/43) with a long disease-free survival after local radiation therapy, while B-CLL were usually generalized. For patients in stage IV, the prognosis of B-CLL was significantly superior to that of IC, which in turn was superior to the prognosis of cases referred to as 'high-grade' NHL. The difficulties in the morphologic distinction between B-CLL and IC on one hand and between ICp and some 'high-grade' NHL on the other hand, as well as the clinical significance of these distinctions, are discussed.

A series of 85 thymis biopsies and specimens from thymectomies were re-examined. Forty-five of these were taken from patients with myasthenia gravis. A relatively low frequency of thymitis (57%) was found in these patients, while the frequency of thymoma (9%) was as expected. Two cases of thymitis in thyrotoxicosis were included in the material. In all, 22 thymomas of various kinds (18% of the total material) were diagnosed. A fairly low proportion of these thymomas (18%) were from patients with myasthenia gravis.

In a retrospective analysis of 334 cases of non-Hodgkin's lymphoma observed between 1969 and 1978, 250 cases could be classified according to the Kiel classification. Clinicopathologic correlation was analysed for these latter cases. Irrespective of the morphologic appearance, all cases initially in stage I showed an excellent prognosis after radiation therapy alone, whereas the prognosis for stage II was similar to stages III and IV. For stages II-IV, 3 major prognostic groups with significantly differing survival curves were identified. The median survival times were one, 3 and more than 7 years, respectively. The pathologic and clinical significance of the Kiel classification is discussed.

Net enzyme activities of normal human blood cells were measured, and isoelectric focusing patterns of acid esterase (AcE) (EC 3.1.1.6) and acid phosphatase (AcP) (EC 3.1.3.2) were compared with corresponding data obtained for two acute T-lymphoblastic leukemia cell lines (JM, Molt-4), one acute B-lymphoblastic leukemia cell line (Ball-1), one acute non-B-non-T-lymphoblastic leukemia cell line (KM 3), and one promyelocytic leukemia cell line (HL-60). The AcE isozymes, found in the individual blood cell types, were regularly expressed by the corresponding cell lines. AcP was regularly expressed by lines HL-60 and KM 3, but lines JM, Molt-4, and Ball-1 showed additional isozymes and/or reduction of the intensity of the typical isozymes found in the presumed normal counterparts. This phenomenon resulted partly in an obscuration of the typical isozyme patterns. Our study documents the applicability of isozyme mapping to the characterization of permanent hematopoietic cell lines. The results suggest that long-term culture conditions can repress phenotypic properties and/or derepress gene activities.

A primary pancreatic tumour in a 6-year-old boy was removed by radical excision. From both light and electron microscopic observations the tumour was considered to be of exocrine origin, with some differentiation towards acinar cells. Although the tumour was highly differentiated, it was regarded as probably malignant because of tumour growth into the surrounding fibrous capsule. The case is discussed in relation to earlier rare reports of pancreatic tumours in infants and children.

This study describes the opposing effects that interleukin (IL) 4 exerts on the B cell stimulatory factor (BSF-MP6) and IL 2-dependent proliferation and differentiation of cells of one selected B-type chronic lymphocytic leukemia cell clone (I83), which depend on the nature of the activation inducer. In I83 cells activated by a 1-h pulse of 12-O-tetradecanoylphorbol 13-acetate, the BSF-MP6-dependent DNA synthesis was strongly enhanced by 50-100 U/ml of recombinant IL 4. Recombinant IL 2 stimulation was necessary only when a suboptimal dose of BSF-MP6 was used. The differentiation was also markedly enhanced by IL 4 as measured by quantitation of IgM secretion both at the population (enzyme-linked immunosorbent assay analyses of the supernatant) and single-cell level (enzyme-linked immunospot technique), by morphological examination of the maturation stage and flow cytometric analysis of differentiation-associated surface antigens (CD11c, FMC7, PCA-1 and CD38). No Ig isotype switch was found. In contrast, DNA synthesis and differentiation of I83 cells, activated by Staphylococcus aureus Cowan strain I (SAC) and co-stimulated with BSF-MP6 plus IL 2, were strongly inhibited by IL 4, both when it was added simultaneously with SAC or after 2 days of SAC exposure. Analysis of the cell-cycle progression of SAC and BSF-MP6 plus IL 2 and IL 4-stimulated cells by acridine orange staining and fluorescence-activated cell sorter (FACS) analysis demonstrated an arrest of a minor cell population in G0 and a block of the transition of G1 cells to S phase. Neither the enhancing nor the inhibitory effect of IL 4 on the proliferation and differentiation of I83 cells was an indirect effect via IL 4-induced activation of contaminating T cells, monocytes or natural killer cells, as shown by experiments where these cell types were depleted by FACS sorting. Furthermore the expression of CD23 and CD25 was not inhibited by IL 4. The results thus demonstrate contrasting biological effects of IL 4 on clonal leukemic B cells depending on the nature of the activation and progression stimuli. This adds to the emerging picture of a very complex cytokine and cell-to-cell contact-mediated regulation of the activation and subsequent growth and/or differentiation of human B cells.

The prognostic relevance of 4 different serum markers (deoxythymidine kinase = S-TK, lactic dehydrogenase = S-LDH, S-Haptoglobin and S-Orosomucoid) in relation to histopathology according to the Kiel classification, stage and presence or absence of initial symptoms were investigated in 168 consecutive cases of low-grade non-Hodgkin lymphomas (NHL). All serum markers, as well as the other three parameters, gave prognostic information. Univariate analysis yielded a high predictive value (p less than 0.0002) for both S-TK and S-LDH. The best information regarding the probability of survival was, however, obtained from the presence or absence of symptoms from lymphoma manifestations other than those caused by a strictly local tumor mass. Since S-TK and S-LDH correlated well with each other, only the better of them, S-TK, gave information additional to initial symptoms in a multivariate test.

A human hematopoietic cell line (U-937) with exceptional characteristics was derived from a patient with generalized histiocytic lymphoma. The morphology of the cell line was identical to that of the tumor cells in the pleural effusion from which the line was derived. Since Epstein-Barr virus (EBV) carrying diploid lymphoblastoid cell lines unrelated to the tumor population often become established in vitro from non-Burkitt lymphoma explants, several parameters were studied to discriminate the U-937 from such lines: morphology in vitro, growth characteristics, cytochemistry, surface receptor pattern, Ig production, lysozyme production, beta2-microglobulin production, presence of EBV genome and karyotype. In all these respects U-937 differed from prototype lymphoblastoid cell lines. The histiocytic origin of the cell line was shown by its capacity for lysozyme production and the strong esterase activity (naphtol AS-D acetate esterase inhibited by NaF) of the cells. It is therefore concluded that the U-937 is a neoplastic, histiocytic cell line.

The Leukaemia Group of Middle Sweden recently started a new multicentre study of treatment of adult patients with acute leukaemia from 6 centres. The criteria for the diagnosis, subclassification, degree of leukaemic bone marrow infiltration, remission and relapse are to be used by the morphologists of 6 different pathology departments. The reproducibility of the criteria has been studied by 3 of the morphologists concerned, in a retrospective review of a strictly consecutive series of 79 adult patients treated at Södersjukhuset, Stockholm, Sweden, in the years 1978 to 1981. The results show that the reproducibility of the criteria and the concordance of the morphologists when using them increased when the criteria were made more detailed and precise.

Cytologic material was reviewed from 23 mediastinal tumors clinically suspected as thymomas. The thymomas had a characteristic biphasic cell pattern in material obtained by fine needle aspiration biopsy that was easy to recognize and possible to differentiate from carcinoid tumors, malignant lymphomas and oat-cell carcinomas.

An established cell line derived from a human malignant mediastinal teratoma is described. The cell line was composed of slightly atypical fibroblast cells with a population-doubling time of 24 h at the exponential growth phase. The reason why the emerging cell line became fibroblastic although other tissues were present in the original tumor may be that fibroblasts so readily grow in culture. Chromosome banding showed a hypertriploid stemline number, S = 78. Almost all of the analysed karyotypes had seven markers in common. Eleven other markers, occurring at low frequency, were also detected. The origin of all markers except one could be deduced.

U-937 represents a well established permanent human hematopoietic cell line. Electron microscopical and enzyme cytochemical studies as well as the analysis of surface glycoproteins have provided ample evidence for the monocytic origin of U-937. Upon stimulation with the tumour promotor 12-O-tetradecanoylphorbol-13-acetate (TPA), U-937 cells evolve into macrophage-like cells with phagocytic capacities. Since human blood monocytes (BM) are characterized by five acid esterase (AcE; EC 3.1.1.6) isoenzymes which are cell-specific in terms of isoelectric points (pI) and antigenicity, attempts were made in the present study to identify identical isoenzyme patterns in non- and TPA-stimulated U-937 cells. BM, cultured BM, non- and TPA-stimulated U-937 cells, as well as samples of resident human peritoneal macrophages (PM) as clearly-defined functional derivatives of BM, were subjected to isoenzyme analysis using isoelectric focusing (IEF). The five monocyte specific isoenzymes of AcE were identified in both populations of U-937. TPA-stimulated samples showed two additional bands, identical to those appearing in cultured BM after 4 days of glass-adherence and characteristic of resident human PM. Antisera raised against AcE of BM immunoprecipitated the two additional isoenzymes of TPA-stimulated U-937. It is concluded (1) the isoenzyme mapping of AcE documents the monocytic origin of U-937. (2) TPA-stimulation caricatures transformation of BM into resident tissue macrophages as far as pure morphology and AcE isoenzyme patterns are concerned. Thus, AcE isoenzyme mapping is apt for establishing reproducible and standardized criteria of different activation/differentiation states within the monocyte-macrophage lineage.

We have previously shown that non-proliferating human T- but not B-lymphocytes contain demonstrable amounts of acid alpha-naphthyl acetate esterase (ANAE). The usefulness of this histochemical marker for the diagnosis and classification of malignant lymphoid tumors was investigated by use of a panel of established normal and malignant human haematopoietic cell lines and fresh biopsy cells from malignant lymphomas and myelomas. The results showed that not only the T-cell derived acute leukaemia lines, but also histiocytic lymphoma and myeloma lines and some of the lymphoma (Burkitt and lymphocytic) and non-neoplastic lymphoblastoid cell lines with B-cell surface markers expressed strong ANAE reactivity. Some but not all of the immunoglobulin producing myeloma and lymphocytic lymphoma biopsies were ANAE-positive. Inhibition experiments with sodium fluoride and E-600 demonstrated that although the T-lymphocyte specific esterase is predominantly of 'A'-type, the malignant lines contain also non-specific 'B' esterase and pseudocholinesterase. As the presence of the various esterases did not demonstrate any specific distribution pattern among he haematopoietic cell lines of different origin, we concluded that the ANAE marker is no longer T-specific when malignant lymphoid cells are considered, and that the usefulness of this marker in routine diagnostic work therefore is limited.

Staging laparotomy was performed in 36 patients with Hodgkin's disease. The surgical procedure changed the stage in 14 cases or 36% and also revealed subdiaphragmatic disease in 14 patients. Mixed cellularity and nodular sclerosis were the main histopathological types, contributing 44% and 42%, respectively, of the whole material. Postoperative complications occurred in 8 cases (22%)--none was fatal. The average hospital stay was 9.5 days, the longest being 22 days.

Normal and rheumatoid synovial cells have been analyzed in frozen sections and in suspension. HLA-DR-expressing, macrophage-like cells are demonstrated in normal synovial intima and in rheumatoid tissue. Suspended normal synoviocytes equaled peripheral blood non-T lymphocytes as stimulators of mixed lymphocyte reactions, whereas adherent rheumatoid synovial cells were extremely efficient as such stimulators and in presenting soluble antigens to autologous T lymphocytes. This HLA-DR-dependent T lymphocyte regulation might provide a cellular basis for the HLA-D haplotype-arthritis associations.

A series of 22 consecutive cases of thymic tumour was collected and the tumours were reclassified according to a modified classification scheme. Two-thirds of them were benign lympho-epitheliomas, though in one case pleural implants were noted. One-third of the tumours were clearly malignant (carcinomas, lymphomas and seminomas). In one of the seminomas and in a case of Hodgkin's disease of the thymus no signs of recurrence or metastases have been observed in 10 and 8 years respectively. The sex distribution was fairly equal except that all three seminomas were detected in young men. The malignant tumours usually gave rise to symptoms, while the benign ones did not. Four of the lympho-epitheliomas were associated with myasthenia gravis. No other associated syndrome was observed. The possibility that lympho-epitheliomas may be malignant is discussed.

In a retrospective survey of 334 cases of non-Hodgkin lymphoma (NHL), 250 cases could be classified according to both Rappaport's classification and the Kiel classification. All patients initially in stage I had an excellent prognosis irrespective of histology, whereas patients in stages II, III and IV had a worse prognosis that did not significantly differ between stages. Rappaport's classification could separate stages II-IV into 2 different prognostic groups, one favourable and one unfavourable group. According to the Kiel classification, 3 prognostic groups - favourable, intermediate and unfavourable - were found. The survival rate for favourable Rappaport fell in between favourable-Kiel and intermediate-Kiel. Both subgroups within favourable-Rappaport (nodular lymphomas and diffuse well differentiated lymphomas) could actually be subdivided by the Kiel classification into one group with a more truly favourable behaviour and one with an intermediate behaviour. The extent of follicularity among nodular lymphomas and the presence of plasmacytoid differentiation among the small lymphocytic lymphomas were found to be of prognostic importance. In conclusion, we found that the Kiel classification separated the more indolent lymphomas better than Rappaport's classification. No preference was found concerning the high grade lymphomas.

A case of scleroderma with manifestations in the oesophagus and both lungs and a concomitant thymic lympho-epithelioma is presented. This case represents a further documentation of the well-established association between thymoma and collagen disorders.

Cultured cell lines derived from malignant Epstein-Barr virus (EBV)-negative B cells, and representative of the more common types of naturally occurring non-Hodgkin lymphomas and related leukemias, were found to be sensitive to lysis by human natural killer (NK) cells. The observed lysis of such cell lines was mediated by a population of interferon-augmentable, FcR-positive, non-adherent lymphoid cells, which were also able to kill the "standard" NK targets K562 and Molt-4. When the NK susceptibility of the neoplastic, EBV-negative B cells was compared to that of diploid, EBV-carrying, non-neoplastic B lymphoblastoid cell lines (BLCLs) and of the "standard" NK target K562, several distinct patterns were observed. The killing of the neoplastic B cell lines was significantly less than that of K562, but significantly greater than that of the EBV-derived BLCLs of non-neoplastic origin. An additional finding was a similar NK susceptibility profile for the neoplastic, true histiocytic cell line U-937 (i.e., K562 greater than U937 greater than BLCLs). Furthermore, all cell lines, with the exception of the BLCLs, could effectively compete for the observed killing in cold target inhibition assays. The implications of these findings are discussed in relation to both neoplastic and non-neoplastic targets of NK lysis.

Immunohistochemical double-staining was performed on frozen sections from synovial biopsies obtained at arthroscopy from 22 patients with different kinds of synovitis. Not only in specimens from patients with rheumatoid arthritis and seronegative chronic polyarthritis, but also in those from patients with synovitis due to psoriasis, trauma, or crystals, were seen many alpha Leu-1-positive T lymphocytes--in most cases predominantly of the alpha Leu-3a-positive T "helper" cell type--in close contact with HLA-DR-positive macrophages/dendritic cells. Presence of many HLA-DR-positive, often OKM1-negative, and irregular sublining cells characterized all forms of chronic arthritis.