Th. Radaszkiewicz

LONG-TERM INTERFERON THERAPY FOR THROMBOCYTOSIS IN MYELOPROLIFERATIVE DISEASES

31 patients with thrombocytosis associated with myeloproliferative disorders were included in a prospective trial of long-term interferon therapy. 6 patients (19%) had side-effects which required withdrawal of interferon within one year. 22 patients (71%) achieved and maintained a complete response (platelet count less than 440 x 10(9)/l) for at least twelve months, with reduction or abolition of symptoms associated with thrombocytosis and a significant fall in bone-marrow megakaryocytes. At twelve months, 25 patients were randomly allocated to maintenance or withdrawal of interferon. Thrombocytosis recurred rapidly when treatment was stopped, but a second remission could be achieved by resumption of interferon therapy.

Involvement of the central nervous system in malignant lymphomas.

A retrospective histologic study of 145 consecutive autopsy cases of systemic malignant lymphomas (including lymphatic leukemias) was performed. The classification followed the Kiel Classification (Gérard-Marchant et al., 1974). There was an overall secondary CNS involvement in 26.2% of the total or in 30.4% of the non-Hodgkins lymphomas including ALL, with intracranial lesions in 21.4 and 26.1%, respectively, and spinal epidural spread in 5.5 (5.1)%. Peripheral nerve involvement was seen in almost 40% of the examined cases. Ten further cases were isolated (“primary”) intracranial lymphomas without evidence of extraneural deposits or systemic lymphatic disease. The CNS complications in non-Hodgkins lymphomas were diffuse meningeal and/or perivascular infiltration with or without invasion of the nervous parenchyma, and did not differ from those in CNS leukemia. Isolated solid mass lesions in the brain were only present in 7% of the secondary CNS lymphomas, but were seen in all instances of “primary” cerebral lymphomas. The incidence of CNS complications was highest in lymphoblastic lymphomas including ALL (39%), CLL (31%), immunocytic lymphoma (29%), less frequent in immunoblastic (18.7%), and centrocytic lymphomas (16.6%). No intracranial lesion was observed in centroblastic-centrocytic and centroblastic lymphomas which only produced epidural spread. Bone marrow involvement was present in 92.8% of the cases with secondary CNS lesions, and in 83.2% of the epidural lymphomas. Leukemic conversion, present in 44% of the total (52% with ALL), was demonstrated in 83.3% of the cases with secondary brain lesions, but was hardly combined with epidural spread. The histologic pattern of CNS lesions in non-Hodgkins lymphomas and their frequent association with leukemic conversion suggest the importance of hematogenous dissemination rather than of direct spread from bone marrow or local manifestation in multisystem disease. Isolated (“primary”) lymphomas of the CNS which are morphologically identical with the extraneural lymphomas may represent a primary, often lethal manifestation of a multisystem disease with or without secondary generalization.

Recombinant gamma interferon and in vivo induction of HLA-DR antigens

Recombinant human IFN‐γ, used for treatment of melanoma and renal carcinoma, was found to induce HLA‐DR expression on human keratinocytes in vivo. HLA‐DR antigens bound to keratinocytes of the basal and suprabasal layers of the epidermis were observed after intramuscular or intravenous injections of 0.5 mg/kg body weight IFN‐y, 3 times a week. Keratinocyte‐bound HLA‐DR antigens were ftrst observed at the beginning of the third or fourth week of treatment, but HLA‐DQ and HLA‐DP antigens were never detected on keratinocytes. The intracytoplasmic constant (lO chain of the class II molecules was also not detectable within the keratinocytes. Paticnts who received IFN‐α2 therapy, did not exhibit keratinocyte‐bound HLA‐DR antigens.

Primary high-grade malignant lymphomas of bone

Five cases of primary high-grade malignant lymphoma of bone are presented. The tumours occurred at a single site in all the cases and produced osteopathic lesions. Histologically, they were large cell tumours characterized by round to irregularly shaped nuclei with finely distributed heterochromatin and small to medium-sized nucleoli. The cytoplasm was moderate and slightly to moderately basophilic. In one case, giant cells similar to Hodgkin and Sternberg-Reed cells occured. The tumour cells bore B-cell markers but did not express immunoglobulin. Three of the bone tumours were polymorphic centroblastic lymphomas. The remaining two cases were also high-grade malignant B-cell lymphomas which may also be derived from germinal center cells but this could not be further substantiated.

Immunohistologic detection of immunoglobulins in malignant lymphomas and its value in histopathologic diagnosis

Formalin fixed, paraffin embedded material of malignant Non-Hodgkin lymphomas (132 cases), Hodgkin lymphomas (59 cases), angioimmunoblastic lymphadenopathy (2), lymphoepithelioid cell lymphoma (1) and lymph nodes with nonspecific lymphadenitis (8) were studied by a modified immunofluorescence technique for the presence and distribution of immunoglobulins (IgM, IgG, IgA, K,λ). Cells of lymphoblastic lymphomas of the convoluted type and of chronic lymphocytic leukemias were always Ig-negative. In immunocytic lymphomas tumor cells with morphologic features of plasma cells and plasma cell precursors always exhibited cytoplasmic Ig-staining showing monoclonality in two thirds of the cases (IgM/K, IgM/λ, IgG/K, IgM/IgG/K). In extramedullary plasmacytomas all cells displayed a bright cytoplasmic Ig-staining. In centrocytic lymphomas and in centroblastic-centrocytic lymphomas a honeycomb-like pattern of Ig-staining could be observed. Some centroblasts in centroblastic-centrocytic lymphomas and in centroblastic lymphomas showed a granular (surface) staining in addition. Some lymphoblastic lymphomas of the Burkitt type and some of the morphologically “unclassifiable” lymphoblastic lymphomas exhibited cytoplasmic fluorescence indicative of B-cell origin. In immunoblastic lymphomas almost 50% of the tumors investigated contained Ig-containing tumor cells again favouring their B-cell derivation. In cases of Hodgkins disease some Hodgkin- and Reed-Sternberg-cells were positive for IgG/K. In angioimmunoblastic lymphadenopathy Ig-positive intercellular deposits were observed in addition to Ig-positive basement membranes of vessels, plasma cells and plasma cell precursors. All immunoglobulin classes could be detected in this localization though not in single cells. In lymphoepithelioid cell lymphoma (Lennerts lymphoma) only plasma cells and plasma cell precursors gave a positive staining and all immunoglobulin classes were present. In all lymphomas Ig-positive plasma cells and plasma cell precursors were found irrespective of the immunoglobulin content of the tumor cells and may, therefore, be interpreted as being reactive. On the basis of our studies it can be stated that immunomorphologic investigation of conventional biopsy material aids in characterization of Ig-producing lymphomas, and, hence, supplements the classical staining procedures.

Die histomorphologie des Abstoßungsphänomens nach Transplantation der Lunge am Hund

Left homologous lung transplantation was performed in ten dogs. No postoperative immunosuppressive treatment was given. Biopsies were taken daily after transplantation to follow the morphologic changes during rejection. About the fourth day after transplantation, striking morphologic changes were seen in the pneumocytes and differences in the intensity of the reaction were visible between peripheral and central pulmonary regions.

Cortisonresistente Panuveitis — entlarvt als Retinales Lymphom

ZusammenfassungDie früher als Retikulumzellsarkome bezeichneten, hochmalignen Non-Hodgkin Lymphome befallen in ihrer okulozerebralen Form Auge und Zentralnervensystem älterer Patienten. Immunoblastische Lymphome sind selten, meist sind beide Augen, wenn auch in unterschiedlichem Zeitabstand und Ausmaß betroffen. Der okuläre Befall geht der Generalisierung der Erkrankung in Form der ZNS-Beteiligung um Monate bis Jahre voraus. Wir berichten über einen 62jährigen Patienten, der von Sept. 88 bis Sept. 89 bei unauffälligem internen Status eine langsam progrediente Panuveitis des rechten Auges entwickelte. Über Monate bildeten sich disseminierte Pigmentepithelabhebungen, zunehmende Glaskörpertrübungen, ein solides Pseudohypopyon mit schlammartiger Ansammlung von Tumorzellen in der Vorderkammer und ein Sekundärglaukom. Im Nov. 89 kam es zu einer massiven Papillenschwellung links, die Durchführung einer diagnostischen Vitrektomie wurde jedoch vom Patienten zu wiederholten Malen abgelehnt. Die immunhistochemische Aufarbeitung des enukleierten rechten Bulbus ergab ein hochmalignes, polymorphes, zentroblastisches Lymphom mit vielen Immunoblasten. Der Patient unterzog sich einer Radiatio des Neurocraniums und des Spinalkanales, eine intrathekale und intravenöse Chemotherapie wurde durchgeführt. Innerhalb der Nachbeobachtungszeit von über 2 Jahren traten keinerlei okuläre oder zerebrale Lymphom-Rezidive auf, am linken Auge konnte bei klar gebliebener Linse der volle Visus erhalten werden.SummaryA rare form of malignant large-cell non-Hodgkin’s lymphoma or reticulum cell sarkoma is confined to the eye and central nervous system (CNS). We report a 62-year old man, who presented with recalcitrant progressive uveitis in his right eye. Although lymphoma was suspected, the patient refused to undergo vitrectomy. Over one year he developed large blister-like solid scattered lesions of the retinal pigment epithelium (RPE) in the same eye. Repetitive Neuroimaging could not detect any CNS involvement. After developing optic disc-swelling and discrete RPE-changes in the left eye also, the patient underwent enucleation of his right eye. Histopathology and Immunohistochemistry revealed malignant intraocular large cell lymphoma, invading the whole eye. Liquor cytology showed lymphomatous cells. Suffering from high grade malignant lymphoma with CNS involvement, the patient had to undergo radiation therapy of the orbits and neuroachsis as well as intravenous and intrathecal chemotherapy. Papilledema of the left eye resolved quickly and completely, RPE-infiltrations disappeared and led to discrete punched out lesions with no scarring, the lens remained transparent over the whole observation period of 25 months. The patient is surviving for more than 52 months after first suspicion of malignant lymphoma, he has retained full visual acuity in his left eye until now.

Inkompletter, kombinierter, familiärer Immundefekt mit generalisierter Impftuberkulose durch Bacille Calmette Guérin

A case of hereditary incomplete, combined immunodeficiency is reported. The patient, a 20-week-old boy, suffered from severe, generalized tuberculosis after BCG-vaccination. A conspicuous discrepancy was found between the normal number of lymphocytes in the peripheral blood and the severe morphological changes in the organs of the lymphoreticular system (deficient development of thymic structures; absence of lymphocytes in the thymus and the thymus-dependent areas of the periphery as well as in the bursa-dependent structures). A partial primary defect of the stem cells and a secondary insufficiency of the functions with incomplete differentiation due to an insufficiency of the primary lymphatic organs are discussed as possible causative factors. The inability to develop epitheloid cells in connection with the tuberculous infection is interpreted in part as a sequence of a T-cell insufficiency. Bericht über einen Fall von familiärem, inkomplettem, kombiniertem Immundefekt bei einem im Alter von 20 Wochen an einer generalisierten BCG-Tuberkulose verstorbenen Knaben. Dabei fällt eine Diskrepanz zwischen den zunächst normalen peripheren Lymphocytenzahlen und den schweren morphologischen Veränderungen an den lymphoretikulären Organen bei der Obduktion auf (Störung der thymalen Strukturbildung, Fehlen von Lymphocyten im Thymus und in thymusabhängigen Arealen, aber auch in Bursa-Äquivalent-Strukturen). Als mögliche Ursachen des Defektes werden eine partielle primäre Schädigung der Stammzellen und eine sekundäre Störung der Funktionen mit mangelhafter Differenzierung durch die Insuffizienz der primären lymphoiden Organe diskutiert. Das Ausbleiben der Bildung von Epitheloidzellen im Rahmen der tuberkulösen Infektion wird als teilweise Folge einer T-Zell-Insuffizienz gedeutet.

[Bronchospirometric results after single lung homotransplantation in dogs with experimentally induced pulmonary emphysema (author's transl)].

Pulmonary emphysema was induced in 8 bastard dogs by intratracheal instillation of Papain. Development of emphysema was documented by pulmonary function tests. The emphysematous animals underwent single lung homotransplantation. Postoperative bronchospirometric measurements revealed that up to the 6th week after transplantation there is no evidence of serious ventilation perfusion inbalance.

Veränderungen der Lungenfunktion bei experimentell erzeugtem Emphysem vor und nach einseitiger Lungenhomotransplantation am Hund

Bei den bisher durchgefuhrten einseitigen Lungentransplantationen an Patienten mit schwerem Lungenemphysem war es mit einer Ausnahme sehr bald nach der Operation zu einer letalen respiratorischen Insuffizienz gekommen (6, 7). Als Ursache fur dieses respiratorische Versagen werden 2 Mechanismen angenommen: eine schwere Ventilations-Perfusionsstorung, die dadurch entsteht, das das Transplantat eine geringere Gefasresistance hat, als die verbleibende Emphysemlunge und deshalb den grosten Teil des Blutvolumens aufnimmt; die Emphysemlunge ist wegen ihres hohen Gefaswiderstandes schlechter durchblutet und wegen ihrer hohen statischen Compliance und ihres hohen exspiratorischen Atemwegswiderstandes stark geblaht; sie verdrangt das Transplantat auf dessen Seite. Diese Verdrangung fuhrt durch Kompression zu einer Verschlechterung der Ventilation im Transplantat. Aus der dadurch entstehenden Ventilations-Perfusionsstorung resultiert eine immer starker werdende venose Beimischung.