Zusammenfassung Die große Variabilität der klinisch-hämatologischen sowie histologischen Befunde bei Diagnose der chronischen myeloproliferativen Erkrankungen (CMPE) spiegelt sich auch in den signifikant unterschiedlichen Überlebenszeiten der einzelnen Subtypen wider. Der Stellenwert der Knochenmarkhistologie ist im Rahmen prognostischer Untersuchungen teilweise immer noch umstritten, so daß insbesondere bei der CML schwerpunktmäßig nur klinische Parameter zur Risikoabschätzung herangezogen werden. Im Rahmen einer retrospektiven Analyse an insgesamt 1023 Patienten mit CMPE haben wir deshalb versucht, die Wertigkeit der Knochenmarkmorphologie in dieser Hinsicht abzuklären. Weiterhin wurden relative Überlebensraten und ein krankheitsspezifisches Lebenserwartungsdefizit berechnet, welche das alters- und geschlechtsspezifische Sterberisiko insbesondere der alten Patienten berücksichtigen. Die CML zeigte mit einer durchschnittlichen Lebenserwartung von unter 5 Jahren die schlechteste Prognose, wobei Patienten unter Interferon-Therapie signifikant längere Überlebenszeiten erkennen ließen. Demgegenüber fand sich bei der ET keine signifikante Verkürzung der natürlichen Lebenserwartung. Eine bereits geringe Vermehrung der Faserdichte im Knochenmark sowie eine reduzierte Erythropoese waren bei der CML die wesentlichen prognostischen Einflußgrößen. Zusätzlich deuteten Pseudo-Gaucher-Zellen bei Patienten unter Chemotherapie auf einen günstigeren Verlauf hin. Als weiterer hämatologischer Parameter hatte auf der anderen Seite die Anzahl peripherer Myelo- und Erythroblasten einen negativen Einfluß auf die Prognose. Bei der IMF konnten anhand eines vereinfachten multivariaten Prognosemodells drei Risikogruppen abgegrenzt werden, welche signifikant unterschiedliche Überlebenszeiten aufwiesen. Die Histologie des Knochenmarkes übte keinen entscheidenden Einfluß aus, auch wenn Patienten mit initialen (präfibrotischen) Stadien der Erkrankung einen leichten Überlebensvorteil zeigten. Alter bei Diagnose, Grad der Anämie, Thrombozytopenie, Leukozytose sowie ein leuko-erythroblastisches Blutbild waren hier die bedeutenden Variablen. Unsere Ergebnisse untermauern den Stellenwert der Knochenmarkmorphologie bei den CMPE, wobei sich signifikante Beziehungen zur Lebenserwartung der betroffenen Patienten ableiten lassen. Insbesondere bei der CML stellen die Verfaserung und die Reduktion der Erythropoese bei Diagnose unabhängige Prognoseparameter dar, welche bessere Erkenntnisse über den Verlauf erlauben.

An immunohistochemical and morphometric study was performed on bone marrow biopsies in 604 patients with chronic myelogenous leukemia (CML) to compare morphological and clinical features and to evaluate effects of interferon (IFN) and chemotherapy. Following morphometry significant correlations were calculated between number of CD61(+) megakaryocytes, including their precursors with fiber density. This finding is in line with the close functional relationship between megakaryopoiesis and fibroblasts regarding the complex pathomechanism of myelofibrosis. The latter was observed in about 28% of patients already at diagnosis. In a similar way, the frequency of CD68(+) macrophages was correlated with the amount of Ret40f(+) nucleated erythroid precursors, implicating an involvement of this cell lineage in iron turnover, hemoglobin synthesis, and degradation of the expelled nuclei from normoblasts. The (alpha-D-galactosyl residue-expressing) Pseudo-Gaucher cells were detectable in 30% of pretreatment specimens. Moreover, significant associations were calculable between reduction in erythropoiesis or increase in fibers with clinical features such as hemoglobin level, percentages of myelo- and erythroblasts in the peripheral blood, and spleen size. These variables are in keeping with more advanced stages of CML. Based on our morphometric evaluations, a classification into three different histological subgroups: granulocytic, megakaryocytic, and myelofibrotic was carried out. This simplified staging system was correlated with corresponding sets of hematological data. Sequential biopsies in 173 patients with monotherapy by IFN, hydroxyurea (HU), or busulfan (BU) revealed a fibrogenic effect of IFN in contrast to a fiber-reducing property of HU. The dynamics of myelofibrosis and changes of major cell lineages during treatment were readily demonstrable by calculating corresponding indices. These included the ratios between quantitative differences of corresponding variables at repeated examinations and time. Thus, in patients with complete hematological remission following IFN administration, regeneration of erythropoiesis was found to be accompanied by an increase in the total number of CD68(+) macrophages, including activated subpopulations. Histological subgroups showed a transition from a (nonfibrotic) granulocytic and megakaryocyte pattern to the myelofibrotic subtype in about 40% of patients. This change was opposed to a numerical reduction in the myelofibrotic subtype which occurred in 17 patients (36%), but predominantly in those under HU therapy. In conclusion, the striking heterogeneity of bone marrow features in CML warrants a careful morphological evaluation of trephine biopsies and appropriate means of processing to achieve relevant correlations with clinical data and, thus, allows a more elaborate insight into the dynamics of the disease process.

The term 'second opinion' in Germany refers to the response, by a second and independent physician, to a patient's request that their existing diagnostic and/or therapeutic situation be reevaluated. There is neither an obligatory definition of this term nor a legal basis or a basis of profession-policy. In the USA the term 'second opinion' has been established in a somewhat different form. There, it usually refers to a second opinion commissioned by medical insurance companies, most commonly before surgical. The tendency to request a second opinion seems to be increasing in Germany as well. The main motives for asking a second opinion are insecurity in difficult moments (especially in palliative therapeutic situations), as well as the wish to learn more about alternative forms of treatment. Here we report on practical experiences, characteristics of second opinions in surgery and radiooncology, reimbursements, and certain conflicts a second opinion may cause.

Polyneuropathy in Tangier disease can be divided into three clinical types. The most severe form (type III) with a syringomyelia-like syndrome has been described in three cases only. Here, a fourth case of this type is presented. Because of unusual trophic disturbances even leprosy was suspected. Electrodiagnostic findings, including evoked cerebral potentials in this case, were suggestive of a generalized neuropathy with some degree of primary or secondary demyelination and implied possible impairment of central structures. Sural nerve biopsy, including electron microscopy and quantitative analysis, revealed a predominant reduction of smaller myelinated and unmyelinated fibres. The main morphological feature was the abundance of abnormal non-membrane-bound vacuoles in Schwann cells, mostly of the unmyelinated type, and in some endoneurial fibroblasts, macrophages and perineurial cells. There was no inverse relationship between lipid vacuoles and axons in Schwann cell complexes as suspected by others. An excess of endoneurial collagen as well as an increased fascicular area were obvious. In five skin biopsy specimens of different regions typical vacuoles were noted in Schwann cells, histiocytes, nevus cells, and rarely in perineurial cells.

In a retrospective study of 111 patients with aplastic anaemia iliac crest biopsies were evaluated for the presence of morphological features statistically related to the evolution of the disease. Prognostic variables for a transition to acute non-lymphatic leukaemia were: cellular atypias of the three haemopoietic lineages, as observed in the myelodysplastic syndrome, and especially "micromegakaryocytes"; high numbers or irregular distribution of megakaryocytes, or both; and (slight) marrow fibrosis. Clinical variables did not influence these prognostic correlations. Prognosis in relation to death from bone marrow failure without leukaemia might well have been influenced by a strong plasma cell reaction, but this correlation was weakened by clinical factors. On the basis of this study aplastic anaemia can thus be subdivided morphologically into two disease entities--namely, hypocellular myelodysplastic syndrome with a 23-82% risk of acute non-lymphatic leukaemia developing within three years, depending on how many variables associated with acute non-lymphatic leukaemia are present, and non-dysplastic myelohypoplasia.

Polyneuropathy in Tangier disease can be divided into three clinical types. The most severe form (type III) with a syringomyelia-like syndrome has been described in three cases only. Here, a fourth case of this type is presented. Because of unusual trophic disturbances even leprosy was suspected. Electrodiagnostic findings, including evoked cerebral potentials in this case, were suggestive of a generalized neuropathy with some degree of primary or secondary demyelination and implied possible impairment of central structures. Sural nerve biopsy, including electron microscopy and quantitative analysis, revealed a predominant reduction of smaller myelinated and unmyelinated fibres. The main morphological feature was the abundance of abnormal non-membrane-bound vacuoles in Schwann cells, mostly of the unmyelinated type, and in some endoneurial fibroblasts, macrophages and perineurial cells. There was no inverse relationship between lipid vacuoles and axons in Schwann cell complexes as supected by others. An excess of endoneurial collagen as well as an increased fascicular area were obvious. In five skin biopsy specimens of different regions typical vacuoles were noted in Schwann cells, histiocytes, nevus cells, and rarely in perineurial cells.

About 50% of the circulating platelets can be taken from healthy donors by means of the cell separation technique. In order to investigate the effect of cell separation on thrombopoesis bone marrow samples were taken from 12 voluntary donors up to 5 times. The megacaryocytes were analyzed before and after cell separation by morphometric measures and determinations of platelet count and platelet function (adhesion, aggregation, spreading, retraction) were carried out. Removing of large amounts of platelets form the circulation by stimulation of thrombopoesis resulted in an increase of the peripherical platelet count already 48 h after cell separation. Of the platelet functions tested only aggregation induced by collagen was found to be increased after cell separation as compared to that before the procedure.

After a single pulse dose of DMBA, rats develop bone-marrow hypoplasia, which is almost compensated for by regeneration after 16 weeks. Subsequently, dysplastic signs of hemopoiesis appear in all experimental animals as massive extrusion of normoblasts into the peripheral blood, red-cell anisoand poikilocytosis, nuclear deformities, atypical mitoses, and PAS-positivity, as well as megaloblastoid maturation dissociation of erythroblasts and nuclear and granulation anomalies of neutrophilic granulocytes and monocytes, comparable to human “pseudo-Pelger cells” and “paraneutrophils”. At the time of death (112-497 days after DMBA pulse) experimental animals showed hyperplastic bone marrow with increased granulopoietic/erythropoietic ratios and an augmented, mainly erythropoietic, hemopoiesis in the spleen, with splenomegaly in six rats. Splenic hemopoiesis is accompanied by white pulp atrophia. The cause of death was septicopyemia in three rats, anemia in three, and bleeding in one rat. None of the animals developed a leukemic blast phase. Myelodysplastic changes in this experiment are the same as have been shown to precede leukemia in rats treated with five DMBA pulses (Fohlmeister et al. 1981). Possible relations of myelodysplasia and leukemia are discussed.

Seven patients are presented with a chronic lymphoproliferative disorder characterized clinically by splenomegaly, no or discrete lymphnode enlargement, and a varying degree of cytopenia. In blood and bone-marrow smears lymphoid cells of "hairy" appearance are demonstrable which may contain tartrate-resistant acid phosphatase. The finding of a nodular bone-marrow infiltration without fibrosis as well as that of a nodular infiltration of the spleen originating in the white pulp are incompatible with the diagnosis hairy-cell leukemia and place the disease near to chronic lymphocytic leukemia (CLL) or leukemic immunocytoma respectively. A detailed cytologic and cytochemical examination of the infiltrating cells shows deviations from the typical enzymatic pattern of hairy cells and from known enzymatic constellations in CLL and related lymphoproliferative disorders. Thus, we are dealing with an intermediate form, difficult to classify, the separation of which nevertheless seems to be important for therapeutical reasons.

A technique is described to obtain shockfrozen tissue specimens from a beating heart in situ using liquid propane as cooling agent. The method allows to take up to 8 samples from the ischemic area of the left ventricle of a pig heart following acute coronary artery occlusion.

Introduction. Since Block et al., 1953 introduced the term “preleukemia” for certain states of hemopoietic insufficiency preceding acute leukemia, discussion about the nature of this disease has never ceased. Systematic research on this question should be based on a better understanding of the process of leukemogenesis, for which studies in an animal model could be useful. So far, observations have rarely been made during the phase preceding clinical manifestation of induced leukemia, and hematological changes comparable to human “preleukemia” have not been reported. The development of such changes during the induction phase of acute leukemia is described in this paper.

Histochemischer Nachweis hormonseusibler Mammakarzinome mittels markierter LektineAls Erg/inzung zur Hormonrezeptoranalyse im Mammakarzinom ist unbedingt ein Verfahren erforderlich, das zur Beurteilung der Hormonabhfingigkeit auch solcher Tumoren herangezogen werden kann, bei denen aus technischen Grfinden (z.B. zu wenig Gewebe) eine Hormonrezeptorbestimmung nicht m6glich ist.Histochemisch wurden mit dem FITC-markierten Lektin der ErdnuB (peanut agglutinin, PNA) bzw.der Weinbergschnecke (Helix pomatia, HP), die eine hohe Affinit~t zu dem Disaccharid fl-D-Gal(1-3)GalNAc bzw.dem Monosaccharid GalNAc aufweisen, eine Gruppe von Glykoproteinen erfaBt, die am Ende einer durch Hormone induzierten Funktionskette liegen.F/Jr die Beurteilung der Hormonabh~ingigkeit wurde das Vorkommen von freien und sialins/iuresubstituierten Lektinrezeptoren beriicksichtigt.Der Vergleich mit dem Vorkommen von Steroidhormonrezeptoren zeigte bei 46 Karzinomen, dab sich beim Vorliegen von mehreren Hormonrezeptoren in 68% beim alleinigen Nachweis des Ostrogenrezeptors