Klinische Charakterisierung der essentiellen Thrombozythämie im Vergleich zu anderen myeloproliferativen Erkrankungen und reaktiven Thrombozytosen

Summary 60 patients with essential thrombocythemia (ET) have been retrospectively and prospectively followed from 1974 through 1987. The presenting signs and symptoms and the course of the disease were analyzed and compared to 10 patients with persisting reactive thrombocytosis selected from 6000 patients with reactive thrombocytosis and to 50 patients with other myeloproliferative diseases. 54 ET-patients presented with complications, 46 with thrombembolic, 3 with hemorrhagic problems and 5 with thrombembolic and hemorrhagic problems. In 6 patients ET was detected accidentally. Disturbances of the microcirculation, mainly of the fingers and the toes, were the most frequent symptom. The average maximal platelet count was 1 207 000/µl. The average platelet count at diagnosis was 880 000/µl. 16 patients had an elevation of the serum creatinin at diagnosis, which deteriorated during the course of the disease. Bone marrow examinations were performed in 56 patients, histology in 48 patients, cytology in 29 patienst. In contrast to the clinical diagnosis the histological diagnosis was in 4 cases each polycythemia vera and myeloproliferative syndrome without further specifiction. 12 patients died thus far. The causes of death were thrombembolic complications in 9, acute leukemia in 2 patients, in 1 patient the cause of death is not known. 10 years after diagnosis 61% of the patients are still alive. It appears that ET is a more important risk factor for the disturbances of the micro- and marcrocirculation than has been recognized until now. ET is, if thrombembolic complications are avoided, a disease with a relatively benign course.

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Abkürzungsverzeichnis ET essentielle Thromobozythämie - PRT persistierende reaktive Thombozytose - PV Polyzythämia vera - CML chronisch myeloische Leukämie - MF Myelofibrose - CMPE chronische myeloproliferative Erkrankung unklarer Zuordnung - MM megakaryozytäre Myelose - ALP alkalische Leukozytenphosphatase - Hb Hämoglobin Herrn Prof. Dr. N. Zöllner zum 65. Geburtstag gewidmet     

Solitary fibrous tumour of the thyroid: Clinicopathological,immunohistochemical and ultrastructural study of three cases

We describe three cases of solitary fibrous tumour (SFT) arising from thyroid stroma. Grossly, the tumours were clearly delimited but only partly encapsulated. The following histomorphological growth patterns were observed: bundles of cells in storiform configuration; non-structured bundles; prevalence of fibrous matrix; highly cellular, non-structured; prevalence of loose, non-structured extracellular substance; cellular proliferation and vascular spaces in a haemangiopericytic configuration and a lipomatous component. Immunohistochemical investigation demonstrated intense, diffuse vimentin positivity and focal, less intense actin positivity in all three cases. At electron microscopy we observed a primitive cell of mesenchymal type, with cytoplasm poor in organelles and rich in filaments; this cell sometimes presented differentiation characteristics. SFT is at present the most correct term for the lesions presented here despite some morphological characteristics which differ from cases reported in the literature.     

Hürthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study

Of 52 consecutive papillary carcinomas of the thyroid, the following cases were included in this study: one Hürthle cell papillary carcinoma, one papillary carcinoma with foci of Hürthle cells, and 10 cases of papillary carcinoma with abundant mitochondria (volumetric density of mitochondria greater than or equal to 20%). All cases were studied by light microscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunocytochemistry. Our results showed that papillary carcinomas mainly or exclusively composed of Hürthle cells are very rare; that Hürthle cell papillary carcinomas of the thyroid share the biologic characteristics and blend insidiously with the so-called mitochondrion-rich papillary carcinomas; that TEM and SEM can provide useful evidence for achieving the differential diagnosis between Hürthle cell and so-called mitochondrion-rich papillary carcinomas; and that immunocytochemical studies are useless in the aforementioned differential diagnosis.     

Cytomegalovirus infection after orthotopic liver transplantation is restricted by a pre-existing antiviral immune response of the recipient

Infection of the liver by the human cytomegalovirus (HCMV) frequently occurs after orthotopic liver transplantation (OLT). However, the role of viral replication and the inflammatory reaction in the development of HCMV-associated liver dysfunction is unclear. To address this question in vivo, 84 liver biopsy specimens from 74 patients who received an orthotopic liver transplant were investigated by immunohistochemical detection of viral antigens and cell type specific marker proteins. The extent of viral replication was correlated with the HCMV antibody status of donor and recipient. HCMV immediate early antigens were found in 25 of 84 liver tissue sections investigated, hepatocytes being the predominant target cells. Bile duct epithelial cells, endothelial cells, mesenchymal cells and sinusoidal lining cells were also found susceptible to HCMV infection. The detection of viral capsid antigens, nuclear inclusions in infected cells and foci of infected cells were suggestive of permissive infection in these cells. In 25 HCMV-positive liver biopsy specimens, the median extent of HCMV infection was 0.33 (0.02-5.67) infected cells/mm(2) liver tissue. Primary infection of liver transplant recipients (D+/R-) was associated with a significantly higher extent of organ involvement as compared to reinfection or reactivation (D+/R+). In contrast, the extent of inflammatory infiltrates in areas of infected liver cells was higher in tissues of patients with pre-existing immunoreactivity (R+) compared to patients without pre-existing immunoreactivity (R-). In conclusion, these results favour the assumption that the immune response to HCMV is effective in restricting viral spread in the liver.     

Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): Co-expression in metastatic serous ovarian carcinoma

Activation or suppression of intracellular signaling via the mitogen-activated protein kinase (MAPK) family has been linked to expression of matrix metalloproteinases (MMP) in experimental models, but this association has not been demonstrated in clinical material. The objective of this study was to investigate the possible association between expression and activity of MMP, expression of the MMP inducer EMMPRIN, and the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK) and high osmolarity glycerol response kinase (p38) in effusions from patients diagnosed with serous ovarian carcinoma. MAPK level and activity were studied in 55 effusions using immunoblotting. MMP-1, MMP-2, MMP-9 and EMMPRIN expression was studied using immunocytochemistry (ICC) and mRNA in situ hybridization (ISH). The gelatinolytic activity of MMP-2 and MMP-9 was measured by zymography. ERK and phospho-ERK (p-ERK) were detected in 54/55 (98%) and 50/55 (91%) specimens, respectively. JNK and p-JNK were detected in 53/55 (96%) and 38/55 (69%) specimens, respectively. p38 was expressed in 54/55 (98%) specimens, and its phosphorylated form was found in 51/55 (92%). MMP-2 mRNA expression (P=0.048), protein expression (P=0.046) and gelatinolytic activity (P=0.039) correlated with ERK phosphorylative activity. MMP-2 activity also correlated with p38 activity (P=0.017). MMP-9 protein expression correlated with phosphorylation of p38 (P=0.046), but enzyme activity showed inverse relationship with both p-ERK (P=0.05) and p-p38 (P=0.033) expression. EMMPRIN expression correlated with MMP-1 (P<0.001), MMP-2 (P=0.042) and MMP-9 (P=0.029) expression, as well as with ERK activity (P=0.001). Our results present the first evidence of a possible link between MAPK signaling and MMP expression and activity in vivo. These data may expand our understanding regarding the mechanisms by which MMP synthesis is regulated in effusions and possibly affect treatment strategies for this form of malignancy. This revised version was published online in July 2006 with corrections to the Cover Date.     

Differential expression of CD44s and CD44v3-10 in adenocarcinoma cells and reactive mesothelial cells in effusions

The detection of malignant cells in serous effusions obtained from patients diagnosed with cancer marks the presence of metastatic disease and is associated with a poor outcome. The purpose of this study was to evaluate the role of CD44s and CD44v isoforms in the distinction between mesothelial cells and malignant epithelial cells in effusions. Fifty-nine fresh pleural and peritoneal effusions were studied. These consisted of 41 specimens from patients with known gynecological neoplasms, 9 from patients diagnosed with breast adenocarcinoma, and 9 effusions from patients with various nongynecological malignancies or tumors of unknown origin. Forty-three effusions contained malignant/atypical epithelial cells, and 16 effusions were diagnosed as reactive. Three effusions contained exclusively malignant cells. Specimens were stained with anti-CD44s, v3, v5, v6, v7 and v3-10. The presence of staining in cancer cells, benign mesothelial cells and lymphocytes was evaluated. CD44s immunoreactivity was seen in 10 of 43 (23%) cases in malignant/atypical epithelial cells and in 53 of 56 (94%) cases in benign cells. In contrast, CD44v3-10 was seen in 23 of 43 (55%) cases in malignant/atypical epithelial cells and in 3 of 56 (6%) cases in benign cells. We advocate the use of CD44s and CD44v3-10 immunostaining in diagnostic evaluation of difficult serous effusions. Received: 30 August 1999 / Accepted: 8 November 1999     

Extraskeletal myxoid chondrosarcoma: multimodal diagnosis and identification of a new cytogenetic subgroup characterized by t(9;17)(q22;q11)

Extraskeletal myxoid chondrosarcoma is a rare malignant soft tissue tumour that can be difficult to diagnose correctly, especially preoperatively. We describe four cases of extraskeletal myxoid chondrosarcoma of the extremities diagnosed by a multimodal approach. The cytological examination of fine-needle aspirates showed small and round, mildly pleomorphic cells lying in sheets and cords, but also dispersed within a myxoid and metachromatic intercellular substance. Histological, electron microscopic and immunocytochemical examination also yielded findings compatible with the diagnosis of extraskeletal myxoid chondrosarcoma. Cytogenetic analysis demonstrated a t(9;22)(q22;q12) in two tumours and a t(9;17)(q22;q11) in the third and fourth. The translocation t(9;22)(q22;q12) has been described repeatedly in extraskeletal myxoid chondrosarcoma but never in other tumours; hence, the detection of this pathognomonic chromosome abnormality in short-term cultured cells from fine-needle aspirates verified the diagnosis in two of the cases. The t(9;17)(q22;q11) found in the last two cases probably represents a new cytogenetic subgroup of extraskeletal myxoid chondrosarcoma as it, too, is unknown in other contexts. The multimodal approach taken in these four cases enabled a definite diagnosis of a rare malignant tumour whose cytological and histological features alone are usually not sufficiently distinct to rule out other differential diagnostic possibilities. Received: 16 March 1999 / Accepted: 1 June 1999     

Hybridization techniques provide improved sensitivity for HCMV detection and allow quantitation of the virus in clinical samples

Hybridization techniques (slot-blot and in-situ hybridization assays) and immunostaining using murine monoclonal antibodies directed against different proteins of the human cytomegalovirus (HCMV) were compared for their sensitivity and specificity for detection of HCMV. A model system with HCMV infected human embryonic lung fibroblasts and lung biopsy specimens obtained from patients with culture positive HCMV interstitial pneumonia were used for evaluation of these techniques. The hybridization techniques were found to provide an improved sensitivity compared to immunostaining. Additionally a good correlation was found between the virus dose determined by TCID50 and the amount of viral DNA detected by slot-blot hybridization and by the number of autoradiographic silver grains per 100 cells per 2 weeks exposure time detected in the infected fibroblasts by in-situ hybridization. Thus, at least in the model system quantification of the virus was achieved by hybridization assays.     

Rapid Techniques in Diagnostic Electron Microscopy

This paper summarizes the rapid preparation procedures for electron microscopy published thus far and assesses their strengths and weaknesses. We also discuss whether there is a real need for rapid preparation techniques in diagnostic electron microscopic work.