Biomedical subjects
Susanna Müller
Publications and source records attributed to Susanna Müller.
Type II collagen as specific marker for mesenchymal chondrosarcomas compared to other small cell sarcomas of the skeleton.
Mesenchymal chondrosarcoma is a rare, usually highly malignant chondrogenic neoplasm. The diagnosis of mesenchymal chondrosarcoma can be challenging, it nonetheless has important therapeutic and diagnostic implications. Thus, biopsies of mesenchymal chondrosarcomas without conspicuous cartilaginous differentiation cannot be safely distinguished from other small cell mesenchymal neoplasms such as Ewing's sarcoma and peripheral neuroendrocrine tumors, synovial sarcomas and hemangiopericytomas, because all of these neoplasms might show overlapping histological features, and so far, there have been no safe immunohistochemical markers available in order to differentiate these neoplasms. In our study on a large series of mesenchymal chondrosarcomas (n=30) and other small cell sarcomas (Ewing's sarcomas (n=12), synovial sarcomas (n=6), hemangiopericytomas (n=5), small cell osteosarcomas (n=3), and desmoplastic small round cell tumors (n=1)), we could establish the presence of type II collagen in the extracellular tumor matrix of the small cell areas of mesenchymal chondrosarcomas as a specific and sensitive marker to identify mesenchymal chondrosarcomas and to exclude other small cell neoplasms (except chondroblastic areas in small cell osteosarcomas). In contrast, the S-100 protein was less sensitive and vimentin and total collagen content unspecific for discriminating these neoplasms. Thus, the presence of type II collagen in the extracellular tumor matrix significantly facilitates the diagnosis of mesenchymal chondrosarcomas in the absence of histologically visible chondroid matrix formation.
Microtubule-associated protein-2 immunoreactivity: a useful tool in the differential diagnosis of low-grade neuroepithelial tumors.
Complex and variable morphological phenotypes pose a major challenge to the histopathological classification of neuroepithelial tumors. This applies in particular for low-grade gliomas and glio-neuronal tumors. Recently, we and others have identified microtubule-associated protein-2 (MAP2) as an immunohistochemical marker expressed in the majority of glial tumors. Characteristic cell morphologies can be recognized by MAP2 immunoreactivity in different glioma entities, i.e., process sparse oligodendroglial versus densely ramified astrocytic elements. Here, we describe MAP2-immunoreactivity patterns in a large series of various neuroepithelial tumors and related neoplasms (n = 960). Immunohistochemical analysis led to the following conclusions: (1) specific pattern of MAP2-positive tumor cells can be identified in 95% of glial neoplasms; (2) ependymal tumors do not express MAP2 in their rosette-forming cell component; (3) tumors of the pineal gland as well as malignant embryonic tumors are also characterized by abundant MAP2 immunoreactivity; (4) virtually no MAP2 expression can be observed in the neoplastic glial component of glio-neuronal tumors, i.e. gangliogliomas; (5) malignant glial tumor variants (WHO grade III or IV) exhibit different and less specific MAP2 staining patterns compared to their benign counterparts (WHO grade I or II); (6) with the exception of melanomas and small cell lung cancers, MAP2 expression is very rare in metastatic and non-neuroepithelial tumors; (7) glial MAP2 expression was not detected in 56 non-neoplastic lesions. These data point towards MAP2 as valuable diagnostic tool for pattern recognition and differential diagnosis of low-grade neuroepithelial tumors.
Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99.
BACKGROUND: Transplantation of allogeneic haemopoietic stem cells can cure several primary immunodeficiencies. This European report focuses on the long-term results of such procedures done between 1968 and December, 1999, for primary immunodeficiencies. METHODS: The report includes data from 37 centres in 18 countries, which participated in a European registry for stem-cell transplantation in severe combined immuno deficiencies (SCID) and in other immunodeficiency disorders (non-SCID). 1082 transplants in 919 patients were studied (566 in 475 SCID patients, 512 in 444 non-SCID patients; four procedures excluded owing to insufficient data). Minimum follow-up of 6 months was required. FINDINGS: In SCID, 3-year survival with sustained engraftment was significantly better after HLA-identical than after mismatched transplantation (77% vs 54%; p=0.002) and survival improved over time. In HLA-mismatched stem-cell transplantation, B(-) SCID had poorer prognosis than B(+) SCID. However, improvement with time occurred in both SCID phenotypes. In non-SCID, 3-year survival after genotypically HLA-matched, phenotypically HLA-matched, HLA-mismatched related, and unrelated-donor transplantation was 71%, 42%, 42%, and 59%, respectively (p=0.0006). Acute graft versus host disease predicted poor prognosis whatever the donor origin except in related HLA-identical transplantation in SCID. INTERPRETATION: The improvement in survival over time indicates more effective prevention and treatment of disease-related and procedure-related complications--eg, infections and graft versus host disease. An important factor is better prevention of graft versus host disease in the HLA-non-identical setting by use of more efficient methods of T-cell depletion. For non-SCID, stem-cell transplantation can provide a cure, and grafts from unrelated donors are almost as beneficial as those from genetically HLA-identical relatives.
[Allergy-associated colitis. Characterization of an entity and its differential diagnoses].
There is substantial evidence that allergic reactions exist in the gastrointestinal tract (GI). However, patients with food allergy-related enteropathy pose a diagnostic challenge to physicians because the clinical features are variable, unspecific, occur in other gastrointestinal disorders, and specific diagnostic tools are missing. Several recent studies and reviews have focused on the function of eosinophilic granulocytes in GI disease. The role of eosinophils in the pathophysiology of GI hypersensitivity reactions is poorly defined. However, some findings have been reported that imply an involvement of eosinophils in allergic reactions of the gut. The presumptive histology of allergy-associated colitis in colonic and ileal biopsies is based on prominent pure eosinophilic infiltration of a normal lamina propria, submucosa and epithelium with variable degrees of degranulation. An immunoperoxidase stain for eosinophilic peroxidase is supportive in establishing the diagnosis if suspected. Neutrophils or mononuclear infiltrates are not significantly increased and damage to the intestinal tissue is not prominent. Despite characteristic histologic changes in colonic biopsy specimens, a final diagnosis depends on careful clinical examination and exclusion of several differential diagnoses.
Functional and morphologic characterization of eosinophils in the lower intestinal mucosa of patients with food allergy.
OBJECTIVE: The aim of this study was to characterize the functional and morphologic features of eosinophils in the intestinal mucosa of patients with food allergy. METHODS: Eighteen patients with food allergy and 11 controls took part in this study. In every patient, corresponding biopsy samples obtained during colonoscopy were quantitatively assessed by immunohistochemical methods (EPO-I) and subjected to mucosa oxygenation using eosinophilic cationic protein (ECP). Initial basal release, spontaneous and anti-IgE-dependent release, and the total ECP content of mucosal biopsies were studied. RESULTS: Morphologically, mucosal eosinophils in patients with food allergy have distinct features, occur in larger amounts, and show a distinct distribution pattern (i.e., intraepithelial, lamina propria, and submucosa). Their initial basal release is similar to that of controls, but stimulation of the IgE receptor with anti-IgE results in 40-fold activation (p < 0.001). In food allergy patients, the density of eosinophils, the presence of intraepithelial eosinophils, and the rate of degranulation showed a highly significant correlation to the initial basal release of ECP by mucosal tissue (Kendall tau = 0.619, 0.381, and 0.609, respectively; p < 0.05 for all) but not to their capability to be stimulated with anti-IgE. CONCLUSIONS: Eosinophils of the lower intestine of patients with food allergy show characteristic features with regard to morphology, distribution, and functional behavior to IgE receptor stimulation. Immunostaining of eosinophil peroxidase (EPO) detects important characteristic features that are missed with conventional hematoxylin-eosin staining.
Outcome of patients with pre-existing portal vein thrombosis undergoing arterialization of the portal vein during liver transplantation.
Arterialization of the portal vein is being propagated as a technical possibility in liver transplant recipients with pre-existing portal vein thrombosis. In our own small series, portal vein arterialization (PVA) was carried out in four patients undergoing orthotopic liver transplantation. In three of these cases, the portal vein was anastomosed to the aorta via an interposed iliac artery, and in one case, directly to the hepatic artery. After PVA, all transplants showed regular initial function. Two patients died postoperatively after 19 and 50 days, of intra-abdominal haemorrhage and liver necrosis with thrombosis of the portal vein, respectively. A further patient had previously developed fibrosis of the liver, which led to the death of the patient 11 months after PVA. In the remaining patient, chronic rejection requiring re-transplantation developed 24 months after PVA had been performed. These unfavourable results prompt the conclusion that PVA cannot be recommended as a standard clinical procedure.
Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000.
Treatment of chronic granulomatous disease (CGD) with myeloablative bone marrow transplantation is considered risky. This study investigated complications and survival according to different risk factors present at transplantation. The outcomes of 27 transplantations for CGD, from 1985 to 2000, reported to the European Bone Marrow Transplant Registry for primary immunodeficiencies were assessed. Most transplant recipients were children (n = 25), received a myeloablative busulphan-based regimen (n = 23), and had unmodified marrow allografts (n = 23) from human leukocyte antigen (HLA)-identical sibling donors (n = 25). After myeloablative conditioning, all patients fully engrafted with donor cells; after myelosuppressive regimens, 2 of 4 patients fully engrafted. Severe (grade 3 or 4) graft-versus-host disease (GVHD) disease developed in 4 patients: 3 of 9 with pre-existing overt infection, 1 of 2 with acute inflammatory disease. Exacerbation of infection during aplasia was observed in 3 patients; inflammatory flare at the infection site during neutrophil engraftment in 2: all 5 patients belonged to the subgroup of 9 with pre-existing infection. Overall survival was 23 of 27, with 22 of 23 cured of CGD (median follow-up, 2 years). Survival was especially good in patients without infection at the moment of transplantation (18 of 18). Pre-existing infections and inflammatory lesions have cleared in all survivors (except in one with autologous reconstitution). Myeloablative conditioning followed by transplantation of unmodified hemopoietic stem cells, if performed at the first signs of a severe course of the disease, is a valid therapeutic option for children with CGD having an HLA-identical donor.
Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas.
BACKGROUND: Conventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management. METHODS: In the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow-up. RESULTS: The authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so-called "dedifferentiated" phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low-grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis. CONCLUSIONS: These data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low-grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms.