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F Länger

Publications and source records attributed to F Länger.

At least 19 recordsLinked to original sources
PubMed2006

[The importance of immunohistochemistry for the diagnosis of cholangiocarcinomas].

The correct diagnosis of intrahepatic cholangiocarcinoma (CC) is often confounded by the small size of the diagnostic specimen and the wide morphological range of carcinomas metastasising to the liver. Expression analysis of cytokeratins, glycoproteins, mucoproteins, adhesion molecules, receptors and transcription factors has been shown to be a valuable adjunct in the typing of carcinomas. For this study, the expression pattern of 30 well documented antibodies to CC and the most common metastatic adenocarcinomas of the liver were studied. CC show a rather distinct immunophenotype with co-expression of CK7, CK17, CD7 and a lack of CDX2. Although this pattern allows the separation of CC from most metastatic carcinomas, pancreatic carcinomas show a broad overlap with this expression pattern.

Bile Duct Neoplasms↗
PubMed2004

[Osteosarcoma of the pelvisTwo case reports and review of the literature].

Primary malignant neoplasms of the bone are rare. One of the most common bone tumors is osteosarcoma, most often localized in the metaphysis of adolescent long bones. The sacrum is concerned in only about 1%. Primary bone sarcomas of the pelvis are usually recognized after they have grown to a considerable size. Osteosarcoma patients from Germany, Austria, and Switzerland are treated by neoadjuvant chemotherapy combined with complete surgical excision according to the Cooperative Osteosarcoma Study Group (COSS). Based on a review of the literature, diagnosis, treatment, and complications of two cases of sacrum osteosarcoma are introduced.

Adult↗
PubMed2004

[Morphological response to therapy of breast carcinoma].

Neoadjuvant chemotherapy has been extended to earlier stages of breast carcinoma in order to increase the rate of breast conservation by downstaging. Tumour regression can be observed in up to 80% of the cases and the chemosensitivity of the individual tumour can be studied in vivo. Moreover therapy induced regression has been established as an independent prognostic parameter. Characteristic effects of chemotherapy include reduction in cell number, fibrosis, vacuolization of cytoplasm and increased nuclear pleomorphism. Grading, typing and immunohistochemical properties of the carcinomas remain unchanged in the majority of cases. Predictive for the chemosensitivity of tumours are a high nuclear grade, overexpression of Her-2-neu, lack of estrogen receptor expression and lymph node metastases.

Antineoplastic Agents↗
PubMed2004

[Epigenetic changes in breast cancer shown by aberrant promoter methylation].

The aberrant methylation of cytosine residues in the promoter region of growth-regulatory genes is now recognized as an important inactivation mechanism in addition to deletion and mutation in the development and progression of cancer. Principally all pathways regulating proliferation and differentiation, which are perturbed in cancer cells, can be affected. In breast cancer epigenetic inactivation is a frequent and early event displaying great quantitative gene-specific differences during progression. The occurrence of specific aberrant methylation patterns is associated with the histological grade and subtype of mammary carcinoma biopsies.

Breast Neoplasms↗
PubMed2004

Yersinia infection mimicking recurrence of gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. So far, surgical resection has been the only curative treatment, but new options became available with the application of imatinib (Glivec) as a specific molecular inhibitor. Even after complete resection, GISTs have a high rate of recurrence and disease-linked mortality. Here we report on the case of a clinically well 57-year-old woman who presented to us 3 years after resection of a GIST of the small intestine. Abdominal ultrasound and CT scan showed intestinal wall thickening in the area of anastomosis and mesenteric lymphadenopathy, suggesting a recurrence of the primary GIST. However, serological testing was positive for yersinia antibodies. Surgical exploration revealed an asymptomatic infection with Yersinia enterocolitica serotype O9, proven by positive culture and histology, which showed no evidence of malignancy. Prognostic variables for GIST as well as diagnostic measures and limitations for yersiniosis are discussed. In the end, only surgical exploration and histological analysis could establish the final diagnosis. In conclusion, GISTs have a high likelihood of recurrence even after complete resection, but an asymptomatic infection such as yersiniosis must be considered as a differential diagnosis to GIST recurrence.

Diagnosis, Differential↗
PubMed2003

Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML).

The important cell cycle regulatory gene p15(INK4b) has been shown to be inactivated in acute myeloid leukemia and myelodysplastic syndrome. Little is known about the expression and epigenetic modification of this gene in chronic myelomonocytic leukemia (CMML) that belongs to the myelodysplastic/myeloproliferative disorders (MDS/MPD) with a high proportion of blastic transformation. Analysis of bone marrow trephines in a series of 33 CMML cases showed an aberrant p15(INK4b) gene methylation in up to 58% of cases. Methylation was analyzed employing different methylation-specific PCR and genomic sequencing protocols. It turned out to be spread over a broad area of the 5' region and exhibited substantial heterogeneity between cases and even in individual patients. The degree of aberrant methylation was correlated with a reduced mRNA as well as reduced protein expression, and was associated with a higher expression of DNA methyltransferase DNMT 3A. We conclude that aberrant gene methylation is a frequent event in CMML that might contribute to the pathogenesis of this MDS/MPD.

Bone Marrow↗
PubMed2002

[Histopathology of leukaemic non-Hodgkin's lymphoma in bone marrow].

Staging biopsies of the bone marrow in lymphoma patients are among the most important indications and therefore of substantial practical importance. Occasionally it is the only organ infiltrated, and therefore a bone marrow biopsy is the prime diagnostic choice in cases of leukemic lymphomas. A synoptical diagnostic approach relying on immunophenotypic as well as on molecular biological criteria aside from histomorphology (cytomorphology), is of utmost importance for the subtyping of malignant lymphomas. This too can be done reliably on bone marrow biopsies, as comparative studies have yielded a concordance rate of more than 90% with lymphoma typing on corresponding lymph nodes. Cytology and the pattern of infiltrates, (i.e. diffuse, interstitial, nodular peritrabecular and intrasinusoidal), in combination with immunological phenotyping are the mainstays for subtyping, giving clear-cut decisions in most cases of small B-cell lymphoma, mantle zone as well as marginal cell and follicular lymphomas and hairy cell leukemia. Among the blastic variants the most important are the lymphoblastic lymphomas of either B- or T-cell type which have to be discerned from AML and the so-called blastoid mantle cell lymphomas. T-cell lymphomas are rare compared to B-cell lymphomas. Among the rarely seen T-cell neoplasias the lymphoma of large granular lymphocytes is the dominating lymphoma, which in most cases can only be diagnosed reliably by molecular biological means, followed by T-CLL, Sezary's syndrome and hepatosplenic chi delta lymphoma.

Biopsy↗
PubMed2002

[The development of myelofibrosis in prefibrotic cIMF. An investigation of the progression by sequential bone marrow biopsies in 38 patients].

Overt myelofibrosis in bone marrow biopsies as a diagnostic postulate in cIMF has been discarded only recently by the WHO. Therefore, only a few studies have been performed on the evolution of myelofibrosis in "prefibrotic" cIMF by means of sequential bone marrow biopsies. We carried out this study on 38 patients, split up into two groups, A and B according to treatment modalities, to evaluate the dynamics and frequency of myelofibrosis in both groups. Our results indicate a step-wise development of myelofibrosis from a "prefibrotic" to a "classical" cIMF, as 75-80% of the respective patients in both groups progressed to myelofibrosis. However, this evolution seems to be heterogeneous and unpredictable in individual patients, since myelofibrosis could be seen as early as less than 2 years after diagnosis in 12/38 (31.6%) patients, whereas 3 patients remained "prefibrotic" even after up to 6 years of follow-up.

Biopsy, Needle↗
PubMed2002

[Neuroendocrine tumors of the stomach. Surgery therapy and prognosis].

Gastric carcinoid tumors are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like (ECL) cells of the stomach. A classification system distinguishing three types of gastric carcinoid tumors has been proposed: 1) tumors related to chronic atrophic gastritis, 2) tumors associated with Zollinger-Ellison syndrome, and 3) sporadic lesions. It is apparent that hypergastrinemia-associated gastric carcinoids show a rather benign biological behavior. Normo-gastrinemic sporadic lesions, on the other hand, require an aggressive surgical management. We report seven patients with gastric neuroendocrine tumors ("carcinoids"), who underwent surgical treatment in our department between 1988 and 2000. Surgical therapy included total gastrectomy with D2 lymphadenectomy in two cases with type I tumors and for one patient with type III tumor. One patient with a type II tumor was treated by distal subtotal gastrectomy and another by antrectomy. A local excision was performed on one patient with type I tumor. After a mean follow-up of 8 years, 5 of 7 patients are alive without recurrence.

Adult↗
PubMed2001

Demonstration of light chain restricted clonal B-lymphoid infiltrates in archival bone marrow trephines by quantitative real-time polymerase chain reaction.

Assessment of clonality either by demonstrating light chain restriction or showing monoclonal immunoglobulin gene rearrangement is a valuable and indispensable adjunct to diagnosis in hematopathology. The study of light chain restriction by immunohistochemistry on archival material is hampered by a very low sensitivity especially regarding low grade lymphomas of B cell origin. DNA rearrangement studies of the immunoglobulin locus do improve sensitivity markedly but for lymphomas of follicle center origin they are prone to false negative results due to hypermutations. Therefore we developed a new clonality assay based on the quantification of immunoglobulin light chain transcripts using real-time polymerase chain reaction technology, which is also suitable for the analysis of archival bone marrow trephines. We tested the reproducibility and sensitivity of this approach by comparatively analyzing a series of bone marrow trephines with multiple myeloma (n = 26), reactive lymphoid hyperplasia (n = 37), and focal infiltration by low grade B cell lymphoma (n = 29). We could raise the detection rate of clonality from an average of 17% by immunohistochemistry and 66% as assessed by polymerase chain reaction rearrangement studies to 83% by this new technique. Despite false negative results due to light chain hypermutation in some cases, the detection rate of clonality could be improved even for B cell lymphomas of follicle center origin (follicular lymphoma or marginal zone lymphoma) thus making this novel approach a valuable additional tool for the hematopathologist.

B-Lymphocytes↗
PubMed2001

Amplification of growth regulatory genes in intraductal breast cancer is associated with higher nuclear grade but not with the progression to invasiveness.

Ductal carcinoma in situ (DCIS), as an identifiable progenitor lesion of invasive breast cancer, represents a morphologically, biologically, and prognostically heterogeneous disease. It is not clear which molecular mechanisms are involved in progression to infiltrative growth. In this study, 83 DCIS classified according to the Van Nuys grading scheme were examined for amplification of growth regulatory genes that have been found to be amplified in invasive breast cancer (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1 genes). Exact quantification of gene amplification was enabled by a combination of laser microdissection of paraffin-embedded tissue with real-time PCR. In DCIS, gene amplifications of all tested genes were found. The most frequently amplified gene was c-erbB2 found in 21 of 83 (25%) cases. Amplification of the other genes under investigation was observed in 4% to 6% of cases, high-grade DCIS being predominantly affected. High-grade DCIS differed significantly from low- and intermediate-grade DCIS in frequency and level of c-erbB2 amplification. In addition, high-grade DCIS revealed an accumulation of genetic aberrations. Amplification status in pure in situ lesions did not differ from intraductal carcinoma with an infiltrative component, indicating that although associated with a higher nuclear grade gene amplification might not represent an independent prognostic marker of disease progression.

Breast Neoplasms↗
PubMed2000

Detection of gene amplification in intraductal and infiltrating breast cancer by laser-assisted microdissection and quantitative real-time PCR.

Gene amplification is one essential mechanism leading to oncogene activation which is supposed to play a major role in the pathogenesis of invasive breast cancer. However, using standard methodologies the detection of gene amplifications has been limited especially in small-sized lesions, like pre-invasive precursor lesions. The combination of two novel technologies, laser-based microdissection and quantitative real-time PCR, facilitates the detection of low-level amplifications in morphologically defined lesions. As a model system we investigated in situ breast cancer (ductal carcinoma in situ, DCIS) classified according to the morphology-based Van Nuys grading system for amplification of growth-regulatory genes. In this study 83 formalin-fixed, paraffin-embedded archival DCIS specimens were examined after laser-based microdissection by quantitative real-time PCR using the TaqMan detection system for amplification of the c-erbB2, topoisomerase IIalpha, c-myc and cyclinD1 gene. In a subset of 17 DCIS with adjacent infiltrating tumour components we compared intraductal and invasive tumour components in parallel for differences in amplification status. The combination of these new techniques represents an excellent tool to gain new insights into carcinogenesis by analyzing genetic alterations in morphologically identified heterogeneous lesions in breast cancer progression within the very same specimen or even tissue slide.

Antigens, Neoplasm↗
PubMed1998

[Cavitating lung lesions in the course of ANCA-associated vasculitis: differential diagnostic aspects].

Antineutrophil cytoplasmatic antibodies (ANCA)-associated vasculitides (Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome) show quite variable courses. Clinical features of the full blown generalized systemic vasculitis are usually found in the respiratory tract and the kidney. Pulmonary involvement of Wegener's granulomatosis shows commonly nodules and cavitations but also diffuse alveolar hemorrhage. We report the case of a 57 year-old man suffering from dyspnea, thoracal pain, arthralgia, purpura, scleritis and tinitus. Specimen of the kidney showed segmental glomerulosclerosis and tubulointerstitial nephritis. Because of the presence of cANCA Wegener's disease was assumed. Pulmonary infiltrates developed under immunosuppressive treatment with cyclophosphamid. As differential diagnosis of the pulmonary infiltrates, we considered invasive pulmonary aspergillosis as well as infiltrates due to Wegener's granulomatosis. In spite of maximal therapeutic management of patient died of respiratory and cardiovascular failure. The findings at autopsy showed distinct invasive pulmonary aspergillosis and perifocal hemorrhage.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

[Spontaneous Hashimoto-like thyroiditis in cats].

A breeding line of domestic cats spontaneously developing symptoms of hypothyroidism between the 40th and 60th day of life (fur changes, loss of appetite, growth retardation), elevated levels of antibodies against microsomal structures and thyroglobulin, and lymphocytic thyroid infiltration has been recently established at our facility. Aim of our studies was to examine the effect of high iodine ingestion or prophylactic thyroid hormone therapy on functional and morphological characteristics of this Hashimoto-like thyroiditis in cat. From birth to day 80 of life cats were treated with iodine (n = 9; 0.1 mg/l) or thyroxin (n = 13; 2.0 micrograms/ kg/d) respectively. Untreated animals served as controls (n = 12). Cat-serum was tested for thyroid function (TT3, TT4). After 8 weeks the thyroid tissue was submitted to routine histological processing (H&E) and the inflammatory activity was scored. Additionally immunohistological staining was performed for MIB-1, IgG, IgM and MHCII expression. Both untreated hypothyroid (UHC) as well as iodine-treated (IC) cats revealed a significantly higher degree of thyroid inflammation and higher tissue levels of IgM as the thyroxin-substituted animals (TC). Epithelial proliferation decreased significantly in the IC and TC groups as compared to the untreated controls. No significant differences regarding IgG production and HLAII expression were detectable. Early thyroid hormone therapy significantly decreases both incidence and activity of autoimmune thyroiditis in cats as measured by inflammatory infiltration, IgM production and epithelial proliferation. Animals with excess iodide intake, however, show an aggravation of the autoimmune inflammatory activity.

Animals↗
PubMed1996

[Effect of intrathyroidal lymphocytes of Graves' disease patients on xenograft thyroid tissue in the athymic nude mouse].

In this study we investigated the functional and morphological properties of xenotransplanted human thyroid tissue in nude mice following systemic application of intrathyroidal lymphocyte preparations from patients with Graves' disease (GD) and non-toxic nodular goiter (NTG). Thyroid tissue samples from 17 NTG-patients were transplanted into athymic nude mice for a period of 4-5 weeks. Aliquots of lymphocyte preparations from both peripheral blood samples (PBL) and thyroid tissue (ITL) of 13 patients with GD and 12 patients with NTG were analyzed by flow-cytometry (CD3, CD4, CD8, CD56) and injected (i.v.) into transplanted nude mice. Animals injected with saline solution served as a control. After 48 h transplants were harvested and histological (H&E) as well as immunohistological evaluation was performed (MHCII, IgG, IgM). Control animals and mice treated with both PBL and ITL from NTG patients showed regular thyroid tissue without lymphocytic infiltrates or local expression of human immunoglobulins. Application of PBL and ITL of GD patients caused scant to moderate lymphocytic infiltrates with detection of human immunoglobulin production. Injection of GD-ITL was accompanied by a significantly higher proportion of intrathyroidal CD3+ lymphocytes and MHCII expression of adjacent thyroid epithelium as compared to injection of GD-PBL preparations. Our results demonstrate that GD-lymphocytes of both peripheral but especially intrathyroidal origin migrate specifically to human thyroid transplants in the nude mouse model, survive for at least two days, secrete immunoglobulins and induce MHCII expression.

Animals↗