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Stephan Dirnhofer

Publications and source records attributed to Stephan Dirnhofer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Marginal zone lymphoma of the lacrimal gland spreading to the lung and the bone marrow 11 years after first symptoms.

We report on the case of a 52-year-old male presenting with an extranodal marginal zone lymphoma of the mucosa-associated tissue (MALT lymphoma) in the lung 11 years after radiotherapy for a MALT lymphoma of the lacrimal gland, which was primarily diagnosed as dacryoadenitis. Both tumors were investigated by immunohistochemistry and molecular techniques demonstrating their clonal genetic relationship. Both harbored the t(14;18)(q32;q21) and a trisomy 3 and showed identical immunoglobulin heavy-chain gene rearrangements. At the time of pulmonary relapse, clonal CD20- and CD43-positive bone marrow B lymphocytes were detected as well. The elaboration of this case emphasizes the importance of the combined use of modern diagnostic methods for establishment of correct diagnosis of MALT lymphomas at late relapses, which is essential for proper patient management.

Adult↗
PubMed2005

Postmortem diagnostics using MSCT and MRI of a lethal streptococcus group A infection at infancy: a case report.

Postmortem cross-sectional imaging using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) was considered as a base for a minimal invasive postmortem investigation in forensic medicine such as within the Virtopsy approach. We present the case of a 3-year-old girl with a lethal streptococcus group A infection and the findings of postmortem imaging in this kind of natural death. Postmortem MSCT and MRI revealed an edematous occlusion of the larynx at the level of the vocal cords, severe pneumonia with atelectatic parts of both upper lobes and complete atelectasis of both lower lobes, purulent fluid-filled right main bronchus, enlargement of cervical lymph nodes and pharyngeal tonsils, and additionally, a remaining glossopharyngeal cyst as well as an ureter fissus of the right kidney. All relevant autopsy findings could be obtained and visualized by postmortem imaging and confirmed by histological and microbiological investigations supporting the idea of a minimal invasive autopsy technique.

Adenoids↗
PubMed2005

Proposal of a morphologic bone marrow response score for imatinib mesylate treatment in chronic myelogenous leukemia.

Cytogenetic and molecular analyses are essential disease-monitoring parameters in chronic myelogenous leukemia (CML) treated with imatinib. However, a bone marrow morphologic response has not been defined. We reviewed bone marrow histology and cytology of 39 imatinib-treated patients with CML over 49 weeks and introduced a morphologic response score. A significant positive correlation with a complete cytogenetic response was shown for absence of dry tap (P = .04) and abnormal megakaryocytes (P < 0.001), normalization of cellularity (P = .001) and reduction of fibrosis (P = .01), myelopoiesis:erythropoiesis index (P = .001), blast (P = .001) and basophil count (P < 0.001). The morphologic score integrating these parameters showed an early and late correlation with cytogenetic response. In conclusion, morphologic criteria for complete cytogenetic response in patients with CML treated with imatinib can be defined. Persistent high-level morphologic abnormalities herald early on a high likelihood to fail treatment and call for more intense or alternative therapy.

Adult↗
PubMed2005

Placental site trophoblastic tumor of the mediastinum.

Choriocarcinoma has been described as the most frequent subtype of mediastinal germ cell tumors showing trophoblastic differentiation. We report a unique case of a placental site trophoblastic tumor, which developed in the mediastinum of a 14-year-old boy 2 years after the resection of a mature teratoma. The recurrent tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically, diffusely infiltrating large polygonal cells with focal nodular growth and a teratomatous part containing mature intestinal, respiratory, and squamous epithelium with adjacent cutaneous adnexal structures were found. The typical morphologic features included vessel wall infiltration by the neoplastic cells with fibrinoid deposits and geographic necroses within the tumor masses. Characteristic diffuse positivity for melanoma cell adhesion molecule and human leucocyte antigen G was found on immunohistochemical investigation, confirming the diagnosis of placental site trophoblastic tumor. The patient died 1 year later after polychemotherapy. The outcome of this rare tumor is similar to the reported poor clinical outcome in patients with mediastinal choriocarcinomas.

Adolescent↗
PubMed2005

Aberrant expression of cell cycle regulators in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma.

The characteristic Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma, although highly positive for proliferation markers, do not accumulate to excessive cell numbers. These cells are characterized by abortive mitotic cycles, leading to multinucleation or cell death in mitosis. We have previously described high expression of G1-phase cyclins in classical Hodgkin's lymphoma, which could explain the high percentage of cells staining for proliferation markers. To further our understanding of proliferation control in classical Hodgkin's lymphoma, we extended our immunohistochemical analysis to the main S-phase cyclin, cyclin A, and its regulators p21CIP1 and p27KIP1. Expression of proliferating cell nuclear antigen (PCNA) was used as an additional marker for cells being in either S- or G2-phase. In 47% (112/239) of classical Hodgkin's lymphoma cases p21CIP1 was detected within a mean frequency of 15% positive Hodgkin's and Reed-Sternberg cells per case. Similarly, 47% (116/249) of the cases stained positively for p27KIP1 with a mean frequency of expression in Hodgkin's and Reed-Sternberg cells of 12%. In contrast, 90% of the cells in all 246 evaluable classical Hodgkin's lymphoma cases were positive for PCNA. In addition, 98% of Hodgkin's and Reed-Sternberg cells in 99% (250/253) of the cases stained strongly positive for cyclin A. These findings further corroborate the hypothesis that Hodgkin and Reed-Sternberg cells exhibit a disturbed cell cycle with an abnormally short or even absent G1-phase. In contrast to other tumors, expression of PCNA or cyclin A had no prognostic value for patient survival.

Adolescent↗
PubMed2005

Rare expression of T-cell markers in classical Hodgkin's lymphoma.

Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphoma are primarily of B-cell origin, although there are instances of T-cell antigen expression suggesting T-cell origin. We comprehensively analyzed expression of various T-cell antigens in 259 classical Hodgkin's lymphoma cases using the tissue microarray technique. Expression of the T-cell antigens CD2, CD3, CD4, CD5, CD7 and CD8 was assessed by immunohistochemistry. Hodgkin's and Reed-Sternberg cells of T-cell marker-positive cases were microdissected and analyzed by a multiplex polymerase chain reaction for clonal immunoglobulin heavy chain- and T-cell receptor gamma gene rearrangements. In all, 12 cases (5%) expressed at least one T-cell marker in the following order: CD2 in 11 cases, CD4 in five, CD3 in two, and CD5 and CD8 in one case each; there were no CD7-positive cases, and five cases (2%) expressed more than one T-cell antigen. In positive cases, a mean fraction of 40% of the Hodgkin's and Reed-Sternberg cells (range 20-100%) expressed the analyzed T-cell markers. Two cases (<1%) evidenced clonal T-cell receptor gamma gene rearrangement. Phenotypic expression of T-cell antigens in Hodgkin's and Reed-Sternberg cells of classical Hodgkin's lymphoma is rare (5%), while genotypically, less than 1% of classical Hodgkin's lymphomas are of possible T-cell origin. Therefore, T-cell antigen expression on Hodgkin's and Reed-Sternberg cells is aberrant in the majority of cases and only infrequently classical Hodgkin's lymphomas are of T-cell origin.

Antigens, CD↗
PubMed2005

Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors.

EpCam is an epithelial adhesion molecule expressed in a broad range of carcinomas. Clinical trials with specific humanized anti-EpCam antibodies have shown promising results and have been inaugurated in renal cell carcinoma (RCC) therapy. To study the EpCam expression profile, primary renal cell neoplasms as well as corresponding metastases were evaluated by immunohistochemistry in tissue microarrays. EpCam expression in oncocytomas and chromophobe RCCs was determined on conventional large sections. Moderate or strong EpCam expression was found in eighteen percent of clear cell (n=147), 75% of chromophobe (n=12), and 55% of papillary RCCs (n=20), but not in oncocytomas (n=3). On large sections, 90% of chromophobe RCCs (n=20) showed a strong and homogeneous positivity, whereas oncocytomas (n=15) revealed EpCam positivity in single tumor cells or small clusters. Fourteen percent of RCC metastases (n=97) showed EpCam expression. Patients with EpCam expressing clear cell RCC showed a trend toward a better prognosis in a Cox regression analysis including stage, grade, and necrosis. The data suggest EpCam as a potential therapeutic target in a subset of patients with RCC. In addition, expression patterns of EpCam could become a helpful tool in the discrimination of chromophobe RCC and oncocytoma.

Adult↗
PubMed2005

High specificity of combined TRAP and DBA.44 expression for hairy cell leukemia.

Because of marrow fibrosis, bone marrow aspirations are often nonconclusive in patients with hairy cell leukemia (HCL). Therefore, histologic examination is important in HCL but often difficult in cases with low numbers of tumor cells. A combined immunohistochemical positivity for DBA.44 and tartrate-resistant phosphatase was previously found in 100% of HCL and suggested to be specific for this diagnosis. To further assess the diagnostic specificity and sensitivity of this immunohistochemical approach in a higher number of cases, we analyzed 56 HCLs and lymphoma tissue microarrays, including 840 cases of the most frequent non-Hodgkin lymphomas. All HCLs showed combined positivity for these two proteins (100% sensitivity). Both antibodies were often positive in other lymphoma types. DBA.44 reactivity was especially frequent in follicular lymphomas (46%), whereas tartrate-resistant acid phosphatase (TRAP) expression was often seen in mantle cell lymphomas (57%), primary mediastinal large B-cell lymphomas (54%), and chronic lymphocytic leukemia/small lymphocytic lymphoma (41%). A combined DBA.44/TRAP positivity was seen in only 3% of non-HCL non-Hodgkin lymphomas, including cases of diffuse large B-cell lymphomas, follicular lymphomas, chronic lymphatic leukemia/small lymphocytic leukemias, and mantle cell lymphomas. Overall, these data confirm the utility of combined immunohistochemical DBA.44/TRAP expression analysis in confirming the diagnosis of HCL. However, combined positivity for these markers is highly sensitive but not absolutely specific for HCL.

Acid Phosphatase↗
PubMed2005

Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays.

BACKGROUND AND OBJECTIVES: Patients with diffuse large B-cell lymphoma (DLBCL) could benefit from integration of well-established bioclinical prognostic factors with new tools - such as micro-arrays - exploring aberrant gene and/or protein expression. DESIGN AND METHODS: Tissue micro-arrays (TMA) were constructed for the paraffin blocks of 68 patients with de novo DLBCL with nodal presentation, who underwent MACOP-B and were provided with complete clinical information. TMA were tested with specific antibodies against CD10, CD20, CD30, CD79a, CD138, Bcl-2, Bcl-6, IRF4, and IRTA1. RESULTS: The following phenotypic subclassification was made: a) CD10 +/Bcl-6 + or Bcl-6+/IRF4 +, but Bcl-2-/CD30-/CD138-- suggesting B-cells gathering/leaving the germinal center (group 1; n=36); b) Bcl-2+/CD10-/Bcl-6- and CD30+ or CD138+ corresponding to putative non-germinal center B-cells with features of activation or plasmablastic/plasmacellular differentiation (group 2; n=17); c) CD30-/CD138- with extensive Bcl-2 positivity and variable CD10, Bcl-6 and IRF4 combinations (group 3; n=15). Mean IPI scores were 0.6, 1.9 and 1.1 for groups 1, 2 and 3, respectively (p= 0.001). Complete remission (CR) rates were 89%, 53% and 73% (p= 0.015). The 3-year relapse-free survival (RFS) rates are 86%, 41% and 63% (p=0.001) and 42-month overall survival (OS) rates are 91%, 38% and 66% (p=0.0002). INTERPRETATION AND CONCLUSIONS: The present TMA-based study suggests an immunophenotypic profiling system for patients with de novo DLBCL that seems to provide additional prognostic information and contributes to the existing debate on the identification of suitable immunohistochemical surrogates of gene expression profiling results.

Adult↗
PubMed2005

Cyclin B1 expression is an independent prognostic marker for poor outcome in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkin's lymphoma in the Western world; it is characterized by marked genetic, morphological and clinical heterogeneity. The identification of prognostic markers could help to develop risk-adapted treatment strategies. As proliferation of cells is essential for tumour growth, analysis of the cell cycle and its individual phases might give additional information on tumour progression and clinical behaviour. To investigate the prognostic value of proteins specifically related to the cell cycle phases S, G2 and M in DLBCL, the expression of cyclin A as a marker of S phase and cyclin B1 as a G2/M phase marker were analysed in combination with other clinicopathological parameters in a large cohort of patients. Expression of cyclin B1 and cyclin A were determined by immunohistochemistry using tissue microarray methodology. Immunoreactivity for cyclin B1 and cyclin A was correlated with clinical data using a two-sided Fisher's exact test. Impact on overall survival was analysed by the Kaplan-Meier method. A negative prognostic impact was found for expression of cyclin B1. Nuclear and/or cytoplasmic staining in > or = 1% of tumour cells was significantly associated with shorter overall survival in the multivariate analysis (p=0.008). Furthermore, the prognostic impact of cyclin B1 expression was independent of the tumour stage. No prognostic significance was found for expression of cyclin A. In conclusion, this study demonstrates the independent prognostic value of an expression of cyclin B1 in DLBCL and proposes its evaluation as a prognostic marker in the assessment of this entity which is easily applicable in daily routine practice.

Aged↗
PubMed2004

Prevalence of KIT expression in human tumors.

PURPOSE: KIT is a target for imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Gastrointestinal stromal tumors (GISTs) express KIT and respond favorably to imatinib therapy. To determine other tumors in which such a molecular targeted therapy might be indicated, we investigated KIT expression in different human tumor types. Because recent studies in GISTs suggest that KIT-activating mutations predict response to imatinib therapy, we also sequenced a subset of positive tumors. MATERIALS AND METHODS: More than 3,000 tumors from more than 120 different tumor categories were analyzed by immunohistochemistry in a tissue microarray format. Seven commercially available anti-KIT antibodies were initially evaluated. The antibody A4502 (DAKO) was selected for analysis because of a high frequency of positivity in GIST and low staining background in other tissues. To determine the frequency of KIT mutations in various tumor types, the exons 2, 8, 9, 11, 13, and 17 (where mutations previously were reported) were sequenced in 36 tumors with strong KIT expression. RESULTS: KIT positivity was detected in 28 of 28 GISTs (100%), 42 of 50 seminomas (84%), 34 of 52 adenoid-cystic carcinomas (65%), 14 of 39 malignant melanomas (35%), and eight of 47 large-cell carcinomas of the lung (17%), as well as in 47 additional tumor types. KIT mutations were found in six of 12 analyzed GISTs, but only in one of 24 other tumors. CONCLUSION: The results suggest that KIT expression occurs infrequently in most tumor types and that, with the exception of GISTs, KIT gene mutations are rare in immunohistochemically KIT-positive tumors.

Antineoplastic Agents↗
PubMed2004

Frequent EpCam protein expression in human carcinomas.

Expression of the transmembrane glycoprotein EpCam (epithelial cellular adhesion molecule) occurs in normal epithelium of different organs and was described in carcinomas of various sites. Specific anti-EpCam therapies are now being used in clinical trials. Thus, it is of interest to know which tumor types express or overexpress this protein, and in what frequency. We therefore analyzed EpCam expression by immunohistochemistry on a tissue microarray containing 3900 tissue samples of 134 different histological tumor types and subtypes. EpCam expression was detected in 98 of 131 tumor categories. At least a weak EpCam expression in >10% of tumors was observed in 87 of 131 different tumor categories. Adenocarcinomas of the colon (81%) and pancreas (78%), as well as hormone-refractory adenocarcinomas of the prostate (71%), were identified as particularly promising therapy targets with a high fraction of strongly positive tumors. Most soft-tissue tumors and all lymphomas were EpCam negative. It is concluded that anti-EpCam therapies, if proven to be successful, will have broad applications in a wide variety of carcinomas.

Adenocarcinoma↗
PubMed2004

High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer.

Previous studies in small series of patients with invasive breast cancer suggested a prognostic value of Ep-CAM overexpression in primary tumor tissue. To corroborate these findings, we performed a retrospective analysis of Ep-CAM expression using a tissue microarray containing tissue specimens from a large patient set. Ep-CAM expression was evaluated by immunohistochemistry in breast cancer tissue from 1715 patients with documented raw survival data. High level Ep-CAM expression (overexpression) was found in 41.7% of tumor samples, low level expression was found in 48.0% and no expression in 10.3% of tumor samples. Ep-CAM expression predicted poor overall survival in this patient cohort (p < 0.0001). Overall survival decreased significantly with increasing Ep-CAM expression. However, in this patient sample Ep-CAM expression was not an independent prognostic marker by multivariate analysis. Subgroup analysis revealed that Ep-CAM expression was a prognostic marker in node-positive (p < 0.0001) but not in node-negative (p = 0.58) breast cancer patients. Intriguingly, Ep-CAM expression was predictive for a dismal prognosis in patients receiving adjuvant cytotoxic (p = 0.03) or hormonal therapy (p < 0.0001) but not in untreated patients (p = 0.41). In summary, this study provides strong evidence that expression of Ep-CAM is a powerful marker of poor prognosis in node-positive invasive breast carcinoma and a potential predictive marker of sensitivity to adjuvant hormonal and/or cytotoxic treatment modalities.

Aged↗
PubMed2004

Burkitt's lymphoma of the stomach: a case report with molecular cytogenetic analysis.

In 1974, a 28-year-old man presented with a 12 cm sized ulcerated tumor involving the middle third of the stomach, which was originally diagnosed as "lymphosarcoma". Clinical recurrence of the lymphoma resulted in rapidly progressing disease and the patient died 4 months after initial diagnosis. Retrospective work-up of the 29-year-old tumor blocks revealed the typical histologic appearance and phenotype (CD20, CD10, BCL-6 positive) of Burkitt's lymphoma (BL) with a proliferation rate of 95%. By fluorescence in situ hybridization (FISH). the tumor cells were shown to harbor an IGH-MYC fusion indicating the presence of the hallmark Burkitt-translocation t(8;14)(q24;q32). Considering the typical clinical features of BL requiring appropriate treatment regimes the case presented here highlights the importance of modern histopathologic and molecular cytogenetic techniques for the proper classification of such rare lymphomas presenting at atypical sites.

Adult↗
PubMed2004

Is higher income and educational status associated with poorer outcome in patients with Hodgkin's disease?

OBJECTIVES: The aim of the study was to determine the impact of socioeconomic status on relapse-free survival (RFS) in patients with Hodgkin's disease. METHODS: A number of factors were analyzed for their impact on relapse-free and overall survival in Hodgkin's disease using Cox regression. These factors included socioeconomic status (as defined by education and income), different treatment modalities and established clinical risk factors [e.g. age at diagnosis, stage of disease, involvement of three or more lymph nodes, presence or absence of a large mediastinal mass, E stages or elevation of erythrocyte sedimentation rate (ESR)]. The study used an initial sample of 126 patients recruited between 1969 and 1995 and a larger sample of 218 patients (recruited until 2002). Clinical data on disease and treatment characteristics were collected from medical records. RESULTS: In a univariate analysis, the following parameters had impact on RFS: treatment modality (combined treatment resulted in an improved RFS compared with patients treated with chemo- or radiotherapy alone), educational status and income. The 5- and 10-yr relapse-free survival rates were found to increase with decreasing educational level and decreasing average income per month. These results were significant in the initial and total samples and were also significant using multivariate analysis (hazard ratio for highest vs. lowest education group: 5.88; 95% confidence interval 1.87-18.52; for highest vs. lowest income group: 4.36; 95% confidence interval 1.35-14.05). CONCLUSION: Hodgkin's disease appears to be a striking exception from the usual positive correlation between high socioeconomic status and favorable treatment outcome in patients suffering from tumor. It is suggested that future studies on tumor genetics and biology and more detailed analysis of further socioeconomic parameters may be useful in clarifying this observation.

Adult↗
PubMed2003

Sequence analysis and high-throughput immunohistochemical profiling of KIT (CD 117) expression in uveal melanoma using tissue microarrays.

We aimed to immunohistochemically examine the expression of KIT (CD 117) in human posterior uveal melanoma and to analyze KIT-positive tumors for gene mutations. Brought into a tissue microarray (TMA) format were 101 formalin-fixed, paraffin-embedded posterior uveal melanomas. Immunohistochemistry was performed using the polyclonal anti-CD117 antibody from Dako (A4502). In ten selected KIT-positive tumors, exons 2, 8, 9, 11, 13 and 17 were sequenced. Of the 101 cases, 89 (88%) could be evaluated on the TMAs. Immunohistochemistry for CD 117 was weakly positive in 5 cases (6%), moderately positive in 10 cases (12%) and strongly positive in 57 cases (69%). No KIT mutations were detected in the analyzed exons. In conclusion, human posterior uveal melanoma frequently expresses CD117 at high levels. Although KIT mutations could not be found, it appears justified to investigate the utility of imatinib mesylate in the treatment of these patients.

Adult↗