Philipp Ströbel

Georg-August-Universität Göttingen, Göttingen, Lower Saxony, Germany

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Publications (182)732.54 Total impact

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    ABSTRACT: Lymphovascular invasion (LVI) represents a surrogate marker for micrometastatic urothelial carcinoma of the bladder (UCB).
    Der Urologe. Ausg. A. 11/2014;
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    ABSTRACT: Plakophilins 1 and 3 (PKP1/3) are members of the arm-repeat family of catenin proteins and serve as structural components of desmosomes important for cell-cell-adhesion. In addition, PKP1/3 occur as soluble proteins outside of desmosomes, yet their role in the cytoplasm is not known so far. We found that cytoplasmic PKP1/3 were co-precipitated with the RNA-binding proteins FXR1, G3BP, PABPC1 and UPF1 and these PKP1/3 complexes also comprised desmoplakin and PKP2 mRNAs. Moreover, we showed that the interaction of PKP1/3 with G3BP, PABPC1 and UPF1 but not with FXR1 was RNase-sensitive. To address the cytoplasmic function of PKP1/3 we performed gain and loss of function studies. Both PKP1 and PKP3 knock down cell lines showed reduced protein and mRNA levels for desmoplakin and PKP2. Whereas global rates of translation were unaffected, desmoplakin and PKP2 mRNA were destabilized. Furthermore, binding of PKP1/3 to FXR1 was RNA-independent, and both PKP3 and FXR1 stabilized PKP2 mRNA. Our results demonstrate that cytoplasmic PKP1/3 are components of mRNA ribonucleoprotein particles and act as posttranscriptional regulators of gene expression.
    Molecular and cellular biology. 09/2014;
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    ABSTRACT: Pancreatic undifferentiated carcinoma is a heterogeneous group of neoplasms, including pleomorphic giant cell, sarcomatoid, round cell, and rhabdoid carcinomas, the molecular profiles of which have so far been insufficiently characterized. We studied 14 undifferentiated carcinomas with prominent rhabdoid cells, occurring as advanced tumors in seven females and seven males aged 44-96 years (mean: 65 years). Histologically, 10 tumors qualified as pleomorphic giant cell and 4 as monomorphic anaplastic carcinomas. A glandular component, either in the primary or in the metastases, was seen in 5 out of 14 tumors (4 out of 10 pleomorphic giant cell and 1 out of 4 monomorphic anaplastic subtypes, respectively). Osteoclast-like giant cells were absent. Immunohistochemistry revealed coexpression of cytokeratin and vimentin, and loss of membranous β-catenin and E-cadherin staining in the majority of cases. Nuclear SMARCB1 (INI1) expression was lost in 4 out of 14 cases (28%), representing all 4 tumors of the monomorphic anaplastic subtype. FISH and mutation testing of KRAS revealed KRAS amplification in 5 out of 13 (38%) and exon 2 mutations in 6 out of 11 (54%) successfully analyzed cases. A strong correlation was found between KRAS alterations (mutation and/or copy number changes) and intact SMARCB1 expression (7 out of 8; 87%). On the other hand, loss of SMARCB1 expression correlated with the absence of KRAS alterations (3 out of 5 cases; 60%). The results suggest that rhabdoid phenotype in pancreatic undifferentiated rhabdoid carcinomas has a heterogeneous genetic background. SMARCB1 loss is restricted to the anaplastic monomorphic subtype and correlates with the absence of KRAS alterations, whereas the pleomorphic giant cell subtype is characterized by KRAS alterations and intact SMARCB1 expression. Recognition and appropriate subtyping of these rare variants might become necessary for future therapeutic strategies.Modern Pathology advance online publication, 8 August 2014; doi:10.1038/modpathol.2014.100.
    Modern Pathology 08/2014; · 5.25 Impact Factor
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    ABSTRACT: AimsThe current WHO classification of thymic epithelial neoplasms describes types A and AB thymomas as behaving “like benign neoplasms”. However, recent published data suggests that rare cases may exhibit more aggressive behavior. The aim of this study is to assess the frequency of atypical cases, together with determining whether atypia is associated with more advanced disease.Methods and Results121 thymomas (type A (n=68); type AB (n=53)) were retrospectively reviewed for “atypical” features (nuclear pleomorphism, mitotic activity and necrosis). Logistic regression was utilised to ascertain the association with increasing Masoaka-Koga stage. Where available, follow-up data were also reviewed. There were 72 stage I, 42 stage II, 5 stage III and 2 stage IV tumours. Only the presence of necrosis showed a significant association with increased stage on univariate and multivariate analysis. Nuclear atypia and increased mitotic activity were not associated with increasing stage of disease.Conclusion Our data support the concept of there being a more aggressive atypical variant of both type A and AB thymoma and suggests that the presence of necrosis could be used to predict aggressive behaviour.This article is protected by copyright. All rights reserved.
    Histopathology 08/2014; · 2.86 Impact Factor
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    ABSTRACT: CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid.
    Diagnostic pathology. 06/2014; 9(1):116.
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    ABSTRACT: BACKGROUND: CASTLE (Carcinoma showing thymus-like elements) is a rare malignant neoplasm of the thyroid resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus with different biological behaviour and a better prognosis than anaplastic carcinoma of the thyroid. METHODS: We retrospectively investigated 6 cases of this very rare neoplasm in order to investigate the mutational status of KRAS, EGFR, PDGFR-α and KIT, as well as the immunohistochemical expression pattern of CD117, EGFR and COX-2, and possibly find new therapeutic targets. RESULTS: Diagnosis was confirmed by a moderate to strong expression of CD5, CD117 and CK5/6, whereas thyroglobulin, calcitonin and TTF-1 were negative in all cases. Tumors were also positive for COX-2 and in nearly all cases for EGFR. In four cases single nucleotide polymorphisms (SNPs) could be detected in exon 12 of the PDGFR-α gene (rs1873778), in three cases SNPs were found in exon 20 of the EGFR gene (rs1050171). No mutations were found in the KIT and KRAS gene. CONCLUSIONS: All tumors showed a COX-2 expression as well as an EGFR expression except for one case and a wild-type KRAS status. No activating mutations in the EGFR, KIT and PDGFR-α gene could be detected. Our data may indicate a potential for targeted therapies, but if these therapeutic strategies are of benefit in CASTLE remains to be determined. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 06/2014; Diagn Pathol(9):116. · 2.41 Impact Factor
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    ABSTRACT: Due to its profound therapeutic consequences, the distinction between thymoma and T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in mediastinal pathology. One essential diagnostic criterion favouring thymoma is the demonstration of increased numbers of keratin-positive epithelial cells by immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells could lead to detrimental misdiagnoses. We here describe a series of 14 thymic epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of expression of one or more keratins. Cases were analysed for expression of various keratins and desmosomal proteins by immunohistochemistry and immunofluorescence and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged in a multitissue histological array. All 14 cases showed highly reduced expression of at least one keratin, three cases were completely negative for all keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63. Expression of desmosomal proteins was preserved, suggesting intact cell contact structures. Loss of expression of broad-spectrum-keratins and K19 was observed in 3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A proportion of keratin-depleted thymomas contained giant cells, reminiscent of thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an important diagnostic pitfall in the differential diagnosis with T-lymphoblastic lymphoma and can be expected in 5 % of cases. A panel of epithelial markers including p63 is warranted to ensure correct diagnosis of keratin-negative mediastinal tumours.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 06/2014; · 2.68 Impact Factor
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    ABSTRACT: Carney triad (CT) is a rare condition with synchronous or metachronous occurrence of gastrointestinal stromal tumors (GISTs), paragangliomas (PGLs) and pulmonary chondromas in a patient. In contrast to Carney-Stratakis Syndrome (CSS) and familial PGL syndromes, no germline or somatic mutations in the succinate dehydrogenase complex (SDH) subunits A, B, C or D have been found in most tumors and/or patients with CT. Nonetheless, the tumors arising among patients with CT, CSS or familial PGL share a similar morphology with loss of the SDHB subunit on the protein level. For the current study we employed massive parallel bisulfite sequencing to evaluate DNA methylation patterns in CpG islands in proximity to the gene loci of all four SDH subunits. For the first time, we report on a recurrent aberrant dense DNA methylation at the gene locus of the SDH subunit C (SDHC) in tumors of patients with CT, which was not present in tumors of patients with CSS or PGL, or in sporadic GISTs with KIT mutations. This DNA methylation pattern was correlated to a reduced mRNA expression of SDHC, and concurrent loss of the SDHC subunit on the protein level. Collectively, these data suggest epigenetic inactivation of the SDHC gene locus with functional impairment of the succinate dehydrogenase complex as a plausible alternate mechanism of tumorigenesis in CT.
    Endocrine Related Cancer 05/2014; · 5.26 Impact Factor
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    ABSTRACT: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2014; 9(5):596-611. · 4.55 Impact Factor
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    ABSTRACT: Thymic neuroendocrine tumors (TNET) are rare primary epithelial neoplasms of the thymus. This study aimed to determine clinically relevant parameters for their classification and for therapeutic decisions. We performed a comprehensive histological, clinical, and genetic study of 73 TNET cases (13 thymic typical carcinoids [TTC], 40 thymic atypical carcinoids [TAC], and 20 high-grade neuroendocrine carcinomas [HGNEC] of the thymus), contributed by multiple institutions. The mean number of chromosomal imbalances per tumor was 0.8 in TTC (31% aberrant cases) versus 1.1 in TAC (44% aberrant cases) versus 4.7 in HGNEC (75% aberrant cases). Gains of 8q24 (MYC gene locus) were the most frequent alteration and one of the overlapping features between carcinoids and HGNEC. The 5-year survival rates for TTC, TAC, and HGNEC were 100, 60, and 30%. The 10-year survival rates for TTC and TAC were 50 and 30% (P = 0.002). Predictive mitotic cut-off values for TTC versus TAC were 2.5 per 10 high-power fields (HPF; indicating a higher death rate, P = 0.062) and 15 per 10 HPF (indicating higher risk of recurrence, P = 0.036) for separating HGNEC from TAC. We conclude that the current histopathologic classifications of TNET reflect tumor biology and provide important information for therapeutic management. © 2014 Wiley Periodicals, Inc.
    Genes Chromosomes and Cancer 04/2014; · 3.55 Impact Factor
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    ABSTRACT: A lack of reliably informative biomarkers to distinguish indolent and lethal prostate cancer (PCa) is one reason this disease is overtreated. miR-221 has been suggested as a biomarker in high risk PCa, but there is insufficient evidence of its potential utility. Here we report that miR-221 is an independent predictor for cancer-related death, extending and validating earlier findings. By mechanistic investigations we showed that miR-221 regulates cell growth, invasiveness and apoptosis in PCa at least partially via STAT1/STAT3 mediated activation of the JAK/STAT signalling pathway. miR-221 directly inhibits the expression of SOCS3 and IRF2, two oncogenes that negatively regulate this signalling pathway. miR-221 expression sensitized PCa cells for IFN-γ mediated growth inhibition. Our findings suggest that miR-221 offers a novel prognostic biomarker and therapeutic target in high-risk PCa.
    Cancer Research 03/2014; · 9.28 Impact Factor
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    ABSTRACT: SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates.
    Nanoscale 01/2014; · 6.73 Impact Factor
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    ABSTRACT: To evaluate the expression of multiple lymph-specific markers and to test its association with histopathological characteristics and clinical outcomes in patients with urothelial carcinoma of the bladder (UCB) treated by radical cystectomy (RC). Vascular endothelial growth factor-C and -D (VEGF-C/-D), its receptor VEGF receptor-3 (VEGFR-3), and chemokine receptor type 7 (CCR7) expressions were assessed by immunohistochemistry in RC specimens of 119 patients. Semiquantitative analyses of marker expressions were correlated with clinical and pathological characteristics. Univariable and multivariable analyses were performed to identify predictors of disease-specific survival (DSS) and recurrence free survival (RFS). VEGF-C, VEGF-D, VEGFR-3, and CCR7 were overexpressed in 37.8%, 26.2%, 50.4%, and 23.5% of UCB samples, respectively. VEGF-D overexpression was significantly associated with a positive lymph node status (pN+). On univariable analysis, a higher pT stage, pN+, the presence of lymphovascular invasion (LVI) and vascular invasion (VI) (all P<0.001), and overexpressions of VEGF-D (P = 0.049) and VEGFR-3 (P = 0.032) were significantly associated with reduced DSS. On multivariable analysis, pT stage (P = 0.002) and pN+status (P = 0.009) were identified as independent predictors of reduced DSS. In a subgroup of patients without lymph node metastasis (pN0; n = 75), pT stage (P = 0.043) and VEGFR-3 overexpression (P = 0.008) were independent predictors of reduced DSS. Lymph-specific markers are frequently overexpressed in UCB. VEGF-D overexpression is associated with the presence of lymphatic metastasis. In patients without lymph node metastasis at the time of RC, an assessment of VEGFR-3 expression may improve the identification of high-risk patients. These findings require prospective validation to determine the potential benefit of more aggressive adjuvant treatment.
    Urologic Oncology 01/2014; 32(1):54.e9-54.e17. · 3.65 Impact Factor
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    ABSTRACT: Late-onset myasthenia gravis (LOMG) has become the largest MG subgroup, but the underlying pathogenetic mechanisms remain mysterious. Among the few etiological clues are the almost unique serologic parallels between LOMG and thymoma-associated MG (TAMG), notably autoantibodies against acetylcholine receptors, titin, ryanodine receptor, type I interferons or IL-12. This is why we checked LOMG patients for two further peculiar features of TAMG - its associations with the CTLA4(high/gain-of-function) +49A/A genotype and with increased thymic export of naïve T cells into the blood, possibly after defective negative selection in AIRE-deficient thymomas. We analyzed genomic DNA from 116 Caucasian LOMG patients for CTLA4 alleles by PCR/restriction fragment length polymorphism, and blood mononuclear cells for recent thymic emigrants by quantitative PCR for T cell receptor excision circles. In sharp contrast with TAMG, we now find that: i) CTLA4(low) +49G(+) genotypes were more frequent (p = 0.0029) among the 69 LOMG patients with age at onset ≥60 years compared with 172 healthy controls; ii) thymic export of naïve T cells from the non-neoplastic thymuses of 36 LOMG patients was lower (p = 0.0058) at diagnosis than in 77 age-matched controls. These new findings are important because they suggest distinct initiating mechanisms in TAMG and LOMG and hint at aberrant immuno-regulation in the periphery in LOMG. We therefore propose alternate defects in central thymic or peripheral tolerance induction in TAMG and LOMG converging on similar final outcomes. In addition, our data support a 60-year-threshold for onset of 'true LOMG' and an LOMG/early-onset MG overlapping group of patients between 40 and 60.
    Journal of Autoimmunity 12/2013; · 8.15 Impact Factor
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    ABSTRACT: Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 12/2013; · 2.68 Impact Factor
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    ABSTRACT: Diffuse neurofibromatosis/ ganglioneuromatosis, solitary/ plexiform neurofibroma, periampullary carcinoids and gastrointestinal stromal tumour (GIST) are the main gastrointestinal manifestations of neurofibromatosis type 1 (NF-1, von Recklinghausen disease). Inflammatory (juvenile-like) polyps still have not been recognized as specific gastrointestinal manifestations of NF-1. We describe 4 males aged 23-65 years with NF-1 and inflammatory (juvenile-like) gastrointestinal polyps and review the literature for similar cases. Two patients had single polyps (sigmoid colon and antrum, respectively), 1 had two polyps (left colon) and 1 had 3 polyps (distal esophagus and colon). Histology revealed variable appearance ranging from juvenile-like to granulation tissue-rich predominantly inflammatory and hyperplastic. Three lesions showed obliterative vasculopathic changes. None had neurofibromatous or ganglioneuromatous polyps. Review of the literature disclosed 11 similar cases. Most patients presented with severe gastrointestinal symptoms and/or anemia. NF-1-associated inflammatory polyps probably represent specific GI manifestations of this disorder and should be thought of, particularly in patients with GI symptoms. They should be distinguished from inflammatory fibroid polyps and from juvenile-like changes associated with ganglioneuroma/tosis and neurofibroma/tosis. Their etiology remains obscure but different mechanisms including NF-1 inactivation, NF-1-associated vasculopathy and localized mucosal prolapse/damage caused by motility disorders might be involved. This article is protected by copyright. All rights reserved.
    Histopathology 11/2013; · 2.86 Impact Factor
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    ABSTRACT: Myoglobin is a member of the hemoprotein superfamily, which additionally includes hemoglobin, neuroglobin and cytoglobin. Cytoplasmic localized myoglobin functions as a radical scavenger and prevents hypoxia. Besides muscle tissue MB expression could also be observed in other tissues as well as in different types of cancer. For the correlation between the expression of myoglobin, hypoxia-inducible-factor-1α, and capillary density tissue of 86 different renal cell carcinomas were immunohistochemically stained with myoglobin-specific and hypoxia-inducible-factor-1α-specific antibodies as well as with CD31 antibody. Four different renal carcinoma cell lines were cultivated under hypoxic conditions and the expression of myoglobin and hypoxia-inducible-factor-1α was evaluated by real-time PCR and western blot. Renal cell carcinoma including clear cell, papillary, and chromophobe subtypes expressed myoglobin with an inverse relationship to capillary density being highly significant for clear cell renal cell carcinoma. For hypoxia-inducible-factor-1α a significant correlation with capillary density could also be observed in clear cell RCC. In renal cell carcinoma cell lines hypoxia induced a significant increase of myoglobin expression up to 62 fold, whereas hypoxia-inducible-factor-1α only increased up to 5 fold. The PCR results of myoglobin expression could be confirmed by western blot. Myoglobin seems to be a sensitive marker for hypovascularized tumor entities especially during the early phase of hypoxia. Such neoplasias may benefit from an antiangiogenic therapy.
    Experimental and Molecular Pathology 09/2013; · 2.13 Impact Factor
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    ABSTRACT: Morphological complexity hampers the histological classification of thymomas. Our aim was to determine whether the use of novel differentiation and maturation markers of cortical and medullary thymic epithelial cells (cTECs and mTECs) might provide an approach to understanding the underlying biology of these tumours. Fifty-seven thymomas were studied by immunohistochemistry. The cortical markers used were B5T, PRSS16, and cathepsin V. The medullary markers used were CD40, claudin-4, AIRE, and desmin. Involucrin and cytokeratin 10 were used to study terminal mTEC maturation. Irrespective of histological subtype, most thymomas contained distinct areas with cortical and medullary differentiation. Type B1, type B2 and type AB thymomas showed marked bi-lineage differentiation, with lack of terminal mTEC maturation in type AB. Type AB thymomas were unique in showing areas where cells with either cortical or medullary differentiation were intimately 'mixed' at the single-cell level. Type B3 and type A thymomas showed only abortive lineage differentiation and maturation. Thymomas show highly characteristic patterns of bi-lineage TEC differentiation that reflect the histological subtypes recognized by the WHO classification. We hypothesize that thymomas arise from thymic precursor cells with different cortical and/or medullary maturation defects.
    Histopathology 09/2013; · 2.86 Impact Factor
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    ABSTRACT: Rhabdoid morphology resembling that of the aggressive paediatric rhabdoid tumours occurs in various malignancies usually lacking characteristic SMARCB1 (INI1) loss. Little is known about the clinicopathological and molecular characteristics of the rhabdoid phenotype in gastrointestinal stromal tumours (GISTs). Six gastric rhabdoid GISTs were examined by immunohistochemistry, KIT and platelet-derived growth factor receptor-α gene (PDGFRA) mutation analysis, and comparative genomic hybridization (CGH). All tumours expressed KIT, PDGFRA, DOG-1, and SMARCB1 (two of six with a mosaic pattern). Five of six tumours harboured PDGFRA mutations (D842V in four; N659K in one), and one case was wild type for KIT/PDGFRA and succinate dehydrogenase (SDH) A-negative and SDHB-negative by immunohistochemistry. CGH revealed aberrations typical of GISTs (-1p, -14, and -22q in three, five, and three cases, respectively), with a mean of 1.7 aberrations in the epithelioid component and 2.7 in the rhabdoid component. None showed progression (mean follow-up of 25 months). Rhabdoid gastric GISTs are associated with epithelioid morphology and PDGFRA mutations. They harbour CGH aberrations that are typical of ordinary GISTs in both tumour components. The presence of additional genetic alterations in the rhabdoid areas indicates evolution from the epithelioid components, and possible genetic and biological progression. On the basis of our series and previous reports, rhabdoid morphology in GISTs presumably does not imply aggressiveness.
    Histopathology 08/2013; · 2.86 Impact Factor
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    ABSTRACT: Somatic-type malignancy (STM), defined as any sarcoma, carcinoma, leukemia or lymphoma developing in a germ cell tumor, occurs in approximately 2 % of all germ cell tumors. Neuroendocrine carcinoma developing in a mediastinal germ cell tumor has not been previously reported. We here describe a 22-year-old man who underwent resection of a 11-cm mediastinal teratoma which consisted of components of all three germ cell layers with prominent foci of fetal-like liver tissue. The liver areas were surrounded by primitive neuroendocrine structures with ductal and solid growth pattern with a high proliferation rate. We diagnosed an immature mediastinal teratoma with STM, specifically neuroendocrine carcinoma arising in a background of immature liver tissue. Comparative genomic hybridization of dissected tumor tissue revealed chromosomal gains at 12 in the teratoma and neuroendocrine carcinoma component. In summary, clinicians and pathologists should be aware of neuroendocrine carcinoma as a rare type of STM complicating mediastinal germ cell tumors.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2013; · 2.68 Impact Factor

Publication Stats

3k Citations
732.54 Total Impact Points


  • 2014
    • Georg-August-Universität Göttingen
      • Faculty of Medicine
      Göttingen, Lower Saxony, Germany
    • Universitätsklinikum Freiburg
      • Institute of Pathology
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2013
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2010–2013
    • German Cancer Research Center
      • Division of Vascular Oncology and Metastasis
      Heidelberg, Baden-Wuerttemberg, Germany
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
    • University of Münster
      • Department of Urology
      Muenster, North Rhine-Westphalia, Germany
  • 1999–2013
    • University of Wuerzburg
      • • Department of Urology and Paediatric Urology
      • • Institute of Physical and Theoretical Chemistry
      • • Institute for Pathology
      • • Department of Neurology
      Würzburg, Bavaria, Germany
  • 2012
    • Universität Regensburg
      • Department of Neurology
      Ratisbon, Bavaria, Germany
    • Universität Osnabrück
      Osnabrück, Lower Saxony, Germany
  • 2009–2012
    • Universität Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2007–2011
    • Universität Heidelberg
      • • Institute of Pathology (Mannheim)
      • • Department of Urology
      • • II. Medical Clinic
      Heidelberg, Baden-Wuerttemberg, Germany
  • 2009–2010
    • Universitätsmedizin Mannheim
      Mannheim, Baden-Württemberg, Germany
  • 2008
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 2004
    • Central Military Hospital Koblenz
      Coblenz, Rheinland-Pfalz, Germany