D Katenkamp

Friedrich Schiller University Jena, Jena, Thuringia, Germany

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Publications (305)335.1 Total impact

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    ABSTRACT: Pleomorphic undifferentiated sarcomas (formerly known as malignant fibrous histiocytomas) are recognised by the actual WHO classification as an undifferentiated, unclassifiable category of pleomorphic sarcomas which show no definable line of differentiation and are still a diagnosis of exclusion. Therefore, diagnostic, prognostic and therapeutic options of these tumours are urgently needed. Three hundred and twenty-seven spindle cell tumours of a German consultation and reference centre of soft tissue tumours consisting of 200 undifferentiated pleomorphic sarcomas (UPS), 45 low-grade sarcomas (10 low-grade fibromyxoid sarcomas, 32 low-grade myofibroblastic sarcomas and three myxoinflammatory fibroblastic sarcomas) and 82 tumours of the fasciitis family were revisited. The specimens were analysed immunohistochemically with distinct markers including tyrosine kinases and expression correlated with clinicopathological parameters. Additionally, mutational analysis was performed on specimens with high expression of EGFR and FGFR3. At the protein level high IGF2 expression was observed in 86 %, FGFR3 (69 %), PDGFRA (62 %), PDGFRB (39 %), FGFR1 (8 %), EGFR (5 %), KDR/VEGFR2 (3 %), ALK (0 %) and high Ki67 (63 %) in UPS. High expressions of IGF2 and FGFR3 are significantly correlated with a higher grading (p = 0.023 and p = 0.016, respectively) and a high Ki67 index (p = 0.017 and p = 0.001, respectively). No mutations were found in the hot spots of tumour specimens with a high expression of EGFR gene (exons 18-21) and FGFR3 gene (exons 7, 10 and 15). High expressions of IGF2 and FGFR3 are significantly associated with tumour progression, grading and Ki67 and might classify a subgroup of undifferentiated pleomorphic sarcoma. These markers might guide targeted therapies in these neoplasms.
    No preview · Article · May 2014 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Alveolar soft part sarcoma (ASPS) is a distinct type of soft tissue sarcoma holding a specific ASPL-TFE3 fusion transcript. Curative therapy is based on surgical removal, whereas lately, antiangiogenic targeted therapy regimens have proven effective. In ASPS, analysis of small series additionally display mTOR (mammalian target of rapamycin) pathway activity, thus making mTOR a possible additive target in ASPS, because it is in other tumor entities. Therefore, we systematically evaluated mTOR pathway activity in a large series of ASPS in comparison with soft tissue sarcomas of other differentiation (non-ASPS). Upstream and downstream factors of mTOR signaling and ancillary targets were analyzed in 103 cases (22 ASPS, 81 non-ASPS) by immunohistochemistry mostly using phospho-specific antibodies. TFE3 (transcription factor for immunoglobulin heavy-chain enhancer 3) translocation status was determined by FISH and RT-PCR. All ASPS were positive in TFE3 break-apart FISH and exhibited specific fusion products when RNA was available (type 1: 9x, type 2: 11x), whereas TFE3-immunoreactive non-ASPS did not. In ASPS, TFE3-, cMET-, pAKT T308- (all P < .0001), pp70S6K- (P = .002), and p4EBP1 (P = .087) expression levels were elevated, whereas pAKT S473 was decreased (P < .0001). In addition, ASPS exhibited higher TFE3-, cMET-, pAKT T308-, and pp70S6K- expression levels compared with TFE3-immunopositive non-ASPS sarcomas (all P < .001). We demonstrate elevated mTOR complex 1 (mTORC1) activity in ASPS independent of mTOR complex 2 (mTORC2) activation. mTORC1 activity seems to be related to the existence of ASPL-TFE3 fusion transcripts because TFE3-immunoreactive non-ASPS without ASPL-TFE3 fusion transcripts exhibit significantly lower mTORC1 activation status. Small molecule-based targeting of mTOR might therefore represent a potential mechanism in ASPS alone or in combination with contemporary upstream approaches.
    No preview · Article · Jul 2013 · Human pathology
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    ABSTRACT: The aim of this study was to characterize the subgroups of solitary fibrous tumor (SFT) and to investigate the expression of different biomarkers including CD34 and IGF2 in malignant transformation. Two hundred and ninety-four (294) SFTs from a single German consultation center of soft tissue tumors were categorized into the new proposal of SFT designation. We found the fibrous variant in 223 (75.9%), the cellular variant in 65 (22.1%), the fat forming variant in 4 (1.4%), and the giant cell-rich variant in 2 (0.6%) cases. Anatomical location, size, mitotic index, necrosis, cellularity, collagenous ropes, and growth pattern of the vessels were recorded. Criteria of malignancy were found in 68 (23%) tumors. Expression of IGF2, IGF1R, CD34, BCL2, CD99, SMA, S100, PanCK, and Ki67 was analyzed immunohistochemically. Low expression of CD34 and high expression of IGF2 were significantly associated with malignant transformation and the metastatic rate. Moreover the presence of necrosis showed the most significant p-value (p < 0.004). Of all SFTs, the fibrous variant is the most common, followed by the cellular variant. The fat-forming and giant cell-rich variants are very rare. Low expression of CD34 and high expression of IGF2 are significantly associated with malignant transformation, and might be an interesting target of individualized therapy
    No preview · Article · Jan 2013 · Pathology - Research and Practice
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    ABSTRACT: Clear cell sarcoma is a rare and malignant soft tissue tumor that shows phenotypic and immunohistochemical overlap with cutaneous malignant melanoma; identification of biomarkers that differentiate clear cell sarcoma from malignant melanoma is therefore needed. In this study, we performed mutation analysis of BRAF and NRAS, investigated the EWSR1 gene rearrangement and evaluated the protein expression of insulin-like growth factor 2 and insulin-like growth factor 1R in 31 cases of malignant melanoma and 16 cases of clear cell sarcoma. By direct sequencing and high-resolution melting analysis, we identified BRAF and NRAS mutations in 51.6% and 12.9% of malignant melanoma cases, respectively, while none of clear cell sarcoma harbored BRAF or NRAS mutations. Fluorescence in situ hybridization showed that 78.6% of clear cell sarcoma exhibited the t(12;22)(q13;q12) translocation. The presence of type 1, 2, and 3 EWSR1/ATF1 fusion gene transcripts was confirmed by reverse transcriptase polymerase chain reaction analysis, but type 4 and EWSR1/CREB1 fusion gene transcripts were not found. No fusion transcript could be detected in any of the malignant melanoma cases. Additionally, immunohistochemistry showed that the majority of clear cell sarcoma and malignant melanoma had insulin-like growth factor 2 and insulin-like growth factor receptor 1 expression; however the expression of insulin-like growth factor 1R was significantly higher in clear cell sarcoma compared to melanoma (p = .006). Our results suggest that the combination of BRAF and NRAS mutation analysis with fusion gene detection contributes to diagnosis of malignant melanoma and clear cell sarcoma, and that insulin-like growth factor 1R might be a novel target for the treatment of these two malignancies.
    No preview · Article · Mar 2012 · Human pathology
  • Kathrin Nitsche · Bianka Günther · Detlef Katenkamp · Iver Petersen
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    ABSTRACT: The Jena Soft Tissue Tumor Reference Center is the major German pathology institute for consultation of malignant mesenchymal tumors. Here, we present the clinicopathological data on thoracic soft tissue tumors of a two-year period. The tumors were analyzed according to their localization, type (soft tissue tumor, other tumor type, non-neoplastic lesion) and biological behavior. The frequency of the defined soft tissue tumor entities were considered after categorizing the cases according to the WHO Classification of Tumors. Gender and age were also assessed. In total, 1,071 cases of thoracic tumors were recorded within the 2 years. The majority were non-epithelial lesions (75.3%, n = 806/1,071), of which 68.1% (n = 549/806) were malignant or intermediate malignant. 107 non-epithelial lesions involved the lung and 37 the pleura. By far the most common lung and pleural tumors were undifferentiated sarcomas. In the lung, other frequent entities were solitary fibrous tumors, synovial sarcomas and leiomyosarcomas. We also recorded 13 non-epithelial tumors of the heart and 66 tumors of the breast with angiosarcomas being the most frequent subtype. There was a female predominance for vascular neoplasms, while men prevailed for adipocytic tumors. Our study provides information about the frequency, distribution, age and gender of patients with thoracic soft tissue tumors including several rare entities. Thus, it may help in the differential diagnosis of these neoplasms. In addition, we present a model highlighting the potential progression of lung carcinoma to undifferentiated sarcoma via the process of epithelial-mesenchymal transition.
    No preview · Article · Dec 2011 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor whose pathological diagnosis can be difficult. In the literature two cases of EHE were found to harbor a balanced t(1;3)(p36.3;q25) translocation, suggesting a characteristic chromosomal rearrangement as cause for the development of EHE. In this study, 14 cases of EHE were investigated by interphase fluorescence in situ hybridization (FISH) directed against the translocation breakpoint 1p36.3. A subset of cases was also analyzed by comparative genomic hybridization (CGH) and image cytometry. Five out of eight cases that could be successfully analyzed by FISH harbored a chromosomal break in the 1p36.3 region. The break-apart signals were present in diploid nuclei, and less frequently also in tetraploid nuclei. In the latter, the chromosomal break was present twice, suggesting that polyploidy occurred after the chromosomal alteration. DNA cytometry confirmed that tetraploid cells were present in most examined cases with one case indicating almost equal amounts of diploid and tetraploid tumor cells. CGH revealed single chromosomal imbalances of unclear significance. We could confirm that EHE may harbor a recurrent mutation involving the 1p36.3 chromosomal region thus supporting the notion that the t(1;3)(p36.3;q25) translocation is a relevant genetic finding in this tumor entity.
    No preview · Article · Dec 2011 · Cancer Genetics
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    ABSTRACT: Synovial sarcoma is a malignant soft tissue neoplasm which mostly occurs in adolescents and young adults. The tumor is rare in the head and neck region although it has been described at virtually every anatomic site. Synovial sarcoma can mimic benign lesions clinically and histologically and is therefore sometimes difficult to diagnose. We present a case of a synovial sarcoma in the parotid gland of a 72-year old patient. Immunohistochemistry and genetic testing of the tumor were performed to confirm the diagnosis. The treatment options are discussed. The case shows that synovial sarcoma should be considered as a differential diagnosis for uncertain parotid lesions in all age groups.
    No preview · Article · Aug 2011 · Auris, nasus, larynx
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    ABSTRACT: The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.
    No preview · Article · Feb 2011 · Der Pathologe
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    ABSTRACT: Die Einteilung der malignen Weichgewebetumoren erfolgt gemäß der aktuellen WHO-Klassifikation aus dem Jahr 2002 auf der Grundlage der Ähnlichkeit des Tumorgewebes zu Normalgeweben.
    No preview · Chapter · Dec 2010
  • D Katenkamp
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    ABSTRACT: The classification of soft tissue tumors is based on their resemblance to normal non-neoplastic tissues and provides an indication of how the tumor will behave in the further disease course. The current article presents the principles to be considered when classifying tumors into categories and discusses additional findings to be taken into account in the diagnosis. The importance of considering combinations of findings when classifying a tumor is underscored; individual (in particular immunohistochemical) findings can be misleading. A statement on the grade of malignancy of a soft tissue tumor requires its identification as a known entity, otherwise incorrect prediction of its biological behaviour is possible. The category of "intermediate malignancy" has been added to the categories of "benign" and "malignant", whereby locally aggressive and incidentally metastasizing tumors have been included in this new category. The staging of soft tissue tumors according to the TNM system is explained, emphasizing that one important feature compared with carcinomas is the inclusion of depth localisation and grade of malignancy.
    No preview · Article · Oct 2010 · Der Pathologe
  • D. Katenkamp
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    ABSTRACT: The classification of soft tissue tumors is based on their resemblance to normal non-neoplastic tissues and provides an indication of how the tumor will behave in the further disease course. The current article presents the principles to be considered when classifying tumors into categories and discusses additional findings to be taken into account in the diagnosis. The importance of considering combinations of findings when classifying a tumor is underscored; individual (in particular immunohistochemical) findings can be misleading. A statement on the grade of malignancy of a soft tissue tumor requires its identification as a known entity, otherwise incorrect prediction of its biological behaviour is possible. The category of “intermediate malignancy” has been added to the categories of “benign” and “malignant”, whereby locally aggressive and incidentally metastasizing tumors have been included in this new category. The staging of soft tissue tumors according to the TNM system is explained, emphasizing that one important feature compared with carcinomas is the inclusion of depth localisation and grade of malignancy.
    No preview · Article · Feb 2010 · Der Pathologe
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    ABSTRACT: Genomewide expression profiling has identified a number of genes expressed at higher levels in synovial sarcoma than in other sarcomas. Our objectives in this study were (1) to test whether the differentially expressed gene, Transducin-Like Enhancer of split (TLE1) belonging to the groucho/TLE family, is also distinct on the protein level; (2) to evaluate this biomarker in a series of well-characterised synovial sarcomas on standard, full-sized tissue sections and (3) to correlate the expression of TLE1 with t(X;18) and other established biomarkers. Three-hundred and eighty four spindle cell sarcomas from the German consultation and reference centre of soft tissue tumours initially suspected for synovial sarcoma were revisited. Three-hundred and nineteen of these specimens were analysed immunohistochemically using a monoclonal antibody TLE1 and standard, full-sized tissue sections. The nuclear staining was scored semiquantitatively as -, negative; +, weak; ++, moderate and +++, strong positive. Furthermore, 118 specimens among these were further analysed using FISH and/or PCR to detect t(X;18). We correlated the TLE1 expression with the t(X;18) translocation and other established biomarkers (EMA, PanCK, CK7, CD34 and BCL2). TLE1 expression was observed in 96% of the synovial sarcomas (score+, 249/259) and discriminates them from other soft tissue tumours (p<0.001). Multivariate analysis showed that positive TLE1 staining was a statistically independent diagnostic marker. Furthermore molecular analysis showed that t(X;18) was clearly correlated with TLE1 protein expression (p<0.001). Expression of TLE1 is significantly correlated with t(X;18) and may serve as a new robust diagnostic biomarker in synovial sarcomas and potential therapeutic target.
    No preview · Article · Feb 2010 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: The Jena Institute of Pathology has been serving as a consultation and reference center for soft tissue tumors in Germany since 1978. The present study provides an overview of the clinicopathological data from a two-year period and an update on diagnostics and research. Retrospectively, 7043 cases sent to the institute in the years 2006 and 2007 were analyzed. The majority of cases (>77.7%) were soft tissue tumors, of which 49% were categorized as malignant, 11.4% as intermediate, 35% as benign and 4.6% as tumors of uncertain biological potential. Neoplasms with fibroblastic differentiation were the most frequent. The mean age of patients with a sarcoma was 63 years. The molecular pathological analysis of soft tissue tumors has attained a major role in diagnosis. This is further advanced at the Jena institute in the context of a German Federal Ministry of Education and Research (BMBF) project for molecular sarcoma diagnosis with the aim of developing and validating DNA probes for in situ hybridization detection of translocations and their associated chromosomal breaks on the one hand, and DNA chips for the detection of fusion transcripts on the other. Research projects relate to the analysis of specific biomarkers in large tumor collectives and the pathomechanisms in several sarcoma entities.
    No preview · Article · Feb 2010 · Der Pathologe
  • T Knösel · B Schulz · K Katenkamp · D Katenkamp · I Petersen
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    ABSTRACT: Soft-tissue tumors with haemangiopericytoma (HPC)-like growth patterns can now be divided into three categories: (1) The solitary fibrous tumour (SFT) group with its variants; (2) lesions showing clear evidence of myoid/pericytic differentiation and corresponding to "true" HPCs (myopericytoma/glomangiopericytoma and a subset of sinonasal HPCs); (3) neoplasms that occasionally display HPC-like features (e.g. synovial sarcoma). In this study 268 intrathoracic and extrathoracic SFTs from the German consultation and reference center of soft tissue tumors in Jena were evaluated and analyzed immunohistochemically with antibodies CD34, Bcl-2, CD99, SMA, S100, PanCK and Ki-67. Furthermore, SFTs were categorized into the newly proposed SFT designation: Fibrous variant, cellular variant (more than 90% hypercellularity), fat-forming variant, giant cell-rich variant and malignant SFTs. This article should provide insights into the diagnosis of this entity with emphasis on the new international standard.
    No preview · Article · Dec 2009 · Der Pathologe
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    ABSTRACT: Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC. This finding may have implications both for the diagnosis and treatment of these tumors.
    Full-text · Article · Dec 2009 · American Journal Of Pathology
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    ABSTRACT: Level of Evidence: V, Expert Opinion
    No preview · Article · Nov 2009 · Foot & Ankle International
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    ABSTRACT: Intraosseous hemangioma of the mandible is a rare tumor. In this report, we present a case with a particularly prominent osteolysis and discuss the histological features of bone degradation. We describe a 64-year-old female patient with a cystic tumor mass of the mandible leading to pathologic bone fracture. X-ray analysis was suggestive for aneurysmatic bone cyst. A segment resection was performed. The histological examination revealed a mesenchymal tumor with numerous capillaries and dilated vessels immunohistochemically being positive for CD31, but not for D2-40. In addition, there was a remarkable increase of osteoclasts that sometimes exhibited Howship's lacunae. The tumor was diagnosed as intraosseous hemangioma with prominent bone degradation. Based on our histological findings, it should be further investigated whether there could be an association between angiogenesis and osteoclastogenesis as a central pathway leading to bone destruction in the case of intraosseous hemangiomas.
    No preview · Article · Oct 2009 · Oral and Maxillofacial Surgery
  • Source
    Kathrin Katenkamp · Detlef Katenkamp
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    ABSTRACT: In recent years, new tumor entities have been described and previously known tumor types have undergone a reassessment. This article offers an overview of recent developments in the classification and interpretation of soft tissue tumors. Selective review of publications from 1990 until 2008 from the literature database of the Consultation and Referral Center for Soft Tissue Tumors in Jena. The current status of the classification and morphological diagnosis of these tumors is described. The description of the biological behavior of soft tissue tumors has become more detailed with the introduction of two intermediate categories ("intermediate, locally aggressive" and "intermediate, rarely metastasizing"). There have also been some changes in terminology. Previously established terms such as "malignant fibrous histiocytoma" or "hemangiopericytoma" will be used much less often in future, because these tumor types have been reinterpreted. The WHO recommends that highly differentiated liposarcoma be renamed "atypical lipomatous tumor." Molecular diagnostic techniques have become firmly established as an ancillary diagnostic method. The importance of molecular tumor characterization for individually tailored therapy is already becoming clear. Optimal diagnosis is the prerequisite for effective therapy and can be achieved only with state-of-the-art knowledge of the pathology of soft tissue tumors.
    Preview · Article · Sep 2009 · Deutsches Ärzteblatt International

  • No preview · Article · Sep 2009 · EJC Supplements
  • K Fruth · T Hansen · D Katenkamp · W Mann · B.M. Lippert
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    ABSTRACT: Primary malignant mesenchymal neoplasms of the larynx are rare. Sarcomas of the larynx account for <1% of all malignant laryngeal mesenchymal neoplasms. This report examines a case of a recurring laryngeal, initial benign-appearing mesenchymal tumour, which first changed its clinical phenotype without any histological signs of malignancy and later also its histological appearance with signs of malignancy. Finally, it even underwent a transformation into a higher grade of malignancy. In addition to this, the difficulties of allocating this tumour to the correct sarcoma subentity are shown.
    No preview · Article · Aug 2009 · Auris, nasus, larynx

Publication Stats

3k Citations
335.10 Total Impact Points

Institutions

  • 1970-2014
    • Friedrich Schiller University Jena
      • Institute of Pathology
      Jena, Thuringia, Germany
  • 1974-2013
    • Universitätsklinikum Jena
      • Institute of Pathology
      Jena, Thuringia, Germany
  • 2009
    • Johannes Gutenberg-Universität Mainz
      • Department of Otolaryngology, Head and Neck Surgery
      Mayence, Rheinland-Pfalz, Germany
  • 2005
    • Martin Luther University of Halle-Wittenberg
      • Institut für Pathologie
      Halle, Saxony-Anhalt, Germany
  • 2002
    • German Cancer Research Center
      Heidelburg, Baden-Württemberg, Germany
  • 1998
    • Brigham and Women's Hospital
      Boston, Massachusetts, United States
  • 1997
    • University of British Columbia - Vancouver
      • Department of Pathology and Laboratory Medicine
      Vancouver, British Columbia, Canada
  • 1996
    • Institut für Pathologie und Molekularpathologie
      Gelsenkirchen, North Rhine-Westphalia, Germany
  • 1988
    • Pathologisches Institut Bremerhaven
      Bremerhaven, Bremen, Germany
  • 1979-1981
    • University of Greifswald
      • Institute of Pathology
      Griefswald, Mecklenburg-Vorpommern, Germany