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  • Wiley  (5)
  • Buchfelder, Michael  (5)
  • 1
    In: Neuropathology and Applied Neurobiology, Wiley, Vol. 41, No. 6 ( 2015-10), p. 733-742
    Abstract: The differential diagnosis of cystic epithelial masses of the sellar region, especially the histopathological differentiation of craniopharyngiomas and R athke's cleft cysts, poses a challenge even to experienced diagnosticians. Recently, BRAF V 600 E mutations have been described as a genetic hallmark of papillary craniopharyngiomas. We investigated a series of 33 R athke's cleft cysts to determine the frequency of BRAF V 600 E mutations and its suitability as an additional diagnostic marker for the differentiation of cystic lesions of the sellar region. Methods Thirty‐three R athke's cleft cysts and 18 papillary craniopharyngiomas were analysed for BRAF mutational status by immunohistochemistry using a monoclonal antibody ( VE 1) that selectively recognizes the BRAF V 600 E mutant epitope and additional BRAF pyrosequencing in a subset of samples. Results Thirty of 33 specimens diagnosed as R athke's cleft cysts were negative by VE 1 immunohistochemistry and pyrosequencing, whereas in three cysts and in all the 18 papillary craniopharyngiomas, a BRAF V 600 E mutation was detected. Clinical and histological re‐evaluation of the three BRAF V 600 E mutated cases formerly diagnosed as R athke's cleft cysts revealed unusual presentations. Two of them were rediagnosed as papillary craniopharyngiomas. The patient of the third case had a history of craniopharyngioma operated 14 years before, and reoperation showed a cystic epithelial lesion with unclear histology. Conclusions The determination of BRAF mutational status is recommended in any cystic sellar lesion and can in most cases be provided by VE 1 immunohistochemistry even in specimens of low cellularity. Confirmation by (pyro‐)sequencing should be attempted whenever sufficient epithelium is available due to variable staining results.
    Type of Medium: Online Resource
    ISSN: 0305-1846 , 1365-2990
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2008293-9
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  • 2
    In: Clinical Endocrinology, Wiley, Vol. 89, No. 4 ( 2018-10), p. 454-458
    Abstract: Almost half of the cases of Cushing's disease ( CD ) tumours carry recurrent activating somatic mutations in the ubiquitin‐specific protease eight gene ( USP 8 ). The USP 8 mutational status could predict remission in patients with CD , so our objective was to correlate the presence of somatic USP 8 mutations with the rate of recurrence after transsphenoidal surgery ( TSS ) retrospectively. Design Biochemical, radiological and clinical data were retrospectively assessed in 48 patients. USP 8 mutational status was determined from corticotroph tumour samples. Association between USP 8 mutational status, remission and recurrence was investigated. Patients Patients with Cushing's disease from a single‐centre cohort who underwent TSS between 1991 and 2012. Measurements Long‐term remission and recurrence rate after TSS with at least 6 months follow‐up. Biochemical, radiological and clinical data, including sex, age at diagnosis, tumour size and pre‐operative hormonal levels. USP 8 mutational status. Results Patients with USP 8 mutant corticotroph tumours (18 of 48; 37%) were diagnosed significantly earlier (mean ±  SD 46 ± 10 years vs 53 ± 11 years; P  =   0.028) and presented with higher pre‐operative 24‐hour urinary‐free cortisol levels (median IQR μg/24 hours 1174.0, 1184.5 vs 480.0, 405.3; P  =   0.045). The incidence of recurrence in a 10‐year follow‐up was significantly higher in patients with USP 8 mutant tumours after the initial remission (58% vs 18% P  =   0.026). Recurrence appeared significantly earlier in these patients (months 70, 44‐97 95% CI vs 102, 86‐119 95% CI ; P  =   0.019). Conclusion Recurrence appears to be more frequent and earlier after TSS in patients with USP 8 mutant corticotroph tumours.
    Type of Medium: Online Resource
    ISSN: 0300-0664 , 1365-2265
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2004597-9
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  • 3
    In: CNS Neuroscience & Therapeutics, Wiley, Vol. 23, No. 7 ( 2017-07), p. 620-626
    Abstract: Pituicytoma is a rare neoplasm of the sella region. Tumor resection is the primary treatment option, but remains subtotal due to excessive bleeding in many cases. The search for alternative or additional treatment regimens is necessary. Aims We aimed to determine the receptor expression of pituicytoma to find alternatives or supplements to surgical therapy in the use of targeted therapies. Methods Pituicytoma samples were collected from three institutions between 2006 and 2015 and were stained for vascular endothelial growth factors ( VEGF ), thyroid transcription factor ( TTF 1), and somatostatin receptors ( SSTR 2/3/5). The stains were classified from 0=no staining to +++=strong staining. A complementary retrospective analysis of the patient charts regarding sex, age, and primary symptoms, pituitary function, and perioperative complications was performed. Results Ten samples were analyzed; mean patient age was 57.8 years SD 16.3 years. Seven samples were acquired from male patients (one relapse) and three from female. All tumors stained strongly positive (+++) for VEGF ‐R. Six samples stained positive for TTF 1. As for somatostatin receptors, three samples were slightly positive for SSTR 2; seven were negative. SSTR 3 was + in one, three were ++, three were +++, and three were 0. SSTR 5 stained +++ in 1, ++ in 5, + in 1, and 0 in three patients. Conclusions Pituicytomas were generally positive for VEGFR and showed regular expression of SSTR 3 and 5 indicating a possible treatment option through targeted therapies in cases where resection remains insufficient. Further research is necessary as to whether tumor growth can be inhibited using these pathways.
    Type of Medium: Online Resource
    ISSN: 1755-5930 , 1755-5949
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2423467-9
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  • 4
    In: Brain Pathology, Wiley, Vol. 25, No. 1 ( 2015-01), p. 1-10
    Abstract: Adamantinomatous craniopharyngiomas ( adaCP ) cause hypothalamic pituitary dysfunction. Elucidation of pathomechanisms underlying tumor progression is essential for the development of targeted chemotherapeutic treatment options. In order to study the mechanisms of tumor outgrowth, we implanted human primary adaCP tissue from three different surgical specimens stereotactically into the brain of immunodeficient mice (n = 20). Three months after tumor inoculation, magnetic resonance imaging and histology confirmed tumor engraftment in all 20 mice (100%) that obtained tissue transplants. The lesions invaded adjoining brain tissue with micro finger‐shaped protrusions. Immunohistochemical comparison of the primary tumor and xenotransplants revealed a similar amount of proliferation ( Mib ‐1) and cytokeratin expression pattern ( KL ‐1). Whole tumor reconstruction using serial sections confirmed whirl‐like cell clusters with nuclear β‐catenin accumulations at the tumor brain border. These whirls were surrounded by a belt of C laudin‐1 expressing cells, showed an activated epidermal growth factor receptor ( EGFR ) and distinct CD 133 as well as p21 WAF1/Cip1 positivity, indicating a tumor stem cell phenotype. Consistent with our previous in vitro studies, intracranial xenotransplants of adaCP confirmed cells with nuclear β‐catenin and activated EGFR being the driving force of tumor outgrowth. This model provides the possibility to study in vivo tumor cell migration and to test novel treatment regimens targeting this tumor stem cell niche.
    Type of Medium: Online Resource
    ISSN: 1015-6305 , 1750-3639
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2029927-8
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  • 5
    In: Brain Pathology, Wiley, Vol. 27, No. 6 ( 2017-11), p. 839-845
    Abstract: IgG4‐related disease is an immune‐mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG‐related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4‐related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4‐related disease and, thus, IgG4‐related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4‐related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4‐positive cells per high power field and a ratio of IgG4/IgG‐positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non‐IgG‐related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4‐related disease in other organs should be modified for IgG4‐related hypophysitis, accordingly.
    Type of Medium: Online Resource
    ISSN: 1015-6305 , 1750-3639
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2029927-8
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