Publications by authors named "Angelika Reiner-Concin"

17 Publications

  • Page 1 of 1

Increasing use of immunotherapy and prolonged survival among younger patients with primary CNS lymphoma: a population-based study.

Acta Oncol 2019 Jul 17;58(7):967-976. Epub 2019 Apr 17.

b Comprehensive Cancer Center , Medical University of Vienna , Vienna , Austria.

Primary CNS lymphoma is a highly aggressive and rare type of extranodal non-Hodgkin lymphoma. Although, new therapeutic approaches have led to improved survival, the management of the disease poses a challenge, practice patterns vary across institutions and countries, and remain ill-defined for vulnerable patient subgroups. Using information from the Austrian Brain Tumor Registry we followed a population-based cohort of 189 patients newly diagnosed from 2005 to 2010 through various lines of treatment until death or last follow-up (12-31-2016). Prognostic factors and treatment-related data were integrated in a comprehensive survival analysis including conditional survival estimates. We find variable patterns of first-line treatment with increasing use of rituximab and high-dose methotrexate (HDMTX)-based poly-chemotherapy after 2007, paralleled by an increase in median overall survival restricted to patients aged below 70 years. In the entire cohort, 5-year overall survival was 24.4% while 5-year conditional survival increased with every year postdiagnosis. In conclusion, we show that the use of poly-chemotherapy and immunotherapy has disseminated to community practice to a fair extent and survival has increased over time at least in younger patients. Annually increasing conditional survival rates provide clinicians with an adequate and encouraging prognostic measure.
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http://dx.doi.org/10.1080/0284186X.2019.1599137DOI Listing
July 2019

Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values.

Breast 2014 Jun 7;23(3):259-63. Epub 2014 Mar 7.

Department of Pathology, University College Hospital, London, United Kingdom.

The Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5.
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http://dx.doi.org/10.1016/j.breast.2014.02.003DOI Listing
June 2014

Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series.

Acta Neuropathol 2013 Sep 31;126(3):365-84. Epub 2013 Jul 31.

Institute of Neurology, Medical University Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria.

Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-β (Aβ), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aβ deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aβ parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.
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http://dx.doi.org/10.1007/s00401-013-1157-yDOI Listing
September 2013

A Case of simultaneous occurrence of Marine - Lenhart syndrome and a papillary thyroid microcarcinoma.

BMC Endocr Disord 2013 May 8;13:16. Epub 2013 May 8.

Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, 1090, Austria.

Background: Marine-Lenhart syndrome is defined as the co-occurrence of Graves' disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule.

Case Presentation: A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 μIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves' disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter.

Conclusions: Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves' disease rule out papillary thyroid carcinoma.
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http://dx.doi.org/10.1186/1472-6823-13-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654942PMC
May 2013

Duplex reverse-hybridization assay for the simultaneous detection of KRAS/BRAF mutations in FFPE-extracted genomic DNA from colorectal cancer specimens.

Dis Markers 2013 ;34(3):171-7

Second Department of Medicine, Donauspital, Vienna, Austria.

We report the performance evaluation of a non-quantitative reverse-hybridization assay (KRAS-BRAF StripAssay) designed for the simultaneous detection of 10 mutations in codons 12 and 13 of the KRAS gene and BRAF mutation V600E. Dilution experiments using DNA from tumor cell lines or from formalin-fixed paraffin-embedded (FFPE) colorectal cancer (CRC) tissue were performed to assess assay sensitivity. Using 50 ng of total DNA (mutant and wild-type), the KRAS-BRAF StripAssay demonstrated a detection limit of 1% mutant sequence in a background of wild-type DNA. With respect to BRAF V600E, the KRAS-BRAF StripAssay was evaluated using 60 FFPE CRC samples previously analyzed by high resolution melting (HRM). Test strip hybridization identified 2/60 (3%) samples to carry the BRAF V600E mutation, and results were in agreement with those obtained by HRM analysis. This work demonstrates the KRAS-BRAF StripAssay to be a robust and sensitive method for the detection of common KRAS/BRAF mutations in genomic DNA isolated from FFPE tissue samples.
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http://dx.doi.org/10.3233/DMA-120960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810114PMC
July 2013

Clinical and economic aspects of KRAS mutational status as predictor for epidermal growth factor receptor inhibitor therapy in metastatic colorectal cancer patients.

Oncology 2011 13;81(5-6):359-64. Epub 2012 Jan 13.

Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna), LB Cluster Translational Oncology, 3rd Medical Department, Centre for Oncology and Haematology, Kaiser Franz Josef-Spital, Vienna, Austria.

Treatment of metastasized colorectal cancer (mCRC) patients with anti-epidermal growth factor receptor (EGFR)-directed monoclonal antibodies is driven by the results of the KRAS mutational status (wild type [WT]/mutated [MUT]). To find out as to what extent the treatment selection based on the KRAS status had impact on overall costs, a retrospective analysis was performed. Of 73 mCRC patients 31.5% were MUT carriers. Costs of EGFR inhibitor treatment for WT patients were significantly higher compared to those for patients with MUT (p = 0.005). Higher treatment costs in WT carriers reflect a significantly higher number of treatment cycles (p = 0.012) in this cohort of patients. Savings of drug costs minus the costs for the determination of KRAS status accounted for EUR 779.42 (SD ±336.28) per patient per cycle. The routine use of KRAS screening is a cost-effective strategy. Costs of unnecessary monoclonal EGFR inhibitor treatment can be saved in MUT patients.
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http://dx.doi.org/10.1159/000334919DOI Listing
June 2012

A peculiar constellation of tau pathology defines a subset of dementia in the elderly.

Acta Neuropathol 2011 Aug 25;122(2):205-22. Epub 2011 Mar 25.

Institute of Neurology, Medical University Vienna, Austria.

Sporadic tauopathies are characterized by differential cellular and topographical predominance of phospho-tau immunoreactivity and biochemical distinction of the tau protein. Established entities include progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and argyrophilic grain disease. During a community-based longitudinal study on aging, we detected tau pathologies not compatible with these categories. We immunostained for different phospho-tau epitopes, 4R and 3R tau isoforms, α-synuclein, amyloid-β, and phospho-TDP-43, analyzed the MAPT and ApoE genes, and performed western blotting for the tau protein. The mean age of patients (4 women, 3 men) was 83.8 years. Clinical presentations combined dementia with psychiatric symptoms and/or parkinsonism. In addition to neurofibrillary tangles and diffuse neuronal cytoplasmic tau immunoreactivity, the neuropathology was characterized by peculiar cytopathologies (diffuse granular immunopositivity of astrocytic processes and patchy accumulation of thin threads) in a distinctive distribution (frontal and temporal cortices, hippocampus, amygdala, basal ganglia, locus coeruleus, and substantia nigra). Argyrophilic grains were detected in four patients. Few to moderate densities of neuritic plaques but widespread phospho-TDP-43 pathology was observed in five patients. There was variability in the H1/H2 and ApoE alleles and biochemical features of tau protein. We propose these cases as complex tauopathy with a characteristic constellation: some features of primary tauopathies and Alzheimer's disease mixed with additional cytopathologies including a distinctive astrogliopathy, in a characteristic distribution of lesions. These complex tauopathies in the elderly deserve specific diagnostic and eventually therapeutic considerations.
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http://dx.doi.org/10.1007/s00401-011-0819-xDOI Listing
August 2011

Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM) definitions.

Eur J Cancer 2011 Apr 16;47(6):887-94. Epub 2010 Dec 16.

Department of Pathology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary.

Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer.
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http://dx.doi.org/10.1016/j.ejca.2010.11.011DOI Listing
April 2011

Nodal-stage classification in invasive lobular breast carcinoma: influence of different interpretations of the pTNM classification.

J Clin Oncol 2010 Feb 19;28(6):999-1004. Epub 2010 Jan 19.

University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, the Netherlands.

PURPOSE Application of current nodal status classification is complicated in lobular breast carcinoma metastases. The aim of this study was to define the optimal interpretation of the pTNM classification in sentinel node (SN) -positive patients to select patients with limited or with a high risk of non-SN involvement. PATIENTS AND METHODS SN metastases of 392 patients with lobular breast carcinoma were reclassified according to interpretations of the European Working Group for Breast Screening Pathology (EWGBSP) and guidelines by Turner et al, and the predictive power for non-SN involvement was assessed. Results Reclassification according to definitions of EWGBSP and Turner et al resulted in different pN classification in 73 patients (19%). The rate of non-SN involvement in the 40 patients with isolated tumor cells according to Turner et al and with micrometastases according to EWGBSP was 20%, which is comparable to the established rate for micrometastases. The rate of non-SN involvement in the 29 patients with micrometastases according to Turner et al and with macrometastases according to EWGBSP was 48%, which is comparable to the established rate for macrometastases. Therefore, the EWGBSP method to classify SN tumor load better reflected the risk of non-SN involvement than the Turner et al system. CONCLUSION Compared with the guidelines by Turner et al, the EWGBSP definitions better reflect SN metastatic tumor load and allow better differentiation between patients with lobular breast carcinoma who have a limited or a high risk of non-SN metastases. Therefore, we suggest using the EWGBSP definitions in these patients to select high-risk patients who may benefit from additional local and/or systemic therapy.
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http://dx.doi.org/10.1200/JCO.2009.22.0723DOI Listing
February 2010

Pathology role in adjuvant setting.

Cancer Treat Res 2009 ;151:41-61

Department of Pathology, Danube Hospital, Vienna, Austria.

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http://dx.doi.org/10.1007/978-0-387-75115-3_4DOI Listing
August 2010

The Austrian Brain Tumour Registry: a cooperative way to establish a population-based brain tumour registry.

J Neurooncol 2009 Dec 28;95(3):401-411. Epub 2009 Jun 28.

Institute of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1097, Vienna, Austria.

In Austria, registration of malignant brain tumours is legally mandatory, whereas benign and borderline tumours are not reported. The Austrian Brain Tumour Registry (ABTR) was initiated under the auspices of the Austrian Society of Neuropathology for the registration of malignant and non-malignant brain tumours. All Austrian neuropathology units involved in brain tumour diagnostics contribute data on primary brain tumours. Non-microscopically verified cases are added by the Austrian National Cancer Registry to ensure a population-based dataset. In 2005, we registered a total of 1,688 newly diagnosed primary brain tumours in a population of 8.2 million inhabitants with an overall age-adjusted incidence rate of 18.1/100,000 person-years. Non-malignant cases constituted 866 cases (51.3%). The incidence rate was higher in females (18.6/100,000) as compared to males (17.8/100,000), while 95/1,688 (5.6%) cases were diagnosed in children (<18 years). The most common histology was meningioma (n = 504, 29.9%) followed by glioblastoma (n = 340, 20.1%) and pituitary adenoma (n = 151, 8.9%). Comparison with the Central Brain Tumor Registry of the United States (CBTRUS) database showed high congruency of findings. The ABTR model led by neuropathologists in collaboration with epidemiologists and the Austrian National Cancer Registry presents a cooperative way to establish a population-based brain tumour registry with high quality data. This setting links cancer registration to the mission of medical practice and research as defined by the World Medical Association in the Declaration of Helsinki. The continued operation of ABTR will aid in monitoring changes in incidence and in identifying regional disease clusters or geographic variations in brain tumour morbidity/mortality.
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http://dx.doi.org/10.1007/s11060-009-9938-9DOI Listing
December 2009

External Quality Assurance in Immunohistochemistry - Is It the Solution to a Complex Problem?

Breast Care (Basel) 2008;3(2):78-79. Epub 2008 Apr 22.

Dept. of Pathology, Donauspital, Vienna, Austria.

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http://dx.doi.org/10.1159/000126738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931078PMC
April 2008

Validation of clinical prediction rules for a low probability of nonsentinel and extensive lymph node involvement in breast cancer patients.

Am J Surg 2007 Sep;194(3):288-93

Department of Surgical Pathology, Bács-Kiskun County Teaching Hospital, Nyiri út 38, H-6000 Kecskemét, Hungary.

Background: Two recently developed clinical prediction rules aim to anticipate the lack of nonsentinel lymph node metastases and the involvement of less than 4 lymph nodes in breast cancer patients with positive sentinel lymph nodes (SLNs).

Methods: The University of Louisville Breast SLN Study clinical prediction rules were validated on an independent set of SLN-positive patients with tumors < or = 15 mm.

Results: The data on 475 and 473 patients, respectively, were used for the validation. The areas under the receiver operating characteristic curves were similar to the originals for both predictive tools (.70 and .76). The lowest score of 1 identified 5 of 7 patients with disease limited to the SLNs and 161 of 165 as having less than 4 involved lymph nodes.

Conclusions: A subset of patients with SLN-only involvement and less than 4 metastatic lymph nodes can probably be identified by means of the Louisville clinical prediction rules, but prediction of the lack of non-SLN metastasis seems less reliable.
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http://dx.doi.org/10.1016/j.amjsurg.2007.02.014DOI Listing
September 2007

Sentinel lymph node biopsy and non-sentinel node involvement in special type breast carcinomas with a good prognosis.

Eur J Cancer 2007 Jun 24;43(9):1407-14. Epub 2007 May 24.

Department of Pathology, Bács-Kiskun County Teaching Hospital, Nyiri út 38, H-6000 Kecskemét, Hungary.

This study aimed at identifying factors related to sentinel lymph node (SLN) involvement in patients with tubular, cribriform, mucinous or papillary breast carcinoma and those related to non-SLN metastases if an SLN was positive. Multivariate analyses involved logistic and stepwise regressions. The SLNs harboured metastases in 85 of 572 cases, 78 of whom underwent axillary dissection; 19 presented non-SLN positive disease. Lack of lymphovascular invasion, a tumour size < or = 10 mm and a single SLN removed were the factors predicting an SLN metastasis rate <10%, and patients with these features could be candidates for no surgical axillary staging. A positive SLN proportion of < or = 50% and no lymphovascular invasion were associated with a <10% rate of non-SLN invasion; patients with a positive SLN and these features could be candidates for the omission of completion axillary dissection. The opposite presentation of these factors would mandate SLN biopsy and axillary dissection, respectively.
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http://dx.doi.org/10.1016/j.ejca.2007.04.004DOI Listing
June 2007

Sentinel lymph node biopsy in staging small (up to 15 mm) breast carcinomas. Results from a European multi-institutional study.

Pathol Oncol Res 2007 27;13(1):5-14. Epub 2007 Mar 27.

Department of Pathology, Bács-Kiskun County Teaching Hospital, Kecskemét, H-6000, Hungary.

Sentinel lymph node (SLN) biopsy has become the preferred method for the nodal staging of early breast cancer, but controversy exists regarding its universal use and consequences in small tumors. 2929 cases of breast carcinomas not larger than 15 mm and staged with SLN biopsy with or without axillary dissection were collected from the authors' institutions. The pathology of the SLNs included multilevel hematoxylin and eosin (HE) staining. Cytokeratin immunohistochemistry (IHC) was commonly used for cases negative with HE staining. Variables influencing SLN involvement and non-SLN involvement were studied with logistic regression. Factors that influenced SLN involvement included tumor size, multifocality, grade and age. Small tumors up to 4 mm (including in situ and microinvasive carcinomas) seem to have SLN involvement in less than 10%. Non-SLN metastases were associated with tumor grade, the ratio of involved SLNs and SLN involvement type. Isolated tumor cells were not likely to be associated with further nodal load, whereas micrometastases had some subsets with low risk of non-SLN involvement and subsets with higher proportion of further nodal spread. In situ and microinvasive carcinomas have a very low risk of SLN involvement, therefore, these tumors might not need SLN biopsy for staging, and this may be the approach used for very small invasive carcinomas. If an SLN is involved, isolated tumor cells are rarely if ever associated with non-SLN metastases, and subsets of micrometastatic SLN involvement may be approached similarly. With macrometastases the risk of non-SLN involvement increases, and further axillary treatment should be generally indicated.
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http://dx.doi.org/10.1007/BF02893435DOI Listing
July 2007

A rare case of interstitial pneumonitis after tandem high-dose melphalan conditioning and autologous stem cell transplantation in multiple myeloma.

Eur J Haematol 2004 Aug;73(2):143-6

Second Department of Medicine, Danube Hospital, Vienna, Austria.

A 57-yr-old woman with multiple myeloma received an autologous tandem transplant at a 4-month interval. She was conditioned twice with 225 mg/m2 melphalan. After the second transplant, interstitial pneumonitis (IP) ensued. The clinical course was life threatening and mechanical ventilation was required for 32 d. All attempts to identify an infectious agent failed. A presumptive diagnosis of idiopathic IP, possibly related to melphalan toxicity, was made. High-dose methylprednisolone administration led to rapid and durable improvement. Melphalan was employed for conditioning in the tandem setting with an interval of only 3-4 months between two courses or a dose elevation to 225 instead of 200 mg/m2, may have induced IP which responded favorably to methylprednisolone.
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http://dx.doi.org/10.1111/j.1600-0609.2004.00276.xDOI Listing
August 2004
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