Publications by authors named "Jana Dvořáčková"

47 Publications

Is autoimmune pancreatitis a risk factor for pancreatic adenocarcinoma?

Vnitr Lek 2021 ;67(1):9-13

Immunoglobulin G4-related diseases (IgG4-RD) are a group of diseases characterized by high serum levels of immunoglobulin G4 (IgG4), increased lymphocyte and plasma cell with IgG4 positivity in the parenchyma of some organs, and storiform fibrosis. The most frequently affected organ is the pancreas. This is an autoimmune form of pancreatitis, which can be divided into two types: Type 1, which is significantly more common than Type 2, is high in IgG4 in the pancreatic parenchyma and shows a fundamental difference in the noted presence of extrapancreatic disorders. In general, chronic inflammation is a risk factor in the development of carcinomas. Chronic pancreatitis is an accepted risk factor for the development of pancreatic cancer. The question is whether this also applies to autoimmune pancreatitis (AIP), which has some mediators of inflammation in common with sporadic pancreatitis, and what role the presence of IgG4 plays. The vast majority of the work on this topic consists of case reports, yet, even based on our own experience, we would like to say that there is a relationship between the autoimmune form of pancreatitis and pancreatic cancer, which usually occurs in the first two years after diagnosis of AIP. Also significant is the fact that the group of people with AIP, who is a clinical manifestation of IgG4-RD, was found to have an even higher incidence of extrapancreatic cancer than in the pancreas itself. Differentiating AIP from pancreatic cancer can sometimes be problematic since these diseases can both present as focal pancreatic lesions. IgG4 has been considered useful for AIP diagnosis, however, IgG4 levels can be slightly elevated, as in the case with pancreatic adenocarcinoma. IgG4 levels of over twice the upper limit are rare among patients with pancreatic adenocarcinoma. However, cases of simultaneous presentation of pancreatic cancer and AIP have been documented and should not be neglected. AIP is a condition where regular followup is mandatory, including from the perspective of possible cancerogenesis.
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March 2021

Metal particles in mucus and hypertrophic tissue of the inferior nasal turbinates from the human upper respiratory tract.

Environ Sci Pollut Res Int 2020 Aug 15;27(22):28146-28154. Epub 2020 May 15.

Center of Advanced Innovation Technologies, VŠB-Technical University of Ostrava, 17. listopadu 15/2172, Poruba, 708 33, Ostrava, Czech Republic.

Mucosal surfaces are the first mechanical barrier preventing the entry of foreign particles into the organism. The study addresses the detection and analysis of metal-based solid particles in cytological mucus samples from the surface of human hypertrophic tissue in the inferior nasal turbinates in patients diagnosed with chronic rhinitis. Solid particles were characterized by scanning electron microscopy and Raman microspectroscopy; all the biological samples were also subjected to vibration magnetometry. Since the upper airways are the first part of the respiratory tract, which is exposed to inhaled particles, it can be assumed that inhaled particles may be partially deposited in this region. Scanning electron microscopy revealed the presence of metal-based solid particles/clusters in the majority of the analysed cytological mucus samples and also in hypertrophic tissues; in all groups, the particles were of submicron size. Raman microspectroscopy detected the presence of particles/clusters based on amorphous carbon, graphite, calcium carbonate, anatase and barite only in the hypertrophic tissue. The obtained results show that the composition of some of the solid particles (i.e. Ba, Zn, Fe and Ti) detected in the mucus from the surface of the hypertrophic tissues resembled the particles found in the hypertrophic tissue itself. It can be assumed that after the capture of the inhaled particles by the mucus, they penetrate into the deeper layers of tissue.
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http://dx.doi.org/10.1007/s11356-020-09156-7DOI Listing
August 2020

The role of metabolic syndrome in the induction of chronic pancreatitis after a first attack of acute pancreatitis - multicenter trial.

Vnitr Lek 2020 ;66(8):12-16

Background: Metabolic syndrome is a serious societal problem worldwide. In the Czech Republic more than 30% of the adult population are sufferers. The role of recurrent acute pancreatitis in the induction of chronic pancreatitis, following the socalled „mechanistic definition“ of chronic pancreatitis, has been unequivocally confirmed. However, there are a number of factors that may contribute to the development of chronic pancreatitis. The first aim of the study was to determine whether the metabolic syndrome may affect the development of chronic pancreatitis. The second question we asked ourselves was whether even one acute attack of pancreatitis could be an inductive factor in chronic pancreatitis.

Methods: Based on data obtained retrospectively from a total of 264 people diagnosed with chronic pancreatitis in 4 centers, a total of 59 people (22.3%) diagnosed within 36 months of a first attack of acute pancreatitis was obtained. Etiologies of either genetically induced pancreatitis or autoimmune pancreatitis were excluded. Diagnostics to identify the presence of metabolic syndrome were run on the 59 persons so obtained using the criteria from the socalled „harmonized“ definition of 2009 (obesity, arterial hypertension, hypertriglyceridemia, type 2 diabetes mellitus and a decreased level of HDL cholesterol).

Results: Comparing the findings of the individual components of metabolic syndrome in persons with chronic pancreatitis after a 1st attack of acute pancreatitis with the metabolic syndrome and in persons with chronic pancreatitis after the 1st attack of acute pancreatitis but without metabolic syndrome, a statistically significant difference in obesity was found (82.5% vs. 28.5%), hypertriglyceridemia (82.3% vs 17.8%) and arterial hypertension (70.5% vs 21.4%). The interval during which chronic pancreatitis occurred after acute pancreatitis averaged 12 months (10-14 months) in subjects with metabolic syndrome, whereas in the group without metabolic syndrome the interval was longer, 20 months (16-29 months).

Conclusion: Our results show that even one attack of acute pancreatitis (regardless of etiology) can be an inductive factor in chronic pancreatitis. The presence of metabolic syndrome can accelerate the development of chronic pancreatitis after one has had acute pancreatitis.
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March 2021

Cardiac papillary fibroelastomas: A 10-year single-center surgical experience and long-term echocardiographic follow-up study.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Mar 18;164(1):84-91. Epub 2019 Nov 18.

Department of Cardiac Surgery, University Hospital Ostrava, Ostrava, Czech Republic.

Aims: Limited contemporary data are available on the clinical and echocardiographic outcomes after surgery for cardiac papillary fibroelastoma (CPF). The aim of this study was to review the clinical manifestations, pathological characteristics, surgical management, and prognoses of patients with histologically verified CPF, who underwent surgery at our cardiac surgery center from 2008 to 2018.

Methods And Results: Twelve patients of median age 62 years (28 to 77 years) were treated. Embolic stroke or transient ischemic attack (five patients, 42%) were the only CPF clinical manifestations. Eleven (92%) tumors were localized on the valves, with the aortic valve being the most common tumor site (seven patients; 58%). Multiple factor analysis revealed no independent predictor of CPF-related embolization. Simple shave tumor excision was sufficient in most patients (10 patients, 83%). No operative or tumor-related late mortality during the median follow-up period of 4.7 years (1.1 to 10.2 years) was recorded. Asymptomatic metachronous valve tumor recurrence (in a location different from that of the original tumor) was revealed in two patients (17%) by transesophageal echocardiography (TEE), not detected by transthoracic echocardiography (TTE). One of these two patients underwent repeated surgery for CPF but later suffered a recurrent embolic stroke, due to another tumor recurrence.

Conclusion: CPF can be safely and effectively treated surgically. TEE is superior to the TTE option in CPF post-operative recurrence detection. There is a clear need for a prospective study to determine criteria for embolization risk stratification and optimum management in patients with CPF.
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http://dx.doi.org/10.5507/bp.2019.053DOI Listing
March 2020

The changes of angiogenesis and immune regulations in stromal microenvironment of cutaneous melanomas.

Cesk Patol 2019 ;55(3):170-175

Tumour microenvironment contributes to growth and metastasis, where angiogenesis and immune alteration suppressing its effectory function belong to main factors. Our study is focused on an analysis of microvascular density (MVD), quantification of FOXP3+ T regulatory lymphocytes (Tregs) and PD-L1 lymphocytes, which are associated with a tumour-cells immune escape mechanism. We examined 95 cutaneous melanomas devided in four groups according to TNM classification - pT1 (35), pT2 (21), pT3 (21), pT4 (18) and 25 melanocytic nevi as a control group. Investigated parameters were detected on paraffin embedded tissues by indirect immunohistochemistry, and evaluated by light microscope in central (C) and at peripheral regions (P) on a 1mm2 „hot spot“ region (the area of the highest density). We found a significant MVD increase correlating with a stage of disease, mostly at the edge of tumours (p=0,0001). Lymphocytic PD-L1 expresion was increased in melanomas of pT3 and pT4 stages, also predominantly at the periphery of lesions (p=0,0001). Numbers of FOXP3 lymphocytes positively correlated with a melanoma stage, where higher values were observed in central areas (p=0,008). Our study documents that stimulation of angiogenesis and induction of an adaptive immune response correlate with a melanoma stage. The most prominent changes are at the tumour periphery confirming heterogeneity of a tumour stroma, which is more prominent in advanced tumours, and which may contribute to higher agresivity of these stages.
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December 2019

Congenital fetal heart defect - an agreement between fetal echocardiography and autopsy findings.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Mar 23;164(1):92-99. Epub 2019 Sep 23.

Department of Pathology, University Hospital Ostrava, Ostrava, Czech Republic.

Aims: To determine the frequency of pregnancy terminations due to prenatal congenital heart defect (CHD) and assess the agreement fetal echocardiography (FECHO) and autopsy findings.

Methods: The data were retrospectively assessed between 2008 and 2017 in a population of 116 698 live births. The correlations between the FECHO and autopsy findings were classified into five levels of agreement: complete, partial, altered diagnosis, disagreement, and unfeasible autopsy.

Results: Totally, 293 CHDs were identified and 49% of families (143/293) decided to terminate the pregnancy. In 1% (2/143) of cases, the autopsy could not be performed, for the other 99% (141/143), the pathologist confirmed the presence of CHDs. Complete agreement between FECHO and autopsy was achieved in 85% (122/143). In 10% (14/143) of cases, the pathologist found minor findings, which were not described in the FECHO. In 4% (5/143) of cases, the pathologist changed the main diagnosis.

Conclusion: Altogether, the results indicated that FECHO is a highly sensitive method for the prenatal detection of CHD but is incapable of detecting the complete spectrum of cardiac defects. Autopsies verified the diagnosis, confirmed the overall impairment in the fetus, and provided data for further counselling of the affected family.
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http://dx.doi.org/10.5507/bp.2019.042DOI Listing
March 2020

Idiopathic inflammatory bowel disease and the first type of autoimmune form of pancreatitis: case report.

Vnitr Lek 2019 ;65(7-8):520-523

The autoimmune form of pancreatitis (AIP) is divided into the following two subtypes. The 1st subtype is characterized by the high presence of immunoglobulin G4 in the blood serum and tissue of some organs which are in the close connection to the so called IgG4 associated disorders. The typical diagnostic signs of AIP are the histomorphological changes. This type of AIP is more frequent than the 2nd type with which has however some common histomorphological signs and mainly the positive response to the administered steroids used in the initial treatment. Whilst the 1st type of AIP is typically connected to the disorders of various organs such are the biliary tract, salivary and lacrimal glands, retroperitoneal fibrosis, reins, prostate gland and the next ones, the 2nd type of AIP is significantly connected to the inflammatory bowel disease only. Inflammatory bowel diseases are rarely present in the 1st type of AIP on the contrary. In our case report we mention the first published observations performed in the Czech Republic when the 1st type of AIP is succeeded by the inflammatory bowel disease - Crohn´s disease.
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October 2019

Pancreatic Solid Focal Lesions: Differential Diagnosis between Autoimmune Pancreatitis and Pancreatic Cancer.

Dig Dis 2019 10;37(5):416-421. Epub 2019 May 10.

Faculty of Medicine, Masaryk University, Brno, Czechia,

Background: Diagnosis of pancreatic cancer (PC) in early stages is still challenging for gastroenterologists. The early detection of cancer is one of the utmost importance for the successful therapy of this malignancy. An accurate differential diagnosis of focal pancreatic lesions plays also an important role, whether it is differential diagnosis of chronic pancreatitis from PC or autoimmune pancreatitis (AIP) from PC. Raised serum immunoglobulin G4 (IgG4) levels to twice the normal value are considered one of significant diagnostic features of type 1 AIP. However, IgG4 can be increased also in patients with PC, but levels usually do not exceed twice the normal value.

Methods: In years 2012-2017, IgG4 serum levels were examined in 115 patients with histologically confirmed PC. Patients with PC and elevated IgG4 level (above 135 mg/dL) had tested their histological resection specimens or bioptic specimens from pancreatic lesion, with targeted detection of the presence of IgG4 and plasmocytes in the pancreatic tissue and changes characteristic for type 1 AIP.

Results: A plasmatic IgG4 level in 115 patients with diagnosed PC was higher than 135 mg/dL in 14 patients (12.2%). Out of them, 2 patients (1.7%) revealed a serum IgG4 level higher than double the normal value, that is, higher than 270.0 mg/dL (suggestive of AIP). One patient met histological criteria for diagnosis of AIP in the simultaneous presence of PC.

Conclusion: Diagnosis of early cancer stages, particularly differentiating AIP from PC can be sometimes problematic. IgG4 levels can be slightly elevated also in case of PC. A targeted biopsy of the pancreas is the method of choice in cases suspected from a focal form of AIP and we recommend to prefer it over other modalities, such as, for example, response to steroid therapy.
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http://dx.doi.org/10.1159/000499762DOI Listing
July 2019

Macrophages of the subcutaneous and omental fatty tissue in obese patients: Immunohistochemical phenotyping of M2 subtypes in relation to type 2 diabetes.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020 Jun 9;164(2):133-137. Epub 2019 Apr 9.

Department of Histology and Embryology, Faculty of Medicine University of Ostrava, Ostrava, Czech Republic.

Background And Aims: Macrophages are linked to the initiation of the chronic inflammation believed to underlie the changes taking place in the white fatty tissue of obese people. Both the number of macrophages, but their functional status, play an important role in the development of inflammation. Classically, macrophages are divided into two types: pro-inflammatory (M1) and anti-inflammatory (M2) types, and based on current immunological studies, further views on the functional distribution of macrophages are suggested. In this study, we evaluated the M1 and M2 macrophages ratio in obese subjects with, or without diabetes. To identify all macrophages, we used CD68 expression, while CD204 expression is typically used for the M2 macrophage.

Materials And Methods: During bariatric surgery, carried out in obese people with and without type 2 diabetes (T2D), we obtained subcutaneous adipose tissue from the navel and omental adipose tissue. We also obtained the same tissue from people with a physiological range of BMI from a judicial autopsy. Applying immunohistochemical staining anti-CD68 and anti-CD204, we carried out a quantitative evaluation of the number of macrophages.

Results: We found CD68+ and CD204+ positive macrophages in perivascular spaces and between fat cells, both isolated and in larger infiltrates. They were also present in so-called "crown-like structures" (CLS) around dying adipocytes. Quantitative analysis showed an increased number of macrophages in all obese patients compared to the control group of non-obese, individuals without T2D. The most striking observation was the macrophage increase in the visceral fatty tissue of diabetics. The number of CD68 and CD204 positive macrophages was statistically significantly smaller in patients without T2D.

Conclusion: We demonstrated a significantly greater number of macrophages in visceral adipose tissue, especially in patients with T2D. Our results also show a positive correlation between the presence of T2D and the total number of macrophages; a significantly greater number of macrophages were found in visceral adipose tissue, especially in patients with T2D.
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http://dx.doi.org/10.5507/bp.2019.011DOI Listing
June 2020

L1CAM as a Negative Prognostic Factor in Endometrioid Endometrial Adenocarcinoma FIGO Stage IA-IB.

Anticancer Res 2019 Jan;39(1):421-424

Department of Obstetrics and Gynecology, University Hospital Ostrava, Ostrava Poruba, Czech Republic.

Aims: In this study, we aimed to investigate how positivity for L1 cell adhesion molecule (L1CAM) was associated with outcome and relapse pattern in patients with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IA-IB endometrial cancer.

Materials And Methods: This retrospective study included 358 patients who underwent surgical treatment for endometrial carcinoma. Tumor samples from 312 patients (87.2%) were available for L1CAM analysis by immunohistochemistry.

Results: Of the 312 tumor samples analyzed, 93 (29.8%) were L1CAM-positive. L1CAM positivity was significantly more common in grade 3 compared to grade 1-2 carcinomas (p=0.02). Patients with L1CAM positivity more commonly experienced disease progression. Distant metastasis was significantly associated with L1CAM positivity (p=0.01). Progression-free interval and overall survival did not significantly differ between L1CAM-positive and L1CAM-negative cases.

Conclusion: L1CAM is a promising independent prognostic marker associated with aggressive tumor behavior and recurrence risk, but not with overall survival.
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http://dx.doi.org/10.21873/anticanres.13128DOI Listing
January 2019

Settled iron-based road dust and its characteristics and possible association with detection in human tissues.

Environ Sci Pollut Res Int 2019 Jan 30;26(3):2950-2959. Epub 2018 Nov 30.

Center for Advanced Innovation Technologies, VŠB-Technical University of Ostrava,, 70800, Ostrava, Czech Republic.

Settled road dust was examined to detect the presence of non-airborne submicron and nano-sized iron-based particles and to characterize these particles. Samples were collected from a road surface near a busy road junction in the city of Ostrava, Czech Republic, once a month from March to October. The eight collected samples were subjected to a combination of experimental techniques including elemental analysis, Raman microspectroscopy, scanning electron microscopy (SEM) analysis, and magnetometry. The data thereby obtained confirmed the presence of non-agglomerated spherical nano-sized iron-based particles, with average sizes ranging from 2 down to 490 nm. There are several sources in road traffic which generate road dust particles, including exhaust and non-exhaust processes. Some of them (e.g., brake wear) produce iron as the dominant metallic element. Raman microspectroscopy revealed forms of iron (mainly as oxides, FeO, and mixtures of FeO and FeO). Moreover, FeO was also detected in samples of human tissues from the upper and lower respiratory tract. In view of the fact that no agglomeration of those particles was found by SEM, it is supposed that these particles may be easily resuspended and represent a risk to human health due to inhalation exposure, as proved by the detection of particles with similar morphology and phase composition in human tissues.
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http://dx.doi.org/10.1007/s11356-018-3841-xDOI Listing
January 2019

Factors That Predict the Growth of Residual Nonfunctional Pituitary Adenomas: Correlations between Relapse and Cell Cycle Markers.

Biomed Res Int 2018 10;2018:1876290. Epub 2018 Jul 10.

Department of Neurosurgery, University Hospital Ostrava, Czech Republic.

Introduction: Nonfunctional pituitary adenomas are treated surgically, and even partial resection can improve or eliminate clinical symptoms. Notably, progression requires further intervention, which presents an increased risk, especially in older patients. This study investigated whether the histopathological characteristics of nonfunctional adenomas could predict recurrence.

Materials And Methods: Data were obtained retrospectively from 30 patients who underwent surgery for the partial resection of pituitary adenomas. Remnant tumor growth was observed in 17 patients, while the residual tumor was unchanged more than 7 years after surgery in 13 patients. Statistical analysis was performed to investigate correlations between remnant tumor progression and tumor histopathological findings, including protein expression of p21, p27, p53, and Ki-67.

Results And Discussion: Remnant tumors that demonstrated regrowth showed significantly higher protein expression of p21 and Ki-67. Expression of the p53 tumor suppressor was also higher in this group, but the difference was at the limit of statistical significance.

Conclusion: Tumors with high expression of p21 and p53 and with a high Ki-67 index were more likely to show residual pituitary adenoma progression. Such cases should undergo frequent radiological examination and timely reoperation, and radiosurgery should be considered.
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http://dx.doi.org/10.1155/2018/1876290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077672PMC
December 2018

M1/M2 macrophage polarization in human obese adipose tissue.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018 Jun 16;162(2):79-82. Epub 2018 May 16.

Department of Histology and Embryology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic.

Obesity and insulin resistance are closely associated with chronic inflammation in adipose tissue, where macrophages play an important role. Adipose tissue macrophages can be divided into two main phenotypes: the classical M1 macrophages and alternatively activated macrophages M2. M1 macrophages produce pro-inflammatory cytokines (TNF-α, interleukin IL-6 and MCP-1) and thus contribute to the development of insulin resistance. On the other hand, M2 macrophages, anti-inflammatory, are involved in the maintenance of tissue homeostasis and are typical in the adipose tissue of slender individuals. Macrophages can also play a role in the pathogenesis of other serious illnesses such as cardiovascular diseases or cancer. This article reviews the latest data on macrophage polarization in adipose tissue.
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http://dx.doi.org/10.5507/bp.2018.015DOI Listing
June 2018

IDH Mutation Analysis in Glioma Patients by CADMA Compared with SNaPshot Assay and two Immunohistochemical Methods.

Pathol Oncol Res 2019 Jul 19;25(3):971-978. Epub 2018 Mar 19.

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 779 00, Olomouc, Czech Republic.

Mutations in IDH1/2 genes are a marker of good prognosis for glioma patients, associated with low grade gliomas and secondary glioblastomas. Immunohistochemistry and Sanger sequencing are current standards for IDH1/2 genotyping while many other methods exist. The aim of this study was to validate Competitive amplification of differentially melting amplicons (CADMA) PCR for IDH genotyping by comparison with SNaPshot assay and two immunohistochemical methods. In our study, 87 glioma patients (46 from Olomouc and 41 from Ostrava) were analyzed. IDH1/2 mutations in native bioptical samples were analyzed at DNA level by CADMA and SNaPshot while IDH1 mutations in FFPE samples were analyzed at protein level by two IHC methods. CADMA PCR sensitivity for IDH1 was 96.4% and specificity 100% for 86 concluded samples. SNaPshot assay sensitivity was 92.9% and specificity of 100% for 85 concluded samples. IHC in the laboratory no. 2 reached sensitivity 85.7% and specificity 100% for 86 concluded samples. IHC in the laboratory no. 4 reached sensitivity of 96.4% and specificity of 79.7% in 74 concluded samples. Only one IDH2 mutation was found by SNaPshot while CADMA yielded false negative result. In conclusion, CADMA is a valid method for IDH1 p.(R132H) testing with higher sensitivity than SNaPshot assay. Also, molecular genetic methods of IDH1 testing from native samples were more robust than IHC from FFPE.
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http://dx.doi.org/10.1007/s12253-018-0413-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614140PMC
July 2019

Crohn's disease - genetic factors and progress of the disease.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018 Jun 18;162(2):139-143. Epub 2018 Jan 18.

Department of Internal Medicine, University Hospital Ostrava, Czech Republic.

Background And Objectives: Crohn's disease is a multifactorial inflammatory disease affecting mainly the gastrointestinal tract. The genetic factors that are involved in the disease include mainly three mutations of the gene NOD2/CARD15 (R702W, G908R, 3020insC). The aim of this study was to determine the relationship between the presence of these variants and disease phenotype.

Material And Methods: 70 patients with Crohn's disease were examined for the presence of the above-mentioned mutations. The researchers used the medical records to retrospectively obtain clinical data and together with the information obtained prospectively according to the protocol they analysed the connection between gene mutations and disease phenotype.

Results: At least one mutation was found in 22 patients with Crohn's disease (32%), four patients were found to have two different mutations (composed heterozygotes - 6%) and six patients (9%) were homozygotes for the 3020insC gene. No significant differences were found between the groups with wild-type form and the mutated form of the NOD2 / CARD15 gene with respect to age at the time of diagnosis, form of the disease or localization according to the Montreal classification.

Conclusion: Mutations of the NOD2 / CARD15 gene did not significantly affect the frequency of reoperations, homozygotes with 3020insC gene mutations, however, represented a high risk group. The phenotype was not related significantly to the presence of the examined mutations.
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http://dx.doi.org/10.5507/bp.2017.058DOI Listing
June 2018

Low intrapatient variability of histomorphological findings in periprosthetic tissues from revised metal/ceramic on polyethylene joint arthroplasties.

J Biomed Mater Res B Appl Biomater 2018 07 16;106(5):2008-2018. Epub 2017 Oct 16.

Department of Pathology, University Hospital Ostrava, Ostrava-Poruba, 708 52, Czech Republic.

The type of tissue response to implant by-products can be determined by examination of periprosthetic tissues. However, little is known about the most suitable location for tissue sampling. The main goal of this study was to evaluate the extent of variability in tissue response in relation to location of tissue sampling, implant fixation, age and sex in total joint arthroplasties with metal-on-polyethylene or ceramic-on-polyethylene bearing pairs. We processed 236 histology slides from 21 patients and focused on the association between the location of tissue samples and histological features. The presence of the synovial hyperplasia showed a significant association with the particular sampling site. A higher density of high endothelial cell venules was seen in the samples from around the joint, and polyethylene particles were more abundant in noncemented TJA but both findings did not show statistically significant association with the sampling site. The results showed a relatively small variance in the tissue response to prosthetic by-products among tissues sampled from the same patient. Our findings indicate that tissue samples retrieved from similar distance from around the TJA during the revision operation show comparable results of histological analysis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2008-2018, 2018.
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http://dx.doi.org/10.1002/jbm.b.33990DOI Listing
July 2018

Are goblet cell carcinoids a group of heterogeneous tumors?

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017 Sep 12;161(3):281-285. Epub 2017 Jun 12.

Department of Pathology, University of Ostrava and University Hospital Ostrava, Czech Republic.

Background: Goblet cell carcinoids belong to neuroendocrine tumors, according to the WHO classification. The tumors are diagnosed based on a typical histological pattern and using neuroendocrine markers. However, some tumors do not react with these markers and yet expression of proliferative markers is high. Do these tumors belong to G1 and G2 neuroendocrine tumors?

Methods: The sample comprised nine cases of tumors of the appendix identified by immunohistological methods as goblet cell carcinoids or adenocarcinoma ex goblet cell carcinoid.

Results: In six cases, hematoxylin and eosin staining revealed tumors completely or 90% made of characteristic large tumor cells observed in typical goblet cell carcinoids. The remaining three cases were identified as adenocarcinomas arising ex goblet cell carcinoids. Immunohistological examination revealed that in four cases of typical goblet cell carcinoids, expression of neuroendocrine markers was low or completely negative. Yet in two cases, the Ki-67 proliferative index exceeded the 20% cut-off for inclusion in the G1 and G2 category.

Conclusions: Goblet cell carcinoids are a heterogeneous group of tumors that may express neuroendocrine markers in a small number of tumor cells or are negative to these markers. However, high expression of the proliferative marker Ki-67 exceeds the criteria for G1 and G2 neuroendocrine tumors. It is our opinion that these tumors may be classified as a specific type of carcinoma.
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http://dx.doi.org/10.5507/bp.2017.027DOI Listing
September 2017

[The rational diagnostic of cholangiocarcinoma].

Vnitr Lek 2016 Feb;62(2):125-33

Cholangiocarcinoma (CC) is a rare malignant tumour arising from cholangiocytes, and its prognosis is usually unfavourable, mostly as a result of late diagnosis of the tumour. The current incidence of cholangiocarcinoma in the Czech Republic is 1.4/100,000 inhabitants per year; in less than 30 % of patients with CC, one of the known risk factors can be identified, most frequently, primary sclerosing cholangitis. Only patients with early diagnosed and surgically amenable cholangiocarcinoma are likely to have a longer survival time; in their case, survival for more than five years has been achieved in 20 % to 40 %. From the perspective of the need for early diagnosis of CC, a significant part is played by imaging and histopathologic evaluation; the early diagnostic significance of oncomarkers is limited. The rational early diagnosis of CC consists in effective use of differentiated advantages of different imaging modalities - MRI with DSA appears to be the optimal method, endosonography is a sensitive method for the identification of malignancy in the hepatic hilum or distal common bile duct, MRCP (magnetic resonance cholangiopancreatography) is used to display pathological changes in the biliary tree, ERCP (endoscopic retrograde cholangiopancreatography) allows material removal for histopathological examination. Other new approaches are also beneficial, such as IDUS - intraductal ultrasonography of biliary tract or SPY-GLASS, enabling examination of the bile ducts by direct view with the possibility of taking targeted biopsies. Sensitivity and specificity of histology and cytology can be increased by using the molecular cytogenetic FISH method, i.e. fluorescence in situ by hybridization, with a specificity of 97 %.
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February 2016

[Hypoglycemia in a solitary fibrous tumor of the liver].

Cesk Patol 2016 ;52(1):41-4

A 64-year-old patient developed sudden hypoglycemia leading to unconsciousness. Hypoglycemic episodes recurred on several occasions but were not accompanied by unconsciousness. Magnetic resonance imaging revealed a liver tumor in the right lobe sized 20.0 × 14.6 × 19.0 cm. No other masses were detected. Right hemihepatectomy was indicated but could not be performed due to heavy bleeding near the tumor. Histological examination showed a relatively cellular tumor made of elongated bland cells. The mitotic index was fewer than 4 mitoses per 10 HPF. The tumor was without necrosis or hemorrhage. The excised tumor was not encapsulated and showed no signs of invasive growth. On immunohistological examination, the tumor expressed NSE, CD34, CD99, Bcl2 and STAT6; Ki-67 was positive in approximately 20% of the cells. Both the histological pattern and immunophenotype were suggestive of solitary fibrous tumor of the liver. Given its size, cellularity and relatively high expression of the proliferation marker Ki-67, the tumor was classified as potentially malignant. The patient underwent embolization of arteries supplying the tumor with blood. The effect of the procedure on the tumor will only be assessed later. Hypoglycemia has resolved and the patient feels well.
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January 2017

Therapeutic Potential of Adipose-Derived Therapeutic Factor Concentrate for Treating Critical Limb Ischemia.

Cell Transplant 2016 30;25(9):1623-1633. Epub 2015 Oct 30.

Radiodiagnostic Institute, University Hospital Ostrava, Ostrava, Czech Republic.

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.
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http://dx.doi.org/10.3727/096368915X689767DOI Listing
November 2017

Micro- and Nanosized Particles in Nasal Mucosa: A Pilot Study.

Biomed Res Int 2015 1;2015:505986. Epub 2015 Jun 1.

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Ostrava, 17. Listopadu 1790, 708 52 Ostrava, Czech Republic ; Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic.

Objective: The aim of this prospective study is to evaluate presence and quantity of micro- and nanosized particles (NPs) and interindividual differences in their distribution and composition in nasal mucosa.

Methods: Six samples of nasal mucosa obtained by mucotomy from patients with chronic hypertrophic rhinosinusitis were examined. Samples divided into 4 parts according to the distance from the nostrils were analyzed by scanning electron microscopy and Raman microspectroscopy to detect solid particles and characterize their morphology and composition. A novel method of quantification of the particles was designed and used to evaluate interindividual differences in distribution of the particles. The findings were compared with patients' employment history.

Results: In all the samples, NPs of different elemental composition were found (iron, barium, copper, titanium, etc.), predominantly in the parts most distant from nostrils, in various depths from the surface of the mucosa and interindividual differences in their quantity and composition were found, possibly in relation to professional exposition.

Conclusions: This study has proven the possibility of quantification of distribution of micro- and nanosized particles in tissue samples and that the NPs may deposit in deeper layers of mucosa and their elemental composition may be related to professional exposition to the sources of NPs.
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http://dx.doi.org/10.1155/2015/505986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466340PMC
March 2016

The changes of angiogenesis and immune cell infiltration in the intra- and peri-tumoral melanoma microenvironment.

Int J Mol Sci 2015 Apr 9;16(4):7876-89. Epub 2015 Apr 9.

CGB Laboratory, a.s., Laboratory of Molecular Genetics and Pathology, AGEL Research and Training Institute-Ostrava-Vitkovice Branch, Korenskeho 10, Ostrava 71000, Czech Republic.

Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups--pT1 (35), pT2 (17), pT3 (18) and pT4 (12)--and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.
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http://dx.doi.org/10.3390/ijms16047876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425055PMC
April 2015

[Autoimmune pancreatitis - diagnostic consensus].

Vnitr Lek 2015 Feb;61(2):114-8

The autoimmune type of pancreatitis represents the specific disease of pancreas, with significant contribution of autoimmune processes in its etiopathogenesis. Currently, there are two proved subtypes of this particular pancreatopathy, which are defined clinically, histomorphologically and serologically. They have many histomorphological signs in common, but differ in the presence of so-called granulocytic epithelial lesions (GEL), which are absent in subtype 1. The subtype 1 is characterized by the presence of gammaglobulines, esp. immunoglobuline G4 and IgG4 positive extrapancreatic lesions. The subtype 2 is typically associated with the inflammatory bowel diseases, esp. ulcerative colitis. But the common characteristic of both subtypes is the fact response to applied steroid treatment. Due to diverse diagnostic criteria in the past, in 2011 the consensus for the diagnosis of autoimmune pancreatitis was announced. It is based on clinical symptoms, biochemical results, the results got by using of imaging methods, histomorphology and positive response to steroid treatment. The matter to be solved is the question of early differential diagnosis between focal autoimmune pancreatitis and adenocarcinoma of pancreatic head. From imaging methods are MRI/CT, MRCP (in Asia ERCP), EUS with targeted biopsy of the gland (under EUS control), are recommended as the methods of choice.
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February 2015

Immunoglobulin G4, autoimmune pancreatitis and pancreatic cancer.

Dig Dis 2015 17;33(1):86-90. Epub 2014 Dec 17.

Academic Centre of Gastroenterology, Department of Internal Medicine, University Hospital Ostrava, Ostrava, Czech Republic.

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer.

Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis.

Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit.

Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy.
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http://dx.doi.org/10.1159/000368337DOI Listing
August 2015

An isolated metastasis to the heart from a malignant phyllodes tumor with osteosarcomatous differentiation.

Cesk Patol 2014 ;50(4):146-9

A 74-year-old woman was admitted in a serious condition due to the failing right heart. A CT scan revealed a tumor infiltration through the interventricular septum in the right heart, spreading from the apex as far as under the tricuspid valve. The tumor penetrated into the conus of the pulmonary artery, bulging and markedly narrowing the lumen. As a result of the tumor infiltration, the patient died from cardiac failure. Histological examination of the tumor revealed atypical elongated cells and areas of large cells with significantly enlarged hyperchromatic and lobulated nuclei. In some portions, the tumors had a biphasic appearance. The tumor cells resembled epithelial tissue but immunohistological analyses to detect cytokeratins yielded negative results. The elongated cells expressed desmin and smooth muscle actin. A vast majority of the tumor was solid or hard, histologically corresponding to osteosarcoma. Later, it was found that the patient undergone right-sided mastectomy for a malignant phyllodes tumor with osteosarcomatous differentiation three years previously. The metastasis to the heart was the only metastasis detected by the autopsy.
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November 2015

Is there an intermediate-risk non-seminoma? long-term treatment results from a single center.

J BUON 2014 Jul-Sep;19(3):775-9

Department of Oncology, University Hospital Ostrava, Ostrava, Czech Republic.

Purpose: We retrospectively assessed the treatment results of patients with testicular non-seminoma to evaluate possible predictive and prognostic factors.

Methods: 189 patients with testicular non-seminoma treated between 2000 and 2012 were retrospectively evaluated. Treatment was based on orchiectomy plus chemotherapy (bleomycin/etoposide/cisplatin and vinblastine/ifosfamide/ cisplatin); retroperitoneal lymphadenectomy was only performed for residual disease after chemotherapy. The treatment protocol was updated regularly according to international standards. Overall survival (OS) was evaluated with the Kaplan-Meier method at a significance level of 5% according to stage, Karnofsky performance status (KPS), and chemotherapy dose intensity.

Results: OS differed significantly for patients at different TNM stages (p=0.000); however, detailed analysis revealed significantly worse survival only in stage IIIC (10-year OS for IIIC vs IIIA+B, 35 vs 88%, p=0.001), while the difference between IIIB and lower stages was not significant (p=0.383). Patients with no chemotherapy dose reduction had significantly higher OS than those with any kind of dose reduction (10-year OS 96 vs 0%, p=0.000). For stage IIIC disease, however, dose intensity had no influence on OS (p=0.167). KPS had no prognostic significance for OS (KPS<80 vs ≥80, p=0.627) for stage IIIA+B and for stage IIIC.

Conclusion: The standard of care for testicular non-seminoma offers excellent prognosis with no significant differences in OS for good- and intermediate-risk patients. Reduction of chemotherapy dose negatively impacted OS in patients with stage IIIA+B and thus should be avoided.
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November 2014

Lymphangiogenesis and its correlation with the VEGF expression and the sentinel lymph node in cutaneous melanomas.

Biomed Res Int 2014 25;2014:372979. Epub 2014 Jun 25.

Center of Nanotechnology, VSB-Technical University, Ostrava, Czech Republic.

The aim of the study is to evaluate the density of intratumoral and peritumoral lymphatic vessels in primary cutaneous melanomas and to assess their correlation with the status of sentinel lymph nodes and the VEGF expression in tumor cells and stromal cells. A total of 40 patients were enrolled in the study: the melanomas were radically excised with the extirpation of the sentinel lymph node. The study subjects were divided into two groups: 20 cases with positive and 20 cases with negative sentinel lymph node results. The density of lymphatic vessels was evaluated by the antibody D2-40 and the VEGF expression was investigated in the semiquantitative way. The VEGF expression in melanoma cells and the stromal cells was negative to variable positive at both SLN negative and SLN positive patients in all pT stages. In the group of SLN positive patients, the density of intratumoral lymphatic vessels was low up to moderate, while it was observed to be absent, somewhere on the low level in the group of SLN negative patients. On the other side, the density of peritumoral lymphatic vessels was equally numerous at both SLN negative and SLN positive patients. The lymphatic invasion was found out at 4 SLN positive patients only. The ulceration was chiefly in the group of LN positive patients. The results show that the density of lymphangiogenesis and the intensity of the VEGF expression are considered to be an unreliable predictor of melanoma metastasis to the sentinel lymph node, but the ulceration and the lymphatic invasion can predict the potential for metastasis.
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http://dx.doi.org/10.1155/2014/372979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096056PMC
October 2015

[Risk factors and progression predictors of Barrett´s oesophagus to adenocarcinoma].

Vnitr Lek 2014 May-Jun;60(5-6):467-73

Gastroesophageal reflux disease is a quite common disorder, and the condition affects some 40 per cent of population in the course of their lifetime. Fortunately, about half of the patients examined due to clear symptoms do not manifest macroscopic damage of the oesophageal mucosa, and serious endoscopic findings (Barrett's oesophagus) are observed in only a small percentage of patients (10%). Barrett's oesophagus is a serious complication - precancerous condition with a 30-fold higher risk of development of oesophageal adenocarcinoma when compared with patients without this condition. The article presents risk factors and predictors of progression of the Barrett's oesophagus into the stage of adenocarcinoma. The main risk factors associated with oesophageal adenocarcinoma are male sex, white race, gastroesophageal reflux.
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October 2015

Recurrent salivary pleomorphic adenoma shows increased immunohistologic expression of bcl-2 oncoprotein.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015 Sep 14;159(3):460-5. Epub 2014 Mar 14.

Department of Pathology, University Hospital Ostrava.

Background: Internal cell biology, including apoptotic regulation, is presumed to play a key role in the development of recurrent pleomorphic adenoma (PA).

Aim: The aim of our study was to determine the relevance of B-cell lymphoma 2 (bcl-2) oncoprotein immunoexpression and distribution in primary PA, and its recurrence.

Methods: Ten primary-non-recurrent, 14 primary-to-recur, and 28 recurrences of parotid PA patients aged 19-73 (mean 40.7±16.7) years were enrolled. The bcl-2 expression was compared between groups using a semi-quantitative histoscore, defined as the multiple of the percentage of cells by the intensity of immunostaining.

Results: Widely varying bcl-2 immunoreaction was found in the epithelial areas of 91.7% of primary and 85.2% of recurrent PA. Similarly varying but much less, immunopositivity was found in the myxoid areas of 62.5% of primary and 71.4% of recurrent tumours. No obvious differences in the bcl-2 staining intensity or pattern of specific epithelial morphologic structures in either the primary-non-recurrent, primary-to-recur or recurrent tumours were found. In both the mesenchymal and epithelial areas of PA, the differences in bcl-2 immunohistoscore between the primary-non-recurrent and primary-to-recur groups were not statistically significant (P=0.62, respectively 0.51). In the mesenchymal areas, the study revealed a significantly increased histoscore in recurrent tumours compared to their corresponding primaries (P=0.01). Increased bcl-2 expression in recurrent PA suggests an exaggerated aggressiveness of that tumor.

Conclusion: The fact that a significant difference in the histoscore was found exclusively in the myxoid component seems to accord with the reported prevalence of the latter in recurrent and metastatic PA.
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http://dx.doi.org/10.5507/bp.2014.013DOI Listing
September 2015

Uterine tumors resembling ovarian sex cord tumors (UTROSCT). Report of a case with lymph node metastasis.

Cesk Patol 2014 Jan;50(1):46-9

Unlabelled: Uterine tumors resembling ovarian sex cord tumors (UTROSCT) have an uncertain histogenesis. Although generally considered to be benign, they metastasize in some cases. We report the case of a 53-year-old woman who presented with vaginal bleeding. Clinical examination revealed a tumor sized 1.5 cm in diameter localized in the subendometrial region of the uterine wall. Histologically, the tumor consisted of epithelioid oval cells arranged in solid nests, trabeculae and ribbons. Immunohistochemically, approximately 1% of tumor cells expressed strong desmin positivity, calponin in 10% of cells, WT1 in 80% cells, and Ki-67 was positive in about 5 % of tumor cells. All the other immunohistochemical reactions applied including anti-cytokeratin antibodies were negative. The RT-PCR method for identification of the JAZF1-JJAZ1 fusion transcript was negative. In one lymph node in the right iliac artery region, a metastasis of UTROSCT was found. This finding adds to the previously reported UTROSCT cases with metastatic spread.

Keywords: uterine tumors resembling ovarian sex cord tumors - UTROSCT - metastasis - lymph node.
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January 2014