Systemic lupus erythematosus and secondary antiphospholipid syndrome in native sisters with reduced fertility.

OBJECTIVE: Systemic lupus erythematosus (SLE) and secondary anti-phospholipid syndrome (APS II) can cause increased morbidity and mortality of the fetus. We followed the course of fertility of two sisters with these two basic diseases. METHODS: In the Center for Immunology of Reproduction, we confi rmed both sisters had increased levels of some selected anti-phospholipid antibodies (against phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, DL-glycerole, anexin V, phoshatidic acid, cardiolipin, beta2-glycoprotein I), anti-nuclear, and anti-DNA antibodies. During the established immunosuppressive and hormonal therapy at the time of SLE remission, both sisters became pregnant. There was a physiological progression of pregnancy until the 19th week. RESULTS: At the 20th week of pregnancy, the older sister miscarried again, and the younger sister developed hypertension in the 31st week of pregnancy which was terminated by caesarean section. CONCLUSION: In our causal evaluation, we addressed two serious autoimmune diseases (SLE, APS II) in two sisters and described their course of pregnancy. However, only one of them became a happy mother.

The Use of CT Pattern in Differentiating Non-invasive, Minimally Invasive and Invasive Variants of Lung Adenocarcinoma.

BACKGROUND/AIM: This study determined whether computed tomography (CT) is an appropriate means by which to differentiate non-invasive and minimally invasive forms of pulmonary adenocarcinoma from the invasive variant. PATIENTS AND METHODS: A total of 64 patients (38 men and 26 women, aged 42-76, mean age 64), who underwent surgery for pulmonary adenocarcinoma and a chest CT no less than 1 month before surgery, were included in the study. Lesions exhibiting ground glass opacity or ground glass opacity with a solid component of 5 mm or smaller, were defined as minimally invasive or non-invasive adenocarcinomas. CT findings were correlated with histopathological examination. RESULTS: Distinguishing minimally invasive and non-invasive adenocarcinoma from invasive adenocarcinoma using CT was achieved with a sensitivity of 77.7%, a specificity of 97.8%, a positive predictive value of 93.3%, and a negative predictive value of 91.8%. CONCLUSION: CT can be useful in assessing the degree of invasiveness of pulmonary adenocarcinoma and is a potential tool for the individualization of treatment.

Thyroid transcription factor 1 and p63 expression is associated with survival outcome in patients with non-small cell lung cancer treated with erlotinib.

While erlotinib is primarily administered to patients with non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations, it is also prescribed to patients with wild type (wt) EGFR in higher lines of treatment. However, there is no predictive marker for erlotinib efficacy in patients with EGFR wt. Certain immunohistochemical (IHC) parameters, including thyroid transcription factor 1 (TTF1) and p63, have been reported to indicate predictive power in patients with EGFR wt. The present study focused on retrospective data from the University Hospital in Pilsen using the TULUNG register. TTF1 and p63 expression data were extracted from the hospital information system and merged with registry data to calculate progression-free survival (PFS) and overall survival (OS) rates. A cohort of 345 patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) exhibited similar erlotinib efficacies when TTF1 and p63 were ignored. However, significant differences were reported in PFS and OS rates of a subgroup of 126 patients where TTF1 and p63 parameters were known. In a univariate analysis, group A (ADC TTF1+/p63-) achieved PFS of 2.6 months, group B (SSC TTF1-/p63+) 1.9 months and group C (did not fit into groups A or B, i.e., ADC TTF1-/p63+ or SCC TTF1+/p63-) 1.4 months (P=0.006). Median OS was 14.2, 19.1 and 5.3 months for A, B and C, respectively (P=0.002). Furthermore, a multivariate analysis demonstrated IHC markers to be the only significant parameters for PFS and OS. Group C had a negative prognostic factor for PFS [hazard ratio (HR), 1.812; P=0.02] and OS (HR=2.367; P=0.01). In conclusion, patients with EGFR wt and lung carcinomas without TTF1 and p63 expression typical for ADC (TTF1+/p633-) or SCC (TTF1-/p63+) do not appear to be suitable candidates for erlotinib treatment.

Echinococcus multilocularis: Diagnostic problem in a liver core biopsy.

Echinococcus multilocularis causes an aggressive form of hydatidosis whose histomorphological picture is generally not well recognized. We report a case of 39-year-old women presenting with poorly circumscribed nodules in the right hepatic lobe. Owing to the clinical suspicion of focal nodular hyperplasia and hepatocellular adenoma, a core biopsy was performed. The histological findings of necrotic fibrous tissue infiltrated by narrow epithelial cords and small cysts containing cytokeratin positive material were in concordance with the diagnosis of cholangiocarcinoma. Subsequent examination of the surgically resected necrotic nodules with a vital tissue at the periphery corresponded to a reparative fibrosis accompanied by a striking ductular proliferation. Serological and molecular genetic work-up led to the diagnosis of Echinococcus multilocularis. The aim of this report is to point out the unusual histological features of the solid foci of alveolar hydatidosis, which consisted of necrotic fibrous tissue with ductular reaction. Such findings in a core biopsy may simulate regressively altered carcinoma.

Aggressive pulmonary adenocarcinoma with new FGFR translocation and cMET mutation not responsive to crizotinib and nintedanib treatment: a case report.

The onset of routine use of the next generation sequencing (NGS) leads to discovery of new mutations in non-small cell lung cancer (NSCLC). In addition, comprehension of therapeutic potential of these genetic alterations in clinical practice is needed and required. Both, rare mutations and the therapeutic considerations they prompt, are dealt with in our case report describing a new fusion mutation of the fibroblast growth factor receptor (FGFR). Our case report describes a 45-year Caucasian female, non-smoker, with the tyrosine-protein kinase Met (cMET) skip 14 mutation and a newly described fibroblast growth factor receptor-cholinergic receptor, nicotinic, alpha 6 (FGFR-CHNRA6) fusion. The tumor in this patient showed aggressive growth and was resistant to all treatment modalities administered (including combination chemotherapy with bevacizumab, pemetrexed and nintedanib), with the exception of very short efficacy of crizotinib. The patient died 5 months after diagnosis. According to the published literature, a theoretical future solution could be to administer multidimensional targeted therapy simultaneously.

Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens.

Pulmonary small cell carcinoma (SCLC) can be usually diagnosed based on the morphological evaluation of routine histological or cytological preparations. However, immunohistochemistry may be also necessary in problematic cases. Insulinoma-associated 1 (INSM1) has recently been reported as a highly sensitive and specific marker that displays positivity in ~90%-100% of poorly differentiated pulmonary neuroendocrine tumors. We compared diagnostic performance of INSM1 and previously reported composite marker CD56 + p16 + thyroid transcription factor-1 (TTF1) in the diagnosis of SCLC in small biopsy specimens and cytoblocks. The composite marker CD56 + p16 + TTF1 correctly classified 100% of SCLC cases, and its sensitivity was significantly higher than the sensitivity of INSM1. Among 100 SCLC cases, CD56, TTF1, and p16 each individually classified more specimens correctly than INSM1 (CD56: 84%, TTF1: 89%, p16: 95%, INSM1: 81%); the difference was statistically significant only for p16. INSM1 showed the lowest classification agreement between paired biopsy and cytoblock specimens (κ = 0.182), whereas CD56 and p16 displayed perfect agreement (κ = 1) and TTF1 showed moderate agreement (κ = 0.4). Although INSM1 is reportedly the most specific marker of SCLC, its sensitivity is not superior to p16 or composite marker CD56 + TTF1 + p16. Based on this study, we propose the following algorithm, which, in the appropriate clinical and histological context, may be useful in establishing the correct diagnosis of SCLC: First, INSM1 detection is performed, and if the result is negative, CD56 is added, followed successively by p16 and TTF1 if all previously applied markers are negative. This approach should detect most, if not all, SCLC cases, while successively trading specificity for sensitivity.

Esophageal dysplasia and adenocarcinoma: a study with double immunostaining for intestinal and gastric markers.

Columnar lined esophagus is a complication of long term gastroesophageal reflux disease and the main precursor of esophageal adenocarcinoma. Incomplete intestinal metaplasia in reflux esophagitis represents one of the most important risk factors for neoplastic transformation through the metaplasia-dysplasia-adenocarcinoma sequence. However, recent studies suggest that cardiac type mucosa also shows molecular abnormalities which are similar to those of incomplete intestinal metaplasia. Immunohistochemically, three types of esophageal dysplasia and adenocarcinoma are recognized: adenomatous-intestinal, hybrid/mixed and foveolar gastric types. We are interested in the phenotypes of these dysplasias and adenocarcinomas, especially in the possible relationship between them. For this reason, we evaluated the immunohistochemical expression of intestinal and gastric markers in a series of 30 cases of esophageal high-grade dysplasia (high-grade intraepithelial neoplasia) and of 70 adenocarcinomas. For immunohistochemical classification, we used double immunohistochemical reactions CDX2/MUC5AC and CDX2/MUC6, respectively. In cases of incomplete intestinal metaplasia, hybrid/mixed high-grade dysplasia and hybrid/mixed adenocarcinoma, we found the expression of gastric mucins MUC5AC and MUC6 only in cells with intestinal differentiation (with nuclear positivity for CDX2). The double immunostaining excluded the presence of the cells with "pure" foveolar gastric phenotype in hybrid lesions. Thus, the hybrid category actually represents the intestinal type dysplasia/adenocarcinoma (which is known to have a better prognosis than the foveolar gastric type). Keywords: immunohistochemistry - double immunostaining - reflux esophagitis - Barrett esophagus - esophageal dysplasia - esophageal adenocarcinoma.

P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma in small biopsies and cytology specimens.

Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or cytological specimens based on cytomorphology; however in ambiguous cases diagnosis requires additional support by immunohistochemistry. While TP53 and RB1 alterations with secondary overexpression of p16 are mainstay events in SCLC pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not yet been fully investigated. We examined the expression of p16, CD56, synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary carcinoids and non-small cell lung carcinomas, and compared diagnostic performance of these markers in the diagnosis of SCLC. P16 was positive in 95 of 101 SCLCs, and displayed highest diagnostic sensitivity of ~94%. Composite biomarkers CD56+p16+TTF1 and CD56+p16+SYP were both able to detect correctly all SCLC cases. Importantly, three (~3%) SCLC cases completely negative for all conventional markers displayed diffuse positivity for p16. CD56 and p16 demonstrated highest concordance between paired small biopsy and cytology specimens. 50% of squamous cell carcinomas, ~41% of adenocarcinoma/NSCLC-favour adenocarcinoma cases, and ~93% of extrapulmonary small cell carcinomas also showed p16-positivity. Combination of CD56, p16 and TTF1 produced diagnostic classifier that outperformed best single marker CD56 in differential diagnosis between SCLC and NSCLC. In conclusion, in the appropriate morphological context p16 represents a useful supplementary marker for diagnosis of SCLC, even in cases where only cytological material is available.

Predictive relevance of miR-34a, miR-224 and miR-342 in patients with advanced squamous cell carcinoma of the lung undergoing palliative chemotherapy.

Attributing to their pathophysiological role and stability in biological samples, microRNAs (miRNAs) have the potential to become valuable predictive markers for non-small cell lung cancer (NSCLC). Samples of biopsy tissue constitute suitable material for miRNA profiling with the aim of predicting the effect of palliative chemotherapy. The present study group included 81 patients (74 males, 7 females, all smokers or former smokers) with the squamous cell carcinoma (SCC) histological subtype of NSCLC at a late stage (3B or 4). All patients received palliative chemotherapy based on platinum derivatives in combination with paclitaxel or gemcitabine. The expression of 17 selected miRNAs was measured by reverse transcription-quantitative polymerase chain reaction in tumor tissue macrodissected from formalin-fixed paraffin-embedded (FFPE) tissue samples. To predict the effect of palliative chemotherapy, the association between gene expression levels and overall survival (OS) time was analyzed. From the 17 miRNAs of interest, low expression levels of miR-342 and high expression levels of miR-34a and miR-224 were associated with a reduced OS time in subgroups of patients based on smoking status and treatment modality. Using cluster analysis, associations between combinations of miR-34a, -224 and -342 expression levels with patient survival were identified. The present study revealed that patients with the simultaneous high expression of miR-224 and -342 had a similar prognostic outcome to those with the low expression of miR-224 and -342, which was significantly reduced, compared with patients exhibiting high expression of either miR-224 or miR-342 with low expression of the other. We hypothesize that the effect of a particular miRNA is dependent on the expression level of other members of the miRNA network. This finding appears to complicate survival analyses based on individual miRNAs as markers. In conclusion, the present study provides evidence that specific miRNAs were associated with OS time, which may be candidate predictors for the effectiveness of palliative treatment in SCC lung cancer patients. This objective can be better achieved by combining more markers together than by using individual miRNAs.

A more sensitive detection of micrometastases of NSCLC in lymph nodes using the one-step nucleic acid amplification (OSNA) method.

BACKGROUND: Detection of tumor cells in lymph nodes (LNs) removed during the treatment of pulmonary tumor by radical surgery is limited by the possibilities of standard histopathological methods. The goal of this study was to obtain more accurate pTNM status by a more sensitive detection of micrometastases in LNs. METHODS: A total of 885 LNs, an average of 13.8 LNs per patient, were removed during 64 surgeries. LNs from the same zone were pooled together as a group, five groups of LNs were examined in each patient. A total of 320 groups of LNs were examined. One-step nucleic acid amplification (OSNA) method was compared to standard histopathological examination with haematoxylin-eosin (H&E) staining and CK19 immunohistochemistry, specifically by an ultimate analysis of all intraoperatively removed LNs. RESULTS: Identical results for H&E and OSNA examinations were recorded in 286 groups of LNs (89.4%). In total, positive examinations were recorded in 27 groups of LNs (8.4%) using the OSNA method, which were H&E negative. In seven groups of LNs (2.2%), the H&E examination was positive, while OSNA method produced negative results. CONCLUSIONS: The OSNA examination led to a higher pTNM stage classification in 14 (21.9%) patients. The clinical significance remains the subject of follow-up research.

[Hamartoma of mature cardiac myocytes. Autopsy case report]. / Hamartom ze zralých kardiomyocytu. Pitevní kazuistika.

Hamartoma of mature cardiac myocytes (HMCM) is a rare benign pseudoneoplastic myocardial lesion. We describe a case of 39-year-old Bulgarian woman living in the Czech Republic, who died because of rupture of anterior communicating artery aneurysm, and severe bronchopneumonia. An incidental finding at the autopsy was a whitish unencapsulated and not sharply demarcated tumor of the left ventricle and adjacent area of interventricular septum, which protruded above the plane of section. Microscopically the tumor consisted of various different forms of disorganized hypertrophic mature cardiac myocytes without vacuolization of cytoplasm, focally in a "herringbone" pattern. Dilated venules and thickened intramural coronary arteries, and intervening bands of connective tissue were present between cardiomyocytes in the tumor. Immunohistochemical staining of MIB1 for the detection of proliferative activity was completely negative. No inflammatory infiltration, adipose tissue or calcifications were present in the tumor.

Solitary Fibrous Tumor - Less Common Neoplasms of the Pleural Cavity.

PURPOSE: solitary fibrous tumors (SFT) represent a heterogeneous group of primary pleural neoplasms with a low incidence rate and of which the biological origin, which consists of mesenchymal cells, is uncertain. METHODS: The authors present herewith a retrospective analysis of 22 patients with SFTs who were diagnosed and surgically treated between the years 2000-2015. The preoperative tumors were successfully verified morphologically by transthoracic core needle biopsy under CT control in 27.3% of patients. Surgical approaches were either posterolateral thoracotomy or videothoracoscopy. The follow-up median was 45 months (range 1-188 months). RESULTS: Twenty tumors were surgically removed radically, two tumors were found to be unresectable due to the considerable tumor size. From histological point of view 81.8% of tumors were SFT with low malignant potential, 18.2% of tumors with high malignant potential. Despite the radical extirpation of the SFT, it relapsed in two patients. CONCLUSION: The gold standard of SFT treatment is radical surgical removal; however, patients at risk of recurrence require additional follow-ups. The results of adjuvant therapy in recurrent and malignant forms of SFTs are the subject of discussion and further study.

[Patient with Three EGFR Mutations - Gradual Development of Resistance to Previous Targeted Treatment]. / Pacientka se tremi EGFR mutacemi - postupný rozvoj rezistence na predchozí cílenou lécbu.

BACKGROUND: Patients with sensitive EGFR mutations are already being treated with first and second generation tyrosine kinase inhibitors (TKIs). However, resistance to these drugs occurs over time, and over half of all cases is caused by a mutation (T790M) in the EGFR kinase domain. Osimertinib offers a new treatment option that overcomes this problem. Unfortunately, resistance to this drug also develops after several months of treatment and is caused by another mutation (C797S) in EGFR. CASE REPORT: Our case report provides evidence for the progressive development of EGFR-TKI resistance in a patient with a deletion of exon 19 in the EGFR gene. First, based on a mutation (T790M) identified after afatinib treatment and a subsequent mutation (C797S) mutation identified after osimertinib treatment. We mention overcoming this resistance (C797S) mutation by using 4th generation EGFR-TKI and other alternative procedures (chemotherapy, immunotherapy, and combinations of older EGFR-TKI generations). We also mention a rare case of peritoneal metastasis that occurred after previous treatment with osimertinib that we attempted to ameliorate by using erlotinib because the impaired condition of the patient did not allow treatment by chemotherapy. There are documented cases in which erlotinib has been successfully given to patients with peritoneal metastases and patients with the EGFR mutation C797S following progression to afatinib. This was not the case in our patient, probably because of the remaining EGFR mutation T790M. CONCLUSION: In our case report, erlotinib did not show efficacy after progression to osimetinib. Nowadays, chemotherapy is the only possible treatment in patients with good a performance status. The next-generation of TKIs are undergoing promising developments.Key words: EGFR - deletion on exon 19 - mutation T790M - mutation C797S - afatinib - osimertinibSubmitted: 12. 9. 2017Accepted: 12. 10. 2017 This project was supported by grant AZV 17-30 748A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

[Serrated adenomas and carcinomas of the colon]. / Serrated adenomy a karcinomy tlustého streva.

Approximately 5 - 35 % of colorectal carcinomas arise through serrated carcinogenesis. The precursor of such carcinomas are serrated adenomas, which differ from conventional adenomas morphologically as well as genetically. Herein, we provide a basic overview of serrated lesions of the large intestine with the focus on histological diagnosis and molecular biology.

Pyloric gland adenoma: a histologic, immunohistochemical and molecular genetic study of 23 cases.

Pyloric gland adenoma is a rare neoplasm with a gastric epithelial differentiation. We report 23 cases of pyloric gland adenoma in older persons, with a mean age of 74 years (range 52 - 87 years). They occurred in the esophagus (3 cases), corporal gastric mucosa (7 cases), duodenum (10 cases), gallbladder (2 cases), and choledochus (one case). Histologically, they were characterized by closely packed pyloric gland-type tubules with a monolayer of cuboidal to low columnar epithelial cells containing basally located round nuclei, and a superficial layer of tall, columnar, foveolar-type epithelium. Immunohistochemically, most tumor glands expressed pyloric gland mucin MUC6, whereas MUC5AC was positive in superficial gastric foveolar epithelium, and in a minority of glands. In addition, scattered neuroendocrine cells positive for chromogranin A and/or synaptophysin were seen in all cases. In 3 cases (two cases in the gallbladder and one case in the esophagus), areas of intestinal metaplasia with CK20, CDX2, and MUC2 positivity were found. Focal low-grade dysplasia was found in five cases (21.7%), and diffuse high-grade dysplasia was seen in one adenoma (4.4%), i.e., 6 of 23 PGAs (26.1%) showed dysplastic features. In one esophageal case, an invasive adenocarcinoma was diagnosed. Scattered p53 positive cells were found in all cases. Their number was higher in lesions with low-grade dysplasia and it was substantially increased in adenoma with high-grade dysplasia and in adenocarcinoma. Our molecular genetic results indicate that pyloric gland adenomas neoplastic nature is associated with p53 accumulation, mutations in oncogenes GNAS, KRAS, CTTNB1 and tumor suppressor genes SMAD4, and TP53. Pyloric gland adenoma can evolve into dysplasia and adenocarcinoma.

Anti-tumour necrosis factor treatment of severe psoriasis complicated by Epstein-Barr Virus hepatitis and subsequently by chronic hepatitis.

A case is described of severe acute hepatitis in 47-year-old woman with chronic psoriasis and psoriatic arthritis treated with infliximab. Although clinical, serological and laboratory results were compatible with acute EBV hepatitis, it was difficult to differentiate between EBV infection and other non-infectious causes of hepatitis. The patient gradually developed chronic hepatitis with liver steatosis and efficient treatment with adalimumab had to be stopped. This case presents an uncommon complication that may arise from the use of biologic therapy and calls for caution in long-term management of psoriatic patients with internal comorbidities.

Predictive and prognostic significance of sodium levels in patients with NSCLC treated by erlotinib.

BACKGROUND: Hyponatremia is a well-known phenomenon in cancer patients. The aim of our retrospective study was to assess the relationship of natremia levels to predict treatment with erlotinib and also to assess the prognosis of patients with hyponatremia. PATIENTS AND METODS: We analyzed data of 544 patients with advanced-stage non-small cell lung cancer (NSCLC) treated with erlotinib. RESULTS: Hyponatremia was measured in 21.5 % of patients before treatment with erlotinib. We found a significant increase in the effectiveness of treatment with erlotinib in patients with normal levels of sodium to hyponatremic patients. Progression-free survival (PFS) and overall survival (OS) were also significantly higher in patients with normal natremia. Multivariate Cox model analysis demonstrated that natremia was an independent factor for PFS and OS. CONSLUSION: We reported hyponatremia not only as a prognostic marker in NSCLC patients but also as predictive marker of erlotinib treatment efficacy, being an independent factor at the present large retrospective study. Its possible effect in clinical practice is bigger thanks the simple possibility of testing of hyponatremia and the low cost of this biomarker.

Intestinal metaplasia of the stomach and esophagus: an immunohistochemical study of 60 cases including comparison with normal and inflamed intestinal mucosa.

Recently, a new classification of intestinal metaplasia (IM) using immunohistochemical mucin markers was proposed. Two following types of IM were defined: (1) a mixed gastric and intestinal type also called incomplete IM; (2) a purely intestinal type, also called complete IM. We present a series of 30 cases of gastric IM and 30 cases of IM of the esophagus, using this new classification. In all gastric cases, IM developed in the mucus-neck region in the form of incomplete IM. Toward the mucosa surface, it matured gradually into complete IM. This maturation showed a gradual reduction of both foveolar mucin MUC5AC and pyloric gland mucin MUC6. In two of 30 cases, IM was of the incomplete hyperproliferative type. In one case, focal high-grade adenomatous dysplasia was found in the incomplete IM. In the esophageal cases, IM was found in inflamed cardiac-type mucosa, and it was usually of the incomplete type, with almost diffuse positivity for MUC5AC and with rare positivity of MUC6. The goblet cells and some cylindrical cells expressed intestinal mucin MUC2. The proliferation was higher than in the complete IM, and in one case, focal low grade adenomatous dysplasia was found. In addition, we examined the expression of mucins in normal and inflamed intestinal mucosa. These cases included 50 duodenal biopsies, 50 biopsies from the ileum, and 50 biopsies from the colon. The inflamed cases included celiac disease, Crohn's disease, and ulcerative colitis. Some goblet cells of the normal intestinal mucosa expressed both MUC2 and MUC5AC. More numerous MUC5AC+ goblet cells were found in the inflamed intestinal mucosa. In the duodenal and small intestinal mucosa, even the MUC6 positivity of a few goblet or cylindrical cells was found. In sum, our results indicate that incomplete IM is an initial step of the metaplastic process. It can mature into complete IM, or alternatively, it can develop dysplasia or adenocarcinoma. In addition, we found that gastric-type mucins are also present in normal or inflamed intestinal mucosa, and that the expression of these mucins is even enhanced in some inflammatory conditions. The expression of MUC5AC in complete IM and in normal or inflamed mucosa suggests that MUC5AC cannot be regarded as a marker of immaturity. In Barrett esophagus, our results were similar to those of previous studies, except for CDX2 of which reactivity was seen also in incomplete type of IM.

Surgical treatment of colorectal cancer pulmonary metastases: 12-year results.

UNLABELLED: The objective of the present study was to retrospectively analyze a cohort of patients who underwent surgery for colorectal cancer pulmonary metastases during a 12-year period. PATIENTS AND METHODS: The sample included 75 patients who were monitored in terms of overall survival (OS) and disease-free interval (DFI) in relation to patient's age, preoperative values of biomarkers, type of surgery, number and size of metastases, occurrence of complications and length of hospitalisation. RESULTS: A total of 95 surgical interventions were performed and 133 metastases were removed. Out of these, 28% of patients were free of any signs of relapse or disease progression for 5 years after metastasectomy. Those with two or more metastases are 2.3-times more at risk of disease progression. Tissue polypeptide specific antigen (TPS) values above the 140 IU/l cut-off point increase the risk of progression 3.9-times. The five-year survival rate among the group was 45%. Patients with 2 or more metastases are 2.7-times more at risk of death. TPS values above the 140 IU/l cut-off increase the risk of death 5.5 times, and carbohydrate antigen CA19-9 values above the 28 IU/ml cut-off point increase the risk of death by 3.2 times. CONCLUSION: The number of metastases and the preoperative TPS values are decisive prognostic factors influencing both OS and DFI.

[Where does Ewing sarcoma end and begin - two cases of unusual bone tumors with t(20;22)(EWSR1-NFATc2) alteration]. / Kde koncí a zacíná diagnóza Ewingova sarkomu - popis dvou neobvyklých kostních nádoru s translokací t(20;22)(EWSR1-NFATc2).

The authors present two cases of Ewing-like sarcoma of the humerus and femur of a 12-year-old boy and a 28-year-old male, respectively. Identical morphology in both tumors consisted of multiple solid nests with a mosaic collection of small, round, uniform cells with clear cytoplasm and no apparent nuclear atypia. A monotonous structural arrangement, including both rich vascularity of bordering septae and significant admixtures of eosinophil leucocytes, resulted in a final organoid "neuroendocrine-like" pattern. Immunohistochemistry revealed diffuse strong CD10, CD99 and CD138 positivity. Detailed molecular analysis in both tumors confirmed translocation t(20;22) resulting in an EWSR1-NFATc2 fusion gene. Additionally, this translocation was accompanied by amplification of the proximal part of the genes and surrounding areas. Clinically, both neoplasms behaved aggressively and they were primarily chemoresistant. Four years later, the patient with the lesion in the humerus developed a massive local recurrence with a disruption of osteosynthesis. The last follow-up disclosed suspicious metastatic deposits in the lung. The boy with the femoral tumor underwent a total femoral prosthesis and there are no signs of local or systemic recurrence after 11 months of follow-up. The authors discuss the taxonomic placement of these rare examples of Ewing-like sarcoma family in the light of new molecular discoveries.