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Nase kazuistika popisuje připad nekuřaka s generalizovaným plicnim adenokarcinomem s ALK translokaci. Po uvodnich dvou liniich chemoterapie byl ziskan přistup ke crizotinibu, na kterem brzy doslo ke vzniku drobne druhostranne leze, vyhodnocene jako metastaza v kontralateralni plici. Progresi v prave plici ale nezabranilo ani užiti ALK inhibitorů vyssi generace (ceritinib, alectinib, lorlatinib). Nasledně bylo prokazano, že přicinou teto progrese neni metastaticke onemocněni prave plice v podobě adenokarcinomu, ale přeměna ve skvamozni plicni karcinom s ALK translokaci. Timto sdělenim bychom proto radi upozornili na tuto eventualitu, kdy při atypickem radiologickem vývoji je na zvaženi rebiopsie progredujici leze.

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.

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.

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.

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.

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.

Introduction: The surgical therapy of selected secondary pulmonary tumors, including both solitary and multiple or bilateral tumours, is currently a generally accepted therapeutic procedure demonstrably extend- ing the long term survival of these patients. Purpose: The purpose of the present study is a ten-year retrospective analysis of a group of patients who un- derwent surgery due to pulmonary metastases of various primary tumors. Methods: In 2000-2009, 87 patients (of which 44 were male with a median age of 64 years) with secondary pulmonary tumors underwent surgery at the departments of the authors of this study. Solitary metastases were found in 60 patients, multiple metastases in the remaining patients, while 13 patients had bilateral metastases. The median disease-free period from surgery of the primary tumor was 31 months. Results: In total, 74 unilateral and 13 bilateral surgeries were performed in one or two periods. The most com- mon type of surgery included anatomical pulmonary resections (32 procedures), wedge resections (29 proce- dures) and laser excisions (24 procedures). In total, the radical resection was performed in 156 metastases. Post-operative morbidity was 17.2 % with zero mortality. A proportion of 50.6 % of operated patients survived after resection of metastases with median survival of 39 months. The overall three-year and fi ve-year survivals in the group were 57 % and 38 %, respectively. A proportion of 35.6 % of patients live after resection of metas- tases without disease progression, and the median is 15 months. Conclusion: The achieved results confi rm the positive role of pulmonary metastasectomy in the therapy of dis- seminated cancer disease (Tab. 1, Fig. 5, Ref. 34). Full Text in PDF www.elis.sk. Hematogeneous pulmonary metastases are generally consid- ered as a sign of advanced generalization of malignant disease. Up to one third of malignant tumors have pulmonary metastases, and in most of them the lungs are even the fi rst site of dissemination. Nevertheless, in a signifi cant number of patients, the pulmonary affl iction is stopped or eliminated during the dissemination of metastases, and these patients may benefi t from radical resection of metastases (1, 2). Surgical therapy of the selected secondary pulmonary tumors, not only solitary but also multiple or bilateral, is today generally the accepted therapeutic procedure which de- monstrably extends long term survival of these patients with ac- ceptable peri-operative morbidity and mortality. The purpose of the following study is a retrospective analysis of a group of patients who underwent surgery due to pulmonary metastases of various primary tumors over a period of ten years. Material and methods

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.We analyzed data of 544 patients with advanced-stage non-small cell lung cancer (NSCLC) treated with erlotinib.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.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.

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.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.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.The number of metastases and the preoperative TPS values are decisive prognostic factors influencing both OS and DFI.

DNA methylation is one of major factors in cancer progression. We observed multiple genes involved in cancer-related signaling and focused on patients with advanced non-small cell lung cancer (NSCLC) and evaluated methylation in relation to various clinical parameters.Thirty genes were examined in 121 NSCLC patients using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) method. Correlations to gender, smoking status, tumor subtype, disease stage and EGFR/KRAS mutation status were performed by chi-square test.90% of tumors exhibited methylation of at least one gene. Most frequently methylated were cadherin-13 (CDH13), Ras associated domain-containing protein (RASSF1A), Wilms' tumor protein (WT1), adenomatous polyposis coli protein (APC), paired box protein Pax-5 (PAX5), estrogen receptor (ESR1), an inhibitor of cyclin-dependent kinase p15 (CDKN2B), paired box protein Pax-6 (PAX6), transcription factor GATA-5 (GATA5) and cell adhesion molecule 4 (IGSF4). Overall methylation (any gene) was increased in adenocarcinomas (p=0.0329), unrelated to gender or disease stage. Several genes exhibited variable methylation with gender (CDH13, p0.001; GATA5, p=0.02; PAX6, p=0.01 and ESR1, p=0.03), smoking (CDH13, p=0.002), or epidermal growth factor receptor (EGFR) mutation status [Von Hippel-Lindau disease tumor supresor (VHL), p=0.001; CDKN2B, p=0.02; CDH13, p=0.02; APC, p=0.04 and ESR1, p=0.04].Differences in gene methylation associated with gender, smoking and EGFR mutation suggest potential for prediction in relation to management of tyrosine kinase inhibitor therapy.

Therapy by tyrosine kinase inhibitors (TKI) has become inevitable in treatment of advanced NSCLC. Mutations in EGFR and KRAS genes have been identified as the main potential predictive and prognostic factors. Here the clinical implications of EGFR/KRAS mutations in patients from two separate trials treated with gefitinib or erlotinib are analysed.A total of 360 patients (269 gefitinib and 91 erlotinib) were evaluated. Mutations in EGFR (exon 19 and 21) and KRAS (codons 12 and 13) and their impact on response and survival with respect to tumor subtype and smoking status were assessed.Adenocarcinomas revealed 399 days to progression (TTP) and 548 days overall survival (OS) for EGFR mutated vs. 119 days to progression and 137 days survival for non-mutated, p0.0001 (TTP) and p=0.0001 (OS). No EGFR effect was recorded for squamous cell tumors. For smoking status, both EGFR-mutated smokers and non-smokers profited from TKI therapy. Smokers: 243 vs. 122 days (mutated vs. non-mutated), p=0.0284 (TTP) and 244 vs. 126 days, p=0.0396 (OS); non-smokers: 390 vs. 71 days, p0.0001, (TTP) and 548 vs. 135 days, p0.0001 (OS). KRAS mutation in tumors did not result in a poorer prognosis in the subtype-selected groups, nor did it present as a negative factor in smokers.EGFR mutations possess statistical significance for a better therapy response and longer survival in all patients with adenocarcinomas (smokers as well as non-smokers). KRAS does not seem an "a priori" negative factor for TKI-based treatment of NSCLC.

A 34-year-old woman with a 1-year history of hypertension was admitted to the internal department of the catchment hospital on March 31, 2000, with dyspnea, chest discomfort, and vomiting. On April 11, cephalea with paroxysmal hypertension appeared. An ultrasonographic examination showed a suspected right adrenal pheochromocytoma. On April 18, the patient was transferred to our hospital, and a right adrenal tumor was diagnosed by CT scan. After her admission to the coronary unit, periodic fluctuations of blood pressure (and heart rate) were found. The blood pressure ranged between 65/40 and 270/150 mm Hg, with a 10-minute periodicity. During hypertension, pallor was present, accompanied by cephalea and sinus bradycardia, which was changing …

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord–stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical “square off” quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff (PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohistochemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1–AE3 by paranuclear dot-like or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immunohistochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical “square off” quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohistochemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of 12p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon–intron junctions in c-kit and PDFGRA genes.

Congenital epulis is a rare, soft-tissue benign condition that presents at birth. It arises from the alveolar mucosa and occurs more frequently in the maxilla, mainly in the frontal region. This condition may interfere with respiration, feeding or lip closure. Surgical excision is the only possible treatment, although spontaneous regression has been reported. This article presents the case of a female infant with a solid ovoid mass protruding from the oral cavity. Treatment of this lesion was surgical, and histopathological examination confirmed the clinical diagnosis of congenital epulis. Postsurgical follow-up was without complications; examination of the infant 5 months later has revealed only mild left frontal alveolar ridge hypoplasia without any sign of recurrence.