Impact of autoimmune gastritis on chronic urticaria in paediatric patients - pathophysiological point of views.

We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION: Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN: • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW: • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.

Significance of transcriptionally-active high-risk human papillomavirus in sinonasal squamous cell carcinoma: Case series and a meta-analysis.

Sinonasal cancers represent a highly heterogeneous group of head and neck cancers, for which etiological and prognostic significance of high-risk human papillomavirus (HPV) infections has not yet been conclusively established. We investigated the presence of transcriptionally-active high-risk HPV in a series of 34 sinonasal squamous cell cancer (SNSCC) cases and evaluated the effect of transcriptionally-active HPV on the overall survival. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the prevalence of HPV positivity across histological subtypes of SNSCC. The presence of transcriptionally-active HPV was detected by HPV mRNA using the polymerase chain reaction (PCR) or in situ hybridization (ISH). p16 expression was evaluated as a surrogate marker for transcriptionally-active HPV infection by immunohistochemistry (IHC), the presence of high-risk HPV DNA was tested by PCR and the HPV genotypes were determined by sequencing of PCR amplicons. Transcriptionally-active HPV infections were found in ~25% of the SNSCC cases. The role of HPV infection in keratinizing SNSCC may be higher than previously reported (~32% in our study vs. ~0-6.3% in all other studies). Patients with transcriptionally-active HPV-positive SNSCCs were more likely to be diagnosed at earlier stages (p<0.05) and displayed better mean overall survival, although the difference between HPV-positive and HPV-negative groups was not statistically significant. In contrast to other non-oropharyngeal squamous cell carcinomas (non-OPSCCs) of the head and neck, in SNSCCs, p16/IHC and p16/IHC+HPV DNA displayed high specificity as surrogate markers of transcriptionally-active HPV infections. However, p16/IHC may have significantly lower sensitivity as a surrogate marker of transcriptionally-active HPV in SNSCCs compared to OPSCCs. Furthermore, in our group of SNSCCs, all cases positive for high-risk HPV DNA by PCR were also transcriptionally-active (causative) infections with positive HPV mRNA by ISH. Our results imply a possible different role of HPV-mediated carcinogenesis of squamous cell epithelium in oropharyngeal and sinonasal sites with the latter displaying a lower proportion of causative HPV infections; nevertheless, most cases positive for high-risk HPV DNA, p16/IHC or combination thereof were also found positive for transcriptionally-active HPV. The prognostic significance of HPV status in SNSCCs remains inconclusive and future studies should investigate the presence of transcriptionally-active HPV by direct HPV testing.

[Complications arising out of insufficient reporting of clinical data to the pathologist investigating placentas]. / Komplikace vyplývající z neposkytnutí relevantních klinických údaju patologovi vysetrujícímu placenty.

OBJECTIVE: To inform gynecologists-obstetricians about the problems associated with pathological examination of placentas, with special regard to the possibility of crucial role of complete and relevant clinical data in establishing the correct pathological diagnosis. DESIGN: Case report and overview of the problems associated with examination of placentas by pathologist. SETTING: Sikl´s Institute of Pathology, Faculty Hospital and Medical Faculty Pilzen of the Charles University in Prague; Biopticka laborator, s.r.o., Pilzen. METHODS: Own observation in the setting of routine pathological examination. RESULTS: Case report representing a typical complication resulting from insufficient interdisciplinary communication describes a case of unsatisfactory result of pathological investigation of placenta due to the missing clinical information about complications of the late phase of pregnancy which eventually led to intrauterine death of the fetus. Due to the absence of the clinical information of paramount importance, the initial investigation of placenta was untargeted and thus imperfect. Therefore, the primary investigation of the placenta did not reveal pathological changes responsible for the complications of pregnancy. It was only the revision of material necessitated by the information additionally conveyed by gynecologist-obstetrician leading to the final correct pathological diagnosis, which even averted the possibility of serious forensic consequences. CONCLUSION: The basic prerequisite for proper pathological examination of placenta is sharing the available clinical data with the pathologist performing the morphological investigation, mainly focusing on complications of pregnancy. Lack of such information causes examination of placenta more difficult and sometimes even unable to interpret, as the interpretation of morphological changes of placenta have to interpreted in the context of clinical data on the course of pregnancy. Regarding the extreme emotional and possibly even legal consequences of lethal complications of pregnancy or delivery, the correct pathological diagnosis may be of crucial importance.

Alveolar echinococcosis - a rare disease with differential diagnostic problems.

INTRODUCTION: Alveolar echinococcosis is a life-threatening zoonotic parasitic disease. Its incidence is rare. In some cases, the correct and timely diagnosis can be difficult. CASE REPORT: The authors present the case of a young patient with liver, diaphragm and lung involvement. The suspicion of echinococcus infection was made on the basis of medical history, clinical symptoms, and a combination of ultrasonography, computed tomography, magnetic resonance imaging tests and serological methods. The patient underwent multimodal treatment with albendazole and en-bloc resection of the liver, lung and diaphragm. The definitive diagnosis of alveolar echinococcosis was determined from samples of the resected tissues using histopathology and polymerase chain reaction methods. The patient has been followed regularly and is on life-long treatment with albendazole. CONCLUSION: The precise diagnosis and multimodal therapy of alveolar echinococcosis is fundamental from the point of view of patient long-term survival. KEY WORDS: alveolar echinococcosis - diagnosis - multimodal treatment - follow-up.

Protein expression of ATP-binding cassette transporters ABCC10 and ABCC11 associates with survival of colorectal cancer patients.

PURPOSE: This study investigated the prognostic importance of protein expression of ATP-binding cassette (ABC) transporters ABCC10 and ABCC11 in colorectal cancer. METHODS: Protein content of ABCC10 and ABCC11 was assessed in tumor tissue blocks of 140 colorectal cancer patients and associated with survival of patients with regard to 5-fluorouracil-based therapy. RESULTS: Low ABCC10 protein content in tumors increased hazard ratio of patient's death more than three times in comparison with high ABCC10-expressing tumors (P = 0.004). In contrast, the low ABCC11 content increased the hazard ratio of cancer recurrence in patients almost four times (P = 0.016). Analysis of patients treated with regimens based on 5-fluorouracil revealed that patients with low ABCC11 content in their tumors had shorter disease-free interval than those with higher content (P = 0.024). CONCLUSIONS: The present study shows for the first time that the protein expression of ABCC10 significantly associates with overall survival and the expression of ABCC11 with disease-free interval of colorectal cancer patients and provides strong impulse for further validation of their prognostic value in colorectal cancer.

[Lynch Syndrome -  the Pathologist's Diagnosis]. / Diagnóza Lynchova syndromu od patologa.

Lynch syndrome (formerly known as hereditary non-polyposis colorectal cancer) is the most com-mon hereditary colorectal cancer syndrome. The syndrome is caused by a germline mutation of one of the mismatch repair (MMR) genes responsible for DNA replication error repair. Impaired function of the proteins encoded by these genes leads to microsatellite instability (MSI), which is associated with increased incidence of neoplasms: mainly colorectal cancer. According to recent estimates, up to 5% of all colorectal cancers are associated with Lynch syndrome. Due to this relatively high frequency, familial occurence, absence of premorbid phenotype, and development of malignant tumors at a reproductive age, a correct diagnosis is important not only from an ethical but also from an economical point of view. Unfortunately, clinical means of diagnosis, namely, the revised Bethesda guidelines designed to detect patients suitable for genetic testing for Lynch syndrome, lack sufficient sensitivity. The methods associated with modern pathology are more sensitive than the clinical criteria used to detect patients suspected of having Lynch syndrome. Pathological diagnostics are based on direct or indirect detection of MSI. Indirect methods include analysis of morphological signs associated with MSI in histological samples from colorectal carcinoma patients and immunohistochemical investigation of MMR protein expression. To rule out sporadic cases caused by epigenetic inactivation of an MMR gene, molecular genetic investigation of the BRAF gene and methylation analysis of the MLH1 promoter are performed during diagnostic workup. A suspicion of Lynch syndrome based on the results of the methods mentioned above should be proven by detection of a germline mutation in an MMR gene in peripheral blood leukocytes.

[Predictive and prognostic factors of gastric cancer]. / Prediktivní a prognostické faktory karcinomu zaludku.

INTRODUCTION: Gastric cancer is a frequent malignant disease with poor prognosis. Most patients undergo only palliative treatment. Chemotherapy is another alternative but its effect differs in individual patients. METHOD: This is retrospective study. We enrolled 54 patients (N=54) according to the inclusion criteria. We performed quantification of gene expression of selected genes and some microRNA from tumour tissue, which was used for the diagnosis. Statistical analysis of the data was performed. RESULTS: We demonstrated a predictive value of gene expression of thynidylate synthase in tumour tissue for a therapeutic effect of chemotherapy based on 5-Fluorouracil or Capecitabine. At the same time, we demonstrated a predictive value of miR181, miR150, mir192 and miR342 microRNA levels from the tumour tissue. In addition, we succeeded to demonstrate a predictive value of miR221, miR224, miR520 and miR375 microRNA levels for a therapeutic effect of chemotherapy based on platinum derivates. CONCLUSION: Thanks to the use of efficient therapy predictors, we can distinguish those patients who will profit from chemotherapy from patients where an effect cannot be expected. Thanks to personified oncology therapy the quality of life of some patients can be improved while reducing the costs of the therapy by avoiding inefficient chemotherapy. Only an early diagnosis of gastric cancer can reverse the adverse prognosis of patients with this disease. KEY WORDS: gastric cancer - microRNA - prognostic markers - predictive markers.

Utility of immunohistochemical investigation of SDHB and molecular genetic analysis of SDH genes in the differential diagnosis of mesenchymal tumors of GIT.

Loss of expression of beta subunit of succinate dehydrogenase (SDHB) was proved to be present in a subgroup of KIT/PDGFRA wt gastrointestinal stromal tumors (GISTs). To evaluate possible diagnostic utility of SDHB immunohistochemistry in the differential diagnostics of mesenchymal tumors of gastrointestinal tract (GIT), 11 cases of KIT/PDGFRA wt GISTs, 12 gastric schwannomas (GSs), 20 solitary fibrous tumors (SFTs), 4 leiomyomas (LMs), 16 leiomyosarcomas (LMSs), 5 synovial sarcomas (SSs), 3 endometrioid stromal sarcomas (ESSs), and 1 ileal inflammatory myofibroblastic tumor (IMT) were investigated for SDHB immunoexpression together with molecular genetic analysis of genes encoding succinate dehydrogenase (SDH). Three recent cases of KIT/PDGFRA mutant GISTs were used as controls. Among the 11 KIT/PDGFRA wt GISTs, 6 expressed SDHB, 1 of them harboring a sequence change of SDHD. All SDHB-negative cases were SDHB-D wt. In 1 of the control GIST cases molecular genetic analysis revealed an SDHD sequence change in addition to a mutation in KIT exon 11. No SFT was truly SDHB-negative, but in 2 of them the staining was impossible to analyze. Furthermore, 1 SFT carried an SDHB and another 1 SDHD sequence change. All GSs, LMs, LMSs, SSs, ESSs, and IMT were SDHB-positive or non-analyzable, and SDHB-D wt. Additional factors may play a role in regulating expression of SDHB. Furthermore, SDHB immunohistochemistry alone may be misleading in excluding tumors other than GIST (especially SFT) in the differential diagnosis of KIT/PDGFRA wt mesenchymal tumors of GIT.

[Detection of cancer stem cells in ovarian cancer]. / Detekce nádorových kmenových bunek karcinomu ovaria.

OBJECTIVE: Detection of cancer stem cells (CSCs) in ovarian cancer, influence of CSCs on overall survival, disease free interval. Results in comparison with literature. DESIGN: Original study. SETTINGS: Department of Gynaecology and Obstetrics, Faculty Hospital Pilsen and Medical Faculty in Pilsen, Charles University, Sikls Institute of Pathology, Faculty Hospital Pilsen and Medical Faculty in Pilsen, Charles University. METHODS: 23 specimens of papillary-serous ovarian carcinoma and 4 specimens of endometroid ovarian carcinoma were included in the study. Specific antibodies to CD44 and CD133 antigens were used. Immunoreaction of both CD44 and CD133 was evaluated for the high power field. RESULTS: There was no significant correlation between CD44 expression and disease free interval and overall survival. CD133 expression was not evaluated due to an inadequate immunoreaction antibody - antigene. CONCLUSION: We did not find any statistically correlation between CD44 expression and overall survival and disease free interval in our series of patients with ovarian carcinoma. It seems to be better to use different antibody for CD133 detection.

[Predictive diagnosis of HER2 in gastric adenocarcinoma]. / Prediktivní diagnostika HER2 v adenokarcinomu zaludku.

Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). This receptor is overexpressed in approximately 20% of gastric adenocarcinomas. The overexpression is associated with a worse prognosis, but on the other hand, patients with HER2-positive cancers were shown to benefit from the addition of trastuzumab to standard chemotherapy. To begin the targeted therapy with trastuzumab, HER2 testing is now mandatory with immunohistochemistry being the primary test followed by in situ hybridization analysis of HER2 amplification in cases with equivocal immunopositivity (score 2+). The immunohistochemical HER2 scoring system has been modified to include incomplete basolateral and lateral membrane staining, and to differentiate between surgical and endoscopical samples of the tumor. Benefit from trastuzumab treatment can be expected in tumors showing an immunohistochemical score 3+, and in cases with score 2+ and a positive finding of HER2 amplification. Clinical trials with further monoclonal antibodies and receptor tyrosine kinase inhibitors are recently ongoing to broaden the spectrum of possibilities of a multitargeted approach to the treatment of gastric cancer.

[Mucinous adenocarcinoma of the appendix--case report]. / Mucinózni adenokarcinom apendixu--kazuistika.

The authors are describing a case of a patient with the diagnosis of the appendicular cancer. The 66-year-old patient underwent appendectomy because of signs of acute appendicitis, and than in the next step right-sided hemicolectomy because of histological finding of the mucinous adenocarcinoma of the appendix. Mucinous adenocarcinoma is the most common type of appendicular cancer, none the less this diagnosis is very rare.

[Ovarian tumor as a complication in diagnosis of the extraintestinal gastrointestinal stromal tumor--two case reports]. / Nádor ovaria jako komplikace diagnostiky extraintestinálního gastrointestinálního stromálního tumoru--dve kazuistiky.

OBJECTIVE: The aim of this study is to address difficulties in diagnosis of the extraintestinal gastrointestinal stromal tumor (GIST) when even in ovary is the tumor. One should ever think of the GIST in the case of peritoneal dissemination of the spindle/epithelioid cell tumor. In contrary, the late intraabdominal recurrence of primary both epithelial and non-epithelial tumor of genital tract can be undistinguishable by pure morphology. Complete clinical records and accurate operation field topography are both of great value. Documenting this phenomenon, presented is both late intraabdominal dissemination of primary uterine endometrial stromal sarcoma and massive ovarian involvement by extraintestinal GIST. DESIGN: Two case reports. SETTING: Biopsy Lab s.r.o. and Sikl's Department of Pathology, Charles University and Faculty Hospital, Pilsen. METHODS: The two casuistic reports are covered in detail including broad immunohistochemistry (LSAB+, Dako) and genetics (ABI Prism 310, PE/Applied Biosystems). RESULTS: In 75-year-old woman, 5 cm tumor in maximum diameter of the mesentery was diagnosed as an extraintestinal GIST. Multiple peritoneal recurrence occurred ten years later and the tumor has been reclassified as a disseminated endometroid stromal sarcoma. Ultimately, comprehensive search of clinical files confirmed hysterectomy and adnexotomy in 1973. The second case describes 49-year-old woman operated for tumorous obliteration of the small pelvis where a tumor 9 cm in maximum diameter was found. Initially, predominant epitheloid morphology of the tumor led to the diagnosis of primary epithelial malignancy, sex-cord stromal tumor or metastatic melanoma of the ovary. Finally, the help of immunohistochemistry and molecular biology rendered the tumor as an extraintestinal GIST, ovarian primary not excluded.

[Endoscopic cytoscopy in examination of the digestive tract]. / Význam endoskopické cytoskopie u vysetrení trávicího traktu.

A number of new endoscopic methods have been developed recently, which aim to allow the most accurate possible viewing of the mucosa of the digestive tract. These procedures include endoscopic cytoscopy, which together with confocal endoscopy is a technique of so-called endoscopic microscopy. By means of enodcytoscopy it is possible to view "in vivo" the morphological details of the surface of the mucosa of the digestive tract. The mucosa must, however, be thoroughly cleaned and stained with methylene blue. The paper presents our own initial experience of this method, which may lead to faster and more accurate diagnosis of pre-tumorous or tumourous inflammation processes in the mucosa of the digestive tract.