Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy: A European multicenter cohort study.

BACKGROUND AND OBJECTIVES: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status. METHODS: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex. RESULTS: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60-75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89-3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67-3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28-2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72-3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05-2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63-3.42, p = 0.005), respectively. CONCLUSION: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.

Pancreatic Neuroendocrine Microtumors (WHO 2022) Are Not Always Low-Grade Neoplasms: A Case with a Highly Increased Proliferation Rate.

Traditionally considered non-functional low proliferative benign neuroendocrine proliferations measuring less than 5 mm, pancreatic (neuro)endocrine microadenomas are now classified as pancreatic neuroendocrine microtumors in the 2022 WHO classification of endocrine and neuroendocrine tumors. This case report discussed the features of an incidentally identified 4.7-mm glucagon-expressing pancreatic neuroendocrine microtumor with MEN1 mutation only, chromosomally stable and an epigenetic alpha-like phenotype. The tumor was associated with an unexplained increased proliferation rate in Ki-67 of 15%. There was no associated DAXX/ATRX deficiency. The presented case challenges the conventional thought of a low proliferative disease of the so-called "pancreatic neuroendocrine microadenomas" and provides additional support to the 2022 WHO classification that also requires grading of these neoplasms. Despite exhibiting molecular features of less aggressive behavior, the case also underscores the biological complexity of pancreatic neuroendocrine microtumors. By recognizing the heterogenous spectrum of neuroendocrine neoplasms, the current case also contributes to ongoing discussions on how to optimize the clinical management of such tumors.

Somatic Genomic and Transcriptomic Characterization of Primary Ovarian Serous Borderline Tumors and Low-Grade Serous Carcinomas.

Low-grade serous carcinoma (LGSC) may develop from serous borderline tumor (SBT) tissue, where the micropapillary type (mSBT) presents the highest risk for progression. The sensitivity of LGSC to standard chemotherapy is limited, so alternative therapeutic approaches, including targeted treatment, are needed. However, knowledge about the molecular landscape of LGSC and mSBT is limited. A sample set of 137 pathologically well-defined cases (LGSC, 97; mSBT, 40) was analyzed using capture DNA next-generation sequencing (727 genes) and RNA next-generation sequencing (147 genes) to show the landscape of somatic mutations, gene fusions, expression pattern, and prognostic and predictive relevance. Class 4/5 mutations in the main driver genes (KRAS, BRAF, NRAS, ERBB2, USP9X) were detected in 48% (14/29) of mSBT cases and 63% (47/75) of LGSC cases. The USP9X mutation was detected in only 17% of LGSC cases. RNA next-generation sequencing revealed gene fusions in 6 of 64 LGSC cases (9%) and 2 of 33 mSBT cases (9%), and a heterogeneous expression profile across LGSC and mSBT. No molecular characteristics were associated with greater survival. The somatic genomic and transcriptomic profiles of 35 mSBT and 85 LGSC cases are compared for the first time. Candidate oncogenic gene fusions involving BRAF, FGFR2, or NF1 as a fusion partner were identified. Molecular testing of LGSC may be used in clinical practice to reveal therapeutically significant targets.

News in WHO 2021 classification of tumours of the central nervous system.

The aim of the presented communication is to clearly inform the general professional public about the newly approved modifications in this classification, including the newly approved types of tumours. A significant change is the new grading system for these tumours, including the innovative involvement of tumour profiling at the molecular level in the system for determining the degree of tumour differentiation and the application of the principle of integrated diagnostics, i. e. the synthesis of available histopathological and molecular findings in CNS tumors.

Molecular pathological profiling of selected tumors of the central nervous system using the MLPA method.

The current progress and increasing knowledge about the genetic causes of cancer opens up new possibilities for its treatment. However, it is necessary to combine the results obtained using classical pathological methods with sensitive, multiplex molecular pathological methods. The method that meets the required criteria is MLPA based on multiplex PCR reaction. This method detects both changes in gene copy number and DNA methylation and, last but not least, point mutations. The MLPA reaction is applicable to even highly fragmented DNA. At the same time, it is a robust method that can be performed on standard thermocyclers, the fluorescent tip label requires automatic sequencers. Up to 50 genetic markers can be tested in one reaction, a number that allows a diagnostic and prognostic conclusion. All these features lead to the routine use of MLPA analysis not only in diagnosis but also in cancer research. The present article aims to summarize the different types of MLPA reactions, its benefits, but also the potential pitfalls.

Multi-branch cooperation on SARS-CoV-2 omicron capture: a case report.

Shortly after the WHOs first notice a suspected case of omicron SARS-CoV-2 was reported in Liberec, Czech Republic. The primary goal of the following actions was to test the presence of the variant and stop the spread of the virus variant. On November 25 a sixty-year-old lady, who had recently returned from Namibia, visited a GP with flu-like symptoms and a rash on her chest. The antigen test was positive for SARS-CoV-2, a PCR test was planned. At that time, it was not known that a new variant of concern was spreading from Africa. On November 26 in the morning the GP announced a suspected omicron case to the Regional public health authority, who organized the following steps. A mobile sampling team was sent to the patient's home immediately, sample transported into the regional hospital and analyzed with the help of the national reference laboratory. The captured virus SARS-CoV-2 fitted the description of the omicron variant, was shared in the GISAID database and named hCoV-19/Czech Republic/KNL_2021-110119140/2021. Contact tracing was started immediately, eleven persons were tested and quarantined. One of them positive with no further spread. It is the first documented omicron case in the Czech Republic and one of the first cases in Europe, with an excellent systemic response to the alert. The laboratory was able to detect the omicron variant instantly after the request. This case also demonstrates how easily the virus spreads on long distances and how important it might be to increase the uptake of the booster vaccine.

Radiation-associated angiosarcoma of the breast: An international multicenter analysis.

INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.

CPR-related injuries after non-traumatic out-of-hospital cardiac arrest: Survivors versus non-survivors.

AIM: There have been no direct comparisons of cardiopulmonary resuscitation (CPR)-related injuries between those who die during CPR and those who survive to intensive care unit (ICU) admission. This study aimed to compare the incidence, severity, and impact on survival rate of these injuries and potential influencing factors. METHOD: This retrospective multicenter study analyzed autopsy reports of patients who experienced out-of-hospital cardiac arrest (OHCA) and were not admitted to hospital. CPR-related injuries were compared to OHCA patients with clinical suspicion of CPR-related injury confirmed on imaging when admitted to the ICU. RESULTS: A total of 859 out-of-hospital cardiac arrests (OHCA) were divided into 2 groups: those who died during CPR and underwent autopsy (DEAD [n = 628]); and those who experienced return of spontaneous circulation and admitted to the ICU (ICU [n = 231]). Multivariable analyses revealed that independent factors of 30-day mortality included no bystander arrest, cardiac etiology, no shockable rhythm, and CPR-related injury. Trauma was independently associated with older age, bystander CPR, cardiac etiology, duration of CPR, and no defibrillation. CPR-related injury occurred in 30 (13%) patients in the ICU group and 547 (87%) in the DEAD group (p < 0.0001). Comparison of injuries revealed that those in the DEAD group experienced more thoracic injuries, rib(s) and sternal fractures, and fewer liver injuries compared to those in the ICU group, without differences in injury severity. CONCLUSION: CPR-related injuries were observed more frequently in those who died compared with those who survived to ICU admission. Injury was an independent factor of 30-day mortality.

Urachal yolk sac tumor penetrating the bladder as a diagnostic challenge: a case report and review of the literature.

BACKGROUND: Yolk sac tumor (YST) is a germ cell tumor. It is primarily located in the gonads but can also occur extragonadally (extragonadal yolk sac tumor - EGYST), most commonly in the pelvis, retroperitoneum or mediastinum. Only a few YSTs of the urachus have been described. CASE REPORT: We present a rare case report of a 37-year-old male with episodes of macroscopic hematuria. The histological specimen obtained by transurethral resection showed a solid, and in some parts papillary infiltrative, high-grade tumor with numerous areas of marked nuclear atypia and clear invasion between the detrusor bundles. Glandular pattern has been observed in only minority of the tumor. Immunohistochemistry showed significant positivity for GPC3, SALL4 and cytokeratins AE1/AE3, while KRT7 and GATA3 were negative. We concluded that the biopsy findings were consistent with urothelial carcinoma with infrequent YST differentiation. In definitive surgical specimens we found a malignant epithelial, glandular and cystically arranged tumor of germinal appearance arising from urachus. The surrounding urothelium was free of invasive or in situ tumor changes. We reclassified the tumor as a urachal YST. CONCLUSION: EGYST was suspected because glandular and hepatoid structures were found, but the presence of these structures should be verified by immunohistochemistry.

Molecular testing in endometrial carcinoma (Joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists).

Molecular classification of endometrial carcinoma is becoming an important part of the diagnostic process with direct therapeutic implications. Recent international guidelines, including the joint ESGO-ESTRO-ESP recommendation, include the molecular classification into standard diagnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th) edition of the WHO classification of Female Genital Tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of Czech Medical Association of J. E. Purkyně (Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. The result of this meeting is a joint recommendation for molecular testing of endometrial carcinoma in routine diagnostic practice in the Czech Republic.

Molecular testing in endometrial carcinoma - joint recommendation of Czech Oncological Society, Oncogynecological Section of the Czech Gynecological and Obstetrical Society, Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists.

Molecular classification of endometrial carcinoma is becoming an important part of the dia-gnostic process with direct therapeutic implications. Recent international guidelines, including the joint recommendation of the European Society of Gynaecological Oncology, the European Society for Radiotherapy and Oncology and the European Society of Pathology include the molecular classification into standard dia-gnostic algorithms. Molecular testing of endometrial carcinomas is also recommended in the latest (5th edition) of the World Health Organization classification of female genital tumors. Due to the need to implement these recommendations in practice, representatives of four professional societies of the Czech Medical Association of J. E. Purkyně (the Czech Oncological Society, the Oncogynecological Section of the Czech Gynecological and Obstetrical Society, the Society of Radiation Oncology, Biology and Physics, and the Society of Czech Pathologists) organized a meeting focused on this topic. Recommendation for molecular testing of endometrial carcinoma in routine dia-gnostic practice in the Czech Republic.

Colon cancer patients with mismatch repair deficiency are more likely to present as acute surgical cases.

BACKGROUND: The effect of the genetic imprint on the emergency presentation of colon cancer remains unclear. The disparity between tumours evolving along different carcinogenetic pathways has not been studied systematically. This retrospective multicenter cohort study evaluates the association between mismatch repair status and the risk for acute surgery of colon cancer. PATIENTS AND METHODS: A retrospective multicenter cohort study including in total 870 patients from three different countries. Scandinavian cohort (Finland and Sweden), including a total of 412 patients operated between January 1, 1995 and December 31, 2010, was validated against a cohort from the Czech Republic, including a total of 458 patients, operated between January 1, 2018 and December 31, 2019. The proficiency or deficiency of mismatch repair was determined by immunohistochemistry. Primary outcome was the risk for acute colon cancer surgery given as the Odds Ratio (OR) in the univariable and multivariable analyses. Acute colon cancer surgery was defined as surgery performed during the same hospital admission as when the diagnosis of colon cancer was made. RESULTS: Of the 870 patients (399 females [46%]) included in the analyses, median age at surgery was 69 [interquartile range, 61-76] years, deficient Mismatch Repair (dMMR) status was found in 190 patients (22%), and 179 patients (21%) underwent acute surgery during the same hospital admission as when the diagnosis of colon cancer was made. In the Scandinavian cohort, a significant association between dMMR status and acute surgery was seen in both the univariable (OR 1.82, 95% CI 1.11-3.02, P = 0.017) and the multivariable (OR = 2.21, 95% CI 1.28-3.95, P = 0.005) analyses. This was confirmed in the Czech validation cohort in both the univariable (OR = 1.94, 95% CI 1.09-3.26, P = 0.022) and the multivariable (OR = 1.77, 95% CI 1.15-3.18, P = 0.021) analyses. CONCLUSION: This multicenter study reveals a strong association between acute colon cancer surgery and dMMR tumour status.

The role of vascularization on changes in ligamentum flavum mechanical properties and development of hypertrophy in patients with lumbar spinal stenosis.

BACKGROUND CONTEXT: Ligamentum flavum (LF) induced lumbar spinal stenosis (LSS) is conditioned not only by its "gathering" but especially by hypertrophy. Previous studies have examined the pathophysiology and biochemical changes that cause the hypertrophy. Some studies have described a link between chronic LF inflammation and neovascularization but others have reported highly hypovascular LF tissue in LSS patients. Currently, there is no practical application for our knowledge of the pathophysiology of the LF hypertrophy. Considerations for future treatment include influencing this hypertrophy at the level of tissue mediators, which may slow the development of LSS. To our knowledge, there is no study of micromechanical properties of native LF to date. PURPOSE: (1) To clarify the changes in vascularization, chondroid metaplasia, and the presence of inflammatory cell infiltration in LF associated with LSS. (2) To quantify changes in the micromechanical properties associated with LF degenerative processes. STUDY DESIGN/SETTING: Vascular density analysis of degenerated and healthy human LF combined with measurement of micromechanical properties. METHODS: The study involved 35 patients who underwent surgery between November 1, 2015 and October 1, 2016. The LSS group consisted of 20 patients and the control group consisted of 15 patients. LF samples were obtained during the operation and were used for histopathological and nanoindentation examinations. Sample vascularization was examined as microvascular density (Lv), which was morphometrically evaluated using semiautomatic detection in conjunction with NIS-Elements AR image analysis software. Samples were also histologically examined for the presence of chondroid metaplasia and inflammation. Mechanical properties of native LF samples were analyzed using the Hysitron TI 950 TriboIndenter nanomechanical testing system. RESULTS: Vascular density was significantly lower in the LSS group. However, after excluding the effect of age, the difference was not significant. There was high association between Lv and age. With each increasing year of age, Lv decreased by 11.5 mm2. Vascular density decreased up to the age of 50. Over the age of 50, changes were no longer significant and Lv appeared to stabilize. No correlation was observed between Lv and the presence of inflammation or metaplasia; however, LSS patients had a significantly increased incidence of chondroid metaplasia and inflammatory signs. The mechanical properties of control group samples showed significantly higher stiffness than those samples obtained from the LSS group. CONCLUSION: This study showed that Lv changes were not dependent on LSS but were age-dependent. Vascular density was found to decrease up to the age of 50. A significantly higher incidence of chondroid metaplasia and inflammation was observed in LSS patients. The mechanical property values measured by nanoindentation showed high microstructural heterogeneity of the tested ligaments. Our results showed that healthy ligaments were significantly stiffer than LSS ligaments. CLINICAL SIGNIFICANCE: Prevention of the loss of LF vascularization during aging may influence stiffness of LF which in turn may slow down the LF degenerative processes and delay onset of LSS.

Changes in histopathological classification of neuroendocrine tumors in 5th edition of WHO classification of gastrointestinal tract tumors (2019).

In a brief review is presented a summary of news in the classification of neuroendocrine neoplasms of the digestive system, as they were introduced in the 5th edition of the WHO Classification of Digestive System Tumors published in summer 2019.

Universality of indeterminate growth in lizards rejected: the micro-CT reveals contrasting timing of growth cartilage persistence in iguanas, agamas, and chameleons.

Squamate reptiles are considered to exhibit indeterminate growth. Nevertheless, current literature disputes the available definitions of this growth type, presents new theoretical models, and questions its universality in cold-blooded vertebrates. We have followed up on our previous research employing micro-CT to explore growth plate cartilage (GPC) in the epiphysis of long bones, which is responsible for longitudinal skeletal growth by the endochondral ossification process. We focused on numerous and highly diversified group of the Iguania clade comprising Acrodonta (agamas and chameleons) and Pleurodonta ("iguanas"). We recorded the absence of GPC in most of the examined adult Pleurodonta specimens and interpret it as an irreversible arrest of skeletal growth. This finding clearly rejects the universality of indeterminate growth in lizards. On the other hand, we found apparent GPC preservation in most of the adult specimens belonging to Acrodonta. This suggests a preserved ability to continue body growth throughout most of their life. We discuss the uncovered disparity between Acrodonta and Pleurodonta and emphasize the importance of GPC degradation timing.

Results of morphological screening for Lynch syndrome during the period 2013-2016.

The introduction of a screening system for Lynch syndrome in pathology laboratories in Plzen yielded 24 diagnoses of Lynch syndrome during the period of 2013-2016, 20 of them presenting with colorectal cancer. In 8 of those 24 cases germline mutations of MMR genes, previously not recognized as pathogenic with certainty, were detected. Although the frequency of Lynch syndrome in patients with colorectal cancer was only 0.34 % in total, following introduction of the universal immunohistochemical investigation of MMR (mismatch repair) proteins expression in all colorectal cancers examined in Sikl´s Institute of Pathology the frequency per year in this department reached 2.4 %. The results favor universal immunohistochemical screening for Lynch syndrome in colorectal and endometrial cancer cases over a selective approach based on a combination of clinical and morphological criteria. Increased effectiveness of the universal approach is not brought about only by higher sensitivity of the immunohistochemical examination per se, but also by the possibility of automation of the process leading to increased adherence even of pathologists not directly engaged in Lynch syndrome management. However, the introduction of a nation-wide universal screening system requires support from the government and health insurance companies. Keywords: colorectal cancer - endometrial cancer - immunohistochemistry - Lynch syndrome - MMR - screening.

The expression of PD-L1 in patients with castrate prostate cancer treated with enzalutamide.

PURPOSE: The purpose of our retrospectively study was to evaluate the PD-L1 expression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. METHODS: A total of 33 patients with mCRPC were treated with enzalutamide. All patients were previously treated by one or two lines of chemotherapy. Enzalutamide was administered in the standard dose (160 mg orally once daily as four 40 mg capsules). No corticosteroids were concomitantly administered. PD-L1 expression was determined semiquantitavely by immunohistochemistry. RESULTS: Enzalutamide was well tolerated with predominantly G1-2 toxicity. G3-4 anaemia was found in 6 patients and G3-4 thrombocytopenia in 2 patients. One patient had cerebral hemorrhage. The median progression free survival (PFS) was 7.0 months (95% CI 6.1-7.9). The median overall survival (OS) was 8.4 months (95% CI: 5.1-11.7). The shorter OS was noted in the subgroup of patients with decreasing hemoglobin levels during enzalutamide treatment with hazard ratio (HR) 0.155 (95% CI 0.053-0.449) and in patients with Gleason score 8-10 with HR 0.334 (95% CI 0.12-0.927) according to the regression analysis. All tissue samples were scored as negative in the detection of PD-L1. CONCLUSIONS: The expression of PD-L1 in prostate cancer cells as potential new predictive biomarker was not confirmed. Further studies are needed to clarify this topic.

The prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression in patients with locally advanced rectal adenocarcinoma.

PURPOSE: To evaluate the prognostic effect of neoadjuvant chemoradiotherapy on the change of programmed death ligand 1 (PD-L1) expression in patients with locally advanced rectal adenocarcinoma, by comparing PD-L1 expression in pretreatment biopsies and PD-L1 expression in pathological specimens after neoadjuvant chemoradiotherapy. METHODS: A total of 25 patients with rectal adenocarcinoma were evaluated. Patients were treated by neoadjuvant chemoradiotherapy (radiotherapy:44Gy normofraxionation; chemotherapy: capecitabine 825 mg/m2 in two daily doses). Surgery was performed 6-8 weeks after the chemoradiotherapy completion. PD-L1 expression was determined in endoscopic biopsies and in resected specimens with immunohistochemistry. RESULTS: All 25 patients received radiotherapy without interruption, while concomitant chemotherapy was discontinued prematurely in one patient because of hematological toxicity. In 13 patients sphincter-saving surgery were performed, and 12 patients underwent rectum resection. Downstaging was noticed in 17 patients. Stable disease was found in 5 patients, and progression in 3. The median disease free survival (DFS) was not reached. Three-year DFS was 54.3% (95% CI 34.3-74.2). The median overall survival (OS) was 60 months (95% CI 48-60). Three-year OS was 75 % (95% CI 57.7-92.3). No PD-L1 expression was noticed in pretreatment biopsy and in resected tissue after chemoradiotherapy. CONCLUSION: No prognostic effect of neoadjuvant chemoradiotherapy on the change of PD-L1 expression was demonstrated in patients with locally advanced rectal adenocarcinoma.

[Lymph node metastasis of Merkel cell carcinoma without known cutaneous primary - case report]. / Uzlinová metastáza karcinomu z Merkelových bunek bez kozního primárního loziska - kazuistické sdelení.

Merkel cell carcinoma is a rare cutaneous tumor with an aggressive clinical course. In most cases it is associated with Merkel cell polyomavirus infection. Exceptionally, the tumor can present as a lymph node metastasis without a discernible cutaneous primary. In this report we present the case of a 42 year-old man with inguinal lymphadenopathy, histologically consistent with Merkel cell carcinoma. Tumor cells expressed immunohistochemically chromogranin-A, synaptophysin and displayed dot-like positivity for cytokeratin 20. The genome of MCPyV in neoplastic cells was detected using real-time PCR. A cutaneous primary has not been identified neither during the dermatologic examination, nor with PET CT scan.

Spectrum of Gastroenteropancreatic NENs in Routine Histological Examinations of Bioptic and Surgical Specimen: A Study of 161 Cases Collected from 17 Departments of Pathology in the Czech Republic.

Objective. To characterize GEP-NENs in routine biopsies and surgical specimen in the Czech Republic and to evaluate how WHO Classification (2010) is acceptable in diagnostic practice. Methods. Paraffin-embedded blocks and bioptic reports were collected from 17 departments of pathology. Histologic slides were stained with H&E and immunohistologically for CgA, synaptophysin, and Ki-67. Results. Out of 28 gastric NENs, there were 22 NETs, G1, 5 NETs, G2, and 1 NEC. Ten duodenal NENs were NETs, G1. Among 27 NENs of jejunum and ileum, 23 were NETs, G1, 2 NETs, G2, and 1 NEC and 1 mixed adenoneuroendocrine carcinoma (MANEC). Among 42 appendiceal "incidentalomas", 39 were NETs G1, 2 goblet cell carcinoids, and 1 MANEC. Out of 34 large intestinal NENs, 30 were NETs, G1, 3 NETs, G2, and 1 NEC. One small intestinal and 6 large bowel neoplasms were reclassified as poorly differentiated adenocarcinomas. In 12 pancreatic NENs, there were 7 NETs, G1, 3 NETs, G2, and 2 NECs. Conclusions. Our study demonstrates differences in GEP-NENs frequency in sites of origin in our region, comparing to other countries. Regarding routine bioptic diagnostics, we gave evidence that the WHO 2010 classification of NENs is fully acceptable for exact categorisation of tumours.