Dose Reduction in Pediatric Oncology Patients with Delayed Total-Body [18F]FDG PET/CT.

Our aim was to define a lower limit of reduced injected activity in delayed [18F]FDG total-body (TB) PET/CT in pediatric oncology patients. Methods: In this single-center prospective study, children were scanned for 20 min with TB PET/CT, 120 min after intravenous administration of a 4.07 ± 0.49 MBq/kg dose of [18F]FDG. Five randomly subsampled low-count reconstructions were generated using », ⅛, [Formula: see text], and [Formula: see text] of the counts in the full-dose list-mode reference standard acquisition (20 min), to simulate dose reduction. For the 2 lowest-count reconstructions, smoothing was applied. Background uptake was measured with volumes of interest placed on the ascending aorta, right liver lobe, and third lumbar vertebra body (L3). Tumor lesions were segmented using a 40% isocontour volume-of-interest approach. Signal-to-noise ratio, tumor-to-background ratio, and contrast-to-noise ratio were calculated. Three physicians identified malignant lesions independently and assessed the image quality using a 5-point Likert scale. Results: In total, 113 malignant lesions were identified in 18 patients, who met the inclusion criteria. Of these lesions, 87.6% were quantifiable. Liver SUVmean did not change significantly, whereas a lower signal-to-noise ratio was observed in all low-count reconstructions compared with the reference standard (P < 0.0001) because of higher noise rates. Tumor uptake (SUVmax), tumor-to-background ratio, and total lesion count were significantly lower in the reconstructions with [Formula: see text] and [Formula: see text] of the counts of the reference standard (P < 0.001). Contrast-to-noise ratio and clinical image quality were significantly lower in all low-count reconstructions than with the reference standard. Conclusion: Dose reduction for delayed [18F]FDG TB PET/CT imaging in children is possible without loss of image quality or lesion conspicuity. However, our results indicate that to maintain comparable tumor uptake and lesion conspicuity, PET centers should not reduce the injected [18F]FDG activity below 0.5 MBq/kg when using TB PET/CT in pediatric imaging at 120 min after injection.

Germline mutational variants of Turkish ovarian cancer patients suspected of Hereditary Breast and Ovarian Cancer (HBOC) by next-generation sequencing.

Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135-2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC.

The effect of hand fine motor skills on peritoneal dialysis-related peritonitis.

INTRODUCTION: We aimed to evaluate the relationship between the hand fine motor skills of peritoneal dialysis (PD) practitioners and PD-related peritonitis. METHODS: This multicenter prospective observational study was conducted with 120 incident PD patients. Patients were divided into two groups who had PD-related peritonitis within the first year as Group 1, and those who did not as Group 2. Hand fine motor skills were evaluated by Nine-Hole Peg Test (NHPT) and Nut Screwing Test (NST). RESULTS: Initial NHPT (28.5 ± 6.0 s vs. 25.8 ± 5.0 s, p = 0.011) and NST (82.3 (61.5-102.8) s versus 65.3 (52.3-88.5) s p = 0.023) scores were significantly higher in Group 1 than Group 2. In multivariate logistic regression analysis, NHPT, Body Mass Index, Mini-Mental Test, self PD practitioner, and catheter complications were found to be independent variables in predicting PD-related peritonitis. CONCLUSION: Decreased hand fine motor skills of PD patients is a risk factor for peritonitis.

Separation of Boron and Arsenic from Geothermal Water with Novel Gel-Type Chelating Ion Exchange Resins: Batch and Column Sorption-Elution Studies.

In this research, the removal of boron and arsenic from geothermal water was examined by using novel N-methyl-d-glucamine functionalized gel-like resins (abbreviated as 1JW and 2JW) synthesized by the membrane emulsification method. The outcomes were compared with those of commercially available boron selective chelating ion exchange resin (Diaion CRB 05). According to the results obtained with the novel resins, it was possible to reduce both boron and arsenic concentrations in geothermal water by using these novel gel-like chelating resins below their permissible levels for agricultural irrigation (<1 mg B/L) and drinking water (<0.01 mg As/L) by using the batch method. The optimum resin concentration required for almost complete boron removal (more than 95%) with the two chelating resins was determined to be 2 g/L. The novel gel-like chelating resins 1JW and 2JW achieved 94% of arsenic removal by using the resin concentration of 8 g/L, while the required resin concentration was 32 g/L for 94% of arsenic removal using commercially available Diaion CRB05 resin. In addition, the column performance characteristics of the novel chelating resins for the separation of boron were studied, and the results were compared to those obtained with Diaion CRB05. According to the column data obtained, the total resin capacities of the Diaion CRB05, 1JW, and 2JW resins were calculated as 6.29, 5.08, and 4.64 mg B/mL-resin, respectively.

Identification of Cutinolytic Esterase from Microplastic-Associated Microbiota Using Functional Metagenomics and Its Plastic Degrading Potential.

Plastic pollution has threatened biodiversity and human health by shrinking habitats, reducing food quality, and limiting the activities of organisms. Therefore, global interest in discovering novel enzymes capable of degrading plastics has increased considerably. Within this context, the functional metagenomic approach, which allows for unlocking the functional potential of uncultivable microbial biodiversity, was used to discover a plastic-degrading enzyme. First, metagenomic libraries derived from microplastic-associated microbiota were screened for esterases capable of degrading both tributyrin and polycaprolactone. Clone KAD01 produced esterase highly active against p-nitrophenyl esters (C2-C16). The gene corresponding to the enzyme activity showed moderate identity (≤ 55.94%) to any known esterases/cutinases. The gene was extracellularly expressed with a 6× histidine tag in E. coli BL21(DE3), extracellularly. Titer of the enzyme (CEstKAD01) was raised from 21.32 to 35.17 U/mL by the statistical optimization of expression conditions and media components. CEstKAD01 was most active at pH 7.0 and 30 °C. It was noteworthy stable over a wide pH (6.0-10.0) and temperature (20-50 °C). The enzyme was active and stable in elevated NaCl concentrations up to 12% (w/v). Pre-incubation of CEstKAD01 with Mg2+, Mn2+, and Ca2+ increased the enzyme activity. CEstKAD01 displayed an excellent tolerance against various chemicals and solvents. It was determined that 1 mg of the enzyme caused the release of 5.39 ± 0.18 mM fatty acids from 1 g apple cutin in 120 min. Km and Vmax values of CEstKAD01 against p-nitrophenyl butyrate were calculated to be 1.48 mM and 20.37 µmol/min, respectively. The enzyme caused 6.94 ± 0.55, 8.71 ± 0.56, 7.47 ± 0.47, and 9.22 ± 0.18% of weight loss in polystyrene, high-density polyethylene, low-density polyethylene, and polyvinyl chloride after 30-day incubation. The scanning electron microscopy (SEM) analysis indicated the formation of holes and pits on the plastic surfaces supporting the degradation. In addition, the change in chemical structure in plastics treated with the enzyme was determined by Fourier Transform Infrared Spectroscopy (FTIR) analysis. Finally, the degradation products were found to have no genotoxic potential. To our knowledge, no cutinolytic esterase with the potential to degrade polystyrene (PS), high-density polyethylene (HDPE), low-density polyethylene (LDPE), and polyvinyl chloride (PVC) has been identified from metagenomes derived from microplastic-associated microbiota.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.

Imaging Cancer in Neuroradiology.

Neuroimaging plays a pivotal role in the diagnosis, management, and prognostication of brain tumors. Recently, the World Health Organization published the fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS5), which places greater emphasis on tumor genetics and molecular markers to complement the existing histological and immunohistochemical approaches. Recent advances in computational power allowed modern neuro-oncological imaging to move from a strictly morphology-based discipline to advanced neuroimaging techniques with quantifiable tissue characteristics such as tumor cellularity, microstructural organization, hemodynamic, functional, and metabolic features, providing more precise tumor diagnosis and management. The aim of this review is to highlight the key imaging features of the recently published CNS5, outlining the current imaging standards and summarizing the latest advances in neuro-oncological imaging techniques and their role in complementing traditional brain tumor imaging and management.

A 49-Year-Old Woman With Exertional Dyspnea and Dizziness.

CASE PRESENTATION: A 49-year-old woman with a history of right breast cancer status post radiation therapy presented to our ED with increasing chest pain, exertional dyspnea, fatigue, and dizziness for several weeks. She denied syncope or near-syncope, and she had no personal or family history of cardiac disease. Her outpatient medications included tamoxifen and venlafaxine.

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody.

With the majority of CD8+ T cells residing and functioning in tissue, not blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics in humans offers the means for studying their key role in adaptive immune response and memory. This study is the first report on using positron emission tomography (PET) dynamic imaging and compartmental kinetic modeling for in vivo measurement of whole-body biodistribution of CD8+ T cells in human subjects. For this, a 89Zr-labeled minibody with high affinity for human CD8 (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy subjects (N=3) and in COVID-19 convalescent patients (N=5). The high detection sensitivity, total-body coverage, and the use of dynamic scans enabled the study of kinetics simultaneously in spleen, bone marrow, liver, lungs, thymus, lymph nodes, and tonsils, at reduced radiation doses compared to prior studies. Analysis and modeling of the kinetics was consistent with T cell trafficking effects expected from immunobiology of lymphoid organs, suggesting early uptake in spleen and bone marrow followed by redistribution and delayed increasing uptake in lymph nodes, tonsils, and thymus. Tissue-to-blood ratios from the first 7 h of CD8-targeted imaging showed significantly higher values in the bone marrow of COVID-19 patients compared to controls, with an increasing trend between 2 and 6 months post-infection, consistent with net influx rates obtained by kinetic modeling and flow cytometry analysis of peripheral blood samples. These results provide the platform for using dynamic PET scans and kinetic modelling to study total-body immunological response and memory.

18F-FDG gallbladder uptake: observation from a total-body PET/CT scanner.

BACKGROUND: Total-body positron emission tomography/computed tomography (PET/CT) scanners are characterized by higher signal collection efficiency and greater spatial resolution compared to conventional scanners, allowing for delayed imaging and improved image quality. These advantages may also lead to better detection of physiological processes that diagnostic imaging professionals should be aware of. The gallbladder (GB) is not usually visualized as an 18F-2-fluorodeoxyglucose (18F-FDG)-avid structure in routine clinical PET/CT studies; however, with the total-body PET/CT, we have been increasingly visualizing GB activity without it being involved in an inflammatory or neoplastic process. The aim of this study was to report visualization rates and characteristics of GB 18F-FDG uptake observed in both healthy and oncological subjects scanned on a total-body PET/CT system. MATERIALS AND METHODS: Scans from 73 participants (48 healthy and 25 with newly diagnosed lymphoma) who underwent 18F-FDG total-body PET/CT were retrospectively reviewed. Subjects were scanned at multiple timepoints up to 3 h post-injection. Gallbladder 18F-FDG activity was graded using liver uptake as a reference, and the pattern was qualified as present in the wall, lumen, or both. Participants' characteristics, such as age, sex, body-mass index, blood glucose, and other clinical parameters, were collected to assess for any significant correlation with GB 18F-FDG uptake. RESULTS: All 73 subjects showed GB uptake at one or more imaging timepoints. An increase in uptake intensity overtime was observed up until the 180-min scan, and the visualization rate of GB 18F-FDG uptake was 100% in the 120- and 180-min post-injection scans. GB wall uptake was detected in a significant number of patients (44/73, 60%), especially at early timepoint scans, whereas luminal activity was detected in 71/73 (97%) subjects, especially at later timepoint scans. No significant correlation was found between GB uptake intensity/pattern and subjects' characteristics. CONCLUSION: The consistent observation of GB 18F-FDG uptake recorded in this study in healthy participants and subjects with a new oncological diagnosis indicates that this is a normal physiologic finding rather than representing an exception.

Blanching Defects at the Pressure Points: Observations from Dynamic Total-Body PET/CT Studies.

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using 18F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or 18F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different 18F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers.

Circulating lncRNA H19 may be a useful marker of response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Novel biomarkers are needed to predict the effectiveness of the treatment of presurgical neoadjuvant chemotherapy (NAC) in breast cancer (BC). OBJECTIVE: This is an exploratory study to assess the impact of 3 cancer-related long non-coding RNAs (lncRNAs) (H19, MALAT1 and GA5) in blood plasma of patients with BC in predicting the response to NAC. METHODS: The plasma levels of RNAs were relatively measured by quantitative PCR at baseline, and at the end of the fourth cycle of NAC in patients with locally advanced BC. RESULTS: Only H19 was associated with patients' characteristics, and with the response to NAC. Higher plasma expression of H19 was associated with younger age at diagnosis, triple negative tumors, and Ki-67 index. Patients with a pathological complete response (20%) had lower pre-therapeutic levels of H19 compared with the non-complete responders (relative levels 0.1 vs 0.2, respectively, P: 0.04). In addition, the patients with higher degree of downstaging of initial tumors had lower baseline levels of H19 among non-complete responders. CONCLUSION: Our study reveals that H19, but not MALAT1 and GAS5, may be a useful marker of response to NAC in BC.

Henna Application in the Prevention of Capecitabine-Induced Hand-Foot Syndrome in Breast and Colorectal Cancer Patients.

AIM: This study investigates the prophylactic effect of henna on the occurrence of hand-foot syndrome (HFS) in patients receiving capecitabine for breast and colorectal cancer. METHOD: This experimental study was carried out between May 2014 and May 2015. In this self-control experimental study, 52 patients with breast and colorectal cancer were included on the first day of capecitabine treatment and had a minimum follow-up of 3 cycles. One hand/foot of each patient constituted the study hand/foot, whereas the others constituted the control. Henna was administered to the study hand/foot on the first day of treatment and application renewed weekly. Development of grade 1-3 toxicity was set as the termination criterion for study. RESULTS: Painful skin changes such as rawness, intumescence and bulla formation, blocking the daily activities or self-care were observed in 26.9% of the patients in the 3rd or 4th cycles of treatment. Development time and severity of skin changes over time did not differ significantly between the study and the control hand/foot. CONCLUSION: Further studies with a larger sample size are needed to conclude on the prophylactic effect of henna in the management of the HFS.

Interleukin-10 is increased in successful drug desensitization regardless of the hypersensitivity reaction type.

BACKGROUND: Little is known about the mechanism of desensitization in hypersensitivity drug reactions. OBJECTIVE: The aim of this study was to evaluate the effects of drug desensitization on some cytokine levels in patients desensitized for drug hypersensitivity reactions. METHODS: Patients with a hypersensitivity reaction to any drug for whom desensitization was planned with the culprit drug, patients who could tolerate the same drugs and healthy subjects who were not exposed to these drugs were enrolled. Bead-based Milliplex MAP multiplex technology was used to determine interleukin (IL)-4, IL-5, interferon-γ and IL-10 levels in the sera of the subjects as a baseline and 24 hours after desensitization had been completed in the patients. RESULTS: A total of 26 patients (16 female [61.5%]; mean age 48.46 ± 15.97 years old), 10 control patients (5 female [50%]; mean age 47.4 ± 15.4 years old) and 5 healthy subjects (3 female [60%]; mean age 34.2 ± 5.6 years old) were enrolled. Four of the 26 patients did not tolerate the procedure and were grouped as the 'unsuccessful desensitization group' whereas 22 patients successfully completed the procedure and formed the 'successful desensitization group.' Baseline cytokine levels in the 3 groups were not statistically different. Postdesensitization IL-10 levels in the successful desensitization group were significantly higher than their initial levels (p = 0.005) whereas none of the cytokine levels significantly changed in the unsuccessful desensitization group. The rise in IL-10 levels was greater in chemotherapeutic desensitizations when compared to other drugs (p = 0.006). CONCLUSION: Successful desensitization independent of the hypersensitivity reaction type seems to be related to the increase of IL-10.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year-OS (P=.001) and 10 year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium: An immunohistochemical and clinicopathologic study.

Undifferentiated/dedifferentiated endometrial carcinomas (UCE/DCEs) of the endometrium are rare tumors with poor prognosis. There are few clinicopathologic studies with detailed immunohistochemical analysis regarding UCE/DCEs.We evaluated the diagnostic value of a selected tumor stem-cell marker and epithelial-mesenchymal transition (EMT) markers, in addition to previously studied markers in identifying UCE/DCEs from other types of high-grade endometrial carcinomas.Eleven cases of UCE/DCEs with complete clinical follow-up that were diagnosed between 2006 and 2015 were included in the study. For immunohistochemical comparison, 11 clinically matched cases for each type of other high-grade endometrial carcinomas (high-grade endometrioid (F3-EC), serous [SC], and clear cell carcinoma [CCC]) were used as a control group. An immunohistochemical analysis including fascin, SALL4, E-cadherin, and ß-catenin, in addition to epithelial and neuroendocrine markers was performed in each case.The majority of UCE/DCEs displayed diffuse expression of fascin (81.9%) and loss of E-cadherin expression (54.5%). SALL4 expression was detected in 36.3% of the UCE/DCE cases. SALL4 expression was significantly more frequent in UCE/DCEs than all other high-grade carcinomas (P < 0.001). Loss of E-cadherin and fascin expression was significantly more frequent in UCE/DCEs than high-grade endometrioid and clear cell adenocarcinomas (P = 0.012, 0.014 and P = 0.01, 0.003, respectively).We suggest that loss of E-cadherin expression together with fascin and SALL4 immunopositivity in addition to morphologic features have an impact in differential diagnosis of UCE/DCEs from other high-grade endometrial carcinomas.

BRAF, NRAS, KIT, TERT, GNAQ/GNA11 mutation profile analysis of head and neck mucosal melanomas: a study of 42 cases.

Head and neck mucosal melanoma (HNMuM), which occurs mostly in the sinonasal and oral cavity, constitutes less than 1% of all malignant melanomas. Treatment options fail to improve the prognosis of this aggressive tumour that has low overall survival rates. Thus, development of new targeted therapies is essential. Unfortunately, limited data exist regarding their molecular profile. BRAF, NRAS, KIT, TERT and GNAQ/GNA11 oncogene mutations were investigated in 42 HNMuMs (28 sinonasal, 13 oral, 1 nasopharyngeal). Mutation rates were as follows: BRAF (4.8%), NRAS (4.8%), KIT (9.5%), TERT (7.5%), GNAQ/GNA11 (0%). Among 11 cases that harboured mutations (26%), 10 (91%) were located in sinonasal and one (9%) in the oral cavity. The literature was reviewed with comparison of frequencies based on the gathered data. NRAS and TERT promoter mutation rates were significantly higher in sinonasal than in oral location (p<0.05). Our results indicated that BRAF, NRAS, KIT, TERT and GNAQ/GNA11 gene mutations occur at low frequencies in HNMuMs, and subgroups (oral versus sinonasal) differ in their molecular profile. Low rates of aforementioned mutations and activation of oncogenes by pathways other than sun exposure support the distinctive nature of HNMuMs with regard to their cutaneous counterparts.

A Selected Immunohistochemical Panel Aids in Differential Diagnosis and Prognostic Stratification of Subtypes of High-grade Endometrial Carcinoma: A Clinicopathologic and Immunohistochemical Study at a Single Institution.

This study aimed to investigate whether a selected immunohistochemical panel (estrogen receptor, p53, ARID1A, PPP2R1A, HNF-1ß) could contribute to the diagnostic process of high-grade endometrial carcinomas (HG-ECs). We also aimed to analyze the correlation of these immunohistochemical results with several morphologic variables and survival data. After revising the diagnosis of 78 HG-ECs, immunohistochemical analysis was performed for each case. After immunohistochemical analysis, a specific diagnosis of prototypic HG-EC was established in most of the cases that were uncertain due to morphologic ambiguity. In the univariate analysis, older patient age, type II morphology, undifferentiated carcinoma and carcinosarcoma type of histology, altered p53 immunostaining, strong membranous staining of PPP2R1A, presence of lymphovascular invasion in serous carcinoma, and microcystic, elongated, and fragmented-type infiltration pattern in endometrioid carcinoma were significantly related to poor prognosis. In the multivariate analysis, only older patient age and carcinosarcoma or undifferentiated/dedifferentiated carcinoma type histology were found to be significantly poor prognostic factors (P=0.011), whereas advanced FIGO stage and type II histology were found to be correlated with poor prognosis, but did not reach statistical significance. We suggest that immunohistochemistry should be used in the differential diagnosis of HG-ECs, especially those with ambiguous morphology. Markers used in this study made a valuable contribution to the diagnostic process as well as prediction of prognosis.