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BACKGROUND The global pandemic of the coronavirus disease 2019 represents a major concern for health services worldwide, and has also induced major changes in cytopathology practice. AIM We aimed to verify the diagnostic performance of cytological evaluation under a new safety protocol during the pandemic compared to the standard pre-pandemic procedure. We also aimed to assess how cytological diagnoses and sampling were impacted during the pandemic period compared to the pandemic-free period in 2019. MATERIALS AND METHODS Cytological samples of peritoneal washings taken during the first 10 months of the pandemic emergency in Italy (March 11, 2020 to January 11, 2021) were compared to samples from the preceding 10-month time frame (May 11, 2019 to March 10, 2020). RESULTS One hundred ninety-five specimens were analysed in the present study. We observed no noticeable differences in cytological diagnoses during the pandemic period compared to the pre-pandemic period. The case numbers by diagnostic category for the pre-pandemic vs pandemic periods, respectively, were as follows: non-diagnostic, 0 vs 0 cases; negative for malignancy, 86 vs 52 cases; atypia of uncertain significance, 7 vs 1 cases; suspicious for malignancy, 0 vs 2 cases; malignant, 42 vs 4 cases. CONCLUSION While a consistent reduction in the number of cytological examinations has been observed during the COVID-19 period, our institutional safety protocol for processing cytological samples did not affect the diagnostic reliability of peritoneal washing cytology.

Mixed neuroendocrine/non-neuroendocrine neoplasms (MiNEN) are rare mixed epithelial neoplasms in which a neuroendocrine component is combined with a non-neuroendocrine component. Here, we provide the clinical, pathologic, and molecular report of a 73-year-old-man presenting with an intestinal MiNEN. The lesion was composed of a well-differentiated G3 neuroendocrine tumor and a colloid adenocarcinoma. The molecular characterization was performed using a multigene next-generation sequencing panel. The neoplasm displayed microsatellite instability due to MLH1 promoter methylation. The extended molecular profile documented the same mutations affecting ARID1A, ASXL1, BLM, and RNF43 genes in both components, indicating a monoclonal origin of the tumor. Regarding component-specific gene mutations, BRCA2 was specifically altered in the neuroendocrine area. It may represent a new actionable target for precision oncology in MiNEN, but the lack of its alteration in the colloid component calls for further considerations on intratumor heterogeneity. The most important finding with potential immediate implications regards the presence of microsatellite instability: it indicates that this molecular alteration should become part of the diagnostic algorithm for these rare neoplasms.

Up to now, a vaginal well-differentiated neuroendocrine tumor (NET) has never been well described in the literature. A 2-cm vaginal nodule morphologically revealed a proliferation of mild to moderately atypical eosinophilic epithelioid cells, without tumor cell necrosis. Immunohistochemistry (IHC) showed positivity for CK (AE1/AE3), chromogranin A, and synaptophysin, focal positivity for CDX2, and negativity for PAX8 and TTF1. Metastatic origin was excluded by imaging and the morphological context with benign mucinous glands as present in the surgical resection specimen. Considering mitotic index and Mib1/Ki67 (8 mitoses/2 mm2; >20%), the case was diagnosed as vaginal NET G2 in the light of the WHO 2020 grading system for the gynecologic neuroendocrine neoplasms (NENs). Ranges of Mib1-Ki67 are not yet standardized. Currently, mitotic index and tumor cell necrosis were taken into consideration for the grading system. Gynecologic NENs still represent a diagnostic challenge. A clinico-radiologic workup and an appropriate diagnostic path ruling out the metastatic nature are mandatory to achieve the diagnosis.

Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens.Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed.Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482).Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.

Pancreatic ductal adenocarcinoma (PDAC) with microsatellite instability (MSI)/defective mismatch repair (dMMR) is the only subtype of pancreatic cancer with potential response to immunotherapy. Here, we report the histo-molecular characterization of MSI/dMMR PDAC with immunohistochemistry, MSI-based PCR, and next-generation sequencing. Five paradigmatic cases have been identified. The main results include the first report in pancreatic cancer of MSI/dMMR intra-tumor heterogeneity, the presence of microsatellite-stable metastases from MSI/dMMR primary and recurrent B2M gene inactivation, which may confer resistance to immunotherapy. In addition to the classic PDAC drivers, ARID1A was the most common mutated gene in the cohort. Intra-tumor heterogeneity, B2M inactivation, and metastatic sites should be carefully considered in MSI/dMMR PDAC, which should also be investigated in routine diagnostic practice with specific molecular analysis. The chromatin remodeler ARID1A represents another potential driver gene in this context.

Background: In the setting of kidney transplantation, histopathology of kidney biopsies is a key element in the organ assessment and allocation. Despite the broad diffusion of the Remuzzi–Karpinski score on preimplantation kidney biopsies, scientific evidence of its correlation to the transplantation outcome is controversial. The main issues affecting the prognostic value of histopathology are the referral to general on-call pathologists and the semiquantitative feature of the score, which can raise issues of interpretation. Digital pathology has shown very reliable and effective in the oncological diagnosis and treatment; however, the spread of such technologies is lagging behind in the field of transplantation. The aim of our study was to create a digital online platform where whole-slide images (WSI) of preimplantation kidney biopsies could be uploaded and stored. Methods: We included 210 kidney biopsies collected between January 2015 and December 2019 from the joint collaboration of the transplantation centers of Padua and Verona. The selected slides, stained with hematoxylin and eosin, were digitized and uploaded on a shared web platform. For each case, the on-call pathologists' Remuzzi grades were obtained from the original report, together with the clinical data and the posttransplantation follow-up. Results: The storage of WSI of preimplantation kidney biopsies would have several clinical, scientific, and educational advantages. The clinical utility relies on the possibility to consult online expert pathologists and real-time quality checks of diagnosis. From the perspective of follow-up, the archived digitized biopsies can offer a useful comparison to posttransplantation biopsies. In addition, the digital online platform is a precious tool for multidisciplinary meetings aimed both at the clinical discussion and at the design of research projects. Furthermore, this archive of readily available WSI is an important educational resource for the training of professionals. Conclusions: Finally, the web platform lays the foundation for the introduction of artificial intelligence in the field of transplantation that would help create new diagnostic algorithms and tools with the final aim of increasing the precision of organ assessment and its predictive value for transplant outcome.

In the last two decades, there has been marked development in virtual slide technology as well as its application in various subspecialties of pathology. In particular, there have been several studies examining the utility of whole slide imaging (WSI) in breast and gynecological pathology. The aim of this systematic review is to analyse published evidence regarding validation studies of WSI applied specifically to the female genital tract and breast pathology.A systematic search was carried out in Pubmed and Embase databases and studies dealing with the validation of a WSI system for breast and gynaecological pathology. The topics evaluated concerned expertise of engaged pathologists, varied specimens, scanners, washout period, experience viewing WSI, and diagnostic concordance of WSI to traditional light microscopic diagnoses.Of 1467 publications retrieved, 23 studies were included. Most of these studies concerned breast pathology. Validation guidelines recommended by the College of American Pathologists pertaining to a dataset of at least 60 cases, washout period, and recording intra-observer variability were followed by most studies. Major challenges encountered with WSI included difficulty identifying high-grade nuclear atypia and mitotic count for borderline ovarian tumors, interpretation of squamous intraepithelial lesions in liquid-based cervical cytology, and grading breast cancer.Published data demonstrates the value of utilizing WSI in breast and gynecological pathology. Key issues reported with WSI systems were problems related to focus, resolution and the contrast and brightness of immunohistochemical staining patterns. Grading breast cancer and mitotic count remained challenging in WSI as in conventional microscopy.

Juvenile polyposis (JP) is a rare familial syndrome characterized by the development of numerous hamartomatous polyps of the gastrointestinal tract and by an increased risk of developing gastrointestinal cancers. It follows a pattern of autosomal dominant inheritance and is associated with germline variants of SMAD4 or BMPR1A genes. Differential diagnosis may be difficult based on histology alone, due to morphological similarities to other familial syndromes. Here we report a case of familial JP diagnosed in a 50-years woman with a familial history positive for gastrointestinal cancers and other tumor types. The patient presented with severe iron deficiency anemia and showed numerous polyps in the stomach and jejunum according to endoscopy and imaging. She underwent an intra-gastric laparoscopic removal of the major gastric polyp, followed by jejunal exploration and resection of a segment with multiple neoformations. Histological examination revealed the presence of hamartomatous polyposis. Gastric and intestinal samples were analyzed with next-generation sequencing. Molecular analysis showed that the patient harbored a germline splicing site variant of SMAD4, c.1139 + 3A > G, which was complemented by different somatic variants of the same gene in the different polyps. Immunohistochemistry for SMAD4 confirmed loss of protein expression in the polyps, with regular expression in normal cells. cDNA sequencing further confirmed the findings. We thus definitively diagnosed the woman as having JP thanks to an integrated approach based on histology, immunohistochemistry and molecular analysis. The identified variants, all previously reported as variants of unknown significance, were classified as pathogenic as they complemented each other leading to SMAD4 loss.

Conférence virtuelle; International audience; In this paper, a miniaturized omnidirectional circularly polarized (OCP) antenna for Internet-of-Things (IoT) applications is presented. The CP waveform is synthesized by combining two linearly polarized antenna elements which act as electric and magnetic dipole, respectively. The vertical and the horizontally polarized elements are integrated and fed by a single port. The OCP antenna achieves a CP bandwidth covering 80 MHz from 2.4 to 2.48 GHz. The results show that the antenna can provide at 2.44 GHz an axial ratio lower than 3 dB and gain variations of less than 1.1 dB over all azimuth angles. The OCP antenna is printed on two cost-effective FR-4 PCBs and it is very low profile. Thanks to its radiation and geometric properties, the proposed antenna solution fits well in specific IoT use cases where a monopole-type radiation pattern is required.

Up to now, a vaginal well-differentiated neuroendocrine tumor (NET) has never been well described in the literature. A 2-cm vaginal nodule morphologically revealed a proliferation of mild to moderately atypical eosinophilic epithelioid cells, without tumor cell necrosis. Immunohistochemistry (IHC) showed positivity for CK (AE1/AE3), chromogranin A, and synaptophysin, focal positivity for CDX2, and negativity for PAX8 and TTF1. Metastatic origin was excluded by imaging and the morphological context with benign mucinous glands as present in the surgical resection specimen. Considering mitotic index and Mib1/Ki67 (8 mitoses/2 mm

Objective:In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women.Methods:A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements.Results:Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported.Conclusion:After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

This work of thesis aims at finding an innovative reconfigurable antenna whose peculiarity is offering a two different orthogonal polarization by using mechanism of reconfigurability based on PIN diodes.

Among 622 slaughtered horses from eastern Europe, 156 thyroid glands were selected on the basis of macroscopic alterations (e.g., determination of volume and weight). In the 80% of these thyroids, microscopic alterations consistent with a diagnosis of Hashimoto thyroiditis-like disease were found. In particular, a subverted architecture of the thyroid gland with colloid rarefaction, lymphocytic infiltration, and fibrosis was noted. The confirmation of the histopathological diagnosis of an equine Hashimoto thyroiditis-like disease was provided by the increased serum concentration of thyroglobulin, of antithyroglobulin, and of antithyroid peroxidase autoantibodies. Despite evidence consistent with an Hashimoto thyroiditis-like disease in eastern European horses, the etiopathogenesis of this autoimmune disorder deserves further investigation. In this respect, in some horses histopathological alterations in the pituitary gland may suggest an as-yet-unidentified disorder within the hypothalamus-pituitary adrenal axis associated with Hashimoto thyroiditis.

Objective: In this study, the serum lipid profile, including total cholesterol (TC), triglycerides (TG), high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C), has been investigated in colorectal cancer patients (CRC) with and without synchronous distant metastases. The aim of this study was to verify whether the presence of metastases was associated to serum lipid abnormalities, and whether lipoprotein abnormalities were linked to the nutritional status. Methods: The fasting serum lipid profile was examined in 84 CRC patients using colorimetric methods. To determine the nutritional status, the body mass index (BMI) was calculated and serum albumin was measured. Results: Patients with distant metastases showed significantly higher levels of TC, LDL-C and the LDL-C/HDL-C ratio than patients without metastases (p< 0.05). The presence of metastases was positively associated with TC, LDL-C and the LDL-C/HDL-C ratio, being independent of sex, age and BMI. Conclusions: Elevated serum lipid levels may facilitate the development of distant metastasis in CRC patients.