Use of digital pathology and artificial intelligence for the diagnosis of Helicobacter pylori in gastric biopsies.

Objective: A common source of concern about digital pathology (DP) is that limited resolution could be a reason for an increased risk of malpractice. A frequent question being raised about this technology is whether it can be used to reliably detect Helicobacter pylori (HP) in gastric biopsies, which can be a significant burden in routine work. The main goal of this work is to show that a reliable diagnosis of HP infection can be made by DP even at low magnification. The secondary goal is to demonstrate that artificial intelligence (AI) algorithms can diagnose HP infections on virtual slides with sufficient accuracy. Methods: The method we propose is based on the Warthin-Starry (W-S) silver stain which allows faster detection of HP in virtual slides. A software tool, based on regular expressions, performed a specific search to select 679 biopsies on which a W-S stain was done. From this dataset 185 virtual slides were selected to be assessed by WSI and compared with microscopy slide readings. To determine whether HP infections could be accurately diagnosed with machine learning. AI was used as a service (AIaaS) on a neural network-based web platform trained with 468 images. A test dataset of 210 images was used to assess the classifier performance. Results: In 185 gastric biopsies read with DP we recorded only 4 false positives and 4 false negatives with an overall agreement of 95.6%. Compared with microscopy, defined as the "gold standard" for the diagnosis of HP infections, WSI had a sensitivity and specificity of 0.95 and 0.96, respectively. The ROC curve of our AI classifier generated on a testing dataset of 210 images had an AUC of 0.938. Conclusions: This study demonstrates that DP and AI can be used to reliably identify HP at 20X resolution.

Isolated tumour cells in a sentinel lymph node of apparent early-stage ovarian cancer: Ultrastaging of all other 27 lymph nodes.

Sentinel lymph node (SLN) biopsy in apparent early-stage ovarian cancer may spare the surgical staging with extensive retroperitoneal dissection and its associated morbidity. However, SLN biopsy in ovarian cancer is still experimental and under investigation. A 46-year-old post-menopausal woman with bilateral apparent stage IC1 endometrioid ovarian cancer underwent surgical staging by SLN biopsy and subsequent comprehensive laparoscopic pelvic and para-aortic lymphadenectomy. Out of 4 SLNs submitted to ultrastaging, one was positive for isolated tumour cells (ITCs). We submitted to ultra-staging all the other 24 pelvic and para-aortic non-SLNs, which were reported negative for disease. This is the first reported case of comprehensive lymphadenectomy after SLN biopsy with universal ultrastaging of all non-SLNs in ovarian cancer. The presence of ITCs in only one SLN, with all other 27 lymph nodes negative at ultrastaging, is consistent with the SLN concept and the assumption of a reliable lymphatic pathway in ovarian cancer.

Thyroid Gland Metastasis From Endometrial Carcinoma Causing Acute Severe Dyspnea.

Thyroid metastasis from cervical carcinomas is an extremely rare disease; therefore, only a few cases have so far been reported in the literature. Due to the lack of data and the heterogeneity of clinical cases, the percentage of patients affected by thyroid metastases eligible to undergo surgery is not easily predictable. This report describes a rare case of endometrioid adenocarcinoma metastasized to the thyroid gland. A 72-year-old woman was referred to the ENT department of our hospital (Ospedale Degli Infermi di Biella, Italy) presenting with dyspnea and rapidly worsening condition, in need of emergency surgery. The peculiarity of this case lies in the metastasis isotype rarity, in its voluminous dimension, and in its mediastinal localization, which required the intervention of a multidisciplinary team to establish successful treatment planning.

Whole-Slide Imaging Allows Pathologists to Work Remotely in Regions with Severe Logistical Constraints Due to Covid-19 Pandemic.

INTRODUCTION: In this study, we report on our experience using digital pathology to overcome the severe limitations imposed on health care by the Covid-19 outbreak in Northern Italy. Social distancing had a major impact on public transportation, causing it to run with reduced timetables. This resulted in a major challenge for hospital commuters. To limit the presence in our hospital of no more than two pathologists at a time out of four, a web-based digital pathology system (DPS) was employed to work remotely. SUBJECTS AND METHODS: We used a DPS in which a scanner, a laboratory information system, a storage device, and a web server were interfaced so that tissue slides could be viewed over the Internet by whole-slide imaging (WSI). After a brief internal verification test, the activity on the DPS was recorded, taking track of a set of performance and efficiency indicators. At the end of the study, 405 cases were signed out remotely. RESULTS: Of 693 cases, 58.4% were signed out remotely by WSI, while 8.4% needed to be kept on hold to return to the original microscope slide. In three cases, at least one slide had to be rescanned. In eight cases, one slide was recut. Panel discussion by WSI was necessary in 34 cases, a condition in which all pathologists were asked for their opinion. A consultation with a more experienced colleague was necessary in 17 cases. CONCLUSIONS: We show that WSI easily allows pathologists to overcome the problems caused by the severe social distancing measures imposed by the Covid-19 pandemic. Our experience shows that soon there will not be alternatives to digital pathology, given that there is no assurance that other similar outbreaks will not occur.

The Case of a Serous Borderline Ovarian Tumor in a 15-Year Old Pregnant Adolescent: Sonographic Characteristics and Surgical Management.

OBJECTIVE: This study aimed to describe a rare case of a serous borderline ovarian tumor (BOT) diagnosed during pregnancy in a 15-year old adolescent. RESULTS: The suspect of BOT was raised at a transvaginal ultrasound scan in early first trimester (at 5 weeks of amenorrhea), due to the presence of a moderately vascularized irregular papilla in the context of a unilocular low-level right ovarian cyst. The patient and her parents required termination of pregnancy, irrespective of the diagnosis of an ovarian lesion. After termination of pregnancy, the patient underwent laparoscopic enucleation of the ovarian mass, omentectomy, and peritoneal biopsies. No intra-abdominal spillage of the ovarian mass occurred, and the surgical specimens were put in an endobag and extracted transvaginally. Final pathological examination confirmed the diagnosis of a serous borderline ovarian tumor. The patient of free of disease after 8 months of follow-up. CONCLUSION: Although rare, borderline ovarian tumors can be diagnosed in an adolescent during pregnancy. The combination of specific sonographic assessment and minimally invasive conservative surgery appears as a very effective approach in this type of patient. KEY POINTS: · BOTs can occur in pregnant adolescents.. · Transvaginal ultrasound is crucial to suspect BOT.. · Laparoscopic conservative treatment is feasible..

Correction: PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. AIMS: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. METHODS: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. RESULTS: A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. CONCLUSION: We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding.

A Wolf in Sheep's Clothing: A Sporadic Juvenile Polyp of the Colon Harboring an Intramucosal Adenocarcinoma.

We describe a solitary peduncolated polypoid lesion with a bilobated head in the transverse colon mucosa of a 51-year-old Caucasian man. Histologically, the lesion was consistent with juvenile polyp (JP), but showing a few dysplastic glands and a focus of intramucosal adenocarcinoma. This finding suggests that, at least in adults, even the sporadic JPs might carry an inherent potential for malignancy, which has so far only been pointed out for syndromic lesions. Additionally, we observed p53 overexpression in both the dysplastic lesions and in the invasive cells but not in the remaining epithelium. We can argue that p53 immunohistochemistry may be helpful in differentiating hyperplastic regenerative atypia of the epithelium, frequently found in JPs, from true dysplasia, a much more rare change in the sporadic JPs.