Utilization of an artificial intelligence-enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study.

Background: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool.

Methods: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained.

Methylated DNA markers for plasma detection of ovarian cancer: Discovery, validation, and clinical feasibility.

Objective: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma.

Methods: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls.

BRAF Rearrangements and BRAF V600E Mutations Are Seen in a Subset of Pancreatic Carcinomas With Acinar Differentiation.

Context.—: Comprehensive genomic profiling has demonstrated that approximately 20% of pancreatic carcinomas with acinar differentiation harbor potentially targetable BRAF fusions that activate the MAPK pathway.

Objectives.

Tao brush endometrial cytology is a sensitive diagnostic tool for cancer and hyperplasia among women presenting to clinic with abnormal uterine bleeding.

Background: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology.

Methods: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled.

Theragnostic chromosomal rearrangements in treatment-naive pancreatic ductal adenocarcinomas obtained via endoscopic ultrasound.

A crucial mutational mechanism in malignancy is structural variation, in which chromosomal rearrangements alter gene functions that drive cancer progression. Herein, the presence and pattern of structural variations were investigated in twelve prospectively acquired treatment-naïve pancreatic cancers specimens obtained via endoscopic ultrasound (EUS). In many patients, this diagnostic biopsy procedure and specimen is the only opportunity to identify somatic clinically relevant actionable alterations that may impact their care and outcome.

RNA-Seq Reveals Differences in Expressed Tumor Mutation Burden in Colorectal and Endometrial Cancers with and without Defective DNA-Mismatch Repair.

Tumor mutation burden (TMB) is an emerging biomarker of immunotherapy response. RNA sequencing in FFPE tissue samples was used for determining TMB in microsatellite-stable (MSS) and microsatellite instability-high (MSI-H) tumors in patients with colorectal or endometrial cancer. Tissue from tumors and paired normal tissue from 46 MSI-H and 12 MSS cases were included.

Does Transfusion of Red Blood Cells Impact Germline Genetic Test Results?

Purpose: molecular testing is often indicated for recently transfused patients. However, there are no guidelines regarding the potential interference from donor DNA or whether it is necessary to wait for a period of time post-transfusion prior to genetic testing. While the majority of patients are transfused in the non-trauma setting using leukoreduced (LR) red blood cell products, the degree of leukoreduction varies among centers and is not universally practiced.

Molecular and Immunohistochemical Analysis of Mucinous Cystic Neoplasm of the Liver.

Objectives: Mucinous cystic neoplasm of the liver is characterized by neoplastic mucinous and/or biliary epithelium surrounded by ovarian-type stroma. Immunohistochemical studies have shown that the ovarian-type stroma expresses estrogen receptor, suggesting potential hormonal responsiveness. The molecular biology of mucinous cystic neoplasm of the liver remains poorly studied.

Maternal T Cells in the Human Placental Villi Support an Allograft Response during Noninfectious Villitis.

During human pregnancy, proinflammatory responses in the placenta can cause severe fetal complications, including growth restriction, preterm birth, and stillbirth. Villitis of unknown etiology (VUE), an inflammatory condition characterized by the infiltration of maternal CD8 T cells into the placenta, is hypothesized to be secondary to either a tissue rejection response to the haploidentical fetus or from an undiagnosed infection. In this study, we characterized the global TCR β-chain profile in human T cells isolated from placentae diagnosed with VUE compared with control and infectious villitis-placentae by immunoSEQ.

Upregulation of HLA-Class I and II in Placentas Diagnosed with Villitis of Unknown Etiology.

The placenta utilizes many mechanisms to protect the haploidentical fetus from recognition by the maternal immune system. However, in cases of villitis of unknown etiology (VUE), maternal lymphocytes gain access into the placenta, causing significant health risks for the fetus. Evidence suggests that VUE is a rejection response between the mother and the haploidentical fetus.

Clinicopathologic, Immunohistochemical, and Molecular Characteristics of Ovarian Serous Carcinoma With Mixed Morphologic Features of High-grade and Low-grade Serous Carcinoma.

Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study.

Combining copy number, methylation markers, and mutations as a panel for endometrial cancer detection via intravaginal tampon collection.

Objective: We aimed to assess whether endometrial cancer (EC) can be detected in shed DNA collected with vaginal tampon by analyzing copy number, methylation markers, and mutations.

Methods: Tampons were collected prior to hysterectomy from 38 EC patients and 28 women with benign indications. Extracted tampon DNA underwent the following: 1) low-coverage whole genome sequencing (LC-WGS) to assess copy number, 2) pyrosequencing to measure percent promotor methylation of HOXA9, RASSF1, and CDH13 and 3) next generation sequencing (NGS) to identify mutations in 19 genes associated with EC identified through The Cancer Genome Atlas.

The placenta: A site of end-organ damage after Fontan operation. A case series.

Background: Placental insufficiency may be the cause of the high preterm birth rate in women after Fontan operation. In this study we reviewed the clinical course and pregnancy outcome of women with Fontan physiology with a focus on placental pathology.

Methods: We reviewed clinical charts and placental pathology from 7 women with Fontan physiology who had pregnancies at Mayo Clinic, Rochester, Minnesota.

A data science approach for the classification of low-grade and high-grade ovarian serous carcinomas.

Background: Copy Number Alternations (CNAs) is defined as somatic gain or loss of DNA regions. The profiles of CNAs may provide a fingerprint specific to a tumor type or tumor grade. Low-coverage sequencing for reporting CNAs has recently gained interest since successfully translated into clinical applications.

An Enlarging Metastatic Calcified Liver Lesion of an Occult Melanoma.

Calcified liver lesions are caused by a wide variety of factors. The most common lesions are inflammatory liver lesions followed by benign and malignant neoplasms. Hemangioma, one of the most common benign hepatic neoplasm in adults, often contains calcifications, in up to 20% of cases secondary to fibrosis and thrombosis of blood vessels.

Incidence of major hemorrhage after aggressive image-guided liver mass biopsy in the era of individualized medicine.

Purpose: To analyze a large volume of image-guided liver mass biopsies to assess for an increased incidence of major hemorrhage after aggressive liver mass sampling, and to determine if coaxial technique reduces major hemorrhage rate.

Methods: Patients who underwent image-guided liver mass biopsy over a 15-year period (December 7, 2001-September 22, 2016) were retrospectively identified. An aggressive biopsy was defined as a biopsy event in which ≥ 4 core needle passes were performed.

Analysis of Cell-Free DNA to Assess Risk of Tumoremia Following Endoscopic Ultrasound Fine-Needle Aspiration of Pancreatic Adenocarcinomas.

Background & Aims: Cellular and nuclear material from tumors disseminates into the bloodstream (tumoremia), but it is not clear whether medical procedures cause release of this material or contribute to formation of metastases. We performed a prospective study of blood samples from patients with pancreatic adenocarcinoma (PDAC) to determine whether endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) associates with markers of tumoremia.

Methods: We obtained peripheral blood from 104 patients (35 with PDAC) before and after EUS-FNA of primary tumors; blood samples from 69 healthy individuals were used as controls.

Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.

Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA.

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery.

Background: The ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM).

Results: Prior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists.