A Pipeline for Evaluation of Machine Learning/Artificial Intelligence Models to Quantify Programmed Death Ligand 1 Immunohistochemistry.

Immunohistochemistry (IHC) is used to guide treatment decisions in multiple cancer types. For treatment with checkpoint inhibitors, programmed death ligand 1 (PD-L1) IHC is used as a companion diagnostic. However, the scoring of PD-L1 is complicated by its expression in cancer and immune cells.

Quantitative Imaging Analysis Fluorescence In Situ Hybridization Validation for Clinical HER2 Testing in Breast Cancer.

Context.—: Quantitative imaging is a promising tool that is gaining wide use across several areas of pathology. Although there has been increasing adoption of morphologic and immunohistochemical analysis, the adoption of evaluation of fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue has been limited because of complexity and lack of practice guidelines.

Morphologic Characteristics and Mutational Analysis of Fumarate Hydratase Deficient Kidney and Smooth Muscle Tumors.

Objectives: Fumarate hydratase (FH)-deficient tumors can occur due to germline or somatic mutations and have distinctive morphologic features. The aims of this study are to refine morphologic criteria and identify mutations in FH-deficient smooth muscle tumors (SMTs).

Methods: The morphology of SMTs and kidney tumors submitted to a national reference laboratory for FH immunohistochemistry (IHC) was reviewed by two gynecologic and two genitourinary pathologists, respectively.

Molecular testing in fine-needle aspiration of thyroid nodules.

Background: Thyroid nodules are commonly faced by clinicians as palpable nodules or incidentally identified on imaging. Nodules that are found to be suspicious by imaging can be biopsied by fine needle aspiration, which can yield material for molecular testing to refine the diagnosis.

Methods: The current literature concerning molecular testing in thyroid nodules including available commercial assays was reviewed and summarized.

Histopathological Correlation of Chromosome 12 Polysomy by Fluorescence in Situ Hybridization in Adipocytic Neoplasms.

Identification of amplification by fluorescence in situ hybridization is an important diagnostic tool for evaluation of adipocytic neoplasms. Rarely, neoplasms can show increased copies of and CEP12 probes (polysomy) without amplification (CEP12 ratio <2.0).

Histologic and Molecular Characterization of Non-Small Cell Lung Carcinoma With Discordant ROS1 Immunohistochemistry and Fluorescence In Situ Hybridization.

Introduction: ROS1 immunohistochemical (IHC) positivity requires follow-up with confirmatory testing such as fluorescence in situ hybridization (FISH). Identifying predictive characteristics of false positive ROS1 IHC cases could aid in optimizing testing algorithms, decrease testing costs and preserve tissue.

Materials And Methods: Retrospective results were retrieved for 2054 patients with non-small cell lung carcinoma submitted to our laboratory for molecular testing.

PD-L1 Tumor Cell Expression in Upper Tract Urothelial Carcinomas is Associated With Higher Pathologic Stage.

Background: Upper tract urothelial carcinomas (UTUCs) are a rare and unique subset of urothelial carcinoma (UC). Patients with UTUC may qualify for treatment with immune checkpoint inhibitors if their tumor cells express programmed death ligand-1 (PD-L1). While several large studies have looked at PD-L1 expression in UC, most have not investigated UTUC as a separate group, and most have not used Food and Drug Administration approved PD-L1 stains and scoring systems.

Application of the Roche Cobas® HPV 4800 in Formalin-Fixed, Paraffin-Embedded Samples for Head and Neck Squamous Cell Carcinomas.

Testing for high risk human papillomavirus (HR-HPV) status is standard of care in squamous cell carcinomas of the oropharynx as well as cervical lymph node squamous cell carcinomas of unknown primary origin. DNA or RNA in-situ hybridization (ISH) and p16 immunohistochemistry, widely used currently for HPV detection are operator-dependent. In addition, DNA ISH has a relatively low sensitivity, and p16 is not entirely specific for HR-HPV infection.

Differential outcomes of patients with thyroid FNA diagnoses of AUS/FLUS with and without nuclear atypia: The potential need for separation in the Bethesda System.

Background: In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks.

Successful lung cancer EGFR sequencing from DNA extracted from TTF-1 immunohistochemistry slides: a new means to extend insufficient tissue.

Lung cancer biopsy material is limited and is used for morphologic diagnosis and immunohistochemical and molecular testing. This can lead to tissue exhaustion, resulting in repeat biopsies (when clinically possible), delayed testing, and increased risks. Consequently, there is a need to optimize preanalytical specimen use for molecular testing.

Multi-Institutional Evaluation of Interrater Agreement of Variant Classification Based on the 2017 Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer.

This multi-institutional study was undertaken to evaluate interrater reliability of the 2017 Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists guidelines for interpretation and reporting of oncology sequence variants and to assess current practices and perceptions surrounding these guidelines. Fifty-one variants were distributed to 20 participants from 10 institutions for classification using the new guidelines. Agreement was assessed using chance-corrected agreement (Cohen κ).

Tumor PD-L1 expression in malignant pleural and peritoneal mesothelioma by Dako PD-L1 22C3 pharmDx and Dako PD-L1 28-8 pharmDx assays.

Malignant mesothelioma (MM) is an aggressive neoplasm with poor prognosis. The Dako PD-L1 22C3 and 28-8 pharmDx assays are approved by the US Food and Drug Administration (FDA) as companion and complementary diagnostics for the anti-PD-1 drugs pembrolizumab and nivolumab, respectively. Data from multiple clinical trials indicate that immunotherapy has antitumor activity in advanced malignant pleural (MPM) and peritoneal mesothelioma (MPeM).

GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin.

Assessment of mutational load in biopsy tissue provides additional information about genomic instability to histological classifications of Barrett's esophagus.

Purpose: Progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is associated with accumulated genomic instability. Current risk stratification of BE for EAC relies on histological classification and grade of dysplasia. However, histology alone cannot assess the risk of patients with inconsistent or non-dysplastic BE histology.

The value of mutational profiling of the cytocentrifugation supernatant fluid from fine-needle aspiration of pancreatic solid mass lesions.

Fine-needle aspiration (FNA) of pancreatic solid masses can be significantly impacted by sampling variation. Molecular analysis of tumor DNA can be an aid for more definitive diagnosis. The aim of this study was to evaluate how molecular analysis of the cell-free cytocentrifugation supernatant DNA can help reduce sampling variability and increase diagnostic yield.

MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features.

Background: MicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.

A case of primary intrahepatic gastrinoma.

Gastrinoma is an uncommon but important cause of peptic ulcer disease. These tumors are most commonly located in the duodenum or pancreas. We present a case of a primary intrahepatic gastrinoma.

Expression of mir-21 and mir-143 in cervical specimens ranging from histologically normal through to invasive cervical cancer.

Background: MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples.

DNA hypermethylation, Her-2/neu overexpression and p53 mutations in ovarian carcinoma.

Objectives: To define patterns of aberrant DNA methylation, p53 mutation and Her-2/neu overexpression in tissues from benign (n=29), malignant (n=100), and border line malignant ovaries (n=10), as compared to normal (n=68) ovarian tissues. Further, to explore the relationship between the presence of genetic and epigenetic abnormalities in ovarian cancers, and assess the association between epigenetic changes and clinical stage of malignancy at presentation and response to therapy.

Methods: The methylation status of 23 genes that were previously reported associated with various epithelial malignancies was assessed in normal and abnormal ovarian tissues by methylation-specific PCR.