Diagnostic modalities in the mediastinum and the role of bronchoscopy in mediastinal assessment: a narrative review.

Background And Objective: Diagnosis of pathology in the mediastinum has proven quite challenging, given the wide variability of both benign and malignant diseases that affect a diverse array of structures. This complexity has led to the development of many different non-invasive and invasive diagnostic modalities. Historically, diagnosis of the mediastinum has relied on different imaging modalities such as chest X-ray, computed tomography (CT), magnetic resonance imaging, and positron emission topography.

Characterization of gastric/gastrointestinal-like immunophenotypes in endometrial endometrioid adenocarcinomas, including endometrioid adenocarcinomas with mucinous differentiation.

Endometrial mucinous carcinoma of the gastric [gastrointestinal] type (MCG) is a rare, possibly aggressive subtype of endometrial cancer that should be distinguished from its potential mimics, including endometrioid carcinoma (EEC). Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in EEC without any discernible gastric/gastrointestinal-type morphology. Immunohistochemical analyses for KRT(CK)7, KRT20, CDX2, ER, SATB2, MUC6, PAX8, and HIK1083 were performed on 81 EEC, inclusive of consecutively archived low grade [with (n = 22) and without (n = 47) mucinous differentiation] and high grade (n = 12) cases.

PI3Kγ inhibition circumvents inflammation and vascular leak in SARS-CoV-2 and other infections.

Virulent infectious agents such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and methicillin-resistant (MRSA) induce tissue damage that recruits neutrophils, monocyte, and macrophages, leading to T cell exhaustion, fibrosis, vascular leak, epithelial cell depletion, and fatal organ damage. Neutrophils, monocytes, and macrophages recruited to pathogen-infected lungs, including SARS-CoV-2-infected lungs, express phosphatidylinositol 3-kinase gamma (PI3Kγ), a signaling protein that coordinates both granulocyte and monocyte trafficking to diseased tissues and immune-suppressive, profibrotic transcription in myeloid cells. PI3Kγ deletion and inhibition with the clinical PI3Kγ inhibitor eganelisib promoted survival in models of infectious diseases, including SARS-CoV-2 and MRSA, by suppressing inflammation, vascular leak, organ damage, and cytokine storm.

Fumarate Hydratase-Deficient Leiomyoma of the Uterine Corpus: Comparative Morphologic Analysis of Protein-Deficient Tumors With and Without Pathogenic Germline Fumarate Hydratase Gene Mutations.

Deficiency of fumarate hydratase (FH) protein expression in uterine corpus leiomyomas may be attributable to either germline or somatic mutations of the gene, the former being definitional for the hereditary leiomyomatosis and renal cell cancer syndrome. The authors assess whether, using previously reported FH-associated morphologic features, FH protein-deficient uterine corpus leiomyomas associated with a pathogenic germline mutations of the gene (group 1) are distinguishable from FH protein-deficient uterine corpus leiomyomas without such mutations (and whose FH protein loss is presumed to be attributable to somatic/epigenetic inactivation or other unknown phenomena: group 2). Groups 1 and 2 were compared regarding a variety of clinicopathologic features, including 7 core "FH-associated" tumoral morphologic features: staghorn vasculature; alveolar-type edema; bizarre nuclei; chain-like tumor nuclei; hyaline cytoplasmic globules; prominent nucleoli, intranuclear inclusions, and perinucleolar halos; and prominent eosinophilic/fibrillary cytoplasm.

Accurate genome-wide genotyping from archival tissue to explore the contribution of common genetic variants to pre-cancer outcomes.

Purpose: The contribution of common genetic variants to pre-cancer progression is understudied due to long follow-up time, rarity of poor outcomes and lack of available germline DNA collection. Alternatively, DNA from diagnostic archival tissue is available, but its somatic nature, limited quantity and suboptimal quality would require an accurate cost-effective genome-wide germline genotyping methodology.

Experimental Design: Blood and tissue DNA from 10 individuals were used to benchmark the accuracy of Single Nucleotide Polymorphisms (SNP) genotypes, Polygenic Risk Scores (PRS) or HLA haplotypes using low-coverage whole-genome sequencing (lc-WGS) and genotype imputation.

B3 thymoma mimicking poorly differentiated thyroid carcinoma: Diagnostic pitfalls of anterior mediastinal mass fine needle aspiration.

B3 thymoma is a rare malignant type of thymic epithelial neoplasm found in the anterior mediastinum. Diagnosis of thymoma from fine needle aspiration (FNA) can be challenging due to the infrequency of sampling and its morphologic overlap with other entities such as squamous cell carcinoma, lymphoma or thyroid carcinoma. We report a case of B3 thymoma mimicking poorly differentiated thyroid carcinoma.

The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ.

Microenvironmental and molecular factors mediating the progression of Breast Ductal Carcinoma In Situ (DCIS) are not well understood, impeding the development of prevention strategies and the safe testing of treatment de-escalation. We addressed methodological barriers and characterized the mutational, transcriptional, histological, and microenvironmental landscape across 85 multiple microdissected regions from 39 cases. Most somatic alterations, including whole-genome duplications, were clonal, but genetic divergence increased with physical distance.

Using computer-assisted content analysis to advance anal dysplasia natural history research.

Objective: Our study aim was to validate the use of computer-aided narrative content analysis in the extraction of standard diagnostic categories using an archived cytology database that included individually overread reference classification.

Design: A retrospective analysis of narrative anal cytology results collected on HIV-infected patients at the University of California, San Diego between January and December 2001.

Methods: We used computer-assisted content analysis extraction methodology using Wordstat 8.

Rectal endometriosis mimicking primary rectal adenocarcinoma.

Endometriosis is a benign entity defined as the presence of endometrium tissue outside of uterine cavity. It is a common disease involving peritoneum, pelvic organs, gastrointestinal tract, and so on. Diagnosis based on cytology specimen can be challenge when we encounter increased cytological atypia in the glandular epithelium, with abundant inflammatory cells and debris in the background.

PTEN Loss and ARID1A Mutation in an HPV-positive Metastatic Adenocarcinoma Diagnosed Almost 18 yr After an Intact Cone Excision for Endocervical Adenocarcinoma In Situ.

There have been previous reports of neoplasms with the morphology of endocervical adenocarcinoma in situ (AIS) that secondarily involve the ovaries, presumably through transtubal spread, with a smaller subset metastasizing to distant sites. These ovarian metastases have been discovered up to 7 yr postexcision of the endocervical lesion, consistent with the known potential for overtly invasive cervical carcinomas to recur late after primary curative management. Herein, we present a case of a premenopausal woman with a pelvic mass classified as metastatic human papillomavirus (HPV)-associated endocervical adenocarcinoma (p16-block immunoreactive, high-risk HPV positive by in situ hybridization with PTEN loss, ARID1A, and PBRM1 mutations detected by qualitative next-generation sequencing), identified 17.

Nonmass enhancement lesions of the breast on core needle biopsy: outcomes, frequency of malignancy, and pathologic findings.

Nonmass enhancement (NME) on breast magnetic resonance imaging (MRI) is defined as an area whose internal enhancement characteristics can be distinguished from the normal surrounding breast parenchyma, without an associated mass in the Breast Imaging Reporting and Data System lexicon. In this study, we evaluated the pathologic correlates of NME lesions of the breast identified on MRI at our institution, including the frequency of atypical or malignant lesions in the core needle biopsies (CNBs), performed after such a radiologic finding. A retrospective study was performed on all CNBs performed for NME on breast MRI between 2010 and 2019.

Mutational profiling of micro-dissected pre-malignant lesions from archived specimens.

Background: Systematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery.

Independent Validation of Tumor Budding Activity and Cell Nest Size as Determinants of Patient Outcome in Squamous Cell Carcinoma of the Uterine Cervix.

A novel 3-tiered grading system that combines tumor budding activity and cell nest size has been found to be highly prognostic in squamous cell carcinomas (SCCs) of various sites, including lung, oral cavity, larynx, hypopharynx, and esophagus. A similar grading system has recently been proposed for SCC of the uterine cervix. In this study, we appraise this grading system in an institutional cohort of cervical SCC to assess its prognostic value in an independent dataset.

Normal human lymph node T follicular helper cells and germinal center B cells accessed via fine needle aspirations.

Germinal centers (GC) are critically important for maturation of the antibody response and generation of memory B cells, processes that form the basis for long-term protection from pathogens. GCs only occur in lymphoid tissue, such as lymph nodes, and are not present in blood. Therefore, GC B cells and GC T follicular helper (T) cells are not well-studied in humans under normal healthy conditions, due to the limited availability of healthy lymph node samples.

Intranodal palisaded myofibroblastoma of para-esophageal lymph node: Case report with cytologic and histologic findings.

Intranodal palisaded myofibroblastoma is a rare lymph node mesenchymal neoplasm that most commonly arises in inguinal lymph nodes. There is limited data about cytologic features of this tumor and its diagnostic pitfalls. The combination of bland appearing spindle cells, fibrillary matrix, and hemosiderin pigments are the characteristic features of this neoplasm in cytologic specimens.

Implementation of the 2018 American Society of Clinical Oncology/College of American Pathologists Guidelines on HER2/neu Assessment by FISH in breast cancers: predicted impact in a single institutional cohort.

The 2018 American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) update modified the interpretation guidelines for human epidermal growth factor receptor 2 (HER2) testing by incorporating immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) results in a subset of cases. Importantly, the new guidelines eliminate "equivocal" results, as well as the use of alternative chromosome 17 probes as the primary strategy for resolving the indeterminate FISH results. Herein, we investigate the predicted impact of implementing the 2018 ASCO/CAP guidelines on HER2 assessment by FISH in breast cancers, using data from a single institution.

Breast cancers with a HER2/CEP17 ratio of 2.0 or greater and an average HER2 copy number of less than 4.0 per cell: frequency, immunohistochemical correlation, and clinicopathological features.

The 2013 American Society of Clinical Oncology and College of American Pathologists (ASCO/CAP) guidelines classified breast cancers with a fluorescence in situ hybridization dual-probe HER2/CEP17 ratio of 2 or greater as "amplified," inclusive of cases with a HER2 copy number less than 4. The 2018 ASCO/CAP update assigns HER2/neu status for the latter group in a fashion that is highly dependent on the associated immunohistochemical findings. Herein, the authors define the frequency, immunohistochemical correlates, and other clinicopathological features of breast cancers with HER2/CEP17 ratio of 2 or greater and HER2/neu copy number less than 4 (group A), based on an analysis of an institutional cohort assessed for HER2/neu status by both florescence in situ hybridization and immunohistochemistry and scored using 2013 ASCO/CAP criteria.

Comparative Pathologic Analysis of Breast Cancers Classified as HER2/neu-Amplified by FISH Using a Standard HER2/CEP17 Dual Probe and an Alternative Chromosome 17 Control Probe.

At our institution, breast cancer cases that generate an equivocal HER2/neu (HER2) result by fluorescence in situ hybridization (FISH) using the dual HER2/chromosome enumeration probe (CEP17) are reflexed to an assay that utilizes an alternative control probe (lissencephaly gene1 [LIS1] [17p13.3]/retinoic acid receptor α [RARA] [17q21.2]).

A Single Institutional Experience With the Paris System for Reporting Urinary Cytology: Correlation of Cytology and Histology in 194 Cases.

Objectives: The Paris System for Reporting Urinary Cytology (TPS) is designed to standardize the criteria and terminology used in urinary tract cytology reporting. The aim of this study was to evaluate the impact of implementing TPS and to analyze the correlation with follow-up biopsies in order to assess its reproducibility.

Methods: Urinary tract cytology specimens with follow-up biopsies over a 2-year period were reviewed and reclassified according to TPS criteria.

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer.

Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not.

Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change.

Several studies have documented phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy [NACT], but many of these studies are limited by the fact that they did not account for the baseline rate of expected phenotypic change between biopsies and resections in the absence of NACT. Herein, we assess whether the NACT-associated rate of phenotypic change is significantly different than would be expected in a control population of patients that did not receive NACT. From a pathologic database, we documented the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) phenotypes of consecutive invasive breast carcinomas (n=826), as well as the subset in which at least one of these tests was assessed in both the biopsy and resection (n=340).

Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor-2 Testing in Breast Cancer: Assessing the Value of Repeated Centralized Testing in Excision Specimens.

At some tertiary breast care centers, where many patients are referred from other institutions, it is routine to repeat testing for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) in excision specimens if these tests were performed on the preceding biopsy at the referring facility. The goal of this study is to assess the value of this practice. We documented results from ER, PR, and HER2 testing in 541 consecutive invasive breast cancers excised over a 2.

Her2/neu Status Determination in Breast Cancer: A Single Institutional Experience Using a Dual-Testing Approach With Immunohistochemistry and Fluorescence In Situ Hybridization.

Objectives: According to current guidelines, either immunohistochemistry (IHC) or in situ hybridization (ISH) can be used to determine human epidermal growth factor receptor 2 (Her2/neu) status in breast carcinoma. While the guidelines explicitly delineate result interpretation, there is no consensus on the most appropriate testing algorithm.

Methods: The Her2/neu statuses of 369 consecutive cases of invasive breast cancer (from 351 patients) were assessed in a dual-testing algorithm that uses both IHC and fluorescence ISH (FISH).

Mutational Profiling Can Establish Clonal or Independent Origin in Synchronous Bilateral Breast and Other Tumors.

Background: Synchronous tumors can be independent primary tumors or a primary-metastatic (clonal) pair, which may have clinical implications. Mutational profiling of tumor DNA is increasingly common in the clinic. We investigated whether mutational profiling can distinguish independent from clonal tumors in breast and other cancers, using a carefully defined test based on the Clonal Likelihood Score (CLS = 100 x # shared high confidence (HC) mutations/ # total HC mutations).