Coffin-Siris Syndrome and SMARCB1 Mutation Presenting With Schwannomatosis: A Case Report and Literature Review.

Coffin-Siris syndrome (CSS) is a rare genetic condition associated with mutations in genes responsible for the modulation of gene expression and chromatin remodeling. Patients with CSS commonly present with congenital anomalies, intellectual disabilities, and developmental delays. We describe a case of a 28-year-old woman with a confirmed diagnosis of CSS and mutation who presents with multiple schwannomas and an intra-abdominal neurofibroma.

RET splice site variants in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC.

Deceptive learning in histopathology.

Aims: Deep learning holds immense potential for histopathology, automating tasks that are simple for expert pathologists and revealing novel biology for tasks that were previously considered difficult or impossible to solve by eye alone. However, the extent to which the visual strategies learned by deep learning models in histopathological analysis are trustworthy or not has yet to be systematically analysed. Here, we systematically evaluate deep neural networks (DNNs) trained for histopathological analysis in order to understand if their learned strategies are trustworthy or deceptive.

Lifetime Exposure to Cigarette Smoke, B-Cell Tumor Immune Infiltration, and Immunoglobulin Abundance in Ovarian Tumors.

Background: Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the impact of smoke exposure across the life-course on B-cell infiltration and Ig abundance in ovarian tumors.

Methods: We measured markers of B and plasma cells and Ig isotypes using multiplex immunofluorescence on 395 ovarian cancer tumors in the Nurses' Health Study (NHS)/NHSII.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

Background: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC.

WITHDRAWN: Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer.

The authors have withdrawn their manuscript owing to incorrect handling of multiple measures in the survival analyses. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

The relationship of lifetime history of depression on the ovarian tumor immune microenvironment.

Background: Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response.

Methods: We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215).

Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma.

Introduction: In clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.

Methods: Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley's K analysis, a methodology adapted from ecology.

Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies.

Background: Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ovarian tumor immune microenvironment, it is critical to understand methodologic issues related to measurement of immune cells on tissue microarrays (TMA) using multiplex immunofluorescence (mIF) assays.

Methods: In two prospective cohorts, we collected formalin-fixed, paraffin-embedded ovarian tumors from 486 cases and created seven TMAs.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches.

Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis.

Lifetime Exposure to Cigarette Smoke and Risk of Ovarian Cancer by T-cell Tumor Immune Infiltration.

Background: Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts the ovarian tumor immune microenvironment.

Methods: Participants in the Nurses' Health Study (NHS) and NHSII reported on early life exposure to cigarette smoke and personal smoking history on questionnaires (n = 165,760).

Utilizing digital pathology to quantify stromal caveolin-1 expression in malignant and benign ovarian tumors: Associations with clinicopathological parameters and clinical outcomes.

Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expression were quantified in serous OvCa and benign ovarian tissue in two, independent cohorts-one quantified expression using immunohistochemistry (IHC) and the other using multiplex immunofluorescence (IF) with digital image analysis designed to target CAF-specific expression.

Sclerosing Polycystic Adenoma: Conclusive Clinical and Molecular Evidence of Its Neoplastic Nature.

Sclerosing polycystic adenosis, initially considered a non-neoplastic salivary gland lesion and classified as such in the 2017 WHO Classification of Head and Neck Tumors, has been the subject of controversy regarding its possible neoplastic nature. The reporting of recurrent PI3K pathway alteration represents evidence to support these lesions as being neoplastic and more appropriately referred to as sclerosing polycystic adenoma (SPA). Herein, we provide additional evidence that supports the classification of SPA as a true neoplasm.

Identification of Targetable Gene Fusions and Structural Rearrangements to Foster Precision Medicine in Wild-Type Pancreatic Cancer.

Unlabelled: It has recently been described that alternative oncogenic drivers may be found in wild-type ( ) pancreatic cancers. This study aimed to determine the incidence of targetable gene fusions present in pancreatic adenocarcinoma and response to targeted therapy.

Methods: One hundred consecutive patients with pancreatic adenocarcinoma who underwent targeted next-generation sequencing using DNA sequencing with RNA sequencing (n = 47) or without RNA sequencing (n = 53) at a single institution were included in the study.

Guideline-Adherent Clinical Validation of a Comprehensive 170-Gene DNA/RNA Panel for Determination of Small Variants, Copy Number Variations, Splice Variants, and Fusions on a Next-Generation Sequencing Platform in the CLIA Setting.

We describe the clinical validation of a targeted DNA and RNA-based next-generation sequencing (NGS) assay at two clinical molecular diagnostic laboratories. This assay employs simultaneous DNA and RNA analysis of all coding exons to detect small variants (single-nucleotide variants, insertions, and deletions) in 148 genes, amplifications in 59 genes, and fusions and splice variants in 55 genes. During independent validations at two sites, 234 individual specimens were tested, including clinical formalin-fixed, paraffin-embedded (FFPE) tumor specimens, reference material, and cell lines.

Sclerosing epithelioid fibrosarcoma: cytologic characterization with histologic, immunohistologic, molecular, and clinical correlation of 8 cases.

Introduction: Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon malignant fibroblastic neoplasm. The diagnosis is typically made on core needle biopsy or resection specimens. Cytomorphologic characterization of SEF has been limited to rare case reports in the literature.

Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes.

ERBB4 Expression in Ovarian Serous Carcinoma Resistant to Platinum-Based Therapy.

Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories.

Practical Applications of Digital Pathology.

Background: Virtual microscopy and advances in machine learning have paved the way for the ever-expanding field of digital pathology. Multiple image-based computing environments capable of performing automated quantitative and morphological analyses are the foundation on which digital pathology is built.

Methods: The applications for digital pathology in the clinical setting are numerous and are explored along with the digital software environments themselves, as well as the different analytical modalities specific to digital pathology.

Should cervical cancer screening begin at age 21 for everyone? A quantitative analysis in a high-risk, low-income, African American/Hispanic young-adult population.

The American College of Obstetricians and Gynecologists has recommended modifying the baseline cervical cancer screening age from earlier of three years after first sexual intercourse or age 21 to age 21. In this study, we tracked abnormal cytologic diagnoses, with an emphasis on high-grade cervical lesions, in a high-risk, low-income, African American/Hispanic young-adult population. The intention was to assess if delaying cancer screening to 21 years of age would be effective in this subpopulation.

Retroperitoneal cystic lymphangioma in an adult: A case report and review of the literature.

Lymphangiomas are rare benign cystic tumors of the lymphatic system. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas, and approximately 186 cases have been reported. They may clinically present as a palpable abdominal mass and can cause diagnostic dilemmas with other retroperitoneal cystic tumors, including those arising from the liver, kidney and pancreas.

Localized cavernous hemangioma of the uterus involving adenomyotic foci.

Localized cavernous hemangioma of the uterus is an extremely rare lesion that often presents with heavy uterine bleeding and/or pelvic pain. Though more cases exist for pregnant women, some isolated case reports involve non-pregnant women. The diagnosis is difficult and requires a high index of clinical and radiological suspicion.