Replication stress marker phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.

Background: Ovarian cancer treatment includes cytoreductive surgery, platinum-based chemotherapy, and often poly (ADP-ribose) polymerase (PARP) inhibitors. Homologous recombination (HR)-deficiency is a well-established predictor of therapy sensitivity. However, over 50% of HR-proficient tumors also exhibit sensitivity to standard-of-care treatments.

Robotic-Assisted Bronchoscopy for the Diagnosis of Lung Lesions: Experience With the Use of Frozen Sections as an Aid to Confirm the Localization of Lesions During the Procedure.

Context.—: Robotic-assisted navigation bronchoscopy (R-ANB) is used to target peripheral pulmonary nodules that are difficult to biopsy using conventional approaches. Frozen sections are requested to confirm these lesions have been localized and/or to diagnose neoplasms that can be immediately resected.

Spatiotemporal architecture of immune cells and cancer-associated fibroblasts in high-grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSOC), the deadliest form of ovarian cancer, is typically diagnosed after it has metastasized and often relapses after standard-of-care platinum-based chemotherapy, likely due to advanced tumor stage, heterogeneity, and immune evasion and tumor-promoting signaling from the tumor microenvironment. To understand how spatial heterogeneity contributes to HGSOC progression and early relapse, we profiled an HGSOC tissue microarray of patient-matched longitudinal samples from 42 patients. We found spatial patterns associated with early relapse, including changes in T cell localization, malformed tertiary lymphoid structure (TLS)-like aggregates, and increased podoplanin-positive cancer-associated fibroblasts (CAFs).

Guidelines for Pathologic Diagnosis of Mesothelioma: 2023 Update of the Consensus Statement From the International Mesothelioma Interest Group.

Context.—: Mesothelioma is an uncommon tumor that can be difficult to diagnose.

Objective.

INHBA(+) cancer-associated fibroblasts generate an immunosuppressive tumor microenvironment in ovarian cancer.

Effective targeting of cancer-associated fibroblasts (CAFs) is hindered by the lack of specific biomarkers and a poor understanding of the mechanisms by which different populations of CAFs contribute to cancer progression. While the role of TGFβ in CAFs is well-studied, less attention has been focused on a structurally and functionally similar protein, Activin A (encoded by INHBA). Here, we identified INHBA(+) CAFs as key players in tumor promotion and immunosuppression.

Multilayer outperforms single-layer slide scanning in AI-based classification of whole slide images with low-burden acid-fast mycobacteria (AFB).

Manual screening of Ziehl-Neelsen (ZN)-stained slides that are negative or contain rare acid-fast mycobacteria (AFB) is labor-intensive and requires repetitive refocusing to visualize AFB candidates under the microscope. Whole slide image (WSI) scanners have enabled implementation of AI to classify digital ZN-stained slides as AFB+ or AFB-. By default, these scanners acquire a single-layer WSI.

Ciliated Cells in Ovarian Cancer Decrease with Increasing Tumor Grade and Disease Progression.

Ciliated cell markers expressed in epithelial ovarian cancers (EOC) are associated with improved survival. We examined the distribution of cells expressing ciliated cell markers in various EOC histologies and stages. Immunohistochemistry and/or multiplex immunofluorescence were used to determine the expression of FOXJ1 and/or CAPS (ciliated cell markers) in tissue microarrays including 4 normal fallopian tubes, 6 normal endometria, 16 cystadenomas, 25 borderline tumors, 21 low-grade carcinomas, and 118 high-grade carcinomas (HGSOC) (46 serous, 29 endometrioid, 30 clear cell, 13 mucinous).

Dynamic Changes in the Extracellular Matrix in Primary, Metastatic, and Recurrent Ovarian Cancers.

Cancer-associated fibroblasts (CAFs) and their extracellular matrix are active participants in cancer progression. While it is known that functionally different subpopulations of CAFs co-exist in ovarian cancer, it is unclear whether certain CAF subsets are enriched during metastatic progression and/or chemotherapy. Using computational image analyses of patient-matched primary high-grade serous ovarian carcinomas, synchronous pre-chemotherapy metastases, and metachronous post-chemotherapy metastases from 42 patients, we documented the dynamic spatiotemporal changes in the extracellular matrix, fibroblasts, epithelial cells, immune cells, and CAF subsets expressing different extracellular matrix components.

FOXC2 Promotes Vasculogenic Mimicry in Ovarian Cancer.

FOXC2 is a forkhead family transcription factor that plays a critical role in specifying mesenchymal cell fate during embryogenesis. FOXC2 expression is associated with increased metastasis and poor survival in various solid malignancies. Using in vitro and in vivo assays in mouse ovarian cancer cell lines, we confirmed the previously reported mechanisms by which FOXC2 could promote cancer growth, metastasis, and drug resistance, including epithelial-mesenchymal transition, stem cell-like differentiation, and resistance to anoikis.

Computational pathology in ovarian cancer.

Histopathologic evaluations of tissue sections are key to diagnosing and managing ovarian cancer. Pathologists empirically assess and integrate visual information, such as cellular density, nuclear atypia, mitotic figures, architectural growth patterns, and higher-order patterns, to determine the tumor type and grade, which guides oncologists in selecting appropriate treatment options. Latent data embedded in pathology slides can be extracted using computational imaging.

Focal Serous Tubal Intra-Epithelial Carcinoma Lesions Are Associated With Global Changes in the Fallopian Tube Epithelia and Stroma.

Objective: Serous tubal intra-epithelial carcinoma (STIC) lesions are thought to be precursors to high-grade serous ovarian cancer (HGSOC), but HGSOC is not always accompanied by STIC. Our study was designed to determine if there are global visual and subvisual microenvironmental differences between fallopian tubes with and without STIC lesions.

Methods: Computational image analyses were used to identify potential morphometric and topologic differences in stromal and epithelial cells in samples from three age-matched groups of fallopian tubes.

Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas.

Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM).

Comparison of Nuclear Grade, Necrosis, and Histologic Subtype Between Biopsy and Resection in Pleural Malignant Mesothelioma: An International Multi-Institutional Analysis.

Objectives: Numerous studies on malignant mesothelioma (MM) highlight the prognostic importance of histologic subtype, nuclear grade, and necrosis. This study compares these parameters in paired biopsy and resection specimens of pleural MM.

Methods: Histologic subtype, percentage of epithelioid morphology, nuclear grade, and the presence or absence of necrosis were compared in 429 paired biopsies and resection specimens of pleural MM from 19 institutions.

Clinico-pathologic findings in patients with median arcuate ligament syndrome (celiac artery compression syndrome).

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals.

The concept of mesothelioma in situ, with consideration of its potential impact on cytology diagnosis.

Diffuse malignant mesothelioma (MM) is an incurable tumour of the serosal membranes, which is often caused by exposure to asbestos and commonly diagnosed at advanced stage. Malignant mesothelioma in situ (MMIS) is now included as diagnostic category by the World Health Organization (WHO). However, our international survey of 34 pulmonary pathologists with an interest in MM diagnosis highlights inconsistency regarding how the diagnosis is being made by experts, despite published guidelines.

Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases.

Malignant peritoneal mesothelioma historically carried a grim prognosis, but outcomes have improved substantially in recent decades. The prognostic significance of clinical, morphologic, and immunophenotypic features remains ill-defined. This multi-institutional cohort comprises 225 malignant peritoneal mesotheliomas, which were assessed for 21 clinical, morphologic, and immunohistochemical parameters.

Challenges in Ki-67 assessments in pulmonary large-cell neuroendocrine carcinomas.

Aims: To gather the best available evidence regarding Ki-67% values in large-cell neuroendocrine carcinoma (LCNEC) and determine whether certain cut-off values could serve as a prognostic feature in LCNEC.

Methods And Results: Aperio ScanScope AT Turbo, eSlide Manager and ImageScope software (Leica Biosystems) were used to measure Ki-67% in 77 resected LCNEC diagnosed by World Health Organisation (WHO) criteria. Cases were stratified into six classes by 10% Ki-67 increments.

Multiplatform molecular test performance in indeterminate thyroid nodules.

Background: Approximately 25% of thyroid nodule fine-needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.

Methods: We evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive).

Are Epithelial Ovarian Cancers of the Mesenchymal Subtype Actually Intraperitoneal Metastases to the Ovary?

Primary ovarian high-grade serous carcinoma (HGSC) has been classified into 4 molecular subtypes: Immunoreactive, Proliferative, Differentiated, and Mesenchymal (Mes), of which the Mes subtype (Mes-HGSC) is associated with the worst clinical outcomes. We propose that Mes-HGSC comprise clusters of cancer and associated stromal cells that detached from tumors in the upper abdomen/omentum and disseminated in the peritoneal cavity, including to the ovary. Using comparative analyses of multiple transcriptomic data sets, we provide the following evidence that the phenotype of Mes-HGSC matches the phenotype of tumors in the upper abdomen/omentum: (1) irrespective of the primary ovarian HGSC molecular subtype, matched upper abdominal/omental metastases were typically of the Mes subtype, (2) the Mes subtype was present at the ovarian site only in patients with concurrent upper abdominal/omental metastases and not in those with HGSC confined to the ovary, and (3) ovarian Mes-HGSC had an expression profile characteristic of stromal cells in the upper abdominal/omental metastases.

A CNN-based active learning framework to identify mycobacteria in digitized Ziehl-Neelsen stained human tissues.

Tuberculosis is the most common mycobacterial disease that affects humans worldwide. Rapid and reliable diagnosis of mycobacteria is crucial to identify infected individuals, to initiate and monitor treatment and to minimize or prevent transmission. Microscopic identification of acid-fast mycobacteria (AFB) in tissue sections is usually accomplished by examining Ziehl-Neelsen (ZN) stained slides in which AFB appear bright red against the blue background.

Pathologists should probably forget about kappa. Percent agreement, diagnostic specificity and related metrics provide more clinically applicable measures of interobserver variability.

Kappa statistics have been widely used in the pathology literature to compare interobserver diagnostic variability (IOV) among different pathologists but there has been limited discussion about the clinical significance of kappa scores. Five representative and recent pathology papers were queried using clinically relevant specific questions to learn how IOV was evaluated and how the clinical applicability of results was interpreted. The papers supported our anecdotal impression that pathologists usually assess IOV using Cohen's or Fleiss' kappa statistics and interpret the results using some variation of the scale proposed by Landis and Koch.

HOXB13 controls cell state through super-enhancers.

Expression of the homeodomain transcription factor HOXB13 has been demonstrated in several malignancies but its role in tumorigenesis remains elusive. We observed high levels of HOXB13 in poorly differentiated pediatric tumors including a highly aggressive childhood neoplasm - malignant rhabdoid tumor. In a xenograft model of rhabdoid tumor, knockout of HOXB13 diminished tumor growth while partial knockdown of HOXB13 promoted differentiation of tumor cells into bone.