TRAIL agonists rescue mice from radiation-induced lung, skin or esophageal injury.

Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.

Advancing Artificial Intelligence Integration Into the Pathology Workflow: Exploring Opportunities in Gastrointestinal Tract Biopsies.

This review aims to present a comprehensive overview of the current landscape of artificial intelligence (AI) applications in the analysis of tubular gastrointestinal biopsies. These publications cover a spectrum of conditions, ranging from inflammatory ailments to malignancies. Moving beyond the conventional diagnosis based on hematoxylin and eosin-stained whole-slide images, the review explores additional implications of AI, including its involvement in interpreting immunohistochemical results, molecular subtyping, and the identification of cellular spatial biomarkers.

Utility of Wnt family member 9b (Wnt9b) immunohistochemistry in the cytologic diagnosis of metastatic breast carcinoma.

Wnt family member 9b (Wnt9b) has been demonstrated as a valuable marker for breast cancer diagnosis in surgical pathology. In this study, we examined the utility of Wnt9b in diagnosing metastatic breast carcinoma in cytology samples. Cell blocks from fine needle aspirations (FNA) and fluid specimens of 96 metastatic breast carcinomas and 123 primary and metastatic non-breast neoplasms from various organ systems were evaluated by Wnt9b and GATA3 immunohistochemistry (IHC).

In Search of Calcifications : Histologic Analysis and Diagnostic Yield of Stereotactic Core Needle Breast Biopsies.

Objectives: Stereotactic core needle biopsy (SCNB) is used in the diagnostic assessment of suspicious mammographic calcifications to rule out breast ductal carcinoma in situ (DCIS). With advances in imaging technology and increased biopsy tissue volume, the detection rate of calcifications and DCIS in SCNB is unclear.

Methods: This retrospective study included 916 consecutive SCNBs for calcifications performed on 893 patients in a 2-year period.

Defining triple-negative breast cancer with neuroendocrine differentiation (TNBC-NED).

Primary breast neuroendocrine (NE) neoplasms are uncommon, and definitions harbor controversy. We retrospectively collected 73 triple-negative breast cancers (TNBC) and evaluated NE biomarker expression along with p53 aberrant staining (which correlates with TP53 gene mutation) and Rb protein loss by immunohistochemistry. In the study cohort, we found 11 (15%) cases of TNBC with neuroendocrine differentiation (TNBC-NED) showing positivity for one or more NE markers (synaptophysin/chromogranin/insulinoma-associated protein 1 [INSM1]).

Comprehensive Genomic Profiling of NF2-Mutated Kidney Tumors Reveals Potential Targets for Therapy.

Genomic alterations (GA) in NF2 tumor-suppressor gene have been associated with aggressive behavior in kidney tumors. We used comprehensive genomic profiling (CGP) to evaluate the frequencies of NF2 GA in histologic subtypes of kidney tumors and co-occurring GA in other genes and biomarkers. Advanced kidney tumors included 1875 clear cell (ccRCC), 405 papillary (pRCC), 108 chromophobe (chRCC), 171 sarcomatoid (sRCC), 61 collecting duct (cdRCC), 49 medullary (mRCC), 134 unclassified (uRCC), 906 urothelial carcinoma of renal pelvis (UC), and 147 Wilms tumors underwent hybrid-capture based CGP to evaluate all classes of GA.

"Growing fibroadenoma": Are there clinical and pathological features predicting a phyllodes tumor on surgical excision?

In cases of growth of FA on imaging, core needle biopsies (CNB) are often performed to rule out phyllodes tumor (PT). We aim to focus on "growing FAs" and to identify clinical and histopathologic features that are likely to predict a PT on excision. Thirty-four FAs with radiologic documentation of growth were included.

From Immunohistochemistry to New Digital Ecosystems: A State-of-the-Art Biomarker Review for Precision Breast Cancer Medicine.

Breast cancers represent complex ecosystem-like networks of malignant cells and their associated microenvironment. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are biomarkers ubiquitous to clinical practice in evaluating prognosis and predicting response to therapy. Recent feats in breast cancer have led to a new digital era, and advanced clinical trials have resulted in a growing number of personalized therapies with corresponding biomarkers.

Mass-forming ductal carcinoma in situ: An ultrasonographic and histopathologic correlation study.

Ultrasound (US) guided core needle biopsy (CNB) for mass lesions resulting in a diagnosis of ductal carcinoma in situ (DCIS) is often considered radiologically discordant and generates surgical planning difficulty. One hundred cases of US-guided CNB for mass lesions diagnosed as DCIS were collected from 2013 to 2021. Histological features were reviewed and correlated with radiology and surgical excision findings.

Microinvasive breast cancer and the role of sentinel lymph node biopsy.

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making.

A Rare Case of Esophagitis Dissecans Superficialis Occurring with Barrett's Esophagus.

Esophagitis dissecans superficialis (EDS) is a rare but benign disease of the esophagus often identified endoscopically by sloughing of the superficial esophageal mucosa. We present an asymptomatic 66-year-old patient found to have EDS in the setting of Barrett's esophagus. The association of EDS with Barrett's esophagus has not been previously reported.

Utility of secretagogin as a marker for the diagnosis of lung neuroendocrine carcinoma.

Small-cell lung cancers (SCLC) and large-cell neuroendocrine carcinomas (LCNEC) are two types of high-grade pulmonary neuroendocrine carcinomas (NECs). Diagnostic neuroendocrine markers commonly include synaptophysin, chromogranin A, CD56, and insulinoma-associated protein 1 (INSM1). In this study, the utility of secretagogin (SCGN) was examined in the context of pulmonary NEC diagnosis.

Xanthogranulomatous cholangitis mimicking cholangiocarcinoma: Case report and review of literature.

Introduction: Xanthogranulomatous cholangitis is an extremely rare diagnosis and is believed to be an extension of xanthogranulomatous cholecystitis, a benign inflammatory process characterized by lipid-laden foamy macrophages (called "xanthoma cells") occurring in a background of chronic inflammation consisting of lymphocytes, plasma cells, and eosinophils. Here, we report a case of xanthogranulomatous cholangitis mimicking cholangiocarcinoma.

Case Presentation: A 72 year old male with history of recurrent cholangitis had preoperative workup highly suggestive of intrahepatic cholangiocarcinoma.

Stromal computational signatures predict upgrade to invasive carcinoma in mass-forming DCIS: A brief report of 44 cases.

Mass-forming ductal carcinoma in situ (DCIS) detected on core needle biopsy (CNB) is often a radiology-pathology discordance and thought to represent missed invasive carcinoma. This brief report applied supervised machine learning (ML) for image segmentation to investigate a series of 44 mass-forming DCIS cases, with the primary focus being stromal computational signatures. The area under the curve (AUC) for receiver operator curves (ROC) in relation to upgrade to invasive carcinoma from DCIS were as follows: high myxoid stromal ratio (MSR): 0.

Wnt Family Member 9b (Wnt9b) Is a New Sensitive and Specific Marker for Breast Cancer.

Confirming the tumor origin is often a diagnostic challenge in pathology and carries significant therapeutic impacts. Cytokeratin 7, estrogen receptor, and GATA binding protein 3 (GATA3) are well-established diagnostic markers frequently used to support a tumor's breast origin. However, their specificities still have room to improve.

Immunohistochemical HER2 score correlates with response to neoadjuvant chemotherapy in HER2-positive primary breast cancer.

Purpose: The accuracy of biomarker assessment in breast cancer (BC) is paramount for therapy decisions and informs prognosis. We investigated neoadjuvant chemotherapy (NAC) response in HER2-positive BC with respect to immunohistochemistry (IHC) and in situ hybridization (ISH) results. We aimed to determine the role of HER2 protein expression in predicting NAC response and long-term outcome in two HER2-positive groups: IHC 3 + versus IHC 2 + ISH amplified groups.

Mutations in DNA Repair Genes and Clinical Outcomes of Patients With Metastatic Colorectal Cancer Receiving Oxaliplatin or Irinotecan-containing Regimens.

Objectives: First-line regimens in the treatment of metastatic colorectal cancer (mCRC) combine a fluoropyrimidine with oxaliplatin (FOLFOX/XELOX) or irinotecan (FOLFIRI). There is limited efficacy data to guide the selection of one treatment over the other. This study investigated whether mutations affecting DNA damage response (DDR) could differentially influence the response to oxaliplatin and irinotecan-containing regimens.

PAX8 Expression in Breast Cancer.

PAX8 expression is frequently detected in renal, thyroidal, and Müllerian carcinomas, and PAX8 immunohistochemistry is often used to confirm the origin of these tumors. Tumors metastatic to the breast may masquerade as primary breast lesions. PAX8 is strongly expressed in tumors of Müllerian origin and largely negative in breast primaries, but an immunohistochemical expression of PAX8 in breast cancer has not been systematically evaluated in a large series.

Characterization of Clinical Cases of Malignant PEComa via Comprehensive Genomic Profiling of DNA and RNA.

Purpose: Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal soft tissue neoplasm often linked to mTOR pathway activation via TSC2 mutation. We analyzed a series of 31 consecutive metastatic PEComa (mPEComa) cases using a combined DNA/RNA hybrid capture-based comprehensive genomic profiling (CGP) assay to assess the genomic landscape of mPEComa.

Patients And Methods: Formalin-fixed, paraffin-embedded (FFPE) blocks or slides were obtained from tumors from 31 unique patients with mPEC-oma.

Validation and performance comparison of three SARS-CoV-2 antibody assays.

Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly being used during the current pandemic of coronavirus disease 2019 (COVID-19), although its clinical and epidemiologic utilities are still debatable. Characterizing these assays provides scientific basis to best use them. The current study assessed one chemiluminescent assay (Abbott COVID-2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo total antibody test) using 113 blood samples from 71 PCR-confirmed COVID-19 hospitalized patients, 119 samples with potential cross-reactions, and 1068 negative controls including 942 pre-pandemic samples.