Recent advancements in biomarkers and molecular diagnostics in hormonal receptor-positive breast cancer.

Molecular applications have limited use in breast cancer compared to other cancer types. In recent years, with an improving appreciation of the molecular genetics of breast cancer and innovative novel targeted and immune-mediated therapeutics, opportunities have arisen for more biomarker analysis and molecular applications in the diagnosis and treatment of both locally advanced and metastatic breast cancers. In hormone receptor-positive, HER2-negative breast cancers, a growing number of revolutionized personalized therapies are in clinical use or on trials, such as CDK4/6 inhibitors and immune checkpoint inhibitors in adjuvant and neoadjuvant settings, and PIK3CA inhibitors in metastatic disease.

Aberrant expression of collagen type X in solid tumor stroma is associated with EMT, immunosuppressive and pro-metastatic pathways, bone marrow stromal cell signatures, and poor survival prognosis.

Background: Collagen type X (ColXα1, encoded by ) is expressed specifically in the cartilage-to-bone transition, in bone marrow cells, and in osteoarthritic (OA) cartilage. We have previously shown that ColXα1 is expressed in breast tumor stroma, correlates with tumor-infiltrating lymphocytes, and predicts poor adjuvant therapy outcomes in ER/HER2 breast cancer. However, the underlying molecular mechanisms for these effects are unknown.

Excision of a supergiant spinal schwannoma: illustrative case.

Background: The authors report on a patient who presented with an extremely large presacral schwannoma and subsequent mass effect-induced hydronephrosis and kidney failure. To the authors' knowledge, this case represents the largest radiographically verified spinal schwannoma in the medical literature. The tumor presented here was more than three times as large as a typical giant schwannoma.

Locoregional event or dyssynchronous distant metastasis: clinicopathological and molecular analysis of contralateral axillary lymph node metastasis in breast cancer patients.

Aims: Contralateral axillary lymph node metastasis (CAM) is a rare clinical condition in patients with breast cancer (BC). CAM can be either a locoregional event or a distant metastasis. Molecular application for clonal evolution in BC has not been reported in CAM cases.

Enabling the clinical application of artificial intelligence in genomics: a perspective of the AMIA Genomics and Translational Bioinformatics Workgroup.

Objective: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space.

Process: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members.

Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features: A Clinicopathologic and Molecular Study of 18 Cases.

Triple-negative breast cancer (TNBC) is a heterogenous group of tumors. Most TNBCs are high-grade aggressive tumors, but a minority of TNBCs are not high grade, with relatively indolent behavior and specific morphologic and molecular features. We performed a clinicopathologic and molecular assessment of 18 non-high-grade TNBCs with apocrine and/or histiocytoid features.

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.

Whole slide image features predict pathologic complete response and poor clinical outcomes in triple-negative breast cancer.

Introduction: Breast cancers are complex ecosystem like networks of malignant cells and their associated microenvironment. Applications for machine intelligence and the tumoral microenvironment are expanding frontiers in pathology. Previously, computational approaches have been developed to quantify and spatially analyze immune cells, proportionate stroma, and detect tumor budding.

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]).

Clinical features of patients with -deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. and mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes.

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.

Describing IgA Myeloma: An Immunophenotypic and Molecular Approach.

Plasma cell myeloma (PCM) is defined as a clonal disease of terminally differentiated plasma cells that secrete immunoglobulin. The biologic underpinnings of IgA-type multiple myeloma's (IgAMM) aggressive nature, including its increased morbidity and mortality, have not been elucidated. We describe the clinical, phenotypic, and cytogenetic characteristics of IgA-MM.

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.

Lung Findings in a Patient with a History of Nicotine Vaping and Cannabis Smoking.

We report a collection of lung findings in a patient with a remote history of cigarette smoking, but now engaged in heavy nicotine vaping with daily edible and combustible cannabis use. Computed tomography (CT) imaging demonstrated numerous, small, and bilateral nodules with ground-glass appearance. The largest nodule is demonstrated in the right upper lung lobe.

A Novel Superpixel Approach to the Tumoral Microenvironment in Colorectal Cancer.

Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract. The stroma and the tumoral microenvironment (TME) represent ecosystem-like biological networks and are new frontiers in CRC. The present study demonstrates the use of a novel machine learning-based superpixel approach for whole slide images to unravel this biology.

Nature and Significance of Stromal Differentiation, PD-L1, and VISTA in GIST.

The role of stromal differentiation (SD), program death-ligand 1 (PD-L1), and v-domain Ig suppressor of T cell activation (VISTA) in gastrointestinal stromal tumor (GIST) is largely unknown. Looking forward, the assessment of SD and immune check point inhibition will become more ubiquitous in surgical pathology. Immature, myxoid stroma has been found to be a poor prognostic signature in many cancer subtypes (colon, breast, cervix, esophagus, stomach); although little is known regarding its significance in GIST.

Molecular markers of risk of subsequent invasive breast cancer in women with ductal carcinoma in situ: protocol for a population-based cohort study.

Introduction: Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of invasive breast cancer (IBC). Many DCIS patients are either undertreated or overtreated. The overarching goal of the study described here is to facilitate detection of patients with DCIS at risk of IBC development.

How Does Invasive Breast Cancer Oncotype Dx Recurrence Score on Core Needle Biopsies Influence Neoadjuvant Treatment Decision? A Descriptive Study.

Background: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens.

Aim: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations.

Association of current molecular subtypes in urothelial carcinoma with patterns of muscularis propria invasion.

Urothelial carcinoma is subdivided into luminal (L), basal (B), and p53-wild-type (WT) molecular subtypes, with basal and p53-WT groups showing more aggressive course and poor treatment response, respectively. The literature on molecular subtypes of UC includes a mixture of different stages. We investigated the molecular profile and outcome of pure cohort of muscle invasive bladder carcinoma (MIBC) considering two distinct patterns of muscularis propria (MP) invasion.

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.

Apocrine ductal carcinoma in situ associated with testosterone therapy in a transgender individual.

We report the first case of apocrine ductal carcinoma in situ (DCIS) in a female-to-male transgender individual on testosterone therapy (TT). The gender confirmation total mastectomy revealed 2 cm DCIS with apocrine cytology, high nuclear grade with associated calcification, and necrosis. Immunohistochemistry revealed the DCIS was negative for ER, positive for AR with HER2/neu overexpression (3+).

Infiltrating immune cells in benign breast disease and risk of subsequent invasive breast cancer.

Background: It is well established that tumors are antigenic and can induce an immune response by the host, entailing lymphocytic infiltration of the tumor and surrounding stroma. The extent and composition of the immune response to the tumor, assessed through evaluation of tumor-infiltrating lymphocyte counts, has been shown in many studies to have prognostic and predictive value for invasive breast cancer, but currently, there is little evidence regarding the association between infiltrating immune cell counts (IICCs) in women with benign breast disease (BBD) and risk of subsequent invasive breast cancer.

Methods: Using a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest, we conducted a nested case-control study in which cases were women who developed a subsequent invasive breast cancer during follow-up and controls were individually matched to cases on age at BBD diagnosis.

Elastin in the Tumor Microenvironment.

Elastic fibers are found in the extracellular matrix (ECM) of tissues requiring resilience and depend on elasticity. Elastin and its degradation products have multiple roles in the oncologic process. In many malignancies, the remodeled ECM expresses high levels of the elastin protein which may have either positive or negative effects on tumor growth.