Use of p53 immunohistochemistry can improve diagnostic agreement for differentiated vulvar intraepithelial neoplasia (dVIN): an international reproducibility study.

Aims: Differentiated or HPV-independent vulvar intraepithelial neoplasia (dVIN) can progress rapidly to invasive cancer and accurate pathological diagnosis is essential to facilitate appropriate interventions. Histological similarities of dVIN with non-neoplastic lesions, however, often make the diagnosis less reproducible. We investigated among a diverse group of pathologists whether the diagnostic agreement improves with the use of p53 immunohistochemistry (IHC) interpreted using the pattern-based schema.

Predictive Histopathological Markers for Upstaging to Invasive Carcinoma after a Biopsy Diagnosis of Ductal Carcinoma in situ of the Breast: A Hypothesis-Generating Systematic Review.

Introduction: Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear.

Reproducibility of Equivocal HER2 In Situ Hybridization Groups 3 and 4, and Comparison With HER2 mRNA Expression: The Thin Line Between Amplified and Nonamplified Breast Cancers.

Context.—: Breast carcinomas (BCs) with equivocal HER2 (human epidermal growth factor receptor 2) immunohistochemistry are subjected to in situ hybridization (ISH) to assess HER2 copy numbers. Infrequently, dual-probe ISH also provides equivocal results, designated as ISH groups 2, 3, or 4.

A Comparison Between Immunohistochemistry and mRNA Expression to Identify Human Epidermal Growth Factor Receptor 2-Low Breast Cancer.

Context.—: Breast cancers (BCs) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) have become a targetable subset because of novel antibody-drug conjugates. HER2 immunohistochemistry (IHC) is the recommended assay for HER2 classification but is associated with limited interobserver agreement concerning HER2-low identification.

Risk perception of patients with ductal carcinoma (DCIS) of the breast and their healthcare practitioners: The importance of histopathological terminology, and the gaps in our knowledge.

Despite ductal carcinoma (DCIS) being a non-obligatory precursor of invasive breast carcinoma, its diagnosis generates substantial psychological distress. The limited knowledge about the natural history of DCIS contributes to the insufficient transmission of information about DCIS to patients and the general population. The uncertainty about the progression risk to invasive carcinoma hampers adequate communication by clinicians.

Systematic assessment of HER2 status in ductal carcinoma in situ of the breast: a perspective on the potential clinical relevance.

In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear.

Metabolic adaptation towards glycolysis supports resistance to neoadjuvant chemotherapy in early triple negative breast cancers.

Background: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency.

HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study.

About half of breast cancers (BC) without amplification of the human epidermal growth factor receptor 2 (HER2) have a low HER2 protein expression level (HER2-low). The clinical impact of HER2-low and the response to neoadjuvant chemotherapy (NAC) is unclear. This study aimed to assess the association between HER2-low BC and pathological response to NAC.

Predictive markers for pathological complete response (pCR) after neo-adjuvant chemotherapy in HER2-positive breast carcinoma.

Objectives: Patients with HER2-positive invasive breast cancer that is node-positive and/or larger than 3 cm are generally treated with neoadjuvant chemotherapy (NAC). We aimed to identify predictive markers for pathological complete response (pCR) after NAC in HER2-positive breast carcinoma.

Methods: Hematoxylin/eosin-stained slides of 43 HER2-positive breast carcinoma biopsies were histopathologically reviewed.

HER2-Low Breast Cancer: Incidence, Clinicopathologic Features, and Survival Outcomes From Real-World Data of a Large Nationwide Cohort.

Patients with breast cancer (BC) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) could benefit from novel antibody-drug conjugates. However, there is conflicting information regarding the characteristics of HER2-low BC and its outcome. We assessed the clinicopathologic characteristics and outcomes of HER2-low BC using real-world data from the Dutch National Pathology Registry.

Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer: Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria? An International Interobserver Study.

The classification of human epidermal growth factor receptor 2 (HER2) expression is optimized to detect HER2-amplified breast cancer (BC). However, novel HER2-targeting agents are also effective for BCs with low levels of HER2. This raises the question whether the current guidelines for HER2 testing are sufficiently reproducible to identify HER2-low BC.

Breast-implant Related Silicone Lymphadenopathy: Asteroid Bodies do not Always Equal Sarcoidosis!

Silicone breast implants are frequently used for breast augmentation for cosmetic purposes, as well as for breast reconstruction after prophylactic or therapeutic mastectomy. Silicone lymphadenopathy is a well-known complication of silicone breast implants. Silicone droplets are present in the breast tissue through 'silicone bleeding' of the implant or because of implant rupture.

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine.

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer.

The Use of Pan-Tropomyosin Receptor Kinase Immunohistochemistry as a Screening Tool for the Detection of Neurotrophic Tropomyosin-Related Kinase Fusions: Real-World Data from a National Multicentric Retrospective Study.

Introduction: The neurotrophic tropomyosin-related kinase (NTRK) genes encode the tropomyosin receptor kinases (TRKs). Patients with solid tumors harboring an oncogenic NTRK fusion are eligible for treatment with TRK inhibitors. NTRK fusion is often associated with TRK overexpression.

Inter-observer agreement for the histological diagnosis of invasive lobular breast carcinoma.

Invasive lobular breast carcinoma (ILC) is the second most common breast carcinoma (BC) subtype and is mainly driven by loss of E-cadherin expression. Correct classification of BC as ILC is important for patient treatment. This study assessed the degree of agreement among pathologists for the diagnosis of ILC.

Interobserver Agreement of PD-L1/SP142 Immunohistochemistry and Tumor-Infiltrating Lymphocytes (TILs) in Distant Metastases of Triple-Negative Breast Cancer: A Proof-of-Concept Study. A Report on Behalf of the International Immuno-Oncology Biomarker Working Group.

Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the assessment of PD-L1/SP142 immunohistochemistry and TILs.

Interobserver variability in the assessment of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative invasive breast carcinoma influences the association with pathological complete response: the IVITA study.

High stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC) are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Histopathological assessment of sTILs in TNBC biopsies is characterized by substantial interobserver variability, but it is unknown whether this affects its association with pCR. Here, we aimed to investigate the degree of interobserver variability in an international study, and its impact on the relationship between sTILs and pCR.

Artefactual Epithelial Displacement in a Papilloma with Extensive Usual Duct Hyperplasia Mimics a Solid Papillary Carcinoma with Invasive Growth.

Mammary solid papillary carcinoma and usual duct hyperplasia (UDH) of the breast are morphological look-alikes, characterized by cellular streaming, solid growth, and a lack of high-grade nuclear atypia. Here, we report a challenging papillary lesion in the breast of a 48-year-old woman that presented with a double pitfall. A core needle biopsy showed a solid papillary proliferation of epithelial cells with oval to round overlapping nuclei, surrounded by a sclerotic stroma.

Histological interpretation of differentiated vulvar intraepithelial neoplasia (dVIN) remains challenging-observations from a bi-national ring-study.

Differentiated vulvar intraepithelial neoplasia (dVIN) is a premalignant lesion that is known to progress rapidly to invasive carcinoma. Accurate histological diagnosis is therefore crucial to allow appropriate treatment. To identify reliable diagnostic features, we evaluated the inter-observer agreement in the histological assessment of dVIN, among a bi-national, multi-institutional group of pathologists.