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* Context.--The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. Objective.--To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. Data Sources.--Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. Conclusions.--The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes. doi: 10.5858/arpa.2022-0060-RA, The International Collaboration on Cancer Reporting (ICCR) stems from an unprecedented effort to provide standards for evidence-based reporting of the pathologic diagnosis of different types of cancers, including all parameters [...]

Background and Objectives: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter‐)national pathology and cancer organizations. Methods and Results: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. Conclusions: This first international dataset for invasive cancer of the breast is intended to promote high‐quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients. [ABSTRACT FROM AUTHOR]

The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics after surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. In the present study, we define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both 'prognosis' and 'proliferation' gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multigene prognostic assays, particularly in estrogen receptor-positive patients. Simultaneous examination of p16(INK4A) expression, which predicts tumours that have bypassed cellular senescence, revealed that intermediate levels of p16(INK4A) correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16(INK4A), termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as 'low risk', an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, the present study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline methods of predicting breast cancer prognosis.

Tumour protein 63 (p63) is a transcription factor of the p53 gene family, encoded by the TP63 gene located at chromosome 3q28, which regulates the activity of genes involved in growth and development of the ectoderm and derived tissues. p63 protein is normally expressed in the nuclei of the basal cell layer of glandular organs, including breast, in squamous epithelium and in urothelium. p63 immunohistochemical (IHC) staining has several applications in diagnostic breast pathology. It is commonly used to demonstrate myoepithelial cells at the epithelial stromal interface to differentiate benign and in situ lesions from invasive carcinoma and to characterize and classify papillary lesions including the distinction of breast intraduct papilloma from skin hidradenoma. p63 IHC is also used to identify and profile lesions showing myoepithelial cell and/or squamous differentiation, e.g. adenomyoepithelioma, salivary gland‐like tumours including adenoid cystic carcinoma, and metaplastic breast carcinoma including low‐grade adenosquamous carcinoma. This article reviews the applications of p63 IHC in diagnostic breast pathology and outlines a practical approach to the diagnosis and characterization of breast lesions through the identification of normal and abnormal p63 protein expression. The biology of p63, the range of available antibodies with emphasis on staining specificity and sensitivity, and pitfalls in interpretation are also discussed. The TP63 gene in humans, which shows a specific genomic structure, resulting in either TAp63 (p63) isoform or ΔNp63 (p40) isoform. As illustrated in the figure, both isoforms contain a DNA‐binding domain (Orange box) and an oligomerization domain (Grey box). TAp63 contains an N‐terminal transactivation (TA) domain (Green box), while ΔNp63 has an alternative terminus (Yellow box). Antibodies against conventional pan‐p63 (TP63) bind to the DNA binding domain common to both isoforms (TAp63 and p40) and does not distinguish between them. Antibodies against TAp63 bind to the N‐terminal TA domain, while antibodies specific to ΔNp63 (p40) bind to the alternative terminus. Each isoform has variant isotypes (α, β, γ, δ, and ε). [ABSTRACT FROM AUTHOR]

To the Editor.--We welcome the recently published American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) clinical practice guideline focused update for human epidermal growth factor receptor [...]

Breast cancer (BC) is a heterogeneous disease, encompassing a diverse spectrum of tumours with varying morphological, biological, and clinical phenotypes. Although tumours may show phenotypic overlap, they often display different biological behaviour and response to therapy. Advances in high‐throughput molecular techniques and bioinformatics have contributed to improved understanding of BC biology and refinement of molecular taxonomy with the identification of specific molecular subclasses. Although the traditional pathological morphological classification of BC is of paramount importance and provides diagnostic and prognostic information, current interest focusses on the use of a single gene and multigene assays to stratify BC into distinct groups to guide decisions on systemic therapy. This review considers approaches to the classification of BC, including their limitations, and with particular emphasis on the fundamental role of morphology in establishing an accurate diagnosis of primary invasive carcinoma of breast origin. This forms the basis for further morphological characterization and for all other approaches to BC classification that are used to provide prognostic and therapeutic predictive information. [ABSTRACT FROM AUTHOR]

Aims: Although evaluation of nuclear morphology is important for the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely upon the subjective evaluation of several features that may result in inter‐ and intraobserver variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. Methods and results: ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC‐NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied‐sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut‐offs in IBC‐NST, compared to normal epithelial cells, were < ×1.2 and > ×1.4 that of mean maximum Feret's diameter and < ×1.6 and > ×2.4 that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low‐grade IBC‐NST versus tubular carcinoma, low‐grade DCIS versus UDH and CCC versus FEA. No differences in the nuclear features between grade‐matched DCIS and IBC‐NST were identified. Conclusion: This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology. [ABSTRACT FROM AUTHOR]

Aims: Although rare, malignant sarcomatoid breast tumours without evidence of epithelial differentiation comprise a diagnostic challenge with management implications. Earlier studies have generally considered these to be primary breast sarcomas; however, supporting evidence is lacking and management remains variable. This study aimed to provide an evidence‐based approach to improve the consistency of diagnosis and management for such cases. Methods and results: A large series (n = 140) of metaplastic breast carcinoma (MBC) diagnosed in Nottingham over 18 years was analysed. Only cases with available data on immunohistochemical expression of cytokeratins (CKs) were included. The prevalence and pattern of expression for various CKs were assessed and details of tumours negative for CKs were collected. A diagnostic approach based on our experience is provided. Forty‐seven cases (34%) showed foci of conventional type invasive breast carcinoma or ductal carcinoma in situ (DCIS), while 93 cases (66%) were diagnosed as MBC based on morphology and/or CK expression. Ninety‐seven cases (69%) were negative for one or more CKs, with 18 cases (13%) negative for five or more CKs. Eight cases (6%) lacked expression of all CKs tested. Further examination showed evidence of carcinomatous nature in five cases, and three were diagnosed as MBC following extensive diagnostic work‐up and based on our experience. Conclusion: This study suggests that MBC represents a spectrum of neoplasms, with some lacking CK expression. Sarcomatoid neoplasms of the breast lacking evidence of carcinomatous morphology and CK expression may represent an extreme end of differentiation that can be considered as carcinomas rather than sarcomas for management purposes (following extensive work‐up). [ABSTRACT FROM AUTHOR]