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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] more...

Aims: The International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter‐)national pathology and cancer organisations, is an initiative aimed at providing a unified international approach to reporting cancer. ICCR recently published new data sets for the reporting of invasive breast carcinoma, surgically removed lymph nodes for breast tumours and ductal carcinoma in situ, variants of lobular carcinoma in situ and low‐grade lesions. The data set in this paper addresses the neoadjuvant setting. The aim is to promote high‐quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment that can be used for subsequent management decisions for each patient. Methods: The ICCR convened expert panels of breast pathologists with a representative surgeon and oncologist to critically review and discuss current evidence. Feedback from the international public consultation was critical in the development of this data set. Results: The expert panel concluded that a dedicated data set was required for reporting of breast specimens post‐neoadjuvant therapy with inclusion of data elements specific to the neoadjuvant setting as core or non‐core elements. This data set proposes a practical approach for handling and reporting breast resection specimens following neoadjuvant therapy. The comments for each data element clarify terminology, discuss available evidence and highlight areas with limited evidence that need further study. This data set overlaps with, and should be used in conjunction with, the data sets for the reporting of invasive breast carcinoma and surgically removed lymph nodes from patients with breast tumours, as appropriate. Key issues specific to the neoadjuvant setting are included in this paper. The entire data set is freely available on the ICCR website. Conclusions: High‐quality, standardised reporting of tumour response and residual disease after neoadjuvant treatment are critical for subsequent management decisions for each patient. [ABSTRACT FROM AUTHOR] more...

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] more...

Background: This study, using real-world data, assesses the impact of RS testing on treatment pathways and the associated economic consequences of such testing. This paper pertains to lobular breast cancer. Methods: A retrospective, observational study was undertaken between 2011 and 2019 on a cross-section of hormone receptor-positive (HR+), HER2-negative, lymph node-negative, early-stage breast cancer patients. All patients had ILC and had RS testing in Ireland. The patient population is representative of the national population. Patients were classified as low (RS ≤ 25) or high (RS > 25) risk. Patients aged ≤50 were stratified as low (RS 0–15), intermediate (RS 16–25), or high risk (RS > 25). Results: A total of 168 patients were included, most of whom had grade 2 (G2) tumors (n = 154, 92%). Overall, 155 patients (92.3%) had low RS (≤25), 12 (7.1%) had high RS (>25), and 1 (0.6%) had unknown RS status. In 29 (17.5%) patients aged ≤50 at diagnosis, RS was ≤15 in 16 (55%), 16–20 in 6 (21%), 21–25 in 5 (17%), >25 in 1 (3.5%), and unknown in 1 (3.5%). Post RS testing, 126 patients (78%) had a change in chemotherapy recommendation; all to hormone therapy. In total, only 35 patients (22%) received chemotherapy. RS testing achieved a 75% reduction in chemotherapy use, resulting in savings of €921,543.84 in treatment costs, and net savings of €387,283.84. Conclusions: The use of this test resulted in a 75% reduction in chemotherapy and a significant cost savings in our publicly funded health system. [ABSTRACT FROM AUTHOR] more...

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] more...

Background and aims: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry‐equivocal score. Methods and results: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in‐situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2‐amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5–< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2‐non‐amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2‐amplified and HER2‐non‐amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2‐amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37–102.00; P = 0.02], and histological grade 3 in HER2 non‐amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61–19.00; P = 0.007). Conclusion: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry‐equivocal score who would benefit from NAT. [ABSTRACT FROM AUTHOR] more...

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] more...

Apocrine change is recognised in benign, atypical and malignant lesions of the breast. Apocrine metaplasia, a frequent finding in the breast of women over the age of 25 years, is most commonly seen in benign cysts with a simple or papillary configuration. Apocrine change is also recognised in other benign lesions including sclerosing adenosis, now known as apocrine adenosis. Apocrine atypia usually refers to cytological atypia in which there is at least threefold variation in nuclear size but architectural atypia may also occur. The distinction between atypical apocrine hyperplasia and non-high-grade apocrine ductal carcinoma in situ may be difficult due to the relative rarity of these entities and the lack of validated diagnostic criteria. Lobular carcinoma in situ (LCIS) with apocrine change is considered to be a variant of pleomorphic LCIS. An apocrine variant of encapsulated papillary carcinoma is also recognised. Apocrine change is described in invasive carcinoma, including no special type, lobular, micropapillary and mucinous variants. The recent WHO 2019 update recognises 'carcinoma with apocrine differentiation' as a special type breast carcinoma based on the presence of apocrine morphology in at least 90% of the tumour. Tumours with apocrine morphology are usually but not always hormone receptor negative. Human epidermal growth factor receptor 2 (HER-2) status is variable. Molecular studies have identified breast tumours with apocrine features and high expression of androgen receptor mRNA including 'luminal androgen receptor tumours' and 'molecular apocrine tumours'. The term 'pure apocrine carcinoma' has been proposed to describe an invasive carcinoma with apocrine morphology that is oestrogen and progesterone receptor negative and androgen receptor positive. HER-2 status may be positive or negative. This article reviews the pathology of benign, atypical and malignant apocrine lesions of the breast, with emphasis on diagnostic criteria including an approach to evaluation of apocrine lesions on needle core biopsy, and recent advances in our understanding of invasive apocrine carcinoma. [ABSTRACT FROM AUTHOR] more...

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] more...

The authors examined the utility of axillary ultrasound (aUS) and primary tumor biomarker profile in identifying patients with axillary complete pathological response. Topics mentioned include the use of the Picture Archiving and Communication System software to measure cortical thickness, association between aUS lymph node appearances, tumor biomarker profile, and histological LN status post-neoadjuvant chemotherapy, and absence of a fatty hilum on aUS. more...

A 64-year-old woman underwent vacuum-assisted excision (VAE) for a biopsy-proven radial scar in the right breast detected during screening mammography. A follow-up mammogram was performed at 1 year following multidisciplinary team discussion. This demonstrated a 1 cm mass adjacent to the biopsy clip at the site of the prior VAE. A repeat biopsy of the mass was performed which revealed benign scar tissue. This is the first reported case of post-VAE scar tissue mimicking breast carcinoma on mammography. [ABSTRACT FROM AUTHOR] more...

Simple Summary: Breast cancers that lack expression of the predictive markers oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are known as triple-negative breast cancers (TNBCs) and are generally considered to have a poor prognosis. As available targeted treatments are not effective, aggressive chemotherapy is frequently advocated for patients with TNBC. It is now becoming apparent that TNBC is not one entity but constitutes a range of malignancies with different clinical behaviour. This paper reviews 7 distinct histological subtypes of TNBC where the overall prognosis is favourable, and aggressive systemic treatment is generally not indicated. Their recognition and separation from the larger group of no special type TNBC are important. The members of the European Working Group for Breast Screening Pathology review the morphology, known molecular features and reported outcomes, and formulate a consensus statement regarding the approach to the subtypes that are associated with a favourable prognosis. Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review. [ABSTRACT FROM AUTHOR] more...

- A review of 15 cases of unilateral renal dysplasia is presented. Seven patients came to medical attention with urinary tract infection. Only 4 presented with an abdominal mass. Eight patients were found to have ipsilateral ureteric anomalies and 4 of these also had contralateral ureteric problems. Five patients had extra-renal anomalies and these included Turner's syndrome, scoliosis and congenital dislocation of the hip. Histological examination, in all cases, revealed the presence of primitive ducts surrounded by concentric layers of cellular mesenchyme. Metaplastic cartilage was noted in only 7 of the 15 cases. [ABSTRACT FROM AUTHOR] more...

* 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. [ABSTRACT FROM AUTHOR] more...

The authors discuss the clinical practice guideline by the American Society of Clinical Oncology and College of American Pathologists on the update for human epidermal growth factor receptor 2 (HER2) testing in invasive breast carcinoma. Topics discussed include the 2007 diagnostic requirements for HER2 positivity, the HER2 fluorescent in situ hybridization (FISH) assays from Breast Cancer International Research Group studies, and the application of the 2007 guideline for FISH-tested tumors. more...