Cylindroma of the Breast: A Rare Differential for Breast Cancer on Core Biopsies, Case Report and Review of Literature.

Breast cancers of either ductal or lobular pathology make up the vast majority of breast malignancies. Other cancers occur rarely in the breast. Benign pathology can at times mimic breast cancers on imaging and initial needle biopsies. We report a rare breast pathology of cylindroma. Cylindromas are usually benign, rare dermatologic lesions most commonly associated with head or neck locations. They more commonly occur as sporadic and solitary masses. Less commonly is an autosomal-dominant multi-centric form of this disease. Malignant cylindromas are very rare. We present a patient with findings of a cylindroma of the breast after excision. This was initially felt to be concerning for breast cancer on imaging and core biopsy. Treatment of cylindromas of the breast is excision. Sentinel lymph node dissection is not indicated, nor are adjuvant therapies when identified in the breast. This lesion needs to be included in the differential diagnosis for breast cancer. If cylindromas can be accurately diagnosed preoperatively, this would negate the need for consideration of axillary nodal surgery and adjuvant therapies.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

PURPOSE: In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. METHODS: Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. RESULTS: Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2- to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2- (5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). CONCLUSION: Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Beyond Rarity: Insights Into the Diagnosis and Histopathology of Breast Granular Cell Tumors.

Breast granular cell tumors, which are benign and rare tumors of the breast, pose a diagnostic challenge due to their rarity and nuanced clinical presentations. This article explores a unique case of a 41-year-old female with a biopsy-confirmed granular cell tumor, shedding light on the intricacies involved in diagnosis. Rooted in a neuroectodermal origin, particularly Schwann cells, these tumors demand a multidimensional diagnostic approach for accurate identification. Despite their predominantly benign nature, malignant variants exist, necessitating a thorough histomorphology examination, supported by immunohistochemistry, for precise classification. This article contributes to our understanding of breast pathology and emphasizes the pivotal role of histopathology in unraveling complexities associated with granular cell tumors, reaffirming the importance of a comprehensive diagnostic approach.

Sarcomatoid Carcinoma of the Breast: An Unusual Clinical Presentation.

Breast sarcomatoid carcinoma, which are malignant tumors that form from the mesenchymal tissue of the mammary gland, are extremely uncommon and come in two varieties: primary and secondary (development associated to therapy). Breast sarcomas are malignancies that are aggressive and have a bad prognosis. Multidisciplinary surgery, chemotherapy, and radiotherapy are among the treatment possibilities. This case report reports a case of 35-year-old female presented to our hospital with a palpable tumor in her right breast and pungent discharge from her nipples. These signs persisted for over five years. A sarcomatoid breast cancer was discovered by postoperative histology.

Mucocele-like Lesions: Radiologic-Pathologic Correlation.

Mucocele-like lesions (MLLs) of the breast are rare lesions described as dilated, mucin-filled cysts associated with rupture and extracellular mucin in the surrounding stroma. These lesions are of clinical concern because they can coexist with a spectrum of atypical and malignant findings, including atypical ductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma including mucinous carcinoma. Imaging findings of MLLs are nonspecific and varied, although the most common initial finding is that of incidental coarse heterogeneous calcifications on mammography. Occasionally, an asymmetry or mass may be found with or without calcifications, and such MLLs have a higher rate of upgrade to malignancy at excision. Pathology findings are often descriptive given the small sample received from percutaneous biopsy, and the primary consideration is to report any associated atypia, including atypical ductal hyperplasia. There is consensus in the literature that MLLs with atypia on biopsy should undergo excision because of the average reported 17.5% (20/114) upgrade rate to malignancy. The upgrade rate for MLLs without atypia averages 4.1% (14/341). Therefore, imaging surveillance may be a reasonable alternative to excision for MLLs with no atypia on a case-by-case basis. We review MLL imaging findings, pathology findings, and clinical management and present 3 cases from our institution to add to the literature on these rare lesions.

Proficiency testing of diagnosis in histopathology and immunohistochemistry of breast pathology in China: results from a pilot work of National Single Disease Quality Control Program for breast cancer.

AIM: Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. METHODS: This national PT plan is designed and implemented according to the "Conformity assessment-General requirements for proficiency testing" (GB/T27043-2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). RESULTS: Our study demonstrated that the median PT score was 89.5 (54-100). Two institutions with scores < 67 were deemed unacceptable. The accuracy of histologic type, ER, PR, HER2, and Ki67 was satisfactory (all > 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR < 1% weak expression as positive staining (1.4%), and no evaluation of histologic grade in ILC, MC, and IMC (5.8%). CONCLUSIONS: our nationwide PT program exhibited a satisfactory baseline assessment of the diagnostic capability of pathologists in China. More importantly, we identify some areas for further improvement.

The Impact of Virtual Reality on Anxiety and Pain During US-Guided Breast Biopsies: A Randomized Controlled Clinical Trial.

OBJECTIVE: To investigate the efficacy of immersive virtual reality (VR) in combination with standard local anesthetic for mitigating anxiety and pain during US-guided breast biopsies compared to local anesthetic alone. METHODS: Patients scheduled for US-guided biopsy were invited to participate. Eligible patients were females 18 years of age or older. Patients were randomized to VR or control group at a 1:1 ratio. Patients in the VR group underwent biopsy with the addition of a VR experience and patients in the control group underwent usual biopsy. Patient-perceived levels of anxiety and pain were collected before and after biopsy via the State-Trait Anxiety Inventory (STAI) and Visual Analog Scale (VAS). Physiological data were captured during biopsy using a clinically validated wristband. Differences in anxiety, pain, and physiologic data were compared between the VR and control group. RESULTS: Sixty patients were enrolled. After excluding 2 patients with VR device malfunction, there were 29 patients in the VR and 29 patients in the control group for analysis. The VR group had reduced anxiety compared to the control group based on postintervention STAI (P <.001) and VAS (P = .036). The VR group did not have lower pain based on postintervention VAS (P = .555). Physiological measures showed higher RR intervals and decreased skin conductance levels, which are associated with lower anxiety levels in the VR group. CONCLUSION: Use of VR in addition to standard local anesthetic for US-guided breast biopsies was associated with reduced patient anxiety. Virtual reality may be a useful tool to improve the patient biopsy experience.

Predictive and prognostic biomarkers in breast tumours.

In the age of precision medicine, extensive research has investigated tumour biomarkers to predict the behaviour of cancer and/or response to treatment in order to better understand the prognosis and treatment of disease. In breast cancer, significant progress has been made to categorise a common disease into subtypes defined by intrinsic tumour biology, measured by tumour biomarkers. This review encompasses the established biomarkers within breast cancer with the most up-to-date information regarding their understanding and clinical use as predictive and/or prognostic markers of breast cancer.

Tumour 63 protein (p63) in breast pathology: biology, immunohistochemistry, diagnostic applications, and pitfalls.

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, ß, γ, δ, and ε).

Automated analysis of the total choline resonance peak in breast proton magnetic resonance spectroscopy.

The aim of the current study was to compare the performance of fully automated software with human expert interpretation of single-voxel proton magnetic resonance spectroscopy (1H-MRS) spectra in the assessment of breast lesions. Breast magnetic resonance imaging (MRI) (including contrast-enhanced T1-weighted, T2-weighted, and diffusion-weighted imaging) and 1H-MRS images of 74 consecutive patients were acquired on a 3-T positron emission tomography-MRI scanner then automatically imported into and analyzed by SpecTec-ULR 1.1 software (LifeTec Solutions GmbH). All ensuing 117 spectra were additionally independently analyzed and interpreted by two blinded radiologists. Histopathology of at least 24 months of imaging follow-up served as the reference standard. Nonparametric Spearman's correlation coefficients for all measured parameters (signal-to-noise ratio [SNR] and integral of total choline [tCho]), Passing and Bablok regression, and receiver operating characteristic analysis, were calculated to assess test diagnostic performance, as well as to compare automated with manual reading. Based on 117 spectra of 74 patients, the area under the curve for tCho SNR and integrals ranged from 0.768 to 0.814 and from 0.721 to 0.784 to distinguish benign from malignant tissue, respectively. Neither method displayed significant differences between measurements (automated vs. human expert readers, p > 0.05), in line with the results from the univariate Spearman's rank correlation coefficients, as well as the Passing and Bablok regression analysis. It was concluded that this pilot study demonstrates that 1H-MRS data from breast MRI can be automatically exported and interpreted by SpecTec-ULR 1.1 software. The diagnostic performance of this software was not inferior to human expert readers.

Machine learning classification of diagnostic accuracy in pathologists interpreting breast biopsies.

OBJECTIVE: This study explores the feasibility of using machine learning to predict accurate versus inaccurate diagnoses made by pathologists based on their spatiotemporal viewing behavior when evaluating digital breast biopsy images. MATERIALS AND METHODS: The study gathered data from 140 pathologists of varying experience levels who each reviewed a set of 14 digital whole slide images of breast biopsy tissue. Pathologists' viewing behavior, including zooming and panning actions, was recorded during image evaluation. A total of 30 features were extracted from the viewing behavior data, and 4 machine learning algorithms were used to build classifiers for predicting diagnostic accuracy. RESULTS: The Random Forest classifier demonstrated the best overall performance, achieving a test accuracy of 0.81 and area under the receiver-operator characteristic curve of 0.86. Features related to attention distribution and focus on critical regions of interest were found to be important predictors of diagnostic accuracy. Further including case-level and pathologist-level information incrementally improved classifier performance. DISCUSSION: Results suggest that pathologists' viewing behavior during digital image evaluation can be leveraged to predict diagnostic accuracy, affording automated feedback and decision support systems based on viewing behavior to aid in training and, ultimately, clinical practice. They also carry implications for basic research examining the interplay between perception, thought, and action in diagnostic decision-making. CONCLUSION: The classifiers developed herein have potential applications in training and clinical settings to provide timely feedback and support to pathologists during diagnostic decision-making. Further research could explore the generalizability of these findings to other medical domains and varied levels of expertise.

Adenomyoepithelioma of the Breast: Radiologic-Pathologic Correlation and Management.

Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.

Tubular Adenoma of the Breast: Radiologic-Pathologic Correlation.

Breast tubular adenomas (TAs) are rare, benign glandular epithelial tumors that arise from a proliferation of acini in the terminal duct lobular units. In the literature, 40 TA cases have previously been reported, and we describe 5 additional cases in this article. In the small number of reported cases, TAs present most often in women of reproductive age but may also occur in postmenopausal women. Mammographically and sonographically, TAs are almost indistinguishable from fibroadenomas (FAs), and they typically present on US as hypoechoic, oval, circumscribed, parallel masses with variable internal vascularity. TAs can also be seen on mammography as oval masses with microlobulated margins, or as grouped coarse, heterogeneous microcalcifications with or without associated mass or asymmetry. On MRI, TAs present as heterogeneously enhancing, T2-hyperintense oval masses with persistent kinetics. Histopathologically, TAs consist of closely packed round tubules with minimal stroma, in distinction to FAs, which have a prominent stromal component that surrounds and can distort the associated tubules. Because of their benign classification and excellent prognosis, patients with biopsy-confirmed TAs may resume routine screening. Complete surgical excision may be considered for cosmetic purposes or for TAs exhibiting associated suspicious calcifications or rapid growth.

Sixteen-Year Institutional Review of Magnetic Resonance Imaging-Guided Breast Biopsies: Trends in Histologic Diagnoses With Radiologic Correlation.

Background: Breast magnetic resonance imaging (MRI) is an important imaging tool for the management of breast cancer patients and for screening women at high risk for breast cancer. Objectives: To examine long-term trends in the distribution of histologic diagnoses obtained from MRI-guided breast biopsies. Design: Retrospective analysis. Methods: We retrospectively reviewed the distribution of histologic diagnoses of MRI-guided breast biopsies from 2004 to 2019. All cases underwent central pathology review and lesions were classified based on the most prominent histologic finding present. Magnetic resonance imaging features were extracted from radiology reports when available and correlated with pathology diagnoses. Results: Four hundred ninety-four MRI-guided biopsies were performed on 440 patients; overall, 73% of biopsies were benign and 27% were malignant. The annual percentages of benign and malignant diagnoses remained similar throughout the 16-year period. Of the benign entities commonly identified, the percentage of benign papillary and sclerosing lesions detected in the benign biopsies increased significantly (13% in 2004-2011 vs 31% in 2012-2019, P = .03). The mean size of malignant lesions was larger than benign lesions (30.1 mm compared with 14.2 mm, P = .045); otherwise, there were no distinguishing radiologic features between benign and malignant lesions. Conclusion: The specificity of breast MRI remained constant over a 16-year period; however, there was a shift in the distribution of benign diagnoses with increased detection and biopsy of benign papillary and sclerosing lesions. Monitoring the distribution of breast MRI biopsy diagnoses over time with radiology-pathology correlation might improve the suboptimal specificity of breast MRI.

The impact of nurse navigation on timeliness to treatment for benign high-risk breast pathology.

PURPOSE: High-risk breast pathology is a breast cancer risk factor for which timely treatment is crucial. Nurse navigation programs have been implemented to minimize delays in patient care. This study evaluated nurse navigation in terms of timeliness to surgery for patients with high-risk breast pathology. METHODS: This was a single-institution, retrospective review of patients with identified high-risk breast pathology undergoing lumpectomy between January 2017 and June 2019. Patients were stratified into cohorts based on periods with and without nurse navigation. Preoperative and postoperative time to care as well as demographic and tumor characteristics were compared using univariate and multivariate analysis. RESULTS: 100 patients had assigned nurse navigators and 29 patients did not. Nurse navigation was associated with reduced time from referral to date of surgery (DOS) by 16.9 days (p = 0.003). Patients > 75 years had a shorter time to first appointment (p = 0.03), and patients with Medicare insurance had a reduced time from referral to DOS (p = 0.005). 20% of all patients were upstaged to cancer on final surgical pathology. CONCLUSION: Nurse navigation was significantly associated with decreased time to care for patients with high-risk breast pathology undergoing lumpectomy. We recommend nurse navigation programs as part of a comprehensive approach for patients with high-risk breast pathology.

Ultrasound as a Method for Early Diagnosis of Breast Pathology.

INTRODUCTION: Ultrasound is a non-invasive, low-cost technique that does not use ionising radiation and provides a "real-time" image, and for these reasons, this method is ideal in several situations. PURPOSE: To demonstrate breast ultrasound evaluation as a first-line diagnostic method and to evaluate the variation of breast characteristics with age. MATERIAL AND METHODS: A total of 105 women with a mean age of 30 years participated and were divided into three age groups: 18-39, 40-59, and 60-79 years, excluding participants subject to mastectomy. After completing the informed consent, all participants answered personal and sociodemographic questions, such as personal and family history, menstrual cycle, pregnancy, ultrasound, and mammography, among others. They were then submitted to a bilateral breast ultrasound examination. Subsequently, all the images and their data were analysed, and a technical report of the examination was given to all the participants. RESULTS: A total of 105 women with a mean age of 30 years participated, 58 of whom underwent the examination for the first time. In 31, changes (of which only 7 were known) were diagnosed. It was verified that, according to age group, the density of the breast stroma varied; older women have less breast density. CONCLUSIONS: Ultrasound is a good method for breast evaluation and can be considered important for the early evaluation of breast pathology and follow-up of the pathology.

Second opinion (external specialist referral) practice of breast pathology: the Nottingham experience.

AIMS: Breast pathology is a challenging field, and discrepancies in diagnoses exist and can affect patient management. This study aims to review a breast referral practice and assess the pattern and frequency of breast lesions sent for an external expert review and evaluate potential impacts on patients' care. METHODS AND RESULTS: Seven hundred and forty cases that were referred to Nottingham City Hospital for a second opinion between 2019 and 2022 which have slides and reports were retrieved and reviewed. Reasons for referral, initial diagnosis, proffered specialist opinion and any discrepancy or potential impacts of management were assessed. The most frequent entities were papillary lesions (19%), fibroepithelial lesions (17%), invasive carcinomas that were sent for confirmation of the invasive diagnosis or subtyping of the invasive tumour (17%), intraductal epithelial proliferation with atypia (9%) and spindle cell lesions (8%). Other entities included biphasic tumours such as adenomyoepithelioma, as well as vascular and nipple lesions. Few cases were sent for prognostic classification or comments on the management, and in occasional cases no initial diagnosis was offered. After reviewing the cases by the expert pathologists, the initial diagnosis was confirmed or one of the suggested diagnoses was preferred in 79% of cases, including 129 cases (17%) in which the opinion resulted minor changes in the management. Significant changes in the classification of lesions were made in 132 cases (18%) which resulted in significant change in the patient management recommendation. In 14 cases (2%) a final classification was not possible, and further specialist opinion was obtained. Comments on the differential diagnosis and advice on further patient management were provided in most cases. CONCLUSIONS: This study demonstrates the value of external referral of challenging, rare and difficult to classify breast lesions. It also highlights the most common breast lesions that are likely to be challenging, and specialist opinion can refine their classification to improve patient care.

Mucocele-Like Lesion of the Breast.

Mucocele-like lesions (MLLs) of the breast are rare neoplasms characterized by dilated, mucin-filled epithelial ducts or cysts that can rupture and expel their contents into the surrounding stroma. They are frequently associated with atypia, dysplastic change, and, more recently, pre-malignant and malignant conditions like atypical ductal hyperplasia, ductal carcinoma, invasive carcinoma, or mucinous carcinoma. The malignant potential of MLLs is often challenging to determine from the initial histologic evaluation of a core-needle biopsy due to copious mucin and low cellularity. Therefore, at initial presentation, MLLs should be surgically excised and thoroughly evaluated for malignancy. In this paper, we present a rare case of an MLL and explore the radiology, histology, carcinogenic potential, diagnostic evaluation, and suggested management of the condition.