Core needle biopsy of benign, borderline and in-situ problematic lesions of the breast: Diagnosis, differential diagnosis and immunohistochemistry.

Core needle biopsy (CNB) is the most common sampling technique for the histologic evaluation of breast abnormalities. Diagnosing benign proliferative, borderline and some in-situ lesions in CNB is challenging and subject to a significant degree of interobserver variability. In addition, due to the inherent limitations of CNB, "upgrading" to a more significant pathology at excision is an important consideration for some lesions. Pathologists carry a major responsibility in patient diagnosis, risk stratification and management. Familiarity with the histologic features and the clinical significance of these common and problematic lesions encountered in CNB is necessary for adequate treatment and patient follow-up. This review will focus on benign, atypical and in-situ epithelial proliferations, papillary lesions, radial sclerosing lesions, adenosis and cellular fibroepithelial lesions. Highlights of histologic features, useful strategies for accurate diagnosis, basic immunohistochemistry and management will be presented.

Computational pathology definitions, best practices, and recommendations for regulatory guidance: a white paper from the Digital Pathology Association.

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage.

INTRODUCTION: In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage. MATERIALS AND METHODS: Our information system was searched to identify all patients who underwent excisional procedures for invasive breast carcinoma from January 1, 2014 to December 31, 2015. The tumor size on CNB and final excision, the number of cases in which the CNB size was larger, and the percentage of cases in which using the CNB tumor size changed the final pT stage were recorded. RESULTS: From 1380 primary breast excisions/mastectomies, a total of 870 cases were included. In 82 (9.4%) the CNB tumor size was larger (63 of 82 cases) or no residual tumor was identified on excision (19 of 82 cases). From these 82 cases, 40 (48.7%) were properly staged on the basis of CNB tumor size, 16 (19.5%) were not staged, and 26 (31.7%) were staged using the final excision tumor size. Change in stage occurred in 7 of these 26 patients. CONCLUSION: Our study revealed that in most cases, the largest tumor size is found in the excision/mastectomy specimen. However, in 9.4% (82 of 870), the CNB contains the most accurate tumor size for pT staging. On the basis of our results, including the largest linear tumor extent on the CNB report is recommended.

P40 Immunostain Does Not Outperform p63 as a Myoepithelial Cell Marker in the Daily Practice of Breast Pathology.

P40 antibody has been shown to be a more specific squamous and basal cell marker compared with p63. As detection of myoepithelial cells (MECs) plays a critical role in breast pathology, and the fact that p40 targets an isoform of p63, this study was designed to compare these antibodies in a variety of lesions, especially those with an sclerotic stroma and carcinoma in situ. All studied lesions were selected from the daily cases of the 3 authors and stained with p63, p40, and calponin immunohistochemical stains. Thirty-four cases (and 19 internal controls) were included. Seventy percent constituted sclerotic lesions (12 cases) and ductal carcinoma in situ (12 cases). P40 and p63 stained all lesions and showed a similar patchy staining pattern in 50% of ductal carcinoma in situ and sclerotic lesions. Compared with internal controls, p40 and p63 demonstrated decreased staining intensity in up to 70% and 8% of all cases, respectively, with no cross-reactivity with mesenchymal cells and minor cross-reactivity with epithelial cells. In our study, p40 did not outperform p63 as a MEC marker. p40 showed a decreased intensity in a higher number of cases (P<0.0001). In our opinion, p63 continues to be the best nuclear marker for the detection of MECs in the daily practice of breast pathology.

Concurrent BRAF and PTEN mutations in melanoma of unknown origin presenting as a breast mass.

BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast. Ultrasound showed a 1-cm solid mass, initially diagnosed as invasive ductal carcinoma on biopsy. During pre-operative workup, a second mass was identified and biopsied. Immunohistochemical stains performed on the second mass biopsy demonstrated that the neoplastic cells were positive for cytokeratin AE1/3, pan-melanoma, tyrosinase, and SOX-10 and negative for CK7, CAM5.2, and GATA-3. Subsequent workup showed widespread metastatic disease involving the liver, lungs, bones, and brain. The brain metastasis tested positive for BRAF p.V600E and PTEN p.R130Efs*4 mutations. Thorough skin and eye examination did not reveal a primary melanoma. CONCLUSION: Only few reports have been published of melanoma presenting as a breast mass. This is an interesting case due to the clinical presentation, diagnostic challenges, and genetic mutations profile.

Alchemy: A Web 2.0 Real-time Quality Assurance Platform for Human Immunodeficiency Virus, Hepatitis C Virus, and BK Virus Quantitation Assays.

BACKGROUND: The molecular diagnostics laboratory faces the challenge of improving test turnaround time (TAT). Low and consistent TATs are of great clinical and regulatory importance, especially for molecular virology tests. Laboratory information systems (LISs) contain all the data elements necessary to do accurate quality assurance (QA) reporting of TAT and other measures, but these reports are in most cases still performed manually: a time-consuming and error-prone task. The aim of this study was to develop a web-based real-time QA platform that would automate QA reporting in the molecular diagnostics laboratory at our institution, and minimize the time expended in preparing these reports. METHODS: Using a standard Linux, Nginx, MariaDB, PHP stack virtual machine running atop a Dell Precision 5810, we designed and built a web-based QA platform, code-named Alchemy. Data files pulled periodically from the LIS in comma-separated value format were used to autogenerate QA reports for the human immunodeficiency virus (HIV) quantitation, hepatitis C virus (HCV) quantitation, and BK virus (BKV) quantitation. Alchemy allowed the user to select a specific timeframe to be analyzed and calculated key QA statistics in real-time, including the average TAT in days, tests falling outside the expected TAT ranges, and test result ranges. RESULTS: Before implementing Alchemy, reporting QA for the HIV, HCV, and BKV quantitation assays took 45-60 min of personnel time per test every month. With Alchemy, that time has decreased to 15 min total per month. Alchemy allowed the user to select specific periods of time and analyzed the TAT data in-depth without the need of extensive manual calculations. CONCLUSIONS: Alchemy has significantly decreased the time and the human error associated with QA report generation in our molecular diagnostics laboratory. Other tests will be added to this web-based platform in future updates. This effort shows the utility of informatician-supervised resident/fellow programming projects as learning opportunities and workflow improvements in the molecular laboratory.

Differential Gene Expression in Ductal Carcinoma In Situ of the Breast Based on ERBB2 Status.

BACKGROUND: The molecular signature of ductal carcinoma in situ (DCIS) in the breast is not well understood. Erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly known as HER2/neu]) positivity in DCIS is predictive of coexistent early invasive breast carcinoma. The aim of this study is to identify the gene-expression signature profiles of estrogen receptor (ER)/progesterone receptor (PR)-positive, ERBB2, and triple-negative subtypes of DCIS. METHODS: Based on ER, PR, and ERBB2 status, a total of 18 high nuclear grade DCIS cases with no evidence of invasive breast carcinoma were selected along with 6 non-neoplastic controls. The 3 study groups were defined as ER/PR-positive, ERBB2, and triple-negative subtypes. RESULTS: A total of 49 genes were differentially expressed in the ERBB2 subtype compared with the ER/PR-positive and triple-negative groups. PROM1 was overexpressed in the ERBB2 subtype compared with ER/PR-positive and triple-negative subtypes. Other genes differentially expressed included TAOK1, AREG, AGR3, PEG10, and MMP9. CONCLUSIONS: Our study identified unique gene signatures in ERBB2-positive DCIS, which may be associated with the development of invasive breast carcinoma. The results may enhance our understanding of the progression of breast cancer and become the basis for developing new predictive biomarkers and therapeutic targets for DCIS.

Expression of Basal-like Biomarkers in Triple Negative Invasive Breast Carcinoma in Puerto Rico.

OBJECTIVE: Routine Progesterone and Estrogen hormone receptor proteins and human epidermal growth factor receptor 2 (HER-2) analysis on invasive breast carcinomas provide therapeutic and prognostic values, revealing significant subgroups: luminal A, luminal B, HER-2 and the "triple negative" tumors. The aim of this study was to determine the expression of basal cytokeratins and Epidermal Growth Factor Receptor in "triple negative" invasive breast carcinomas in Puerto Rico women. METHODS: All invasive breast carcinoma cases received from 2008 to 2010 were included. Assessment of tumoral expression of Estrogen Receptor, Progesterone Receptor and HER-2 was performed. The cases were divided into groups based on their molecular categories and analyzed according to the age. "Triple negative" tumors were further analyzed according to their expression of Epidermal Growth Factor Receptor and cytokeratins 5/6 and 14. RESULTS: From 717 cases reviewed, 487 cases of invasive breast carcinoma were included. The molecular categories were 66%, 10%, 9% and 15% for the luminal A, luminal B, Her-2 and "triple negative" groups, respectively. No significant difference (p= 0.64) was observed between the molecular categories and the age of the patients. Assessment of basal cytokeratins and Epidermal Growth Factor Receptor expression was performed on 41 "triple negative" tumors; 71% expressed at least one basal cytokeratin or Epidermal Growth Factor Receptor and 29% were negative to all markers. CONCLUSION: Prevalence and relation between the molecular categories and the expression of basal cytokeratins in "triple negative" tumors in our population is comparable to other published data.

Poor cell block adequacy rate for molecular testing improved with the addition of Diff-Quik-stained smears: Need for better cell block processing.

BACKGROUND: In the era of personalized medicine, requests for molecular testing of specimens obtained with minimally invasive procedures such as fine-needle aspiration have been increasing. Although cell blocks (CBs) are the recommended specimens for molecular testing, their performance has not been well analyzed. The objective of this study was to assess the frequency and types of samples deemed unsatisfactory for molecular testing (quantity not sufficient [QNS]). METHODS: One year after the implementation of careful monitoring of QNS cases, cases submitted for lung cancer molecular testing were analyzed for the QNS rate. When the cases were rejected for the inadequacy of CBs of cytology specimens, air-dried, Diff-Quik (DQ)-stained smears were reviewed and used if they were adequate. The QNS rates were compared across 4 specimen categories: large resection, small biopsy, CB alone, and CB with DQ smears. RESULTS: One hundred seventy-six cases were studied, and 45 (25.6%) were unsatisfactory. Only 1 of 73 large resection specimens was rejected because of decalcification. The QNS rate for small biopsy specimens was 35.9% (28 of 78), whereas 64% (16 of 25) of cytology cases ordered on CBs were rejected. In combination with DQ smears, the QNS rate of cytology specimens was 32% (8 of 25), which was a significant improvement over CBs only (P = .024) and was not significantly different from the QNS rate for small biopsies (P = .671). CONCLUSIONS: The utilization of DQ-stained smears for molecular testing improves the adequacy of cytologic samples and provides a minimally invasive alternative to surgical biopsy when molecular analysis of tumor material is necessary.