Summary Hormone receptor status is an integral component of decision-making in breast cancer management. IHC4 score is an algorithm that combines hormone receptor, HER2, and Ki-67 status to provide a ...semiquantitative prognostic score for breast cancer. High accuracy and low interobserver variance are important to ensure the score is accurately calculated; however, few previous efforts have been made to measure or decrease interobserver variance. We developed a Web-based training tool, called “Score the Core” (STC) using tissue microarrays to train pathologists to visually score estrogen receptor (using the 300-point H score), progesterone receptor (percent positive), and Ki-67 (percent positive). STC used a reference score calculated from a reproducible manual counting method. Pathologists in the Athena Breast Health Network and pathology residents at associated institutions completed the exercise. By using STC, pathologists improved their estrogen receptor H score and progesterone receptor and Ki-67 proportion assessment and demonstrated a good correlation between pathologist and reference scores. In addition, we collected information about pathologist performance that allowed us to compare individual pathologists and measures of agreement. Pathologists' assessment of the proportion of positive cells was closer to the reference than their assessment of the relative intensity of positive cells. Careful training and assessment should be used to ensure the accuracy of breast biomarkers. This is particularly important as breast cancer diagnostics become increasingly quantitative and reproducible. Our training tool is a novel approach for pathologist training that can serve as an important component of ongoing quality assessment and can improve the accuracy of breast cancer prognostic biomarkers.
Summary ProEx C is an antibody cocktail targeting the expression of topoisomerase II α and minichromosome maintenance protein 2. ProEx C staining is being used mainly to assist in diagnoses of ...dysplasia in gynecological specimens. This study was designed to determine the utility of ProEx C in assessing the urothelial lesions. Sixty-four patient specimens were divided into 5 groups: group I, 22 benign; group II, 13 low-grade noninvasive papillary urothelial carcinoma; group III, 10 high-grade urothelial carcinoma in situ (flat lesion); and group IV, 19 high-grade noninvasive papillary and invasive urothelial carcinomas. ProEx C reactions were scored in basal, parabasal, intermediate, and superficial cell layers. A sample was recorded as positive when nuclear staining was seen in the cells of the intermediate and/or superficial layers. Of 22 cases in group I, 21 were negative for ProEx C with a specificity of 95%. Of 13 cases in group II, 11 had positive results with sensitivity of 85%. All cases in groups III and IV had positive staining pattern with ProEx C with a sensitivity of 100%. In this study, ProEx C stain had an overall 95% sensitivity and specificity with positive and negative predictive values of 98% and 91%, respectively, for detection of urothelial carcinoma. We conclude that ProEx C is effective in differentiating carcinoma in situ and benign urothelial lesions. It also resolves issues in low- versus high-grade papillary urothelial carcinomas. To our knowledge, this is the first publication on the diagnostic application of ProEx C in histopathology of the urothelial lesions.
Abstract Breast pathology relies on gross dissection for accurate diagnostic work, but challenges can necessitate submission of high tissue volumes resulting in excess labor, laboratory costs, and ...delays. To address these issues, a quality initiative was created through implementation of the Faxitron PathVision specimen radiography system as part of the breast gross dissection protocol; this report documents its impact on workflow and clinical care. Retrospective data from 459 patients who underwent simple or modified radical mastectomy at our institution between May 2012 and December 2014 were collected. Comparison was made between the mastectomy specimen control group before radiography use (233 patients, 340 breasts) and Faxitron group that underwent postoperative radiography (226 patients, 338 breasts). We observed a statistically significant decrease in mean number of blocks between control and Faxitron groups (47.0 vs 39.7 blocks; P < .0001), for calculated cost savings of US $146 per mastectomy. A statistically significant decrease in pathology report turnaround time was also observed (4.2 vs 3.8 days; P = .038). Postoperative mastectomy specimen radiography has increased workflow efficiency and decreased histology costs and pathology report turnaround time. These findings may underestimate actual benefits and highlight the importance of quality improvement projects in anatomical pathology.
Minimally invasive breast biopsy procedures performed for suspicious imaging findings have expanded the role of breast imaging in the management of breast diseases. The first portion of this article ...reviews the current procedures for performing a core-needle biopsy under stereotactic, ultrasound, and MR imaging guidance. The second portion of the article addresses the management of the patient after the biopsy, including assessment for concordance of radiology and pathology findings and potential underestimation of disease.
Abstract Breast cancer is the leading cause of cancer in women and the third leading cause of cancer mortality in the United States. We report a case of a patient who underwent bilateral simple ...mastectomies and right sentinel node biopsy for invasive lobular carcinoma in the right breast. An ipsilateral sentinel lymph node showed a microscopic focus of ductal elements. Although residual lobular carcinoma was identified in the right breast, no ductal carcinoma was identified in either breast. The ducts were discrete distributed in a 3-mm focus in the lymph node parenchyma as well as the subcapsular sinus. By immunohistochemistry, the ducts were positive for cytokeratin, estrogen receptor/progesterone receptor and did not show a myoepithelial layer by P63 or smooth-muscle myosin heavy-chain staining. The differential diagnosis includes heterotopic epithelial inclusions and benign mechanical transport. Mechanical transport of the breast tissue was ruled out because primary tumor type in the breast and the ductal structures in the lymph nodes were of different types. The diagnosis of occult metastatic tumor was based on the lack of the myoepithelial layers associated with the ductal structures. The diagnostic dilemma of the differential diagnoses is discussed, and pertinent literature is reviewed.
Summary The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss ...has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high-density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression with patient outcomes and clinicopathologic variables. Expression of GATA3 was significantly increased in breast cancer, in situ lesions, and hyperplastic tissue compared with normal breast tissue. GATA3 expression decreased with increasing tumor grade. Low GATA3 expression was a significant predictor of disease-related death in all patients, as well as in subgroups of estrogen receptor–positive or low-grade patients. In addition, low GATA3 expression correlated with increased tumor size and estrogen and progesterone receptor negativity. GATA3 is an important predictor of disease outcome in breast cancer patients. This finding has been validated in a diverse set of populations. Thus, GATA3 expression has utility as a prognostic indicator in breast cancer.