Mitotic counts in one high power field in breast core biopsies is equivalent to counts in 10 high power fields.

Mitotic rate is an important prognostic predictor in invasive breast carcinoma. Current guidelines recommend counting mitoses from 10 contiguous high power fields (HPFs) in the core biopsy. We propose a method to score mitotic activity in 1 HPF at the most mitotically active area of the tumour edge, or the interface between invasive tumour and benign breast tissue. We propose a score of 1, 2, or 3, corresponding to ≤1, 2, or ≥3 mitoses in 1 HPF, respectively. A total of 141 breast core biopsies with corresponding surgical excisions were blindly examined. We counted the number of mitotic figures in 1 HPF and in 10 contiguous HPFs in the core biopsy and compared with the mitotic count from 10 contiguous HPFs in the excision which is considered the gold standard. Concordance rates and interobserver agreement rates were calculated. The concordance rate was 82.3%, 78.7% and 82.3% between 1 HPF versus 10 HPFs in the core biopsy, 1 HPF in the core biopsy versus 10 HPFs in the excision and 10 HPFs in the core biopsy vs 10 HPFs in the excision, respectively. In the core biopsy, all three investigators agreed in 73.8% and 83.7% of the cases using the 1 HPF method and the 10 HPFs method, respectively; in the excision specimen, agreement was reached in 82.3% of the cases. The 1 HPF method showed similar concordance rate and interobserver agreement compared to the conventional method in the prediction of the mitotic score in the excision in all score groups. When stratified by mitotic score, the 1 HPF method predicted superior correlation with excision in the score 1 group than the 10 HPFs method, but not in the score 2 or 3 groups. From these findings we conclude that the proposed 1 HPF method can be used in clinical practice to grade invasive breast carcinomas in core biopsies, with the possibility of being utilised in small biopsies with less than 10 HPFs of invasive carcinoma.

National Accreditation Program for Breast Centers Demonstrates Improved Compliance with Post-Mastectomy Radiation Therapy Quality Measure.

BACKGROUND: The National Accreditation Program for Breast Centers (NAPBC) was established in 2008 by the American College of Surgeons as a quality-improvement program for patients with breast disease. An NAPBC quality measure states post-mastectomy patients with ≥4 positive lymph nodes should receive lymph node radiation therapy (PMRT). Our objective was to examine how NAPBC accreditation has affected compliance with this quality measure. STUDY DESIGN: Women who underwent mastectomy at either an NAPBC-accredited center or a Commission on Cancer-only accredited hospital were identified (2006 to 2013) in the National Cancer Data Base. The NAPBC centers accredited from 2009 to 2011 were included in the analysis. Patients were nested within centers using a mixed effects model to identify PMRT rates at each center before and after accreditation, adjusting for patient and tumor characteristics. RESULTS: Of 34,752 patients from 477 NAPBC-accredited centers and 958 Commission on Cancer-only accredited hospitals who underwent mastectomy with ≥4 positive lymph nodes, 21,638 patients received PMRT during the study period (62.3%). The NAPBC centers yielded a significantly higher rate of PMRT than Commission on Cancer hospitals (66.0% vs 59.2%; p < 0.001). For each year of accreditation (2009 to 2011), centers had significantly higher rates of radiation in the accreditation year compared with the year before accreditation (p < 0.001). Within those centers, the rate of radiation increased post-accreditation in each accreditation year (2009: 62.1% to 71.9%; 2010: 65.5% to 73.2%; 2011: 67.5% to 70.4%). CONCLUSIONS: The NAPBC accreditation is associated with higher PMRT rates and better adherence to the PMRT quality measure. Future studies with more centers and longer follow-up are needed to determine whether this trend continues.

The Value of Combined Large Format Histopathology Technique to Assess the Surgically Removed Breast Tissue following Neoadjuvant Chemotherapy: A Single Institution Study of 40 Cases.

Historically, neoadjuvant chemotherapy has been used to treat patients with advanced breast disease in an attempt to convert them into candidates for breast conservation surgery. The ultimate goal of histopathologic examination of the specimens removed after neoadjuvant chemotherapy is the identification of either residual disease or positive identification of the tumor bed. We report a series of 40 patients treated with neoadjuvant chemotherapy and evaluation of the surgical specimens by a combination of standard histopathology and the use of large format histopathology techniques.

Fixation time does not affect expression of HER2/neu: a pilot study.

It is said that HER2/neu expression by immunohistochemical analysis varies with the time of fixation. The purpose of this pilot study was to determine the impact of the length of fixation in 10% buffered formalin on the expression of HER2/neu by immunohistochemical analysis. We studied tissue samples from 10 invasive breast cancer cases after fixation for 3, 48, 72, 96, and 120 hours. The tissue was processed immediately after fixation, resembling routine practice. The 50 resulting blocks were then batch stained with PATHWAY HER2/neu clone 4B5 rabbit monoclonal antibody using the Ventana Ultraview DAB detection kit in a Ventana BenchMark XT processor (Ventana, Tucson, AZ). The stained slides were reviewed and scored. We found no significant difference in the intensity of the stain or the percentage of cells stained regardless of the time in fixation. Fixation times between 3 and 120 hours in 10% buffered formalin do not appear to have an impact on the expression of HER2/neu by immunohistochemical analysis.

Fixation time does not affect the expression of estrogen receptor.

The purpose of this pilot study was to determine the impact of the length of fixation in 10% buffered formalin on the expression of estrogen receptor by immunohistochemical analysis. We studied tissue samples from 10 invasive breast cancer cases after fixation for 1, 3, 6, and 9 to 10 hours. The tissue was processed immediately after fixation, resembling routine practice. Then the 40 blocks were incubated with antiestrogen receptors SP1, 6F11, and 1D5. The stained slides were reviewed and scored. We found no significant difference in the intensity of the stain or the percentage of cells stained regardless of the time in fixation or the antibody used. Fixation times between 1 and 9 hours in 10% formalin do not seem to have an impact on the expression of estrogen receptor by immunohistochemical analysis, at least in these high-expressing tumors.

Guideline implementation for breast healthcare in low- and middle-income countries: diagnosis resource allocation.

A key determinant of breast cancer outcome in any population is the degree to which newly detected cancers can be diagnosed correctly so that therapy can be selected properly and provided in a timely fashion. A multidisciplinary panel of experts reviewed diagnosis guideline tables and discussed core implementation issues and process indicators based on the resource stratification guidelines. Issues were then summarized in the context of 1) clinical assessment, 2) diagnostic breast imaging, 3) tissue sampling, 4) surgical pathology, 5) laboratory tests and metastatic imaging, and 6) the healthcare system. Patient history provides important information for the clinical assessment of breast and comorbid disease that may influence therapy choices. Focused clinical breast examination and complete physical examination provide guidance on the extent of disease, the presence of metastatic disease, and the ability to tolerate aggressive therapeutic regimens. Breast imaging improves preoperative diagnostic assessment and also permits image-guided needle sampling. Diagnostic mammography was not considered mandatory in low- and middle-income countries when resources are lacking. Needle biopsy is preferred to surgical excision for the initial diagnosis of suspicious breast lesions, unless resources are unavailable. Mastectomy should never be used as a method of tissue diagnosis. The availability of predictive tumor markers, especially estrogen receptor testing, is critical when endocrine therapies are available; quality assessment of immunohistochemistry testing is important to avoid false-negative results. Incremental allocation of resources can help address economic disparities and help ensure equity in access to timely diagnosis.

Breast pathology guideline implementation in low- and middle-income countries.

The quality of breast healthcare delivery and the ultimate clinical outcome for patients with breast cancer are directly related to the quality of breast pathology practices within the healthcare system. The Breast Health Global Initiative (BHGI) held its third Global Summit in Budapest, Hungary from October 1 to 4, 2007, bringing together internationally recognized experts to address the implementation of breast healthcare guidelines for the early detection, diagnosis, and treatment in low-income and middle-income countries (LMCs). From this group, a subgroup of experts met to address the specific needs and concerns related to breast pathology program implementation in LMCs. Specific recommendations were made by the group and process indicators identified in the areas of personnel and training, cytology and histopathology interpretation, accuracy of pathology interpretation, pathology reporting, tumor staging, causes of diagnostic errors, use of immunohistochemical markers, and special requirements to facilitate breast conservation therapy. The group agreed that the financial burden of establishing and maintaining breast pathology services is counterbalanced by the cost savings from decreased adverse effects and excessive use of treatment resources that result from incorrect or incomplete pathologic diagnosis. Proper training in breast pathology for pathologists and laboratory technicians is critical and provides the underpinnings of programmatic success for any country at any level of economic wealth.

Re-establishing a surgical pathology service in Kumasi, Ghana: case report and discussion of barriers and key elements of a successful collaboration between low- and high-resource countries.

At Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, a breakdown of technical equipment and lack of pathologists resulted in closure of the surgical pathology laboratory in 2004. At an international meeting in January 2005, 1 USA and 1 Norwegian pathologist were asked if their departments could help with the pathology problem at KATH. This article describes the proposals, the barriers encountered, and the key elements of the final successful collaboration between a low-resource and a high-resource country. The proposal to the USA hospital focused on receiving specimens for diagnosis. A detailed proposal was not developed, as several key operational barriers were identified early on, including legal issues, technical capacity issues, and staff capacity issues. The proposal to the University Hospital of North Norway (UNN) resulted in development of a 5-year plan to reestablish surgical pathology at KATH. Two KATH technicians came to UNN and trained in the histopathology laboratory for 3 months. On their return, they started producing slides at KATH. Since April 2006, weekly shipments of hematoxylin and eosin (H & E) stained slides have been sent to UNN by courier service. When needed, paraffin blocks are sent on request. In March 2006, 2 young Ghanaian physicians were received as trainees at the UNN to do full resident work and training with the aim of being approved as specialists in pathology in Ghana by 2010. Full surgical pathology service and training of new pathologists on site are expected to be reestablished at KATH by 2010.

Nodal stage classification for breast carcinoma: improving interobserver reproducibility through standardized histologic criteria and image-based training.

PURPOSE: Reliable pathologic stage classification of axillary lymph nodes is an important determinant of prognosis and therapeutic decision making for patients with invasive breast cancer. Pathologists' distinction between micrometastasis (pN1mi) and isolated tumor cells [ITC; pN0(i+)] is variable using the American Joint Committee on Cancer (AJCC) Staging Manual (Sixth Edition). We sought to determine whether a set of clearly defined histologic criteria could lead to reproducible nodal classification by pathologists. PATIENTS AND METHODS: Digital images of sentinel lymph node biopsies from 56 patients with small-volume nodal metastases were examined by six experienced breast pathologists (MDs), first as a pre-test, and again as a post-test after studying a training program that outlined and illustrated the classification criteria. RESULTS: Post-test results, after study of the training program, were significantly improved. Compared with the reference MD, agreement improved from 76.2% (pre-test kappa = 0.575; standard deviation [SD], 0.25) to 97.3% (post-test kappa = 0.947; SD, 0.049). Multirater analysis of agreement among the six MDs improved from 71.5% (pre-test kappa = 0.487; ASE, 0.039) to 95.7% (post-test kappa = 0.915; ASE, 0.037). Agreement on lobular carcinoma metastasis classification improved from 55% (23 of 42; pre-test) to 100% (42 of 42; post-test) (P < .001), and agreement on ITC classification in nodal parenchyma improved from 67.6% (69 of 102; pre-test) to 98.0% (100 of 102; post-test; P < .001). CONCLUSION: Application of current definitions for classification of small-volume nodal metastases are inconsistent, leading to variable classification of ITC and micrometastases. Reproducibility of pathologic nodal stage classification is achievable through study of a training set to clarify the AJCC criteria.

Papillary lesions of the breast.

Papillary lesions of the breast include a variety of benign, atypical, and malignant lesions whose hallmark is the formation of either papillary tufts composed only of epithelium, or true papillary structures with fibrovascular support and epithelium. The precise diagnosis has significance because of the variability in treatment modalities. This article attempts to describe the basic features seen in papillary-type lesions and their correlation with imaging studies.

Discrimination of breast cancer by anti-malignin antibody serum test in women undergoing biopsy.

PURPOSE: The anti-malignin antibody serum (AMAS) test (Oncolab, Boston, MA) has been reported as 97% sensitive and 95% specific for malignancies. To objectively assess accuracy of this test for discrimination of breast cancer, we studied a series of women undergoing core breast biopsy. SUBJECTS AND METHODS: Seventy-one core-needle breast biopsies were classified as malignant, suspicious, or benign by two independent pathologists blinded to AMAS results. Corresponding sera were read as AMAS positive, negative, or borderline by criteria used by Oncolab and also using criteria derived from receiver-operator curves based on values for slow (S-tag), fast (F-tag), and their difference (Net-tag) antibody reported by Oncolab. We calculated sensitivity and specificity and analyzed distributions by Fisher's exact test. RESULTS: Biopsies were read as 42 (59%) benign, 12 (17%) suspicious, and 17 (24%) malignant. By Oncolab criteria, sensitivity (59%) and specificity (62%) were maximized by pooling suspicious with malignant and AMAS borderline with positive (P = 0.098). Receiver-operator curves showed best sensitivity (62%) and specificity (69%) for the criterion AMAS positive if Net-Tag > 135 microg/mL or S-Tag > 220 microg/mL (P = 0.015). CONCLUSIONS: The AMAS test discriminates suspicious and malignant from benign lesions, but sensitivity is insufficient to identify patients to be spared biopsy and false-positive rates are too high for population screening.

Diagnosis of breast cancer in countries with limited resources.

Accurate diagnosis is a necessary step in the management of breast cancer. In women with breast cancer, diagnosis can confirm the presence of the disease, reduce treatment delays, and clarify the predictive and prognostic features of the cancer, which help in planning treatment and counseling women. In women with benign breast conditions, accurate diagnosis avoids erroneous treatment for breast cancer, which can have devastating consequences for the woman and unnecessarily consumes resources. The panel distinguishes between a "clinical diagnosis" of breast cancer (one based on signs and symptoms and imaging findings) and a "pathologic diagnosis" of breast cancer (one based on microscopic examination of cellular or tissue samples). The panel agrees that all women should have a pathologic diagnosis of breast cancer before they are given definitive treatment for the disease, no matter how strongly their clinical findings suggest cancer. The tools for clinical diagnosis include history, clinical breast examination, ultrasound, and diagnostic mammography; these tools provide valuable information and play important supplemental roles in ascertaining the presence of breast cancer. Mammography and ultrasound also help determine the extent of disease within the breast, which is essential when breast-conserving therapy can be offered to women. The tools for pathologic diagnosis include fine-needle aspiration biopsy, core needle biopsy, and standard surgical biopsy. The panel noted that each of these tools has potential benefits and limitations in the limited-resource setting, and concluded that the choice among them must be based on the available tools and expertise. The triple test-checking for correlation of pathology findings, imaging findings, and clinical findings-was identified as a critical practice in diagnosing breast cancer. Panelists uniformly agreed that mastectomy should not be used to diagnose breast cancer, noting that accurate diagnosis can be made by less invasive means. Expertise in pathology was identified as a key requirement for ensuring reliable diagnostic findings. Several approaches were proposed for improving breast pathology, including training pathologists, establishing pathology services in centralized facilities, and organizing international pathology services.