3D digital breast cancer models with multimodal fusion algorithms

Breast cancer image fusion consists of registering and visualizing different sets of a patient synchronized torso and radiological images into a 3D model. Breast spatial interpretation and visualization by the treating physician can be augmented with a patient-specific digital breast model that integrates radiological images. But the absence of a ground truth for a good correlation between surface and radiological information has impaired the development of potential clinical applications.A new image acquisition protocol was designed to acquire breast Magnetic Resonance Imaging (MRI) and 3D surface scan data with surface markers on the patient’s breasts and torso. A patient-specific digital breast model integrating the real breast torso and the tumor location was created and validated with a MRI/3D surface scan fusion algorithm in 16 breast cancer patients.This protocol was used to quantify breast shape differences between different modalities, and to measure the target registration error of several variants of the MRI/3D scan fusion algorithm. The fusion of single breasts without the biomechanical model of pose transformation had acceptable registration errors and accurate tumor locations. The performance of the fusion algorithm was not affected by breast volume. Further research and virtual clinical interfaces could lead to fast integration of this fusion technology into clinical practice.     

Erroneous diagnosis of primary fibrosarcoma of the breast: The value of the multidisciplinary breast team approach

Diagnostic errors occur in the preanalytic, analytic, and postanalytic phases of specimen processing. Correlating clinical and imaging information with gross and microscopic findings is crucial to limit errors and unnecessary treatment. Herein, we report the case of a 54-year-old woman who presented with left breast bloody nipple discharge and subsequently underwent central duct excision. Pathology revealed a high-grade sarcoma. The patient presented to our institution for further management. Upon secondary pathology review and DNA fingerprinting analysis, the correct interpretation was rendered. Our case demonstrates the importance of clinical correlation and review of pathology slides prior to definitive therapy.     

Inter‐Institutional Pathology Consultation: The Importance of Breast Pathology Subspecialization in a Setting of Tertiary Cancer Center

Inter‐institutional pathology consultation (IPC) has shown to be significant in patient care. The purpose of the study was to evaluate the impact of IPC for breast biopsies in our institution. A total of 502 consecutive consult cases of breast core needle biopsies were reviewed. The original pathology reports from the referring institutions and our reports were compared for all cases. All cases were reviewed by specialized breast pathologists. Discordance was divided into minor and major based on the impact on patient care. We reviewed the subsequent excisional biopsy for all discordant cases. Discordance was seen in 104 (20.7%) cases; 40 (8%) had a major discordance and 64 (13%) had a minor discordance. Subsequent surgical excision was available for 25 (62.5%) cases with major discordance and for 13 (20.3%) with minor discordance. Our interpretation changed management in 15 (3%) patients, while 25 (5%) had a potential of management change. The cases with major discordance could be subcategorized into five groups, malignant 5 (12.5%), premalignant 16 (40%), biomarkers 10 (25%), fibroepithelial lesions 6 (15%), and others 3 (7.5%). Our findings support the value of IPC review in decreasing the likelihood of diagnostic errors that may lead to significant impact on patient care. It is necessary that outside pathology material in the referral settings been reviewed by a specialized breast pathologist.     

Artificial intelligence in digital breast pathology: Techniques and applications

Breast cancer is the most common cancer and second leading cause of cancer-related death worldwide. The mainstay of breast cancer workup is histopathological diagnosis - which guides therapy and prognosis. However, emerging knowledge about the complex nature of cancer and the availability of tailored therapies have exposed opportunities for improvements in diagnostic precision. In parallel, advances in artificial intelligence (AI) along with the growing digitization of pathology slides for the primary diagnosis are a promising approach to meet the demand for more accurate detection, classification and prediction of behaviour of breast tumours. In this article, we cover the current and prospective uses of AI in digital pathology for breast cancer, review the basics of digital pathology and AI, and outline outstanding challenges in the field.     

Breast Cancers Found with Digital Breast Tomosynthesis: A Comparison of Pathology and Histologic Grade

To compare the pathology and histologic grading of breast cancers detected with digital breast tomosynthesis to those found with conventional digital mammography. The institutional review board approved this study. A database search for all breast cancers diagnosed from June 2012 through December 2013 was performed. Imaging records for these cancers were reviewed and patients who had screening mammography with tomosynthesis as their initial examination were selected. Five dedicated breast imaging radiologists reviewed each of these screening mammograms to determine whether the cancer was visible on conventional digital mammography or whether tomosynthesis was needed to identify the cancer. A cancer was considered mammographically occult if all five radiologists agreed that the cancer could not be seen on conventional digital mammography. The size, pathology and histologic grading for all diagnosed breast cancers were then reviewed. The Mann–Whitney U and Fisher exact tests were utilized to determine any association between imaging findings and cancer size, pathologic type and histologic grade. Sixty‐five cancers in 63 patients were identified. Ten of these cancers were considered occult on conventional digital mammography and detected with the addition of tomosynthesis. These mammographically occult cancers were significantly associated with Nottingham grade 1 histologic pathology (p = 0.02), were smaller (median size: 6 mm versus 10 mm, p = 0.07) and none demonstrated axillary nodal metastases. Breast cancers identified through the addition of tomosynthesis are associated with Nottingham grade 1 histologic pathology and prognostically more favorable than cancers identified with conventional digital mammography alone.     

Sentinel node mapping for breast cancer: the operative experience of a breast surgeon in a rural community

Sentinel lymph node biopsy has become an accepted procedure for staging the axilla in early stage breast cancer. Our objectives were to review our practice of sentinel lymph node (SLN) mapping in breast cancer, to determine the impact of frozen section (FS) analysis of the SLN on patient management, and to compare our results to national data. We retrospectively reviewed the medical records of our patients with breast cancer who underwent SLN mapping with or without axillary lymph node dissection (ALND) between 1999 and 2006. During this period, 478 patients were treated for breast cancer, with 227 patients undergoing SLN mapping. The SLN was identified in 201 patients, with a positive SLN found in 52 patients (25.9%). There was a discrepancy between the intraoperative analysis (FS/touch prep) and final pathology in 20 patients (11.3%). Nineteen of those patients had a negative FS with positive final pathology. Six of these patients underwent completion ALND. One patient had a false-positive FS with a negative ALND. No axillary recurrences were observed. Eight patients (3.5%) developed postoperative complications. Our practice has been to use intraoperative evaluation of the SLN to reduce the number of patients requiring a secondary ALND. In our study, six patients returned to the operating room for a completion ALND. Our complication rate and axillary recurrence rates were similar to national data.     

Why current breast pathology practices must be evaluated. A Susan G. Komen for the Cure white paper: June 2006

Ending breast cancer has long been the mission of Susan G. Komen for the Cure. To this end, the organization has a strong interest and proven track record in ensuring public investment in quality breast health and breast cancer care. Recently, Susan G. Komen for the Cure identified major issues in the practice of pathology that have a negative impact on the lives of thousands of breast cancer patients in the United States. These issues were identified through a comprehensive literature review and interviews conducted in 2005-2006 with experts in oncology, breast pathology, surgery, and radiology. The interviewees practiced in community, academic, and cooperative group settings. Komen for the Cure has identified four areas that have a direct impact on the quality of care breast cancer patients receive in the United States, the accuracy of breast pathology diagnostics, the effects of current health insurance, and reimbursement policies on patients who are evaluated for a possible breast cancer diagnosis, the substantial decrease in tissue banking participation, particularly during a time of rapid advances in biologically correlated clinical science and the role for the Susan G. Komen for the Cure, pathology professional societies and the Federal government in ensuring that breast pathology practices meet the highest possible standards in the United States Concerns surrounding the quality and practice of breast pathology are not limited to diagnostic accuracy. Other considerations include, training and proficiency of pathologists who are evaluating breast specimens, the lack of integration of pathologists in the clinical care team, inadequate compensation for the amount of work required to thoroughly analyze specimens, potential loss in translational research as a result of medical privacy regulations, and the lack of mandatory uniform pathology practice standards without any way to measure the degree of variation or to remedy it.     

Overview of Telepathology

Telepathology is the practice of remote pathology using telecommunication links to enable the electronic transmission of digital pathology images. Telepathology can be used for remotely rendering primary diagnoses, second opinion consultations, quality assurance, education, and research purposes. The use of telepathology for clinical patient care has been limited mostly to large academic institutions. Barriers that have limited its widespread use include prohibitive costs, legal and regulatory issues, technologic drawbacks, resistance from pathologists, and above all a lack of universal standards. This article provides an overview of telepathology technology and applications.     

Breast cancer surgery with augmented reality

Introduction: Innovations in 3D spatial technology and augmented reality imaging driven by digital high-tech industrial science have accelerated experimental advances in breast cancer imaging and the development of medical procedures aimed to reduce invasiveness. Presentation of case: A 57-year-old post-menopausal woman presented with screen-detected left-sided breast cancer. After undergoing all staging and pre-operative studies the patient was proposed for conservative breast surgery with tumor localization. During surgery, an experimental digital and non-invasive intra-operative localization method with augmented reality was compared with the standard pre-operative localization with carbon tattooing (institutional protocol). The breast surgeon wearing an augmented reality headset (Hololens) was able to visualize the tumor location projection inside the patient’s left breast in the usual supine position. Discussion: This work describes, to our knowledge, the first experimental test with a digital non-invasive method for intra-operative breast cancer localization using augmented reality to guide breast conservative surgery. In this case, a successful overlap of the previous standard pre-operative marks with carbon tattooing and tumor visualization inside the patient’s breast with augmented reality was obtained. Conclusion: Breast cancer conservative guided surgery with augmented reality can pave the way for a digital non-invasive method for intra-operative tumor localization.     

Mandatory second opinion in surgical pathology referral material: clinical consequences of major disagreements

Second opinion in pathology is intended to expose clinically significant errors that have a direct impact on patient care. Before definitive treatment of referred patients, our institution requires a second opinion of outside surgical pathology slides. We sought to determine if this local standard of practice has a measurable impact on patient care via clinical and pathologic follow-up. 5629 second opinion surgical pathology cases seen at the University of Iowa Hospitals and Clinics were studied. Each case was classified as: no diagnostic disagreement, minor diagnostic disagreement, or major diagnostic disagreement by the second opinion pathologist at the time of referral. A major diagnostic disagreement was defined as a change in pathologic diagnosis with potential for significant change in treatment or prognosis. Major diagnostic disagreements were categorized by organ system and according to the clinical significance of the changed diagnosis based on clinical and pathologic follow-up. Second opinion surgical pathology resulted in 132 (2.3% of total cases) major diagnostic disagreements and 507 (9.0%) cases with minor disagreements. The organ systems involved in the majority of the major disagreements were the female reproductive tract (32), gastrointestinal tract (27), and skin (24). Of the 132 major diagnostic disagreements, 68 (1.2% of total cases reviewed) prompted changes in the clinical management as a result of the second opinion interpretation. These findings support the idea that mandatory second opinion is an important part of patient care in the referral setting.     

Changing patterns of care for occult breast lesions in a community teaching hospital

We performed a retrospective analysis of 384 consecutive stereotactic breast biopsies (SBBs) from March 1995 through January 1999 and compared it with our historical breast biopsy experience. Two hundred forty-four patients underwent biopsies for microcalcifications and 135 patients for abnormal mammographic densities. Pathology diagnoses included 302 patients with benign disease, 35 patients with atypical ductal hyperplasia, 4 patients with lobular carcinoma in situ, 29 patients with ductal carcinoma in situ, and 9 patients with invasive breast cancer. These diagnostic rates were compared with our prior needle-localized pathology findings. For the study period, the number of mammograms, open biopsies, and needle-localized biopsies remained stable. The number of SBBs, however, increased progressively in every year. Medicare reimbursement for SBB was $921.19, and for breast biopsy after needle localization, $1566.22. Our study strongly suggests that the availability of SBB has significantly lowered the threshold for recommending biopsy of abnormal mammograms. The increased utilization of SBB almost certainly indicates an increase in the overall cost of breast care. This cost must be balanced against substantial potential benefits of this minimally invasive technique: possible earlier diagnosis of atypical and precancerous lesions, patient reassurance in cases of uncertain mammographic interpretation, and a reduced need for follow-up of indeterminate mammograms.     

Interobserver interpretative reproducibility of GOLDFISH,a first generation gold-facilitated autometallographic bright field in situ hybridization assay for HER-2/neu amplification in invasive mammary carcinoma

Clinical laboratory testing for HER-2/neu gene amplification by fluorescence in situ hybridization is not widely used in diagnostic pathology laboratories. A bright field alternative permitting direct visualization of gene amplification using conventional microscopy may be more readily incorporated into routine diagnostic pathology practice. Interobserver reproducibility represents an important component of the validation of such an assay. We tested the hypothesis that a first-generation bright field alternative to fluorescence in situ hybridization, a Nanogold (Nanoprobes, Inc, Yaphank, NY, USA) (or gold-label)/autometallographic assay for HER-2/neu gene amplification in breast carcinoma, can be reproducibly interpreted by pathologists. Reference standard was direct fluorescence in situ hybridization supplemented by RNA/RNA in situ hybridization. Reproducibility of selected conventional histologic parameters was captured based on a hematoxylin and eosin slide accompanying the GOLDFISH preparation (gold-facilitated autometallographic in situ hybridization) as an indication of comparative reproducibility. The average kappa among GOLDFISH observers was 0.84, which was at least or concordant of observers scoring nuclear grade (kappa = 0.50) and the presence of in situ carcinoma (kappa = 0.57) by conventional histopathology. The GOLDFISH assay was specifically designed for qualitative interpretation, thus obviating the need for oil immersion microscopy and signal enumeration, and its interpretation was highly reproducible among five pathologists.     

Pathologists' agreement with experts and reproducibility of breast ductal carcinoma-in-situ classification schemes

Several histologic classifications for breast ductal carcinoma in situ (DCIS) have been proposed. This study assessed the diagnostic agreement and reproducibility of three DCIS classifications (Holland [HL], modified Lagios [LA], and Van Nuys [VN]) by comparing the interpretations of pathologists without expertise in breast pathology with those of three breast pathology experts, each a proponent of one classification. Seven nonexpert pathologists in New Hampshire and three experts evaluated 40 slides of DCIS according to the three classifications. Twenty slides were reinterpreted by each nonexpert pathologist. Diagnostic accuracy (nonexperts compared with experts) and reproducibility were evaluated using inter- and intrarater techniques (kappa statistic). Final DCIS grade and nuclear grade were reported most accurately among nonexpert pathologists using HL (kappa = 0.53 and 0.49, respectively) compared with LA and VN (kappa = 0.29 and 0.35, respectively, for both classifications). An intermediate DCIS grade was assessed most accurately using HL and LA, and a high grade (group 3) was assessed most accurately using VN. Diagnostic reproducibility was highest using HL (kappa = 0.49). The VN interpretation of necrosis (present or absent) was reported more accurately than the LA criteria (extensive, focal, or absent; kappa = 0.59 and 0.45, respectively), but reproducibility of each was comparable (kappa = 0.48 and 0.46, respectively). Intrarater agreement was high overall. Comparing all three classifications, final DCIS grade was reported best using HL. Nuclear grade (cytodifferentiation) using HL and the presence or absence of necrosis were the criteria diagnosed most accurately and reproducibly. Establishing one internationally approved set of interpretive definitions, with acceptable accuracy and reproducibility among both pathologists with and without expertise in breast pathology interpretation, will assist researchers in evaluating treatment effectiveness and characterizing the natural history of DCIS breast lesions.     

Development of an intraoperative pathology consultation service at a free-standing ambulatory surgical center: clinical and economic impact for patients undergoing breast cancer surgery

BackgroundSecond surgeries represent a significant detriment to breast cancer patients. We examined the impact an intraoperative pathology consultation service had on multiple facets of breast cancer surgery.MethodsWe compared the 8 months before the establishment of a pathology laboratory, when intraoperative pathology consultation was not available, with the 8 months subsequent, when it was performed routinely.ResultsThe average number of surgeries per patient decreased from 1.5 to 1.23, and the number of patients requiring one surgery increased from 59% to 80%. Re-excisions decreased from 26% to 9%. Frozen section allowed 93% of node-positive patients to avoid a second surgery for axillary lymph node dissection. A cost analysis showed savings between $400 and $600 per breast cancer patient, even when accounting for fewer axillary lymph node dissections based on the American College of Surgeons Oncology Group Z0011 data.ConclusionsIncorporation of routine intraoperative margin/sentinel lymph node assessment at an outpatient breast surgery center is feasible, and results in significant clinical benefit to the patient. Use of frozen section decreased both the time and cost required to treat patients.     

微小乳腺癌的直接数字化X线征象与临床查体及病理关系的分析

目的分析微小乳腺癌的直接数字化X线征象,并探讨其与临床查体及病理的关系。方法回顾性分析经手术、病理证实的微小乳腺癌68例。采用直接数字化乳腺X线机后处理工作站屏幕阅读方式。结果X线征象为结节者39例,单纯钙化14例,结构紊乱8例,致密影7例,除单纯钙化外,其他征象伴有钙化者37例。临床触诊阳性42例,阴性26例。本组15例(占22%)为非浸润性癌,不可触及微小癌中46%为非浸润性癌。结论微小乳腺癌X线表现为结节、单纯钙化、结构紊乱或致密影,细钙化是微小癌重要X线征象。直接数字化X线摄影对诊断临床触诊阴性的微小乳腺癌有重要价值。     

Digital analysis of x-ray pictures in diagnostics and monitoring of post trauma reflex sympathetic dystrophy]

The aim of this paper was to evaluate the digital quality analysis of X-ray pictures in patients with post trauma reflex sympathetic dystrophy. Radiograms of 30 patients were scanned and exposed to optic density analysis. This method increases the possibilities of bone pathology interpretation.     

Surgical management of the patient with invasive carcinoma discovered at reduction mammoplasty

The diagnosis of invasive carcinoma presents a surgical dilemma when discovered incidentally at breast reduction mammoplasty. Subsequent surgical and therapeutic management for such cases have not been established. Although management and treatment may vary according to patient preference, a review of the literature of the past four decades yielded scant discussion of the topic. We describe two cases of occult breast carcinomas that were not evident on preoperative breast screening, but were discovered on the pathology exam of reduction mammoplasty specimen. The purpose of our publication is to recommend a surgical approach for the patient in such a situation.     

Breast necrosis following harvest of internal mammary artery.

The use of internal mammary artery is well established not only in cardiac surgery for coronary artery bypass grafting but also in plastic surgery for breast reconstruction with free autologus tissue. The complications that follow harvest of internal mammary artery for heart surgery usually relate to the wound. This case report documents the first case of complete breast infarction following such a procedure in a patient who had no prior history of breast pathology. The histology of the breast showed extensive calcification of the intima and media of small to medium sized vessels, a condition called calciphylaxis, which is largely unknown outside the fields of nephrology and dermatology.     

Incidence of False Positive Rotator Cuff Pathology in MRIs of Patients with Adhesive Capsulitis

The purpose of this study was to compare the incidence of presumed rotator cuff pathology based on radiologist and surgeon interpretation of preoperative magnetic resonance images (MRIs) with actual rotator cuff pathology found intraoperatively in patients undergoing arthroscopic capsular release for adhesive capsulitis.The medical records of 38 consecutive patients who underwent arthroscopic glenohumeral capsular release for adhesive capsulitis between September 2001 and May 2007 were retrospectively reviewed. Radiologist and surgeon predicted status of the rotator cuff by prospective MRI interpretation was compared to the actual status of the rotator cuff intraoperatively. Radiologists' preoperative MRI interpretations predicted a 57.9% incidence of rotator cuff pathology, while operative findings revealed a true incidence of only 13.2% (P<.0001). Radiologists accurately predicted the absence or presence of a rotator cuff tear in 19 of 38 cases (50%), compared to the surgeon, who correctly interpreted 29 of 38 MRIs (76.3%).Interpretations of shoulder MRIs in patients with adhesive capsulitis may provide misleading information regarding rotator cuff pathology. The actual findings of shoulder MRI scans may lead to the appearance of false rotator cuff pathology in this population, and a high percentage of false positive MRI reports of rotator cuff tears was observed in these patients. If MRI is chosen as a diagnostic adjunct in this patient population, careful consideration should be given to its interpretation to avoid unnecessary or possibly aggravating surgical intervention.