Cecily Quinn

A pathologic assessment of adequate margin status in breast-conserving therapy

BackgroundThe definition of a clear margin in breast-conserving therapy is uncertain. The purpose of this study was to correlate the tumor-margin distance of the excision specimen with the presence of residual tumor at reoperation. We also analyzed predictors of compromised margins and of residual disease.MethodsAll patients who underwent breast-conserving therapy for invasive disease from 1999 to 2003 were reviewed. Pathologic characteristics and the precise tumor distance from the radial margin were recorded. A radial margin was compromised if invasive or (ductal) in situ carcinoma was <5 mm from the margin.ResultsOf the 612 patients who underwent breast conservation, 211 (34%) had compromised margins, and 39 had undetermined margins. Of the 161 patients who had a reoperation for compromised margins, 87 (54%) had residual disease. Residual disease after reoperation was present in 58% (56 of 96), 56% (9 of 16), and 45% (22 of 49) of those with tumor-margin distances <1 mm, ≥1 and <2 mm, and ≥2 and <5 mm, respectively. There was a progressive decline in residual disease for each millimeter until a rate of 22% for tumor-margin distances of ≥4 mm and <5 mm was reached. Pathologic size (P = .004), an extensive intraductal component (P = .002), referral from a symptomatic rather than a population-based screening program (P = .02), and the absence of a preoperative diagnosis by core biopsy (P < .0001) were predictive of compromised margins. Only young age (<45 years) was predictive of finding residual disease on reoperation (P = .02).ConclusionsA total of 45% of patients who had tumor 2 to 5 mm from the radial margin had residual disease on reoperation. Our results support a policy of requiring a 5-mm margin in patients undergoing breast-conserving therapy for invasive disease.The definition of a clear margin in breast-conserving therapy is uncertain. The purpose of this study was to correlate the tumor-margin distance of the excision specimen with the presence of residual tumor at reoperation. We also analyzed predictors of compromised margins and of residual disease. All patients who underwent breast-conserving therapy for invasive disease from 1999 to 2003 were reviewed. Pathologic characteristics and the precise tumor distance from the radial margin were recorded. A radial margin was compromised if invasive or (ductal) in situ carcinoma was <5 mm from the margin. Of the 612 patients who underwent breast conservation, 211 (34%) had compromised margins, and 39 had undetermined margins. Of the 161 patients who had a reoperation for compromised margins, 87 (54%) had residual disease. Residual disease after reoperation was present in 58% (56 of 96), 56% (9 of 16), and 45% (22 of 49) of those with tumor-margin distances <1 mm, ≥1 and <2 mm, and ≥2 and <5 mm, respectively. There was a progressive decline in residual disease for each millimeter until a rate of 22% for tumor-margin distances of ≥4 mm and <5 mm was reached. Pathologic size (P = .004), an extensive intraductal component (P = .002), referral from a symptomatic rather than a population-based screening program (P = .02), and the absence of a preoperative diagnosis by core biopsy (P < .0001) were predictive of compromised margins. Only young age (<45 years) was predictive of finding residual disease on reoperation (P = .02). A total of 45% of patients who had tumor 2 to 5 mm from the radial margin had residual disease on reoperation. Our results support a policy of requiring a 5-mm margin in patients undergoing breast-conserving therapy for invasive disease.

The accuracy of ultrasound, stereotactic, and clinical core biopsies in the diagnosis of breast cancer, with an analysis of false-negative cases.

Objective:Preoperative core biopsy in breast cancer is becoming the standard of care. The aim of this study was to analyze the various methods of core biopsy with respect to diagnostic accuracy and to examine the management and outcome of those patients with false-negative biopsies. Methods:All patients undergoing core biopsy for breast abnormalities over a 5-year period (1999–2003) were reviewed. The accuracy rates for each method of core biopsy, the histologic agreement between the core pathology and subsequent excision pathology, and the length of follow-up for cases of benign disease were studied. Patients whose biopsies were benign but who were subsequently diagnosed with cancer underwent detailed review. Results:There were 2427 core biopsies performed over the 5-year period, resulting in a final diagnosis of cancer in 1384 patients, benign disease in 954 patients, and atypical disease in 89 patients. Biopsy type consisted of 1279 ultrasound-guided cores, 739 clinically guided cores, and 409 stereotactic-guided cores. The overall false-negative rate was 6.1%, with specific rates for ultrasound-, clinical-, and stereotactic-guided cores of 1.7%, 13%, and 8.9%, respectively. False-negative biopsies occurred in 85 patients, and in 8 of these patients the diagnosis was delayed by greater than 2 months. In all other false-negative cases, “triple assessment” review allowed prompt recognition of discordant biopsy results and further evaluation. Conclusion:Ultrasound guidance should be used to perform core biopsies in evaluating all breast abnormalities visible on ultrasound. Adherence to principles of triple assessment following biopsy allows for early recognition of the majority of false-negative cases.

Impact of a national external quality assessment scheme for breast pathology in the UK

Background: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. Aims/Methods: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using κ statistics. Results: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high—this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit—this included histological grading; (3) where consistency could be improved but only by changing the system of classification—this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved—this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. Conclusions: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

Angiogenesis, thrombospondin, and ductal carcinoma in situ of the breast

Angiogenesis, the growth of new vessels from existing vasculature, plays an essential role in tumour development. The process involves interaction between a variety of cells, growth factors, and components of the extracellular matrix, regulated by pro-angiogenic and anti-angiogenic factors. This review profiles these factors, outlines the available methods for measuring new vessel formation, and discusses the importance of angiogenesis in breast cancer, with emphasis on ductal carcinoma in situ.

c‐erbB‐3 protein expression in human breast cancer: comparison with other tumour variables and survival

c‐erbB‐3 protein expression was investigated immunohistochemically in a series of 97 malignant breast tumours using the monoclonal antibody RTJ1. Twenty‐eight cases (28.8%) showed c‐erbB‐3 overexpression, 31 cases (32%) showed normal levels of c‐erbB‐3 and 38 cases (39.2%) were c‐erbB‐3 negative. c‐erbB‐3 overexpression was positively but not significantly related to negative lymph node status and survival over a 10‐year follow‐up period.

Factors affecting metastases to non-sentinel lymph nodes in breast cancer.

Aims: Because sentinel lymph node (SLN) biopsy for breast cancer has become well established, one of the challenges now is to determine which patients require a completion axillary dissection following a positive SLN biopsy. Methods: A prospective database of patients who underwent SLN biopsy for invasive breast cancer from July 1999 to November 2002 (n  =  180) was analysed. Fifty four patients (30%) had one or more positive SLN, and all underwent a completion axillary dissection. This subgroup was further analysed to delineate which factors predicted non-SLN metastasis. Results: Twenty six of the 54 patients with a positive SLN had additional metastases in non-SLNs. Significant variables that predicted non-SLN metastasis included extranodal extension (odds ratio (OR), 17.399; 95% confidence interval (CI), 1.69 to 178.96) and macrometastasis within the SLN (OR, 6.985; 95% CI, 1.291 to 37.785). Conclusions: In patients with invasive breast cancer and a positive SLN, extranodal extension or macrometastasis within the SLN were both independent predictors of non-SLN involvement.

Radial scars/complex sclerosing lesions and malignancy in a screening programme : incidence and histological features revisited

Aims:  Radial scars (RS) are benign entities, frequently identified on screening mammography, which may be associated with malignancy. Much debate has been generated with regard to the optimum management of RS. We present our experience of RS in the first 5 years of a screening programme. The aim was to evaluate (i) the incidence of atypia and malignancy and (ii) the value of the preoperative core biopsy. We also further characterize the histological features.

Columnar cell lesions of the breast

Columnar cell lesions of the breast comprise a group of conditions characterized by dilation of terminal duct lobular units lined by columnar epithelial cells, ranging from one or two layers of benign epithelium to stratified epithelium with atypia. Although these lesions have been recognized by pathologists for many years, they have recently assumed a new significance due to their increased detection as mammographic calcification, the potential for overdiagnosis as ductal carcinoma in situ (DCIS) and their possible relationship to invasive carcinoma. This short overview aims to outline the pathological features and likely clinical significance of these lesions, with emphasis on diagnostic criteria, terminology and classification, and management strategies.

Correlation of needle core biopsy with excision histology in screen-detected B3 lesions: the Merrion Breast Screening Unit experience

Aims: Needle core biopsy (NCB) is a widely-used technique for non-operative evaluation of screen-detected breast lesions. Although most NCBs are B2 (benign) or B5 (malignant), some fall into the B3 category of “uncertain malignant potential”. This study aims to categorise the lesions prompting a B3 NCB in the Merrion Breast Screening Unit, and establish the incidence of malignancy on subsequent excision biopsy. Methods: Patients attending the Merrion Breast Screening Unit in Dublin between 2000 and 2008 who had a B3 NCB were identified. The NCB pathology reports were reviewed and the diagnosis correlated with excision histology; the latter was classified as benign, atypical or malignant. Lesion-specific positive predictive values (PPVs) for malignancy were derived. Results: 141 patients with a B3 NCB were identified. The most frequent lesions on NCB were radial scar (RS; n = 57), atypical intraductal epithelial proliferation (AIDEP; n = 25) and papillary lesion (n = 24). The final diagnosis was malignant in 22 patients (16%), atypical in 40 (28%) and benign in 79 (56%). Two of the patients with a malignant diagnosis had invasive carcinoma. The lesion-specific PPVs were: lobular neoplasia 50%, AIDEP 32%, columnar cell lesion with atypia 12.5%, RS 12.3%, papillary lesion 8.3%, suspected phyllodes tumour 7.7%, and spindle cell lesion 0%. Atypia on RS NCB predicted an atypical or malignant excision diagnosis, but atypia on papillary lesion NCB did not. Conclusions: One-sixth of B3 NCBs in this series proved to be malignant on excision. The PPV for malignancy varied according to lesion type.

Thrombospondin 1 protein expression relates to good prognostic indices in ductal carcinoma in situ of the breast

Aim: Angiogenesis plays an important role in tumour growth and has been shown to occur around both in situ and invasive tumours. The degree of angiogenesis within tumours depends on the balance of pro-angiogenic and anti-angiogenic factors. One such anti-angiogenic factor is thrombospondin 1 (TSP-1). This study investigates the pattern of expression of TSP-1 in ductal carcinoma in situ (DCIS) of the breast and its relation to the surrounding microvessel pattern and density. Materials/Methods: The expression of TSP-1 was studied in formalin fixed, paraffin wax embedded sections from 58 cases of pure DCIS, using a monoclonal antibody against TSP-1 and the avidin–biotin–diaminobenzidine immunoperoxidase detection system. Vessels were stained with a monoclonal antibody to the endothelial cell marker CD31. Stromal microvessel density was assessed by counting “hot spots” within 500 μm of the basement membrane of involved ducts using a 25 point Chalkey graticule. Results: TSP-1 staining of the basement membrane around duct spaces with DCIS was seen in 69% of cases. In addition, staining of the stroma between involved duct spaces was seen in 31% of cases, with a fibrillary pattern identical to that seen in invasive breast carcinomas. In 12% of cases no staining for TSP-1 was seen. Two patterns of vascularity were identified. A cuff of vessels immediately adjacent to the basement membrane of ducts with DCIS was seen in 71% of cases. The presence of stromal TSP-1 was significantly associated with DCIS showing no/little necrosis (p = 0.01) and no/little periductal inflammation (p = 0.04). There was a trend between the presence of stromal TSP-1 and tumour cell negativity for p53 (p = 0.087). The stromal microvessel Chalkey point count ranged between 3.33 and 16. An increased stromal microvessel count was associated with high histological grade (p = 0.02), extensive necrosis (p = 0.047), and pronounced periductal inflammation (p = 0.049). There was no association between the presence of stromal TSP-1 and stromal microvessel density. Conclusions: TSP-1 is expressed in the stroma around DCIS and in the immediately adjacent basement membrane. Expression of stromal TSP-1 is lost in DCIS with more aggressive histological features. The absence of a relation with microvessel density suggests that other angiogenic factors may play an important role in DCIS.