Aim: The aim of the present study was to evaluate the risk of axillary non-sentinel lymph-node metastases (ALN) in breast cancer patients presenting macrometastasis (Mac-m) in the sentinel lymph node (SN).Materials and methods: A retrospective series of 1464 breast cancers from patients who underwent ALN dissection following the diagnosis of Mac-m in the sentinel node (SN) was studied. In all the cases the MAC-m linear size was evaluated and correlated with presence or absence of non-SN ALN metastases.Results: Non-SN metastases were detected in 644 \ 1464 cases (43.98%). The risk of further axillary metastases ranged from 20.2% (37/183) in cases with Mac-m between 2 and 2.9 mm, to 65.3% (262/401) in cases with Mac-m measuring > 10 mm. The risk of non-SN ALN metastases showed a 3% increase, parallel to each mm increment in SN metastasis size. The data evaluated with the receiver operating characteristic (ROC) curve showed that the Mac-m could be subdivided according to a new cut-off of 7 mm. pT1 tumours, with Mac-m < 7 mm had a risk of non-SN ALN metastases of <30%. Furthermore 109/127 of these (85.8%) had 3 or less non-SN ALN-metastases.Conclusions: The present data give a detailed description on the risk of non-SN ALN involvement, that may be useful in the evaluation of breast cancer patients. It is suggested that a Mac-m size of <7 mm is related to a low residual axillary disease burden in breast cancer patients with small (pT1) tumours. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100% agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.

Aim: The aim of the study was to identify if radiotherapy can be safely avoided in a selected subgroup of largely screening detected small invasive breast cancer.Methods: One hundred and eighty-eight patients with node negative invasive early breast cancer <= 1 cm (<= T1b) treated in our centre between 1990 and 2004 were retrospectively followed for local, regional and distant recurrences. Treatment involved adequate local excision by breast conserving surgery (BCS). Axillary staging was performed by a four node axillary sampling until 2000, following which sentinel lymph node sampling was employed. All sections were assessed histologically by haematoxylin and eosin stained sections. The inked margins were reported as being involved, close and clear. Radiotherapy (RT) was employed only if the resected margins were inadequate, and in those with involved axillary nodes who refused further completion axillary clearance.Results: Ninety-four patients (Group A) had BCS alone and 79 patients (Group 13) had both BCS and RT. There was no ipsilateral breast tumour recurrence (IBTR) in 88 patients in Group A, corresponding to an actuarial freedom from IBTR of 96%, 91% and 88.1% at 5 years, 8 years and 9 years. In Group B, there was no IBTR in 75 patients corresponding to an actuarial freedom from IBTR of 97%, 94.9% and 90.6% at 5 years, 8 years and 10 years.Conclusion: Our experience over 14 years has shown that it is possible to safely avoid radiotherapy in a selected subgroup of small invasive breast cancer. (C) 2007 Elsevier Ltd. All rights reserved.

Apocrine metaplasia is a very common finding in the female breast after the age of 25. It is so common that many people regard it as a normal component of the breast. This, however, is only really the case in apocrine sweat glands of the axilla and in the peri-areolar apocrine glands. The apocrine cell does, however, contribute to a number of different breast lesions, some of which are very taxing diagnostically; apocrine variants of both in-situ and invasive cancer are encountered. This review considers the common apocrine metaplastic lesions seen in fibrocystic change as well as apocrine adenoma, apocrine change within sclerosing adenosis, atypical apocrine lesions and apocrine malignancies.

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.

AIM:The study compared the accuracy and success rate of two techniques, methylene blue alone versus combined methylene blue and radioactive colloid in sentinel lymph node localisation in the management early breast cancer. METHODS:Three hundred and twenty-nine patients with tumours less than 2 cm on ultrasound assessment were prospectively evaluated. One hundred and seventy-three patients (Group A) underwent sentinel lymph node localisation using 1 ml of 1% methylene blue. A combined technique of both methylene blue and radioactive colloid was used in 156 patients (Group B). Application of both was subdermal and subareolar. Sentinel lymph nodes were examined by standard microscopy. Patients underwent breast conservation surgery or mastectomy and sentinel node guided four node axillary sampling+/-clearance. RESULTS:In Group A, the sentinel lymph node identification rate was 96.5%. The negative predictive value was 96.3%, with false negative of 3.7% and accuracy of 87.4%. In group B the identification rate for sentinel lymph node was 98.7%, with false negative of 4.1%, negative predictive value of 96%, and accuracy of 83.8%. CONCLUSION:Sentinel lymph node localisation using methylene blue or combined dye and radioactive tracer technique predicts the axillary lymph node status in early breast cancer with comparable success rates, accuracy and false negative rates. The combined technique facilitates quicker identification of sentinel lymph node; however the dye technique alone can be used successfully in centres without nuclear medicine facilities.

Aims: Apocrine adenosis (AA) is generally considered a benign disease of the breast. However, recent studies have suggested a precancerous potential for some of these lesions. The aim was to investigate the status of cell cycle proteins previously reported to be deregulated in breast cancer to identify their possible role in AA. Methods and results: The cases were categorized into AA without atypia (NAA) and atypical AA (AAA). Using immunohistochemistry, the expression of cyclin D1, cyclin A, p27, p21, p16, pRb and Ki67 was determined in 29 NAA and 16 AAA cases. Cyclin D1, p21 and cyclin A were overexpressed in 58.6%, 51.7% and 31.8% of the NAA cases, respectively, whereas 81.3%, 62.5% and 41.7% of the AAA cases showed overexpression of cyclin D1, p21 and cyclin A, respectively. All cases were negative for p16, whereas pRb was expressed in all cases. Furthermore, proliferation in AA (4.5%) was significantly higher than that of normal breast epithelium (1%). There was no statistical significance in the degree of proliferation between the NAA (3.7%) and AAA (4.8%) groups. Conclusions: The study indicates that NAA and AAA are biologically similar. A subset of AA defined by increased proliferation and significant cell cycle alterations may be susceptible to oncogenesis.

BACKGROUND. The latest edition of the tumor-lymph node-metastasis (TNM) classification of malignant tumors distinguishes between isolated tumor cells (pN0) and micrometastases (pN1mi). The reproducibility of these categories has not been assessed previously.METHODS. Digital images from 50 cases with low-volume lymph node involvement from axillary sentinel lymph nodes were circulated twice for evaluation (Evaluation Rounds 1 and 2) among the members of the European Working Group for Breast Screening Pathology, and the members were asked to categorize lesions as micrometastasis, isolated tumor cells, or something else and to classify each case into a pathologic lymph node (pN) category of the pathologic TNM system. Methods for improving the low reproducibility of the categorizations were discussed between the two evaluation rounds. K Statistics were used for the assessment of interobserver variability.RESULTS. The K value for the consistency of categorizing low-volume lymph node load into micro metastasis, isolated tumor cells, or neither of those changed from 0.39 to 0.49 between Evaluation Rounds 1 and 2, but it was slightly lower for the pN categories (0.35 and 0.44, respectively). Interpretation of the definitions of isolated tumor cells (especially with respect to their localization within the lymph node), lack of guidance on how to measure them if they were multiple, and lack of any definitions for multiple simultaneous foci of lymph node involvement were listed among the causes of discordant diagnoses.CONCLUSIONS. The results of the current study indicated that the definitions available have minor contradictions and do not permit a reproducible distinction between micrometastases and isolated tumor cells. Refinement of these definitions, therefore, is required. One refinement that may improve reproducibility is suggested in this report. (C) 2004 American Cancer Society.

Aims: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. Methods: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. Results: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. Conclusions: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Non-operative diagnosis has become the norm in breast disease assessment and, until relatively recently, fine needle aspiration cytology has been the sampling method of choice. The introduction of automated core biopsy guns in the mid 1990s led to the additional introduction of core biopsy in assessment units. This paper presents a summary of the guidance on handling and routine reporting of breast needle core biopsy specimens in the context of breast disease multidisciplinary assessment. This guidance has been produced by the UK National Coordinating Committee for Breast Screening Pathology and is endorsed by the European Commission working group on breast screening pathology.

Non-operative diagnosis has become the norm in breast disease assessment and, until relatively recently, fine needle aspiration cytology has been the sampling method of choice. The introduction of automated core biopsy guns in the mid 1990s led to the additional introduction of core biopsy in assessment units. This paper presents a summary of the guidance on handling and routine reporting of breast needle core biopsy specimens in the context of breast disease multidisciplinary assessment. This guidance has been produced by the UK National Coordinating Committee for Breast Screening Pathology and is endorsed by the European Commission working group on breast screening pathology.

Non-operative diagnosis has become the norm in breast disease assessment and, until relatively recently, fine needle aspiration cytology has been the sampling method of choice. The introduction of automated core biopsy guns in the mid 1990s led to the additional introduction of core biopsy in assessment units. This paper presents a summary of the guidance on handling and routine reporting of breast needle core biopsy specimens in the context of breast disease multidisciplinary assessment. This guidance has been produced by the UK National Coordinating Committee for Breast Screening Pathology and is endorsed by the European Commission working group on breast screening pathology.

Background. Integrin cell adhesion molecules are fundamental to numerous cellular functions including anchorage, differentiation and proliferation. Reduced expression of certain alpha and beta integrin subunits in primary breast cancer cells has been correlated with increased invasion and metastasis. Conversely, over-expression of the alpha(6) subunit has been linked to poorer survival. The objective of this study was to measure the survival of a cohort with breast carcinoma in relation to integrin expression and to evaluate their potential as prognostic indicators.Method. Integrin expression on samples from 99 consecutive patients with breast cancer was assayed using monoclonal antibodies to the subunits alpha(1,2,3,6,v) and beta(1,3,4,5). This cohort has now been followed prospectively for almost five years allowing for early assessment of survival in relation to integrin expression.Results. Whilst analysis of the data confirmed the relation of survival to proven predictors of tumour grade, tumour size and vascular invasion, statistical significance was not demonstrated with regard to both lymph node status and all integrin subunits studied.Conclusion. Previous research correlating certain integrin subunits with survival has not been confirmed in this study. Despite proven molecular importance in tumour cell adhesion, invasion and metastasis, integrin expression would appear not to translate clinically as independent indicators of prognosis, at least in the short-term. (C) 2004 Elsevier Ltd. All rights reserved.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

CytopathologyVolume 14, Issue 1 p. 38-39 Fine needle aspiration from the upper arm in a postmastectomy patient S. Pomplun, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorN. Singh, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorP. N. Plowman, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorC. A. Wells, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this author S. Pomplun, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorN. Singh, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorP. N. Plowman, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this authorC. A. Wells, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London, UKSearch for more papers by this author First published: 17 March 2003 https://doi.org/10.1046/j.1365-2303.2003.11142.xCitations: 1 N. Singh, Department of Histopathology, St Bartholomew's Hospital, West Smithfield, London EC1 7BE, UK Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Citing Literature Volume14, Issue1February 2003Pages 38-39 RelatedInformation

Inadequate rates (IR) in FNAC from different sources were compared. The rates were lowest when FNAC was performed by a cytopathologist (12%) and highest when done by a non‐cytopathologist (32%). These differences were mirrored in high IRs in breast cancer cases. IR was not significantly improved when non‐cytopathologist FNAC was attended by a cytotechnician.

Loss of heterozygosity (LOH) and allelic imbalance (AI) at loci reported to show allele loss and/or imbalance in preinvasive and invasive breast cancer were examined in 41 cases of apocrine metaplasia (APM) of the breast using a microdissection technique, polymorphic microsatellite markers, and the polymerase chain reaction (PCR). Occasional examples of LOH and/or AI were identified in 2/28 (7.1%) informative cases at 1p (MYCL1), 2/14 (14.3%) at 11q (INT2), 1/15 (6.7%) at 13q (D13S267), 3/22 (13.6%) at 16q (D16S539), 2/23 (8.7%) at 17p (TP53), and 1/11 (9.1%) at 17p (D17S513) and 3/16 (18.8%) at 17q (D17S250). The finding of LOH/AI in cases of APM indicates that a subset of APM appears clonal, but the significance of allelic loss or imbalance in the pathogenesis of APM or its possible subsequent progression to carcinoma is not yet clear and requires further investigation. Clinical follow-up of these particular cases of APM showing LOH/AI would be of further value.

In early breast cancer axillary nodes are usually impalpable and over 50% of such patients may have an axillary clearance when no nodes are involved. This work identifies axillary node status by imaging with a Tc-99m radiolabelled anti-Polymorphic Epithelial Mucin, humanised monoclonal antibody (human milk fat globule 1), prior to surgery in 30 patients. Change detection analysis of image data with probability mapping is undertaken. A specificity of 93% and positive predictive value of 92% (both 100% if a second cancer in the axilla with negative nodes is considered) were found. A strategy for combining negative imaging with the sentinel node procedure is presented.