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Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed., (© 2024 John Wiley & Sons Ltd.)

Aims: Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH., Methods and Results: Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences., Conclusions: Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours., (© 2023 John Wiley & Sons Ltd.)

Aims: Breast hamartomas are an under-recognised lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude 'no significant lesion' or 'normal breast tissue', leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas with the aim of identifying specific signs to facilitate their diagnosis and to differentiate them from normal breast and fibroepithelial lesions., Methods and Results: Forty-seven breast hamartomas were reassessed (histological diagnosis and imaging features). An immunohistochemical study [oestrogen receptor (ER), progesterone receptor (PR), CD34, high-mobility group A2 (HMGA2)] was performed. On breast imaging, hamartomas most often presented as probably benign solid masses with circumscribed margins and variable densities. Histologically, breast hamartomas resembled normal breast, although their stromal component was predominant, separating randomly scattered epithelial elements with areas of pure collagenous stroma. Pseudoangiomatous stromal hyperplasia (PASH) was present in 93.6% of cases and CD34 antibody highlighted intralobular, perilobular and interlobular distribution of CD34-positive fibroblasts. By comparison, CD34 was mainly expressed in the intralobular normal breast tissue stroma. Hamartoma stromal cells expressed HMGA2, ER and PR in 79%, 66% and 76.3% of our cases, respectively, compared to 7.7%, 23% and 19% in normal breast tissue, respectively (P < 0.0001; P = 0.0005; P < 0.0001)., Conclusions: After ascertaining that core needle biopsy is effectively intralesional, breast hamartomas can be diagnosed with confidence by taking into account the presence of stromal changes, PASH, interlobular distribution of CD34-positive fibroblasts, HMGA2 and hormonal receptor stromal expression., (© 2021 John Wiley & Sons Ltd.)

Aims: Mammary amyloid is an uncommon and easily overlooked pathological diagnosis with ambivalent presentation. Herein, we delineate the clinicopathological and radiographic characteristics of mammary amyloid., Methods and Results: The Department of Pathology database was searched from 1993 to 2019 for keywords 'breast' and 'amyloid', yielding 32 cases from 23 patients, including consultation cases. All patients were female, age range = 52-81 (mean = 67.4 years). The left breast was involved more than the right (43 versus 33%, respectively); bilateral amyloid involvement was also present (24%). Amyloid was most often associated with a benign histopathological diagnosis (57%), lymphoma in 39% [all B cell lymphomas; five of nine were mucosa-associated lymphoid tissue (MALT) lymphoma] and rarely with a concurrent epithelial malignancy (invasive lobular carcinoma, 4%). Of the 14 patients with available clinical history, amyloid presented as a mass clinically or radiographically (six patients, 43%), as microcalcifications (five patients, 36%), and only occasionally as an asymmetry (14%) or fibroglandular density (7%). Microscopic examination detected microcalcifications in an additional nine cases (total 14 patients; 44% of the cohort). Interestingly, one patient had concurrent epithelial and haematological malignancy and amyloid within an axillary lymph node. Co-morbidities included autoimmune diseases and multiple myeloma., Conclusion: The majority of mammary amyloid cases are associated with benign histopathological findings, while imaging most frequently noted microcalcifications or mass lesions. To avoid overlooking amyloid as simply fat necrosis or fibroelastotic stromal change, a low threshold for performing ancillary stains should be considered in elderly women with benign core needle findings performed for mass lesions or microcalcifications., (© 2021 John Wiley & Sons Ltd.)

Iatrogenic changes within the breast can provide challenges for the histopathologist in routine practice. Diagnostic procedures, such as core biopsies, result in reactive changes and can cause displacement of benign and malignant cells, the interpretation of which may cause difficulties in the resection specimen. Breast augmentation surgery with implants or injection of fillers, performed for cosmetic reasons or as part of a reconstructive process following removal of breast cancer, also produces reactive changes locally and at distant sites that may mimic cancer. The entity of implant-associated anaplastic large-cell lymphoma is now well recognized, with progress in our understanding of the underlying biological factors that drive its development. Chemotherapy and radiotherapy used in the treatment of breast cancer causes characteristic changes in normal breast tissue, and can alter the histological appearance and receptor status of the tumour. Radiotherapy to the breast, for breast cancer or childhood malignancies, increases the risk of developing a secondary malignancy in the breast long after treatment. In this review, we describe some of the iatrogenic changes that may be seen in histological specimens from the breast., (© 2016 John Wiley & Sons Ltd.)

Aims: Because of the introduction of mammography screening programmes in Europe, the number of breast biopsies performed is increasing. We investigated the influence of immunohistochemistry (IHC) on the final diagnosis of breast biopsies by comparing the primary diagnoses (based on the results of haematoxylin and eosin staining only) with the final diagnoses (based on the additional information provided by IHC)., Methods and Results: We analysed the breast biopsies which were performed at the University of Halle-Wittenberg between 2006 and 2010 and for which the pathologist requested IHC for making the final diagnosis. According to the B-categorization scheme, the primary diagnosis changed in 37 of a total of 429 biopsies (8.6%). In 18 of these biopsies (48.6%) the category changed from B1-B2 to B3-B5 or vice versa, which would imply a different work-up. Only 77% of the primary diagnoses of breast cancer in situ were confirmed., Conclusion: IHC has a considerable influence on the final diagnosis of breast biopsies in several situations, including those in which the biopsied women are at risk of inadequate therapeutic intervention. The influence is particularly notable among those biopsies for which IHC is performed in order to assess the suspicion of breast cancer in situ., (© 2013 John Wiley & Sons Ltd.)

Aims: To provide updated evidence of the outcome of breast lesions of uncertain malignant potential (B3) and suspicious of malignancy (B4) diagnosed on needle core biopsy (NCB) and analyse the outcome of the different types of intraductal epithelial atypia., Methods and Results: One-hundred and forty-nine B3 and 26 B4 NCBs diagnosed over a 2-year period (2007-2008) were compared with those diagnosed over a previous 2-year period (1998-2000). The proportion of B3 diagnoses increased from 3.1% to 4.5%, and the positive predictive value (PPV) of malignancy of a B3 core decreased from 25% to 10%. Increased diagnosis of radial scar and reductions in the PPV of lobular neoplasia and of atypical intraductal proliferation may explain the reduction in the PPV of the B3 group as a whole. There were no significant changes in the proportion of B4 diagnosis (1.1% and 0.8%) or the PPV of B4 (83% and 88%). Review of cores with intraductal atypia showed a wide range of PPVs, from 100% for suspicious of ductal carcinoma in situ, to 40% for atypical ductal hyperplasia categorized as B3, and 14% for isolated flat epithelial atypia., Conclusion: The study has found a decrease in the PPV for a B3 diagnosis and suggests possible explanations., (© 2011 Blackwell Publishing Limited.)

Aims: To conduct an internet-based study using virtual slides (VS) of sterotactic core biopsy specimens of non-palpable breast lesions in order to evaluate interobserver reproducibility between pathologists., Methods and Results: A total of 18 breast lesions, determined to be histologically complex by two pathologists, were selected. Digitized VSs were then created using QuickTime Virtual Reality technology (Apple, Cupertino, CA, USA) and posted on the world-wide web. In all, 10 pathologists completed the evaluations of 18 VSs using the five diagnostic categories (B1-B5) from the European guidelines for quality assurance in breast cancer screening and diagnosis. Their results were compared with those of every other participating pathologist, and were then individually compared with the results of a highly experienced breast pathologist (referee). Of the 18 cases, 10 (56%) were classified by the referee as borderline (B3 and B4). Comparisons with reference values showed a less than satisfactory level of reproducibility (median kappa(w) = 0.60). As regards interobserver reproducibility, results showed that, in general, the level of agreement was not satisfactory (median kappa(w) = 0.53)., Conclusions: Overall, the findings are comparable to those quality control studies using circulating slides when analysis is done on borderline cases.

Aims: To document the spectrum of lesions associated with mucin extravasation (ME) in breast core biopsy specimens, and to correlate with open surgical excisions., Methods and Results: Thirty-nine lesions in 37 women with ME on core biopsies constituted the study group. Fibrocystic change (FC), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were found in 21 (53.8%), 13 (33.3%) and four (10.3%) core biopsy specimens, respectively, with one (2.6%) consisting only of mucin pools. Except for the latter, all disclosed mucocoele-like lesions (MLL) accompanying ME. Columnar cell lesions (CCL) were frequently observed (84.6%). On open biopsy, three cases underdiagnosed on core biopsy included FC that later disclosed ADH; one ADH lesion on core later upgraded to DCIS; and a case of mucin pools that revealed mucinous carcinoma on excision. The extent of CCL on core biopsy appeared to predict sinister lesions on open excision. For calcified lesions that were completely removed on core biopsy, there were no malignant lesions discovered on open excision that had not already been diagnosed preoperatively., Conclusions: ME and MLL on core biopsy warrant close radiological-pathological correlation. When the entire radiological abnormality has been removed with large core mammotome biopsy specimens, surgery may potentially be avoided in histologically benign lesions, although such an approach requires further validation.

Objective: To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine needle aspiration cytology (FNAC) for the diagnosis of non-palpable breast lesions., Patients and Methods: From January 2002 to December 2004, 470 women with 478 mammographically detected non-palpable breast lesions had US or stereotactically guided FNAC of the breast lesion. Subsequent histological evaluation of the same lesion was performed at the Institute of Oncology Ljubljana, Slovenia. The correlation between the original cytological and histological diagnosis was assessed and the sensitivity, specificity, positive predictive value and negative predictive value were calculated., Results: Among US-guided FNACs, 144 (53.5%) were histologically verified benign lesions and 125 (46.5%) were carcinomas. Cytological diagnoses were: true positive (TP) in 63 cases (50.4%), suspicious in 35 (28%), false negative (FN) in eight (6.4%), and in 19 (15.2%) cases, the material was inadequate for diagnosis. In the stereotactically guided FNAC group, there were 209 women with 209 lesions, with 95 (45%) histologically proven carcinomas and 114 (55%) benign lesions. Cytological diagnoses were TP in 49 (51.6%) cases, true suspicious in 21 (22.1%), FN in nine (9.5%), and in 16 (16.8%) cases, the material was not adequate for the diagnosis., Conclusion: The sensitivity of 88.7% and specificity of 98.6% for US-guided FNAC and 84.5% and 100% for stereotactically guided FNAC, respectively, suggest that clinicians can rely upon cytological diagnosis for planning further management of women with non-palpable breast lesions.

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image-guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1-C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER-2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence-based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

Objective: Imprint cytology provides a rapid preliminary diagnosis shortly after the completion of breast biopsy. This study aims to assess the validity of imprint cytology for the pre-operative diagnosis of non-palpable mammographic solid lesions excised by vacuum-assisted breast biopsy (VABB)., Methods: Seventy-two women with non-palpable Breast Imaging Reporting and Data System 3 and 4 mammographic solid lesions without microcalcifications underwent VABB on the stereotactic Fischer's table with 11-G Mammotome vacuum probes. Imprint samples were examined (Diff-Quick stain, modified Papanicolaou stain and May-Grünwald-Giemsa). The cores were dipped into a CytoRich Red Collection fluid for a few seconds in order to obtain samples with the use of the specimen wash. After the completion of cytological procedures, the core was prepared for routine pathological study. The pathologist was blind to the preliminary cytological results. The cytological and pathological diagnoses were comparatively evaluated., Results: The sensitivity of the cytological imprints for cancer was 90%. The specificity of the method for cancer diagnosis was 100%. Two precursor lesions were present in the material: one case of atypical ductal hyperplasia, which was successfully detected, and one case of lobular neoplasia, which escaped detection. The cytological imprints were inadequate in four out of 72 cases (5.6%), but none of them were included within the malignant subgroup., Conclusions: Imprint cytology seems to be an important adjunctive tool in the management of patients with non-palpable mammographic solid lesions. Its very satisfactory sensitivity and optimal specificity could establish its use in general clinical practice.

Aims: Recent studies have suggested that benign papillary lesions without atypia [benign papilloma (BP)] diagnosed on breast core needle biopsy (CNB) may not require excision. However, most have studied only small numbers of cases and scant data are available on the utility of immunohistochemistry in the categorization of papillary lesions on CNB. In the largest published series of BP identified on CNB, we studied the impact of immunohistochemistry on the accuracy of a CNB diagnosis of BP., Methods and Results: Breast CNBs (n = 129) with a diagnosis of papillary lesion were immunostained for calponin, p63 and cytokeratin 5/6. Haematoxylin and eosin and immunostained slides were independently reviewed by four breast pathologists. BP was the final excision diagnosis in 35 cases. With the use of immunohistochemistry, the positive predictive value (PPV) of BP diagnosis by the four individual pathologists increased from 72.7-83.3% (mean 79.2%) to 77.8-87.5% (82.1%), the negative predictive value (NPV) increased from 77.8-98.5% (88.6%) to 100% for all four participants and overall accuracy increased from 78.7-92.6% (84.7%) to 90.7-95.4% (92.8%). No case of invasive carcinoma was diagnosed as BP on CNB by any participant. The frequency of ductal carcinoma in situ following a BP diagnosis on CNB ranged from 2.5% to 4.8% (4%) but was only 0-3% (2.3%) after excluding cases that were radiologically suspicious for malignancy., Conclusions: Immunohistochemistry increases accuracy of BP diagnosis in CNB specimens. Benign papillary lesions diagnosed on CNB do not require excision in the absence of suspicious clinical/radiological findings.

Considerable progress has been made in understanding breast lesions utilizing molecular methods, but conventional morphology, simple immunohistochemical stains and common sense still prevail in diagnosing the vast majority of breast disease. The focus of this review is to identify the most common breast lesions sent to our consultation practice, and to reiterate salient diagnostic features, differential diagnoses and common pitfalls in identifying these lesions. Separation of epithelial proliferative lesions and differentiation between usual epithelial hyperplasia (UEH) and atypical ductal hyperplasia (ADH) are the most common problems encountered in our Consultation practice. Differentiation between UEH and ADH is based on the assumption that ADH is a clonal process, recognized by a uniform phenotype and more recently described immunohistochemical markers such as differential cytokeratin and also hormone receptor expression. Difficulty in subtyping invasive carcinomas and exclusion of in situ and/or invasive carcinoma in a sclerosing lesion is also commonly noted. Finally, problems in distinguishing various papillary and fibroepithelial lesions are also encountered. The use of common immunohistochemical stains such as various cytokeratin and myoepithelial markers, E-cadherin and hormone receptors is helpful in solving most of these diagnostic dilemmas.

In this study a review of 1948 nipple discharge (ND) samples from 1530 patients in the age range of 18-83 years was undertaken to determine whether cytological findings from ND smears could provide useful diagnostic information regarding various breast lesions. The study included 1494 females and 36 males and was carried out during a period of 20 years 8 months. The clinical information in all patients was obtained from clinicians (coauthors), medical records and a review of biopsies in 205 patients who had undergone surgery following the cytodiagnosis. Of the ND samples examined, 1480 were unilateral while 468 were from 234 bilateral ND. The cytodiagnoses were: benign 624, inadequate (despite two to three repeat samples) 492, inflammatory 96, papillary lesion not otherwise specified (NOS) 229, suspicious 22 (21 females, one male) and malignant 67 (63 females, four males). A breast biopsy in the 22 suspicious cases revealed breast carcinoma in 18 cases (females n = 17, male n = 1), atypical ductal hyperplasia (female n = 1), fibroadenoma (female n = 1) and a papilloma in two females. In the 67 cases with a diagnosis of malignancy 65 revealed a breast carcinoma in the biopsy (female n = 62, male n = 3) while one female was diagnosed as fibroadenoma and one male as florid gynaecomastia. In 63 cases (females n = 61; males n = 2) with clinical lumpy areas consistent with the diagnosis of fibrocystic condition in ND, the biopsy confirmed a fibrocystic process. In 53 of 229 cases with ND findings suggestive of a papillary lesion (NOS) the biopsy revealed a papilloma in 41 cases while in 12 cases no lesion was found. In the remaining cases of all the groups only a clinical follow-up and appropriate investigations were performed with no untoward outcome. Based on our study it is felt that cytological examination of ND smears seems to be a reasonably specific method in the diagnosis of malignant and suspicious cases but may be somewhat less specific for other diagnoses.

Definitive immediate diagnosis in breast fine needle aspiration cytology (FNAC) remains the aim for cytopathologists. We reviewed 72 consecutive equivocal (C3 and C4) aspirates with respect to 16 cytomorphological criteria. We assessed the power of each criterion at predicting either a malignant [positive predictive value (PPV)] or a benign [negative predictive value (NPV)] diagnosis by correlation with follow-up histology. Blind review led to 34% of cases being correctly definitively diagnosed. Eccentrically placed epithelial cell nuclei (PPV = 88%, sensitivity = 67%, specificity = 87%) and coarse nuclear chromatin (PPV = 81%, sensitivity = 72%, specificity = 83%) are the features that are most useful in predicting malignancy in this selected series. The presence of myoepithelial cells within epithelial groups is not a good indicator of a benign diagnosis (NPV = 24%, sensitivity = 80%, specificity = 53%).

Mammary hamartoma is a breast lesion rarely reported by fine-needle aspiration cytology (FNAC). We report on our experience of FNAC in nine cases confirmed by biopsy. We searched hospital case files for mammary hamartoma or similar lesions (fibrolipomas, lipomas, fibromas, etc.), and cases included were only those in which both FNAC and a histopathological study had been performed. The cytological features that were analysed included epithelial components, mesenchymal fragments and isolated cells dispersed in the background. The patients ranged in age from 25 to 58 years (mean 40 years), and the lesions were predominantly in the right breast and upper outer quadrant. The duration varied from 1 to 20 years. Mammographic features were characteristic revealing well-circumscribed masses of heterogeneous radiodensity and by ultrasonography were hypoechoic without calcification. Grossly, these lesions were oval to round, well-demarcated masses, ranging in diameter from 10 to 80 mm. The tumours were firm, rubbery and white, consisting largely of dense fibroconnective tissue with variable amounts of adipose tissue and glandular elements. Cytological samples showed two components, epithelial and mesenchymal. The cellularity was variable and was composed of lobular cells forming acini, ductal cells, occasional apocrine and foamy cells; myoepithelial cells and isolated naked nuclei were also observed. Adipose tissue and dense fibrous tissue were observed, occasionally with epithelial cells attached, and this finding was an important feature for diagnosis. We considered that the cytological findings could help to diagnose mammary hamartoma, FNAC making a rapid and very important technique for the diagnosis of this pathology.

Aims: We investigated the origin of myoid cells in benign stromo-epithelial lesions of the breast in order to ascertain their myoepithelial or myofibroblastic origin., Methods and Results: We selected 22 stromo-epithelial lesions of the breast and reviewed their morphological features at haematoxylin-eosin (H&E) level. The lesions were classified as fibrous stromo-epithelial lesions (without evidence of myoid differentiation at H&E level) (13 cases), type 1 myoid stromo-epithelial lesions (myoid cells directly merging with the myoepithelial layer) (three cases), type 2 myoid stromo-epithelial lesions (bundles of myoid cells unrelated to the glands) (six cases). All cases were studied immunohistochemically and myoid stromo-epithelial lesions were also studied with electron microscopy. The myoid component in two out of three cases of type 1 myoid lesions showed immunohistochemically co-expression of smooth muscle and myoepithelial markers. In contrast, the remainder showed immunohistochemical results identical to those found in type 2 myoid lesions (positivity with SMA, desmin, calponin, CD34 and bcl2 and negativity with cytokeratin 14 and p63). Ultrastructural study confirmed the presence of cells with myoepithelial features in type 1 myoid lesions and of cells with myofibroblastic features in type 2 myoid lesions., Conclusions: Myoid cell differentiation is common in stromo-epithelial lesions of the breast, and is evident in H&E sections in up to 40% of cases. In addition, the origin of myoid cells is myofibroblastic in most cases, but in some cases, cells present immunohistochemical and ultrastructural evidence of myoepithelial origin.

Spontaneous or expressible nipple discharge may occur in palpable and nonpalpable breast lesions. The aim of the study was to evaluate the sensitivity and specificity of nipple discharge cytology in palpable and nonpalpable breast lesions. One hundred and seventy-four nipple discharge specimens were reviewed, of which 82 had corresponding surgical pathology, including 34 palpable breast lesions and 48 nonpalpable breast lesions. There was good correlation between nipple discharge cytology and concomitant fine needle aspiration (FNA) cytology. Nipple discharge cytology is as specific as concomitant FNA cytology but is slightly less sensitive in detecting papillomas or malignant lesions. The sensitivity and specificity of the nonpalpable and palpable breast lesions were similar. Nipple discharge cytology is very helpful in detecting an underlying breast lesion even if the case has no palpable mass in the breast.

Aims: The aim of our study was to investigate the clinical, pathological and immunohistochemical features of breast hamartomas, in order to obtain a detailed profile of this somewhat uncommon lesion., Methods and Results: This study presents a clinical, pathological and immunohistochemical analysis of 24 breast hamartomas. Four cases of fibrocystic breast changes were used as a control group. The immunohistochemical panel induced oestrogen (ER) and progesterone (PR) receptors, c-erbB-2 protein, p53, Ki67, CK-MNF116, and vimentin. The patients ranged in age from 30 to 78 years (mean 48 years). All patients presented with a palpable unilateral mass. Three patients showed two hamartomas in the same breast. Tumours ranged from 20 to 50 mm in diameter. Typical macroscopic and microscopic features were noted. Immunohistochemical studies showed ER and PR receptor positivity in epithelial cells as well as in the stromal cells in all 24 cases. No c-erbB-2 protein over-expression was noted. p53 expression was not observed. Ki67 showed 2-3% positivity in epithelial cells and not in stromal cells in most cases., Conclusions: There was no association with side, ethnic origin or dietary habits. The immunohistochemistry of hamartomas is generally similar to normal breast or fibrocystic breast tissue. Ki67 together with receptor positivity may reflect some proliferative activity and explain observed faster growth of hamartoma during pregnancy and lactation.

Calcific deposits in soft tissue are rare and may clinically resemble a tumour. It seems feasible, therefore, to investigate them by the non-invasive technique of fine needle aspiration cytology (FNAC). In this study three cases with extensive accumulation of acellular calcific material in the breast are described in which FNAC was indicative of soft tissue calcinosis. In all cases routine mammogram had shown a partially cystic opacity. All other investigations were normal and no significant family or medical history was present. Cytopreparations in all cases showed only abundant acellular calcium. The patients had no further treatment and on follow up were clinically well with no changes. The cases are interesting, since the cytohistological findings in the aspirate sample appeared to be strongly indicative of soft tissue calcinosis.

Collagenous spherulosis is a rare incidental finding seen in association with benign breast lesions. Cytological findings in three cases of collagenous spherulosis diagnosed on fine needle aspiration are presented. The presence of hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears was a diagnostic feature. Associated lesions were atypical papillary hyperplasia (2) and fibroadenoma (1). Adenoid cystic carcinoma was the close differential diagnosis on cytology. Awareness of this entity is important to avoid a false positive diagnosis of malignancy.

Is there a better way to assess performance in breast cytology? Results generated from a series of breast fine needle aspirates (BrFNA) are semi-qualitative and therefore sensitivity, specificity and accuracy are not necessarily the best measures of effectiveness. This paper considers the likelihood ratio of cancer (LR+), which can provide the probabilities for cancer being present or absent for cancer across the range of diagnostic categories used in the National Health Service Breast Screening Programme (NHSBSP), i.e. C1 to C5. Using LR+, receiver operating characteristic (ROC) curves can be generated and used to compare performance between pathologists, laboratories or years. These are illustrated using test results from 1997 to 1999 for the Derbyshire Royal Infirmary. LR + and ROC are meaningful measures. They could replace the 12 calculations currently used for the evaluation of effectiveness of BrFNA in the National Health Service Breast Screening Programme (NHSBSP) and for validation of pathologists' performance.

This study is a review of the quality of FNA cytology results for breast lesions approximately 18 months before and 10 months after a change from a rapid diagnosis FNA service with consultant pathologist aspirators to a conventional FNA service with clinician aspirators of varied experience. The setting was symptomatic breast clinic in a large hospital in rural New Zealand acting as a tertiary referral centre for a population of 550,000. The results were collected retrospectively and prospectively. The quality of results for pathologist aspirators (total 810) and clinician aspirators (total 403) was compared using the definitions of the NHS Breast Screening Program Guidelines for Cytology Procedures and Reporting in Breast Cancer Screening. There were statistically significant differences in specificity (biopsy cases only) with 73% for pathologists and 49% for clinicians, specificity (full) with 74% and 56%, inadequate rate with 23% and 37%, and complete sensitivity with 76% and 67%. The use of pathologist aspirators allowed the specimens to be reported in a few minutes. Specimens taken by clinicians took at least 30 min to report. The financial aspects of the two approaches are discussed. When compared with clinician aspirators, pathologist aspirators obtained better quality results and these were reported more quickly.

During the first 7.5 years of breast cancer screening in South Australia, 88 radial scar/complex sclerosing lesions were among the mammographically detected abnormalities. A false-positive cytological diagnosis by fine needle biopsy was given in three of 69 such cases with satisfactory smears, a false-positive rate of 4.3% in this particular group. A review of the smears suggested that the false-positive diagnoses could have been avoided if a total or near total absence of a benign epithelial component had been included among the criteria for a malignant diagnosis. However, even after review, atypia was considered sufficiently worrying to be reported as a suspicion of malignancy in 7% of cases.

Aims: To investigate the prevalence of squamous epidermoid inclusion cysts after wide-core needle biopsy., Methods and Results: Epidermoid inclusion cysts were found in five of 17 surgical excisions (29%) after preliminary wide-core needle biopsies in a 7-month period. Thereafter they were not seen in 26 subsequent postwide-core surgical excisions in a period of 6 months., Conclusions: The cysts appear to be an iatrogenic complication of wide-core biopsy, and need morphological recognition in order to avoid confusion with spontaneous squamous metaplasia of benign or malignant breast epithelium. Longer term implications are unknown.

Fine needle aspirates of the breast (FNAB) (n = 362; 204 malignant, 158 benign), prepared by cytocentrifuge methods and stained by the Papanicolaou technique, were analysed using a semi-automated image analysis system at a low magnification which precluded resolution of nuclear detail. The measured parameters were integrated optical density, fractal textural dimension, number of cellular objects (single cells and contiguous groups of cells), distance between cellular objects (mean, s.d., skewness and kurtosis), area of cellular objects (mean, s.d., skewness, kurtosis) and the nearest neighbour statistic. The cases were divided into a 200-case training set and a 162-case test set. Analysis was performed by logistic regression and the multi-layer Perceptron type of artificial neural network. Logistic regression and the neural network produced similar performances with a sensitivity of 82-83%, specificity 85% and a positive predictive value for a malignant result of 85%. A non-parametric analysis of all the predictor variables showed that all except the mean area of cellular objects and the s.d. of this measurement were significant discriminants (P < 0.05), but most were highly interrelated and this was reflected in the selection of only three predictor variables by forward and backward conditional logistic regression. This study shows that much diagnostic information is present in low power views of FNAB, and that image analysis could form the basis of a semi-automated decision-support aid.

Fifteen samples of non-tumoural breast tissue, 24 cases of benign lesions, four biopsies of inflammatory carcinomas and 94 tumour samples of primitive mammary carcinomas were analysed for HLA class II expression. We found, first, that HLA class II antigens were detectable in all cases of non-neoplastic breast tissue. Secondly, HLA class II antigen expression was notably increased in benign neoplasms and hyperplastic lesions. In contrast, only 32 out of 94 carcinomas showed expression of HLA-DR antigens, 17 tumours had HLA-DP antigens and 11 carcinomas were positive for the presence of DQ molecules. The expression of class II antigen was associated with the degree of histological differentiation (P < 0.05) but was independent of stromal leucocytic infiltration. Thirdly, HLA-DR was very strongly expressed in intravascular tumoural thrombi, especially in the 'inflammatory carcinomas'. The immunophenotype of inflammatory infiltrate was analysed in benign and malignant lesions. In malignant lesions the mean number of inflammatory cells was significantly higher than in benign lesions. Interestingly, we found no differences in the amount and composition of inflammatory infiltrate between HLA-DR positive and negative tumours.

Nucleolar organizer region-associated proteins are argyrophilic and may be visualized by silver stains. This study is a prospective analysis of the AgNOR counts in a range of breast lesions seen in fine needle aspiration (FNA) smears. A total of 72 cases including ductal carcinomas (n = 24), fibrocystic change (n = 24), fibroadenoma (n = 16), proliferative lesions (n = 4) and miscellaneous lesions (n = 4) were studied. The ductal carcinomas showed higher AgNOR counts (mean 16.63 +/- 7.09) compared with the non-malignant lesions (mean 6.39 +/- 1.96), the difference being statistically significant. A cut off AgNOR score of 11 could reliably discriminate malignant from non-malignant lesions. In ductal carcinomas, the AgNOR scores showed a tendency to increase with higher grades of malignancy. There was no correlation with the presence or absence of lymph node metastases at the time of presentation. It is concluded that AgNOR counting, although tedious, is inexpensive, and provides useful information regarding cellular proliferation, and can supplement information obtained by more sophisticated techniques.