Diagnosis Of Flat Epithelial Atypia Research Articles

The Clinical Significance of Flat Epithelial Atypia on Core Biopsy: A Single Institution Experience

The clinical significance and management (surgical excision vs. follow-up) of the patients with the diagnosis of Flat Epithelial Atypia (FEA) on Core Needle Biopsy (CNB) varies between institutions, largely due to uncertainty of its biologic potential and its association with more advanced lesions. In this study, we attempted to determine the clinical significance of FEA on CNB based on the upgrade on subsequent excisions, using a single institution experience. Retrospective histopathologic review was performed on CNB with diagnosis of pure FEA for a period of 11 years (January 2010-December 2021) and subsequent excisions by using standardized criteria and precise terminology. Cases with co-existing Atypical Ductal Hyperplasia (ADH) or more advanced lesions (ductal carcinoma in-situ or invasive mammary carcinoma) within the same biopsy cores were excluded from the study. Cases with FEA on CNB without subsequent excisions were also excluded. Our results showed 26.7% upgraded cases of pure FEA to either ADH or in situ carcinoma on the subsequent excisions. Overall, therefore, our findings support surgical excision when FEA is diagnosed on CNB.

Is Excisional Biopsy Needed for Pure FEA Diagnosed on a Core Biopsy?

The management of flat epithelial atypia (FEA) on core needle biopsy remains controversial. The upstaging rates after surgical excision are variable. In this study, we seek to determine the upstaging rate of FEA at our institution. Patients with a diagnosis of FEA were identified from the institution's pathology database from 2009 to 2018. Patients were included in the study if FEA alone, without atypia or cancer, was identified on core needle biopsy. Patient demographics, imaging, management, and pathology characteristics were obtained. Statistical analysis performed using IBM SPSS 26.0 (Armonk, NY, USA). FEA was diagnosed on core needle biopsy in 235 patients from 2009 to December 2018. Forty-eight patients met the inclusion criteria. The majority of patients presented with calcifications on mammogram (n = 21, 64%) with the remainder as masses (n = 6, 18%) or architectural distortion (n = 6, 18%). Of those, 15 (31%) patients declined surgical excision, of which none developed cancer over a mean follow-up of 4.4 years. Of the 33 (69%) patients undergoing excisional biopsy, 17 (52%) confirmed FEA, 11 (33%) had benign findings, and 3 (9%) demonstrated atypical ductal hyperplasia on final pathology. One (3%) case revealed ductal carcinoma in situ (DCIS) and 1 (3%) was upgraded to invasive cancer for an overall upstaging rate of 4% (2/48). After a mean follow-up of 3.4 years, none of the excisional biopsy patients developed invasive breast cancer. Adjuvant therapy was used in the cases of DCIS and invasive cancer; however, chemoprevention with raloxifene or tamoxifen was not chosen by any of the remaining patients. In our cohort, expectant management of FEA alone appears to be a safe option as our upstaging rate to DCIS or invasive cancer for FEA diagnosed on core biopsy was only 4%. Our study suggests that close follow-up is a safe and feasible option for pure FEA without a radiographic discordance found on core biopsy.

Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary

AbstractThe aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1–3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6–25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.

Flat epithelial atypia: conservative management of patients without residual microcalcifications post-vacuum-assisted breast biopsy.

To determine the malignancy rate (defined in this study as stability or absence of malignancy developed on close imaging follow-up post-biopsy) of conservative management in patients with a vacuum-assisted breast biopsy (VAB) diagnosis of flat epithelial atypia (FEA), performed on single group of microcalcifications, completely removed during procedure. This is a retrospective, monocentric, observational study, approved by IRB. Inclusion criteria were: VAB performed on a single group of microcalcifications; the absence of residual calcifications post-VAB; diagnosis of isolated FEA as the most advanced proliferative lesion; radiological follow-up at least of 12 months. The personal history of breast cancer or other high-risk lesions was an exclusion criteria. The patients enrolled were conservatively managed, without surgical excision, through close follow-up: the first two mammographies performed with an interval of 6 months after biopsy, followed by annual mammographic and clinical checks. 48 consecutive patients were enrolled in the study, all females, with age range of 39-76 years (mean 53,3 years) and radiological follow-up range of 13-75 months (mean 41.5 months). All the lesions were classified as BI-RADS 4b. The diameter range of the group of calcifications was 3-10 mm (mean 5, 6 mm). In each patient, 7 to 15 samples (mean 11) were obtained. Among all the patients, there was only one case (2%) of new microcalcifications, developed in the same breast, 26 months after and 8 mm from the site of previous VAB, and interpreted as ADH at surgical excision. All the checks of the other patients were negative. Even with a limited follow-up, we found a malignancy rate lower than 2%, through a defined population. Further studies with bigger number of patients and extended follow-up are needed to reinforce this hypothesis. Advances in knowledge: Surgical excision may not be necessary in patients with VAB diagnosis of isolated FEA, without residual microcalcifications post-procedure and considered concordant with the mammographic presentation, considering the low rate of malignancy at subsequent follow-ups.

Majority of flat epithelial atypia diagnosed on biopsy do not require surgical excision

BackgroundBorderline risk lesions such as flat epithelial atypia (FEA) are increasingly being diagnosed on biopsy. The need for surgery is being debated. In this study, we determined the frequency of histological upgrade following a diagnosis of FEA on biopsy and evaluated potential predictive factors. MethodsRetrospective review was done of 194 women who underwent biopsy of indeterminate lesions (total 195 lesions) that were diagnosed as FEA. The review covered a 10-year period. Cases where malignancy was also present together with FEA within the same biopsy cores were excluded. ResultsLesions diagnosed as FEA on biopsy were mostly asymptomatic and presented as microcalcifications on mammogram. Flat epithelial atypia was the only abnormality detected in one-third of cases, was associated with a benign or another borderline lesion in another third and was associated with atypical ductal hyperplasia (ADH) in another third. Six patients (3.1%) were later found to have ductal carcinoma-in-situ (DCIS) at surgery. The presence of ADH in the biopsy was the only predictor of histological upgrade to malignancy (P = 0.04, OR 11.24, 95% CI 1.10 – 115.10), and was present in 5 of the 6 patients. Surgery was advised in the last patient because of radiology-pathology discordance. Thirty-six lesions (18.5%) were not excised and no interval progression or malignancy was found on follow up. ConclusionHistological upgrade to malignancy was uncommon in lesions found on biopsy to be FEA. Non-operative management of biopsy-proven FEA can be considered in the absence of ADH and radiology-pathology discordance.

Abstract P1-01-11: Nuclear immunohistochemical IKK-ϵexpression in flat epithelial atypia (FEA) of the breast: A predictor of ipsilateral ADH, in-situ or invasive malignancy?

Abstract Background:Flat Epithelial Atypia of the breast (FEA) is associated with in situ and invasive low grade neoplasia. However, the role of excision after FEA on biopsy is controversial as rates of upgrading to atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) or invasive carcinoma in subsequent excision are relatively low. Problems include difficulties in inter-observer reproducibility and lack of morphologic or immunohistochemistry (IHC) tools that better identify cases at risk for concurrent ADH/Carcinoma. Nuclear image analysis may be useful, but is not widely available. IKK-ϵ, part of the NF-kB activating pathway, is absent in normal breast epithelium and non atypical (usual) ductal hyperplasia, but is over-expressed in &amp;gt;30% of breast cancers. In addition, in our experience ADH/DCIS shows IKK-ϵ staining, mostly cytoplasmic. Of note, in prostate cancer, nuclear accumulation of IKK-ϵ has been described in hormone sensitive prostate disease while cytoplasmic accumulation is associated with metastatic progression. No previous studies of IKK-ϵ levels in FEA are reported. Here we report IKK-ϵ status in FEA and correlation with ipsilateral, synchronous ADH, DCIS or invasive carcinoma. Method: Resection specimens from 61 patients with diagnosis of FEA were retrieved. Presence of ADH/carcinoma and laterality (ipsi or contralateral) was recorded. Synchronous neoplasia was defined as ADH, DCIS or invasive carcinoma diagnosed within 6 months of the diagnosis of FEA. Presence of FEA was confirmed by three observers using strict morphologic criteria. IHC for IKK-ϵ was performed using ABCAM, rabbit anti-IKK-ϵ (ab7891) and pH 6 citrate buffer heat-induced epitope retrieval for 20 minutes. IHC slides were scanned and FEA regions captured for blind scoring of nuclear and cytoplasmic staining. Cut off for positive nuclear staining was 10% and cytoplasmic staining was graded as negative, weak, moderate or strong positive. Results:40 patients had ipsilateral synchronous ADH/carcinoma, and 21 did not. Within these groups, 6 patients had contralateral ADH/carcinoma (2 with and 4 without ipsilateral neoplasia). While cytoplasmic staining showed no difference between the groups, nuclear positivity was more frequent in cases with ipsilateral synchronous ADH/carcinoma, χ2(1, N = 61) = 5.1, p = .025 (Table 1). In contrast, there was no correlation between IKK-ϵ staining and ADH/carcinoma in the opposite breast (p=.25). Table 1Nuclear IKK-eSynchronous Ipsilateral ADH/DCIS/Carcinoma Negative (%)Positive (%)TotalNegative10 (48)11 (52)21Positive10 (25)30 (75)40 Conclusion:Nuclear IKK-ϵ staining may prove useful in predicting synchronous ipsilateral ADH or malignancy in cases of FEA in biopsy material. Given its more frequent association with ipsilateral synchronous ADH/carcinoma, IKK-ϵ nuclear expression in FEA may represent a step in continuous local oncogenesis rather than a general marker of risk. Given the pleiotropic role of IKK-ϵ in growth and survival, the significance of the shift from nuclear staining in FEA to cytoplasmic staining in ADH/DCIS may reflect different signaling pathways and requires further investigation. Further validation of our findings in larger cohorts is necessary. Citation Format: Williams PA, Parra-Herran CE, Ayroud Y, Islam S, Gravel DH, Robertson SJ, Pratt C. Nuclear immunohistochemical IKK-ϵexpression in flat epithelial atypia (FEA) of the breast: A predictor of ipsilateral ADH, in-situ or invasive malignancy?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-01-11.

Abstract P1-02-11: Flat epithelial atypia on breast core biopsy: Is excision warranted?

Abstract Columnar cell lesions of the breast are common findings in core biopsies for mammographically indeterminate calcifications. Atypical columnar cell lesions, also referred to as flat epithelial atypia (FEA), confer a mildly increased risk of subsequent carcinoma and are often co-localized with other patterns of atypia. The management of FEA diagnosed on core biopsy remains controversial with studies reporting carcinoma on excisional biopsy in 13 to 67% of cases. We report the frequency of carcinoma in excision specimens after a diagnosis of FEA on core biopsy over a nine year period at Carolinas Medical Center. Cases were identified from our files for the period from January 2004 through October 2012. Core biopsies with FEA as the most “advanced” lesion were included. Exclusion criteria included another pattern of atypia, carcinoma in situ, or invasive carcinoma in ipsilateral core biopsies performed concurrently or within four months of the core biopsy with FEA alone. The pathology reports for excision specimens following a core biopsy with FEA alone were retrieved. For each core biopsy with pure FEA, the histologic and mammographic findings were correlated. A total of 116 cases with a diagnosis of FEA on core biopsy were identified. Two (2) cases were ultrasound core biopsies, 1 was MRI-guided, and the remaining 113 cases were stereotactic core biopsies performed for calcifications. FEA was the most advanced lesion in 53 cases (46%), corresponding to 55 core biopsies. In the 63 cases with FEA and a more advanced lesion, 34 (29%) contained atypical ductal hyperplasia, 6 (5%) atypical lobular hyperplasia, 4 (3%) atypical ductal and lobular hyperplasia, 11 (10%) ductal carcinoma in situ, 2 (2%) lobular carcinoma in situ, and 6 (5%) invasive carcinoma. Of the 55 core biopsies with FEA alone, excision pathology reports were unavailable for 11 cases, and an ipsilateral core biopsy contained a more advanced lesion in 6 cases. Of the 38 remaining cases, 4 excision specimens (11%) contained carcinoma and 8 specimens (21%) contained another, higher risk pattern of atypia (atypical ductal hyperplasia or atypical lobular hyperplasia). Excision results are summarized in the table below: 10 (26%) contained no residual atypia, 16 (42%) residual FEA, 7 (18%) atypical ductal hyperplasia, 1 (3%) atypical lobular hyperplasia, 3 (8%) ductal carcinoma in situ, and 1 (3%) invasive carcinoma. Excision Findings after Pure FEA on Core BiopsyTotalNo AtypiaFEAADHALHDCISInvasive3810 (26%)16 (42%)7 (18%)1 (3%)3 (8%)1 (3%) The data from a nine year period at our institution demonstrate an 11% upgrade rate to carcinoma for patients with a diagnosis of FEA on core biopsy. The higher risk patterns of atypia (atypical ductal hyperplasia or atypical lobular hyperplasia) found in 21% of cases also impact risk stratification and future clinical and radiographic follow-up. In total, future clinical management was altered in 32% of patients based on excision specimen results. The findings support performing an excisional biopsy for a core biopsy containing FEA. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-11.

Flat Epithelial Atypia: Comparison Between 9-Gauge and 11-Gauge Devices

BackgroundThis study aimed to establish if women with a diagnosis of flat epithelial atypia (FEA) without residual microcalcifications at stereotactic vacuum-assisted breast biopsy (VABB) could be managed with mammographic follow-up (FU) instead of surgery and to compare 9-gauge and 11-gauge devices. Patients and MethodsFrom October 2003 to January 2011, 2382 VABB procedures were performed (1373 with 11-gauge and 1009 with 9-gauge). We found 121 cases of pure FEA that were surgically treated: 57 with a 9-gauge device (group 1) and 64 with an 11-gauge device (group 2). The underestimation rate (UR) of malignancy for patients without and those with residual microcalcifications for each VABB device was calculated. Differences between groups were analyzed with the Fischer exact test. ResultsThe overall UR of FEA was 4% (2 of 57) with the 9-gauge device and 8% (5 of 64) with the 11-gauge device. With a 9-gauge device, the UR for patients without residual microcalcifications was 0% (0 of 46), and the UR for patients with residual microcalcifications was 18% (2 of 11). With an 11-gauge device, the UR for patients without residual microcalcifications was 0% (0 of 39), the UR for patients with residual microcalcifications at post-biopsy mammograms was 16% (5 of 25). With a 9-gauge device, 80% (46 of 57) of patients did not have residual microcalcifications after VABB. With an 11-gauge device, 60% (39 of 64) of patients had no residual microcalcifications after VABB. Differences between the 9-gauge and 11-gauge devices were statistically significant (P < .05). ConclusionWomen with FEA without residual microcalcifications after VABB can be managed conservatively. Nine-gauge VABB is associated with a lower percentage of residual microcalcifications compared with an 11-gauge device, but it is safe to follow patients with FEA if all calcifications are removed with the core biopsy.

Morphological parameters of lobular in situ neoplasia in stereotactic 11‐gauge vacuum‐assisted needle core biopsy do not predict the presence of malignancy on subsequent surgical excision

The management of lobular in situ neoplasia (LN) when diagnosed on core biopsy remains a controversial issue. The present study aimed to investigate the association between morphological parameters of LN on vacuum-assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision (SE). The study included 14 pathology departments in Italy. Available slides from 859 cases of VANCB reporting an original diagnosis of flat epithelial atypia, atypical ductal hyperplasia or LN, all with subsequent surgical excision, were reviewed. Overall, 286 cases of LN, pure or associated with other lesions, were identified, and a malignant outcome was reported at excision for 51 cases (17.8%). Among the 149 cases of pure LN, an increased risk of malignancy emerged in women in mammographic categories R4-R5 as compared with those in categories R2-R3 (OR 2.46; P=0.048). In the series, a statistically significant decreased malignancy risk emerged among cases without determinant microcalcifications (P=0.04). Our results suggest that the diagnosis of pure LN on VANCB warrants follow-up excision, because clinicopathological parameters do not allow the prediction of which cases will present carcinoma at surgical excision.

Abstract P5-01-13: Flat Epithelial Atypia: Management and outcome in three Dutch teaching hospitals

Abstract Background: Flat Epithelial Atypia (FEA) is a presumably neoplastic alteration of terminal duct-lobular units, characterized by the replacement of native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The architecture shows stratification of epithelial cells. FEA is often accompanied by microcalcifications and therefore discovered in biopsies following screening mammography. FEA is frequently seen in association with ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ), lobular neoplasia and invasive tubular carcinomas. There is emerging evidence suggesting FEA may represent a precursor to DCIS. The risk of subsequent breast carcinoma remains to be defined. The aim of this study is therefore to inventorise the management and outcome of solitary FEA in histological biopsies in three Dutch teaching hospitals. Materials and Methods: Data of this retrospective multicentre study were collected in a database. Local pathology databases were screened with the terms: ‘FEA’, ‘Flat Epithelial Atypia’, ‘columnar atypia’ and Dutch equivalents. Results were manually screened, only including solitary FEA. Patient files were viewed for information on presentation, mammography, ultrasound and management: surgery vs follow-up. In case of excision, definitive pathology was added. Results: We included 103 patients showing only solitary FEA in the primary biopsy. Management of these patients consisted of follow-up for 60 patients (58,3%) and surgery for 43 patients (41,7%, 49 excisions): lumpectomy (42) or mastectomy (7). Reason for choosing mastectomy was preventive in case of contralateral breast cancer or increased familial or genetic risk. Definitive pathology of lumpectomy or mastectomy showed no abnormalities or solitary FEA in 31 patients; other findings were ADH in 7, LCIS in 4 and DCIS in 7 patients. Some patients showed more than one finding. Invasive breast cancer (IBC) was detected in 3 patients. Only one mastectomy showed invasive disease, located in a different lobe, however. No incidents occurred in the follow-up group. Conclusions: No consistent management exists concerning solitary FEA in these three hospitals. Also, one hospital used the diagnosis of FEA inconsistently and interchangingly with other terms. Lack of this study is the retrospective gathering of data, making it difficult to detect the reasons for the chosen management. DCIS or IBC was discovered in 20,4% of all surgical specimens. It was concluded that FEA should be seen as a red flag, indicating the possible presence of a more malignant lesion. Additional research is warranted concerning long term follow-up for this patient group. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-13.

Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy

15±30% of malignancies detected through screening programs are ductal carcinoma in situ (DCIS), and the majority of DCIS cases present in the form of mammographic microcalcification. This study was performed in order to determine the value of features in predicting invasive disease in patients with mammographic calcification and to help determine which patients (with, Core Needle Biopsy-diagnosed DCIS) are the most appropriate candidates for Sentinel Lymph Node (SLN) biopsy. The original aspect of this study was to select patients with mammographic microcalcification but without an associated mass. The factor that we identified to be associated with invasive disease at final surgical excision was the presence of necrosis at core histology. SLN biopsy or complete axillary lymph node dissection was performed in 22 (40%) patients of whom only one (4.5%) had a micrometastasis. Further larger studies are needed to see if it would be interesting to propose a SLN biopsy in case of necrosis on CNB-diagnosed DCIS with microcalcifications but not associated with a mass.

Flat epithelial atypia diagnosed on core needle biopsy—Clinical challenge

AimThis paper describes our experience of 20 cases identified in the FEA vacuum core biopsy. BackgroundScreening mammography has contributed to the increased recognition of early cancer, premalignant and preinvasive breast lesions. A premalignant lesion called FEA (flat epithelial atypia), although rarely recognized as the only lesion in the core biopsy, is a major challenge in clinical proceedings. Increasing recognition is associated with an increasing use of the vacuum core biopsy as a tool for verifying nonpalpable lesions identified by mammography, and suspected of being breast cancer. Materials and methodsOf 4326 mammotome biopsies performed at our institution in 2000–2006, FEA was diagnosed in 20 patients (0.46%). These patients underwent surgery for reexcsion. Data were collected for clinical, radiological and pathological findings to assess factors associated with the underestimation of invasive lesions. ResultsAmong 20 patients with FEA diagnosis, the mean age was 59.6, range 52–71. When compared to the ADH group (mean age 55.45), the FEA patients were found to be statistically significantly older (p=0.0002). Two patients 2/20 (10%) showed underestimation, with invasive cancer on the final pathology were G1 tubular cancer T1b, and G2 lobular cancer T1a. ConclusionAlthough FEA is rarely diagnosed as the only lesion in a core biopsy, the ever more common use of this diagnostic technique forces us to establish a clear clinical practice. The problem is the underestimation of invasive lesions in the case of primary diagnosis of FEA. It seems that some percent of these cases can be identified by certain radiological or pathological features, thus helping implement appropriate clinical management.

P5-11-14: Flat Epithelial Atypia of the Breast: A Single Institution Experience.

Abstract Background: Flat epithelial atypia of the breast is a relatively new entity of unknown significance. Our objective is to evaluate our surgical experience with this diagnosis. Methods: A single institution database of breast patients from 2005–2010 was used to identify women who were diagnosed with flat epithelial atypia on core biopsy and subsequently underwent surgical excision. Patient data regarding history, type and reason for biopsy, and associated pathology was collected. Individuals diagnosed with flat epithelia atypia and cancer on core biopsies in the same breast were excluded. Results: There were 52 patients who underwent surgical excision for the primary diagnosis of flat epithelial atypia. There were 3 (6%) patients with a personal history of breast cancer, 14 (27%) patients with a family history of breast cancer, and 11 (21%) patients with a concurrent new diagnosis of breast cancer in the contralateral breast. Core biopsy was recommended in most (81%) cases because of suspicious calcifications on mammography. Twenty-eight (54%) patients were found to have flat epithelial atypia associated with other atypical breast hyperplasia and 24 (46%) had flat epithelial atypia as the most significant lesion on core biopsy. In 8 (15%) patients, there was a sonographic correlate that was biopsied; 5 had only flat epithelial atypia and 3 had flat epithelial atypia associated with other atypical hyperplasia. Of the 52 patients there were 4 (8%) patients who upstaged to ductal carcinoma in-situ on surgical excision. There were no cases of invasive carcinoma. All ductal carcinoma in-situ cases were associated with other atypical breast hyperplasia, not flat epithelial atypia alone. Conclusion: Though flat epithelial atypia may be associated with an increased risk of breast cancer, surgical excision of pure flat epithelial atypia may not be necessary. Larger studies are needed to corroborate these findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-14.

Core biopsies of the breast: Diagnostic pitfalls

The incidence of breast cancer is increasing worldwide. In this review article, the authors compare and contrast the incidence of breast cancer, and the inherent differences in the United States (US) and India in screening techniques used for diagnosing breast cancer. In spite of these differences, core biopsies of the breast are common for diagnosis of breast cancer in both countries. The authors describe "Best Practices" in the reporting and processing of core biopsies and in the analysis of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor Receptor 2 (Her2/neu). The pitfalls in the diagnosis of fibroepithelial lesions of the breast on core biopsy are discussed, as also the significance of pseudoangiomatous stromal hyperplasia of the breast (PASH) is discussed in core biopsy. In this review, the management and diagnosis of flat epithelial atypia and radiation atypia are elaborated and the use of immunohistochemistry (IHC) in papillary lesions, phyllodes tumor, and complex sclerosing lesions (radial scars) is illustrated. Rarer lesions such as mucinous and histiocytoid carcinoma are also discussed.

Flat epithelial atypia is a common subtype of B3 breast lesions and is associated with noninvasive cancer but not with invasive cancer in final excision histology

The biological behavior and the optimal management of benign breast lesions with uncertain malignant potential, the so-called B3 lesions, found in breast needle core biopsies is still under debate. We addressed this study to compare histologic findings in B3 needle core biopsies with final excision specimens to determine associated rates of malignancy. Consecutive needle core biopsies were performed in a 3-year period (January 1, 2006-December 31, 2008). Biopsies were image-guided (31 by ultrasound, 85 stereotactic vacuum-assisted, 6 unknown) for evaluation of breast abnormalities. We reviewed 122 needle core biopsies with B3 lesions of 91 symptomatic patients and 31 screen-detected women and compared the B3 histologic subtypes with the final excision histology. A total of 1845 needle core biopsies were performed and B3 lesions comprised 6.6% of all B categories. The most common histologic subtype in biopsies was flat epithelia atypia in 35.2%, followed by papillary lesions in 21% and atypical ductal hyperplasia in 20%. Reports on excision specimens were available in 66% (81 patients). Final excision histology was benign in 73 (90.2%) and malignant in 8 (9.8%) patients (2 invasive cancer, 6 ductal carcinoma in situ). Of all B3 subtypes, atypical ductal hyperplasia and flat epithelial atypia were associated with malignancy, whereas only atypical ductal hyperplasia was accompanied by invasive cancer. Of all lesions, flat epithelial atypia was most frequently found in excision specimens (18%). In our study, flat epithelial atypia and atypical ductal hyperplasia are common lesions of the B3 category in needle core biopsies of the breast. Both lesions are associated with malignancy, whereas only atypical ductal hyperplasia was related to invasive cancer. We conclude that an excision biopsy after diagnosis of flat epithelial atypia is recommended depending on clinical and radiologic findings.

Flat Epithelial Atypia and Atypical Ductal Hyperplasia: Carcinoma Underestimation Rate

This study was carried out to determine the underestimation rate of carcinoma upon surgical biopsy after a diagnosis of flat epithelial atypia and atypical ductal hyperplasia and 11-gauge vacuum-assisted breast biopsy. A retrospective review was conducted of 476 vacuum-assisted breast biopsy performed from May 2005 to January 2007 and a total of 70 cases of atypia were identified. Fifty cases (71%) were categorized as pure atypical ductal hyperplasia, 18 (26%) as pure flat epithelial atypia and two (3%) as concomitant flat epithelial atypia and atypical ductal hyperplasia. Each group were compared with the subsequent open surgical specimens. Surgical biopsy was performed in 44 patients with atypical ductal hyperplasia, 15 patients with flat epithelial atypia, and two patients with flat epithelial atypia and atypical ductal hyperplasia. Five cases of atypical ductal hyperplasia were upgraded to ductal carcinoma in situ, three cases of flat epithelial atypia yielded one ductal carcinoma in situ and two cases of invasive ductal carcinoma, and one case of flat epithelial atypia/atypical ductal hyperplasia had invasive ductal carcinoma. The overall rate of malignancy was 16% for atypical ductal hyperplasia (including flat epithelial atypia/atypical ductal hyperplasia patients) and 20% for flat epithelial atypia. The presence of flat epithelial atypia and atypical ductal hyperplasia at biopsy requires careful consideration, and surgical excision should be suggested.

Flat Epithelial Atypia on Core Needle Biopsy

The clinical significance and management (surgical excision vs. follow-up) of the patients with the diagnosis of flat epithelial atypia (FEA) on core needle biopsy (CNB) are actually under discussion. Using standardized criteria and precise terminology, we analyzed retrospectively our CNB diagnosis of FEA, dividing patients with pure FEA as the most advanced pathologic lesion from patients with FEA associated to atypical ductal hyperplasia (FEA+ADH). Both the categories were correlated with radiologic data and findings on subsequent surgery. We evaluated 875 core needle biopsies (11-gauge stereotactic vacuum-assisted procedure), performed over a 5-year period. A CNB diagnosis of pure FEA was made in 33/875 (3.7%) cases; in other 11 (1.2%) cases we observed the coexistence of FEA and ADH. Subsequent surgical excisions were available in 20/33 pure FEA and in 10/11 FEA+ADH: of the 20 patients with pure FEA on CNB, none had either ductal carcinoma in situ or invasive carcinoma in their excisional biopsy, whereas 3/10 (30%) FEA+ADH on CNB showed, at subsequent surgery, more advanced lesions (2 ductal carcinoma in situ, 1 invasive carcinoma). Our results suggest that patients with an 11-gauge vacuum-assisted CNB diagnosis of pure FEA (especially if related to a small radiologic target, completely or almost completely removed by the needle biopsy procedure) could be spared surgical excision and managed with close radiologic follow-up.

Flache epitheliale Atypie

According to the WHO, flat epithelial atypia (FEA) is defined as a neoplastic epithelial proliferation of ductal type in either a single or in multiple terminal duct lobular unit(s) limited to the periphery of the ductules in a clinging growth pattern. The atypical cells may form between one and several layers of epithelial cells that show low grade cytologic atypia. FEA most often presents as mammographic microcalcifications, which are typically round (secretory type and psammomatous calcification in an eosinophilic matrix, so-called ossifying calcifications). Clinical relevance is dependent on whether the lesion appears in isolation or whether it is an excision biopsy or a minimally invasive biopsy. Currently available data suggest that the risk of subsequent breast carcinoma in the ipsilateral breast is very low following the diagnosis of FEA. The differential diagnosis should include atypical ductal hyperplasia, low-grade clinging ductal carcinoma in situ, blunt duct adenosis and apocrine metaplasia.

Diagnosis of flat epithelial atypia after stereotactic vacuum-assisted biopsy of the breast: what is the best management: systematic surgery for all or follow-up?

Diagnosis of flat epithelial atypia after stereotactic vacuum-assisted biopsy of the breast: what is the best management: systematic surgery for all or follow-up?

Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast

Interobserver reproducibility in the diagnosis of flat epithelial atypia of the breast