Columnar Cell Lesions Research Articles

Proliferative epithelial changes in tumour adjacent tissue in Sri Lankan women with breast carcinoma: do morphological changes support molecular models of breast carcinogenesis?

BackgroundThe multistep molecular model of breast carcinogenesis is based on the oestrogen receptor(ER) status of the tumour. Its two main arms comprise ER-positive and ER-negative breast carcinomas(BCa), which are associated with Nottingham grade(NG) of the tumour and different proliferative epithelial changes. According to the model, columnar cell lesions(CCL), lobular carcinoma in-situ(LCIS) and atypical ductal hyperplasia(ADH), low-grade ductal carcinoma in-situ (LG-DCIS) are associated with low grade ER-positive tumours and microglandular adenosis (MGA), pleomorphic LCIS(PLCIS), high-grade DCIS(HG-DCIS) are associated with ER-negative high grade tumours. This study aims to describe the association between proliferative epithelial changes in breast tissue adjacent to tumour, in relation to the ER status and NG of the tumour.MethodsThis descriptive cross-sectional study included 420, wide local excision and mastectomy specimens of BCa from National Hospital of Sri Lanka, between 2017–2019. The histopathological features of the tumour and proliferative epithelial changes in tumour adjacent tissue within 10 mm distance from the tumour-host interface were evaluated independently by two pathologists. The ER, PR(Progesterone receptor) and HER2 status assessed by immunohistochemistry(IHC) was reviewed. The associations between above epithelial lesions and ER status and NG{categorised as low grade (NG1 and NG2) and high grade (NG3)} of the tumour were analyzed.ResultsER positive BCa showed significant associations with CCH (p = 0.04), FEA (p = 0.035) and LGDCIS (p < 0.001). Although PLCIS was more frequent in ER positive tumours, the association did not attain statistical significance. ER negative BCa showed a significant association with HGDCIS (p = 0.016). CCLs as a whole (p = 0.005) and also CCC (p = 0.006) and FEA (p = 0.048) and LGDCIS (p < 0.001) showed significant associations with low NG tumours. High NG tumours showed a significant association with HGDCIS (p < 0.001). Microglandular adenosis was not identified in our study population.ConclusionThese morphological findings support the multistep molecular based pathogenetic pathways of breast carcinoma in the studied setting in South Asia. Identification of these proliferative epithelial components in a core biopsy that is negative for BCa, should prompt for close clinicoradiological correlation, and if necessary re-biopsy of women suspected of harbouring a BCa.

Dimorphic cells: a common feature throughout the low nuclear grade breast neoplasia spectrum

Columnar cell lesions (CCLs) are recognized precursor lesions of the low nuclear grade breast neoplasia family. CCLs are cystic enlarged terminal duct lobular units with monotonous (monoclonal) columnar-type luminal cells. CCLs without atypia are regarded as benign and CCLs with atypia as true precursor lesions with clonal molecular changes, a certain progression risk, and an association with more advanced lesions. However, reproducibility of designating atypia in CCL is not optimal, and no objective markers of atypia have been identified, although 16q loss seems to be associated with atypical CCLs. Dimorphic (“pale”) cell populations have been described in low nuclear grade ductal carcinoma in situ (DCIS) but not in CCLs and atypical ductal hyperplasia (ADH). Therefore, we searched for pale cells in CCL (N = 60), ADH (N = 41), and DCIS grade 1 (N = 84). Diagnostic criteria were derived from the WHO, and atypia was designated according to the Schnitt criteria. Pale cells occurred in 0% (0/30), 73% (22/30), 56% (23/41), and 76% (64/84) of CCLs without atypia, CCLs with atypia, ADH, and DCIS grade 1, respectively. Pale cells expressed ERα, E-cadherin and p120 and variably cyclin D1, and lacked expression of CK5 and p63. In conclusion, dimorphic “pale” cells occur throughout the low nuclear grade progression spectrum, increasing in frequency with progression. Interestingly, CCL lesions without atypia do not seem to bear showed pale cells, indicating that the presence of pale cells may serve as a diagnostic morphological feature of atypia in CCLs.

Are Columnar Cell Lesions the Earliest Non-Obligate Precursor in the Low-Grade Breast Neoplasia Pathway?

Columnar cell lesions (CCLs) of the breast comprise a spectrum of morphologic alterations of the terminal duct lobular unit involving variably dilated and enlarged acini lined by columnar epithelial cells. The World Health Organization currently classifies CCLs without atypia as columnar cell change (CCC) and columnar cell hyperplasia (CCH), whereas flat epithelial atypia (FEA) is a unifying term encompassing both CCC and CCH with cytologic atypia. CCLs have been increasingly recognized in stereotactic core needle biopsies (CNBs) performed for the assessment of calcifications. CCLs are believed to represent the earliest non-obligate precursor of low-grade invasive breast carcinomas as they share molecular alterations and often coexist with entities in the low-grade breast neoplasia pathway. Despite this association, however, the risk of progression of CCLs to invasive breast carcinoma appears low and may not exceed that of concurrent proliferative lesions. As the reported upgrade rates of pure CCL/FEA when identified as the most advanced high-risk lesion on CNB vary widely, the management of FEA diagnosed on CNB remains controversial. This review will include a historical overview of CCLs and will examine histologic diagnostic criteria, molecular alterations, prognosis and issues related to upgrade rates and clinical management.

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Abstract PD11-04: A multi-feature AI-based solution for cancer diagnosis in breast biopsies: A prospective blinded multi-site clinical study

Abstract Objective This study aimed to clinically validate the performance of a multi-feature AI-based solution on detection of invasive versus in situ carcinomas and in situ ductal carcinoma high grade from atypical ductal hyperplasia/low grade DCIS compared to rigorous ground truth (GT) established by multiple blinded expert pathologists in breast biopsies. Design Performance of the AI solution was prospectively tested on breast biopsies from two medical institutions in different geographies. AI results were compared against the ground truth (GT) established by consensus of two subspecialist breast pathologists. The study endpoints were detection of invasive carcinoma (IDC, ILC) and DCIS/ADH, including differentiating between different DCIS grades and ADH. ADH and DCIS Low Grade were pooled together because of similar clinical management when diagnosed on a biopsy. Results Six pathologists participated in the study and reported on 436 breast biopsies (841 H&amp;E slides), including 156 invasive (including 31 rare subtypes), 135 DCIS/ADH and 145 benign diagnoses. The AI solution demonstrated high performance when compared with the GT with an AUC of 0.99 for the detection of invasive carcinoma (specificity and sensitivity of 93.6% and 95.5% respectively) and with AUC of 0.95 for the detection of DCIS/ADH. The AI solution differentiated well between subtypes/grades of invasive and in-situ cancers with an AUC of 0.97 for IDC vs. ILC and AUC of 0.92 for DCIS high grade vs. low grade/ADH, respectively. Only 11 (7%) cases had discrepancies on invasive diagnosis, 4 of these between invasive versus benign diagnosis encompassing one case on which the invasive component was only represented by rare lympho-vascular invasion, two cases of ILC (one with a diffuse pattern and the second in a case with granulomatous mastitis with multinucleated giant cells and hemosiderin-laden macrophages) and one rare case of tubular carcinoma surrounded by flat epithelial atypia and columnar cell lesions. Fifteen cases (11%) had discrepancies on DCIS/ADH diagnosis between the two specialist pathologists necessitating a third assessment by a specialist to establish GT. Six of these cases also necessitated a review on a multihead microscope to reach a consensus decision, since there was no majority even after 3 reviews. Conclusion This blinded multi-site study reports the successful clinical validation of a multi-feature AI-based solution in detecting and automatically imparting clinically relevant diagnostic parameters regarding invasive and in situ breast carcinoma, offering an important tool for computer-aided diagnosis in routine pathology practice. Citation Format: Anne Vincent-Salomon, Guillaume Bataillon, Alona Nudelman, Judith Sandbank, Anat Albrecht Shach, Lucie Thibault, Lilach Bien, Rachel Mikulinsky, Ira Krasnitsky, Ronen Heled, Chaim Linhart, Manuela Vecsler, Daphna Laifenfeld. A multi-feature AI-based solution for cancer diagnosis in breast biopsies: A prospective blinded multi-site clinical study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-04.

Machine learning-based image analysis for accelerating the diagnosis of complicated preneoplastic and neoplastic ductal lesions in breast biopsy tissues.

Diagnosis of breast preneoplastic and neoplastic lesions is difficult due to their similar morphology in breast biopsy specimens. To diagnose these lesions, pathologists perform immunohistochemical analysis and consult with expert breast pathologists. These additional examinations are time-consuming and expensive. Artificial intelligence (AI)-based image analysis has recently improved, and may help in ordinal pathological diagnosis. Here, we showed the significance of machine learning-based image analysis of breast preneoplastic and neoplastic lesions for facilitating high-throughput diagnosis. Images were obtained from normal mammary glands, hyperplastic lesions, preneoplastic lesions and neoplastic lesions, such as usual ductal hyperplasia (UDH), columnar cell lesion (CCL), ductal carcinoma in situ (DCIS), and DCIS with comedo necrosis (comedo DCIS) in breast biopsy specimens. The original enhanced convoluted neural network (CNN) system was used for analyzing the pathological images. The AI-based image analysis provided the following area under the curve values (AUC): normal lesion versus DCIS, 0.9902; DCIS versus comedo DCIS, 0.9942; normal lesion versus CCL, 0.9786; and UDH versus DCIS, 1.000. Multiple comparison analysis showed precision and recall scores similar to those of single comparison analysis. Based on the gradient-weighted class activation mapping (Grad-CAM) used to visualize the important regions reflecting the result of CNN analysis, the ratio of stromal tissue in the whole weighted area was significantly higher in UDH and CCL than that in DCIS. These analyses may provide a more accurate and rapid pathological diagnosis of patients. Moreover, Grad-CAM identifies uncharted important histological characteristics for newer pathological findings and targets of research for understanding diseases.

Risk factors for breast cancer development by tumor characteristics among women with benign breast disease

BackgroundAmong women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown.MethodsUsing a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models.ResultsBreast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14–14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21–3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size.ConclusionMost tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status.

Learning from the wastage: histomorphology of columnar cell lesions and other changes in surgical pathology breast specimens

Introduction: In recent few decades, widespread use of mammography has resulted in increased detection of precursor and preinvasive breast lesions such as atypical ductal hyperplasia, ductal carcinoma in situ and, a type of breast lesion termed, ‘Flat epithelial atypia” which belongs to the group of columnar cell lesions with atypia. Although in India, invasive breast cancer is still most common presentation than early preinvasive lesions, with advanced diagnostic set up and increased awareness, early detection of preinvasive lesions is bound to be increased in future. For their accurate diagnosis, it is very necessary to be aware and alert about the morphology of these lesions. Objectives: Present study was undertaken to study the morphology of Columnar Cell Lesion and other changes in Surgical Biopsy specimens received in Histopathology laboratory of a tertiary health care centre. Materials and Methods: Excessive sections were taken from breast tissue surrounding the primary lesion in mastectomy or wide local excision specimens received over two-year duration and were examined for various changes in the epithelium and in the stroma especially columnar cell lesions and other precursor lesions. Results: A spectrum of precursor lesions including columnar cell lesions could be commonly seen in most of the specimens. Their morphology and differential diagnosis could be studied in details in these sections which otherwise are wasted usually. Conclusion: The tissue surrounding primary lesion in surgical pathology breast specimens is a good source to study the detailed morphology of columnar cell lesions and other lesions to get familiar with them for their accurate detection and early diagnosis in future. Keywords: Precursor breast lesions, Columnar cell lesions, Flat epithelial atypia, Ductal hyperplasia.

Analysis and correlation of imaging findings with the anatomopathological study of bi-rads 4a lesions

Introduction: The Breast Imaging Reporting and Data System (BI-RADS®) was developed to standardize reports based on imaging findings, classifying them into six categories. Its fourth edition proposed the subdivision of category 4 into three subcategories according to malignancy suspicion. Category 4A shows likelihood of malignancy between 2% and 10%, and diagnosis by biopsy is recommended. Frequent histological findings in the literature for 4A lesions include fibrocystic breast changes, fibroadenoma, columnar cell lesions with atypia, stromal sclerosis, inflammatory disorders, and proliferative epithelial lesions. Objectives: To show the most relevant radiological and histological findings for the BI-RADS® 4A subcategory, corroborating its likelihood ratio of malignancy. Method: This is a cross-sectional study based on the review of medical records of patients submitted to the anatomopathological study of BI-RADS 4A lesions in public and private health services from Curitiba, Paraná, Southern Brazil, between March and September 2019. The findings were subsequently correlated with histopathological results. Results: A total of 727 core needle breast biopsies were performed – 78.6% guided by ultrasound and 21.4% by stereotaxy. Approximately 35.8% of ultrasound-guided procedures (group X) and 55.4% of stereotaxic biopsies (group Y) were classified as BI-RADS 4A. Among the main imaging findings in group X, solid nodules, solid cystic lesions, and solid heterogeneous areas stood out. Group Y presented clusters of heterogeneous, punctate, amorphous microcalcifications, and findings that did not fit the BI-RADS classification. Benign changes predominated among the histopathological findings in both groups. The malignancy rate according to guidelines of the European classification for anatomopathological results of breast lesions4 remained around 2% in group X and 8.7% in group Y. Conclusion: Based on the results obtained, we concluded that the malignancy rates of biopsies from patients classified as BI-RADS 4A were within the acceptable values established by the literature. However, they varied considerably according to the biopsy method chosen, presenting higher values in patients submitted to stereotaxy.

Diagnostic upgrade of atypical ductal hyperplasia of the breast based on evaluation of histopathological features and calcification on core needle biopsy.

Atypical ductal hyperplasia (ADH) of breast is increasingly diagnosed in core needle biopsy (CNB). As higher-grade lesions were found in the excision in a substantial proportion of ADH on CNB, factors predicting risk of subsequent upgrade are clinically significant. This study aims to investigate relevant histopathological factors in CNB that could predict diagnostic upgrade at excision. One hundred and forty-three cases of CNB with paired subsequent excision were evaluated for multiple clinicopathological parameters related to CNB sampling, ADH morphology, calcification and other co-existing histological features, and which of these parameters were associated with diagnostic upgrade at subsequent excisions were determined. Forty-eight cases (34.3%) were upgraded to malignancy, including 15 invasive cancers and 33 ductal carcinomas in situ (DCIS). An increased tissue area occupied by ADH (P=0.026), a higher number of ADH foci (P=0.004), the presence of solid pattern (P=0.037) and older age (P=0.012) were positively associated with upgrade, while negative associations were found with the presence of micropapillary pattern (P=0.025), co-existing columnar cell lesions (CCL) (P=0.001) and the presence of calcifications (P=0.009). Multivariate logistic regression analysis showed that the number of ADH foci (HR=2.810, P=0.013) was an independent positive predictor, while co-existing CCL (HR=0.391, P=0.013) was an independent negative predictor for upgrade. Patients with ADH in CNB showing the presence of co-existing CCL and a lower number of ADH foci have a lower risk of disease upgrade at excision, and are potential candidates for observation-only management.

Caracterización de la expresión de galectina-3 mediante inmunohistoquímica en lesiones intraepiteliales de glándula mamaria de perras sin evidencia de tumor

Las lesiones intraepiteliales (LIEs) son anormalidades morfológicas locales de los ductosy los lobulillos de la glándula mamaria que incrementan el riesgo de cáncer. Los programasde detección temprana de cáncer de seno han incrementado la identificaciónde LIEs. En este sentido, en perras se ha propuesto las LIEs como modelo comparativocon humanos. La galectina-3 está involucrada con la progresión del cáncer en mujeresy hembras caninas pero su papel en el comportamiento biológico de las neoplasias escontradictorio según la célula de origen. El objetivo de este trabajo fue caracterizar laexpresión de la galectina-3 por medio de inmunohistoquímica en 19 glándulas mamarias(GM) de seis perras sin evidencia de tumor que contenían 50 tipos de LIEs y 7 carcinomasinvasivos, teniendo en cuenta el porcentaje de células positivas y la intensidaddel color de la inmunoreacción. No hubo inmunomarcación para galectina-3 en lasadenosis, las hiperplasias ductales usuales, la hiperplasia lobular atípica, las lesiones decélulas columnares, los carcinomas complejos o las hiperplasias complejas. Un papiloma/adenoma con hiperplasia de acinos tuvo inmunomarcación multifocal en 11–50% delas células con moderada intensidad. Dos carcinomas in situ del subtipo lobular (unode grado histológico nuclear intermedio y el otro de alto grado) tuvieron marcación en10% de las células, pero uno tuvo intensidad baja y el otro, intensidad moderada. Loshallazgos sugieren que el papel de la galectina-3 es poco importante en la iniciación delas LIEs, pero sugieren que es una proteína de interés en la progresión de estas lesionesque posiblemente interactúa en el comportamiento biológico de esta enfermedad.

Columnar Cell Lesions in patients with Invasive Breast Carcinoma and their correlation with clinico-pathological characteristics.

Columnar Cell Lesions in patients with Invasive Breast Carcinoma and their correlation with clinico-pathological characteristics.

Histopathological Study of the Relationship of Columnar Cell Lesions to Carcinoma Breast

Histopathological Study of the Relationship of Columnar Cell Lesions to Carcinoma Breast

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis.

A study of incidence of columnar cell lesions in neoplastic and non –neoplastic lesions of breast

Background: Columnar cell lesions of breast are increasingly being encountered in breast biopsies because of their associated micro calcifications which are detected on mammographic screening.Observational studies suggest the co-existence of Columnar cell lesions with more advanced lesions of breast like Ductal carcinoma in situ,Atypical ductal hyperplasia and Invasive carcinoma. The presence of Columnar cell lesionneeds careful search for otheratypical breast lesionsin proximity. Aim: To study the occurrence of Columnar cell lesions in Neoplastic and NonNeoplastic breast lesions and evaluate the type of lesion with respect to category of breast lesion.Materials and methods: This is an observational study conducted in the Department of Pathology,Gandhi hospitalfrom January 2016 to December 2017.H&E stained sections of Neoplastic and Non-Neoplastic breast lesions were reviewed andassociated Columnar cell changes were evaluated.Results:Total200 breast lesions were studiedout of which 134 showed Columnar cell lesions. 90% cases of fibrocystic disease and 60% of fibroadenoma cases were associated with CCL and the predominant type of lesionis Columnar cell change. 80% cases of Ductal carcinoma insituand 40% of Infiltrative duct cell carcinoma cases showed CCL and the common lesion is Columnar cell hyperplasia without atypia.Conclusion: Columnar cell lesions were observed in both Neoplastic and Non-Neoplastic breast lesions. Based on previous observational studies cancer risk associated with CCL is only mild on long term follow up. However detection of CCL in biopsy should prompt additional scrutiny for other pathological changes.

Abstract ES2-1: The pathology of high risk proliferative lesions of the breast

Abstract A number of breast lesions diagnosed by pathologic examination of breast tissue are known to confer an increased risk for future development of breast cancer. Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are lesions conferring a moderately increased risk of 4-5x over baseline. Lobular carcinoma in situ (LCIS) and variants confer a markedly increased risk of 8-10x over the baseline. The magnitude of the risk, the effect of the patient's age and family history, the laterality of the future malignancy and the type of subsequent cancer development are different between all these high risk proliferative breast lesions. In addition, the spectrum of columnar cell lesions of the breast are thought to represent an early non-obligate precursor in the development of the low grade neoplasia of the breast. Of interest, many of these lesions share common genetic abnormalities that are different than those seen in high grade in situ and invasive carcinomas of the breast. These observations have implications for our current understanding of the breast cancer progression model and our recommendations for the therapeutic management of patients with high risk proliferative lesions of the breast. Citation Format: Siziopikou KP. The pathology of high risk proliferative lesions of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES2-1.

Abstract LB-378: Ankyrin repeat domain 30A as a novel molecular marker of columnar alterations in benign breast disease and subsequent breast cancer in African American women

Abstract An estimated 1.6 million breast biopsies are performed annually in the United States, and the vast majority are benign. Benign breast disease is an established breast cancer risk factor for both Caucasian and African American women. Yet little is still known about benign breast tissue from African American women, who suffer from disproportionately high-grade tumors and poorer breast cancer survival. To better characterize the risk of breast cancer among African American women with benign breast disease, we assessed benign breast disease pathology of African American women in our metropolitan Detroit cohort (n = 3,737). We classified benign breast lesions for pathological characteristics and used logistic regression to estimate subsequent breast cancer risk with histological characteristics. We observed that women whose biopsies showed columnar alterations, columnar cell lesions of the breast, were 1.78-fold more likely to develop an invasive breast cancer [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.19-2.65] after adjusting for age at biopsy, biopsy year, and overall impression. Columnar alterations were not found to be significantly associated with risk of developing ductal carcinoma in situ (DCIS) among African American women [OR 1.53, 95% CI 0.83-2.82]. Next, to identify molecular markers associated with columnar alterations in benign breast lesions, we performed gene expression analyses on biopsy tissues from 27 African American women that subsequently developed an invasive breast cancer. Transcriptional profiling of these lesions identified differentially expressed genes significantly associated with columnar alterations, including ankyrin repeat domain 30A (ANKRD30A). ANKRD30A, also known as NY-BR-1, is a mammary tissue-specific differentiation antigen that is overexpressed in breast cancers. Increased expression of ANKRD30A in benign breast lesions with columnar alterations may be indicative of subsequent breast cancer development. Taken together, novel molecular markers, including ANKRD30A, and ethnicity can lead to better risk assessment and earlier diagnosis of breast cancer. Citation Format: Andreana N. Holowatyj, Rouba Ali-Fehmi, Julie J. Ruterbusch, Eman Abdulfatah, Vishakha Pardeshi, Woodlyne Roquiz, Baraa Alosh, Sudeshna Bandyopadhyay, Derek Radisky, Michele L. Cote. Ankyrin repeat domain 30A as a novel molecular marker of columnar alterations in benign breast disease and subsequent breast cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-378.

Diagnosis of Columnar Cell Lesions and Atypical Ductal Hyperplasia by Ultrasound-Guided Core Biopsy: Findings Associated with Underestimation of Breast Carcinoma

The aim of the study described here was to determine underestimation rates and identify radiologic predictors of underestimation for columnar cell lesions (CCLs) and atypical ductal hyperplasia (ADH) detected by ultrasound-guided core needle biopsy. A total of 103 CCLs and ADH lesions in 100 patients diagnosed by ultrasound-guided core needle biopsy were evaluated. Breast sonographic and mammographic findings were reviewed, and underestimation rates were determined by surgical excision, percutaneous vacuum-assisted excision or 2-y imaging follow-up. All underestimated lesions were ductal carcinoma in situ, and the underestimation rates of flat epithelial atypia (FEA), FEA + ADH and ADH were 5.9% (1/17), 44.4% (4/9) and 27.3% (12/44), respectively. There was no underestimation of CCLs without atypia. The presence of calcifications on ultrasound was significantly associated with underestimation (p = 0.010). Therefore, except for CCLs without atypia, all other lesions may require excision, especially when calcification is present on ultrasound or when FEA + ADH is found.

Does flat epithelial atypia have rounder nuclei than columnar cell change/hyperplasia? A morphometric approach to columnar cell lesions of the breast.

Columnar cell lesions of the breast encompass columnar cell change/hyperplasia (CCC/CCH) and flat epithelial atypia (FEA). These have attracted researchers because emerging data suggest that FEA may represent the earliest histologically detectable non-obligate precursor of breast cancer. However, it is occasionally difficult to distinguish FEA from CCC/CCH because of similar histology. Although the nuclei of FEA are frequently described as relatively round compared with those of CCC/CCH, there are few morphometric studies to support this statement. The aim of this study was to provide objective data as to the nuclear shape in columnar cell lesions. As a shape descriptor, we adopted ellipticity that is defined by the formula 2b/2a, where a is the length of the long axis of the ellipse and b is the length of the short axis. Contrary to circularity, ellipticity reflects the overall configuration of an ellipse irrespective of surface irregularity. Our image analysis included generating whole slide images, extracting glandular cell nuclei, measuring nuclear ellipticity, and superimposing graded colors based on execution of results on the captured images. A total of 7917 nuclei extracted from 22 FEA images and 5010 nuclei extracted from 13 CCC/CCH images were analyzed. There was a significant difference in nuclear roundness between FEA and CCC/CCH with mean ellipticity values of 0.723 and 0.679, respectively (p<0.001, Welch's t test). Furthermore, FEA with malignancy had significantly rounder nuclei than FEA without malignancy (p<0.001). Our preliminary results suggest that nuclear ellipticity is a key parameter in reproducibly classifying columnar cell lesions of the breast.

Abstract P5-09-07: Using the power of the internet to deliver breast teaching in Africa

Abstract Introduction: Delivering high quality breast teaching to African countries is of utmost importance. Our previous audit of breast cancer reporting in Africa has identified areas that would benefit from teaching and education. However, time and resource issues limit the ability to deliver teachings to a large number of African pathologists in person. Method As part of a comprehensive national in house teaching for senior trainees in Nigeria, a distant module of teaching was delivered by a team of UK pathologists using a freely available internet application. Results Distant teaching formed part of a two week residential postgraduate histopathology course that was designed for trainees preparing for their exit Histopathology exam. Sixty African pathologists attended the teaching. Previous auditing of breast cancer reporting indicated the need for education on macroscopic specimen handling, typing and grading of breast cancer. Other topics included an update on inflammatory breast cancer which has a high incidence in Africa and columnar cell lesions that are increasingly being encountered by African pathologists in the context of breast screening. A set of anonymous virtual slides were scanned and distributed to delegates before the course date. Teaching was delivered using Skype application that only required a computer with internet access at the UK and Nigeria. We utilised video-conferencing which allowed trainees to see their lecturers and vice versa. The new data sharing facility of the application allows simultaneous sharing of Power Point presentations, with annotation which facilitates interactive discussion. A slide seminar using the previously circulated virtual slides, covering areas of diagnostic challenges morphologically and by immunohistochemistry was also delivered. An approach to diagnosing these lesions was delivered with re-focussing on tumor typing and grading. Participants were able to ask questions and interact with the UK-based tutors thorough the sessions. The feedback collected from attendees was excellent. Conclusion Distant teaching using freely available internet applications is a valuable, time and cost effective method that allows sharing educational material including lectures and slide seminars in an interactive manner. It is particularly useful in delivering teaching to resource-poor countries. Citation Format: Shaaban AM, Abdulkareem F, Rotimi O. Using the power of the internet to deliver breast teaching in Africa. [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 P5-09-07.