Atypical Lobular Hyperplasia Research Articles

Upgrade at excisional biopsy after a core needle biopsy diagnosis of classic lobular carcinoma in situ

BackgroundManagement of patients with classic lobular carcinoma in situ diagnosed on core needle biopsy remains controversial, in part because of clinicopathologic overlap with atypical lobular hyperplasia. Although atypical lobular hyperplasia on core needle biopsy is observed because of its low upgrade rate (~1%), consensus is lacking for lobular carcinoma in situ. Therefore, we evaluated lobular carcinoma in situ upgrade rates. MethodsWith institutional review board approval, we identified 90 patients (from October 2008 to December 2019) with lobular carcinoma in situ on core needle biopsy as their highest-risk lesion. We excluded patients with concurrent ipsilateral cancer. Variables associated with upgrade were assessed with logistic regression. ResultsOf the 90 patients, 81 (90%), median age 55 y, underwent surgical excision. Indications for diagnostic core needle biopsy included mammographic calcifications (48, 53.3%), mass/distortion (28, 31.1%), and non-mass enhancement (12, 13.3%). Final surgical pathology upgraded 11 of 81 patients (13.6%, 95% CI: 7.8%–22.7%) to cancer: invasive lobular (n = 7), invasive ductal (n = 1), and ductal carcinoma in situ/pleomorphic lobular carcinoma in situ (n = 3). Only 1 patient with invasive cancer was node-positive. Concurrent contralateral cancer (OR 4.41, 95% CI: 1.06–17.38, P = .04) and larger lesion size (OR 1.78 per 1 cm, 95% CI: 1.19–2.95, P = .005) predicted upgrade. ConclusionOur data suggest that, unlike atypical lobular hyperplasia, lobular carcinoma in situ identified on core needle biopsy should be surgically excised. The high proportion of upgrades to early stage invasive lobular carcinoma underscores the value of this approach.

Patients with benign papilloma diagnosed on core biopsies and concordant pathology-radiology findings can be followed: experiences from multi-specialty high-risk breast lesion conferences in an academic center.

To determine whether patients with benign papilloma diagnosed on core biopsy can be spared from surgery. We prospectively reviewed 150 consecutive core biopsy-diagnosed papilloma cases at a multi-specialty high-risk breast lesion conference to determine whether surgical excision was necessary. Of these 150 cases, 148 had concordant radiologic-pathologic features. Six were excluded due to lack of the first imaging follow-up until analysis. 112 were benign papillomas; 17 were papillomas involved by atypical ductal hyperplasia (atypical papilloma); 6 papillomas had ADH in adjacent tissue but not involving the papilloma; 2 papillomas were involved by atypical lobular hyperplasia (ALH); and 5 papillomas had ALH in adjacent tissue. Two were radiology-pathology (rad-path) discordant. Thirty-nine of the 112 benign papillomas were excised with no upgrade to carcinoma; 73 were followed with no disease progression during follow-up (185-1279days). Fifteen of 17 atypical papillomas were surgically excised with 4 (26.7%) upgraded to carcinoma. Four of the 6 patients with ADH adjacent to a benign papilloma underwent excision with 2 upgrades to carcinoma. None of the patients with papilloma, which was either involved by ALH or had ALH in adjacent tissue had upgrade or disease progression during follow-up (204-1159days). Finally, the two cases with discordant path-rad discordant were excised with no upgrade. Our data confirm that rad-path concordant benign papillomas diagnosed on core biopsy do not require surgery. It also supports the value of a formal multi-specialty review of all benign papilloma cases to create a consensus management plan.

Atypical lobular hyperplasia on core needle biopsy: contemporary results from a large community hospital breast program.

The management of biopsy proven atypical lobular hyperplasia (ALH) is controversial. Although upgrade rates are low, excisional biopsy is often performed to rule out occult breast cancer. In this study, we analyzed our experience with excisional biopsy for ALH diagnosed in the digital tomosynthesis era with radiographic concordance in the community hospital setting. This study included 93 consecutive patients diagnosed with pure ALH on core biopsy from January 2013-December 2017 who underwent subsequent excisional biopsy. Potential clinical, radiographic and pathologic predictors of upgrading were analyzed. At the time of excisional biopsy, five patients (5.4%) were upgraded to DCIS or invasive breast cancer. There was also a trend towards higher upgrade rates in patients with contralateral breast cancer (p = 0.06), biopsy performed by ultrasound or MRI (p = 0.07) and extensive ALH (p = 0.10). Other clinical, radiographic and pathologic variables were not predictive of upgrade rate (p > 0.1 for all). Patients with pure ALH with radiographic concordance have a low risk of pathologic upgrading on excisional biopsy. Potential predictors of upgrade rate warrant further analysis in a larger dataset.

Baseline Screening MRI Uptake and Findings in Women with ≥ 20% Lifetime Risk of Breast Cancer.

The American Cancer Society recommends screening magnetic resonance imaging (MRI) for patients with a ≥ 20% lifetime breast cancer risk. This study assesses the outcomes of baseline MRI screens in women from a high-risk breast clinic (HRBC). We retrospectively reviewed patients from our institution's HRBC, excluding those with prior breast cancer and predisposing genetic mutations. Screening MRI was recommended for a lifetime risk of ≥ 20% using the Tyrer-Cuzick model. We determined baseline MRI results, biopsy rates, and frequency of MRI-detected high-risk lesions (HRLs) and breast cancers. Overall, 319 women attended our HRBC; median age was 48years and 4.7% had prior atypia/lobular carcinoma in situ. Screening MRI was recommended for 282 patients, of whom 196 (69.5%) completed a baseline screen. A Breast Imaging-Reporting and Data System (BIRADS) 3 or 4 finding occurred in 19.6% of patients; 23 (12.3%) required 6-month follow-up MRI, 16 (8.6%) underwent core biopsy, and 4 (2.1%) underwent excisional biopsy after initial core. An additional 7 (3.7%) patients had a non-breast incidental finding. An HRL was identified in 2 (1.1%) patients (atypical ductal and lobular hyperplasia, respectively), and 2 (1.1%) were diagnosed with T1N0 breast cancers. In the setting of an HRBC, 70% of women with a ≥ 20% lifetime risk of breast cancer pursued screening MRI when recommended. On baseline screen, the rate of MRI-detected breast cancer was low (1%); however, malignancies were mammographically occult and identified at an early stage. Despite a low cancer rate, nearly one in four women required additional diagnostic investigation. Prescreening counselling should include a discussion of this possibility, and longer-term follow-up of screening MRI is needed in this high-risk population.

Upgrade Rate of Flat Epithelial Atypia Diagnosed at Stereotactic Core Needle Biopsy of Microcalcifications: Is Excisional Biopsy Indicated?

Whether the optimal management of pure flat epithelial atypia (FEA) found on core needle biopsy (CNB) specimens is surgical excision or imaging follow-up remains controversial. This study aimed to determine the upgrade rate to ductal carcinoma in situ (DCIS), invasive carcinoma or a high-risk lesion (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ), and it explored the relationship between a family history of breast cancer and the risk of upgrade. Cases with pure FEA found on stereotactic CNB of microcalcifications between March 2011 to December 2017 were followed by excisional biopsy or periodic imaging. The proportion of cases upgraded to a high-risk lesion and the odds of upgrade as related to a family history of breast cancer were determined with 95% confidence intervals (CIs). We identified 622 cases of pure FEA; 101 (16.2%) underwent surgical excision and 269 (43.2%) had imaging follow-up of ≥ 24 months. There were no upgrades to DCIS or invasive cancer in any of these 370 individuals (0%), and 4.6% (17/370; 95% CI: 2.9%-7.2%) were upgraded to a high-risk lesion. There was a nonstatistically significant trend between family history and upgrade to high-risk lesion (odds ratio 1.72 [95% CI: 0.65%-4.57%]). In our study, the upgrade rate of pure FEA to malignancy was 0%. We suggest that regular imaging follow-up is an appropriate alternative to surgery. Because of potential differences in biopsy techniques and pathologist interpretation of the primary biopsy, individual institutions should audit their own results prior to altering their management of FEA.

Do Histopathology and Clinical Outcomes of Breast Atypia Vary by Race/Ethnicity?

BackgroundThe clinical behavior of breast cancer varies by racial and ethnic makeup (REM), but the impact of REM on the clinical outcomes of breast atypia remains understudied. We examined the impact of REM on risk of underlying or subsequent carcinoma following a diagnosis of breast atypia. MethodsIn this retrospective, single-institution chart review, adult women diagnosed with breast atypia (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ) were stratified by REM. Regression modeling was used to estimate risk of underlying or subsequent carcinoma. ResultsWe identified 539 patients with breast atypia, including 15 Hispanic (2.8%), 127 non-Hispanic black (23.6%), and 397 non-Hispanic white women (73.7%). Diagnoses included 75.1% atypical ductal hyperplasia (n = 405), 4.6% atypical lobular hyperplasia (n = 25), and 20.2% lobular carcinoma in situ (n = 109). Rates for each type of atypia did not vary by REM (P = 0.33). Of those with atypia on needle biopsy, the rate of underlying carcinoma at excision was 17.3%. After adjustment, REM was not associated with greater risk for carcinoma at excision (P = 0.41). Of those with atypia alone on surgical excision, the rate of a subsequent carcinoma diagnosis was 15.4% (median follow-up 49 mo). REM was not associated with a long-term risk for carcinoma (P = 0.37) or differences in time to subsequent carcinoma (log-rank P = 0.52). Chemoprevention uptake rates were low (10.6%), especially among Hispanic (0%) and non-Hispanic black (3.8%) patients (P = 0.01). ConclusionsAmong patients with atypia, REM does not appear to influence type of histologic atypia, risk for carcinoma, or clinical outcome, despite differences in chemoprevention rates.

Non-invasive lobular neoplasia of the breast: Morphologic features, clinical presentation, and management dilemmas.

The designation of noninvasive lobular neoplasia applies to atypical epithelial proliferations composed of noncohesive cells secondary to loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of noninvasive lobular neoplasia encompasses atypical lobular hyperplasia (ALH) and classic lobular carcinoma in situ (classic LCIS) and two LCIS variants, namely florid LCIS (F-LCIS) and pleomorphic LCIS (P-LCIS), as defined in the World Health Organization (WHO) Classification of Tumors of the Breast 5th ed. Herein, we review the morphologic, immunohistochemical, and molecular features of noninvasive lobular neoplasia, with special emphasis on F-LCIS and P-LCIS. We also review imaging features, management at core needle biopsy, upgrade rates at surgical excision, and clinical management dilemmas.

OP0070 THE RISK OF PRECANCEROUS LESIONS OF THE BREAST AND CERVIX UTERI IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES: A NATIONWIDE POPULATION STUDY IN TAIWAN

Background:Precancerous lesions are pathologically atypical tissues which share part of abnormal features of cancerous tissue under microscopic examination but lack the ability of uninhibited growth and distant metastasis. Some of the measures to screen for precancerous tissues have gained popularity because supporting evidence indicates the beneficial effects on cancer incidence and mortality [1, 2]. However, the roles of these screenings and the risk of precancerous lesions in patients with autoimmune diseases have not been clarified. We aim to exam the risk of precancerous lesions among different autoimmune diseases.Objectives:To determine whether the Taiwanese autoimmune rheumatic diseases (ARDs) patients have a higher risk of precancerous lesions of the breast and cervix uteri.Methods:The Taiwan national breast cancer screening program provides biennially mammography for women above 45 years old or with a positive family history of breast cancer above 40 years old. The national cervical cancer screening program provides Pap smear test once every three years for women age above 30 years old. Using the National Health Insurance (NHI) database, we identified a cohort of 6 different groups of ARDs patients in Taiwan between 2004 and 2014. We linked the data from the national screening program of breast and cervical cancer and the NHI database to estimate the standardized incidence ratios (SIRs) of precancerous lesions (atypical lobular and ductal hyperplasia of the breast, carcinoma in situ of the breast, cervical intraepithelial neoplasia 1 to 3 of cervix uteri and carcinoma in situ of cervix uteri) in patients with ARDs compared with the general population.Results:From 2004-2014, we identified 64,904 patients with autoimmune diseases. Table 1 shows the number of patients receiving the screening programs. The standardized incidence ratio (SIR) of precancerous lesion of the breast was elevated in patients with rheumatoid arthritis (SIR, 2.21; 95% CI, 1.21-3.46) and Sjögren syndrome (SIR, 5.77; 95% CI, 2.63-9.85). The incidence of precancerous lesion of cervix uteri was elevated in patients with surveyed ARDs compared with the normal population, particularly for patients with systemic lupus erythematosus (SIR 28.94; 95% CI, 24.52-33.70) and inflammatory bowel disease (SIR, 27.50; 95% CI, 7.40-56.32) (Table 2).Table 1.Breast screen and Pap smear test in patients with autoimmune rheumatic diseasesRheumatoid arthritis (n=28289)Systemic lupus erythematosus (n=11609)Sjögren syndrome (n=17647)Systemic sclerosis (n=1489)Vasculitis(n=3050)Inflammatory bowel disease (n=2820)Female patients21199980815785104312251034Breast screening (n, %)6296 (29.70%)1382 (14.09%)4737 (30.01%)276 (26.46%)67 (5.47%)215 (20.79%)Pap smear (n, %)12827 (60.51%)6495 (66.22%)9961 (63.10%)670 (64.24%)1114 (90.94%)665 (64.31%)Table 2.Standardized incidence ratio (SIR) of precancerous lesion of the breast and cervix uteri in patients with autoimmune rheumatic diseasesPrecancerous lesion of BreastPrecancerous lesion of CervixSIR (95% CI)SIR (95% CI)Rheumatoid arthritis2.21 (1.21-3.46)5.32 (4.25-6.50)Systemic lupus erythematosus1.34 (0.27-2.93)28.94 (24.52-33.70)Sjögren syndrome5.77 (2.63-9.85)8.32(5.72-11.34)Systemic sclerosis6.45 (0.72-15.54)7.93 (2.90-14.80)Vasculitis0.007.68 (1.54-16.83)Inflammatory bowel diseases0.0027.50 (7.40-56.32)Conclusion:Precancerous lesions in the breast and cervix uteri were higher in female patients with ARDs and they should receive stringent screening program.

The Evolving Spectrum of Precursor Lesions of Cervical Adenocarcinomas.

Modern classification schemes divide cervical adenocarcinomas into human papillomavirus (HPV)-associated and HPV-independent types. The precursor lesions of the former are well known and comprise HPV-associated (usual/endocervical) adenocarcinoma in situ (AIS) and the much less common stratified mucin-producing intraepithelial lesion (SMILE). The precursor lesions of HPV-independent cervical adenocarcinomas are much less well known, although postulated precursors of gastric-type adenocarcinoma include atypical lobular endocervical glandular hyperplasia and gastric-type AIS. In this review, we cover HPV-associated and HPV-independent precursor lesions of cervical adenocarcinomas concentrating on diagnostic criteria (morphology and immunophenotype) and differential diagnosis. We propose a uniform terminology and diagnostic criteria for precursor lesions showing intestinal differentiation with goblet cells because this may be a feature of both HPV-associated and HPV-independent AIS.

Inter-observer reproducibility of classical lobular neoplasia (B3 lesions) in preoperative breast biopsies: a study of the Swiss Working Group of breast and gynecopathologists

PurposeClassical type of lobular neoplasia (LN) spans a spectrum of disease, including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), classical lobular neoplasia (LN), and the three-tiered classification of lobular intraepithelial neoplasia (LIN-1, -2, -3). This study addressed inter-observer variability of classical lobular neoplasias (LN) (B3 lesions) in preoperative breast biopsies among breast and gynecopathologistsMethodsA retrospective, observational, cross-sectional study was conducted. 40 preoperative digital images of breast core/vacuum biopsies were analyzed by eight experienced breast- and gynecopathologists. Evaluation criteria were ALH, LCIS, LN classic, LIN-1, LIN-2, LIN-3, focal B3 (one focus), extensive B3 (> one focus). Kappa-index and Chi-square tests were used for statistics. Digital scanned slides were provided to each participant. Agreement between the categories was defined as at least six of eight (cut-off 75%) concordant diagnoses.ResultsThe highest agreement between eight pathologists was reached using the category lobular neoplasia (LN, classical), 26/40 (65%) cases were diagnosed as such. Agreements in other categories was low or poor: 12/40 (30%) (ALH), 9/40 (22%) (LCIS), 8/40 (20%) (LIN-1), 8/40 (20%) (focal B3), 3/40 (7.5%) (LIN-2), and 2/40 (5%) (extensive B3). Chi-square-test (classical LN versus the other nomenclatures) was significant (p = 0.001137).ConclusionOur data suggest that among Swiss breast pathologists, the most reproducible diagnosis for B3 lobular lesions is the category of classical LN. These data further support lack of consistent data in retrospective studies using different terminologies. Validation of reproducible nomenclature is warranted in further studies. This information is useful especially in view of retro- and prospective data analysis with different diagnostic categories.

Evaluation of atypical hyperplasia after percutaneous vacuum-assisted biopsy of suspicious calcifications

Introduction: Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and flat epithelial atypia (FEA) are part of a heterogeneous group of lesions with uncertain malignant potential and varying rates of malignancy after wide excision. They represent a clinical challenge, given the lack of well-defined approach recommendations. Objective: To determine the local rate of "upgrade" to malignancy (invasive carcinoma or in situ) after wide excision of ADH, ALH, LCIS (classic lobular neoplasia) diagnosed by percutaneous vacuum-assisted biopsy performed only in suspicious calcifications, as well as analyze radiological and histopathological parameters that can be associated with a higher risk of "upgrade". Material and Methods: This is a retrospective analysis of 117 patients diagnosed with ADH, LCIS, and FEA after percutaneous vacuum-assisted biopsy of suspicious calcifications, from 2015 to 2018. We evaluated radiological parameters – lesion size, morphology of the calcifications, diameter of the needle, and presence of residual calcifications – and histopathological parameters – extension of atypia (focal or multifocal) and association with other atypias. Results: Among the 106 patients included, 77 (73%) underwent surgery, with a rate of "upgrade" to malignancy of 19.5% (10 ductal carcinomas in situ, of which 30% had high grade) and 5 had invasive carcinomas (4 ductal and 1 tubular, all with low grade). In the subgroup analysis, the rate of "upgrade" was 31% for ADH, 14.7% for FEA, and 7.7% for LCIS. Needle diameter (9Gx11G) (p=0.48), presence of residual calcifications (less than 90% of the cluster removed) (p=0.73), and mean cluster extension (calculated based on the original mammography) (p=0.66) showed no statistically significant correlation with an increase in the rate of "upgrade". Amorphous calcifications predominated (60%), followed by fine pleomorphic ones, with rates of "upgrade" of 11% and 35%, respectively. Regarding histological parameters, we found no statistically significant difference between groups with focal (up to 2 foci) and multifocal atypia or association with other atypias. Conclusion: Our rate of "upgrade" to malignancy was similar to that of the published literature, and we found no statistically significant radiological or histological criteria for a greater risk of "upgrade".

Atypical Ductal Hyperplasia and Lobular Neoplasia: Update and Easing of Guidelines.

OBJECTIVE. Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are among high-risk lesions that have been previously recommended for surgical excision when diagnosed on core needle biopsy. Recent studies have examined whether imaging surveillance is a reasonable alternative to surgical management for these lesions. This article synthesizes the evidence regarding management of atypical hyperplasia and LCIS diagnosed on core needle biopsy and clinical implications of these diagnoses on future breast cancer risk as well as highlights areas of further research needed to improve practice guidelines for these high-risk lesions. CONCLUSION. Although surgical excision is still recommended after diagnosis of ADH on core needle biopsy, in specific circumstances ALH and LCIS can safely be managed by imaging surveillance.

Pathologic Evaluation of Breast Tissue From Transmasculine Individuals Undergoing Gender-Affirming Chest Masculinization.

Bilateral mastectomy for chest masculinization is one of the gender-affirming procedures for transmasculine individuals. To optimize gross handling protocols and assess histopathologic findings in transmasculine breast tissue specimens. We identified all gender-affirming mastectomies from 2015 to 2018. We sequentially identified reduction mammoplasty (RM) cases for macromastia from the same period as control. Significant findings were defined as atypical ductal or lobular hyperplasia (ADH, ALH), ductal or lobular carcinoma in situ (DCIS, LCIS), or invasive carcinoma. Significant findings were present in 6 of 211 gender-affirming mastectomies (2.8%) as follows: ADH (n = 5) and LCIS together with ALH (n = 1). By comparison, 19 of 273 RM specimens (7%) yielded significant findings as follows: ALH (n = 11), ADH (n = 4), LCIS (n = 2), DCIS (n = 1), and invasive lobular carcinoma (n = 1). In the gender-affirming group, 142 transmen underwent androgen therapy before surgery, of whom 2 had significant pathologic findings. Thirty and 41 individuals had a family history of breast cancer in the gender-affirming and RM group, of whom 1 and 3 individuals had significant pathologic findings, respectively. Our study demonstrates that we handle transmasculine mastectomy specimens by examining 2.8 times more slides on average than for RMs, with a 2.5 times lower rate of significant pathologic findings. Prior family history of breast cancer or the use of androgen therapy before surgery in gender-affirming individuals did not increase the risk of identifying significant breast lesions. We recommend submitting 4 tissue blocks per mastectomy for individuals undergoing gender-affirming breast surgery.

Outcomes of classic lobular neoplasia diagnosed on breast core needle biopsy: a retrospective multi-center study.

Management of classic lobular neoplasia (cLN) diagnosed on core needle biopsy (CNB) is controversial. Our aim in this study was to review cases of cLN diagnosed on CNB to determine the rate and risk factors of an upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma on excision. All breast CNBs with a diagnosis of atypical lobular hyperplasia (ALH) or classic lobular carcinoma in situ (cLCIS) from three different institutions within a single health care system between 2013 and 2018 were retrieved. Cases with any additional high-risk lesions in the same CNB or discordant radiological-pathological correlation were excluded. Information about age, personal history of prior or concurrent breast cancer (P/CBC), and radiological and histological findings were recorded. A total of 287 cLN cases underwent surgical excision. Analysis of these 287 cLN cases showed 11 (3.8%) upgrade lesions on excision. Among the 172 ALH cases, there were 3 (1.7%) upgrades, which were all invasive lobular carcinomas (ILCs). On the other hand, 8 of 115 (7%) cLCIS cases revealed upgrade on excision (2 ILC, 5 DCIS. and 1 ILC + DCIS). Statistical analysis revealed that cLN cases with P/CBC, radiological asymmetry, or architectural distortion had a statistically significant higher upgrade rate on excision. Our findings revealed a low upgrade rate (3.8%) on the excision of classic lobular neoplasia diagnosed on breast core needle biopsy. Clinicoradiological surveillance can be appropriate when lobular neoplasia is identified on core biopsy with pathological radiological concordance in patients without a history of breast cancer, with the caveat that radiological asymmetry and architectural distortion are associated with a significant increase in an upgrade on excision.

Flat epithelial atypia: are we being too aggressive?

The malignant upgrade rate of flat epithelial atypia (FEA) diagnosed on core needle biopsy varies between 0 and 30%. Excision versus observation with radiological follow-up for these lesions remains controversial. We hypothesize that the local rate of FEA is low and that close radiological surveillance is a reasonable treatment option for patients diagnosed with pure FEA on breast needle core needle biopsy. This study was a retrospective review of a prospectively collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006 and 2016 were included in our analysis. Patients who had FEA present together with either in situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on preoperative imaging, the method of extraction, and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review was performed to confirm our results and help reduce inter-observer bias. The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 12%. Age at time of diagnosis, size of original lesion on mammogram, presence of atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia on core needle biopsy, the use of vacuum-assisted biopsy (VAB), or concordant imaging did not significantly correlate with malignant upgrade risk. None of the patients who were managed with radiological follow-up had malignant upgrade during follow-up. Patients undergoing radiological follow-up alone were more likely to have a VAB, concordant imaging, and no concurrent ADH. Our local malignant upgrade rate is consistent with published literature. We suggest radiological follow-up is a safe alternative in patients with pure flat epithelial atypia and concordant imaging, particularly those patients with small lesions in which microcalcifications can be removed completely with vacuum-assisted biopsy.

Benign breast papilloma: Is surgical excision necessary?

In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

Monitoring the progression of lobular breast carcinoma using multiphoton microscopy

Atypical lobular hyperplasia and lobular carcinoma in situ are often considered as non-obligate precursor lesions to invasive lobular carcinoma (ILC). The visualization of cell morphology changes during the progression of a lobular carcinoma has an important role in the real-time diagnosis of tumor staging. Also, monitoring the changes of collagen during tumorigenesis is vitally important for studying the efficiency of cancer cells entering surrounding tissues, as well as the metastatic potential. In this study, we compare the imaging quality of histological sections without staining and the haematoxylin and eosin (H&E)-stained samples of normal breast lobules by using multiphoton microscopy (MPM) based on two-photon excited fluorescence and second harmonic generation. It was found that the H&E-stained samples have a higher imaging contrast than the histological sections. Furthermore, we prove that MPM can be used not only to reveal changes in the tissue microstructure but can also provide information about collagen that cannot be rendered directly by the H&E-stained sample. Using Fourier analysis, we found significant differences in the morphology of collagen during the progression of the lobular carcinoma. In addition, at the invasion front of the ILC, we found that collagen was arranged parallel to the fat boundary by MPM. These results indicate that MPM can provide insights into trends of collagen reorganization and histological changes throughout breast tumor development and has potential as a clinical tool for evaluating the pathological character of breast cancer.

Association between ultrasound morphologic features and histopathological findings of lobular carcinoma.

IntroductionDespite the incidence and recurrence rates of breast cancer, there are currently no biomarkers to predict which cases will develop into lobular carcinoma (LC).The purpose of this study was to determine the association between ultrasound morphologic characteristics of LC and histopathological classifications.MethodsA retrospective, cross‐sectional study was conducted on the ultrasound images and histopathological reports of 100 patients with a confirmed LC diagnosis between January 2013 and December 2016.ResultsMorphologic ultrasound characteristics most frequently reported in the dataset of positively diagnosed LC patients were; irregular ultrasound shape (86%), hypoechoic echogenicity (88%), poorly circumscribed margin (95%), posterior acoustic enhancement (93%) and absent calcifications (81%). Using Fisher's extract test, it was found that stromal fibrosis, single file type pattern, atypical lobular hyperplasia and LC Grade II were significantly correlated with irregular shape and hypoechoic echogenicity.ConclusionA prognostic predictor tool can be designed from this study's findings which can then be used in practice to raise awareness of the unique morphometric markers related to LC of the breast.

Breast Atypia as a Biomarker of Risk

Provide a summary of available evidence on breast atypia as a biomarker of risk. With an increase in independent studies on atypical hyperplasia (AH), knowledge has advanced recently regarding its subsequent associated breast cancer risk. For women with AH, absolute risk can be estimated generally as ~ 1% per year, and a greater extent of disease appears to further increase risk. Although both breasts are at increased risk, the risk is higher for the ipsilateral breast. In women with AH, a family history of breast cancer does not confer significantly increased risk. Risk is similar for atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH), with some reports suggesting mildly higher risk for ALH. Prevention medications reduce breast cancer risk by ~ 70% in AH. Women with AH should be counseled on their increased risk and the option of prevention medication.

Incidental atypical hyperplasia/LCIS in mammoplasty specimens and subsequent risk of breast cancer.

1561 Background: Proliferative breast lesions with atypia (atypical hyperplasia and lobular carcinoma in-situ (LCIS)) increase the risk of breast cancer (BC). Most cases are diagnosed in the context of an abnormal mammogram. Little is known about BC risk for patients with these lesions who are asymptomatic. Mammoplasty specimens allow us to study breast tissue in asymptomatic healthy women. We previously published the rate of atypia in the largest reported mammoplasty cohort. The aim of this study is to examine the risk of BC in the atypia cohort. Methods: Breast pathology reports were retrospectively reviewed for evidence of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH) or LCIS in bilateral reduction mammoplasty specimens from five institutions within a single healthcare system between 1990 to 2017. Patients with prior or concurrent BC or prior atypia were excluded. Data was extracted from electronic medical records using natural language processing and manual review to assess subsequent risk of BC. Results: From our mammoplasty cohort of 4771 patients, 295 patients were found to have atypia (6.2%) at baseline. 40 of these patients were lost to follow-up and excluded from the study. For the remaining 255 patients, 13 had severe ADH bordering on ductal carcinoma in situ, 52 had LCIS, 119 had ALH, and 71 had ADH at baseline. The median age at baseline was 52.1 (range 17.9 – 74.3). With a median follow-up of 7.7 years, of the 255 patients 9 patients developed BC (8 invasive carcinomas, 1 ductal carcinoma in situ). 81.3% of the cohort did not receive chemoprevention. Only one patient out of the nine who developed BC received chemoprevention. The risk of developing BC among women with atypia at baseline was 0.5%, 2.9% and 4.1%, at 3, 5 and 10 years respectively. Conclusions: Patients with asymptomatic atypias found in reduction mammoplasty specimens appear to be at lower risk of developing BC than those diagnosed with atypia in the context of an abnormal mammogram. These results may provide guidance on how to manage this group of patients related to future screening and/or chemoprevention.