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Adenosis is a benign breast condition whose lesions can mimic breast carcinoma and is evaluated for malignancy with the Breast Imaging-Reporting and Data System (BI-RADS). We construct and validate the performance of modality-specific enhancement (MSE)-Breast Net based on multimodal ultrasound images and compare it to the BI-RADS in differentiating adenosis from breast cancer. A total of 179 patients with breast carcinoma and 229 patients with adenosis were included in this retrospective, two-institution study, then divided into a training cohort (institution I, n = 292) and a validation cohort (institution II, n = 116). In the training cohort, the final model had a significantly greater AUC (0.82; P < 0.05) than B-mode-based model (0.69, 95% CI [0.49-0.90]). In the validation cohort, the AUC of the final model was 0.81, greater than that of the BI-RADS (0.75, P < 0.05). The multimodal model outperformed the individual and bimodal models, reaching a significantly greater AUC of 0.87 (95% CI = 0.69-1.0) (P < 0.05). MSE-Breast Net, based on multimodal ultrasound images, exhibited better diagnostic performance than the BI-RADS in differentiating adenosis from breast cancer and may contribute to clinical diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fibrocystic changes are commonly seen in clinically symptomatic patients and during imaging workup of screening-detected findings. The term "fibrocystic changes" encompasses a broad spectrum of specific benign pathologic entities. Recognition of classically benign findings of fibrocystic changes, including cysts and layering calcifications, can prevent unnecessary follow-ups and biopsies. Imaging findings such as solid masses, nonlayering calcifications, and architectural distortion may require core needle biopsy for diagnosis. In these cases, understanding the varied appearances of fibrocystic change aids determination of radiologic-pathologic concordance. Management of fibrocystic change is typically conservative., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination. Benign proliferative breast diseases are well recognized in young females. Benign biphasic proliferation of epithelial and myoepithelial cells has been observed, among which adeno-myoepithelial adenosis is one of the rare morphologies published in the literature with the tendency to recur and poses a risk for low-grade malignant transformation. Here, we report a case of a young female who had a history of recurrent breast lump mimicking phyllodes tumor and eventually diagnosed as adeno-myoepithelial adenosis on histopathological examination.

Adenosquamous proliferation (ASP) is known to occur in the central nidus of radial sclerosing lesions (RSL) of the breast. However, their significance is debated and remains largely unknown. In addition, there is a histologic overlap between ASP and low-grade adenosquamous carcinomas (LGASC). We conducted a large retrospective review of 247 RSLs to evaluate the prevalence of ASP and quantitatively analyze associated histologic features of RSLs including size, stromal cellularity, and presence of chronic inflammation. The central nidus of RSLs were classified as hyalinized in 121 cases (49%), cellular in 37 cases (15%), and equally mixed hyalinized and cellular in 89 (36%). ASP occurred in 92 of 247 RSLs (37.2%). Cases with ASP were significantly associated with a cellular stroma; 78.4% of RSLS with cellular stroma had ASP versus just 11.6% of hyalinized RSLs. In our large cohort, inflammation is commonly found in RSLs with ASP (p= <0.001). In conclusion, we confirm that ASP is statistically more likely to be found in RSLs with a cellular stroma. In addition, ASP is commonly associated with chronic inflammation. The finding challenges the notion that prominent lymphocytes are a diagnostic clue to LGASC on limited biopsy material., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fibrocystic disease of breast is characterized by lumpiness and discomfort. Our 48-year-old perimenopausal patient had a painless progressively enlarging non-tender lump in her right breast since 1 year. On physical examination a 10 × 8 cm firm non-tender lump was observed occupying almost the whole breast, whose surface was nodular though not fixed. The operative specimen appeared like a honeycomb with multiple cavities filled with yellowish firm material typical of tuberculosis. Surprisingly, histology found neither this nor malignancy. Radical breast excision is never warranted except if the latter is confirmed.

Introduction: Flat epithelial atypia (FEA), lobular neoplasia (LN), papillary lesions (PL), radial scar (RS) and atypical ductal hyperplasia (ADH) are lesions of uncertain malignant potential and classified as B3 lesions by the European guidelines for quality assurance in breast cancer screening and diagnosis. Current management is usually wide local excision (WE), surveillance may be sufficient for some. We investigated the upgrade rate of B3 lesions to breast malignancy in a subsequent resection specimen after diagnosis on core needle-or vacuum assisted biopsy (CNB-VAB) in a national population-based series., Methods: Using data from the Belgian Cancer Registry (BCR) between January 1, 2013 and December 31, 2016, inclusion criteria were new diagnosis of a B3 lesion on CNB or VAB with subsequent histological assessment on a wider excision specimen. Histological agreement between first- and follow-up investigation was analyzed to determine the upgrade risk to ductal adenocarcinoma in situ (DCIS) or invasive breast cancer (IC) according to the type of B3 lesion., Results: Of 1855 diagnosed B3 lesions, 812 were included in this study: 551 after CNB-261 after VAB. After diagnosis on CNB and VAB, we found 19.0% and 14.9% upgrade to malignancy respectively. Upgrade risks after CNB and VAB were: FEA 39.5% and 17.6%; LN 40.5% and 4.3%; PL 10.4% and 12.5%; RS 25.7%and 0.0%; ADH 29.5% and 20.0%., Conclusion: Based on the observed upgrade rate we propose three recommendations: first, resection of ADH, and FEA with WE; second, resection of RS and classical LN with therapeutic VAB and further surveillance when radio-pathological correlation is concordant; third, surveillance of PL., (Copyright © 2023. Published by Elsevier Inc.)

Background: Fibroadenomas are the most common benign breast lesions in women. They present as a unilateral mass and can rapidly enlarge in size through hormonal changes. Fibroadenomas could be classified as small or giant, and as simple or complex. They are classified as 'giant' when the size exceeds 5 cm and/or weight 500 gram; and as 'complex' if one of the following characteristics is present: cysts with a size >3 mm, epithelial calcifications, sclerosing adenosis and papillary apocrine metaplasia. Giant fibroadenomas can cause compression of surrounding breast tissue or breast asymmetry, requiring surgical excision in order to preserve a normal breast shape., Case: A 26-year-old pregnant woman was referred with a palpable mass of her right breast. The mass rapidly increased in size to a diameter of 13 cm during the second trimester of her pregnancy. A tru-cut biopsy confirmed a fibroadenoma. The rapid growth and compression of normal breast tissues indicated a lumpectomy during her pregnancy. The mass was easily excised without any consequences for the pregnancy. Pathological examination showed a complex giant fibroadenoma., Conclusion: A unique case of a pregnant woman with rapid progression of a fibroadenoma that met the criteria of a complex and giant fibroadenoma, was presented. This case emphasizes the importance of timely surgical intervention, even during pregnancy, to prevent permanent breast tissue damage.

The presented case describes the difficulties of diagnosis of the breast microglandular adenosis (MGA), taken by clinicians for a malignant process due to the nature of growth and large size. Criteria for histological and immunohistochemical diagnosis and differentiation of MGA with malignant neoplasms, in particular, with tubular breast carcinoma, are presented. Taking into account the rarity of the pathology and the absence of described cases in the Russian-language literature, the observation is of interest to pathologists and clinicians.

Purpose: This study assessed the upgrade rates of high-risk lesions (HRLs) in the breast diagnosed by MRI-guided core biopsy and evaluated imaging and clinical features associated with upgrade to malignancy., Methods: This IRB-approved, retrospective study included MRI-guided breast biopsy exams yielding HRLs from August 1, 2011, to August 31, 2020. HRLs included atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, and papilloma. Only lesions that underwent excision or at least 2 years of MRI imaging follow-up were included. For each HRL, patient history, imaging features, and outcomes were recorded., Results: Seventy-two lesions in 65 patients were included in the study, with 8/72 (11.1%) of the lesions upgraded to malignancy. Upgrade rates were 16.7% (2/12) for ADH, 100% (1/1) for pleomorphic LCIS, 40% (2/5) for other LCIS, 0% (0/19) for ALH, 0% (0/18) for papilloma, and 0% (0/7) for radial scar/complex sclerosing lesion. Additionally, two cases of marked ADH bordering on DCIS and one case of marked ALH bordering on LCIS, were upgraded. Lesions were more likely to be upgraded if they presented as T2 hypointense (versus isotense, OR 6.46, 95% CI 1.27-32.92) or as linear or segmental non-mass enhancement (NME, versus focal or regional, p = 0.008)., Conclusion: Our data support the recommendation that ADH and LCIS on MRI-guided biopsy warrant surgical excision due to high upgrade rates. HRLs that present as T2 hypointense, or as linear or segmental NME, should be viewed with suspicion as these were associated with higher upgrade rates to malignancy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: When Core Needle Biopsy (CNB) demonstrates Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Intraductal Papilloma (IDP), or Radial Scar/Complex Sclerosing Lesion (RS), excisional biopsy (EB) is often performed to rule out underlying malignancy with upstage rates (UR) ranging between 1 and 20%. The COVID-19 pandemic led to delayed EB for many patients. We sought to evaluate whether this delay was associated with higher UR., Methods: We performed a retrospective analysis of women who underwent CNB and then EB for ADH, FEA, IDP, or RS between 2017 and 2021 using an IRB-approved repository. UR was evaluated by days between CNB and EB., Results: 473 patients met inclusion. 55 were upstaged to cancer (11.6%). 178 patients had pure ADH on CNB and 37 were upstaged (20.8%). 50 patients had pure FEA and 3 were upstaged (6%). 132 had pure IDP and 7 were upstaged (5.3%). 98 had pure RS and 1 was upstaged (1%). 7/15 (46.7%) had a combination of diagnoses or diagnosis with palpable mass and were upstaged. Days between CNB and EB were < 60 for 275 patients (58.1%), 60-90 for 108 (22.8%), 91-120 for 43 (9.1%), and > 120 for 47 (9.9%). There was no significant difference in UR (10.9% for < 60, 14.8% for 60-90, 7% for 90-120, and 12.8% for > 120, p = 0.54). UR for ADH was clinically increased after 60 days (27.8 vs. 17.5%), but this did not reach statistical significance (p = 0.1)., Conclusion: Surgical delay was not associated with an increased UR., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: B3 lesions are a heterogeneous group of breast lesions of uncertain malignant potential which usually require excision. The aim was to assess the efficacy of 5 years routine radiological or clinical follow-up of patients who had "high-risk" B3 lesions surgically excised, by analyzing recurrence and subsequent development of invasive/in-situ cancer., Patients and Methods: A 10-year retrospective review from 2010 to 2019 was performed of B3 lesions diagnosed on core needle biopsy, including patients who proceeded to surgical excision with a high-risk lesion on final histology. The database recorded 6 specific B3 lesion categories: 1. Atypical ductal hyperplasia (ADH), 2. Radial scars/complex sclerosing lesions (CSLs) with epithelial atypia 3. Classical Lobular neoplasia (ALH/LCIS), 4. Papillary lesions with epithelial atypia, 5. Mixed, 6. Flat epithelial atypia (FEA), including radiological and clinical follow-up data., Results: Six hundred sixteen patients had a B3 lesion after core biopsy. 110 patients had "high risk" lesions. This included 17 (15.5%) Atypical Ductal Hyperplasia (ADH), 22 (20%) radial scars/CSLs with epithelial atypia, 47 (42.7%) classical lobular neoplasia (LCIS/ALH), 7 (6.4%) papillary lesions with epithelial atypia, 13 (11.8%) mixed lesions & 4 (3.6%) Flat Epithelial Atypia (FEA) lesions. 4 of 110 (3.6%) developed invasive/in-situ disease and 4 of 110 (3.6%) developed recurrence during follow-up. 33 of 616 (5.4%) upgraded to invasive/preinvasive disease after surgical excision., Conclusion: Five years of routine radiological surveillance may not be necessary in patients who undergo surgical excision of "high-risk" B3 lesions. Clinical surveillance appears to be of little benefit, especially in patients with radial scars, papillary lesions, and FEA. Subsequent development of invasive/in-situ disease in patients who undergo surgical excision of atypical B3 lesions remains low., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Classification of breast tumors has been evolving in the last decade. Uncommon types of breast neoplasms have been increasingly recognized. While the pathogenesis of a subset of these tumors remains to be ascertained, integration of state-of-the-art knowledge from molecular advancements and clinical practice has enhanced our understanding of these diseases, be they unique to the breast or more frequently seen in other organs. Furthermore, these lesions may have diverse clinical outcomes despite of similar histopathologic and immunophenotypic characteristics or even molecular alterations, thus warranting different clinical management. Therefore, recognizing their salient histologic features and judicious use of ancillary studies is essential to reach the correct diagnosis in the pursuit of personalized medicine. This review provides an update on selective special types of breast neoplasms, with emphasis on their salient clinicopathologic features, diagnostic pitfalls, controversies, and recent molecular genetic advances., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Galactoceles are the common benign cystic breast lesions during pregnancy and lactation. This report describes the cytological findings of a case of long standing galactocele which underwent crystallization and mimicked carcinoma clinically as well as on sonography. A young woman presented with a hard painless lump in the right breast. She noticed the lump during her pregnancy 2.5 years back. Clinically the lesion was hard and sonography was equivocal in categorizing the lesion. An FNAC was performed which showed granular amorphous material along with crystals of various shapes and sizes. A diagnosis of crystallizing galactocele was made and woman was assured about the benign nature of the lesion. The cytological findings of crystallizing galactocele have been reported in very few cases. In the present case, a detailed history and clinical examination followed by fine needle aspiration established the diagnosis of crystallizing galactocele., (© 2022 Wiley Periodicals LLC.)

A 15-year-old male presented to the hospital with a 2-month history of a right parotid mass. Magnetic resonance imaging revealed an encapsulated 3.7 cm mass. Fine-needle aspiration suggested a monomorphic adenoma (prior to utilization of the Milan Classification system). Total parotidectomy was performed with dissection and preservation of the facial nerve. Surgical pathology identified the lesion as sclerosing polycystic adenosis (SPA) after examining the histopathological and immunohistochemistry findings. SPA is a rare lesion which leads to inflammatory changes in the salivary gland. The most common site impacted is the parotid gland but also can affect other major or minor salivary glands. The fibrocystic changes are morphologically like the histological developments of sclerosing adenosis of breast tissue. Those changes consist of fibrosis, apocrine metaplasia, and different degrees of proliferation of ducts, acini, and myoepithelial cells. The pathogenesis of SPA is unknown but recent studies suggest that it could be a neoplasm. Treatment with surgical excision is effective and its' recurrence is rare. This case report details the cytomorphology, histology, and immunohistochemical profile of SPA., (© 2021 Wiley Periodicals LLC.)

Blunt duct adenosis (BDA) is a breast lesion first described by Foote and Stewart in 1945 as a proliferative benign lesion of the terminal duct lobular unit. Throughout recent decades, further literature descriptions of BDA have been confusing. Some consider BDA to be a separate entity, some a growth pattern of columnar cell changes. The WHO 2012 considered BDA and columnar cell changes to be synonyms, while columnar cell lesions, especially those with atypia, are part of a spectrum of early precursors of the low nuclear grade breast neoplasia family. In the updated WHO 2019 version, BDA is mentioned as 'not recommended' terminology for columnar cell lesions without further discussing it, leaving the question open if BDA should be considered a separate entity.Good diagnostic criteria for BDA have however largely been lacking, and its biological background has not yet been unravelled. In this paper, we point out that BDA is mainly associated with benign breast lesions and not with other recognised precursor lesions. Further, 16q loss, which is the hallmark molecular event in the low nuclear grade breast neoplasia family, is lacking in BDA. We therefore hypothesise that BDA may not be a true precursor lesion but a benign polyclonal lesion, and propose morphological diagnostic criteria to better differentiate it from columnar cell lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Apocrine change is recognised in benign, atypical and malignant lesions of the breast. Apocrine metaplasia, a frequent finding in the breast of women over the age of 25 years, is most commonly seen in benign cysts with a simple or papillary configuration. Apocrine change is also recognised in other benign lesions including sclerosing adenosis, now known as apocrine adenosis. Apocrine atypia usually refers to cytological atypia in which there is at least threefold variation in nuclear size but architectural atypia may also occur. The distinction between atypical apocrine hyperplasia and non-high-grade apocrine ductal carcinoma in situ may be difficult due to the relative rarity of these entities and the lack of validated diagnostic criteria. Lobular carcinoma in situ (LCIS) with apocrine change is considered to be a variant of pleomorphic LCIS. An apocrine variant of encapsulated papillary carcinoma is also recognised. Apocrine change is described in invasive carcinoma, including no special type, lobular, micropapillary and mucinous variants. The recent WHO 2019 update recognises 'carcinoma with apocrine differentiation' as a special type breast carcinoma based on the presence of apocrine morphology in at least 90% of the tumour. Tumours with apocrine morphology are usually but not always hormone receptor negative. Human epidermal growth factor receptor 2 (HER-2) status is variable. Molecular studies have identified breast tumours with apocrine features and high expression of androgen receptor mRNA including 'luminal androgen receptor tumours' and 'molecular apocrine tumours'. The term 'pure apocrine carcinoma' has been proposed to describe an invasive carcinoma with apocrine morphology that is oestrogen and progesterone receptor negative and androgen receptor positive. HER-2 status may be positive or negative. This article reviews the pathology of benign, atypical and malignant apocrine lesions of the breast, with emphasis on diagnostic criteria including an approach to evaluation of apocrine lesions on needle core biopsy, and recent advances in our understanding of invasive apocrine carcinoma., (© 2021. The Author(s).)

BACKGROUND. Digital breast tomosynthesis-guided vacuum-assisted breast biopsy (DBT VAB) allows biopsy of findings seen better or exclusively on digital breast tomosynthesis (DBT), including architectural distortion. Although architectural distortion with an associated sonographic mass correlate has a high risk of malignancy, limited data describe the radiologic-pathologic correlation of tomosynthesis-detected architectural distortion without a sonographic correlate. OBJECTIVE. This study evaluates the malignancy rate of architectural distortions without a sonographic correlate that undergo DBT VAB and provides radiologic-pathologic correlation for benign, high-risk, and malignant entities that are associated with architectural distortion. METHODS. We retrospectively reviewed imaging, as well as pathology slides and/or reports, for DBT VABs performed for architectural distortion without a sonographic correlate at a single institution between June 1, 2017, and January 15, 2020. According to the correlative histopathology, cases were categorized as benign, high risk, or malignant, and specific histopathologic diagnoses were summarized. RESULTS. During the study period, 142 patients (mean age, 59 years) underwent DBT VAB for 151 unique architectural distortions without a sonographic correlate. DBT VAB revealed a malignant diagnosis in 27 (18%), a high-risk lesion in 50 (33%), and a benign diagnosis in 74 (49%). Two cases of atypical ductal hyperplasia were upgraded to malignancy, resulting in a final malignancy rate of 19% ( n = 29/151). Most malignant lesions were invasive carcinomas (83%, n = 24/29); most invasive carcinomas were of lobular subtype (54%, n = 13/24). Most high-risk lesions were radial scars/complex sclerosing lesions (62%, n = 31/50). Most benign results represented fibrocystic change (66%, n = 49/74). A subset (11%, n = 8/74) of benign results were considered discordant and subsequently excised, with none representing malignancy. CONCLUSION. The final malignancy rate of 19% in architectural distortion without a sonographic correlate justifies a recommendation for biopsy using DBT VAB. CLINICAL IMPACT. Our results highlight the utility of DBT VAB in the era of DBT. The detailed radiologic-pathologic correlations will assist radiologists in assessing concordance when performing DBT VAB for architectural distortions and provide a reference for future patient management.

Background: The infertile women have an increased risk of developing benign and malignant tumors, in particular, breast cancer. Most studies have examined the role of gene variants in the risk of developing breast cancer, but there is little evidence of genetic risk factors for benign tumors., Aim: To assess the combined genetic risk of developing mastopathy in women with FSHR (rs6165, rs6166) and ESR1 (rs9340799, rs2234693) gene variants., Materials and Methods: The study included 87 infertile women (45 with concomitant fibrocystic mastopathy and 42 without mastopathy)., Results: For rs9340799 and rs2234693 variants of the ESR1 gene, we did not find any significant differences in the distribution of genotypes in infertile women with or without mastopathy. In patients with mastopathy, there was a reliable increase in the frequency of 307Ala/Ala and 680Ser/Ser genotypes of FSHR gene (χ 2  = 6.39, p = 0.012, OR = 4.49 (1.48-13.65)) as compared to patients without mastopathy. In the presence of 307Thr/Thr and 680Asn/Asn genotypes of the FSHR gene, a 4.88-fold reduction of mastopathy risk (χ 2  = 8.06, p = 0.005, OR = 0.21(0.07-0.59)) was observed. The frequency of the FSHR and the ESR1 genotypes combinations - 307Thr/Thr+680Asn/Asn+351AG+397TC was significantly decreased in patients with mastopathy., Conclusions: Our study did not find an association of ESR1 gene variants with the risk of developing of mastopathy in infertile women although heterozygous variants of the ESR1 gene enhanced the "protective" effect of FSHR gene variants and reduced the risk of mastopathy.

Microglandular adenosis (MGA)-related lesions, including atypical MGA (AMGA) and carcinoma involving MGA (C-MGA), are characterized by epithelial atypia, negative hormone receptors, and HER2 status, and can mimic invasive triple negative breast cancer (TNBC) in core needle biopsies (CNB) resulting in selection for treatment with neoadjuvant chemotherapy (NAC). We identified 12 cases of AMGA and/or C-MGA in post-NAC excision specimens (EXC) and analyzed their morphologic and immunohistochemical (IHC) features. All CNBs were initially diagnosed as containing TNBC. Upon re-review, TNBC was confirmed in nine cases. In three CNBs AMGA and/or C-MGA had been interpreted as TNBC. AMGA was initially recognized in only one case but AMGA and/or C-MGA were present in an additional nine CNBs. At EXC, no residual TNBC was present in 5 of 9 EXCs and all 12 cases showed residual AMGA and/or C-MGA. Similar to conventional MGA, AMGA, and C-MGA were positive for S-100, laminin and collagen IV and negative for calponin and p63. Following NAC, these lesions retained their typical staining pattern despite acquiring treatment-related morphologic alterations, most notably of which were areas of single cell growth pattern seen in eight EXCs. This study is the first to report the effects of NAC on AMGA and C-MGA. Our data showed no response of the AMGA and/or C-MGA following NAC in contrast to the high response rate of conventional TNBC. In particular, the infiltrative single cell pattern of post-NAC MGA-related lesions closely mimicked residual TNBC. The persistence of AMGA and C-MGA following NAC supports the notion that these lesions are distinct from conventional TNBC. Our findings also highlight the challenges in recognizing AMGA and C-MGA in CNBs which may lead to unwarranted treatment with NAC in the absence of conventional TNBC.

Microglandular adenosis (MGA) represents a rare neoplasm of the mammary gland, which in a subset of cases may be associated with triple-negative breast cancer (BC). The biology of MGA is poorly understood. In this study, eight MGA cases (n = 4 with and n = 4 without associated BC) were subjected to a comprehensive characterization using immunohistochemistry, genome-wide DNA copy number (CN) profiling, fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and DNA methylation profiling using 850 K arrays and bisulfite pyrosequencing. Median patient age was 61 years (range 57-76 years). MGA lesions were estrogen receptor (ER)-negative, progesterone receptor-negative, HER2-negative, and S100-positive. DNA CN alterations (CNAs) were complex or limited to few gains and losses. CN gain on chromosome 2q was the most common CNA and was validated by FISH in five of eight cases. NGS demonstrated an average of two mutations per case (range 0-5) affecting 10 different genes (ARID1A, ATM, CTNNB1, FBXW7, FGFR2, MET, PIK3CA, PMS2, PTEN, and TP53). CNAs and mutations were similar in MGA and adjacent BC, indicating clonal relatedness. DNA methylation profiling identified aberrant hypermethylation of CpG sites within GATA3, a key transcription factor required for luminal differentiation. Immunohistochemistry showed regular GATA3 protein expression in the normal mammary epithelium and in ER-positive BC. Conversely, GATA3 was reduced or lost in all MGA cases tested (8/8). In conclusion, MGA is characterized by common CN gain on chromosome 2q and loss of GATA3. Epigenetic inactivation of GATA3 may provide a new clue to the peculiar biology of this rare neoplasia., (© 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in women of reproductive age. There is no clear association between PCOS and benign breast disease (BBD). The latter is a frequent benign disorder, affecting women between 20 and 50 years of age. To date, the classification remains controversial, and the risk of developing breast cancer that is associated with these changes is different depending on the histopathological findings. The most frequent changes are breast cysts, which are noted in up to 50% of patients older than 30 years of age. This up-to-date review presents the relationship between PCOS and BBD. In conclusion, there is no clear association between benign breast disease and PCOS. Further studies on a large population with prospectively collected data using updated PCOS criteria are necessary., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Anogenital mammary-like glands, formerly described as ectopic breast tissue, are currently considered to be normal histologic components of the anogenital region. Anogenital mammary-like glands can give rise to many lesions identical to counterparts in the native female breast. We describe four cases of such lesions, including fibroadenoma, gynecomastia-like hyperplasia, and ectopic mammary-type tissue with a spectrum of usual ductal hyperplasia, apocrine metaplasia, adenosis, and pseudolactational change. All four cases occurred in young women (ages 29-38) who presented with vulvar or perianal masses. Similar to previously reported cases, these lesions shared histologic and immunohistochemical characteristics identical to native female breast lesions. Novel findings in our cases included (1) the first case of gynecomastia-like change to be reported in the perianal area of a female, (2) Immunohistochemical staining identifying a 3-layered epithelium characterized by a population of CK14 and CK5/6 positive and hormone receptor negative superficial luminal cells, and (3) diffuse, strong positivity for GATA3 in all cases. Our study adds to the literature on these rare lesions and highlights findings which may be useful in understanding the pathogenesis and improving the diagnosis of anogenital mammary-like gland lesions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Proliferative epithelial lesions are risk factors for breast cancer. They are a heterogeneous group of lesions in which the presence of atypia is related to varying degrees of risk. They should be considered in the differential diagnosis with benign lesions, in situ ductal carcinoma and infiltrating carcinoma. An accurate histopathological diagnosis is important in choosing the best therapeutic option, including vacuum assisted biopsy and surgery. We revise diagnostic criteria and the differential diagnosis of usual ductal hyperplasia, radial scar and complex sclerosing lesions, distinct types of adenosis, papillary lesions, atypical ductal hyperplasia, flat epithelial atypia and lobular neoplasia in situ. Furthermore, we summarize the degree of risk associated with the different conditions and management possibilities., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The aim of this study was to present several cases of benign and malignant nipple lesions and contribute to diagnosis and differential diagnosis., Methods: A retrospective study was conducted on 13 patients. All of the patients were evaluated by ultrasonography, and 11 of them had pathological results. We analyzed the clinical and sonographic features., Results: There were 3 malignant lesions, 7 benign lesions, and 3 congenital nipple dysplasia, listed as follows:Malignant lesions (n = 3, 23%): Paget's disease (PD, n = 3, 23%). All of the patients with PD showed unilateral nipple erosion, discharge, and pain. The ultrasound showed abundant blood flow (n = 3, 23%); 2 patients (n = 2, 15%) had microcalcifications.Benign lesions (n = 7, 54%): Adenoma of the nipple (n = 2, 15%). One patient (n = 1, 8%) had nipple erosion and discharge. Two patients (n = 2, 15%) had a palpable nodule in the nipple. The ultrasound of both patients (n = 2, 15%) showed regular-shaped, clear border nodule with abundant blood flow (n = 2, 15%).Leiomyoma of the nipple (n = 1, 8%): This male patient was characterized by unilateral nipple enlargement and pain. The ultrasound showed a regular nodule with absent blood flow.Plasma cell mastitis (n = 2, 15%): Two patients showed unilateral nipple inversion and pain. One patient (n = 1, 8%) showed swollen and redness. The 2 patients showed a lesion in the gland around the nipple present as an irregular shape and unclear boundary hypoechoic mass.Nipple wart (n = 2, 15%): Two patients showed a unilateral soft exogenous neoplasm. Both of the patients showed a hypoechoic wart; the echo was similar to the nipple, the border was clear, and had no blood flow in the wart.Nipple Dysplasia (n = 3, 23%): Accessory nipple (n = 3, 23%). Two patients (n = 2, 15%) had accessory nipples in the subcoastal area, 1 patient (n = 1, 8%) in the areolar. All of the patients' sonographic features were the same as the nipple.The positive predict value (PPV) of the clinical symptoms: Erosion and discharge are both 75% (P < 0.05). The PPV of the US manifestations: irregular shape, indictinct margin, abundant blood flow, microcalcification, thicken skin in diagnosing malignant lesions are 60%,60%,60%,100%,100%, respectively (P < 0.05)., Conclusions: The characteristic sonographic features together with clinical symptoms contribute to the diagnosis of nipple lesions.

Breast cancer is the most diagnosed cancer among women around the world. The development of computer-aided diagnosis tools is essential to help pathologists to accurately interpret and discriminate between malignant and benign tumors. This paper proposes the development of an automated proliferative breast lesion diagnosis based on machine-learning algorithms. We used Tabu search to select the most significant features. The evaluation of the feature is based on the dependency degree of each attribute in the rough set. The categorization of reduced features was built using five machine-learning algorithms. The proposed models were applied to the BIDMC-MGH and Wisconsin Diagnostic Breast Cancer datasets. The performance measures of the used models were evaluated owing to five criteria. The top performing models were AdaBoost and logistic regression. Comparisons with others works prove the efficiency of the proposed method for superior diagnosis of breast cancer against the reviewed classification techniques., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Habib Dhahri et al.)

Introduction: Microglandular adenosis (MGA) is a rare benign proliferative lesion lacking a myoepithelial cell layer; 27% of all reported cases have progressed to invasive carcinoma. Salivary gland-type carcinomas of the breast are also uncommon, representing 2% of all breast cancers. This wide spectrum of neoplasms tends to be triple negative and generally has an excellent prognosis. Given the rarity of salivary gland-type carcinomas of the breast arising from MGA, there are few reports of these cases in literature. As such, there is uncertainty regarding their diagnosis and treatment strategies., Presentation of Case: We report the rare case of a 66-year-old woman who presented with a triple negative, invasive carcinoma with salivary gland-type features, arising from MGA. The patient underwent mastectomy with sentinel lymph node biopsy, followed by Taxotere and Cyclophosphamide (TC) chemotherapy and 50 Gy in 25 fractions of radiation to her chest wall. We reviewed the available literature on salivary gland-type breast carcinomas arising from MGA., Discussion: Despite the generally unfavourable characteristics associated with carcinoma arising in microglandular adenosis (MGACA), most patients with MGACA have favourable outcomes., Conclusions: The findings of the present case and reviewed cases are consistent with the literature on MGA, atypical MGA (AMGA), and MGACA. Future study of this rare entity is warranted to establish a consensus surrounding its clinical significance and treatment methods., Competing Interests: Declaration of Competing Interest KJJ has served as a consultant for Esai, Genomic Health Inc, Novartis, Purdue Pharma, Pfizer and Roche. She received research support from Astra Zeneca Eli Lilly, and was a speaker for Apobiologix, Novartis, as well as Purdue Pharma. The remaining authors declare that there is no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context.—: Microglandular adenosis is a rare borderline neoplastic lesion of the breast composed of haphazardly located small, round tubules with a single cell layer interspersed within breast stroma and/or adipose tissue. Microglandular adenosis is devoid of a myoepithelial cell layer, and has a characteristic immunophenotype, being positive for S100 and negative for estrogen receptor, progesterone receptor, and HER2/ neu . When associated with cancer, microglandular adenosis and associated invasive carcinoma share the same molecular alterations, including TP53 mutation; therefore, microglandular adenosis is considered a nonobligate precursor of triple (HER2/ neu , estrogen and progesterone receptors)-negative breast carcinoma. Microglandular adenosis is an important diagnostic pitfall as it can be easily mistaken for a low-grade invasive carcinoma., Objective.—: To provide a review of the clinicopathologic features of microglandular adenosis and associated invasive carcinoma, with emphasis on key features separating entities in the differential diagnosis., Data Sources.—: Review of current literature on microglandular adenosis and associated invasive carcinoma and personal experience of authors., Conclusions.—: Microglandular adenosis can mimic breast carcinoma; attention to key features, including morphologic-immunophenotypic correlation, is essential in establishing the diagnosis.

Core needle biopsy (CNB) is the most common sampling technique for the histologic evaluation of breast abnormalities. Diagnosing benign proliferative, borderline and some in-situ lesions in CNB is challenging and subject to a significant degree of interobserver variability. In addition, due to the inherent limitations of CNB, "upgrading" to a more significant pathology at excision is an important consideration for some lesions. Pathologists carry a major responsibility in patient diagnosis, risk stratification and management. Familiarity with the histologic features and the clinical significance of these common and problematic lesions encountered in CNB is necessary for adequate treatment and patient follow-up. This review will focus on benign, atypical and in-situ epithelial proliferations, papillary lesions, radial sclerosing lesions, adenosis and cellular fibroepithelial lesions. Highlights of histologic features, useful strategies for accurate diagnosis, basic immunohistochemistry and management will be presented., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: The clinical significance of radial scar (RS)/complex sclerosing lesion (CSL) with high-risk lesions (epithelial atypia) diagnosed on needle core biopsy is not well defined. We aimed at assessing the upgrade rate to ductal carcinoma in situ (DCIS) and invasive carcinoma on the surgical excision specimen in a large cohort with RS/CSL associated with atypia., Methods: 157 women with a needle core biopsy diagnosis of a RS/CSL with atypia and follow-up histology were studied. Histological findings, including different forms of the atypical lesions and final histological outcome in the excision specimens, were retrieved and analysed, and the upgrade rates for malignancy and for invasive carcinoma were calculated., Results: 69.43% of the cases were associated with atypical ductal hyperplasia (ADH) or atypia not otherwise classifiable, whereas lobular neoplasia was seen in 21.66%. On final histology, 39 cases were malignant (overall upgrade rate of 24.84%); 12 were invasive and 27 had DCIS. The upgrade differed according to the type of atypia and was highest for ADH (35%). When associated with lobular neoplasia, the upgrade rate was 11.76%. The upgrade rate's variability was also considerably lower when considering the upgrade to invasive carcinoma alone for any associated lesion., Conclusions: The upgrade rate for ADH diagnosed on needle core biopsy with RS is similar to that of ADH without RS and therefore should be managed similarly. RS associated with lobular neoplasia is less frequently associated with malignant outcome. Most lesions exhibiting some degree of atypia showed a similar upgrade rate to invasive carcinoma. Management of RS should be based on the concurrent atypical lesion., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The diagnosis of radial scars/complex sclerosing lesions (RSs/CSLs) onpercutaneous biopsy carries a risk of histological underestimation. Consequently, surgical excision is often performed in order to exclude a possible associated malignancy. The aim of this study was to assess the rate of 'upgrade to carcinoma' upon subsequent surgical excision of RS/CSL cases diagnosed on vacuum-assisted large-core biopsy (VALCB). We also analysed the risk factors for upgrade in order to determine a subset of patients who could avoid surgery and benefit from conservative management with clinical and imaging follow-up., Methods and Results: This was a retrospective observational single-centre study on 174 consecutive RS/CSL cases diagnosed on VALCB from May 2008 to October 2015. Univariate analysis was performed to identify clinical, radiological and histological risk factors for upgrade. Surgical excision was performed following VALCB diagnosis of 88 RS/CSL cases with or without associated atypia. The overall rate of surgical upgrade to carcinoma was 9.1% (8/88). None of the benign biopsies without atypia was surgically upgraded. Additional to atypia, risk factors for upgrade were non-incidental finding of the RS/CSL, the mammographic appearance, and the number of fragments obtained during the biopsy procedure (P < 0.05)., Conclusion: We demonstrate that VALCB revealing an RS/CSL is reliable for excluding malignancy when there is no associated atypia and when radiological and histological findings are concordant. In such cases, surgery can be avoided in favour of clinical and imaging follow-up. When an RS/CSL is associated with atypia, the decision to perform surgical excision depends on other associated risk factors., (© 2019 John Wiley & Sons Ltd.)

Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin-stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm 2 , median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm 2 , OR T3vsT1 : 3.42, 95% confidence interval (CI), 1.87-6.28; acini count/TDLU T3vsT1 , OR: 2.40, 95% CI, 1.39-4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD., (©2019 American Association for Cancer Research.)

Microglandular adenosis (MGA) of the breast is exceedingly rare, with only a few case reports and series published to date. Previous studies have elegantly demonstrated the progression of benign MGA to atypical MGA to MGA-in situ carcinoma to invasive carcinoma and therefore suggest MGA as a possible non-obligate precursor lesion to a subset of breast carcinomas. Immunohistochemically, MGA is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2-neu oncoprotein expression, and carcinomas arising in the setting of MGA are often reported to be triple negative. In this article, we present a unique case of an ER+/PR+/HER2- invasive carcinoma associated with MGA and atypical MGA. Our case highlights the diagnostic pitfall of MGA and suggests that MGA is a heterogeneous group of lesions with potential for either luminal-type or basal-type differentiation during progression to breast carcinoma.

Introduction: The purpose of this study was to evaluate mammographic and magnetic resonance imaging (MRI) features in B3 lesions., Patients and Methods: From 2011 to 2018, 139 patients with histologically proven B3 lesions who underwent mammography or/and MRI, were retrospectively reviewed. B3 lesions were classified in: atypical ductal hyperplasia (ADH), lobular neoplasia (LN), papillary lesion (PL), radial scar (RS), flat epithelial atypia (FEA), phyllodes tumor (PT), or mesenchymal lesion. Imaging features evaluated were: the presence of microcalcifications, mass and architectural distortions on mammograms and type of margins (circumscribed, irregular, spiculate), enhancement (mass-like, non-mass-like), size (≤ 15 mm, > 15 mm), and kinetics curves (I, II, III) on MRI. The definitive histologic results confirmed benign lesion or were upgraded to malignancy, and the positive predictive value was calculated., Results: Histologic classification of B3 lesions counted 45 (32.37%) ADH, 12 (8.63%) LN, 25 (17.99%) PL, 5 (3.61%) RS, 31 (22.31%) FEA, 20 (14.39%) PT, and 1 (0.70%) mesenchymal lesion. One hundred seven patients had mammography, and 38 had MRI. In 90 (65%) cases, the histologic diagnosis confirmed B3, in 15 (11%) cases, benign lesion, and in 34 (24%) cases, malignancies were found, with best positive predictive value for mesenchymal tumor (1), ADH (0.36), and FEA (0.4). Significant correlations comparing core needle biopsy groups and microcalcifications (P = .016) and presence of mass (P = .002) and comparing definitive histology with the presence of mass (P = .023), were found. Regarding MRI, the morphology correlated with core needle biopsy groups (P = .038); morphology (P = .024), dimension (P = .040), and kinetic curve (P = .005) correlated with malignancy., Conclusions: The B3 category includes different entities, with various risk of malignancy; their heterogeneity is associated with specific mammographic and MRI features, although further confirmations are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: The evaluation of the surgical margin in breast conservative surgery is a matter of general interest as such treatments are subject to the critical issue of margin status as positive surgical margins can undermine the effectiveness of the procedure. The relatively unexplored ability of millimeter-wave (mm-wave) spectroscopy to provide insight into the dielectric properties of breast tissues was investigated as a precursor to their possible use in assessment of surgical margins., Methods: We assessed the ability of a mm-wave system with a roughly hemispherical sensitive volume of ∼3 mm radius to distinguish malignant breast lesions in prospectively and consecutively collected tumoral and non-tumoral ex-vivo breast tissue samples from 91 patients. We characterized the dielectric properties of 346 sites in these samples, encompassing malignant, fibrocystic disease and normal breast tissues. An expert pathologist subsequently evaluated all measurement sites., Results: At multivariate analysis, mm-wave dielectric properties were significantly correlated to histologic diagnosis and fat content. Further, using 5-fold cross-validation in a Bayesian logistic mixed model that considered the patient as a random effect, the mm-wave dielectric properties of neoplastic tissues were significantly different from normal breast tissues, but not from fibrocystic tissue., Conclusion: Reliable discrimination of malignant from normal, fat-rich breast tissue to a depth compatible with surgical margin assessment requirements was achieved with mm-wave spectroscopy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Reduction mammaplasty (RM) is one of the most common plastic surgery procedures. Despite its cost, the total number of RM procedures continues to increase every year., Objectives: The purpose of this study is to review the prevalence of benign and malignant breast lesions among women who live in the Aegean region of Turkey, based on our university hospital's records and to compare our results with those in the literature., Methods: Seven hundred and thirty-three consecutive female patients who underwent RM between January 2003 and January 2017 in the Department of Plastic, Reconstructive, and Aesthetic Surgery were included in this study., Results: One hundred and sixty-five patients (23.4%) had preoperative breast imaging results. According to the Breast Imaging Reporting and Data System (BIRADS), most of these patients had BI-RADS-2 and BIRADS-1 findings (41.21% and 40%, respectively). Fibrocystic changes were the most common lesions (81.3%). Sixty-eight patients (9.6%) had normal breast tissue on the right side and 34 patients (4.8%) had the same on the left side. Five patients (0.71%) had atypical ductal hyperplasia and no atypical lobular carcinoma. Four patients (0.56%) had occult breast cancer and one patient (0.14%) had benign phyllodes tumor., Conclusions: RM is a good opportunity to detect proliferative lesions and occult breast cancer. While meeting the patient's aesthetic desires, the plastic surgeon should consider for histopathological evaluation. We suggest that every part of the breast tissue should be sent to pathological examination regardless of the weight of the specimen. Even if health insurance does not cover its cost, patients should be informed about the importance of this process., (© 2018 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Microglandular adenosis (MGA) is a rare breast lesion reported to be associated with invasive carcinoma in up to 20% to 30% of cases and has been proposed as a nonobligate precursor to basal-like breast cancers. We identified a case of matrix-producing metaplastic carcinoma with morphologic and immunohistochemical evidence of progression from MGA to atypical MGA, carcinoma in situ, and invasive carcinoma. We performed whole-exome sequencing of each component (MGA, atypical MGA, carcinoma in situ, and cancer) to characterize the mutational landscape of these foci. There was a significant copy number overlap between all foci, including a segmental amplification of the CCND1 locus (partial chromosome 11 trisomy) and MYC (8q24.12-13). Using a bioinformatics approach, we were able to identify 3 putative mutational clusters and recurrent, stop-gain nonsynonymous mutations in both ZNF862 and TP53 that were shared across all foci. Finally, we identified a novel deleterious splice-acceptor site mutation of chr5:5186164 G>T (chromosome 5p15) encoding the gene, ADAMTS16, in the invasive component., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cystic hypersecretory carcinoma is a rare subtype of breast cancer. It is a member of cystic hypersecretory lesions, which include a series of pathological disease lineages: cystic hypersecretory hyperplasia (CHH), CHH with atypia, cystic hypersecretory carcinoma (CHC) and invasive CHC. It was found that most cystic hypersecretion lesions were in situ carcinoma, and only 19 cases of invasive cystic hypersecretion carcinoma were reported., Case Presentation: We are reporting a case of a 63-year-old female who had a lump in her left breast for 3 years. A modified radical mastectomy was done and morphological diagnosis of invasive CHC with axillary node metastasis was made., Conclusions: Owing to a smaller number of reported cases, little is known about the biological behavior, prognosis and molecular study of cystic hypersecretion lesions. Therefore, more cases with follow-up data are needed to reveal the biological behavior of this rare tumor.

Rationale: The term cystic breast lesions is a sonographic diagnosis, which can be categorized as simple, complicated or complex. The complex cysts are deemed as having a low risk of breast cancer. The highly aggressive invasive ductal carcinomas among complex cysts, in particular, are infrequent reported., Patient Concerns: A 56-year-old female with a breast complex cyst who, after fine-needle aspiration, complained about oozing with fluid as well as skin ulceration that did not heal., Diagnoses: An advanced HER-2-enriched invasive ductal carcinoma was diagnosed., Interventions: The patient received neoadjuvant chemotherapy of anti-HER-2 target drug, palliative surgery and following postoperative chemotherapy., Outcomes: The patient was in good general condition at 6 months follow-up after surgery., Lessons: Meticulous ultrasound evaluation of Breast Imaging Reporting and Data System (BI-RADS) category is crucial and indispensable when a complex cyst is found. The radiologist and clinician should be fully awake to its possibility of malignancy, especially fast-growing one in post-menopausal women. Excision biopsy may be preferred for diagnosis.

Microglandular adenosis (MA) of the breast, a benign glandular proliferation, was originally described approximately 35 years ago. The lesion is constituted by small glands, all of the same size. Glands are lined by one layer of cuboidal epithelial cells encircled by basal lamina without any evidence of interposed myoepithelial elements. Cells are positive for low-weight keratins and S-100 protein and negative for estrogen receptor, progesterone receptor, and HER-2. Since then, in the years that followed, several malignant lesions all showing microglandular architecture have been regarded either as a precursor or as an equivalent manifestation of MA. The latter has been associated with a large number of malignancies that include ductal carcinoma in situ, lobular carcinoma in situ, ademyoepithelioma, high-grade basal-like carcinoma, adenoid cystic carcinoma, matrix-producing carcinoma, invasive duct carcinoma not otherwise specified, and spindle cell carcinoma, not to mention acinic cell carcinoma. None of the above tumors were identical to MA. Differences mainly rested not only on the specific structure of the small glands but also on the cytological composition and immunohistochemical features of different lesions. Here, a review of the features of MA together with the differential diagnosis with lesions showing microglandular structure is discussed. MA shows similarities to a lesion named microglandular hamartoma/adenosis of the nasal cavity. The relation of the 2 similar lesions is discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Some fibroepithelial lesions (FEL) of the breast are difficult to classify as cellular fibroadenoma (CFA) or benign phyllodes tumor (BPT) due to overlapping histologic features. This indeterminate group is histologically characterized by prominent stromal cellularity, mild atypia, and mitotic activity. The local recurrence potential of cellular FEL (CFEL) has been insufficiently studied. The objective of this study was to evaluate the histologic features, characterize the long-term follow-up and recurrence rate of CFEL, and compare this data with the recurrence rate of definitive BPT. Ninety CFEL that were <4 cm were recovered from the benign breast disease cohort. The control group comprised of 10 randomly selected patients with BPT. Cases were classified based on a combination of mitotic activity, intracanalicular growth, stromal atypia, stromal prominence, and fat infiltration. None of the CFEL was widely excised. Of the 90 CFEL cases, there were 22 BPT-like, 35 CFA, and 33 indeterminate. The mean age of the patients was 40.1 years. The mean tumor size was 2.4 cm. All patients had at least two years of follow-up (median 27). None of the patients with BPT-like CFEL showed ipsilateral recurrence. Five of the 35 patients with CFA had recurrent ipsilateral CFA. This occurred within 1 to 11 years after the initial diagnosis. One of 33 patients with indeterminate type had a recurrent ipsilateral lesion five years after the initial diagnosis with histologic features of CFA. None of the patients in control group had any recurrence. In conclusion, as a group, CFEL have a low proclivity for recurrence, even when enucleated with close or positive margins. The presence of histologic features of BPT did not correlate with an increased potential for recurrence., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: Until now, no studies have investigated whether women other than those with dense breasts are suitable for adjunctive ultrasonography after negative mammography, and investigated whether all women with negative mammography are suitable for adjunctive ultrasonography., Methods: Based on the Multi-modality Independent Screening Trial in China, a total of 31,918 women aged 45 to 65 years underwent both ultrasonography and mammography. Physicians performed ultrasonography and mammography separately and were blinded to each other's findings until their interpretations had been recorded. For both ultrasonography and mammography, suspicious results and those highly suggestive of a malignancy were confirmed by pathologic examination, whereas other results were confirmed by 1-year follow-up after initial screening., Results: Based on Breast Imaging Reporting and Data System (BIRADS) assessments, 84 (84.8%) of 99 cancers were identified on mammography (detection rate, 2.6/1000), and 61 (61.6%) of 99 cancers were identified on ultrasonography (detection rate, 1.9/1000). Integrated mammography with ultrasonography identified 94 (95.0%) of 99 cancers, with an increment of 11.9% in cancer detection rate (from 2.6/1000 to 2.9/1000) (P < .05). Moreover, among women with BIRADS 3, adjunctive ultrasonography detected no cancers. All 10 additional cancers detected by adjunctive ultrasonography were from women with BIRADS 0 to 2, at a cost of 207 women with false positives. Additionally, dense breasts and benign breast disease were significantly associated with positive ultrasonography after BIRADS 0 to 2 (all P values < .05)., Conclusions: After negative mammography, adjunctive ultrasonography should only be recommended for BIRADS 0 to 2 but not BIRADS 3, especially for women with dense breasts or benign breast disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To fully elucidate the clinicopathological features of breast carcinoma in sclerosing adenosis (SA-BC)., Methods: Clinical and histological characteristics of 206 SA-BCs from 180 patients were retrospectively evaluated. Immunohistochemical phenotype was examined. The clinicopathological relevance of the topographical pattern of SA-BCs was analysed., Results: Overall, up to 46 patients (25.6%) had contralateral cancer, either SA associated or not. Of 99 cases who underwent core needle biopsy (CNB), 36 were underestimated as adenosis or atypical ductal hyperplasia at CNB, 5 invasive cases were misinterpreted as in situ carcinomas, whereas 4 ductal carcinoma in situ (DCIS) cases were overdiagnosed as invasive carcinoma. Microscopically, 163 tumours were in situ, including 136 DCIS, 19 lobular carcinomas in situ (LCIS) and 8 mixed DCIS/LCIS; of these carcinomas in situ (CIS), 37 had microinvasion. The DCIS group exhibited low, intermediate and high grades in 53.7%, 34.6% and 11.8% of cases, respectively, mostly with solid (43.4%) or cribriform (41.9%) pattern. Forty out of 43 invasive cases were invasive ductal carcinoma (IDC), mostly DCIS predominant. Immunophenotypically, luminal A phenotype was identified in 55.1%, 63.2% and 45.0% of DCIS, LCIS and IDC cases, respectively. Topographical type A group (carcinoma being entirely confined to SA, n=176) was characterised by smaller size, less invasiveness, lower grade and more frequency of luminal A immunophenotype compared with type B group (≥ 50% but not all of the carcinomatous lesion being located in SA, n=30) (all P<0.05)., Conclusions: CIS, especially non-high-grade DCIS, represents the most common variant of SA-BC, and luminal A is the most predominant immunophenotype. CNB assessment might be challenging in some SA-BCs. The topographical pattern has great clinicopathological relevance. Careful evaluation of the contralateral breast and long-term follow-up for patients with SA-BC is necessary given its high prevalence of bilaterality., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose:  To compare ratings regarding the depiction, diagnostic accuracy and lesion characterization of conventional synthesized mammography (SM), multiple angulated mammography reconstructions (INSIGHT3D), and standard stack reconstructions in digital breast tomosynthesis for microcalcifications., Materials and Methods:  This is a retrospective, multicase, multireader study. We included patients with digital breast tomosynthesis (DBT), microcalcifications and histology over a period of four months in our institution and the same number of normal cases. Three radiologists, who were blinded to patient data, independently rated the depiction, distribution, morphology and BI-RADS score of microcalcifications in SM, INSIGHT3D and standard stack reconstructions. Deidentified images were presented in random order. Reading time was measured. Friedman and post hoc Nemenyi tests, Cochrane's Q and post hoc Wilcoxon signed rank tests, Fleiss' kappa and receiver operating characteristics were used for statistical analysis., Results:  We included 41 histopathologically proven and 41 normal cases. Depiction of microcalcifications was rated better in INSIGHT3D than in SM and better in stack reconstructions than in INSIGHT3D and SM (P < 0.001). The reading time was lower in SM and INSIGHT3D compared to stack reconstructions (P < 0.001). The diagnostic accuracy and inter-rater correlation were comparable between all tested modes of reconstruction., Conclusions:  INSIGHT3D has higher ratings regarding the depiction of microcalcifications compared to SM while maintaining a short reading time. Our preliminary assessment suggests that INSIGHT3D provides added value to SM., Key Points:   · INSIGHT3D depicts microcalcifications better than synthesized mammography while maintaining a low reading time.. · The diagnostic accuracy and inter-rater correlation were comparable between INSIGHT3D and synthesized mammography.. · INSIGHT3D may be a potential successor to synthesized mammography.., Citation Format: · Neubauer J, Neubauer C, Wicklein J et al. Multiple Angulated Mammography Reconstructions in Digital Breast Tomosynthesis for the Diagnosis of Microcalcifications - Added Value to Standard Stack Reconstructions and Synthesized Mammography. Fortschr Röntgenstr 2018; DOI: 10.1055/s-0044-100726., Competing Interests: J. W. and T. M. are Siemens Healthcare GmbH staff members. All other authors declared that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Multiphoton microscopy has attracted increasing attention and investigations in the field of breast cancer, based on two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG). However, the incidence of breast benign diseases is about 5 to 10 times higher than breast cancer; up to 30% of women suffer from breast benign diseases and require treatment at some time in their lives. Thus, in this study, MPM was applied to image fibroadenoma and fibrocystic lesion, which are two of the most common breast benign diseases. The results show that MPM has the capability to identify the microstructure of lobule and stroma in normal breast tissue, the interaction of compressed ducts with surrounding collagen fiber in fibroadenoma, and the architecture of cysts filled with cystic fluid in fibrocystic disease. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time diagnosis of breast benign diseases in vivo, as well as breast cancer.