Adenomyoepithelial adenosis mimicking phylloides: A diagnostic dilemma.

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.

A rapidly growing fibroadenoma in a pregnant woman: A case report.

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.

Adenosquamous proliferation in radial sclerosing lesions: Histologic spectrum and key features in systematic review of 247 lesions.

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.

The Upgrade Risk of B3 Lesions to (Pre)Invasive Breast Cancer After Diagnosis on Core Needle or Vacuum Assisted Biopsy. A Belgian National Cohort Study.

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.

Honeycomb breast: An appearance of fibrocystic disease.

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.

[Microglandular adenosis of the breast]. / Mikroglandulyarnyi adenoz molochnoi zhelezy.

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.

A case of extensively spreading acinic cell carcinoma of the breast with microglandular features.

Acinic cell carcinoma (ACC) is an exceptionally rare type of breast carcinoma with a low-grade morphology and a favorable prognosis. It is postulated to be a type of invasive carcinoma arising in microglandular adenosis (MGA). We report a case of extensively spreading ACC of the breast with MGA-like features. Macroscopically, yellowish nodules were widely distributed throughout the right breast, up to the axilla, without mass formation. Microscopically, the tumor consisted of two distinct carcinoma components: one was multiple nodular lesions showing invasive carcinoma with fused solid nests, and the other was a widely spreading lesion exhibiting MGA-like features with uniform small single glands. Immunohistochemically, both components were negative for ER, PR, and HER2, and expressed EMA, S100 and lysozyme. The distinct morphology and molecular expression indicated ACC. The single glands in the MGA-like area lacked myoepithelial cells but were linearly surrounded by type IV collagen, a basement membrane component. This case supports the hypothesis that ACC and MGA have the same lineage and indicates that ACC is not necessarily a low-grade malignancy and can be aggressive.

High-risk lesions in the breast diagnosed by MRI-guided core biopsy: upgrade rates and features associated with malignancy.

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.

The effect of delay of excisional biopsy on upstage rate for atypical ductal hyperplasia, flat epithelial atypia, intraductal papilloma, and radial scar.

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.

Value of Long-term Follow-up in Surgically Excised Lesions of Uncertain Malignant Potential in the Breast - Is 5 Years Necessary?

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.

Two cases of mammary acinic cell carcinomas with microglandular structures mimicking microglandular adenosis.

Acinic cell carcinoma (AcCC) of breast is a rare subtype of triple-negative breast carcinoma demonstrating a wide morphologic spectrum. In this study, we perform a detailed morphologic and immunohistochemical description of two cases of the rare entity and review the published relative literature. Histologically, the two cases both showed predominantly microglandular and solid structures overlapping with the histological features of microglandular adenosis (MGA), and one case presented spindle cell metaplastic carcinoma with chondromyxoid matrix as a minor morphologic pattern. In two cases, most of the cancer cells were positive for lysozyme and antitrypsin strongly and extensively, but negative for estrogen receptor (ER), progesterone receptor (PR), androgen receptors (AR) and human epidermal growth factor receptor 2 (HER2). The true relationship between breast AcCC and MGA or carcinoma arising in MGA(CAMGA) may remain unclear; re-excision is advised when the MGA-like content extends to the surgical margins in the setting of breast AcCC. More cases and further molecular investigations are required to elucidate the true histogenesis and give the patients appropriate treatment.

Crystallizing galactocele of the breast masquerading as a malignancy: Report of a rare case with cytological diagnosis.

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.

Update on selective special types of breast neoplasms: Focusing on controversies, differential diagnosis, and molecular genetic advances.

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.

Excision of a sclerosing polycystic adenosis of the deep parotid gland.

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.

Apocrine lesions of the breast.

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.

Blunt duct adenosis: a separate entity from columnar cell lesions?

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.

ESR1 gene variants affect FSHR-depended risk of fibrocystic mastopathy in infertile women.

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 (χ2 = 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 (χ2 = 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.

Polycystic Ovary Syndrome and Fibrocystic Breast Disease: An Updated Review.

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.