Atypical Apocrine Research Articles

B3 lesions of the breast: histological, clinical, and epidemiological aspects : Update

B3lesions of the breast are aheterogeneous group of lesions with uncertain malignant potential encompassing abroad spectrum of histologically distinct alterations that often pose challenging decisions if diagnosed on the preoperative core or vacuum biopsies. B3lesions are mostly detected due to mammographic calcifications or mass lesions and, in most cases, encompass aspectrum of atypical lesions such as atypical ductal hyperplasia, classic lobular neoplasia, flat epithelial atypia, papillomas, fibroepithelial tumors, and rarely other lesions such as mucocele-like lesions, atypical apocrine lesions, and rare stromal proliferations. The use of immunohistochemical stains (estrogen receptors, basal cytokeratin, myoepithelial markers, and stromal marker panel) is useful in the differentiation of these lesions and allowing proper classification. Regarding clinical management of B3lesions, the radiological-pathological correlation of the given entity plays the most important key element for the proper next diagnostic and therapeutic step.

Breast Atypical Apocrine Adenosis: A Case Report and Literature Review

Atypical apocrine adenosis (AAA) is a benign lesion of the breast that is identified more frequently today than in the past when it was considered a rare diagnosis and commonly misdiagnosed as other malignant lesions of the breast. AAA is defined as the presence of apocrine cytology in a recognisable lobular unit associated with sclerosing adenosis. We present a case of an incidental finding of AAA and discuss diagnostic challenges and their implications on clinical management.

The diagnostic utility of EZH2 H-score and Ki-67 index in non-invasive breast apocrine lesions

In diagnostic breast pathology, there is no reliable applicable immunostain to help discern atypical and in situ apocrine lesions from benign apocrine tissue. At present, the diagnosis of non-invasive apocrine lesions remains challenging with current diagnoses rendered based on discrete morphologic characteristics on conventional hematoxylin and eosin staining. Interobserver variability is significant even among subspecialists partly due to lack of adjuvant diagnostic immunohistochemical stains. Herein, we set to elucidate the potential utility of EZH2 and Ki-67 immunostains as tangible tools in non-invasive apocrine proliferations. A cohort of apocrine breast lesions [Benign apocrine hyperplasia (BAH), n = 10; Atypical apocrine hyperplasia (AAH), n = 16; Apocrine ductal carcinoma in situ (ADCIS), n = 12] were subjected to EZH2 immunostaining and analyzed via H-scoring of nuclear expression. Mean H-scores for EZH2 progressively increased from BAH (23.5), to AAH (47.4) and ADCIS (196.4), and showed a significant difference utilizing the Kruskal-Wallis test (p < 0.0001). Further interrogation of Ki-67 demonstrated incremental expression from BAH to AAH and ADCIS at 1.6 %, 4.7 % and 24.7 %, respectively (p < 0.0001, Kruskal-Wallis test), suggesting an association with increased proliferation. Our results demonstrate that a combination of EZH2 and Ki-67 immunostaining may be employed in differentiating among challenging apocrine breast lesions and suggest a putative diagnostic utility for EZH2 and Ki-67 in non-invasive apocrine breast lesions.

Ultrasound Features and Rate of Upgrade to Malignancy in Atypical Apocrine Lesions of the Breast.

To evaluate the ultrasound (US) features and rate of upgrade to malignancy in atypical apocrine lesions (AALs) of the breast, diagnosed on percutaneous needle biopsy. This retrospective study included 17 AALs diagnosed by needle biopsy in 15 patients. For 16 of the 17 AALs, subsequent surgical excision (n = 14) or 8-gauge vacuum-assisted biopsy (n = 2) was performed. Ultrasound features were retrospectively analyzed according to the American College of Radiology Breast Imaging Reporting and Data System lexicon. Of 17 AALs, 13 (76.5%) were atypical apocrine hyperplasia; 3 (17.6%) were atypical apocrine adenosis; and 1 (5.9%) was combined atypical apocrine hyperplasia and atypical apocrine adenosis on needle biopsy. Subsequently, 4 of 16 AALs (25%) were upgraded to malignancy at surgical excision. On US imaging, all 17 lesions presented as masses, which were mainly irregular and noncircumscribed (n = 8) or oval/round and noncircumscribed (n = 7) with isoechogenicity or hypoechogenicity. Rarely, an AAL would show complex cystic and solid echogenicity (n = 1) or appear as a hypoechoic mass with oval shape and a circumscribed margin (n = 1). Atypical apocrine lesions of the breast often showed suspicious malignant features on US imaging. Given the high upgrade rate (25%), the diagnosis of an AAL by needle biopsy warrants subsequent surgical excision.

Apocrine lesions of the breast: part 1 of a two-part review: benign, atypical and in situ apocrine proliferations of the breast

Apocrine morphology is a common phenomenon encountered in everyday breast pathology practice, and is defined as cuboidal or columnar cells exhibiting abundant eosinophilic granular cytoplasm, prominent apical granules, a low...

Relevance of B3 lesions in breast diagnosis – frequency and therapeutic consequences

AbstractWith improvements in breast imaging and minimally invasive interventions, detection of early breast cancer has increased. However, with the improved diagnostic capabilities, the risk of false-positive benign lesions as well as lesions classified as B3 by histopathology has also increased. Varying rates of malignancies are associated with B3 lesions, raising the question of whether such lesions should always be surgically removed. The results of our retrospective analysis should assist in this decision-making process.307 core needle or vacuum-assisted needle biopsies in which B3 lesions were found were examined. The most common lesions were intraductal papillomas (44 %), atypical ductal hyperplasia (22.8 %), flat epithelial atypia (9.4 %), phyllodes tumours (6.5 %), radial scars (5.9 %), LIN 1 (4.9 %), complex fibroadenomas (3.3 %) and LIN 2 (1.6 %). The frequencies depended considerably on whether the tissue was obtained by core biopsy or vacuum biopsy. Stereotactic vacuum biopsy was generally performed in the case of microcalcification not apparent on sonography. Lesions visible on ultrasound had core needle biopsy.Surgery was performed in 254 cases and a malignancy was found in 27.2 % on the final histopathology. Malignancy was found in 24.6 % of 114 cases initially diagnosed as intraductal papilloma. Similarly, cancer was discovered in 48.4 % of the 62 cases of atypical ductal hyperplasia, in 2.4 % of the 41 cases of flat epithelial atypia, complex fibroadenoma and phyllodes tumour, in 20.7 % of the 29 cases of LIN 1 and radial scar as well as in 50 % of the 8 cases of LIN 2, adenomyoepithelioma and atypical apocrine metaplasia.These data indicate the necessity for complete surgical removal of a B3 lesion when it is discovered using the core needle or vacuum-assisted biopsy technique. The decision not to perform surgery can be made when the risk of associated malignancy is deemed low in the clinical pathology conference, but careful follow-up is essential.

Upgrade Rate and Imaging Features of Atypical Apocrine Lesions.

The purpose of our work was to identify imaging features of atypical apocrine lesions and determine the rate of upgrade to ductal carcinoma insitu (DCIS) or invasive carcinoma at excision after such a diagnosis on percutaneous breast biopsy. From January 1, 2006, through October 8, 2013, a total of 33,157 breast core biopsies were performed at University of Pittsburgh Medical Center. Of those, 58 (0.2%) showed atypical apocrine lesions. For 24, atypical apocrine adenosis (AAA) or atypical apocrine metaplasia (AAM) was the only risk lesion, with no known ipsilateral malignancy, and the results of excision were available. The median patient age was 58years (range 43-88). Among 24 atypical apocrine lesions (20 AAA and 4 AAM), four (16.7%; 95% confidence interval: 4.7, 37.4) were upgraded at excision: one invasive ductal carcinoma (grade 2, 0.2cm, estrogen receptor positive, progesterone receptor positive, HER2/Neu negative) and three DCIS (two grade 3, one grade 2). All four upgraded lesions were AAA (20%; 4/20). Twelve AAA were seen as an irregular (n=9) or circumscribed (n=3) mass on ultrasound; three masses had calcifications. Six of 20 (30%) AAA were seen on biopsy of calcifications only and calcifications were within two AAA lesions at histopathology. One AAA (1/20, 5%) was asymmetry only, and one (1/20, 5%) a persistently enhancing MR focus. All four malignancies were masses on ultrasound (three irregular, one circumscribed), and three malignancies had calcifications (two coarse heterogeneous, one amorphous). While concordant with an irregular or circumscribed mass on imaging, with or without amorphous or coarse heterogeneous calcifications, AAA merits excision with a 20% upgrade rate to malignancy. Further study of AAM is warranted.

Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls.

Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change. The term apocrine atypia is used when there is significant cytologic atypia in apocrine cells, characterized by a 3-fold nuclear enlargement, prominent/multiple nucleoli, and hyperchromasia. Atypical apocrine adenosis is diagnosed when apocrine adenosis and apocrine atypia are superimposed. However, there are no definite criteria to distinguish atypical apocrine adenosis from apocrine ductal carcinoma in situ. Immunohistochemical markers can be confounding and may lead to erroneous diagnoses. Atypical apocrine features in sclerosing lesions may be misinterpreted as invasive carcinoma if the underlying lesion is not recognized. In the absence of definite features of malignancy, the diagnosis of apocrine ductal carcinoma in situ may be extremely difficult. In the present article, we review atypical apocrine adenosis focusing on diagnostic challenges and their implications on clinical management.

Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy.

Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n=29) and AAA (n=12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.

Expression of C-KIT, CD24, CD44s, and COX2 in benign and non-invasive apocrine lesions of the breast.

Benign apocrine metaplasia (AM) of the adult breast is a very common, but enigmatic lesion. It has been speculated that AM might be a precursor of malignancy or an indicator of a susceptibility of the breast tissue to develop neoplasia, mainly based on comparing the frequency of AM in breast cancer and non-breast cancer patients [1]. Studies using comparative genomic hybridization have supported this by showing similar molecular alterations in benign and malignant apocrine lesions [2]. Few studies, however, have compared expression of biomarkers involved in tumor progression in AM and progressively more advanced atypical apocrine lesions. The expression of C-KIT, COX2, CD24, and CD44s was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded material of 9 AM, 20 apocrine ductal intraepithelial neoplasia (DIN1c-3) and 40 atypical apocrine lesions (not qualifying for DIN1c-3) and compared to expression of the same biomarkers in adjacent normal ductal epithelium. Of the 66 apocrine lesions, 62 (94%) did not express C-KIT compared to 4/63 (6%) of the normal glands (Fisher's exact, p < 0.001). COX2 was expressed in a significantly higher proportion of apocrine lesions than of normal glands (49 vs. 14%, p < 0.001), and the number of apocrine lesions positive for CD24 was found to be higher with increasing aggressiveness of the lesions (Spearman, p < 0.001). In conclusion, benign and non-invasive proliferative apocrine lesions of the breast display immuno-phenotypical characteristics previously ascribed mainly to malignant transformation. This could lend support to the theory that AM is an early step towards malignant transformation, albeit associated with slow progression to carcinoma.

Surgical excision outcome after radial scar without atypical proliferative lesion on breast core needle biopsy: a single institutional analysis.

Radial scar (RS) has been recognized as a risk factor for developing breast cancer, and excision is recommended for patients with RS identified on core needle biopsy (CNB). However, recent literatures suggest that the increased risk may be caused by concurrent proliferative lesions on the biopsy, rather than radial scar itself. In this study, we investigated the follow-up excision (FUE) results for patients with RS on CNB with no history of a prior or a concurrent breast cancer or atypical proliferative lesions (APLs). A total of 113 RS cases including 32 cases with APLs or carcinoma and 81 cases without APLs on CNB were included in this study. Forty cases (49%) without APLs had FUE. No significant difference in radiologic and clinical findings was identified between cases with FUEs and cases without FUEs. Of the 40 cases with FUE, 9 cases (22.5%) were upgraded including 3 atypical ductal hyperplasias, 4 lobular neoplasias, 1 flat epithelial atypia, and 1 atypical apocrine adenosis. However, no case was upgraded to invasive carcinoma or ductal carcinoma in situ. All cases with mammotome CNBs were not upgraded. Our data suggest that conservative follow-up with imaging rather than surgical excisions may be more appropriate for patients with only RS on biopsy, especially for patients with mammotome CNBs.

Atypical apocrine adenosis diagnosed on breast core biopsy: implications for management.

Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The data from long-term follow up studies of open biopsies suggest that AAA is not a high-risk or precursor lesion. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. The goal of this study was to determine the frequency of carcinoma in excision specimens after a core biopsy diagnosis of AA or AAA. We identified 34 core biopsies of AA (22) and AAA (12) performed between 1996 and 2014. The mean age at diagnosis was 60 years. The most common indications for core biopsy were calcifications (11), a mass or density (18), and a mass or density with calcifications (3). Two cases were detected on magnetic resonance imaging (MRI) studies. Available pathology reports and slides were reviewed, and surgical excision findings were correlated with core biopsy diagnoses. Of the core biopsies with AA or AAA, 7 also contained atypical ductal or lobular hyperplasia (AH) and 4 contained ductal carcinoma in situ or invasive carcinoma. In the absence of coexisting AH or carcinoma in the initial core biopsy specimen, none of the surgical excision specimens after a diagnosis of AA (2) or AAA (7) contained ductal carcinoma in situ or invasive carcinoma. AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.

Abstract P1-02-08: Papillary lesions of the breast on core biopsies: Should routine surgical excision be performed?

Abstract Background: The optimal management of papillary lesions, particularly benign papillomas, detected on core needle biopsies remains debatable. The purpose of this study was to determine the risk of upgrade to malignancy of core biopsy diagnosed papillary lesions on the subsequent surgical excision. Methods: Following institutional ethics review board approval, the pathology database was searched for all papillary lesions diagnosed on core needle biopsies from Jun 2005 to June 2010. The papillary lesions were histologically categorized as benign, atypical, suspicious for malignancy and definite for malignancy. The core biopsy findings were compared with the follow-up excision biopsy material to identify any upgrade to malignancy (i.e. ductal carcinoma in situ or invasive carcinoma). The presence of any associated significant risk lesions such as atypical ductal hyperplasia (ADH) and lobular neoplasia (LN) were also recorded. Results: A total of 113 papillary lesions were diagnosed on core needle biopsies of 98 patients, with a mean age of 57 years. A median of 5 cores of breast tissue were obtained per papillary lesion. Of these papillary lesions, 73 were benign, 25 atypical, 8 suspicious for malignancy and 7 definite for malignancy. The overall excision rate was 83%. Of the 58 benign papillary lesions excised, only one (1.7%) showed malignancy (3mm ductal carcinoma in situ) - of interest, the papillary lesion per se was confirmed benign on excision, while an adjacent focus of flat epithelial atypia was present in the initial core biopsy. Nine papillomas were associated with adjacent ADH and/or LN on excision and the rest of the excisions (n = 48) showed no residual papillary lesion or benign papillomas. Among the 24 excised atypical papillary lesions, the positive predictive value (PPV) for malignancy was 42% (10 in situ papillary carcinomas, 4 of these associated with invasive carcinoma). The remaining excisions disclosed ADH and/or LN (n = 3) or benign breast tissue/papillomas (n = 11). None of the 4 papillary lesions with the apocrine atypia were malignant on excision. Of the 5 excised papillary lesions which were suspicious for malignancy on the cores, all showed malignancy (5 in situ carcinomas; 2 associated with invasive carcinoma) on open surgical biopsy. The PPV for malignancy of the 7 core biopsy diagnosed malignant papillary lesions was 100%. Conclusions: Papillary lesions diagnosed as atypical or suspicious for malignancy on core needle biopsies should be completely excised to exclude malignancy. Our findings suggest, however, that routine surgical excision may not be necessary for core biopsy detected benign papillomas which are not associated with atypia. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-02-08.

MRI-Guided Intervention for Breast Lesions Using the Freehand Technique in a 3.0-T Closed-Bore MRI Scanner: Feasibility and Initial Results

ObjectiveTo report the feasibility of magnetic resonance imaging (MRI)-guided intervention for diagnosing suspicious breast lesions detectable by MRI only, using the freehand technique with a 3.0-T closed-bore MRI scanner.Materials and MethodsFive women with 5 consecutive MRI-only breast lesions underwent MRI-guided intervention: 3 underwent MRI-guided needle localization and 2, MRI-guided vacuum-assisted biopsy. The interventions were performed in a 3.0-T closed-bore MRI system using a dedicated phased-array breast coil with the patients in the prone position; the freehand technique was used. Technical success and histopathologic outcome were analyzed.ResultsMRI showed that four lesions were masses (mean size, 11.5 mm; range, 7-18 mm); and 1, a nonmass-like enhancement (maximum diameter, 21 mm). The locations of the lesions with respect to the breast with index cancer were as follows: different quadrant, same breast - 3 cases; same quadrant, same breast - 1 case; and contralateral breast - 1 case. Histopathologic evaluation of the lesions treated with needle localization disclosed perilobular hemangioma, fibrocystic change, and fibroadenomatous change. The lesions treated with vacuum-assisted biopsy demonstrated a radial scar and atypical apocrine hyperplasia. Follow-up MRI after 2-7 months (mean, 4.6 months) confirmed complete lesion removal in all cases.ConclusionMRI-guided intervention for breast lesions using the freehand technique with a 3.0-T closed-bore MRI scanner is feasible and accurate for diagnosing MRI-only lesions.

Memenin Apokrin Karsinomunun İnce İğne Aspirasyon Sitolojisinde Tanısal Tuzakları

Apocrine carcinoma of the breast is a rare type of invasive breast cancer. It is most fre - quently seen in the postmenopausal period as a unilateral and multicentric mass. A 76-year-old fe - male with a left breast mass for 12 years presented with left areolar retraction and discharge, and ulceration of the breast skin. A fine needle aspiration cytology (FNAC) of the breast mass showed three dimensional clusters of atypical cells with groups in a necrotic background. Those cells were apocrine-like and had hyperchromatic nuclei, cytoplasmic vacuoles and granular cytoplasms. The cytological result was reported as suspicious for malignancy. The patient underwent simple mas - tectomy. Histological examination of the excised specimen revealed apocrine carcinoma. The dif - ferential diagnosis mainly includes benign lesions, such as apocrine adenoma, atypical apocrine adenosis and granular apocrine metaplasia, in addition to apocrine carcinoma.

Atypical Apocrine Adenosis of the Breast: Long-term Follow-up in 37 Patients

Atypical apocrine adenosis is a rare breast lesion in which the cellular population demonstrates cytologic alterations that may be confused with malignancy. The clinical significance and management of atypical apocrine adenosis are unclear because of the lack of long-term follow-up studies. To determine the breast cancer risk in a retrospective series of patients with atypical apocrine adenosis diagnosed in otherwise benign, breast excisional biopsies. We identified 37 atypical apocrine adenosis cases in the Mayo Benign Breast Disease Cohort (9340 women) between 1967 and 1991 with a blinded pathology rereview. Breast cancer diagnoses subsequent to initial atypical apocrine adenosis biopsy were identified (average follow-up, 14 years). The mean age at diagnosis of atypical apocrine adenosis in the group was 59 years. Breast carcinoma subsequently developed in 3 women (8%) with atypical apocrine adenosis, diagnosed after follow-up intervals of 4, 12, and 18 years. The tumor from 1 of the 3 cases (33%) was ductal carcinoma in situ, contralateral to the original biopsy, and the other 2 cases (66%) were invasive carcinoma. Ages at the time of diagnosis of atypical apocrine adenosis were 55, 47, and 63 years for those that developed in situ or invasive carcinoma. (1) Atypical apocrine adenosis was a rare lesion during the accrual era of our cohort (<1% of cases); (2) women found to have atypical apocrine adenosis were, on average, older than were other patients with benign breast disease, however, there does not seem to be an association with age and risk for developing carcinoma in patients diagnosed with atypical apocrine adenosis, as previously suggested; and (3) atypical apocrine adenosis does not appear to be an aggressive lesion and should not be regarded as a direct histologic precursor to breast carcinoma.

Cyclin D-1 protein over-expression is not associated with gene amplification in benign and atypical apocrine lesions of the breast

Cyclin D-1 protein over-expression and/or gene amplification have been shown to be frequent events in subsets of breast carcinomas. Cyclin D-1 is generally considered as a weak oncogene, and its over-expression has been shown to occur in occasional benign breast lesions. In a previous series, we have shown that cyclin D-1 was over-expressed in subsets of apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast and that such over-expression was mostly associated with a significant increase in the proliferative capacity of these lesions. We examined the mechanisms involved in cyclin D-1 over-expression in apocrine lesions. A total of 41 cases were analysed in this study. The cases were divided into: 18 cases of APM and 23 cases of AA. All cases analysed had been previously analysed by immunohistochemistry, and all showed over-expression of the cyclin D-1 protein. Fluorescence in situ hybridisation (FISH) was performed using a dual cyclin D-1 (spectrum orange)/chromosome 11 centromere (spectrum green) DNA probe. The results showed that none of the cases studied had concomitant gene amplification. These results suggest that other post-transcriptional mechanisms might be responsible for cyclin D-1 protein over-expression in benign apocrine lesions. Further studies are needed to understand the mechanisms involved in abnormal cyclin D-1 expression in these lesions.

High-risk lesions diagnosed at MRI-guided vacuum-assisted breast biopsy: can underestimation be predicted?

To evaluate the frequency of diagnosis of high-risk lesions at MRI-guided vacuum-assisted breast biopsy (MRgVABB) and to determine whether underestimation may be predicted. Retrospective review of the medical records of 161 patients who underwent MRgVABB was performed. The underestimation rate was defined as an upgrade of a high-risk lesion at MRgVABB to malignancy at surgery. Clinical data, MRI features of the biopsied lesions, and histological diagnosis of cases with and those without underestimation were compared. Of 161 MRgVABB, histology revealed 31 (19%) high-risk lesions. Of 26 excised high-risk lesions, 13 (50%) were upgraded to malignancy. The underestimation rates of lobular neoplasia, atypical apocrine metaplasia, atypical ductal hyperplasia, and flat epithelial atypia were 50% (4/8), 100% (5/5), 50% (3/6) and 50% (1/2) respectively. There was no underestimation in the cases of benign papilloma without atypia (0/3), and radial scar (0/2). No statistically significant differences (p > 0.1) between the cases with and those without underestimation were seen in patient age, indications for breast MRI, size of lesion on MRI, morphological and kinetic features of biopsied lesions. Imaging and clinical features cannot be used reliably to predict underestimation at MRgVABB. All high-risk lesions diagnosed at MRgVABB require surgical excision.

150 Molecular characterization of apocrine carcinoma of the breast: validation of an apocrine protein signature in a well-defined cohort

The identification as well as the molecular characterization of breast precancerous lesions in terms of increased risk of progression and/or recurrence is becoming a critical issue today as improved non-surgical procedures are detecting cancer at an earlier stage. The strategy we have been pursuing to identify early apocrine breast lesions is based on the postulate that invasive apocrine carcinomas evolve from epithelial cells in terminal duct lobular units (TDLUs) in a stepwise manner that involves apocrine metaplasia of normal breast epithelia, hyperplasia, atypia, and apocrine carcinoma in situ. First, we identify specific protein biomarkers for benign apocrine metaplasia and thereafter we search for biomarkers that are highly overexpressed by pure invasive apocrine carcinomas. Here we present studies in which we have used antibodies against components of a benign apocrine signature that includes 15-prostaglandin dehydrogenase (15-PGDH), a protein that is expressed by all benign apocrine lesions, and markers that are highly overexpressed by pure invasive apocrine carcinomas such as MRP14 (S100A9), psoriasin (S100A7), and p53 to identify precancerous lesions in sclerosing adenosis (SA) with apocrine metaplasia. The latter is a benign proliferative lesion of the breast that exhibits an increase in the size of the TDLUs and characterized by retained two-cell lining, and myoepithelial (ME) and stromal hyperplasia. SA with apocrine metaplasia, i.e. apocrine adenosis (AA), presents with a higher degree of atypical apocrine hyperplasia, and these lesions are believed to be precursors of apocrine carcinoma, in situ and invasive. Analysis of 24 selected SA samples with apocrine metaplasia revealed non-obligate putative apocrine precancerous lesions that displayed some, or in same cases all the three markers associated with pure invasive apocrine carcinomas. These studies also revealed p53 positive, non-apocrine putative precancerous lesions as well as novel phenotypes for ME and some luminal cells characterized by the expression of cytokeratin 15.

Apocrine Ductal Carcinoma In Situ Involving a Sclerosing Lesion With Adenosis: Report of a Case

Apocrine metaplasia is a ubiquitous component of the mammary fibrocystic change spectrum. Although mostly associated with cysts, apocrine metaplasia can also present as a proliferative lesion, rarely with cytologic atypism. Apocrine atypia is characterized by 3-fold nuclear enlargement, multiple nucleoli, and hyperchromatism and generally arises in florid or radial sclerosing lesions. Dramatic apocrine atypia may be very difficult to distinguish from apocrine ductal carcinoma in situ. The latter is distinguished from apocrine atypia by greater extent of the lesion (>0.4 cm) and the presence of greater nuclear pleomorphism with nuclear membrane irregularity. The clinical significance of apocrine atypia is poorly understood and reflects the lack of published outcome studies. Herein, I report a case in which apocrine ductal carcinoma in situ presented as atypical apocrine adenosis in a needle core breast biopsy. It illustrates the problem of assessing apocrine atypia and apocrine ductal carcinoma in situ in small samples.