Sclerosing Adenosis Research Articles

Surgical management for early-stage bilateral breast cancer patients in China.

BackgroundThe aim of this study was to investigate the current surgical management strategy for bilateral breast cancer (BBC) patients and to assess the changes in this strategy in China.MethodsThis is a retrospective review of all patients with early-stage BBC who underwent surgical treatment at the Fudan University Shanghai Cancer Center between June 2007 and June 2014.ResultsA total of 15,337 patients with primary breast cancer were identified. Of these patients, 218 (1.5%) suffered from synchronous bilateral breast cancer (sBBC), and 296 (2.0%) suffered from metachronous bilateral breast cancer (mBBC). Patients with a lobular carcinoma component, those with estrogen receptor-positive cancer, and those with an accompanying sclerosing adenosis in the affected breast tended to develop BBC. The rates of bilateral mastectomy, breast conserving therapy, reconstruction, and combined surgeries were 86.2%, 6.4%, 3.7%, and 3.7%, respectively, for patients with sBBC and 81.1%, 4.4%, 3.0%, and 11.5%, respectively, for patients with mBBC. The interval between bilateral cancers, age at first diagnosis of breast cancer, histopathological type, and stage have significant impacts on the choice of surgery for patients with BBC.ConclusionsBilateral mastectomy was the dominant surgical management for patients with BBC in China, despite the increased application of breast reconstruction surgery observed in recent years. Bilateral prosthetic breast reconstruction was the ideal choice for patients with sBBC. Chinese surgeons should take responsibility for patient education and inform their patients about their surgical options.

Ki-67 expression in sclerosing adenosis and adjacent normal breast terminal ductal lobular units: a nested case–control study from the Mayo Benign Breast Disease Cohort

Sclerosing adenosis (SA) increases risk for invasive breast cancer (BC) 2.1 times relative to that in the general population. Here, we sought to evaluate whether the proliferation marker Ki-67 stratifies risk among women with SA. A nested case-control sample of patients with SA was obtained from the Mayo Clinic Benign Breast Disease Cohort. Ki-67 expression was evaluated in SA lesions and in the adjacent normal terminal duct lobular units (TDLU) in women who did (cases, n=133) or did not (controls, n=239) develop BC. Ki-67 was scored by intensity and number of positively stained cells per one high-power field (magnification, ×40) (40×HPF) for both SA and normal TDLU. Associations of Ki-67 expression with case-control status were assessed using conditional logistic regression. Higher Ki-67 expression was significantly associated with case-control status in both SA (P=0.03) and normal background TDLU (P=0.006). For the SA lesion, >2 average positively stained cells/40×HPF showed an adjusted odds ratio (OR) of 1.9 (95% CI, 1.1-3.4) compared to samples with an average of ≤2 positively stained cells. For background TDLU, lobules with >2 but ≤6 average positively stained cells showed an adjusted OR of 1.3-1.5, whereas those with an average of >6 positively stained cells had an OR of 2.4 (95% CI, 1.1-5.3) compared to those with an average of <2 positively stained cells. Among women with SA, increased Ki-67 expression in either the SA lesion or the normal background TDLU carried an approximately twofold increased odds of subsequent BC as compared to lower Ki-67 expression.

Sclerosing adenosis as a predictor of breast cancer bilaterality and multicentricity.

Breast cancer is occasionally complicated by sclerosing adenosis (SA). Although both lesions usually originate in the terminal duct lobular unit, their pathogenetic relationship has not yet been elucidated. The present study analyzed 63 breast cancer patients with SA (involving a total of 75 breasts) to clarify if coexisting SA increased the frequency of multicentric breast cancer or not. Using the topographical classification proposed in our previous study, breast cancers with SA were classified into the following three types: type A (n = 22), cancer area was completely surrounded by the SA; type B (n = 26), cancer area partially overlapped the SA; and type C (n = 27), cancer area was located separate from the SA. Breast cancers with SA had a significant (P < 0.001) increase in frequency of harboring bilateral and multicentric cancers [17 of 63 (27%) and 15 of 63 (24%), respectively] when compared to breast cancer patients without SA, regardless of topographical type. Breast cancers with SA were less invasive (P < 0.001), of lower histological grade (P = 0.034), and had similar frequency of estrogen receptor-positive (P = 0.21) and HER2-positive (P = 0.74) tumors. In conclusion, contralateral and ipsilateral multicentric breast cancers occurred at a higher frequency in those with SA. Our data suggest that SA is, in addition to lobular neoplasia, a predictor of multicentric breast cancers.

Sclerosing Adenosis of the Breast: Report of Two Cases and Review of the Literature

SummaryBackgroundSclerosing adenosis is a benign, usually asymptomatic lobulocentric proliferative process that involves both the epithelial and the mesenchymal component of the breast. It is commonly an incidental finding in perimenopausal women undergoing screening mammography.Case ReportWe reported on two patients with sclerosing adenosis assessed with mammography, ultrasound, and contrast-enhanced magnetic resonance imaging. Case 1 was a 21-year-old woman with a palpable lesion in her right breast that was depicted as an irregular mass on contrast-enhanced magnetic resonance imaging. Case 2 was an asymptomatic 42-year-old woman with suspicious ultrasound findings in her left breast; contrast-enhanced magnetic resonance imaging showed regional non-mass-like enhancement associated with increased vascularity. Both patients underwent ultrasound-guided vacuum-assisted biopsy. Sclerosing adenosis does not have distinctive radiological features and can mimic a malignant growth process, thus requiring a diagnostic biopsy.ConclusionsSA is a common, benign, generally asymptomatic proliferative lesion of the breast. It is associated with a doubling of the risk of developing breast carcinoma, even though its role in carcinogenesis remains to be elucidated. It does not exhibit distinctive MG, US or even MRI features. Since it may mimic a carcinoma it requires further investigation with a diagnostic biopsy.

Value of ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis

Objective To investigate the value of color Doppler ultrasonography in diagnosis and differential diagnosis of breast sclerosing adenosis (SA).Methods Preoperative sonography in 32 SA,99 invasive ductal carcinoma(IDC),51 ductal carcinoma in situ(DCIS) and 64 fibroadenoma(FA) confirmed by pathology were retrospectively analyzed.Results The average age of SA group was younger than IDC and DCIS groups',but older than FA group's (P ＜0.05).The focal maximum diameter of SA group was the smallest among all(P ＜0.05).All the SA sonograms showed solid hypoechoic lesions,with spiculate margin was less than IDC group and larger than DCIS and FA groups (P ＜0.05).Similar ultrasonic characteristics,such as irregular shape,unclear border,acoustic halos were seen in SA and DCIS groups (P ＞0.05),while IDC group showed the highest rate and FA group had the least(P ＜0.05).SA masses' uneven internal echo,calcification,posterior acoustic attenuation was higher than FA group(P ＜0.05),but less than IDC and DCIS groups(P ＞0.05).Meanwhile,A/T ratios(≥0.7) were higher than DCIS and FA groups,but less than IDC group(P ＞0.05).In addition,SA group had a similar detection rate of the internal blood flow with FA group(P ＞0.05),but less than the IDC and DCIS groups(P ＜0.05).Conelusions Ultrasonography has a significant clinical value in diagnosis and differential breast sclerosing adenosis. Key words: Ultrasonography, Doppler, color; Breast neoplasms; Fibrocystic breast disease

Sclerosing Adenosis: Should We Still Regard It as a Simple Benign Disease? Report of Two Patients with Subsequent Development of Invasive or In-situ Breast Cancer

Sclerosing adenosis belongs to the group of benign proliferative breast diseases. The imaging and histological findings of sclerosing adenosis can mimic invasive ductal carcinoma. The diagnosis of sclerosing adenosis is challenging, and requires the combination of clinical, radiological, and pathological findings. Sclerosing adenosis is associated with a small risk of subsequent breast carcinoma. This report is of two patients with incidentally detected and biopsy-proven sclerosing adenosis. The clinical history, serial mammogram, breast ultrasonography, and preoperative breast magnetic resonance imaging findings are reviewed and the histological slides of the biopsy and surgical specimens are presented. In both patients, serial follow-up ultrasonography 7 years after the initial diagnosis showed mild increase in vascularity in the lesions. Repeat biopsies were performed, which showed invasive ductal carcinoma and ductal carcinoma in situ in patient 1 and patient 2, respectively. The authors recommend long-term follow-up for a sclerosing adenosis because of the risk of breast carcinoma with a long latency period. If any suspicious feature or change in morphology is detected in follow-up imaging, a biopsy should be performed to exclude carcinoma.

Sclerosing adenosis and risk of breast cancer

Over one million American women have a benign breast biopsy annually. Sclerosing adenosis (SA) is a common, but poorly understood benign breast lesion demonstrating increased numbers of distorted lobules accompanied by stromal fibrosis. Few studies of its association with breast cancer have been conducted, with contradictory results. We studied SA in the Mayo Benign Breast Disease (BBD) Cohort, which includes women who had benign biopsies at Mayo-Rochester 1967–2001. Breast cancer risk in defined subsets was assessed using standardized incidence ratios (SIRs), relative to the Iowa Surveillance, Epidemiology, and End Results registry. This BBD cohort of 13,434 women was followed for a median of 15.7 years. SA was present in 3,733 women (27.8 %) who demonstrated an SIR for breast cancer of 2.10 (95 % CI 1.91–2.30) versus an SIR of 1.52 (95 % CI 1.42–1.63) for the 9,701 women without SA. SA was present in 62.4 % of biopsies with proliferative disease without atypia and 55.1 % of biopsies with atypical hyperplasia. The presence of SA stratified risk in subsets of women defined by age, involution status, and family history. However, SA does not further stratify risk in women diagnosed with other forms of proliferative breast disease, either with or without atypia. SA is a common proliferative lesion of the breast which, as a single feature, conveys an approximate doubling of breast cancer risk. Its role in breast carcinogenesis remains undefined; its presence may aid in risk prediction for women after a breast biopsy.

Breast carcinoma arising from sclerosing adenosis: a clinicopathologic and immunohistochemical analysis of 106 cases

<h3>Backgrounds</h3> To elucidate the features of breast carcinoma (BC) arising from sclerosing adenosis (SA). <h3>Methods</h3> 106 BCs arising from SA were collected. Their clin-icopathological characteristics were examined and immunohisto-chemical staining was performed. <h3>Results</h3> (1) The average age of 106 females was 49.4 years. Fifty-nine cases were from the left breast, and 39 from right, 8 bilateral. Only 43 patients have breast masses. (2) Ninety-four (88.7%) cases were carcinoma in situ (CIS), including 75 DCIS, 13 LCIS, 5 mixed DCIS-LCIS, and one CIS showing both ductal and lobular features. Twelve (11.3%) cases were well-differentiated invasive carcinoma, including 8 cases of NOS, one case showing apocrine features and 2 ILC. Distorted glands in CIS were entrapped in fibrous/hyalinized stroma, with inconspicuous myoepithelial cells, mimicing invasive carcinoma. (3) Luminal A, luminal B, basal-like and Her2 overexpression phenotype was identified in 57, 19, 12, 6 cases of CIS, respectively, and 6, 4, 1, 1 cases of invasive cases, respectively. <h3>Conclusions</h3> BC arising from SA was rare. Low-intermediate grade DCIS was the predominant type; luminal A type was the most frequent. Histological appearance of CIS may resemble invasive carcinoma; over-diagnosis should be avoided. To be familiar with this entity is essential to accurate diagnosis and treatment.

Nodular sclerosing adenosis of breast: A diagnostic pitfall in fine needle aspiration cytology

Fine needle aspiration cytology was performed in a 46-year-old female presenting with a breast lump and mammography suggesting a malignancy. The smears were cellular with cohesive clusters and scattered epithelial cells showing moderate nuclear pleomorphism and focal acinar formation. Stromal fragments, benign epithelial cell clusters and a few naked nuclei were noted in the background. Considering the clinical features, mammography findings as well as cytological features, a diagnosis of ductal carcinoma was suggested. Subsequent histopathological examination revealed it to be nodular sclerosing adenosis. The cytohistological correlation of this uncommon lesion, a potential pitfall in breast fine needle aspiration diagnosis which may lead to a false-positive diagnosis is discussed.

Ductal Carcinoma In Situ That Involves Sclerosing Adenosis: High Frequency of Bilateral Breast Cancer Occurrence

BackgroundThe radiologic and pathologic characteristics of ductal carcinoma in situ (DCIS) that involves sclerosing adenosis (SA) (SA DCIS) resemble those of invasive carcinoma. However, differences in the clinical features of these conditions remain unclear. This study was designed to clarify the clinicopathologic characteristics of SA DCIS compared with those of DCIS not involving SA (non,-SA DCIS). MethodsWe retrospectively studied 1309 patients who underwent breast surgery at our hospital between January 2007 and December 2008. A total of 205 cases of DCIS were diagnosed in 198 patients, and 28 (13.7%) cases of breast SA DCIS were diagnosed in 24 patients. We compared clinical characteristics as well as radiologic and pathologic findings between SA DCIS and non-SA DCIS. ResultsSynchronous and metachronous bilateral breast cancer was detected at a significantly higher rate in SA DCIS (9 [38%] of 24 patients) than in non-SA DCIS (22 [13%] of 174 patients; P < .01). As for radiologic findings, architectural distortion was more frequent in patients with SA DCIS than in those with non-SA DCIS (15 [54%] of 28 cases vs. 5 [2%] of 177 cases on mammography; P < .01; and 14 [50%] of 28 cases vs. 4 [2%] of 177 cases on ultrasound; P < .01). The rate of negativity for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was significantly higher in SA DCIS than in non-SA DCIS (5 [18%] of 28 cases vs. 5 [3%] of 177 cases, P = .005) with immunohistochemical studies. ConclusionsThe rate of bilateral breast cancer and of architectural distortion on radiologic studies was higher in patients with SA DCIS than in those with non-SA DCIS. Our findings suggest that patients with SA DCIS should be closely monitored by radiologic and pathologic examinations to detect the presence of contralateral lesions.

Topographical, morphological and immunohistochemical characteristics of carcinoma in situ of the breast involving sclerosing adenosis. Two distinct topographical patterns and histological types of carcinoma in situ

To examine the histopathological features of 24 surgically resected carcinoma in situ (CIS) involving sclerosing adenosis (SA), with special reference to the topographical relationship between CIS and SA. In 13 (54%) lesions, CIS was entirely surrounded by SA (type A) and in 11 (46%), CIS involved SA at least focally but was not confined to the SA area (type B). The mean size of CIS in type B (30.45 mm) was significantly larger than in type A (18.00 mm). The mean size of SA in type A (39.46 mm) was significantly larger than in type B (19.54 mm). Most type A CIS were non-high-grade, and the oestrogen receptor (ER)(+)/progesterone receptor (PgR)(+)/HER2(-) immunophenotype predominated. Most type B CIS were high-grade and six (54%) were ER(-)/PgR(-). Most type A were bcl-2(+)/p53(-) in both SA and CIS areas, but two (18%) apocrine ductal CIS of type B were bcl-2(-)/p53(+) in both SA and CIS areas. Expression of ER and cyclin D1 in SA was not different from that of SA unassociated with cancer. Most CIS involving SA arises within SA and high-grade DCIS tends to grow beyond SA. Occasional CIS may arise outside SA and secondarily involve SA.

Sclerosing adenosis of the breast: radiographic appearance and efficiency of core-needle biopsy

To examine the mammography and ultrasonography findings of patients who have a final histopathological diagnosis of sclerosing adenosis after breast biopsy, and to evaluate the follow-up results of patients who underwent core needle biopsies. Seventy-six of the 723 patients who underwent breast biopsy in our institution were diagnosed with sclerosing adenosis on histopathological examination. Mammography and ultrasonography findings from these 76 lesions were analyzed retrospectively. Thirty-seven of these lesions were sampled by image-guided core needle biopsy; the remaining lesions were excised surgically. Mammograms and ultrasound images of the lesions were re-evaluated, and the post-biopsy medical records of these patients were evaluated. Sclerosing adenosis was the main diagnosis in 41 patients and the complementary diagnosis in 35 patients. Among the first 41 lesions in which sclerosing adenosis was the main diagnosis, there were 18 (44%) mass lesions, 16 (39%) microcalcification clusters, two (5%) lesions with asymmetrical opacity, three (7%) lesions with architectural distortion, and two (5%) lesions with focal acoustical shadowing that was only detected by ultrasonography. No alterations suggesting malignancy were noted during the follow-up examinations of 35 patients who underwent core needle biopsy. Sclerosing adenosis is a benign proliferative disease of the breast that can be confused with malignancy on clinical, radiological, and even histopathological examination. There is no typical radiological criterion for diagnosis. Core needle biopsy or excisional biopsy can be used, depending on the lesion's characteristics. Core needle biopsy can be the first step in the diagnosis of sclerosing adenosis.

Nodular Sclerosing Adenosis Mimicking Malignancy in the Breast: Magnetic Resonance Imaging Findings

The Breast JournalVolume 17, Issue 1 p. 95-97 Nodular Sclerosing Adenosis Mimicking Malignancy in the Breast: Magnetic Resonance Imaging Findings Pelin Seher Oztekin MD, Pelin Seher Oztekin MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this authorIsil Tuncbilek MD, Isil Tuncbilek MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this authorPinar Kosar MD, Pinar Kosar MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this author Serap Gültekin MD, Serap Gültekin MD Faculty of Medicine – Radiology, University of Gazi, Ankara, TurkeySearch for more papers by this authorFahriye Karataş Öztürk MD, Fahriye Karataş Öztürk MD Ankara Government Hospital – Pathology Ankara, TurkeySearch for more papers by this author Pelin Seher Oztekin MD, Pelin Seher Oztekin MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this authorIsil Tuncbilek MD, Isil Tuncbilek MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this authorPinar Kosar MD, Pinar Kosar MD Ankara Training and Research Hospital – Radiology, Ankara, TurkeySearch for more papers by this author Serap Gültekin MD, Serap Gültekin MD Faculty of Medicine – Radiology, University of Gazi, Ankara, TurkeySearch for more papers by this authorFahriye Karataş Öztürk MD, Fahriye Karataş Öztürk MD Ankara Government Hospital – Pathology Ankara, TurkeySearch for more papers by this author First published: 06 December 2010 https://doi.org/10.1111/j.1524-4741.2010.01022.xCitations: 10 Address correspondence and reprint requests to: Pelin Seher Oztekin, Ankara Training and Research Hospital – Radiology, Cebeci Ankara 06340, Turkey, or e-mail: [email protected]. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume17, Issue1January/February 2011Pages 95-97 RelatedInformation

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate is a rare lesion. Here we report the seventh case of such lesions. Histological examination of the transurethral resection of the prostate of a 83-year-old Japanese man showed a small lesion consisted of sclerosing adenosis and basal cell hyperplasia, in addition to the diffuse glandular and fibromuscular hyperplasia. Immunohistochemically, many basal cells in sclerosing adenosis and basal cell hyperplasia areas showed a positive reaction for p63, cytokeratin 5, and D2-40. Additionally, many basal cells in the sclerosing adenosis area and some basal cells in the basal cell hyperplasia area were positive for S-100 protein and alpha-smooth muscle actin, which are myoepithelial cell markers. Finally, we suggest that hybrid sclerosing adenosis and basal cell hyperplasia may be actually a special form of hyperplastic lesion of all components of prostatic tissue, reflecting the unbalanced distribution of glandular, stromal (sclerosing adenosis), and basal cell hyperplasia with the differentiation toward myoepithelial cells predominantly occurring in a sclerosing adenosis area. Additionally, this case showed that D2-40 is a useful marker of basal cells.

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.

Atypical sclerosing adenosis of the prostate: a rare mimic of adenocarcinoma

Sclerosing adenosis of the prostate is a benign, small, acinar proliferation in dense spindle cell stroma, with a distinct immunohistochemical profiles. It is incidentally found in about 2% of transurethral resection specimens. The aim was to describe cases with significant cytological atypia mimicking cancer, which have not been previously reported. We describe five cases of sclerosing adenosis with significant cytological atypia, referred to as atypical sclerosing adenosis (ASA), which were initially considered suspicious or diagnostic of adenocarcinoma. Seven other cases of typical sclerosing adenosis were used as controls. All cases of typical and atypical sclerosing adenosis displayed an intact basal cell layer, which was immunoreactive for high-molecular-weight keratin, S100 protein, smooth muscle actin, and prostate-specific antigen, with no differences between ASA and the control group. Alpha-methylacyl-coenzyme A racemase was negative. Three of four cases of ASA had aneuploid DNA content by digital image analysis. All cases of typical sclerosing adenosis were diploid. During a mean follow-up of 33 months (range 5-73 months), none developed recurrence or prostatic cancer. ASA is an unusual small, acinar proliferation of the prostate that may be mistaken for adenocarcinoma, and should be distinguished from other mimics, including atypical adenomatous hyperplasia, mesonephric remnant hyperplasia, and post-atrophic hyperplasia. ASA is a benign lesion and aggressive treatment is unwarranted.

Characterization of breast precancerous lesions and myoepithelial hyperplasia in sclerosing adenosis with apocrine metaplasia

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.

When is a diagnosis of sclerosing adenosis acceptable at core biopsy?

To determine concordance of imaging findings and diagnosis of sclerosing adenosis at histopathologic core biopsy and to establish the accuracy of core biopsy when cancer was coexistent. From a database of 1,166 percutaneous biopsies in which sclerosing adenosis was reported, 88 (7.5%) lesions were identified, and imaging and histopathologic findings were reviewed for concordance. Sclerosing adenosis proved to be a minor component at core biopsy for 44 lesions, including one invasive ductal carcinoma, one ductal carcinoma in situ (DCIS), one focus of atypical ductal hyperplasia (ADH), and one atypical lobular hyperplasia. Sclerosing adenosis was a major (> or =50%) component for 44 lesions, including four malignancies, all DCIS manifested as clustered calcifications (pleomorphic [n = 2] or amorphous [n = 2]), and seven foci of ADH manifested as amorphous calcifications. In 30 patients with 33 lesions without atypia or malignancy, sclerosing adenosis was the major finding at core biopsy (21 lesions at 14-gauge core biopsy and 12 at 11-gauge vacuum-assisted biopsy); these patients formed the study population. Mammographic (33 lesions) and sonographic (18 lesions) features were recorded. Twenty-seven lesions had at least 20-month follow-up (n = 25) or excision (n = 2). One spiculated mass was considered discordant and was excised, showing a prospectively unrecognized radial sclerosing lesion with several 2-5-mm foci of invasive tubular and lobular carcinoma. Seventeen (53%) of 32 lesions manifested as masses; 10 (59%) were circumscribed, five (29%) were indistinctly marginated (one with punctate calcifications), and two (12%) were partially circumscribed and partially obscured (one with amorphous calcifications). Fifteen (47%) lesions manifested as clustered calcifications; nine (60%) were amorphous and indistinct, four (27%) were pleomorphic, and two (13%) were punctate. Of 27 lesions with acceptable follow-up, 26 (96%) were believed to have been accurately sampled at core biopsy. Of six radial sclerosing lesions associated with the original 88 lesions, only three (50%) were prospectively recognized. Sclerosing adenosis is an acceptable result at core biopsy of circumscribed masses and nonpalpable indistinctly marginated masses and for clustered amorphous, pleomorphic, and punctate calcifications. Recognition and reporting of coexistent radial sclerosing lesions is encouraged and may prompt excision. Malignancy can be seen with sclerosing adenosis; core biopsy was accurate in six (86%) of seven coexistent malignancies in this series.

Atypical ductal hyperplasia and ductal carcinoma in situ of the breast associated with perineural invasion

Perineural invasion is a histologic feature usually diagnostic of invasion in malignancies. In the breast, however, it has been associated with benign lesions such as sclerosing adenosis (SA), complex sclerosing lesion/radial scar (CSL/RS), and ductal carcinoma in situ (DCIS). This article describes perineural invasion associated with atypical ductal hyperplasia (ADH), florid hyperplasia without atypia (FH), and DCIS. All cases with a diagnosis of perineural invasion were selected from a series of 10,000 breast consult cases. Invasive mammary carcinomas were excluded. Fourteen cases of perineural invasion were found and associated with the following diagnoses: ADH (5), DCIS (3), FH (5), and ductal adenoma (1). Nine cases developed in CSL/RS, 4 cases in SA, and 1 case in a previous biopsy site of ductal adenoma; lesions were all less than 3 mm. The glands involving nerves showed cytologic and architectural features of the adjacent ADH, DCIS, and FH. Immunostaining for protein gene product (PGP) 9.5 marked nerves, and smooth muscle actin antibody highlighted the myoepithelial cells around glands. Perineural invasion seen in association with DCIS and ADH, in a background of CSL/RS and SA, may pose difficulty in diagnosis, especially in small biopsy specimens. It should be assessed with care to avoid misinter-pretation as invasive mammary carcinoma. HUM PATHOL 32:785-790. Copyright © 2001 by W.B. Saunders Company

Aneuploidy in sclerosing adenosis may predict an increased risk of malignancy. A study using the AgNOR silver stain

Sclerosing adenosis (SA) of the breast if a disease associated with an increase relative risk of malignancy. The exact incidence and factors influencing malignant transformation in association with SA are not well established. Two counts of the AgNOR silver staining technique have been correlated with ploidy and proliferative activity. The first count which is the mean number of AgNOR granules (mAgNOR), correlates with ploidy. The second count is the percentage of nuclei exhibiting > or = 5 AgNORs/nucleus (pAgNOR) and reflects proliferative activity. The hypothesis in the current study was that aneuploidy, as determined by the AgNOR silver staining technique, may potentially identify lesions of SA with an increased association with malignant breast disease. The AgNOR silver staining technique was performed on 69 cases of SA with the application of the two counts. Of these cases 53 were not associated with malignancy and 16 were associated with synchronous or metachronous carcinoma of the breast, these being 11 cases of invasive ductal carcinoma (IDC), four cases of ductal carcinoma in situ (DCIS) and one case of lobular carcinoma in situ (LCIS). The patient ages ranged from 27 to 84 years (median 53 years) with a median follow up of 28 months. Six of the 53 cases of SA no associated with malignancy (11%) had aneuploid mAgNOR counts of > or = 2.4 whereas 12 of the 16 cases associated with carcinoma (80%) had such counts (p < 0.0005). This included nine cases of IDC, two cases of DCIS and the case of LCIS. Of the six aneuploid cases not associated with malignancy, two cases showed cytological atypia, one case was associated with atypical ductal hyperplasia and one case was seen in a leukemic patient who had received chemotherapy and radiation therapy. The pAgNOR counts showed a statistically less significant correlation with malignancy (p < 0.03). These findings suggest that aneuploidy, measured by the AgNOR silver stein, seen in SA may help identify lesions with a higher relative risk of being associated with breast carcinoma and hence that may require more aggressive management than diploid ones.