Blunt Duct Adenosis Research Articles

Role of columnar cell lesions in breast carcinogenesis: analysis of chromosome 16 copy number changes by multiplex ligation-dependent probe amplification

Columnar cell lesions have been proposed as precursor lesions of low-grade breast cancer. The molecular characteristic of low-grade breast neoplasia is whole-arm loss of chromosome 16q. Copy number changes of 6 genes on 16p and 20 genes on 16q were analysed by multiplex ligation-dependent probe amplification in 165 lesions of 103 patients. Twenty-three columnar cell lesions and 19 atypical ducal hyperplasia lesions arising in columnar cell lesions were included, as well as cases of usual ductal hyperplasia, blunt duct adenosis, ductal carcinoma in situ, lobular neoplasia and invasive carcinoma. Usual ductal hyperplasia and blunt duct adenosis lacked whole-arm losses of 16q. In contrast, columnar cell lesions without atypia, columnar cell lesions with atypia, atypical ductal hyperplasia, low-grade ductal carcinoma in situ and low-grade invasive carcinomas increasingly harboured whole-arm losses of 16q (17%, 27%, 47% and 57%, respectively). However, no recurrent losses in specific genes could be identified. In several patients, columnar cell lesions and atypical ductal hyperplasia harboured similar losses as related ductal carcinoma in situ or invasive carcinomas within the same breast. There were indications for 16q breakpoints near the centromere. Whole-arm gains on 16p were relatively scarce and there was no relation between whole-arm gains of 16p and progression of lesions of the low-grade breast neoplasia family. In conclusion, columnar cell lesions (with and without atypia) often harbour whole-arm losses of 16q, which underlines their role as precursors in low-grade breast carcinogenesis, in contrast with usual ductal hyperplasia and blunt duct adenosis. However, no recurrent losses in specific genes could be identified, pointing to minor events in multiple tumour suppressor genes rather than major events in a single 16q gene contributing to low-grade breast carcinogenesis.

Mammographic and Ultrasonographic Findings of Different Breast Adenosis Lesions.

Aim: To describe imaging features of different breast adenosis lesions.Materials and methods: Mammographic and ultrasonographic findings of patients with different types of adenosis were reviewed retrospectively Tissue samples were obtained either with US-guided core needle biopsy or localization with needle-wire system and surgical excision.Results: Forty-three adenosis lesions were diagnosed in 41 patients: 27 sclerosing adenosis, 13 blunt duct adenosis and 3 microglandular adenosis. Most frequent abnormal findings of sclerosing adenosis were masses with non-circumscribed margins and focal acoustic shadowing without mass configuration (54%) on ultrasonography. Mammography was normal in 54% of sclerosing adenosis, the most common abnormality was architectural distortion (21%). In blunt duct adenosis, usually circumscribed masses (46%) were detected on ultrasonography, clustered punctate microcalcifications (23%) and circumscribed masses (23%) were observed on mammography. All microglandular adenosis lesions were non-circumscribed masses. Premalignant components were detected only with surgical excisional biopsy in three patients that showed suspicious radiological findings and benign pathological result on core biopsy.Conclusion: The adenosis lesions have no pathognomonic characteristics on mammography and ultrasound. Total excision may be considered when suspicious radiological findings are present although core needle biopsy results are benign.

P4-10-09: Hormone Replacement Therapy: A Benign Breast Disease's Risk?

Abstract Background Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer. However relations between use of HRT and benign breast lesions remain contradictory (1-3). Our goal was to investigate whether HRT and its duration use are associated with benign breast lesions. Materials & Methods From 2001 to 2007, 2708 patients with a non palpable breast lesion were referred to our breast care center. Radiological abnormalities were screened either by breast ultrasound mammography, or MRI. Of those, 1 329 patients had a biopsy in our Radiology Unit. We focus on the postmenopausal women (n=739). Clinical data including HRT use extent were reported. Patients with previous history of benign breast disease or malignancy were excluded. Results The analysis was performed on 739 patients. Biopsies yielded a benign result in 414 (56%) of them (fibroadenoma n=71, blunt duct adenosis n=94, fibrocystic disease n=92, epithelial hyperplasia n=56, others n=101), high risk lesions in 57 (8%) (atypical ductal hyperplasia n=28, atypical lobular hyperplasia n=19, lobular carcinoma in situ n=10) and malignancy in 268 (36%) (not studied here). For the 471 patients with benign or high risk breast lesion, the median age was 59 years, 80% had at least one pregnancy and 27% had a family history of breast cancer. Among these 471 patients, 47% of them had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 2 years. The HRT use was not significantly associated with the type of benign or high risk breast disease. No association was observed either between breast disease and duration of HRT (less or more than 7 years respectively).Older age was significantly correlated to atypia or carcinoma (median age at diagnosis 59 y.o in benign lesions, 60 y.o in high risk lesions and 62 y.o in malign lesions, with significant difference) (p<0,0001). Conclusion In this study of postmenopausal women, HRT and its duration use were not associated with the type of benign or high risk breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of HRT use is small, if ever it exists. 1. Finkelde DT, Kitchen PR, Hayes PR, McKinlay MR, Henderson MA 2001 Symptomatic benign breast disease and hormone replacement therapy. Breast 10:127–130 2. Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J 2003 Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Eur J Cancer 39:1738–1745 3. Rohan TE, Miller AB 1999 Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast. Eur J Cancer Prev 8:123–130 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-09.

Differential Diagnosis between Sclerosing Adenosis and Tubular Carcinoma of the Breast under Transmission and Scanning Electron Microscope

The tubular carcinoma of the breast is an uncommon histological subtype of invasive breast cancer, which is generally associated with an excellent prognosis. Previous studies have demonstrated that this well differentiated variant is linked with a low incidence of lymph node involvement, a low rate of local recurrence and a high overall survival rate when compared to standard invasive ductal carcinoma. Due to its favorable prognosis, some studies have proposed that a diagnosis of tubular carcinoma might warrant less aggressive surgical or adjuvant treatment. Histologically, tubular carcinoma may mimic sclerosing adenoma or bluntduct adenosis. Its ductal nature appears well confirmed by the few ultrastructural studies of this mammary cancer. Tubular carcinoma should also be distinguished from microglandular adenosis, an uncommon form of sclerosing adenosis. The aim of this study is to prove that the ultrastructure results can give the correct diagnosis between tubular carcinoma and sclerosing adenosis.

Benign breast lesions in an African population: A 25-year histopathological review of 1864 cases

Objective:The objective of this study was to delineate the prevalence and characterize the histologic pattern of benign breast diseases (BBDs) in the University of Benin Teaching Hospital, Benin City, Nigeria.Materials and Methods:A 25-year-old (1985-2009) retrospective study of all patients presenting with BBD.Results:During the 25-year-old study period, 1864 cases of BBD constituting 72.4% of all breast lesions were seen. The female to male ratio was 28.6:1. An increasing incidence of BBDs was observed. The overall mean age for BBD was 27.5 years, SD±11.3 with an age range of 9-84 years and a peak age occurrence in the third decade. The single most common lesion was fibroadenoma accounting for 43.1% of cases, followed by fibrocystic change (23.8%) with mean ages of 22.3 years and 30.2 years, respectively. Both lesions had a peak occurrence in the third decade. Other major lesions encountered were sclerosing adenosis (7.3%), atypical ductal hyperplasia (3.6%), and blunt duct adenosis (2.3%). Gynecomastia (2.1%) was the predominant lesion in males. Inflammatory lesions constituted 8.1% of cases while stromal and skin lesions accounted for 1.1% and 0.9% of cases respectively.Conclusion:BBDs constituted 70% of breast lumps and were mostly fibroadenoma and fibrocystic change. BBDs occurred predominantly in young females with a peak in the third decade. Though premalignant lesions of atypical hyperplasia were less common, biopsy of all BBDs should be done to exclude these lesions and routine mammographic screening of at risk individuals instituted to increase their detection.

Rapidly-growing nodular pseudoangiomatous stromal hyperplasia of the breast: case report

Pseudoangiomatous stromal hyperplasia is a benign proliferative lesion of the mammary stroma that rarely presents as a localized mass. Pseudoangiomatous stromal hyperplasia is characterized by a dense, collagenous proliferation of the mammary stroma, associated with capillary-like spaces. Pseudoangiomatous stromal hyperplasia can be mistaken with fibroadenoma on radiological examination or with low-grade angiosarcoma on histological examination. Its main importance is its distinction from angiosarcoma. The presented case was a 40-year-old woman who was admitted with a rapidly growing breast tumor. Physical examination revealed an elastic-firm, well-defined, mobile and painless mass in her right breast. Mammograms revealed a 6.7 x 3.7 cm, lobulated, well-circumscribed mass in her right breast but no calcification. Sonographic examination showed a well-defined and homogenous mass, not including any cyst. Based on these findings, a provisional diagnosis of fibroadenoma was made. Considering the rapid growth history of the mass, tumor excision was performed. The excised tumor was well demarcated and had a smooth external surface. Histological examination revealed the tumor to be composed of markedly increased fibrous stroma and scattered epithelial components (cystic dilatation of the ducts, blunt duct adenosis). The fibrous stroma contained numerous anastomosing slit-like spaces. Isolated spindle cells appeared intermittently at the margins of the spaces resembled endothelial cells. Immunohistochemical staining showed that the spindle cells were positive for CD34 and negative for Factor VIII-related antigen. The lesion was diagnosed as nodular pseudoangiomatous stromal hyperplasia.

Abstract P6-09-06: Oral Contraceptive Use and Overall Breast Disease Risk: Cross Sectional Retrospective Study

Abstract Background: Oral contraception (OC) is one of the most widely used means for birth control in the world. In several studies, OC has been associated with a slightly increased risk of breast cancer in current user, and with a decreased risk of benign disease. Little is known about atypical high risk lesions. Our goal was to investigate whether OC use was a risk factor or a protective factor for benign, high risk or malignant breast lesions. Material and methods : From 2001 to 2007, all non-palpable breast lesions referred to biopsy or cytology in Saint Louis hospital were prospectively registered. Demographic and clinical data including oral contraceptive pill use extent were reported. We defined benign lesions (fibroadenoma, blunt duct adenosis, fibrocystic changes, epithelial hyperplasia, others), high risk lesions (atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ and malignant lesions (ductal carcinoma in situ, invasive ductal or lobular carcinoma). The aim was to analyse the correlation between the duration of OC use and the occurrence of the breast disease classified by histology groups. Patients with previous history of benign breast disease or malignancy were excluded. Results: The analysis was performed on 1329 breast lesions. The breakdown of the lesions were as follows: 819 benign lesions (fibroadenoma n=155, blunt duct adenosis n=169, fibrocystic disease n=194, epithelial hyperplasia n=132, others n=170), 104 high risk lesions (atypical ductal hyperplasia n=54, atypical lobular hyperplasia n=29, lobular carcinoma in situ n=21), and 406 malignant lesions (ductal carcinoma in situ n=158, invasive ductal or lobular carcinoma n=248). The duration of oral contraception use was not significantly associated with the occurrence of benign, high risk or malignant breast disease. When focusing on benign lesion subtypes, no association was observed either. Older age was significantly correlated to the occurrence of atypia or carcinoma. Significant difference existed in the median age of apparition 55 y.o and 57 y.o respectively, versus 53 y.o for benign lesion (p< 0,0001), as well as menopausal status at diagnosis (57.7% and 68.3%, respectively, versus 53% for benign lesion) (p< 0,0001). Conclusion: In this cross sectional retrospective study, the duration of OC use was not associated with differential occurrence of benign, high risk and malignant breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of OC use is small, if ever it exists. Results [Table 1] Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-09-06.

Pseudoangiomatous stromal hyperplasia in a complex neoplastic lesion involving anogenital mammary‐like glands

Anogenital mammary-like glands (AMLG) may give rise to various pathologic lesions identical to those known in mammary pathology. Pseudoangiomatous stromal hyperplasia (PASH), a relatively frequent hormonal change associated with different benign and malignant processes in the breast, was only once mentioned in the literature concerning the pathology of AMLG. We present here a new case of PASH in a lesion of AMLG. The present case of PASH is remarkable because of its occurrence within a complex lesion evidencing the changes identical to or reminiscent of blunt duct adenosis, fibroadenoma and hidradenoma papilliferum.

Flache epitheliale Atypie

According to the WHO, flat epithelial atypia (FEA) is defined as a neoplastic epithelial proliferation of ductal type in either a single or in multiple terminal duct lobular unit(s) limited to the periphery of the ductules in a clinging growth pattern. The atypical cells may form between one and several layers of epithelial cells that show low grade cytologic atypia. FEA most often presents as mammographic microcalcifications, which are typically round (secretory type and psammomatous calcification in an eosinophilic matrix, so-called ossifying calcifications). Clinical relevance is dependent on whether the lesion appears in isolation or whether it is an excision biopsy or a minimally invasive biopsy. Currently available data suggest that the risk of subsequent breast carcinoma in the ipsilateral breast is very low following the diagnosis of FEA. The differential diagnosis should include atypical ductal hyperplasia, low-grade clinging ductal carcinoma in situ, blunt duct adenosis and apocrine metaplasia.

Are columnar cell lesions the earliest histologically detectable non-obligate precursor of breast cancer?

Columnar cell lesions (CCLs) are one of the most common abnormalities in the adult female human breast, characterized by the presence of columnar-shaped epithelial cells lining enlarged terminal-duct lobular units. CCLs are being seen increasingly in core biopsies taken for the non-palpable calcifications. The increased incidence may reflect improved delineation and recognition of CCLs by pathologists or a true increase in incidence related to biological and/or environmental factors. Columnar cell-like lesions have been described under a variety of names such as blunt duct adenosis, flat epithelial atypia, and ductal intraepithelial neoplasia type DIN1a. The current histologic classification used by some pathologists divides them into simple columnar cell change and columnar cell hyperplasia, both of which can occur with or without atypia. Columnar cells lack mature luminal or basal/myoepithelial phenotype markers, but they are usually positive for estrogen receptor-alpha. The cellular origin of CCLs and their possible relationship to either expansion or metaplasia of a preexisting normal cell phenotype remains unclear. CCLs are frequently associated with lobular and ductal in situ tumors and invasive lobular and tubular carcinomas. The relationship and natural history of CCLs to invasive ductal carcinoma is enigmatic, but they may prove of clinical relevance when detected by screening mammography.

Therapeutic mammotome excision of BI-RADS 4A breast masses

The aim of this study was to determine the morphologic types, associations, and significance of flat epithelial atypia (FEA) with or without atypical ductal hyperplasia (ADH) in mammotome core needle biopsies. We evaluated the correlation of FEA in core biopsies with follow-up excision biopsies to predict the likelihood of upgrade to carcinoma. We also investigated the utility of Ki-67 in predicting which lesions were associated with carcinoma in the excisional biopsies. Core biopsies with a diagnosis of atypia were categorized as pure FEA, pure ADH, or both. The following parameters were recorded: indication for core biopsies, presence of microcalcifications, inflammation, and stromal changes. A total of 60 core biopsies from 56 patients were studied. Pure ADH, pure FEA, and concomitant FEA and ADH were seen in 13%, 23%, and 64% of core biopsies, respectively. The most common architectural pattern of FEA resembled blunt duct adenosis (52%), followed by cystically dilated ducts with secretions (38%) and apocrine features (10%). Chronic inflammation and stromal changes were noted in 29% and 36% of FEA, respectively. Excisional biopsies in 48 of 56 patients demonstrated ductal carcinoma in situ and/or invasive carcinoma in 10 patients (21%), lobular carcinoma in situ or atypical lobular hyperplasia in 5 (11%), residual ADH in 11 (23%), and no atypia in 24 patients (50%). Three (21%) of 14 pure FEA upgraded to ductal carcinoma in situ and/or invasive carcinoma on excisional biopsy. The staining for Ki-67 in FEA/ADH was similar regardless of whether they were upgraded to carcinoma or not. In summary, we found a strong association between FEA and ADH, which may reflect a biologic progression. Most FEAs have a low-power appearance of a well-circumscribed group of ducts. Chronic inflammation and stromal changes are present in a subset of cases. Flat epithelial atypia shows a risk of upgrade to carcinoma similar to that of ADH and, hence, should be recognized and warrants a follow-up excision.

Significance of flat epithelial atypia on mammotome core needle biopsy: should it be excised?

The aim of this study was to determine the morphologic types, associations, and significance of flat epithelial atypia (FEA) with or without atypical ductal hyperplasia (ADH) in mammotome core needle biopsies. We evaluated the correlation of FEA in core biopsies with follow-up excision biopsies to predict the likelihood of upgrade to carcinoma. We also investigated the utility of Ki-67 in predicting which lesions were associated with carcinoma in the excisional biopsies. Core biopsies with a diagnosis of atypia were categorized as pure FEA, pure ADH, or both. The following parameters were recorded: indication for core biopsies, presence of microcalcifications, inflammation, and stromal changes. A total of 60 core biopsies from 56 patients were studied. Pure ADH, pure FEA, and concomitant FEA and ADH were seen in 13%, 23%, and 64% of core biopsies, respectively. The most common architectural pattern of FEA resembled blunt duct adenosis (52%), followed by cystically dilated ducts with secretions (38%) and apocrine features (10%). Chronic inflammation and stromal changes were noted in 29% and 36% of FEA, respectively. Excisional biopsies in 48 of 56 patients demonstrated ductal carcinoma in situ and/or invasive carcinoma in 10 patients (21%), lobular carcinoma in situ or atypical lobular hyperplasia in 5 (11%), residual ADH in 11 (23%), and no atypia in 24 patients (50%). Three (21%) of 14 pure FEA upgraded to ductal carcinoma in situ and/or invasive carcinoma on excisional biopsy. The staining for Ki-67 in FEA/ADH was similar regardless of whether they were upgraded to carcinoma or not. In summary, we found a strong association between FEA and ADH, which may reflect a biologic progression. Most FEAs have a low-power appearance of a well-circumscribed group of ducts. Chronic inflammation and stromal changes are present in a subset of cases. Flat epithelial atypia shows a risk of upgrade to carcinoma similar to that of ADH and, hence, should be recognized and warrants a follow-up excision.

Histopathologic types of benign breast lesions and the risk of breast cancer: case-control study.

The hypothetical multistep model of carcinogenesis indicates that breast cancer develops via a series of intermediate hyperplastic lesions through in situ to invasive carcinoma. To identify the risk inherent within the different morphologic lesions, we have analyzed the data from 674 benign biopsy specimens comprising 120 cases who subsequently developed breast cancer and 382 controls (matched for age and date of biopsy) spanning a period up to 20 years of follow-up (mean 66.95 months). In this series we have confirmed an increased risk associated with certain types of benign breast lesions. Atypical lobular hyperplasia was the most significant risk factor for breast cancer with more unfavorable outcome in patients <50 years of age (p = 0.003) and a relative risk (RR) of 4.55 (confidence interval [CI] 1.77-11.69). Hyperplasia of usual type showed an RR of 1.53 (CL 1.10-2.13) with a statistically worse probability of survival (cancer-free time) for patients >50 years. For atypical ductal hyperplasia the RR was 2.03 (CI 0.80-1.39). Blunt duct adenosis was significantly more common in cases progressing to breast cancer compared with controls, showing an RR of 2.08 (CI 1.12-2.85). We describe in detail the criteria of morphologic changes observed in blunt duct adenosis and define, for the first time, the level of risk associated with each of its six subtypes. Improved knowledge of breast carcinogenesis will provide insight for defining high-risk groups thus resulting in improved screening and management regimens.

Changed expression of 9-O-acetyl GD3 (CDw60) in benign and atypical proliferative lesions and carcinomas of the human breast.

Expression of gangliosides is affected in various ways by malignant cell transformation. In the present study, we investigated the expression of CDw60, a constituent of O-acetylated disialogangliosides, in benign and atypical proliferative breast diseases, and preinvasive and invasive carcinomas by immunohistochemistry and thin-layer chromatography (TLC). In normal ducts, antibodies to CDw60 (mAb M-T21) reacted to membranes of the Golgi apparatus in the juxtaluminal cell compartment. A similar polarized distribution of Golgi cisterns in epithelial cells was observed in several benign lesions, i.e., fibroadenomas, intraductal papillomas, and gynecomastia. In contrast, blunt duct adenosis and duct hyperplasia exhibited an abnormal cytosolic and cell surface staining, whereas atypical duct hyperplasia showed randomly dispersed immunoreactive Golgi cisterns, indicating loss of epithelial polarity. In mammary carcinomas and in two breast carcinoma cell lines (MCF-7 and EFM-19) the neoplastic cells contained CDw60-immunolabelled Golgi complexes, which were distributed in a disorderly fashion throughout the cytoplasm, thus reflecting a loss of epithelial polarity. Additionally, only well differentiated ductal carcinomas in situ or invasive ductal carcinomas disclosed a strong cell surface labelling, which was absent in lower differentiated carcinomas of the same types. In all carcinomas, the intensity of CDw60 immunostaining decreased with progressing loss of differentiation (grade of dedifferentiation), as demonstrated by staining intensity in paraffin sections and by evaluation of the relative amounts of extracted 9-O-acetyl GD3 by TLC. Our results indicate that abnormal CDw60 expression is already detectable in benign proliferative breast lesions with different risk rates to develop into malignant lesions. Downregulation of CDw60 expression in poorly differentiated invasive carcinomas may be the consequence of loss of cell functions usually associated with poor prognosis.

Telomerase activity in human proliferative breast lesions.

Telomerase, a cellular reverse transcriptase, has been detected in the majority of human malignant tumors, where it provides an escape mechanism from proliferative limitations due to progressive telomere erosion with each cell division. In this study, we used a non-radioactive telomeric repeat amplification protocol (TRAP) with an internal telomerase assay standard for the detection and semiquantitative analysis of 98 single frozen sections of normal breast tissue and benign and malignant breast lesions on an automated laser-fluorescence sequencer. Telomerase activity was detected in 36 of 40 (90%) infiltrating breast carcinomas, whereas no activity was found in nonmalignant breast tissues including blunt duct adenosis, papilloma, ductal hyperplasia and atypical ductal hyperplasia. However, telomerase activity was detected in 59% of ductal in situ carcinomas, suggesting that telomerase reactivation is an early event in breast carcinogenesis. We found a positive correlation between telomerase activity levels and cell proliferation determined by MIB1 immunostaining. No correlation, however, could be demonstrated between telomerase activity and other known breast cancer prognostic indicators. Telomerase activity was also detected in 60% of fibroadenomas indicating that careful interpretation of analysis of telomerase activity in fine needle aspirates is required, since low telomerase activity may not necessarily be an indicator of malignancy in breast tissue.

Benign breast disease: The relationship between its histological features and risk factors for breast cancer

Associations between histologically defined proliferative, but benign, epithelial disorders of the breast and risk factors for breast carcinoma were examined in 568 patients whose breast biopsies were submitted consecutively to the laboratory. Some disorders were associated with multiparity. Blunt duct adenosis was associated with a family history of breast cancer. Apart from a positive association with fibroadenoma, use of oral contraceptives was not associated with any proliferative lesion. Proliferative epithelial lesion changes were not associated with other aspects of obstetric or gynecological history.

Histopathology of benign non-palpable breast lesions identified by mammography.

Over four years the histological features of benign breast diseases, diagnosed after biopsy of non-palpable mammographic abnormalities, were reviewed and correlated with the mammographic appearances. The histological features were compared with those from all other benign biopsy specimens taken during the same period. The incidence of sclerosing adenosis and microcalcifications was considerably higher in the group of non-palpable mammographic lesions; fibrous disease of the breast and radial scar (infiltrating epitheliosis) were also more common. There was no difference in the incidence of epithelial hyperplasia between the two groups. Correlation with the mammographic appearances showed that microcalcification was most often associated with blunt duct adenosis and that stromal distortion or masses were most often caused by fibrous disease.

Determination of growth fractions in benign breast disease (BBD) with monoclonal antibody Ki-67

Certain types of benign breast disease (BBD) carry an increased risk of malignancy. Several morphological criteria such as an atypia score are used to define this group, and the use of a kinetic parameter may provide additional information. Therefore, the growth fractions of 120 benign breast lesions were determined using the monoclonal antibody Ki-67. The values obtained range from 0.3% to 10.8% (average 3.1% +/- 2.2%) compared to breast carcinomas with an average of 15.3% +/- 10.1%, range 0.8% to 47.8%. All specimens were classified using the terminology of Azzopardi. The prevailing histological entities were cystic disease, fibroadenoma, and blunt duct adenosis. Between these groups no differences in growth fractions were observed. Postmenopausal patients had slightly lower values than premenopausal women. Further prospective studies are needed to evaluate whether those cases of BBD with a high number of Ki-67 positive cells have an increased risk of breast cancer, independently from conventional histological classifications.

The patho‐epidemiology of benign proliferative epithelial disorders of the female breast

Benign breast disease is associated with increased risk of subsequent breast cancer, especially when there is evidence of epithelial proliferation. There is no standard terminology for benign proliferative epithelial disorders (BPED), and this hinders direct comparisons between the various studies which have examined their pathology and their relationship to breast cancer. The present paper reviews previous classification schemes for BPED, and proposes an alternative system in which epitheliosis and blunt duct adenosis are the major features, the degree and pattern of the hyperplasias being graded separately. Adoption of this or a similar system as a standard should facilitate future comparative studies of these conditions. As BPED are apparently pre-malignant conditions, an understanding of their aetiology is important because it may help to elucidate the aetiology of breast carcinoma, and to open up avenues for its prevention. If BPED are precursors to breast carcinoma, then risk factors for BPED should also be risk factors for breast carcinoma. To date, in epidemiological studies of BPED, such concordance has not been demonstrated, as consistent risk factors for the BPED have not yet emerged. This may have resulted, at least in part, from differences in the histological categories included in the various studies. Therefore, collaboration between epidemiologists and pathologists may facilitate progress towards an understanding of BPED.

The differential diagnosis of microcalcification. Micro-cyst (blunt duct) adenosis (author's transl)

One hundred and thirty-five operations were carried out because of a finding of microcalcification in the breast. In 10% of these, the calcification was shown histologically to be within foci of micro-cyst (blunt duct) adenosis. Analysis of the radiographic appearances of the microcalcification revealed a characteristic radiographic pattern. The differential diagnosis of groups of calcification in intraduct carcinomas and in benign lesions is discussed.