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Orientador: Jose Vassalo Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: O sistema ductal da mama é revestido por duas camadas de células: uma constituída de células epiteliais luminais e outra de células mioepiteliais (CME). A identificação das CMEs é de grande importância na rotina em patologia cirúrgica, já que estas estão presentes em lesões benignas e geralmente ausentes nas malignas. Contudo, esta identificação morfológica (i.e., à hematoxilina-eosina) pode tornar-se difícil, sendo necessários marcadores imunoistoquímicos mioepiteliais. Até o momento, nenhum marcador mostrou-se, isoladamente, sensível e específico o bastante para auxiliar de maneira fidedigna em dilemas diagnósticos específicos, especialmente em: (1) lesões esclerosantes benignas vs. carcinoma tubular e (2) neoplasias papilíferas. No presente trabalho, dois novos marcadores mioepiteliais (p63 e CD10) foram testados e comparados com marcadores tradicionalmente empregados em patologia cirúrgica (1A4 e calponina). No primeiro dilema diagnóstico, foram estudados 10 casos de adenose esclerosante, 10 casos de cicatriz radiada e 10 casos de carcinoma tubular. Todos os marcadores demonstraram expressão nas CMEs de todas as lesões benignas e foram consistentemente negativos nos casos de carcinoma tubular, porém, p63 e CD10 mostraram maior especificidade. Os marcadores tradicionais mostraram positividade em células estromais em todos os casos de carcinoma tubular, sendo que esta reação-cruzada poderia causar problemas de interpretação ao simular uma camada de CMEs em quatro casos. Contudo, 1A4 mostrou uma positividade mais intensa e reprodutível nas CME. Concluímos, assim, que p63 e CD10 devem ser usados como anticorpos complementares ao 1A4 na distinção entre lesões esclerosantes benignas e carcinoma tubular da mama. No estudo das neoplasias papilíferas, foram avaliados 20 casos incluindo papilomas, papilomas atípicos e carcinomas papilíferos, além do tecido mamário normal adjacente. Todos os marcadores foram difusamente positivos no tecido mamário normal e papilomas, indicando sensibilidades semelhantes na identificação de CME. Uma positividade intensa foi encontrada em 100% dos casos corados para 1A4 e CD10, mas em apenas 76% e 60,5% dos corados para calponina e p63, respectivamente, sendo as diferenças estatisticamente significantes (p

Purpose Adenosis lesions of the breast, including sclerosing adenosis and adenosis tumors, are a group of benign proliferative disorders that may mimic the features of malignancy on imaging. In this study, we aim to describe the features of breast adenosis lesions with suspicious or borderline findings on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods In our database, we identified 49 pathologically proven breast adenosis lesions for which the final assessment of the breast MRI report was classified as either category 4 (n=45) or category 5 (n=4), according to the Breast Imaging Reporting and Data System (BI-RADS) published by the American College of Radiology (ACR). The lesions had a final diagnosis of either pure adenosis (n=33, 67.3%) or mixed adenosis associated with other benign pathologies (n=16, 32.7%). Results Of the 49 adenosis lesions detected on DCE-MRI, 32 (65.3%) appeared as enhancing masses, 16 (32.7%) as nonmass enhancements, and one (2.1%) as a tiny enhancing focus. Analysis of the enhancing masses based on the ACR BI-RADS lexicon revealed that among the mass descriptors, the most common features were irregular shape in 12 (37.5%), noncircumscribed margin in 20 (62.5%), heterogeneous internal pattern in 16 (50.0%), rapid initial enhancement in 32 (100.0%), and wash-out delayed en-hancement pattern in 21 (65.6%). Of the 16 nonmass enhancing lesions, the most common descriptors included focal distribution in seven (43.8%), segmental distribution in six (37.5%), clumped internal pattern in nine (56.3%), rapid initial enhancement in 16 (100.0%), and wash-out delayed enhancement pattern in eight (50.0%). Conclusion Adenosis lesions of the breast may appear suspicious on breast MRI. Awareness of these suspi-cious-appearing features would be helpful in obviating unnecessary breast biopsies.

OBJECTIVE: To analyze the cytologic findings of sclerosing adenosis of the breast. STUDY DESIGN: We reviewed the fine needle aspiration (FNA) cytologic slides of 7 cases ofsclerosing adenosis of the breast and compared the cytologic findings with those of 10 cases of fibroadenoma and 7 cases of fibrocystic change. RESULTS: The smears of sclerosing adenosis were moderately to markedly cellular, consisting of small to large groups of benign epithelial cells arranged with variable architecture. Acinar sheets, scattered individual epithelial cells and small, dense, hyalinized stroma were found in all cases ofsclerosing adenosis. Epithelial cells in sclerosing adenosis appeared more frequently as acinar sheets and discohesive individual cells than did those of fibroadenoma (P

The initial presentation of breast malignancy as noninvasive carcinoma in an area of sclerosing adenosis is unusual. Especially, lobular carcinoma in situ in sclerosing adenosis sometimes can be a potential source of confusion with invasive lobular carcinoma. We report a case of lobular carcinoma in situ presenting in adenosis exhibiting patterns akin to invasive lobular carcinoma, thus leading to potential misdiagnosis. Overall architecture of the lesion as seen at lower power and immunohistochemistry can be useful to distinguish between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma.

53-year-old woman noticed a small nodule in the left lateral breast near the axillary region. Results of a mammogram were normal. The nodule was removed and consisted of a 0.4 3 0.2 3 0.2-cm piece of fat. It contained several small intraductal papillomas with superimposed hyperplasia of ordinary type. Epithelial elements within a nearby small nerve were identified (arrow). The lack of cytologic atypia and an architectural identity to the hyperplastic component of the papilloma led us to believe this was benign epithelium. The patient received no further therapy and is well 5 months later. Perineural involvement by benign breast disease is limited to one report of 2 patients 1 and a review of 1000 consecutive breast lesions coded as sclerosing adenosis. 2 The

Ultrastructural findings are described in two cases of collagenous spherulosis associated with intraductal hyperplasia and sclerosing adenosis. The spherules showed a variable composition of basement membrane, banded collagen, and mineral deposition. Some spherules were connected to the periacinal stroma by a thin pedicle. The authors propose that spherules represent a peculiar form of stromal invagination that could be seen in a variety of breast lesions, rather than a form of intraductal hyperplasia.

Backgrounds To elucidate the features of breast carcinoma (BC) arising from sclerosing adenosis (SA). Methods 106 BCs arising from SA were collected. Their clin-icopathological characteristics were examined and immunohisto-chemical staining was performed. Results (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. Conclusions 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.

Infiltration of the walls of blood vessels by mammary epithelium was found in two cases of sclerosing adenosis. Survey of a series of cases of sclerosing adenosis and severe epitheliosis revealed a 10 per cent incidence of vascular infiltration. Usually only a single vein was involved but in the propositus an artery and two veins were infiltrated. The findings highlight the infiltrative propensities of sclerosing adenosis, already recognised as infiltrating nerve sheaths. The vascular lesions appear to be benign structurally and this is borne out by the clinical behaviour.

The analytical study of the case material has allowed a precise evaluation of the distribution by age groups of the different pathologic processes of the breast, of the localization and dimensions of malignant tumors, as well as the diagnostic accuracy for those cases histologically ascertained and those with a follow-up. The diagnostic accuracy and the consequent reliability of the xeroradiographic method for the diagnosis of breast cancer is distinctly superior to that reported in the literature for traditional mammography, whereas for the differential diagnosis between circumscribed dysplastic manifestations and benign tumors xeromammography is not sufficiently reliable. The authors critically discuss the results and in particular the problem of false positives, which also include diagnostic errors that cannot be avoided in that they directly derive from the pathologic morphology of the disease process (plasma cell mastitis and sclerosing adenosis). As regards the problem of false negatives, they can be reduced within certain limits by resorting to other instrumental investigations. However, there are cases (1% of the malignant neoplasias histologically ascertained) that present a completely negative xeroradiographic finding. These are the limits of the radiologic investigation which cannot in any way be surmounted.

The cytologic diagnosis of the following diseases of the mammary glands may be difficult: lobular carcinoma, sclerosing adenosis, proliferative mastopathy with cell atypia, inflammatory carcinoma and virile carcinoma. The cytologic pattern of these and other diseases of the mammary glands is demonstrated and discussed.

Various mammary lesions may offer considerable clinical as well as histological difficulties concerning the biological behaviour. Among them are sclerosing adenosis, ductular papillomas, proliferating

Intravenous DSA of the breast is a new, hardly invasive, method for demonstrating carcinomas of the breast and for differentiating these from benign lesions. Carcinomas show distinct tumour-staining during the capillary phase, although the criteria which are used on conventional angiography are not recognisable. Semi-malignant tumours show feeble staining. Benign diseases such as fibro-adenomas and focal sclerosing adenosis are not demonstrated by I-V DSA. The indication for intravenous breast DSA is for the clarification of suspicious findings where less invasive methods, such as mammography and cytology, have failed to give a definitive diagnosis.

The ultrastructure of four tubular carcinomas of the breast is described. The neoplastic tubules are single layered and lack a myo-epithelial component, an important feature in distinguishing tubular carcinoma from sclerosing adenosis. Numerous myo-fibroblasts are present in the stroma of all four tumours and, since cells of this type have been recorded only occasionally in the stroma of other types of breast carcinoma, it is suggested that they may be a characteristic feature of tubular carcinomas.

In order to evaluate the clinical usefulness of an electronic real-time linear array scanner in breast diseases, ultrasonography was performed in 148 cases of histologically confirmed palpable breast masses. The real-time images were observed on a television monitor while moving the hand-held transducer probes over the masses. It took only a few minutes to examine and diagnose a palpable mass. Among 45 carcinomas, 39 lesions were correctly diagnosed, four lesions were not detected by ultrasound and two were misdiagnosed as fibroadenomas. On the other hand, ten benign lesions were falsely diagnosed as breast cancers: seven mastopathies (including four sclerosing adenosis), two fibroadenomas and one abscess. The sensitivity and specificity for diagnosing breast cancer were 0.87 and 0.90 respectively. Real-time sonography is a simple, time-saving and useful tool for examining palpable breast masses. However, it should be realised that some breast cancers are difficult to image and differentiate from benign lesions.

Review of sections from 1000 consecutive breast biopsy specimens coded as sclerosing adenosis disclosed nerve or perineural invasion in 20 lesions. Follow-up information showed that all patients with data available were living and well at the time of contact; the median follow-up interval was 7 years. This included 17 patients whose only definitive treatment was the biopsy. Although involvement of nerves by glandular epithelium is usually regarded as a feature of cancerous rather than benign growths, its presence in lesions of the breast does not by itself justify a diagnosis of carcinoma.

A case of endometriosis involving the right uterosacral ligament in which nonneoplastic endometrial glands were present in the perineural space is reported. In the past, epithelial invasion of the perineural space was considered evidence of the presence of malignant disease. Rodin and colleagues,2 however, concluded that the perineural space is not a lymphatic space and that involvement may represent extension into the tissue plane of least resistance. Perineural invasion has been reported in benign conditions of the breast, including chronic cystic disease and sclerosing adenosis. It is important that involvement of the perineural space in endometriosis not be interpreted as evidence of malignancy. We believe that involvement of the perineural space in other nonmalignant conditions will be described in the future.

A case of sclerosing adenosis of the male breast is reported. This very unusual lesion was found at autopsy in a man with pulmonary oat cell carcinoma. In females, sclerosing adenosis is a well-characterized entity. In males, however, it does not normally occur because of the physiologic lack of lobular development. The possible pathomechanism of this lesion is briefly discussed, with an emphasis on presumed lobular stimulation by tumor-elaborated ectopic hormone.

Uptake of thallium in a patient with sclerosing adenosis of the breast was detected. Although thallium has been reported to accumulate in primary carcinoma of the thyroid, lung, and liver, detection of a breast lesion on a thallium scan has not been previously reported.

This report deals with the diagnostic importance of intracytoplasmic lumina. The separation between tubular carcinoma and sclerosing adenosis, and the ultrastructural features of variants of lobular carcinoma are discussed. The role of electron dense granules as well as other markers for neuroendocrine cells are evaluated, and finally, the difficult separation of both small-cell and spindle cell tumors is considered.

A group of five different patients who had extensive sclerosing adenosis with ductules containing cells characteristic of lobular carcinoma were studied (six breasts in all). Because of the complex arrangement of ductules in sclerosing adenosis, the possibility of an invasive lobular carcinoma was considered in two cases. The distinction between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma rests with the overall architecture of the lesion as seen at low power. Foci of sclerosing adenosis, with or without carcinoma in situ, have dilated ductules peripherally, and narrow ones centrally, whereas infiltrating lobular carcinoma has no overall organization. Because of the diagnosis of lobular carcinoma in situ, extended simple mastectomy was performed in three patients, and as expected, the lymph nodes were free of tumor.

The innocuous histologic appearance of tubular carcinoma of the breast and its superficial histologic resemblance to sclerosing adenosis will occasionally present diagnostic problems. A comparative ultrastructural analysis of two tubular carcinomas and three cases of sclerosing adenosis was made that showed definite differences in the pattern of myoepithelial cell differentiation and basal lamina deposition in these two entities. Prominent myoepithelial cells and basal lamina reduplication were both conspicuous features of sclerosing adenosis that appeared to be absent in tubular carcinoma. Intracytoplasmic “pseudo-cysts” were frequently found in sclerosing adenosis, but not in tubular carcinoma. Conversely, intracytoplasmic lumina and incomplete tubular structures were present in tubular carcinoma and seemingly absent in sclerosing adenosis. Such basic ultrastructural differences may help to differentiate these two mammary lesions when diagnostic problems occur at the conventional light microscopic level.

Tumors containing smooth muscle are rare in the breast. A myoepithelial origin for the myoid component of such lesions was postulated in previous reports. Myoepithelial hyperplasia has long been recognized as a common component of some breast lesions, including sclerosing adenosis, papillomas, and fibroadenomas. Three breast tumors composed of variable admixtures of adipose tissue, fibrous tissue, and smooth muscle are described. The authors postulate that the myoid component of two of the three lesions may have arisen in a milieu of myoepithelial hyperplasia. The origin of the myoid component in the third case is not clearly defined.

A re-examination study was made of 18 cases of histologically verified adenosis tumour from 12 different hospitals in Denmark. Four mammographic appearances could be identified. No pathognomonic sign or appearance could be identified. The median age of the patients was 42 years. The mean diameter of the 'tumour' was 2.1 cm. The diagnostic problem of malignant and benign breast disease is discussed.

Sclerosing adenosis is a common proliferative lesion of the mammary lobule which is not associated with an increased risk of developing breast cancer. An unusual case of florid sclerosing adenosis showing extensive cancerization by intraductal carcinoma is reported. The neoplastic nature of the sclerosing lesion can be recognized by the unusual distension of the tubules by cells and the subtle cytological changes, and further confirmed by finding foci of classical intraductal carcinoma.

Immunohistological localisation of elastin was achieved by means of the peroxidase-antiperoxidase method after preliminary trypsinisation of sections from 48 benign breast biopsies. The procedure allows retrospective examination of routinely formalin-fixed, paraffin-embedded breast tissue. In general the immunolocalisation of elastin showed a close microanatomical correlation with the fibres demonstrable in sections from the same blocks by standard elastic-fibre stains. Discrepancies between elastic-fibre stains and elastin immunoreactivity appear to relate to the enhanced avidity of the antibody for immature elastin. In this way sites of recent synthesis of elastin were demonstrated in the inner zone of the periductal elastica, sclerosing adenosis, and in the internal elastic lamina of breast arteries which displayed reduplication of the internal elastic lamina or intimal proliferation.

The ABO(H) cell surface antigens of 13 breast carcinomas and 17 benign breast lesions were tested with a specific red cell adherence assay (SRCA). All 13 breast carcinomas, including 2 lobular carcinomas in situ and 1 noninfiltrating ductal carcinoma, had lost their ABO(H) surface antigens. Fourteen of 17 benign breast lesions had retained their ABO(H) surface antigens. The benign lesions losing their antigens were 1 case each of atypical intraductal hyperplasia, sclerosing adenosis, and intraductal papilloma. SRCA may be a predictor of which benign breast lesions are in fact premalignant.

IN A PREVIOUS publication 1 we reported that severe epithelial hyperplasia of the large ducts was found in 69% of breasts removed for carcinoma and in only 16% of breast tissue diagnosed as "fibrocystic disease." Having defined and used our own criteria for the micropathological characterization of benign breast changes associated with carcinoma of the breast and "fibrocystic disease" of the breast, it became necessary to ascertain the frequency of these changes in clinically normal breasts. This study was undertaken to determine the breast changes in 100 consecutive autopsies of women 20 years of age and older with clinically normal breasts. Methods and Results This histologic study, as our previous study, evaluated severe epithelial hyperplasia of the large ducts, the small ducts, and the acini. The presence or absence of fibrosis, sclerosing adenosis, papillomas, apocrine changes, and cysts was noted. The detailed criteria for microscopic changes was described in a