Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.
C GiardinaGabriella SerioGianluca LeporeTeresa LettiniAnna Maria DalenaAntonio PennellaG D'EreditàT ValenteR Ricco
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Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.Keywords:
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11061 Background: The processing of breast specimens suspicious of ductal carcinoma in situ (DCIS) is hampered by the fact that DCIS is not regularily visible at the gross level. There is no general consensus as how to process those breast specimens. Suggestions lead from examination of the entire tissue sample with a special focus on the resection margins to algorithms such as cutting only those paraffin blocks containing calcifications. Methods: In order to identify the influence of the diagnostic method on the measured extent of a DCIS lesion we compared two approaches. One was based on the examination of a single section and the other on examination of the entire specimen, i.e. cutting multiple 0.5 cm slices to be analyzed as max. 52 x 76 mm whole mount sections. 187 consecutive breast specimens from 186 patients (median patient age 60 years, range 31 to 87 years) from three gynecological institutions between Jan 2004 and Nov 2006 were searched for DCIS. We compared the largest tumor diameter from a single section of a specimen (‘apparent diameter‘, AD) with a ‘reconstructed diameter‘ RD calculated on the basis of the number of 0.5 cm slices taken from a sample and the number of slices containing the DCIS lesion. Results: Complete histological examination of these 187 cases (90 high and 97 low grade DCIS lesions) revealed a statistically significant difference (p=7.5E-9) between the apparent diameter AD (mean 22.4 mm, range 2 to 80 mm) and the reconstructed diameter RD (mean 31.6 mm, range 6 to 76 mm). In 138 cases (73.8%) the true extent of the disease would have been underestimated (RD > AD) if the diagnosis had been based only on a single exemplary section, the mean difference RD-AD being 14.8 mm (range 1–50 mm). In addition, we found 40 invasive cancers (multifocal inside the DCIS lesion, unifocal inside the DCIS and unifocal outside the DCIS). Conclusions: We conclude that the complete examination of a breast specimen helps to determine the true extent of DCIS and additionally helps to identify cases that turn out to be already invasive. Both findings may have important impact on the patients’ further treatment and outcome. No significant financial relationships to disclose.
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Carcinoma in situ
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Carcinoma in situ
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Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.
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Low-grade solid in situ carcinomas of the breast are difficult to classify. The authors investigated 12 cases of in situ carcinomas with equivocal features and correlated their histologic attributes with those of the associated invasive carcinomas as well as with E-cadherin expression in both in situ and invasive disease. E-cadherin–positive in situ lesions were invariably associated with invasive carcinomas of the ductal type. In situ carcinomas that were E-cadherin negative were associated with invasive carcinomas of the lobular type in five of six cases. In all cases, the invasive carcinomas showed the same pattern of E-cadherin reactivity as the in situ lesions. Sharply defined cellular membranes, necrosis, and occasional microacini were seen in both E-cadherin—positive and negative in situ carcinomas, whereas intracytoplasmic lumina and a noncohesive appearance were seen only in E-cadherin—negative lesions.
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