Carcinomas mamários in situ de padrão misto: caracterização imunofenotípica e variação diagnóstica entre observadores

Abstract

The distinction between lobular neoplasia (LN) and ductal carcinoma in situ (DCIS) has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. This group has been called carcinomas in situ with a mixed pattern (CISM). LN and low grade DCIS are frequently associated to columnar cell lesions (CCL). The aims of this study were to evaluate the inter-observer variability in the diagnosis of LN, CDIS and CCL of the breast comparing the original reports and the review of an expert in breast pathology of cases sent in consultation. We also evaluated the immunoexpression of E-cadherin and β-catenin in a series of CISM. This is a retrospective, observational, cross-sectional study. For the analysis of interobserver variability we analyzed 610 cases of breast specimens formally received in consultation for a second opinion in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais, from 2005 to 2010. Interobserver variation between the diagnosis of LN, DCIS and CCL of original report and the reviewer report was compared. Statistical analysis was performed using the Kappa test. For the immunohistochemical study, a total of 25 cases of breast biopsies diagnosed with CISM, performed between 1999 and 2011, were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedonecrosis. The immunophenotype pattern was considered E-cadherin positive and β-catenin positive, or negative. We observed a poor agreement for the diagnosis of columnar cell change (CCC) (Kappa = 0.38), columnar cell hyperplasia (CCH) (Kappa = 0.32) and CCC with atypia (kappa = 0.29). The agreement between the diagnosis of CCH with atypia was considered moderate (kappa = 0.43). However, the agreement between diagnosis of pleomorphic LCIS was considered poor (Kappa = 0.22). Atypical ductal hyperplasia (ADH) (Kappa= 0.44), low-grade DCIS (Kappa= 0.47), intermediate grade DCIS (Kappa= 0.45) and DCIS with microinvasion (Kappa= 0.56) had a moderate agreement in their diagnosis. There was a good agreement in the diagnosis of high grade DCIS (kappa= 0.68). Of the 25 cases analyzed CISM, nineteen (76%) cases presented a mixed cytology and/or architectural pattern, two (8%) presented nuclear pleomorphism, two (8%) presented mixed cytology and nuclear pleomorphism, and two (8%) presented comedonecrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11 cases (44%). In one case, the lesion was negative for both markers and showed nuclear pleomorphis. Thirteen lesions showed negative staining in areas of lobular cytology and positive staining in cells presenting ductal pattern. Our data demonstrate a greater diagnostic agreement in high-grade DCIS, LCIS and ALH. The CCL without atypia and pleomorphic LCIS had the lowest rates of diagnostic concordance. The expression of E-cadherin and β-catenin, in association to cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM.