Morphological and Immunophenotypical Characterization of “Breast Carcinomas In Situ With Mixed Pattern” By Using E-Cadherin and β-Catenin

摘要

Background: The distinction between lobular neoplasia of the breast and ductal carcinoma in situ has important therapeutic implications. In some cases, it is very difficult to determine whether the morphology of the lesion is ductal or lobular. The aim of this study was to evaluate the value of E-cadherin and β-catenin expression through the immune phenotypical characterization of carcinoma in situ with mixed pattern (CISM).Methods: A total of 25 cases of CISM were analyzed considering cytology/mixed architecture (ductal and lobular), nuclear pleomorphism, loss of cell cohesion, and presence of comedo necrosis. The immunophenotype pattern was considered E-cadherin positive and β-catenin positive, or negative.Results: 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 comedo necrosis and nuclear pleomorphism. A complete positivity for E-cadherin and β-catenin was observed in 11cases (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 the ductal pattern.Conclusions: The expression of E-cadherin and β-catenin, combined with cytological and architectural analysis, may highlight different immunophenotypes and improve classification of CISM. INTRODUCTION: In situ breast carcinomas are classified, according to their morphology, as ductal carcinoma in situ (DCIS) or lobular neoplasia (LN), which includes lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). According to the 2012 WHO classification of tumors of the breast, classic LCIS is diagnosed when more than half of the acini of a lobular unit are distended and distorted by a discohesive proliferation of cells with small,uniform nuclei. Lesser involvement by the characteristic cells is diagnosed as ALH. Lesions that show marked nuclear pleomorphism, with or without apocrine features and comedo necrosis are referred as pleomorphic LCIS (PLCIS) [1]. In some cases, the diagnostic criteria based on the morphology of LN are not clear, leading to mistaken diagnosis of intraductal proliferative lesions. The main differential diagnoses of lobular neoplasia are: LN with solid low-grade DCIS, PLCIS and high-grade DCIS. Some in situ carcinomas present unusual cytological and / or architectural features, making it difficult to determine whether the proliferation is lobular or ductal. This group has been called carcinomas in situ with a mixed or indeterminate pattern (CISM) [2, 3].The differential diagnosis of the CISM carries some important implications. Patients with LN are usually clinically monitored and can be offered tamoxifen as a prophylactic therapy to prevent the development of invasive carcinoma [4, 5]. On other hand, patients with DCIS should be treated by surgical removal of the lesion, with clear margins followed by radiotherapy, or mastectomy [6]. When diagnosed by core biopsy, DCIS should betreated with complete excision of the lesion. However, the clinical significance and therapeutic implications of finding LN in core biopsy specimens are still controversial [7, 8].The diagnosis of CISM is extremely rare and studies assessing the differential diagnosis of these lesions are scarce and include only a few patients. The largest series reported between 12 and 28 cases [9, 10]. Previous studies by our group identified 0.08% of CISM among breast biopsies performed in our general hospital [11]. Although rare, when analyzed under light microscope, the CISM lesions are difficult to diagnose and there is lack of epidemiological data linked to their biological behavior. A great progress in the diagnosis of these lesions came with the observation that almost all cases of LN and invasive lobular carcinoma (ILC) lose the immunohistochemistry (IHC) signal for E-cadherin a