Carcinoma arising in microglandular adenosis: An immunohistochemical analysis of 20 intraepithelial and invasive neoplasms

Microglandular adenosis (MGA) of the breast is an uncommon, benign lesion t hat may mimic invasive carcinoma and has recently been recognized as having significant premalignant potential. When carcinomas arise in MGA, there is often a transition from ordinary MGA to atypical MGA (AMGA) to carcinoma. Nineteen cases of carcinoma arising in MGA are reported: 7 invasive carcino mas, 7 intraductal carcinomas (DCIS), and 5 with both invasive and intraduc tal carcinoma. A single case of AMGA without carcinoma is also reported. Th e 20 patients ranged in age from 36 to 81 years (mean 52). The most common clinical presentation was either a palpable mass (13 patients) or a mammogr aphic abnormality (4 patients. All 20 cases contained AMGA, and in some cas es AMGA was the predominant lesion. In 18 of the 19 cases with carcinoma, t here was a clear transition from AMGA to the carcinoma. Twelve cases contai ned ordinary MGA, but in only 2 cases was MGA a prominent component of the lesion. In contrast to ordinary MGA, the glands of AMGA were more irregular ly shaped, closely packed, and cytologically atypical and tended to lack se cretions. A solid, occlusive proliferation of cells in the tubules was seen in 10 cases. All 12 examples of ii? situ carcinoma were either grade 2 or 3 and typically showed a solid proliferation of severely atypical cells wit hin the glands; a cribrifrom pattern was also present in 1 case. The invasi ve carcinomas were morphologically diverse and included 2 with a basaloid m orphology and 2 metaplastic carcinomas. Various immunostains were performed , and each lesion (AMGA, in situ, and invasive carcinoma) was separately as sessed for immunoreactivity. As expected, S-100 was positive in the vast ma jority of AMGA and in situ carcinomas and in all 12 invasive carcinomas. S- 100 beta was also positive in the majority of cases although the staining w as weaker. Laminin and type IV collagen highlighted the basement membrane a round the AMGA and in situ carcinoma and are useful stains in difficult cas es. Except for a single case, ER and PR were negative in all lesions. Cytok eratin 7 (CI( 7) was positive, while cytokeratin 20 (CI( 20) was negative i n all cases, Immunostains for CK903 showed no reactivity in any of the inva sive carcinomas, ii? situ carcinomas, or atypical MGA but was focally prese nt in the associated MGA in 2 of the 8 cases studied. Immunostains for MIB- 1 and p53 were semiquantitatively assessed and both were positive in AMGA b ut tended to show a more intense staining in the carcinomas. Five cases wer e also studied for immunoexpression of alpha-1 antitrypsin (AAT), alpha-1 a ntichymotrypsin (ACTP), lysozyme, and salivary gland amylase. All 5 invasiv e carcinomas were positive for ACTP, though the staining was very focal in about 10% of the cells in a basaloid carcinoma. The in situ carcinoma as we ll as the AMGA in 4 of the 5 cases were positive for ACTP. Three of the 5 i nvasive carcinomas were positive for AAT in 10% to 40% of the cells. The mo st intense positivity for AAT and ACTP was in cells with coarsely granular apocrine appearance evident in 2 of the 5 cases. Four of the 5 invasive car cinomas were positive for lysozyme in 10% to 50% of the cancer cells; the i n situ carcinoma and the associated AMGA showed similar immunoreaction in e ach case. None of the 5 cases showed convincing positivity for salivary gla nd amylase. The MGA in all 5 cases was negative for AAT and ACTP; the MGA i n 1 of the 5 cases was positive for lysozyme. This study confirms the potential of MGA to develop into an invasive carcin oma, more dearly defines the features of AMGA, highlights the importance of AMGA in the evolution of carcinoma from MGA, and expands our knowledge of the immunophenotype of AMGA and the carcinomas arising from it. The diagnos tic criteria briefly noted previously for diagnosis of AMGA and carcinoma a rising in MGA are expanded and formally proposed.