74 Dong-Ju Kim, et al. Figure 5. Immunohistochemistry (IHC) of microglandular adenosis (MGA). IHC of MGA shows positive for pan-cytokeratin (IHC stain, × 400). Figure 6. Immunohistochemistry (IHC) of microglandular adenosis (MGA). IHC of MGA shows negative for SMA (IHC stain, × 400). epidermal growth factor receptor 2 (HER2/neu) [7,8,10,11]. The epithelial cells are also negative for epithelial membrane antigen and gross cystic disease fluid protein 15 as well [5], which is unusual in epithelial breast cancer. A spectrum of lesions, ranging from typical MGA to atypi- cal MGA and carcinoma arising in MGA (MGACA), has been described [3,11-13]. Atypical MGA (MGA with atypia or AMGA) has features of classic MGA but increased irregulari- ty, density of glands, and cytologic atypia such as hyperchro- masia, prominent nucleoli, apoptosis compared to uncompli- cated MGA [8]. AMGA shows a more pleomorphic admixture of connected microacini and larger glands and often discloses budding glandular units and luminal bridging. Intraluminal secretions are usually reduced or absent, instead cellular expan- sion often fills the lumen. Approximately 5-10% of AMGAs have increased Ki67 or p53 labeling, which can be important differential points between MGA and AMGA [8,11,13], as well as important prognostic factors [13]. AMGA probably repre- sents an intermediate lesion in the morphological transition from MGA to invasive carcinoma [8,11,13]. MGACA may show both carcinoma in situ, and invasive carcinoma and has been reported in up to 27% of cases [3,14]. MGA is distinct from mammary carcinoma. The carcinoma component arising in MGA shows various histological features consisting largely of solid nests and glands expanded and filled with cytologically malignant cells. A solid expansile prolifera- tion obliterating the lumen, and severe cytological atypia with frequent apoptotic or mitotic features are observed with an in situ carcinoma [4]. In situ carcinoma tends to retain the un- derlying alveolar growth pattern of MGA, but invasive foci are formed by the coalescent growth of expanding alveolar of in situ carcinoma elements, associated with a desmoplastic stro- mal reaction and often accompanied by lymphocytic infiltra- http://ejbc.kr tion [5]. The epithelial cells may exhibit cytoplasmic clearing and glandular changes comparable to those of MGA. Duct forming carcinoma tends to retain the acinar budding pattern of AMGA, but it can be distinguished by its high mitotic rate, more pronounced cytological abnormality, necrosis, and des- moplastic stromal reaction. The basement membrane, which is usually preserved around the glands of MGA and AMGA, tends to be disrupted in MGACA [15]. The immunohistochemical profile of MGACA is similar to MGA itself [5,7]. As previously stated, MGA has no myoepi- thelial cell layer, and the epithelial cells are usually positive for cytokeratin 7 and S-100 protein (Figure 4) but negative for ER, PR, and HER2/neu. In this context, MGA, AMGA, in situ car- cinoma, and invasive carcinoma have a similar immunohisto- chemical profile [7,8,11,13]. A basement membrane is present in MGA and AMGA, whereas in situ carcinoma is defined by an immunohistochemical study for type IV collagen, laminin, or PAS stain, which is absent in invasive carcinoma [4]. Invasive carcinoma shows a higher percentage of staining for MIB-1 (a cell proliferation marker) and p53 than does AMGA. Despite its characteristic infiltrative growth pattern, aggres- sive local spread or metastasis has not been observed, so MGA is classified as a benign proliferative disease. But, although MGA is a benign lesion, if it is not excised completely, it may recur [15]. Whether MGA is a precancerous lesion or innocent by- stander can be debated [4]. But, recent studies have found a strong relationship between MGA and MGACA, so the cur- rent management for MGA is complete excision, and the ex- cised specimen needs to be sampled thoroughly to rule out the possibility of an associated carcinoma. However, such a rela- tionship is uncertain because of the rarity of the disease. A wide excision with a clear resection margin and careful follow-up is needed for AMGA. Re-excision is recommended in cases with DOI: 10.4048/jbc.2011.14.1.72