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A 57-year-old female presented for her routinely scheduled mammogram, which showed a 4-mm irregular parallel angular hypoechoic mass without posterior features that was radiologically given a BiRADS (Breast Imaging Reporting and Data System)-4A (low suspicion of malignancy). A core needle biopsy was performed, which showed fibrocystic changes with apocrine metaplasia and usual ductal hyperplasia. There was a solitary duct with apocrine cells filling the lumen, which contained strikingly prominent eosinophilic granules on scanning magnification (Figure 1A). Further evaluation revealed disordered nuclear orientation and high-power magnification confirmed a population of cells with pronounced nuclear atypia and striking macronucleoli (Figure 1B and C). Nuclei were at least 3 times larger than neighboring usual apocrine metaplastic cells and rare mitoses were present; a diagnosis of atypical apocrine hyperplasia was rendered, and a comment was entered recommending surgical excision. The patient was lost to follow-up. A 71-year-old female presented for routine mammogram, which showed a 9-mm mixed solid and cystic microlobulated mass with isoechoic solid components, and an interpretation of BiRADS-4A (low suspicion of malignancy) was rendered. Biopsy showed atypical ductal hyperplasia (ADH) and an excision was performed, which showed low-grade ductal carcinoma in situ (DCIS). Focally, a cyst with apocrine metaplasia was identified containing a nucleus nearly 10 times the normal size, easily identifiable at scanning magnification (Figure 2A). On high power, pleomorphism with nucleomegaly as well as macronucleoli relative to typical apocrine metaplasia were observed (Figure 2B and C). Levels revealed a transition into usual apocrine metaplasia, and a diagnosis of atypical apocrine metaplasia (AAM) was made, with no additional surgical recommendations given clear margins for DCIS and AAM. Apocrine metaplasia is the single most common metaplastic lesion in breast pathology and a common routine finding in fibrocystic change. Nuclei are round and larger than usual secretory epithelial nuclei with prominent nucleoli. Type A apocrine cells contain abundant eosinophilic granules, while Type B contain foamy cytoplasm. While follow-up studies are sparse, some data suggest a low upgrade rate of 0% to 5.4% in excision of atypical apocrine adenosis (AAA) identified on biopsy to DCIS or higher. Apocrine atypia is based on the presence of nuclei 3 times the size of normal apocrine nuclei, overly prominent nucleoli, which may be multiple, nuclear membrane irregularities, and hyperchromasia. When present, DCIS architecture, such as cribriform, micropapillary, or solid patterns, are helpful, as are comedonecrosis and mitoses. Caution must be rendered in the use of myoepithelial markers, however, as they may be present focally or entirely absent in apocrine lesions of all types. Entities in the differential include pleomorphic lobular carcinoma in situ (pLCIS), invasive carcinoma (CA), DCIS, ADH, AAA, and AAM. In the case of pLCIS, E-cadherin immunohistochemistry is quite useful, as atypical apocrine proliferations will express E-cadherin, while pLCIS will not. The diagnosis of CA is made based on architecture, presence of stromal desmoplasia, and loss of myoepithelial cell markers, the latter being a potential pitfall in apocrine lesions, while the presence of lobular architecture supports a noninvasive diagnosis. AAA is diagnosed when apocrine cells with atypia involve sclerosing adenosis. In this setting, lobular architecture on low magnification is quite helpful as are myoepithelial markers, only if positive. AAM occurs when pronounced atypia is present within lesions that do not contain supportive architecture or comedonecrosis to support a diagnosis of ADH or DCIS. No criteria exist for the diagnosis of atypical apocrine hyperplasia (apocrine ADH), although some prefer to use a size criteria of 2 mm. CK5/6 and estrogen receptor are not useful as both are negative in apocrine lesions. DCIS can be diagnosed when comedonecrosis and/or more than rare mitotic figures are present or in atypical lesions with supportive architecture involving multiple duct spaces. No consensus recommendations for management currently exist in patients with apocrine AAM or ADH; while some would prefer watchful waiting given the low upgrade rate, others would recommend identical management to ductal lesions of the same type and excise them. 873070 IJSXXX10.1177/1066896919873070International Journal of Surgical PathologyRussell research-article2019