Lessons Learned From 26 Adenomyoepitheliomas of the Breast.

Adenomyoepithelioma (AME) of the breast is a biphasic neoplasm prone to misclassification. To enhance diagnostic awareness, we evaluated 26 AMEs stratified across a spectrum of benign (54%), atypical (27%), special salivary gland-like (12%), and malignant (8%) subtypes. Size and borders stratified the spectrum: benign, atypical, and special subtypes (median: 12 to 18 mm) exhibited lobulated/multilobulated contours, whereas malignant AMEs were larger (median: 27.5 mm) and infiltrative. Cytologic atypia and mitoses were predominant in atypical and malignant subtypes. Overall, 35% of cases were reclassified. Surgical excision corrected 6 core biopsy misinterpretations: 3 benign nodular adenosis-like, 1 unidentified benign AME, 1 benign tubular adenoma-like, and 1 atypical AME mimicking infarcted papilloma. Retrospective review reclassified 3 cases: upgrading 2 benign AMEs to atypical due to cytologic atypia with mitoses, and correcting a metastatic malignant AME misclassified as a papilloma with ductal carcinoma in situ. Aberrant myoepithelium was seen in 19% of cases as loss or heterogeneous p63 and calponin expression. Sequencing of a metastatic malignant AME identified co-occurring AKT1 E17K and GNAS R844C mutations shared between the primary mass and its pulmonary metastasis, confirming clonality. Over a median follow-up of 44 months, the disease-free survival rate was 89%, with one benign local recurrence at 29 months and one malignant pulmonary metastasis at 134 months. Recognizing the histologic spectrum of AMEs allows early detection of these tumors with recurrent or metastatic potential. Given the 35% reclassification rate, excision is recommended for AME-like lesions on core biopsy, particularly those measuring >20 mm.