Case 93

A 73-year-old female with a 3.4 cm breast mass.

1. If the spindle cell component is positive for SMA and the epithelial component is positive for keratin; what's the likely diagnosis?

   A: Adenomyoepithelioma

   B: Malignant adenomyoepithelioma

   C: Metaplastic carcinoma

   D: Epithelial-myoepithelial carcinoma

   E: Encapsulated papillary carcinoma

Answer

Section showed a well circumscribed mass composed of atypical cells with papillary, cribriform and tubular patterns in a hyalinized background. There are mitosis in both component with nuclear atypia; No benign biphasic component is seen. The correct answer is epithelial-myoepithelial carcinoma.

• AME-M may arise from malignant transformation of a pre-existing classic AME, though de novo development cannot be excluded.

• Genetic data on AME-M are limited, but some insights are available.

• PIK3CA and HRAS p.Gln61 hotspot mutations, common in AME, are also detected in AME-M.

• HRAS p.Gln61 mutations are linked to ER-negative AMEs with atypical histology and are often seen in AMEs associated with carcinoma.

• Homozygous CDKN2A deletions may contribute to malignant transformation in ER-negative AMEs.

• TP53 mutations, common in conventional ER-negative breast cancers, are not present in AME-M.

Feature	AME-M	Epithelial-Myoepithelial Carcinoma
Precursor lesion	Often arises from classic benign AME, with identifiable transition	No classic AME component; de novo origin
Transition zone	Transition from benign AME to malignancy can be appreciated	No transition; entire lesion is malignant
Components involved in malignancy	May affect epithelial, myoepithelial, or both components	Both luminal and myoepithelial components show malignant features
Morphologic spectrum	Variable; can resemble NST, lobular, or metaplastic carcinoma (e.g., squamous, spindle, carcinosarcoma, etc.)	Less morphologic diversity; biphasic architecture dominates
Low-power architecture	Often multinodular/multilobulated with residual AME areas	Typically lobulated biphasic pattern without AME background
Myoepithelial cell features	Malignant myoepithelial cells can be spindle or epithelioid, with atypia and high mitotic activity	Similar biphasic population, but without benign precursor context
Immunohistochemistry	Dual expression: luminal (CK7, ER) and myoepithelial (p63, SMA, S100) markers	Same dual expression; IHC helps differentiate from metaplastic carcinoma, not from AME-M
Mitotic activity	May be increased, especially in malignant components	Increased in both epithelial and myoepithelial compartments
Papillary architecture	Rarely present	Rarely described, not a defining feature

Reference: https://tumourclassification.iarc.who.int/chaptercontent/32/32

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD