A 70-year woman with a right breast lump underwent a lumpectomy for a 1.5 cm mass with lobulated margins. The neoplastic cells stain positive for GATA3, CK5, CK7, and GCDFP-15 and negative for TTF-1. ER and PR are focally positive, and p63 is negative within the lesion.
The correct answer is ...
Tall cell carcinoma with reverse polarity (TCCRP).
Tall cell carcinoma with reverse polarity (TCCRP) is a type of invasive breast cancer with papillary architecture. It is characterized by circumscribed nests of tall and columnar epithelial cells lining the fibrovascular cores. The neoplastic cells show bland ovoid nuclei and usually abundant eosinophilic cytoplasm. The nuclei are characteristically present at the luminal/apical surface, hence the name "reverse polarity." Nuclear grooves and intranuclear cytoplasmic inclusions may be seen and require exclusion of metastasis from the thyroid using additional thyroid markers like TTF-1, thyroglobulin, etc. The tumor stains positive for GATA3, other breast markers such as mammaglobin and GCDFP-15, and both high- and low-molecular-weight cytokeratins.
These tumors are often triple negative (ER, PR, and HER2), however, some degree of low hormone receptor positivity may be present, in contrast to solid papillary carcinoma (in situ and invasive) of the breast, which is strongly and diffusely positive for estrogen receptor. Myoepithelial markers such as p63, calponin, and smooth muscle myosin, etc., can be used to differentiate these tumors from intraductal papillomas, which will show intact myoepithelial cells in the periphery and within the fibrovascular cores of papilloma, whereas TCCRP is invasive cancer and has an absence of myoepithelial layer. TCCRP has been shown to harbor mutations in the IDH2 gene, which is present in approximately 80% of the cases and can be used as a diagnostic aid in challenging cases.
Ameya Patil, M.B.B.S.
Resident, Anatomic & Clinical Pathology
Malvika Solanki, M.B.B.S., Ph.D.
Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science