Lymphoepithelioma-like carcinoma of breast—evaluation for Epstein-Barr virus–encoded RNA, human papillomavirus, and markers of basal cell differentiation

• This is the first largest series of a rare subtype of breast cancer (lymphoepithelioma-like carcinoma), which is evaluated for human papillomavirus and for basal cytokeratins with clinical follow-up available of a longer duration.
• We found potential significance of performing basal markers in such cases.
• This is the first series to document unique histopathologic findings such as granulomatous reaction in lymphoepithelioma-like carcinoma of the breast.

This is a largest series of 5 cases of lymphoepithelioma-like carcinoma (LEC) of the breast attempting to look at the expression of basal cytokeratins (CKs), human papillomavirus, and Epstein-Barr virus–encoded RNAs in these tumors. Five cases were selected after stringent evaluation of all breast carcinomas showing dense lymphoid infiltration. Histologically, all these tumors showed the typical histology except 1 tumor that showed an unusual granulomatous response. All tumors were negative for estrogen and progesterone receptors and HER2 (triple negative). Three tumors expressed CK5/6 and high-molecular-weight CK, whereas only the case with nodal metastasis expressed CK14. Analysis for in situ hybridization for Epstein-Barr virus–encoded RNAs and human papillomavirus DNA on paraffin-processed tissues was negative in all tumors. All of these patients received adjuvant therapy. One patient with tumor expressing basal marker, CK5/6, had contralateral breast malignancy after a duration of 53 months of treatment completion. The rest were disease free with the follow-up period in the range of 6 to 105 months. The lymphoepithelioma-like carcinoma of breast expressed basal CK profile that is more CK5/6 positive than CK14. Analysis of basal markers within these tumors may help in refining the definition of these tumors and in classifying them into prognostically relevant groups.