Histopathology 2001, 38, 54±61 Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein±Barr virus infection F Dadmanesh, 1 * J L Peterse, 2 A Sapino, 3 A Fonelli & V Eusebi Department of Oncology, Section of Anatomical Pathology `M. Malpighi', University of Bologna, Italy; 1 Department of Anatomical Pathology, Vancouver Hospital and Health Sciences Center, B.C. Cancer Agency, University of British Columbia, Vancouver, Canada; 2 Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands; and 3 Department of Biological Sciences and Clinical Oncology, Section of Anatomic Pathology, University of Turin, Italy. Date of submission 30 March 2000 Accepted for publication 21 July 2000 Dadmanesh F, Peterse J L, Sapino A, Fonelli A & Eusebi V (2001) Histopathology 38, 54-61 Lymphoepithelioma-like carcinoma of the breast: lack of evidence of Epstein±Barr virus infection Aims: Six cases of lymphoepithelioma-like carcinomas of the breast were studied in order to better define the morphology of this type of breast tumour and to see if these neoplastic lesions are related to Epstein±Barr virus (EBV) infection by analogy with histologically similar tumours located in other organs. Methods and results: The cases were studied with immunohistochemistry using several antibodies and with in-situ hybridization method employing different types of nucleotides in four cases. The cases presented the distinctive morphology of the lymphoepithelioma-like carcinomas as seen in other organs. Specifically Rigaud and Schminke's patterns of growth were observed. In addition, at the edge of the neoplastic lesions, a lymphoepithelial lobulitis was seen. In-situ hybridization failed to reveal any positivity for EBV genome. Conclusion: Lymphoepithelioma-like carcinoma is a specific type of breast tumour, but its relation to EBV has yet to be proven. The differential diagnosis with medullary carcinoma is discussed. Keywords: breast, Epstein±Barr virus, in-situ hybridization, lymphoepithelioma-like carcinoma Introduction Lymphoepithelioma-like carcinomas (LEC) are neo- plasms composed of undifferentiated malignant epithe- lial cells with dense lymphoid stroma. These have been reported in the salivary gland, stomach, lung, thymus, skin and less often in other organs. 1±8 Epstein±Barr virus (EBV) is implicated in the patho- genesis of several lymphoproliferative disorders, as well as epithelial neoplasms, particularly undifferentiated naso- pharyngeal carcinoma (UNPC) and LEC. Studies of EBV in LEC from various sites have shown its consistent association only with LEC of the salivary gland, stomach, lung, and thymus. 2,3,5 In the breast, medullary carcinoma (MC) although not commonly referred to as LEC, shares many macroscopic, microscopic, epidemiological and prog- nostic features with LEC of various sites. Therefore, the hypothesis that EBV could also be involved in the pathogenesis of MC of the breast has been raised and examined by immunophenotyping, in-situ hybridiza- tion (ISH) and polymerase chain reaction (PCR), and failed to show the evidence of EBV. 9,10 Only one case of LEC of the breast has been described and did not show an association with EBV infection by in-situ hybridization. 11 In this study, we report six cases of primary LEC of the breast with distinct histological features. The association of these tumours with EBV infection was also investigated by in-situ hybridization. q 2001 Blackwell Science Limited. Address for correspondence: Dr V Eusebi, Istituto di Anatomia ed Istologia Patalogica, Ospedale Bellaria, Via Altura, 3, 40139 Bologna, Italy. *Present address: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA.