BACKGROUNDWarthin’s tumor (WT) is composed of several cysts that are lined with tall, bilayered oncocytic columnar cells and lymphoid stroma. Within WT, the two components rarely transform into carcinoma or lymphoma, and when it does, carcinoma is the most common type. Approximately 28 cases of lymphoma with WT have been reported, most of which were non-Hodgkin lymphomas, and only a few cases were Hodgkin lymphomas. In the present report, we studied a case of diffuse large B cell lymphoma (DLBCL) arising from follicular lymphoma (FL) with WT in the parotid gland and its immunophenotypic and genetic features.CASE SUMMARYA 67-year-old man presented with a slowly enlarging right cheek mass for 12 years, and the mass began to change in size over a 2-mo time period. Over time, the patient felt mild local pain and right cheek discomfort. His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking. Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm × 8 cm × 7 cm and was well circumscribed by relative normal parotid gland tissue. In cross section, the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance. A small fluid was discovered in the cyst. Bilateral oxyphilic, cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed. Many medium- to large-sized lymphoid cells were observed diffusely in part of the neoplasm, and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm. Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3; neoplastic cells located in coarctate follicular were positive for CD20, Pax-5, bcl-2 and bcl-6; and the adjacent diffusely medium- to large-sized lymphoid cells were positive for Pax-5, bcl-6, CD20, MUM-1, bcl-2 and CD79a. The bcl-6 (3q27) break-apart rearrangement was observed, and an Epstein Barr virus test was negative in the tumor cells. The patient survived 6 months after being diagnosed without any treatment.CONCLUSIONWT-associated lymphoma is a very rare neoplasm in the parotid gland. Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males. This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma. Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.