Primary Endometrial Diffuse Large B-cell Lymphoma: A Rare Disease and Diagnostic Challenge in an Asymptomatic Postmenopausal Woman

Primary endometrial lymphomas are rare malignancies because the female genital tract is usually involved as a secondary site. Here, we present a case of primary endometrial lymphoma diagnosed in a 49-year-old postmenopausal female who was referred to hematology/oncology service for the evaluation of incidental findings of malignant-looking cells on a Pap smear followed by a cervical polyp biopsy that was suggestive of high-grade B-cell lymphoma (Ki-67: 80-90%) on routine screening. The baseline laboratory assessment was unremarkable except for hypochromic normocytic anemia. A bone marrow biopsy was performed to rule out primary involvement and revealed no evidence of lymphoma both on morphology and immunophenotyping. Fluorescence in situ hybridization tests were also negative. Repeat endocervical biopsy with more tissue sampling revealed similar findings. Further workup was pursued including an initial staging positron emission tomography-computed tomography (PET-CT) scan that showed a 3.8 × 2.7 cm, with standardized uptake value (SUV)max of 30.4, malignant-appearing mass extending up to the left posterior cervix and an 11 mm left axillary lymph node with SUVmax of 2.9. An excisional biopsy of the axillary node was negative for malignancy and ruled out nodal involvement. A diagnosis of primary endometrial diffuse large B-cell lymphoma was made on biopsy of posterior cervical mass that revealed diffuse infiltration of large lymphoid cells, positive for B-cell markers, namely, B-cell lymphoma 6 (BCL6), paired box 5 (PAX5+), CD20, and CD19 with methoxyisobutyl isonitrile (MIBI) of 100%, and negative for T-cell and mesenchymal markers, namely, CD3, CD45, CD43, CD138, Melan A, S100, and Vimentin. The disease was staged as 1E (one extranodal site) according to the Ann Arbor staging system. The patient achieved remission after receiving four to six cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) therapy. Interval staging PET-CT scans, performed after the second cycle and at the completion of therapy to assess treatment response, were negative for new disease activity in the uterus. The patient remains in clinical remission to date and is on regular follow-up. This case is a good illustration of the fact that the female genital tract can be the primary site for B-cell lymphomas. If such an abnormality is found incidentally on routine screening, it should not be ignored and the patient should be evaluated further to make the definitive diagnosis so that timely management can be offered. Through this case, we also highlight the role of immunohistochemical studies using specific cell markers in ruling out other possibilities that could mimic lymphomas on tissue biopsy as treatment modalities differ.