Primary Extranodal Marginal Zone B Cell Lymphoma of the Ovary, Fallopian Tube, and Uterus: A Rare Case Report and Review of the Literature

Purpose: To report a rare case of extranodal marginal zone B cell lymphoma of the ovary, fallopian tube, and uterus. Methods: Case report. Results: A 78-year-old nulliparous female with several year-history of intermittent periodic burning in the vulva managed with topical estrogen, presented to her gynecologist due to acute worsening of vulvar pain. A transvaginal ultrasound was performed revealing a left adnexal tubular mass. She was then referred to Gynecology Oncology for management. She endorsed some lower back pain and intermittent tenderness to palpation in bilateral lower pelvis and denied any fever, malaise, unintentional weight loss, or night sweats. Pelvic examination was benign, revealing no adnexal or uterine tenderness, fullness, or masses. Preoperative laboratory results, including a complete blood count, liver enzymes, and serum electrolytes were all within normal limits. The patient elected to proceed with total robotic hysterectomy, bilateral salpingo-oophorectomy, with plan for intraoperative frozen pathology of the adnexal mass. Intraoperative frozen section of the left fallopian tube mass showed a small blue cell tumor, favoring lymphoma, at which point the decision was made to proceed with staging. An infracolic omentectomy was performed and left pelvic sentinel lymph node were sent for analysis. Examination of histologic sections of the ovary revealed effacement of the architecture by a diffuse atypical lymphoid infiltrate composed predominately of small CD20(+) B-lymphocytes, including few with pale cytoplasm. Similar findings were noted in the endometrium, myometrium, serosa, left fallopian tube and ovary, and left pelvic sentinel lymph node (see Figure 2). Immunohistochemical studies showed that the neoplastic cells were positive for PAX-5, and IgM, with low labeling of nuclei by Ki-67 (~10%). They were negative for CD5, Cyclin D1, LEF1, IgG and CD30. CD3 was positive in T cells. ISH for EBV encoded RNA was negative. Flow cytometric immunophenotyping performed on fresh tissue demonstrated an abnormal population of kappa-restricted, CD20(+), CD19(+), CD79b(+), CD22(+), CD5(-), CD10(-), CD23(-) and CD38(-) small B-cells. The neoplastic cells comprised ~70% of lymphocytes. Molecular study was positive for MYD88 mutation but negative for CXCR4 was performed and was not detected. The patient was seen in Bone Marrow Transplant Clinic one month post-operatively. A hepatitis panel and human immunodeficiency virus (HIV) testing were nonreactive and lactate dehydrogenase was within normal limits. SPEP was obtained showing no monoclonal protein; serum free kappa light chain 12.8; serum free lambda light chain 9.4; and kappa:lambda 1.36. Given no IgM monoclonal gammopathy or CXCR4 mutation detected, a diagnosis of marginal zone lymphoma was rendered. A positron emission tomography scan was obtained which showed no evidence of lymphoma after surgical intervention. Through shared decision making with the patient, a plan was made to obtain surveillance imaging twice yearly. Conclusions: Primary EMZL of the female genital tract is uncommon, with involvement of the fallopian tube and ovary being exceedingly rare, with only a few cases reported. To our knowledge, this is only the second case described involving the ovary. EMZL is an indolent lymphoma which can be asymptomatic on presentation. Among symptomatic cases, the clinical presentation tends to depend on the site of the organ involved. For previously described cases of EMZL involving the female genital tract, presenting symptoms were nonspecific including pelvic pain, dysmenorrhea, or menorrhagia, all lacking typical B symptoms commonly seen in lymphomas, making the diagnosis quite difficult. Our patient had a similar clinical presentation with no B symptoms and only intermittent tenderness to pelvic palpation. Marginal zone lymphomas are well known to be associated with autoimmune diseases, infectious etiologies, HIV, hepatitis C virus, or solid organ transplantation. The only other documented case of primary EMZL involving the ovary was associated with endometriosis. The authors hypothesized that the inflammatory mediators seen in endometriosis may share similarities with autoimmune diseases and infections in neoplastic transformation pathways through the stimulation of B-cell proliferation. Our patient was not found to have endometriosis or any of the common associations of autoimmunity or infectious etiology. Among the previously documented cases of primary EMZL involving the fallopian tube and ovary, all received surgery as their only treatment, except for one requiring antibiotics for treatment of a concurrent Acinetobacter infection. All patients were managed with surveillance and proved to be disease free for at least 12 months. Likewise, our patient received surgery will be monitored with active surveillance. In conclusion, although EMZL of the ovary and fallopian tube is extremely rare, it should be maintained on the differential diagnosis if atypical lymphoid cells or dense lymphoid aggregates are observed in the surgical specimen.