{"paper_id":"304bfcd0-e69b-4c92-a63c-49beb3f705ab","body_text":"Primary ovarian non-Hodgkin lymphoma is a very rare and uncommon entity. It accounts\nfor about 1.5% of all ovarian tumors and 0.5% of all the non-Hodgkin lymphomas\n(NHLs). The most common histologic subtype of primary ovarian NHL is diffuse large\nB-cell lymphoma (DLBCL) that accounts for approximately about 20% of all primary\novarian lymphomas. DLBCL is an aggressive and heterogeneous 1  group of NHL\nthat typically present with a rapidly enlarging symptomatic mass, most usually nodal\nenlargement in the neck or abdomen, but may present as a mass lesion anywhere in the\nbody. The most common primary extranodal disease sites involving the DLBCL are the\ngastrointestinal tract, thyroid, kidneys, breast, liver, testis, adrenals, uterine\ncervix, and tonsil but rarely involve the ovaries. 2  Ovarian DLBCL is a rare,\ncomplex type of lymphoma that harbors a favorable prognosis per studies. The 5-year\nsurvival is approximately 70% in ovarian lymphoma per one of the case study\nseries. 3\n\nA 48-year-old female presented to her primary care physician with generalized\nfatigue, lower abdominal discomfort, and 40 pounds of unintentional weight loss.\nComputed tomography of the abdomen done showed fatty liver, hepatomegaly, and a left\nheterogeneous ovarian mass measuring 4 × 4.2 cm ( Figure 1 ) and an enlarged left adrenal gland\nmeasuring 1.5 × 2 cm. Transvaginal ultrasound done showed a heterogeneous solid left\nadnexal mass measuring 7.4 × 5.6 × 6.6 cm. She subsequently had a total abdominal\nhysterectomy with bilateral salpingo-oophorectomy. Her pathology showed that the\nleft ovary displayed near-complete replacement by a diffuse proliferation of large\nsomewhat pleomorphic cells ( Figure\n2 ), with prominent nucleoli ( Figure 3 ), numerous mitotic figures, admixed\nbody macrophages, and punctate areas of necrosis. Immunohistochemistry showed the\nmalignant cells expressed PAX5, CD20, MYC ( Figure 4 ), and BCL2 (weak 30%). Her Ki-67\nproliferation index was greater than 90% ( Figure 5 ). The cells were negative for\nAE1/AE3, S100, CD30, and cyclin D1. An aggressive B-cell lymphoma FISH panel was\npositive for rearrangement of BCL6 and MYC, with no evidence of BCL2 rearrangement;\nthe findings are consistent with the diagnosis of high-grade B-cell\nlymphoma/double-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements by the\nWorld Health Organization classification. Immunohistochemistry for BCL6 and MU M1\nshowed positive staining in the malignant cells. CD10 was negative. The staining\nprofile was consistent with nongerminal center B-cell-like type (non-GCB/ABC) of\nDLBCL. Final pathology results confirmed high-grade CD20-positive DLBCL of the left\novary. A positron electron tomography (PET) scan showed abnormal uptake within a\nsoft-tissue density structure in the right maxillary sinus. She was categorized as\nstage IV Lugano modification of the Ann Arbor Stage due to the involvement of the\nright maxillary sinus. She received dose-adjusted DA-EPOCH-R (etoposide, prednisone,\nvincristine, cyclophosphamide, doxorubicin, rituximab). Positron electron tomography\nscan after 3 cycles showed interval resolution of hypermetabolic polypoid lesions of\nthe right maxillary sinus. She completed total 6 cycles of DA-EPOCH-R. She is\ncurrently being monitored with serial PET scans and continues to be in remission\nafter 1.5 years without any evidence of relapse.\nLeft adnexal mass measuring about 4 × 4.2 cm on computed tomography of the\nabdomen and pelvis.\nHematoxylin & eosin–stained section of the ovarian mass showing a diffuse\nproliferation of large somewhat pleomorphic cells. Photographed at 20×\nmagnification.\nHematoxylin & eosin–stained section of the ovarian mass photographed at\n40× magnification showing the irregular nuclear contours and prominent\nnucleoli.\nOvarian mass photographed at 20× magnification stained with Ki-67\nimmunohistochemistry showing the high proliferation index with >90% of\nthe cells staining positive (brown = positive).\nOvarian mass photographed at 20× magnification stained with MYC\nimmunohistochemistry showing expression in about 50% of the cells (brown =\npositive).\n\nWe report a rare case of primary ovarian non-GCB/ABC DLBCL. Ovarian DLBCL only\naccounts for about 0.5% of total cases of NHL. 4\nPrimary ovarian lymphoma are most often reported in young women with a median age of\n33 to 42 years. 5 , 6 \nBilateral involvement has been previously reported in approximately 38% to 71% of\ncases. 3 , 6 \nThe clinical presentation of ovarian lymphoma can vary among abdominal mass,\nirregular vaginal bleeding, abdominal pain, fever, fatigue, or night sweat’s (B\nsymptoms) or sometimes ascites or pleural effusion. Palpable liver and splenomegaly\ncan also be found on physical examination.\nExtranodal sites with C-MYC and BCL2/BCL6 translocations include the liver, central\nnervous system (CNS), ribs, breast, intestine, sacrum, and stomach and rarely the\novaries. 7  Ovarian lymphomas are extremely rare due to the lack of lymphoid\ntissue in the ovary. The ovarian lymphoma may have its origination from the chronic\ninflammatory cells as a result of the pelvic inflammatory disease in the ovary or\nfrom the lymphoid aggregates in the corpus luteum or from the vessels of ovarian\nhilum. 8  There are different perspectives regarding the origin of a\nprimary ovarian lymphoma, which include its origin from the lymphoid tissues that\nalready exist in the ovary, 9  or that there are tumor-derived cells around the hilum of\nthe ovary or the corpus luteum cells in the form of blood vessels, 10  or the pelvic\ninflammatory disease and endometriosis or autoimmune diseases, causing chronic\novarian inflammation from the reactive lymphocytes and aggregation lymphocytes,\nwhich in turn results in the malignant transformation. 11\nDLBCL is the most common type of lymphoma in the ovary, accounting for about 20% of\nthe total ovarian lymphomas, followed by Burkitt lymphoma. 12  An overall 5-year survival of\n70.0% has been documented in primary ovarian DLBCL based on few case\nstudies, 3 , 12  whereas when detected late, due to a delayed or inaccurate\ndiagnosis, the primary ovarian DLBCL has a poorer outcome with a range of 0 to 36%\nof patients expected to survive for less than 3 years.\nStudies have demonstrated superior outcomes with dose-adjusted EPOCH-R compared with\nstandard chemotherapy like R-CHOP (rituximab, cyclophosphamide, doxorubicin,\nvincristine, and prednisone). 13 - 15  Our patient was treated with\n6 cycles of dose-adjusted EPOCH-R, with subsequent PET scan showing complete\nremission. Because patients with MYC-rearranged lymphoma have an increased risk of\nCNS involvement, she was also treated with intrathecal methotrexate for CNS\nprophylaxis. Following her up for the last 1.5 years, the patient is still in good\ncondition without any relapse.\nIn conclusion, ovarian lymphoma is very uncommon, and it is very difficult to\ndiagnose the primary ovarian lymphoma not only due to its rarity and its\nsimilarities with other female genital system malignancies but also due to\nnonspecific clinical manifestations. The failure to establish an accurate early\nclinical, histopathological diagnosis leads to inappropriate management of these\npatients and unnecessary treatment delays. The presence of an enlarged heterogeneous\novarian mass should always raise the suspicion for ovarian lymphoma, and\nimmunohistochemistry should be utilized for differentiation from other ovarian tumor\nhistopathologies for an appropriate diagnosis. To our knowledge, this is a rare\npresentation of DLBCL/high-grade B-cell lymphoma with MYC and BCL6 translocation\ninvolving the ovaries. There is a need for the physicians and especially oncologists\nto be aware of aggressive primary ovarian lymphomas so that early diagnosis can be\nmade and correct multiagent chemotherapy can be initiated in a timely manner.","source_license":"CC-BY-4.0","license_restricted":false}