A rare presentation of ovarian diffuse large B-cell lymphoma: A case report.

The patient is a 76-year-old female with past medical history of type 2 diabetes mellitus and hyperlipidemia, who initially presented to the emergency department (ED) with endorsements of weight loss and fatigue. The patient recently presented to her primary care physician (PCP) for routine blood work, where she was found to have a calcium level of 14.8 mg/dL and was counseled to present to the ED. Upon admission, she endorsed mild abdominal pain without nausea and/or vomiting with endorsement of unintentional weight loss. Of note, the patient recently underwent a computed tomography (CT) scan, which revealed a large, right adnexal mass measuring 8.9 × 12.5 × 12.1 cm that was heterogenous in nature ( Fig. 1 ). In the ED, her calcium was found to be 12.5 mg/dL with a potassium of 3.3 mmol/L. Her creatinine was elevated to 2.97 mg/dL and hemoglobin of 9.7 g/dL. CT scan was remarkable for noted right-sided adnexal mass. Cancer antigen-125 (CA-125) was elevated to 47 U/mL. The patient was ultimately admitted to the medicine service for workup of hypercalcemia in the setting of a right adnexal mass. Gynecology oncology has consulted for further workup of the known adnexal mas in the setting of hypercalcemia. Carbohydrate antigen 19-9 (CA-19-9) and tumor marker inhibin A and B were within normal limits. The patient ultimately underwent an exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo oophorectomy, omental biopsy, pelvic lymph node dissection and para-aortic lymph node dissection, and pathology of the right ovarian and fallopian tube were remarkable for diffuse large B-cell lymphoma, while fluorescence in situ hybridization (FISH) studies revealed a 5′ BCL6 deletion with 3 copies of BCL2. The patient was ultimately discharged and was to follow up gynecology oncology as an outpatient. Pretreatment FDG-PET/CT scan revealed an avid para-aortic lymph node likely representing site involvement from diffuse large B-cell lymphoma ( Figs. 2 A and 3 ). Since her hospital admission, she completed 6 cycles of rituximab and reduced dose cyclophosphamide, doxorubicin and vincristine. Post therapy, her follow up FDG-PET/CT scan revealed disease resolution. Fig. 1 Initial CT abdomen and pelvis upon admission in the axial (A), sagittal (B) and coronal view (C) demonstrating a large, heterogenous, right adnexal mass (white arrow) measuring 8.9 × 12.1 cm in size thought to be ovarian in etiology. Fig 1: Fig. 2 (A) Pretreatment FDG-PET/CT demonstrating a 1.3 by 1.2 cm right paraaortic lymph node (white arrow) with avid hypermetabolic activity with an SUV Max of 32.1. There was absence of FDG uptake in other tissues noted on FDG-PET/CT. F-18 fluorodeoxyglucose was utilized with FDG-PET/CT imaging from the skull base to the proximal thigh, with an uptake time of 60 minutes. Reference values included mediastinal blood pool of 3.1 SUV max and a volumetric normal liver of 3.6 SUV max. (B) Follow-up FDG-PET/CT scan after completion of 6 months duration of R-mini-CHOP. Imaging without evidence of FDG avidity concerning for malignancy within the chest, abdomen or pelvis consistent with disease remission. Fig 2: Fig. 3 (A) Whole body maximum intensity projection (MIP) in conjunction with whole body FEG-PET/CT. (B) Whole body FDG-PET/CT demonstrating hypermetabolic update (white arrow) with an SUV Max of 32.1. F-18 fluorodeoxyglucose was utilized with FDG-PET/CT imaging from the skull base to the proximal thigh was utilized, with an uptake time of 60 minutes. Reference values included mediastinal blood pool of 3.1 SUV max and a volumetric normal liver of 3.6 SUV max. Fig 3: Initial CT abdomen and pelvis upon admission in the axial (A), sagittal (B) and coronal view (C) demonstrating a large, heterogenous, right adnexal mass (white arrow) measuring 8.9 × 12.1 cm in size thought to be ovarian in etiology. (A) Pretreatment FDG-PET/CT demonstrating a 1.3 by 1.2 cm right paraaortic lymph node (white arrow) with avid hypermetabolic activity with an SUV Max of 32.1. There was absence of FDG uptake in other tissues noted on FDG-PET/CT. F-18 fluorodeoxyglucose was utilized with FDG-PET/CT imaging from the skull base to the proximal thigh, with an uptake time of 60 minutes. Reference values included mediastinal blood pool of 3.1 SUV max and a volumetric normal liver of 3.6 SUV max. (B) Follow-up FDG-PET/CT scan after completion of 6 months duration of R-mini-CHOP. Imaging without evidence of FDG avidity concerning for malignancy within the chest, abdomen or pelvis consistent with disease remission. (A) Whole body maximum intensity projection (MIP) in conjunction with whole body FEG-PET/CT. (B) Whole body FDG-PET/CT demonstrating hypermetabolic update (white arrow) with an SUV Max of 32.1. F-18 fluorodeoxyglucose was utilized with FDG-PET/CT imaging from the skull base to the proximal thigh was utilized, with an uptake time of 60 minutes. Reference values included mediastinal blood pool of 3.1 SUV max and a volumetric normal liver of 3.6 SUV max.

Consent was obtained from the patient and documented that he/she certified use of his/her clinical course for publication of this case report.

Ovarian DLBCL is a rare entity, responsible for only 0.5% of cases of NHL with ovarian involvement [ 4 ] We present a rare case of ovarian DLBCL in an elderly female who achieved complete disease remission after 6 month treatment course with R-mini-CHOP. Our case highlights the importance of maintaining a broad differential when presented with ovarian malignancies, as prompt and accurate diagnosis is essential for treatment and eventual disease remission.

DLBCL, an aggressive malignancy categorized as one of the most common etiologies of NHL, often presents clinically as evolving lymphadenopathy with associated “B” symptoms [ 16 ]. Extra nodal involvement is not uncommon, as noted above; however, ovarian involvement is rare, accounting for 0.5% of cases of NHL. Currently, pathogenesis is under discussion as ovaries are absent of lymphoid tissue. Current hypothesis suggests pathology leading to increased inflammation, such as pelvic inflammatory disease (PID), endometriosis and ovarian cysts, produce lymphocytic infiltrates, increasing one’s risk for malignancy. Because of this infrequency, diagnostic delays often occur, leading to delays in treatment. Typical age of onset is in middle aged women, between 33 and 42 years old [ 9 ]. Typical presentation includes weight loss, night sweats and fatigue, all of which are patient endorsed [ 10 ]. Sung et al. explored common clinical presentations in those with ovarian DLBCL, finding abdominal discomfort to be the most common presenting system [ 17 ]. Interestingly, our patient endorsed abdominal pain as a primary presenting symptom, likely secondary to her 12 cm ovarian mass observed on further imaging. CA-125 is an additional serum study that can be used to prognosticate disease [ 17 ]. Zidan et al. performed a prospective study of 38 patients diagnosed with NHL with analysis of CA-125 levels at initial diagnosis, treatment and at follow-up, finding those with elevated CA-125 levels were noted to have more advanced disease [ 18 ]. Our patient was found to have stage 4 disease, consistent with advanced disease in the setting of elevated CA-125 levels. Our case, along with Ziden et al’s study, highlights the use of CA-125 for early disease prognostication. BCL2 and BCL6 are common mutations associated with extra nodal involvement of DLBCL; however, these translocations specific to the ovarian are rare [ 10 ]. Our patient was found to have 3 copies of BCL2 and a deletion of BCL6, further highlighting this association in ovarian tissue. Imaging findings, although nonspecific, may be helpful in contributing to a diagnosis. Ovarian masses secondary to NHL have been described as “large, hypovascular and homogenous” [ 11 ]. This differs from our case, as her ovarian mass was described as “lobulated and heterogenous” ( Fig. 1 ). Radiographic findings are few due to the small number of cases. Imaging may play a role in differentiating ovarian malignancy, while also providing diagnostic clues [ 19 ]. For example, ovarian cystic teratomas are typically complex masses containing calcium, epithelial components and hair, whereas ovarian sex cord-stromal tumors are categorized as loculated, cystic masses on imaging with solid components [ 19 ]. Future cases should focus on further delineating malignant pathologies, such as ovarian epithelial malignancies from ovarian lymphoma, based on radiographic findings. Initial pretreatment FDG-PET/CT revealed hypermetabolic uptake of para-aortic lymph nodes concerning from malignancy ( Fig. 2 A). Para-aortic lymph nodes are common sites of ovarian cancer metastasis due to proximity of vasculature [ 20 ]. However, this site of metastasis is more common with epithelial ovarian malignancies rather than ovarian lymphoma, highlighting the uniqueness of our case [ 21 ]. Management for DLBCL ovarian involvement includes R-CHOP therapy and is typically associated with favorable outcomes, with a 70% 5-year survival rate [ 9 ] In elderly and frail patients, and in cases where disease burden is low, R-mini-CHOP may be utilized, as this is a reduced dosing regimen of R-CHOP and may be more tolerable to this patient population [ 22 ]. Our patient responded excellent to 6 cycles of R-mini-CHOP with complete disease remission and absence of active disease on most recent FDG-PET/CT scan ( Fig. 2 B). Although generally successful, 20% of patients may be refractory to treatment and 30% may show disease relapse [ 23 ]. In those with early disease relapse or refractory to initial treatment not eligible for transplant, salvage therapy with R-DHAP, R-ICE or R-ESHAP is recommended, followed by maintenance therapy [ 23 ]. In that same patient population eligible for transplant, R-DHAP, R-ICE or R-ESHAP is recommended [ 23 ].

Diffuse large B-cell lymphoma (DLBCL) is one of the most common causes of non-Hodgkin lymphoma (NHL) worldwide, with an annual incidence of 7.2 per 100,000 and diagnosed most commonly in non-Hispanic white males [ 1 ]. Nonmodifiable risk factors include increasing age, a family history of DLBCL and autoimmune conditions, including rheumatoid arthritis and systemic lupus erythematous [ 1 ]. Specific infections may also predispose one to development of DLBCL, including human immunodeficiency virus, hepatitis C and Epstein-Barr virus [ 1 ]. Environmental exposures, including pesticides, benzene and herbicides, have also been linked to DLBCL development. About 70% of affected individuals will present with lymphadenopathy [ 2 ]. Other symptoms include fever, weight loss and night sweats, often referred to as “B” symptoms [ 3 ]. If DLBCL is suspected, prompt diagnosis is essential for early treatment. The gold standard for diagnosis includes excisional biopsy of affected lymph nodes for further immunophenotypic, morphological and genotypic studies to further establish diagnosis and guide treatment [ 3 ]. An aggressive form of lymphoma, DLBCL, has a 5-year survival rate of 60%-70%, while those who do not respond to initial treatment or show disease relapse have a 2-year survival rate of roughly 20%-40% [ 4 ]. Treatment depends on staging of disease. For those with Limited Stage disease (Ann Arbor Stage I or II), most patients respond to rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) [ 3 ]. For those with Advanced Stage disease (Ann Arbor Stage III or IV), R-CHOP maintains the treatment of choice; however, patients with high relapse rates, such as those with double-hit DLBCL, may require more aggressive chemotherapy regimens, including etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) [ 3 ]. A majority of DLBCL cases arise in nodal tissue; however, extra nodal involvement can occur in roughly 30% of cases [ 5 ]. Common extra nodal sites include the lung, central nervous system, gastrointestinal tract, pulmonary system and breast tissue [ 2 ]. As expected, extra nodal involvement is known to have a worse prognosis [ 2 ]. Ovarian DLBCL is a rare manifestation of disease due to lack of lymphoid tissue, accounting for roughly 0.5% of cases of extra nodal involvement [ 4 ]. A majority of ovarian DLBCL are secondary, as primary disease is much rarer, accounting for 0.5% of NHL and 1.5% of all ovarian tumors [ 6 ]. The few cases of primary malignancy may be due to difficult differentiation between primary and secondary disease [ 6 ]. The following criteria proposed by Fox et al. may aid in differentiation, including confinement of lymphoma to the ovary, absence of abnormal cells in peripheral blood smear and/or bone marrow and in the presence of extra-ovarian lesions, several months of progression since the appearance of new lesions and initial diagnosis [ 7 ]. Symptoms of ovarian lymphoma may be similar to those of other ovarian malignancies, including fever, night sweats, weight loss, ascites, bloating and a visible pelvic mass [ 8 ]. Prognostically, typical survival is 70% at 5 years with early detection [ 9 ]. In cases where detection is delayed, 3 year survival is poorer, ranging from 0 to 36%, highlighting the importance of early detection and treatment [ 10 ]. Initial imaging typically involves ultrasound, whereas computed tomography (CT) and/or magnetic resonance imaging (MRI) can be used to further characterize the ovarian mass [ 11 ]. Diagnostically, ovarian biopsy is needed for confirmation and treatment is recommended with a positive pathological diagnosis; however, few cases have described ovarian DLBCL and pathology is often difficult to diagnose from other ovarian malignancies [ 9 , [12] , [13] , [14] ]. Post-treatment, surveillance imaging remains controversial among United States and international guidelines [ 15 ]. In the United states, twice yearly CT imaging is recommended in the first 2 years after diagnosis, whereas international guidelines defer routine screening [ 15 ]. Future the studies should explore the benefit of surveillance imaging in ovarian lymphoma. Here, we present a rare case of an elderly female diagnosed with stage IV ovarian DLBCL successfully treated with 6 cycles of R-mini-CHOP.