Presentation and management of primary mediastinal large B-cell lymphoma: a retrospective cohort analysis

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon subtype of diffuse large B-cell lymphoma (DLBCL) that has molecular similarities to nodular sclerosis classic Hodgkin lymphoma [1]. Constituting 2–3% of nonHodgkin lymphomas and 6–10% of DLBCLs, PMBCL most commonly occurs in young females as a bulky ( 10 cm), anterior mediastinal mass [2]. As such, patients tend to present early with symptoms related to local extension of the disease [2]. Thought to originate from thymic B cells, PMBCL expresses the mature B-cell antigens CD20, CD79a, PAX5, and CD45 on immunohistochemical analysis. PMBCL cells often express CD30, a marker seen in classic Hodgkin lymphoma. The cells are frequently positive for BCL2, BCL6, and MUM1/IRF4, but exhibit low levels of CD10 [1,2]. Due to the rarity of the disease, prospective clinical trials are infrequent, complicating the development of a defined treatment approach. Earlier studies used cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as the standard treatment, later adapted to include rituximab (R-CHOP) [3]. Involved field radiation therapy was administered following chemotherapy–initially routinely, later on an individual basis. More recently, a study Dunleavy et al. used doseadjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) without the routine use of radiation therapy [4]. In our study, we identified 28 cases of PMBCL at the University of Texas Southwestern Medical Center (UTSW) and its affiliated safety net Parkland Health and Hospital System (PHHS) in Dallas, Texas from 2007 to 2017. The institutional review board approved this study. The electronic medical record was queried to identify all patients with a diagnosis of PMBCL based on available clinical, immunophenotypic, and genetic data. Radiologic and hematopathologic data were reviewed by the same clinicians for both sites. Dosing of DA-EPOCH-R adhered to previous standards per nadir neutrophil and platelet count and radiologic response [5]. Eventfree survival was calculated from date of diagnosis until date of progressive disease or relapse. Overall survival was calculated from date of diagnosis until date of last follow-up or death. The demographics, clinical data, treatment regimen, and clinical course of patients are summarized in Table 1. The immunophenotypic and genetic information is presented in Table 2. The patients were predominantly young (median age 33.5 years), African American or Hispanic (25.0 and 35.7%, respectively), and uninsured (53.6%). There was a female predominance (n1⁄4 17, 60.7%). Most patients (n1⁄4 23, 82.1%) presented with early stage (Ann Arbor stage I/II) disease. B symptoms were uncommon (n1⁄4 8, 28.6%). The typical patient had a bulky tumor ( 10 cm, n1⁄4 19, 70.4%) with a median size of 10.6 cm (range 5–19 cm). Extra-mediastinal metastases included the lung (n1⁄4 4, 14.3%), chest wall (n1⁄4 2, 7.1%), pancreas (n1⁄4 1, 3.6%), and liver (n1⁄4 1, 3.6%). Pleural effusions (n1⁄4 6, 21.4%) were nearly as common as pericardial effusions (n1⁄4 7, 25.0%). Lactate dehydrogenase at diagnosis was elevated in the majority of patients (n1⁄4 23, 88.5%) with a median value of 338.5 units/L (range 114–701) (Table 1). Eleven patients (39.3%) were staged by positron emission tomography (PET) prior to treatment. All patients underwent bone marrow biopsy, and none had bone marrow involvement. All 28 tumors were confirmed to be of B-cell origin and expressed CD20 by immunohistochemistry and flow cytometry. Additionally, the following antigens were identified on the lymphoma cells by immunohistochemistry: CD79a (10/ 10), PAX5 (17/17), CD45 (17/17), CD30 (20/22), BCL2 (16/18), BCL6 (21/21), and MUM1/IRF4 (15/16). The lymphoma cells did not express CD5 (0/20) and had infrequent CD10 expression (4/25). Of those tested, the majority had a high rate of cellular proliferation as evidenced by a Ki67 70% (14/21). All tested lymphoma cells were negative for BCL2 (0/9), BCL6 (0/8), or MYC (0/8) rearrangements on fluorescent in situ hybridization (Table 2). Treatment and outcome data were available for 27 of the 28 PMBCL patients. One patient opted to return to his home country for treatment. The median follow-up from date of diagnosis was 36months (range 2–119months). Nine patients (32.1%) received R-CHOP and 18 (64.3%) were treated with DA-EPOCH-R (Table 1). Response was assessed by PET scan after chemotherapy in all patients. For patients receiving radiation therapy, PET scans were repeated afterwards. Seven out of nine patients (77.8%) treated with RCHOP achieved a complete metabolic response (CR) after