PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA - A CLINICOPATHOLOGICAL STUDY OF 141 CASES COMPARED WITH 916 NONMEDIASTINAL LARGE B-CELL LYMPHOMAS, A GELA (GROUPE-DETUDE-DES-LYMPHOMES-DE-LADULTE) STUDY

Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lympho ma (PMLCL) has been considered a separate entity that has specific cli nical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diag nosis were largely homogeneous and distinct from NMLCL, with a predile ction for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level (76% versus 51%, p < 10(4)), a nd frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic diss emination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lym phomas. Histological analysis of the 141 PMLCL evaluated two common pa tterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognos tic indicators. Immunologic and molecular analysis assessed the profil e of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were det ected by in situ hybridization in only two of the 41 cases tested. Mon otypic light chain restriction could be demonstrated in seven of the 4 1 PMLCL tested on fixed-section. Treated with poly-chemotherapy regime ns without radiotherapy, 79% of PMLCL patients achieved a complete rem ission compared with 68% in the NMLCL patient group (p = 0.01). Overal l, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly diffe rent (61 versus 64%). Stratified analysis on the International Prognos tic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survival s between the two lymphoma groups. In conclusion, PMLCL can be combine d with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and sh ould be managed like other high-grade lymphomas of equivalent histolog y. However the uncommon clinical presentation makes it a distinct enti ty.