Large B-cell lymphoma of thymic origin arising in the anterior mediastinum.

Primary mediastinal large-cell lymphomas represent about 6% of all lymphomas in adults (1) and 26% of all childhood non-Hodgkin lymphoma (NHL) (2). Secondary involvement of the mediastinum by lymphomas in adults is far more common, estimated to occur in 15% to 25% of all lymph node lymphomas (1). It occurs in adolescents and young adults, with a median age in the fourth decade. Women are affected twice as often as men (3,4).

Large lymphomas arising in the anterior mediastinum exhibit distinctive clinico-pathologic features as reported by the studies of large series of cases (1,3,5,6,7,8,9,10,11). Mediastinal large-cell lymphomas are of B-cell type and believed to originate in the B cells of the thymus (6,10,11,12,13), which are normally located in the medulla and the extraparenchymal septa (14). Recently, molecular features particular for this type of lymphoma have been identified (15). These are distinctive of other kinds of large B-cell lymphomas, but share some features with Hodgkin lymphoma classic type. They include the activation of nuclear factor (NF)κB, which acts through the nuclear translocation of c-Rel and the subsequent expression of NFκB target genes such as tumor necrosis factor TRAF1. Both c-Rel and TRAF1 are increased substantially in mediastinal large B-cell lymphoma (MLBCL) as compared to diffuse large B-cell lymphoma (DLBCL). Using commercially available antibodies and immunohistochemistry, the combined expression of nuclear c-Rel and TRAF1 was seen in 24 of 45 cases (53%) of MLBCL and in only three of 156 cases (2%) of DLBCL, resulting in a highly specific (98%) diagnostic procedure (15).

In a series of 29 cases (18 women and 11 men), the patients ranged in age from 15 to 73 years, with a median age of 32 years (8). In the largest series studied, 141 patients who had mediastinal large-cell lymphoma were compared with 916 patients who had nonmediastinal large-cell lymphoma (10). The mediastinal lymphomas showed a predilection for women (59%) and persons of relatively young age (37 years); of the patients with nonmediastinal lymphomas, 42% were female, and their mean age was 54 years. Mediastinal lymphomas are usually bulky and commonly extend to adjacent organs—pericardium, pleura, and lung (33% of cases in one series) (4,11). Superior vena cava syndrome may result from local invasion (eight of 29 patients in one series) (8). However, unlike most large-cell lymphomas, mediastinal lymphomas rarely involve the bone marrow (2% vs. 17%) (10) or expand beyond the thoracic cavity. They very rarely involve the central nervous system (CNS), and a leukemic phase seldom develops (13). Levels of serum lactate dehydrogenase become much higher than in nonmediastinal lymphomas (10). Disseminated disease at presentation is uncommon (5). However, relapsed MLBCL involves a variety of extrathoracic and extranodal sites including the CNS, liver, adrenals, and kidneys (4). Despite their high-grade histology and local aggressiveness, mediastinal large-cell lymphomas respond well to various regimens of combination chemotherapy with or without radiotherapy. In an earlier series, 5-year survival was 57% (8). In a more recent large collaborative European study, 79% of patients achieved complete remission, in comparison with 68% of patients with large-cell nonmediastinal lymphomas, and disease-free survival at 3 years was 61% (10).