Primary mediastinal large B-cell lymphoma.

Primary mediastinal large B-cell lymphoma (PMLBCL) is a unique type of B-cell lymphoma probably arising from a putative thymic medulla B-cell. It constitutes 6-10% of all diffuse large B-cell lymphomas (DLBCL), occurring more often in young females. PMLBCL is characterized by a diffuse proliferation of medium to large B-cells associated with sclerosis and a degree of compartmentalisation. Its main molecular characteristics include: gains in 9p segments, p53 mutations, BCL-2 and MAL gene over-expression, somatic mutations of IgVH genes, BCL-6, PIM-1, PAX-5, RhoH/TTF, and c-MYC, and constitutional NF-kappaB activation. The gene expression signature of PMLBCL seems to be much closer to classic Hodgkin lymphoma than to DLBCL. PMLBCL is characterized by a locally invasive anterior mediastinal mass, often producing cough, chest pain, dyspnea, and superior vena cava syndrome. Most PMLBCL patients have stage I-II, bulky disease, with pleural or pericardial effusions in a third of cases. Systemic symptoms, mainly fever or weight loss, are present in <20% of cases; increased LDH levels are observed in 70-80% of cases. Treatment with CHOP regimen followed by radiation therapy was associated with a 5-year survival of 65%. Apparently better results have been reported with third-generation weekly alternating regimens followed by radiation therapy. Any recurrence is almost always seen in the first 2 years of follow-up, and distant relapses tend to involve extranodal organs. Features associated with poor prognosis are poor performance status, pericardial effusion, bulky disease, high serum LDH at diagnosis, and a compromised dose-intensity of anthracycline and cyclophosphamide.