Primary lymphomas of the mediastinum are believed to arise from mediastinal lymph nodes or, when in the anterior mediastinum, the thymus gland (Table 127.1). Primary mediastinal large B-cell lymphoma (PMLBL) is a subtype of diffuse large B-cell lymphoma arising in the mediastinum of putative thymic medullary B-cell origin with distinctive clinical, immunophenotypic, genotypic, and molecular features.¹

PMLBL accounts for ˜2% to 5% of patients with non-Hodgkin lymphoma.^2,3 The tumor typically affects young women, presenting in their third to fourth decade of life with rapidly growing mediastinal masses, often with respiratory symptoms and evidence of intrathoracic extension on imaging.^1,2,4,5 Up to 50% can have signs and symptoms of superior vena cava syndrome at presentation, with facial edema, neck vein distention, and, occasionally, upper extremity swelling and/or deep vein thrombosis.

Despite local invasiveness, distant spread, including bone marrow infiltration, is infrequent at initial presentation. At relapse, however, unusual extranodal sites, such as the liver, kidneys, and central nervous system, are not uncommon.^1,2,4,5

Staging is performed according to the Ann Arbor scheme for lymphoma. Staging is established using both standard radiologic procedures and positron emission tomography (PET), which is helpful in assessing response to treatment.

PMLBL presents as a solid mass lesion, tan to light brown, sometimes with necrosis and hemorrhage.

PMLBL shows a wide morphologic spectrum from case to case.^1,2,4,5 The growth pattern is diffuse and the large cells usually form clusters or sheets (Fig. 127.1).^1,2,4,5 A frequent but not consistent feature is a distinctive fibrosis made up of irregular collagen bands compartmentalizing cellular areas of varying size.^1,2,4,5 The cells range from mediumsized to large (2 to 5 times the size of a small lymphocyte) and have abundant, frequently clear cytoplasm and irregularly round or ovoid nuclei, usually with small nucleoli. Some cases may contain cells with
pleomorphic and/or multilobated nuclei and abundant amphophilic cytoplasm, which may resemble Reed-Sternberg cells and raise suspicion of Hodgkin lymphoma or nonlymphoid tumor. At the periphery of the mass, a variable number of reactive cells such as lymphocytes, macrophages, and granulocytes may be present. In case of regional lymph node involvement, the invasion pattern is carcinoma-like, starting from marginal sinuses, continuously infiltrating and replacing the normal lymphoid tissue.