Mediastinal Lymphoproliferative Disorders

This chapter discusses the clinical, radiologic, histopathologic, and relevant cytogenetic and molecular alterations of reactive and malignant mediastinal lymphoproliferative disorders. All these entities comprise a significant proportion of cases seen by clinicians, radiologists, and pathologists, particularly those specialized in thoracic or hematologic diseases. Clinically, these lesions manifest as mediastinal lymphadenopathy or a mediastinal mass with or without disease elsewhere, and the clinical and radiologic suspicion is usually that of malignancy. A biopsy (fine needle aspiration, core biopsy, video-assisted thoracoscopy, mediastinoscopy, or excisional biopsy) is required to establish a diagnosis and the modality of this procedure depends on the location of a lesion within the mediastinum. Benign or reactive conditions discussed here include sarcoidosis, other granulomatous lymphadenitis with a known etiology, Castleman disease, IgG4-related disease/sclerosing mediastinitis, and the histiocytic disorders Langerhans cell histiocytosis and Rosai-Dorfman disease. For some of these lesions, morphology and a limited panel of ancillary studies are sufficient to establish a diagnosis. However, for some others clinico-radiologic and laboratory correlation (cultures, PCR, serology) are required to render a complete diagnostic interpretation. Malignant mediastinal hematolymphoid disorders discussed here include common and rare neoplasms at this location such as classic Hodgkin lymphoma, non-Hodgkin lymphomas (T-lymphoblastic leukemia/lymphoma, diffuse large B-cell lymphoma, primary mediastinal [thymic] large B-cell lymphoma, mediastinal gray zone lymphoma, T-cell lymphomas), myeloid sarcoma, and follicular dendritic cell (FDC) sarcoma. In contrast to reactive conditions, each of these malignant disorders has a particular clinic-radiologic presentation and tends to present with chest pain, dyspnea, cough, effusions, and superior vena cava syndrome if there is bulky disease. Along with proper morphologic evaluation, the diagnosis of these neoplasms requires the use of ≥1 ancillary studies to arrive at the correct diagnosis, and nowadays most cases require cytogenetics, fluorescence in situ hybridization, and/or molecular analyses to identify potential prognostic or predictive markers.