Pulmonary Lymphoproliferative Disorders

This chapter discusses the clinical, radiologic, histopathologic, and relevant cytogenetic and molecular alterations of reactive and malignant pulmonary lymphoproliferative disorders. All of these entities are rare—particularly when confined to the lung—and can be challenging when not properly recognized by clinicians, radiologists, and pathologists. Benign pulmonary lymphoproliferative lesions likely originate from hyperplasia of the bronchial-associated lymphoid tissue (BALT) secondary to chronic inflammatory stimulus, immune dysregulation, or an autoimmune disorder, and they may present as interstitial lung infiltrates or a mass-forming lesion on imaging. Importantly, persistent stimulus of the BALT may result in progression to pulmonary lymphoma. Reactive lymphoproliferative disorders discussed here include nodular lymphoid hyperplasia, follicular bronchiolitis, diffuse lymphoid hyperplasia/lymphoid interstitial pneumonia, and IgG4-related lung disease. Although the distinction of these lesions from a lymphoproliferative disorder is usually straightforward in a surgical resection, the diagnosis may be difficult in small biopsies. In this instance, the use of ancillary studies is extremely helpful in arriving at the correct diagnosis. Malignant pulmonary hematolymphoid disorders discussed here include non-Hodgkin lymphomas (extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT), diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, lymphomatoid granulomatosis, plasmacytoma, other small B-cell lymphomas, and some T-cell lymphomas), classic Hodgkin lymphoma, and acute leukemia/myeloid sarcoma. Along with the proper morphologic evaluation, the diagnosis of these neoplasms requires the use of ≥1 ancillary studies to arrive at the correct diagnosis, and most cases require cytogenetics, fluorescence in situ hybridization, and/or molecular analyses to identify potential prognostic or predictive markers. Histiocytic disorders of the lung are also discussed in this chapter.