Pathologic Findings of Pulmonary Lymphoproliferative Disorders.

Abstract

Pulmonary lymphoproliferative disorders (PLDs) are a diverse group of rare entities characterized by abnormal lymphoid proliferation within the lung. These include both benign and malignant processes and are classified into five categories in the 2021 WHO Classification of Thoracic Tumors: benign hyperplastic disorders, primary pulmonary neoplasms, secondary involvement of the lung, posttransplant lymphoproliferative disorders, and histiocytic neoplasms. Diagnosing PLDs is often challenging due to their histological similarity to other lymphocyte-rich interstitial lung diseases, including cellular nonspecific interstitial pneumonia (NSIP) and hypersensitivity pneumonitis. A multidisciplinary approach integrating clinical, radiologic, and pathological information is essential to reach an accurate diagnosis. This review focuses on the detailed pathological features of PLDs, particularly benign hyperplastic disorders and primary pulmonary neoplasms. It emphasizes the differential diagnosis and highlights distinguishing characteristics among key subtypes, including lymphoid interstitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia, Castleman disease, IgG4-related disease, and primary pulmonary lymphomas such as MALT lymphoma, diffuse large B-cell lymphoma, and lymphomatoid granulomatosis. Special attention is paid to morphological patterns, immunophenotypes, and diagnostic challenges encountered with small biopsies. Given the broad differential diagnosis and potential overlap with infectious, autoimmune, or immunodeficiency-related conditions, careful clinicopathological correlation remains the cornerstone of accurate classification and appropriate management. This review aims to enhance diagnostic clarity and support effective interdisciplinary evaluation of suspected PLD cases.