A40-33 The Histopathological Mimic: Distinguishing Igg4-related Fibrosing Mediastinitis From Inflammatory Myofibroblastic Tumor

Introduction Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibro-inflammatory disorder affecting multiple organs, including the lungs and mediastinum. Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm often associated with ALK rearrangements. Both conditions share overlapping histopathologic features, including spindle cell proliferation and dense lymphoplasmacytic infiltrates, making accurate diagnosis challenging. Differentiation is critical, as IMT often requires surgical excision and may benefit from targeted therapy, whereas IgG4-RD usually responds to corticosteroids. Case Presentation A 31-year-old female with recurrent pneumonia and celiac disease presented with progressive dyspnea. Chest CT revealed a large mediastinal mass causing near-complete obstruction of the left mainstem bronchus. Bronchoscopy and EBUS-guided biopsies of the mass and regional lymph nodes were non-diagnostic. Worsening airway obstruction and compression of the pulmonary artery prompted a video-assisted thoracoscopic biopsy, which remained inconclusive. Due to ongoing symptoms, she ultimately underwent a left pneumonectomy. Histopathology demonstrated spindle-shaped myofibroblastic cells within a dense inflammatory infiltrate, initially interpreted as IMT. Immunohistochemistry was negative for ALK and other lineage markers, but staining for IgG and IgG4 revealed an IgG4+/IgG+ plasma cell ratio of approximately 50 percent, with focal areas containing up to 500 IgG4-positive plasma cells per high-power field, along with obliterative phlebitis, supporting a diagnosis of IgG4-related fibrosing mediastinitis. Discussion This case highlights the diagnostic challenge of distinguishing IMT from IgG4-RFM. Initial histopathologic features suggested IMT, but comprehensive immunostaining revealed hallmark findings of IgG4-RFM. The novelty of this case lies in the extensive mediastinal involvement causing near-complete bronchial obstruction and pulmonary artery compression, which is rarely reported in IgG4-RFM. To our knowledge, few cases have demonstrated such severe airway compromise that necessitated pneumonectomy, emphasizing the potential for IgG4-RFM to mimic aggressive neoplasms both clinically and histologically. Accurate differentiation is crucial because management differs: IMT often requires surgical excision and may respond to ALK-targeted therapy, whereas IgG4-RFM typically responds to corticosteroids. Early recognition can prevent unnecessary surgery and guide appropriate medical therapy. This case underscores the importance of a multidisciplinary approach integrating clinical, radiologic, histopathologic, immunohistochemical, and molecular data. Awareness of IgG4-RFM’s potential to mimic IMT can improve diagnostic accuracy, inform treatment strategies, and enhance patient outcomes.