Pulmonary Nodules, Thinking Outside the Box

Abstract Granulomatous-lymphocytic interstitial lung disease (GLILD) is a non-infectious pulmonary manifestation of common variable immunodeficiency. If not recognized promptly, it can lead to long-term lung damage, resulting in significant morbidity and mortality. We present a case of a patient diagnosed with GLILD that led to the diagnosis of common variable immunodeficiency (CVID), while at the same time highlighting the importance of a multidisciplinary approach for its diagnosis. A 47-year-old non-smoker female with iron deficiency anemia was referred to the Pulmonary clinic due to bronchocentric and perilymphatic nodular opacities with diffuse lymphadenopathy and splenomegaly seen in computed tomography. The vitals were stable, and the physical exam was unremarkable. Pulmonary function tests revealed normal spirometry, lung volumes and diffusion capacity. Bronchoscopy with endobronchial and transbronchial biopsies was pursued revealing chronic inflammation with lymphoid aggregates but no granulomas or malignant cells. An excisional lymph node biopsy from stations 4R and 7 was also performed, being nondiagnostic. Antinuclear antibodies screen, antineutrophil cytoplasmic antibody test, angiotensin converting enzyme level, and Epstein-Barr antibody profile were negative. She was then referred to Thoracic Surgery for mediastinoscopy with biopsy, demonstrating reactive lymph nodes with histiocytosis. No atypical cell populations were identified on flow cytometry, no organisms were detected on stains and there was no evidence of malignancy. A repeat computed tomography of the chest revealed persistent nodular opacities with lymphadenopathy triggering a repeat diagnostic bronchoscopy with bronchoalveolar lavage, transbronchial biopsy and endobronchial ultrasound with fine needle aspiration re-demonstrating chronic inflammation with lymphoid aggregates. Given the unrevealing biopsies and concern for CVID, with low immunoglobulin A, 14 mg/dL, and immunoglobulin G, 309 mg/dL, the patient was referred again to Thoracic Surgery for a wedge lung biopsy. The surgical pathology showed numerous lymphoid aggregates and ill-defined granulomas (Figure 1) supporting the diagnosis of GLILD. After ruling out active infection and discussing the case with Oncology and Pathology, the diagnosis of CVID was confirmed recommending the initiation of immunoglobulin replacement therapy, from which the patient had good clinical response. By the time of diagnosis, about one-third of patients with CVID have developed chronic lung disease. Even though it is an increasing cause of death in patients with CVID, there is lack of international consensus regarding management of GLILD. Radiologic findings suggestive of GLILD should raise concern for primary immunodeficiency disorders and prompt a multidisciplinary team approach for timely diagnosis and treatment, improving patient outcomes.