ANCA: Antinuetrophil Cytoplasmic Autoantibody
c-ANCA: Cytoplasmic-Antineutrophil Cytoplasmic Autoantibody
CT: Computed Tomography
GPA: Granulomatosis with Polyangiitis
PET: Positive Emission Tomography
RLL: Right Lower Lobe
Granulomatosis with Polyangiitis (GPA) is the most common of the ANCA-associated vasculitides, and most commonly involves kidneys as well as upper and lower respiratory tract . The clinical triad is characterized by upper airway involvement (e.g., sinusitis, otitis, ulcerations), lower respiratory involvement (e.g., cough, chest pain, dyspnea, hemoptysis), and glomerulonephritis; however, up to 22% of patients may have disease limited to the respiratory tract [2-4]. Pulmonary involvement occurs in 70-95% of patients with GPA; most commonly presenting as Diffuse Alveolar Hemorrhage (DAH), reported in 5-45% of cases [1,5]. Tracheobronchial and endobronchial disease is not uncommon and occurs in 10-15% of cases . Hilar adenopathy and mediastinal masses are exceedingly rare in patients with GPA. There are no estimates of the prevalence of these findings; however, a retrospective study with 302 patients reported a frequency of 2% . We describe an unusual case of GPA presenting with a large PET-positive right lower lobe mass and mediastinal adenopathy.
A 70-year-old woman with a distant 10 pack-year smoking history, presented with right shoulder pain, associated with mild pleuritic chest pain. She denied cough, dyspnea, hemoptysis and constitutional symptoms. Vital signs were normal and physical exam was unremarkable. Laboratory data, including blood nitrogen urea and creatinine, were within normal limits. She reported recent air travel, and concern was raised for pulmonary embolism. Chest CT showed a Right Lower Lobe (RLL) mass measuring approximately 5×4 cm (Figure 1). PET scan displayed intense radiotracer uptake in the mass with maximum SUV measured at 13.1 (Figure 2a). Additionally, there was increased uptake in a subcarinal lymph node and multiple right hilar and mediastinal lymph nodes (Figure 2b), with a maximum SUV of 4.5. Given a high suspicion for malignancy, she underwent mediastinoscopy. Bulky adenopathy was identified; biopsies were benign with no evidence of malignancy or granulomata. Flow cytometry was negative. Given the lack of a diagnosis, CT-guided biopsy of the mass was pursued. Sections demonstrated fragments of necrotic tissue with negative cultures. Due to continued concern for malignancy, video-assisted thoracic surgery was scheduled. Pre-operative laboratory evaluation revealed a creatinine of 2.4 mg/dL (baseline 0.6 mg/dL); this was thought to be due to contrast used for the CT-guided biopsy. Four days later, a repeat creatinine was 5.7 mg/dL; surgery was deferred and she was admitted for evaluation of acute kidney injury. Urine microscopy demonstrated proteinuria, hematuria with dysmorphic RBCS and RBC casts, consistent with acute glomerulonephritis. Based on the presentation and urine sediment, empiric treatment was initiated with pulse steroids. Unfortunately, rapid deterioration in renal function ensued, prompting initiation of plasmapheresis and hemodialysis. Renal biopsy was performed (Figures 3 and 4) revealing severe crescentic glomerulonephritis with active cellular crescents involving 90% of the viable glomeruli. Electron microscopy was pauci-immune. C-ANCA positivity was significantly elevated at 11,469 units with ELISA confirmation of antibodies to anti-proteinase 3. Based on the classic findings of pauci-immune glomerulonephritis on renal biopsy as well as the markedly positive C-ANCA titers, the diagnosis of GPA was made. Therapy was initiated with methylprednisolone 1 g daily for 3 days followed by prednisone 60 mg daily, weekly rituximab for 4 weeks, cyclophosphamide 100 mg daily for 7 days followed by 50 mg daily for 7 weeks and 6 sessions of plasmapheresis. Given renal failure, hemodialysis was simultaneously started. Three weeks after initiation of therapy, repeat ANCA titers decreased to 819 units. She remained dialysis dependent for 3 months until sufficient renal functional return was noted and dialysis was discontinued. Chest CT at 3 months (Figure 5) showed reduction in the size of the mass to 1.5 cm in diameter. Immunotherapy was continued. At one year, repeat ANCA titers were negative at 1.4 units and the RLL mass resolved (Figure 6).
Chest CT scan showing RLL mass (4×5 cm).
PET scan showing increased FDG uptake of a) RLL mass and b) mediastinal lymph nodes.
Light microscopy of renal biopsy using Hematoxylin and Eosin stain (H&E stain) showing activecellular crescents within the glomerulus.
Jones basement membrane stain showing extensive crescentic changes and fibrosis.
Three month follow up chest CT, showing reduction in mass size.
One year follow up chest CT, showing resolution of RLL mass with remnant pleural parenchymal scarring.