A 33-year-old woman was admitted for evaluation of multiple air space nodules in the left lung field. Seven years before this presentation, she began to suffer from progressive dyspnea and dry cough. Four years before presentation, she was transferred to a general hospital and diagnosed as having severe emphysema (FVC 1.34 L (35.0%), FEV1 0.61L/sec (20.0%), DLCO 53% of expected value). She was a healthy Hepatitis B virus (HBV) carrier and her alpha 1-antitrypsine levels were 189, 381 and 225.3 mg/dL, by three separate tests. Two years before presentation, she underwent left lung transplantation and had been administered cyclosporine A, azathioprine and corticosteroid for immunosuppression, and lamivudine for HBV management. Preoperative serologic tests revealed CMV IgM antibody negative, CMV IgG antibody positive, HSV IgM antibody negative, HSV IgG antibody positive, VZV IgM antibody negative and VZV IgG antibody positive. EA-IgM antibody was positive and EA-IgG antibody negative. There was no information regarding the donor. During 18 months of follow-up after the transplantation, she showed no signs of rejection or an infectious event. However, a routine follow up plain chest radiograph showed multiple air space nodules in the transplanted lung.
On physical examination, her body temperature, pulse and respiration rates were 36.2 C, 74/min and 20/min. She had a chronic ill-looking appearance and a moon face, although the lung sounds were clear in both lung fields without rales. Laboratory tests revealed a white cell count of 5,440/muL, hemoglobin 11.7 g/dL, platelet 232,000/muL, C-reactive protein (CRP) quantitation 25.9 (reference range; 0-8 mg/L), Wintrobe ESR 58 mm/hr, serum protein 5.6 g/dL, albumin 3.2 g/dL, AST/ALT 19/12 IU/L, BUN 33 mg/dL and creatinine 0.9 mg/dL. Urine analysis was normal and a tuberculosis skin test was negative. Serologic tests indicated that she was CMV IgM and IgG antibodies positive. A CMV PCR from bronchial washing fluid was negative. The EA-IgM and IgG antibodies were positive, and the EBNA-IgG antibody was positive, which is a typical reactivity pattern for EBV reactivation, e.g. EBV-associated lymphoproliferative diseases or epithelial carcinomas, such as nasopharyngeal carcinoma. EBV-PCR using whole blood was negative. Chest high resolution computed tomogram revealed multiple air spaced nodules at the left upper lobe and collapse of the lingular segment. These nodules had speculated margins with accompanying peripheral ground glass opacity, suggesting inflammatory changes (Figure 2A-2C). A comparison of inspiratory and expiratory phase images showed neither mosaic perfusion nor small airway disease. The native right lung showed emphysematous changes, with no interval change. A percutaneous transthoracic needle biopsy was performed on a nodule in the left upper lobe. These nodules consisted of lymphocytes, which by immunohistochemical study revealed positive reactions to L-26 and negative reactions to UCHL-1, Kappa, Lambda, cytokeratin and Ki-1 in the tumor cells. A malignant lymphoma, of high-grade large B-cell type, was confirmed (Figure 2D).
She was given a chemotherapeutic regimen comprising of cytoxan 1200 mg, vincristine 2 mg and prednisone 100 mg for 5 days, and one-week later epirubicin 90 mg was administered before being discharged. Two weeks later the patient developed sudden dyspnea and died of pulmonary edema and a pneumothorax.