Introduction Pulmonary nodules in the immunocompromised patient often represents a diagnostic and therapeutic challenge. This is a case of rapidly growing multiple pulmonary nodules within two months after lung transplantation. Case Presentation RS. is a 32 year-old with end stage lung disease secondary to cystic fibrosis (CF). He had frequent hospitalizations prior to lung transplantation due to exacerbations of his bronchiectasis. Sputum cultures had revealed Stenotrophomonas maltophilia and Mycobacterium abscessus. His pre-transplantation course was also complicated by persistent gastrocutaneous fistula after removal of a gastric feeding tube. He underwent bilateral lung transplantation and subsequently takedown of his persistent gastrocutaneous flstula. Both donor and patient were cytomegalovirus (CMV) seropositive and the patient was Epstein-Barr viins (EBV) seronegative. His postoperative course was uncomplicated except for a persistent small right pleural effusion. He was discharged home doing fairly well. Five weeks after transplantation, he developed fever and a significant fall in spirometry. A bronchoscopy was performed. Bronchoalveolar lavage fluid analysis was normal (differential count, N=20%; L=4%), with negative microbiologic stains and cultures. Transbronchial biopsy specimens showed acute, minimal (Al) rejection. He was treated with high dose methylprednisolone and showed clinical improvement Two weeks later, he redeveloped fever of 39C and right pleuritic chest pain. A chest x-ray, and subsequent CT scan of the chest revealed accumulation of bilateral pleural effusions, left greater than right. There was enhancement of both pleural layers on the right and bibasilar atelectasis. There was also a question of a nodular infiltrate at the left base but this was not definite given the atelectasis. Bilateral thoracenteses showed uncomplicated exudative fluid. His port-a-cath was removed and its tip culture grew coagulase negative methicillin-resistant Staphylococcus. He was treated with a 14 day-course of vancomycin with resolution of his clinical symptoms. Soon after he was discharged, the left pleural fluid culture turned positive with a rapid growing mycobacterium. A repeat CT scan obtained 10 days after the initial study showed slight interval increase in size of the left effusion, improved atelcctasis, and multiple new pleural-based nodular densities throughout both lungs. A thoracoscopic lung biopsy was performed. Lung tissue cultures were negative. Light microscopic examination showed no viral cytopathic changes but revealed large angiocentric nodules with sheets of atypical large lymphocytes and plasma cells, and central coagulative necrosis consistent with polymorphous post-transplant lymphoproliferative disorder (PTLD). Immunoglobulin light chain staining showed polyclonality. In situ hybridization for EBV encoding region (EBER) RNA was positive. His EBV titers remained negative. The nontuberculous mycobacterium was subsequently identified as Mycobacterium abscessus. Discussion The differential diagnosis of pulmonary nodules following solid organ transplantation is diverse. In this particular case, it included PTLD, invasive aspergillosis, abscesses caused by Pseudomonas aeruginosa, Staphy1ococcus spp, CMV, and/or nontuberculous mycobacterial infection. Serial CT scans provide a valuable diagnostic and monitoring tool, however histological diagnosis is mandatory. PTLD is a widely recognized disorder and often catastrophic complication after transplantation. Defective host immunological control of EBV infection predisposes to a spectrum of lymphoid hyperplasia and neoplasia. These lymphoid proliferations are most often of B cell origin and commonly contain the Ebstein-Barr virus The incidence varies depending on the type of organ transplant and ranges from 5 to 9% after lung and heart/lung transplantation. Primary EBV infection after transplantation is a major risk factor. Large proportions of CF patients are EBV seronegative before transplantation and therefore are at higher risk of developing PTLD. The clinical presentation varies and can involve multiple organs including the gastrointestinal tract, liver, lungs, skin, central nervous system and the allograft itself. Treatment includes modulation of immunosuppression, antiviral therapy, surgery, chemotherapy, radiation therapy and adaptive immunotherapy. Overall survival rates range from 25 to 35%. This case of PTLD is unique because it occurred very early following transplantation. To our knowledge, this is the FIRST reported case of PTLD occurring within 2 months after lung transplantation. Prompt reduction of immunosuppression so early following transplantation may, in turn, adversely affect long term graft and/or overall survival. Furthermore, it demonstrates that the absence of EBV seroconversion does not preclude the diagnosis of PTLD. Rapidly growing mycobacteria have been increasingly reported as a cause of sternal osteomyelitis, mediastinitis and pericarditis following thoracotomy procedures. They also are associated with esophageal diseases and gastric interposition surgery presumably as the result of aspiration. Therefore it is not clear how this patient acquired pleural space infection. These organisms are increasingly thought to be pathogenic and treatment is probably necessary. They are probably one of the most difficult-to-treat mycobacterium species and drug susceptibility studies are necessary. The immunocompromised state and drug-drug interactions further compromise the success of treatment in transplant recipients. Conclusion Clinicopathological heterogeneity is the hallmark of PTLD. The diagnosis requires a high index of suspicion in patients at risk. It offers a clear example of how clinical medicine has directly benefited from basic studies in virology and immunology. Rapid progress is being made in the area of therapy, and it remains to be seen whether it becomes the first neoplasm to be completely eliminated by immunological means. Remark Radiographic and histopathologic studies are available for review.
|
|
|
|
|
|
|
|
|
|
|
|