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Thoracic Presentations of Posttransplant Lymphoproliferative Disorders^*

^* From the Division of Cardiothoracic Surgery (Drs. Halkos, JI Miller, and DL Miller), Joseph B. Whitehead Department of Surgery and Department of Anatomic Pathology and Laboratory Medicine (Drs. Mann and Gal), Emory University School of Medicine, Atlanta, GA.

Correspondence to: Michael E. Halkos, MD, Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, 550 Peachtree St, NE, Atlanta, GA 30308-2225; e-mail: mhalkos{at}emory.edu

Background: Posttransplant lymphoproliferative disorders (PTLDs) are rare complications following transplantation. Although organ-specific cases have been reported, primary presentation in the thoracic cavity has not been fully characterized.

Methods: Eleven cases of PTLD with a primary thoracic presentation were identified among 3,085 solid-organ transplant patients and 1,662 bone marrow transplant patients from 1990 to 2001.

Results: There were eight men and three women with a mean age of 49 years. Transplanted organs included lungs (three patients), kidneys (three patients), kidney/pancreas (two patients), allogeneic bone marrow (two patients), and heart (one patient). The time to presentation ranged from 1 to 97 months (median time, 8 months). Six patients developed PTLD within 1 year of undergoing transplantation. Pretransplant serology for Epstein-Barr virus (EBV) and cytomegalovirus was negative in 80% and 78% of cases, respectively. Radiographic evaluation revealed mediastinal adenopathy in 45% of patients, and pulmonary parenchymal lesions in 55%. Fifty-five percent of patients also had extrathoracic involvement. Diagnosis was achieved by CT-guided transthoracic needle biopsy in eight patients, and by open biopsy in three patients. Pathologic analysis revealed monomorphic PTLD (ie, diffuse large B-cell lymphoma) in seven patients, polymorphic PTLD in two patients, anaplastic large cell lymphoma in one patient, and Hodgkin lymphoma in one patient. Eighty-four percent of the specimens evaluated for EBV were determined to be positive by in situ hybridization and/or immunohistochemistry. All patients were initially treated with a reduction in immunosuppression therapy, and six patients (55%) received adjuvant chemotherapy. The overall mortality rate was 64%. Four patients died from complications of PTLD (kidney, two patients; heart, one patient; bone marrow, one patient), and three patients (all lung transplant recipients) died from rejection or infectious complications. The median interval from diagnosis to death was 13 months (range, 1 to 42 months).

Conclusions: Thoracic PTLD can occur in any transplant patient and must be regarded as a potentially fatal complication in the immunosuppressed patient. Heart and lung allograft recipients have the worst prognosis because of the mortality that accompanies rejection with subtherapeutic immunosuppression therapy. Earlier diagnosis and improvements in immunosuppression and chemotherapy may improve survival for these inherently high-risk patients.

Key Words: Epstein-Barr virus • immunosuppression • posttransplant lymphoproliferative disorder • transplantation