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A 55-Year-Old Woman With an Intrapulmonary Nodule in a Transplanted Lung
accp-seek board review question of the month A 55-Year-Old Woman With an Intrapulmonary Nodule in a Transplanted Lung* Stephanie M. Levine, MD, FCCP
(CHEST 2001; 120:2057–2058)
55-year-old woman with pulmonary fibrosis A underwent an uncomplicated right single-lung transplant. In the first posttransplant year, she experienced two episodes of acute rejection requiring augmentation of corticosteroid therapy. Eleven months after the surgery, she presented with a new, 2-cm nodule in her right lung graft. A biopsy specimen is shown in Figure 1. Which of the following would not be considered in the treatment of this diagnosis? A. B. C. D. E.
Chemotherapy Antiviral agents ␣-Interferon Infusion of lymphokine-activated killer cells Increased immunosuppression
Figure 1. Biopsy specimen (hematoxylin-eosin, original ⫻ 400).
*From the ACCP-SEEK program, reprinted with permission. Items are selected by Department Editors Richard S. Irwin, MD, FCCP, and John G. Weg, MD, FCCP. For additional information about the ACCP-SEEK program, phone 1-847-498-1400. Correspondence to: Stephanie M. Levine, MD, FCCP, c/o Schaefer, 22 Sheringham, San Antonio, TX 78218; e-mail: [email protected] CHEST / 120 / 6 / DECEMBER, 2001
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Answer: E. Increased immunosuppression All of the choices should be considered in the treatment of this patient except increasing immunosuppression. This patient has developed a posttransplant lymphoproliferative disorder (PTLD) as shown in the biopsy, which reveals a homogeneous proliferation of lymphocytes. The incidence of PTLD in lung transplant recipients is approximately 6 to 10%, higher than that reported in other solid-organ transplant recipients. PTLD is characterized by a heterogeneous group of lymphocytic proliferations of variable clonality. The development of PTLD has been closely associated with Epstein-Barr infection, either as a primary infection or as reactivation of a latent infection. Those patients whose test results are normal for Epstein-Barr virus prior to transplantation have an increased incidence of developing PTLD, and thus children develop PTLD more often. The majority of PTLDs are non-Hodgkin’s lymphomas, and B-cell tumors are most common. Typical clinical features include involvement of the allograft and, occasionally, other extrapulmonic sites, such as the CNS. PTLD usually develops during the first year. Typical radiographic features include solitary or multiple nodules or infiltrates. Despite initial suggestions that PTLD may correlate with increased levels of immunosuppression, this has not been clearly supported in recent studies. Once diagnosis of PTLD is confirmed, treatment is intended to reduce the intensity of maintenance immunosuppression, in addition to applying stan-
2058
dard measures, such as surgery, radiation, and chemotherapy. Treatments with acyclovir, ganciclovir, ␣-interferon, and adoptive immunotherapy, such as infusion of lymphokine-activated killer cells, have been attempted with variable results. In a recent small study, the 1-year and 2-year actual survival rates, following diagnosis of PTLD in lung transplant recipients, were 50% and 19%, respectively. Selected Readings Aris RM, Maia DM, Neuringer IP, et al. Posttransplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient. Am J Respir Crit Care Med 1996; 154:1712–1717 Armitage JM, Kormos RL, Stuart RS, et al. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant 1991; 10:877– 887 Collins J, Muller NL, Leung AN, et al. Epstein-Barr virusassociated lymphoproliferative disease of the lung: CT and histologic findings. Radiology 1998; 208:749 –759 Davis CL, Wood BL, Sabath DE, et al. Interferon-␣ treatment of posttransplantation lymphoproliferative disorders arising in organ transplant recipients. Transplantation 1998; 66:1770 – 1779 Mihalov ML, Gattuso P, Abraham K, et al. Incidence of posttransplant malignancy among 674 solid-organ transplant recipients at a single center. Clin Transplant 1996; 10:248 –255 Nalesnik MA, Rao AS, Zeevi A, et al. Autologous lymphokineactivated killer cell therapy of lymphoproliferative disorders arising in organ transplant recipients. Transplant Proc 1997; 29:1905–1906 Walker RC, Paya CV, Marshall WE, et al. Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantation. J Heart Lung Transplant 1995; 14:214 –221
ACCP-SEEK Board Review Question of the Month
(CHEST 2001; 120:2057–2058)
55-year-old woman with pulmonary fibrosis A underwent an uncomplicated right single-lung transplant. In the first posttransplant year, she experienced two episodes of acute rejection requiring augmentation of corticosteroid therapy. Eleven months after the surgery, she presented with a new, 2-cm nodule in her right lung graft. A biopsy specimen is shown in Figure 1. Which of the following would not be considered in the treatment of this diagnosis? A. B. C. D. E.
Chemotherapy Antiviral agents ␣-Interferon Infusion of lymphokine-activated killer cells Increased immunosuppression
Figure 1. Biopsy specimen (hematoxylin-eosin, original ⫻ 400).
*From the ACCP-SEEK program, reprinted with permission. Items are selected by Department Editors Richard S. Irwin, MD, FCCP, and John G. Weg, MD, FCCP. For additional information about the ACCP-SEEK program, phone 1-847-498-1400. Correspondence to: Stephanie M. Levine, MD, FCCP, c/o Schaefer, 22 Sheringham, San Antonio, TX 78218; e-mail: [email protected] CHEST / 120 / 6 / DECEMBER, 2001
2057
Answer: E. Increased immunosuppression All of the choices should be considered in the treatment of this patient except increasing immunosuppression. This patient has developed a posttransplant lymphoproliferative disorder (PTLD) as shown in the biopsy, which reveals a homogeneous proliferation of lymphocytes. The incidence of PTLD in lung transplant recipients is approximately 6 to 10%, higher than that reported in other solid-organ transplant recipients. PTLD is characterized by a heterogeneous group of lymphocytic proliferations of variable clonality. The development of PTLD has been closely associated with Epstein-Barr infection, either as a primary infection or as reactivation of a latent infection. Those patients whose test results are normal for Epstein-Barr virus prior to transplantation have an increased incidence of developing PTLD, and thus children develop PTLD more often. The majority of PTLDs are non-Hodgkin’s lymphomas, and B-cell tumors are most common. Typical clinical features include involvement of the allograft and, occasionally, other extrapulmonic sites, such as the CNS. PTLD usually develops during the first year. Typical radiographic features include solitary or multiple nodules or infiltrates. Despite initial suggestions that PTLD may correlate with increased levels of immunosuppression, this has not been clearly supported in recent studies. Once diagnosis of PTLD is confirmed, treatment is intended to reduce the intensity of maintenance immunosuppression, in addition to applying stan-
2058
dard measures, such as surgery, radiation, and chemotherapy. Treatments with acyclovir, ganciclovir, ␣-interferon, and adoptive immunotherapy, such as infusion of lymphokine-activated killer cells, have been attempted with variable results. In a recent small study, the 1-year and 2-year actual survival rates, following diagnosis of PTLD in lung transplant recipients, were 50% and 19%, respectively. Selected Readings Aris RM, Maia DM, Neuringer IP, et al. Posttransplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient. Am J Respir Crit Care Med 1996; 154:1712–1717 Armitage JM, Kormos RL, Stuart RS, et al. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant 1991; 10:877– 887 Collins J, Muller NL, Leung AN, et al. Epstein-Barr virusassociated lymphoproliferative disease of the lung: CT and histologic findings. Radiology 1998; 208:749 –759 Davis CL, Wood BL, Sabath DE, et al. Interferon-␣ treatment of posttransplantation lymphoproliferative disorders arising in organ transplant recipients. Transplantation 1998; 66:1770 – 1779 Mihalov ML, Gattuso P, Abraham K, et al. Incidence of posttransplant malignancy among 674 solid-organ transplant recipients at a single center. Clin Transplant 1996; 10:248 –255 Nalesnik MA, Rao AS, Zeevi A, et al. Autologous lymphokineactivated killer cell therapy of lymphoproliferative disorders arising in organ transplant recipients. Transplant Proc 1997; 29:1905–1906 Walker RC, Paya CV, Marshall WE, et al. Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantation. J Heart Lung Transplant 1995; 14:214 –221
ACCP-SEEK Board Review Question of the Month