CT Findings in Posttransplantation Lymphoproliferative Disorder of Renal Transplants

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1 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved Pictorial Essay T Findings in Posttransplantation Lymphoproliferative Disorder of Renal Transplants Thomas G. Vrachliotis 1,2, Kuldeep K. Vaswani 1, Elizabeth. Davies 3, Elmahdi. Elkhammas 3, William F. ennett 1, James G. ova 1 P osttransplantation lymphoproliferative disorder (PTLD) occurs as a direct sequela of chronic immunosuppression. The Epstein-arr virus is believed to induce PTLD in most patients [1]. pproximately 1% of kidney transplants are affected, and, if untreated, PTLD is almost always fatal [2]. The clinical manifestations of PTLD are nonspecific or silent. Many cases are incidentally detected while imaging the patient for other reasons. Therefore, the radiologist should be familiar with the imaging manifestations of PTLD so that early diagnosis can be made and appropriate treatment started. In this pictorial essay, we show PTLD manifestations on T with emphasis on transplant kidney involvement with or without extension of the mass beyond the confines of the transplanted kidney or to other organs. Posttransplantation Lymphoproliferative Disorder Malignant neoplasms are increased in the chronically immunocompromised patient with Fig year-old man with transplanted right kidney who presented with signs of renal outflow obstruction necessitating nephrostomy tube placement., ontrast-enhanced T scan at level of renal pelvis shows nephrostomy tube in renal pelvis and heterogeneous enhancement of tumor (arrows). T-guided biopsy (not shown) found posttransplantation lymphoproliferative disorder (PTLD). Patient underwent transplant nephrectomy because obstruction failed to resolve., Planar gallium-67 scan in anterior projection performed 1 week after at 48 hr after radionuclide administration shows focal area of increased uptake in mid pelvis (arrow ) consistent with PTLD and corresponding to mass in renal pelvis. Scintigraphy was performed before transplant nephrectomy to assess gallium avidity of tumor for future follow-up. Received September 17, 1999; accepted after revision December 17, Poster Exhibit at the annual meeting of the merican Roentgen Ray Society, New Orleans, May Department of Radiology, Ohio State University Medical enter, Rhodes Hall, 450 West 10th ve., olumbus, OH Present address: Department of Radiology, eth Israel Deaconess Medical enter and Harvard Medical School, 330 rookline ve., oston, M ddress correspondence to T. G. Vrachliotis. 3 Department of Surgery, Ohio State University Medical enter, olumbus, OH JR 2000;175: X/00/ merican Roentgen Ray Society JR:175, July

2 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved Vrachliotis et al. Fig year-old man with kidney and pancreas transplant presented with right-sided abdominal pain and significant drop in hemoglobin. Unenhanced T scan was obtained to determine retroperitoneal bleeding. No bleeding was seen., Unenhanced axial T scan shows transplanted kidney (K) was within normal limits. Pancreatic transplant (P) was heterogeneous and enlarged., Transverse sonogram through right iliac fossa shows well-circumscribed hypoechoic mass arising from transplanted pancreas (arrows)., On longitudinal sonogram through pancreatic transplant, organ is seen replaced by mixed echogenicity mass (arrows ). No normal pancreatic tissue is sonographically identified. Patient underwent Tguided biopsy (not shown); pathology disclosed posttransplantation lymphoproliferative disorder. the most common being skin, cervical, and rectal neoplasms; Kaposi sarcoma; and lymphoma [3]. Lymphoma in transplant patients shows aggressive atypical features unlike the lymphomas that occur in the general population. Furthermore, if detected early and treated by reduction of the immunosuppressive agents, most cases will resolve. ecause these lymphomas are almost always fatal if untreated [2], awareness of their imaging appearance will prompt early diagnosis and intervention. The dose threshold for an immunosuppressive drug above which PTLD increases has not been established [4]. Most of the transplant patients who develop lymphoma are actively infected with Epstein-arr virus, the causative agent for infectious mononucleosis. The virus is also believed to be a cofactor in the development of urkitt s lymphoma [1]. The Epstein-arr virus directly infects lymphocytes in infectious mononucleosis and immunocompromised patients and induces a diffuse polyclonal -lymphocyte proliferation. In infectious mononucleosis, this proliferation is ultimately reversed mainly by an intact cytotoxic 184 T-cell function. In immunocompromised patients, however, weak or suppressed T-cell function leads to an excessive -cell proliferation which results in a disease spectrum ranging from mild diffuse polyclonal adenopathy to malignant monoclonal lymphoma. This disease spectrum, referred to as posttransplant or posttransplantation lymphoproliferative disorder (PTLD), mostly occurs in transplant patients. Most lymphomas in immunocompromised patients are of the -cell nonhodgkin s type, although Hodgkin s, urkitt s, and T-cell lymphomas have been reported [1]. The incidence of malignancies in organ transplant patients is approximately 6% and PTLD accounts for 20% of the tumors [3]. The frequency of PTLD varies depending on the type of transplant: 2.2% of liver, 1% of kidney, 1.8% of heart, and 4.6% of heart lung transplants [1]. Higher rates in heart, liver, and heart lung transplant patients occur at least partially because of the more aggressive immunosuppression required [1]. PTLD occurs as early as 1 month after transplantation [4]. If azathioprine is the im- munosuppressant medication taken, the average length of time to develop PTLD is 48 months, whereas with cyclosporine, it is 15 months [4]. Reduction of immunosuppression is the major form of therapy for PTLD. This treatment may be combined with the administration of acyclovir, an antiviral agent that is given to combat the Epstein-arr virus infection [1, 4]. Imaging Manifestations Extranodal disease (81%) is more common than lymphadenopathy (22%) in patients with PTLD [5]. Single (Figs. 1 and 2) or multiple (Figs. 3 and 4) organ masses are the characteristic radiographic presentations of PTLD [6]. ny of the solid organs, hollow viscera, abdominal, retroperitoneal and iliac lymph nodes (Fig. 5), retroperitoneal musculature, or peritoneum of the abdomen can be involved in PTLD [4, 5]. In a review by Miller et al. [6] the transplanted kidney was the most common site of involvement (47% of renal transplant patients with PTLD). JR:175, July 2000

3 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved T of Renal Transplants D Fig year-old woman with kidney and pancreas transplant who underwent T as part of her diagnostic evaluation for malfunctioning renal transplant., ontrast-enhanced axial T scan through transplanted kidney shows small low-attenuation nonenhancing area that was interpreted as simple cyst (arrow). Renal transplant was otherwise normal on T. P = pancreatic transplant. and, ontrast-enhanced axial T scans through native kidneys show several low-attenuation areas in native kidneys and spleen (arrows) that proved to be posttransplantation lymphoproliferative disorder (PTLD). D, ontrast-enhanced axial T scan through liver and spleen shows several low-attenuation areas in hepatic parenchyma (arrows) that also proved to be PTLD. Sonography is the primary technique for evaluating the complications of renal transplantation. With inconclusive sonographic findings, however, T or MR imaging should be performed to confirm the presence of a mass [7]. Sonographic findings of PTLD include a hypo- or mixed-echogenicity mass. However, small ill-defined PTLD masses cannot be initially identified on sonography, and the diagnosis is made on later sonography when the mass is larger. The diameter usually ranges from 3 to 6 cm at the time of discovery [7]. T findings of PTLD are also nonspecific and may include a nonenhancing (Fig. 6) or peripherally enhancing low-attenuation mass arising from the transplanted kidney (Fig. 7). alcifications in the lymphoprolif- JR:175, July 2000 erative mass may represent tumor necrosis or sequelae after treatment (Figs. 6 and 7). Tumor growth in the renal pelvis can cause renal pelvic outflow obstruction, necessitating the placement of a drainage catheter. Occurrence of PTLD in the renal hilum with hilar vessel encasement was observed in four of five renal transplant patients as reported by li et al. [8]. This predilection for the renal pelvis (Figs. 1 and 4) may indicate predisposition of the anastomotic site for PTLD development [8]. Scintigraphy may be used in the evaluation of patients with residual or recurrent disease in whom the tumor was initially gallium-avid [5] (Figs. 1 and 6). MR findings include a hypointense lesion on T1- and T2-weighted images in the renal hilum that is traversed by renal hilar vessels and shows minimal enhancement [8]. MR imaging is a promising technique in the study of renal transplants because of its multiplanar capabilities, lack of ionizing radiation, and lack of contrast-induced nephrotoxicity. However, its role has not yet been established. onclusion PTLD affecting the transplanted kidney is a common manifestation of the disease in renal transplant patients. Gray-scale sonography and T are the primary imaging techniques, with MR imaging showing promise because of its multiplanar capabilities, superior soft-tissue contrast resolution, and lack of ionizing radiation and nephrotoxic effects. 185

4 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved Vrachliotis et al. Fig year-old man with history of right renal transplant who presented with right-sided flank pain, chills, and fever. T was performed in search of abscess., ontrast-enhanced T scan shows heterogeneously enhancing mass in region of renal pelvis (arrows). T-guided biopsy (not shown) showed necrotic tissue. Patient underwent removal of transplant, and pathology disclosed posttransplantation lymphoproliferative disorder (PTLD). and, ontrast-enhanced T scans show several areas of low-attenuation in liver and spleen (arrows) that are new since prior T and presumed to be PTLD. Fig year-old man with right renal transplant., Unenhanced T scan shows soft tissue density mass in left common iliac bifurcation (arrow ) consistent with posttransplantation lymphoproliferative disorder., Unenhanced T scan at same level as obtained 1 year later shows mass (arrow) has decreased in size after withdrawal of immunosuppression and administration of acyclovir. 186 JR:175, July 2000

5 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved T of Renal Transplants D E F Fig year-old man who underwent right renal transplantation., ontrast-enhanced T scan shows heterogeneous nonenhancing mass (arrow) originating from transplanted organ. Remainder of renal parenchyma shows normal T characteristics., ontrast-enhanced T scan obtained 1 month after reveals slight increase (arrows) in size of tumor. fter patient developed acute rejection, transplanted kidney was removed and hemodialysis instituted., T scan obtained after initiation of hemodialysis shows heterogeneous mass in surgical bed. Mass was attributable to hematoma (arrows) after surgery. D, Planar gallium-67 scan shows residual disease as area of abnormal uptake in right iliac fossa (arrow). E, Follow-up T scan obtained 1 month after reveals posttransplantation lymphoproliferative disorder found on biopsy. F, Follow-up T scan obtained 2 months after biopsy shows significantly smaller mass (arrow ) caused by administration of acyclovir and reduction of immunosuppressive medication. JR:175, July

6 Downloaded from by on 12/15/17 from IP address opyright RRS. For personal use only; all rights reserved Vrachliotis et al. D Fig year-old man with normally functioning left renal transplant. Patient had prior right renal transplant in right iliac fossa that had failed 12 years earlier., Unenhanced () and contrast-enhanced ( and ) T scans show radiographically normal left iliac fossa transplanted kidney. In right iliac fossa, however, large soft tissue density mass (m) originates from rejected transplant with rim of peripheral enhancement (arrows) and dystrophic calcifications. T-guided biopsy (not shown) disclosed posttransplantation lymphoproliferative disorder. D, In follow-up contrast-enhanced T scan 2 months later, after administration of acyclovir and reduction in immunosuppressant medication, mass (m) had decreased in size. = urinary bladder. Findings of PTLD are overall nonspecific; however, a predilection for tumor growth exists in the region of the renal pelvis. combination of imaging techniques, including scintigraphy, may be necessary for the diagnostic examination of such patients. Percutaneous biopsy may be performed to confirm the diagnosis. The role of imaging is crucial because early diagnosis of morphologic abnormalities of the renal transplant will increase the chances for tumor regression through a reduction in the immunosuppressive agents. 188 References 1. Nalesnik M, Makowka L, Starzl TE, et al. The diagnosis and treatment of posttransplant lymphoproliferative disorders. urr Probl Surg 1988; 25: Starzl TE, Nalesnik M, Porter K, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet 1984;1: Penn I. ancers complicating organ transplantation (editorial). N Engl J Med 1990;323: Dodd GD III, Greenler DP, onfer SR. Thoracic and abdominal manifestations of lymphoma occurring in the immunocompromised patient. Radiol lin North m 1992;30: Pickhardt PJ, Siegel MJ. bdominal manifestations of posttransplantation lymphoproliferative disorder. JR 1998;171: Miller WT Jr, Siegel SG, Montone KT. Posttransplantation lymphoproliferative disorder: changing manifestations of disease in a renal transplant population. rit Rev Diagn Imaging 1997;36: laudon M, Kessler M, hampigneulle J, Lefevre F, Hestin D, Renoult E. Lymphoproliferative disorders after renal transplantation: role of medical imaging. Eur Radiol 1998;8: li MG, oakley FV, Hricak H, retan PN. omplex posttransplantation abnormalities of renal allografts: evaluation with MR imaging. Radiology 1999;211: JR:175, July 2000

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