LaurieA. Loevner,MD Posttransplantation RonitL. Karpati,MD PriyaKumar, MD Lymphoproliferative Disorder !1via.Y: YoY'-:',MD Wendy Hsu,MD of the Head and Neck: Imagrng KathleenT. Montone,MD Features in Seven Adultsl Index terms: Headand neck neoplasms,28.34 Head and neck neoplasms,CT, 28.121 11 , 28.121 12, 28.121 1s Head and neck neoplasms,MR, 28.12't 4't 1, 28.'t21 43 Transpfantation,51 .459, 60.459, 76.459,770.4s9, 81 .455 Lymphatic system neoplasms, 997.34 Radiology ?{ffi; 216:361369 Abbreviations: EBV= EpsGin-8arrvirus PTLD : posttransplantation lymphoproliferativedisorder 1 From the Departments of Radiology (L.AL..D.M.Y.) and Pathology(K.T.M.), and the University of Pennsylvania Schoolof Medicine(R.LK., P.K..W.H.), Universityof PennsylvaniaMedical Cen- ter, 3400 Spruce St, Philadelphia, PA 19104. From the 1998 RSNAscientific assembly. Received August 30, 1999; rwision requested October 8; final rwi- sion receivedJanuary 4,20OO; accepted fanuary 12. L.A.L.supported by an RSNA Researchand Education Foundation Scholargranl W.H. supported by the RSNA Researchand Education Foun- dation Medical Student/ScholarAssis- tant prograrn. Address cornespon- Posttransplantation llrnphoproliferative disorder (PTLD) encompasses a family of disor- dence to L.A.L.(e-mall: loevner@oosis ders and includes lynphoid hlperplasia and lymphoid neoplasia, which occur in .rod.upenn.edu). the setting of chronic immunosuppression after solid organ transplantation. In 1968, Starzl (1) @ RSM,2oOO provided an early description of PTLD in renal transplant recipients. PTLD is a challenging complication of organ transplantation (1) and, if untreated, is usually fatal. Because immunosuppression carries an increased risk for the de novo development of malignancy, the occurrence of PTLD is surpassed only by that of cancers of the skin and lips (2). The frequency of PTLD has been reported to range from !o/o to loo/o, with substantial variability depending on the organ transplanted (3-9). Walker et al (8) reported prLD in 6.2o/oof patients after lung transplantation, 5.2o/oof patients after kidney and pancreas transplantation, 2.Oo/oof patients after heart transplantation, and t.4o/oof patients after liver transplantation. The difference in the frequency of PTLD among these groups may be attributed to organ-specific immunosuppressive regimens. The association of Epstein-Barr virus (EBV) infection with the development of PTLD has been well established and is hypothesized to occur through unregulated B-cell proliferation. PTLD encompasses a spectrum of clinical manifestations, in addition to a wide range of histopathologic find- ings, from B-cell hlperplasia to lynphoma. Lesions primarily occur in the gastrointestinal tract, central nervous system, allografted organ, and, less commonly, lymph nodes (6). We performed this study to determine the unusual flndings of PTLD of the head and neck in adult patients who have undergone solid organ transplantation, with lesions involving the Waldeyer ring (lymphoid ring) in the pharynx, as well as lesions involving the cervicallymph nodes.The magnetic Imaging cervical lymph nodes. In the patient who resonance(MR) imaging and computed underwent both CT and MR imaging, CT and MR imaging of the neck were tomographic (CT) flndings will be de- both sets of images were evaluated to- performed in six and two patients, re- scribed. gether. Speciflcally, images were assessed spectively. CT was performed at our in- for the presence of (a) generalized en- stitution with a helical scanner (model largement and/or focal massesof the pha- 9800; GE Medical Systems, Milwaukee, MATERIALS AND METHODS lymphoid tissue and (b) lymph- Wis), with acquisition of a set of 5-mm- ryngeal adenopathy. In addition to size, masses Clinical Data thick transverse images that covered were evaluated for changes in attenua- from the skull base to the aortic arch. The study group consistedof sevenpa- tion and signal intensity (relative to that Two sets of images were obtained during tients (ftve men/ two women), aged of muscle and cerebrospinal fluid) at CT each CT examination, one optimized for 2l-65 years(mean, 42 years),with his- and MR imaging, respectively, which are bone detail and the other optimized for topathologically proved PTLD of the suggestive of increased free water con- soft-tissue detail. Only one patient un- pharyngeal llrnphoid tissue or the cervi- centration. The degree of enhancement derwent CT after intravenous administra- cal nodes. Patients were identifled by was assessedby comparing the attenua- tion of 100 mL of iodinated contrast ma- searching the pathology database for tion or signal intensity of the masses terial (iohexol, Omnipaque; Nycomed, those who had been treatedfor PTLD at with that of muscle, the submandibular Princeton, NJ). In the remaining patients, our institution during 4 years. All pa- glands, and the mucosa. Lymph nodes CT scanswere obtained without contrast tients had undergonecross-sectional im- were considered to be abnormal if they material because of renal insufficiency aging. Our investigation in no way inter- or were enlarged according to radiologic cri- to prevent potential fered with patient care.All patientshad complications in teria (diameter > 1.5 cm in the subman- undergone solid organ transplantation transplanted kidneys. dibular, submental, and jugulodigastric MR images were with between 1987 and 1996. One patient obtained a 1.5-T regions; diameter > 1.0 cm in the re- system (Signa; each underwent heart, kidney, and lung GE Medical Systems) by mainder of the neck) or if there were an using an anteroposterior transplantation; three patients under- volume neck excessive number regardless of their size (Medical went liver transplantation;and one pa- coil Advances, Madison, Wis). (multiple groupings of three or more tient underwent combined kidney and The imaging protocol consisted of a sag- nodes, each at least 5 mm). In addition, pancreastransplantation. The mean age ittal Tl-weighted conventional spin-echo the upper mediastinum and thymic re- (repetition at transplantationwas 35 years (range, sequence time msec/echo gion was assessedfor focal lesions. Radio- : 2I-54 years).Posttransplantation immu- time msec 400-6OO/11-17) followed Iogic findings were compared with results nosuppressivetherapy included pred- by a transverse T2-weighted fast spin- of histologic analysis of the specimens. : nisone (n 7), cyclosporine(n - 5), echo sequence (3,500-4,000/85-90 [ef- The medical records of all patients : : azathioprine(n 3), tacrolimus(n 2), fectivel) and a transverse Tl"-weighted were retrospectively reviewed by one au- : and mycophenolate (n l). Clinical spin-echo sequence (600l ll-17). Images thor (R.L.K.) to determine the predispos- symptomsincluded ear pain, a mononu- of the neck extended from the level of ing disease that led to organ failure, time cleosis-likesyndrome, a palpable neck the cavernous sinus to the upper medias- between transplantation and onset of mass,and facial paresthesiaand numb- tinum. Then, 0.1 mmol of gadopentetate PTLD, presence of PTLD in other organ ness. dimeglumine (Magnevist; Schering, Ber- systems, initial therapy, and response to Iin, Germany) per kilogram of body therapy. weight was intravenously administered, Histopathologic Findings and transverse T1-weighted spin-echo The diagnosisof PTLDwas histopatho- images were obtained with imaging pa- RESULTS logicallyestablished with the presenceof rameters similar to those used for the atypical lymphocltic infiltrates and/or nonenhanced images. Fast spin-echo and AII sevenpatients had abnormalitiesin- destructionof the normal parenchymal contrast-enhanced images were obtained volving the Waldeyer ring, including architectureat the biopsy sites in the after the application of frequency-selec- generalized lymphoid enlargement in neck. PTLDwas classifiedaccording to a tive fat-saturation techniques. For the one patient and focal massesin six pa- systemproposed by Nalesnik et al (10) sagittal T1-weighted localizing sequence, tients. In the six patients with focal and Knowles et al (11), with subtypes the section thickness was 5 mm with a massesinvolving the Waldeyerring (uni- that include plasmocytic hyperplasia, gap of 1 mm, and the field of view was 30 lateral oropharyngeal tonsil in two pa- polymorphous B-cell hyperplasia, poly- cm. All other sequences were performed tients, bilateraloropharyngeal tonsils in morphous B-cell lymphoma, non- with interleaved images and a section one, nasopharyngealadenoids in three, Hodgkin lymphoma, and multiple my- thickness of 5 mm. Other imaging pa- unilateral tonsil and nasopharynx in eloma. rameters included one or two signals ac- one), the lesionswere 2.0-4.5 cm in di- To determine the frequency of EBVin- quired and a 24-26-cm field of view. A ameter (Figs1-3). In the three patients fection in the tissuesaffected by PTLD,in 256 x 128 matrix was used for sagittal who underwent contrast-enhancedCT situ hybridization for the EBV genome and contrast-enhanced Tl-weighted im- (n : l) or MR imaging (n : 2), the was performedwith all specimens.Test- ages, and a 256 x 192 matrix was used massesshowed a prominent centralarea ing included evaluation for EBERI, an for nonenhanced transverse T1- and T2- of low attenuation at CT and a central RNA sequence that is abundantly ex- weighted images. areaof signalintensity similar to that of pressedduring latent EBVinfection, and Images were retrospectively reviewed cerebrospinalfluid at MR imaging, with tandem repeatsof NofI, a DNA sequence in consensusby two