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Home , Organ transplantation

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 neoplasms, 997.34

Radiology ?{ffi; 216:361369

Abbreviations: EBV= EpsGin-8arrvirus PTLD : posttransplantation lymphoproliferativedisorder

1 From the Departments of (L.AL..D.M.Y.) and (K.T.M.), and the University of Pennsylvania Schoolof (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 after solid transplantation. In 1968, Starzl (1) @ RSM,2oOO provided an early description of PTLD in renal transplant recipients. PTLD is a challenging complication of (1) and, if untreated, is usually fatal. Because immunosuppression carries an increased risk for the de novo development of , the occurrence of PTLD is surpassed only by that of 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 transplantation, 5.2o/oof patients after and , 2.Oo/oof patients after transplantation, and t.4o/oof patients after 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) with the development of PTLD has been well established and is hypothesized to occur through unregulated B- 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 ;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 : : (n 3), (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 , 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 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 head and neck radi- thick peripheral tissue that showed en- that is amplified during active EBVinfec- ologists (L.A.L., D.M.Y.), who looked for hancement similar to that of the sub- tion. abnormalities of the Waldeyer ring and mandibular glands (Figs 1, 3). In addi-

364 . Radlology . August 2OOO Loevner et al tion, the attenuation (at CT) or signal intensity (at T1-weightedMR imaging) of residual peripheral solid tissue was simi- lar to that of muscle. One patient had a small mass in the superior mediastinum in the thynic region (Fig 1). In the other three patients with focal massesinvolv- ing the Waldeyer ring, small regions of low attenuation may have been present, but this was not evident becausethe im- ageswere acquired without contrast en- hancement. Three patients had adenopathy in the cervicallymph chains. One patient had a single 7-cm nodal massin the right side of the neck (nodal levels 2 and 3) with a small central area of questionably low attenuation (Fig 4). The other two pa- Figure t. Patient 3. Contmst-enhancedtrans- tients had multiple groupings of three or verse CT scans obtained in a 53-year-old more nodes in the bilateral anterior and woman after bilateral . posterior PTLD was proved with CT-guided biopsy re- spinal accessorycervical lymph sults. (a) Scan obtained at the level of the chains, the sizesof which were within or nasopharynx demonstrates a low-attenuating at the upper limits of normal (Fig2). One mass (anows) at the level of the fossa of patient with multiple groupings of cervi- Rosenmiiller and lateral nasopharyngeal wall cal Iymph nodes also had abdominal on the left. An abscesswas suspected. (b) Scan periaortic adenopathy. obtained 2 cm inferior to a demonstrates ex- Histopathologic tension of the mass to the oropharynx and examination of the tonsil. The mass is charactedzed by a central specimens revealed polyclonal plasmo- hypoattenuating area consistent with necro- cytic hyperplasia(n : 1), polymorphous sis (arrow). Circumferentially, there is a thick B-cell hyperplasia (n : 1), polymor- rind of solid lymphoid tissue (arrowheads). phous B-cell lymphoma (n : 3), non- The mass at this level is predominantly sub- Hodgkin ly'rnphoma (n : I), and multi mucosal within the parapharyngeal space. ple (n : (c) Scan obtained at the level of the upper myeloma l).ln the patientwith thorax demonstrates a small mass (arrow) in , findings on bone ra- the superior mediastinum. diographs were consistent with my- eloma, and myeloma was also confirmed with analysisof bone manow aspirate.In the three patients with pharyngeal le- sionswith imaging findings suggestiveof necrosis,necrosis was confirmed at his- topathologic examination. The EBV ge- nome was detected with immunohisto- chemical results in five of seven specimens,with EBV EBERl-positivere- sults in four of five specimensand EBV NofI tandem repeats-positive results in two of three specimens(two specimens were not tested for EBV NofI tandem re- peats). The interval between transplantation and the onsetof PTLDranged from 3.5 to 108 months (mean,3O months; , L1 months) (Table).All patients initially had PTLD of the neck. Three Datients were subsequentlyfound to have PTLD involving other organ systems/including a. b. the rectosigmoidand in one pa- Figure 2. Patient 5' Nonenhanced transverse CT scans obtained in a 21-year-old man with tient, the periaortic lymph nodes in an- acute onset of PTLD 4 months after kidney and pancreas transplantation. Nonenhanced CT was other, and the allografted kidney in the performed owing to renal failure due to acute reiection of the transplanted kidney. (a) Scan shows third. Patients y/ere treated with combi large masses involving the bilateral tonsils of the Waldeyer ring at the level of the orophar;mx, nation therapy, including which meet at the midline (arrowhead). These were sampled at biopsy, and prLD was proved at reduction in histopathologic examination. (b) Scan obtained more inferiorly demonstrates bilateral lymph their immunosuppressionregimen (n : nodes (allows) that were suspected of being involved with PTLD; however, the nodal diameters 7), (n : 2), chemotherapy(n : remained within normal size cdteria. 2), and (n : 2) (Table).

. Volume 216 Number 2 Posttransplantatlon Lymphoprollferatlve Dlsorder: lmaglng Features . 365 Outcomes in the flve patients with neo- plasia included complete remission (n : 1), partial remission (n : l), and pro- gressive disease (n : 3). At the time of manuscflpt preparation, two patients had died.

DISCUSSION

PTLD is a seriouscomplication of solid organ transplantation, and clinical flnd- ingsrange from focalto disseminateddis- ease.The frequencyhas been reported to range from Io/oto l0o/oin transplant re- cipients,depending on the organ trans- planted (3-9) and the tlpe and length of immunosuppressivetherapy (6,8). With a. b. the potency of current medications Figure 3. Patient 1. Spin-echo MR images in a 44-year-old man in whom PTLD was diagnosed aimed at prevention of organ reiection, 23 months after liver transplantation for chronic active . (a) Nonenhanced sagittal Tl-weighted (400/11, the frequencyof PTLDhas increased(6). image two signals acquired) demonstrates a circumscribed mass (arrows) centered in the region of the left nasopharynx, with central signal intensity similar to In addition, that of the interval betweentrans- cerebrospinal fluid. The peripheral area has a rind of thick lymphoid tissue (arrowheads) that is plantation and the onset of this compli- isointense to muscle. (b) Contrast-enhanced transverse Tl-weighted image (600177, one signal cation hasdecreased (6). PTLD represents acquired) also demonstrates the mass (arrows), which is predominantly submucosal, in the left uncontrolled B-cell proliferation with nasopharynx. This mass was initially interpreted as being an abscess.Biopsy results demonstrated histologic characteristicsthat range from a necrotic mass consistent with polFnorphic B-cell lymphoma. PTLD was also histopathologi- cally demonstrated in the gastrointestinal polymorphic cellular expansionof large tract at rectosigmoid biopsy. and/or small lymphocytesto monomor- phic large cell non-Hodgkin ll.rnphoma. The system used to classify PTLD is constantly evolving in an attempt to ac- commodate the wide range and growing number of subtypesof llrnphoprolifera- tion. Histopathologiccriteria for the di- agnosis of PTLD include lynphocytic proliferation with or without destruction of the underlying architecture of the af- fected tissue (depending on the classifi- cation systemused). Frizzera et al (12) in 1981, Nalesnik et al (10) in 7989, and Knowles et al (11) in 1995 have devel- oped classiflcationssystems that subdi- vide PTLDlesions into three distinct cat- egories:h;,perplastic, poll'rnorphic, and monomorphic (3).More recently,a T-cell form of PTLDhas been reported (13), and this finding representsa rare, Iate, and ii*r" n. Patient 4. Nonenhanced transverse3i ,.un, in a 52-year-oldman who developed aggressivecomplication of organ trans- PTLD of the neck 9 yearsafter undergoing . Intravenous contrast matedal plantation. Unlike its B-cellcounterpart, was not administeredowing to renal insufficiency. (a) Scanobtained at the level of the T-cell PTLD is not thought to be associ- cartilagedemonstrates a 7-cm circumscribednodal massin the right sideof the neck with a small questionably ated with EBVinfection (13). area of low attenuation (arrow). Polymorphic B-cell lymphoma was diagnosedat biopsy, and necrosiswas confirmed at histopathologicexamination. (b) Follow-up scan The role of EBVinfection in patho- obtained the 7 months later showscomplete resolution of the massafter treatment with decreasedimmuno- genesisof PTLD has been firmly estab- suppressivetherapy followed by chemotherapyand radiation therapy. lished(14). EBV infects B lymphocltes,as well as epithelial cells,because the virus attachesto specificreceptors located on the membranesof thesecells. This recep- immunocompetent patient, this process gradually progress to monoclonal lesions tor specificitymay help explain the asso- is kept in check by cytotoxic T lympho- that harbor malignant transformations ciation of EBV in the development of c1tes, which recognize and lyse EBV-in- (5,16). In the setting of solid organ trans- squamouscell carcinomaof the aerodi- fected cells. In the immunocompromised plantation, EBV infection may originate gestivetract epithelium (6,15). patient, however, the suppression of this from the donor or the recipient, and the After the primary infection, latent EBV immunosurveillance processmay lead to infection may represent an acute process persistsfor life. Latent EBVnuclear pro- the unregulated proliferation of B cells or a reactivation process (17,18). pre- teins induce B-cell proliferation. In the (1.6).Tumors are initially polyclonal and transplantation EBV seronegativity is

. . 366 Radlology August 2OOO Loevner et al thought to substantiallyincrease the risk gFFFooo a for the development of PTLD c and, at frH i:q s tE is i?is some institutions, may preclude trans- fg gE 3E'Fe 3E 9.9 E_eE_s o :,; trcr g€ g€g'E & EE plantation (8). E- 8- I- ,i E- E-E- The dinical manifestationsof PTLDcom- monly includea mononucleosis-typesyn- drome (fever, fatigue, sore throat), re- € P P P *.FIE;FP P P gional lpnphoid tumors, or disseminated o (19). ! i. E. 2;p€g+E'.3E. 7.7. disease Lymphoid tumors may be - Es Eg Eee:€Ae:Ee E9Eg nodal or extranodal in origin. Extranodal 6 = ;fr ;r ;u5.9--i5.e;6 ;6:E diseaseis most common and frequently involves the gastrointestinal tract, cen- Ed:+ E;:+ €;!:+E*AEE*g+ P;.! u i:E; EAE--E+E+ &.&EqEEE tral nervous system, and/or allografted organ (6). Allograft involvement may E1' clinically mimic organ rejection, and, H : Ja o fF therefore, biopsy is necessaryto prevent q= 62:o-ua =.^! therapy that will exacerbatethe disease o -*6r'; 3G € process. F =Ed'F= !. s Disseminateddisease, which is d -. llE pA = .: LG =3 the most severeform of PTLD, manifests o Ee''s .c^d c s .='q= | = 5- as sepsis,generalized adenopathy, and A E.ficc RI e db oo multiorgan failure. H:d-eu5 ;H 5 €E CC Therapeuticinterven- &.zdzE zz tions are often ineffective. Becausethe s1'rnptomsof PTLD fre- == E T E EE quently resemblethose of other compli- o 6 co E_ d o cations of transplantation, particularly d .!l ;E eH xE :E*s *e-o-'iH '+:ES infection and organ rejection, a high in- ->.-o- ;'9 E E P F E dex of suspicion for PTLD is crucial to o EF EE fi' FE FE Fi'j. .9 prevent a delay in diagnosis. PTLD T i5 k.a 55 i5 5F i5= dEZdd; should always be considered in the dif- ferential diagnosis of organ rejection in

'6 the setting of chronic abdominal pain or I v=n- with the development of cutaneous le- ^.Y EE EC CE sionsin a transplantrecipient. Oral shed- O-6 aiiE qF+ ,T E E- q= "i=:"i=: 9Ee 9F9E= ding of EBV and elevation of EBV-posi- => FelEr"EEr"E Er"9E€apEu"Eu"€ tive serum leukocytes may aid in the E €$ tBN€BN€BF tEbEtBtBE early diagnosis (7). The work-up of sus- edcdddd pected PTLD usually includes cross-sec-

9, a + tional imaging of the head, , abdo- "' mn9o NO. men, and pelvis (20). Routine imaging of N;-ri 3$ F -5 L.: the neck has not been part of this proto- col. Definitive diagnosisof PTLDis estab- 0 L = Iished on the basis of histopathologic 0,, : Ef. i" F r E analysisof tissue.Specimens are evalu- z !ln -F 7) -F F i F!. FE FF ated for histologic characteristics,cellular G' clonality, EBV infection, and Eb o E tr lyrnphocyteantigen t'?ing. E; d (u G € 'o,u:f ; Eg-o, - o # 3 qd 5 q The imaging appearance PTLD I jziEi6iE of has o c been describedin the lungs, gastrointes- o tinal tract, and central nervous system. .F For intrathoracic PTLD, chest radiogra- 6 ,€EE 6 T phy is a simple and accurate EN o surveillance F ;ai i^ E eE { i CL method (21,22). Findings may include ;.2 uE i: 93. iE e 2 d- Eo ).c- :^ ,iF E= E 3 pulmonary nodules, airspaceconsolida- 't "-$ c o g.s- Ee Fn RE _68 3 F tion, hilar and mediastinal adenopathy, .F 6- #* 5- i" 3' f* 5 pleural and pericardial effusions, and .9 € thymic enlargement (2I,23-25). Al- (' -g Ef; though necrosis is uncommon, it has r o- g e oc G been noted in very large solitary medias- 6 E tF a b IE F g tinal nodal masses(2L,23). |E : *= # s- i i o In intraabdominal PTLD, Iow-attenu- g.E ating mass(es)in the liver and G : xq V\tNh e,';" q. OG present !\o { 3 {. r: n9 may be at CT. Diffuse infiltration 6A<') c- = dz< = = E A = E€ F resulting in hepatomegalyor splenomeg- aly without a discrete mass or masses

. Volume 216 Number 2 Posttransplantatlon Lymphopro!lferatlve Dlsorder: lmaglng Features . 367 may also occur (26). Other abdominal munosuppressivetherapy, chemother- component, which makes their identifi- findings include thickening or dilatation apy, radiation therapy, surgicalexcision, cation difficult at physical examination, of the small bowel, mesentericadenopa- antiviral therapy, and novel immuno- imaging may be paramount in facilitat- thy, and diseasein the kidney, pancreas, modulation techniques. Treatment is ing detection. Finally, imaging is valu- or adrenalglands (27). determinedaccording to the specifichis- able for monitoring the response to treat- Lesionsin the central nervous system topathologic finding. Reduction in immu- ment (Fig 4). were more commonly encountered in nosuppressivemedication (or complete the erabefore ryclosporine (25,28). Cere- cessationin casesof lymphomatous or References bral lesions tlpically manifest as periph- disseminateddisease) is effective and al- 1. StarzlTE. In discussionof: MurrayJE,Wil- erally enhancing masseswith a central most always servesas the initial thera- son RE,Tilney NL, et al. Five yearsexpe- area of low attenuation or with signal peutic option (2,6,19,3I).The likelihood rience with renal transplantation with immunosuppressivedrugs: survival, fu nc- intensity similar to that of cerebrospinal of a responseis directly related to the tion, complications and the role of lym- fluid, and such lesions must be distin- clonality of the tumor. Monoclonal tu- phoqte depletion by thoracic duct fis- guishedfrom infection (25). mors, which more closelyresemble lym- tula. Ann Surg1968; 168:416. PTLD affecting the neck is reportedly phoma, are lesslikely to be affected. Re- 2. Morrison VA, Dunn DL, ManivelJC, Gail- Peczalska KJ, Peterson BA. Clinical char- uncommon, and, therefore, the radio- duction in immunosuppressive therapy actedstics of post-transplant lymphopro- logic manifestations have not been well may be accompaniedby organ rejection liferative disorders. Am J Med 1994; 97: characterized.We have described seven and requiresclose clinical follow-up. Fail- 1.4-24. adult transplant recipients in whom the ure of tumor regressionin the settingof Swerdlow SH. Classification of the oost- primary manifestation transplant lymphoproliferative disorders: of PTLD began decreasedimmunosuppression requires from the past to the present. Semin Diagn with symptoms in the neck. Six patients other treatment modalities, including Pathol 1997; 14:2-7. had focal massesin the Waldeyer ring, chemotherapy and radiation therapy. Ef- 4. Montone KT, Litzky LA, Wurster A, et al. and 50o/oof these patients had central forts in the use of antiviral drugs have Analysis of Epstein-Barr virus-associated posttransplantation necrosisand substantial submucosalex- shown limited clinical utility in the lymphoproliferative treat- disorder after lung transplantation. Sur- tension into the parapharyngeal space. ment of PTLD (2,4,20).Immunothera- gery 7996;119:544-551. These imaging flndings differed from peutic treatmentssuch as anti-B-l;.'rnpho- Benkerrou M, Durandy A, Fischer A. Ther- those of lymphoma in the immunocom- clte monoclonal antibodies/ interferon apy for transplant-related lymphoprolif- petent patient, which frequently appears alfa, and cytotoxic T-cell transfusion are erative disease. Hematol Oncol Clin North Am 7993; 7:467-47 5. as a solid massthat grows exophytically (3). currently under investigation 6. Basgoz N, Preiksaitis JK. Post-transplant into the airway lumen. It is also notewor- Many factors affect the prognosis in lymphoproliferative disorder. Infect Dis thy that in two of the three patients, the patients with PTLD. Early-onsetdisease Clin North Am 1995; 9:9O7-923. necrotic masseswere initially misinter- (within 1 yearof transplantation)is asso- 7. Riddler SA, Breinig MC, McKnight JL. In- preted creased levels of circulating EBv-infected as abscesses.Cervical lymphade- ciated with a better prognosisthan is lymphocytes and decreased EBV nuclear nopathy was also present in more than late-onsetdisease, with mortality ratesof antibody responses are associated 40olo(three of seven) of the patients in 360/oand 70olo,respectively (32). Patients with the development of posttransplant our study, and two imaging patternswere with early-onset PTLD also are more Iymphoproliferative disease in solid or- noted: namely, gan transplant recipients. 1994; a large nodal mass and Iikely to respondto a reductionin immu- 3:972-984. clustersof normal-sizedlyrnph nodes. nosuppressive treatment (32). Heart 8. Walker RC, Paya CV, Marshall WF, et al. There are a few reports of PTLD of the transplantrecipients are reported(27) to Pretransplantation seronegative Epstein- neck describedin the pediatric popula- have a worseprognosis than those with Barr virus status is the primary risk factor post-transplantation tion (27,29,3O).Donnelly et aI (27) noted kidney or liver allografts, perhaps be- for lymphoprolifera- tive disorder in adult heart, lung, and that eight of 27 children (all heart trans- causeof the more potent immunosup- other solid organ transplantations. J Heart plant recipients) developedPTLD of the pressive therapy required after heart Lung Transplant 1995; 1,4:214-221. neck. Lesionsin the Waldeyer ring were transplantation. 9. Reynders CS, Whitman GJ, Chew FS. presentin three patients, and cervicalad- In conclusion, patients with PTLD af- Posttransplant lymphoproliferative disor- der of the lung. AJR Am J Roentgenol enopathy was present in five. Similar to fecting the neck may have focal massesin 1995; 1.4:274-221. our findings, these previously published the Waldeyer ring and lymphadenopa- 10. Nalesnik MA, Jaffe R, Starzl TE, et al. The resultsshowed extensive low attenuation thy that manifestsas largenodal masses pathology of post-transplant lymphopro- in one of the massesin the Waldeyer or an excessivenumber of lymph nodes liferative disorders occurring in the set- ting of cyclosporine A- immu- ring, aswell as in a nodal mass. that are relatively normal in size.Unlike nosuppression. Am J Pathol 1988; 133: It is important to note that micro- in lymphoma in the immunocompetent 173-t92. scopicdisease may be overlookedat im- patient, necrosisin PTLDlesions may be Knowles DM, Cesarman E, Chadburn A, aging. The presence of histopathologi- more common.The presenceof a massor et al. Correlative morphologic and molec- cally proved PTLD in nodes that are massesin ular genetic analysis demonstrates three the Waldeyerring or cervical distinct categories of post-transplanta- normal accordingto imaging criteria em- nodes in patients who have undergone tion lymphoproliferative disease. Blood phasizesthat the absenceof abnormali- organ transplantation should increase 1995; 85:552-565. tiesat imagingdoes not rule out PTLD.It the index of suspicionfor the diagnosis t2 Frizzera G, Hanto DW, Gail-Peczalska KJ, further emphasizesthat, as our findings of PTLD.Masses with low attenuation et al. Polymorphic diffuse B-cell hyper- on plasia and lymphoma in renal transplant suggest,clusters of nodes, although nor- CT scans or signal intensity similar to recipients. Res 1,981,; 4l:4262- mal in size,should be viewed with suspi- that of cerebrospinalfluid on MR images 4279. cion given the appropriate clinical set- should not be mistakenfor abscesses,as 13. Hanson MN, Morrison VA, Peterson BA, ting. was initially the casein two of our pa- et al. Post-transplant T-cell lymphoprolif- erative disorder: an aggressive, late com- There are multiple treatment modali- tients. Becauselesions in the Waldeyer plication of solid organ transplantation. ties for PTLD,including reduction in im- ring frequently have a large submucosal Blood 1996; 88:3626-3633.

368 . Radlology . August 2OOO Loevner et al 14. Hanto DW, Frizzen G, Gall-Peczalska KJ, tive disorders. Leuk Lymphoma 1997; 25: 27. Donnelly LF, Frush DP, Marshall KW, et al. Epstein-Barr virus induced B-cell 1-8. White KS. Lymphoproliferative disorders: lymphoma after renal transplantation: 21 Pickhardt PJ,Siegel MJ, Anderson DC, Ha- CT findings in immunocompromised acyclovir therapy and transition from yashi R, DeBaun MR. Chest children. AJRAmJ Roentgenol 1998;771:. polyclonal to monoclonal B-cell prolifer- as a predictor of outcome in posttrans- 725-731.. ation. N Engl J Med 1,982; 3O6:913-9"18. plantation lymphoproliferative disorder JA Miller WT Jr, Siegel SG, Montone KT. 15. Boulter A, Johnson NW, Birnbaum W, in lung allograft recipients. AJR Am J Posttransplantation lymphoproliferative Teo CG. EDstein-Barr virus associated le- Roentgenol 1998; 1,71:37 5-382. disorder: changing manifestations of dis- sions of the head and neck. Oral Dis 22. Rappaport DC, Chamberlain DW, Shep- easein a renal transplant population. Cdt 1996; 2:117-124. herd FA, Hutcheon MA. Lymphoprolif- Rev Diagn Imaging 1997 ; 38:569 -585. ro. Craig FE, Gulley ML, Banks PM. Posttrans- erative disorders after lung transplanta- 29 Sculerati N, Arriaga M. Otolaryngologic plantation llmphoproliferative disorders. tion: imaging features. Radiology 1998; management of posttransplant lympho- -524. AmJ Clin Pathol 1993; 99:265-276. 2O6:519 oroliferative disease in children. Ann Hodinka RL, Salhany KE, Dodd GD, Ledesma-Medina Baron RL, 17. Montone KT, 23. J, btol nhinol Laryngol l99O; 99:445-450. Lavi E, Rostami A, Tomaszewski Iden- Fuhrman CR. Posttransplant lymphopro- JE. 30. Deschler DG, Osorio R, Ascher NL, Lee tification of Epstein-Barr virus lltic activ- liferative disorder: intrathoracic manifes- KC. Posttransplant lymphoproliferative ity in post-transplantation lymphoprolif- tations. Radiology 7992; 184:65- 69. disorder in patients under primary ta- erative disease.Mod Pathol 1996;9:621- n^ Carignan S, Staples CA, Muller NL. In- crolimus (FK 506) immunosuppression. 630. trathoracic lymphoproliferative disorders Arch Otolaryngol Head Neck Surg 1995; 18. Montone KT, Hodinka RL, Tomaszewski in the immunocompromised patient: CT L21.:1O37-1O47. JE. Identification of Epstein-Barr virus findings. Radiology 1995; 197:53-58. lytic and latent RNA transcdpts in post- 25. Tubman DE, Frick MP, Hanto DW. Lym- 31. Starzl TE, Nalesnik MA, Porter KA, et al. transplant lymphoproliferative disorder. phoma after organ transplantation: ra- Reversibility of lymphomas and lympho- IntJ Surg Pathol 1995;3:119-130. diologic manifestations in the central proliferative lesions developing under cy- t9 Nalesnik MA. Posttransplantation lym- nervous system, thorax, and abdomen. clospodn-steroid therapy. Lancet 1984; phoproliferative disorders (PTLD): cur- Radiology 1983; I49:625- 631.. 1:584-587. rent perspectives. Semin Thorac Cardio- 26. Strouse PJ, Platt JF, Francis IR, Bree RL. Ja. Murray KA, Chor PJ, Turner JF Jr. In- vasc Surg 1996; 8:139 -1,48. Tumorous intrahepatic lymphoprolifera- trathoracic lymphoproliferative disorders 20. Lucas KG, Pollok KE, Emanuel DJ. Post- tive disorder in transplanted . AJR and lymphoma. Curr Probl Diagn Radiol transplant EBV induced lyrnphoprolifera- Am J Roentgenol 1996:,167:11,59 -1162. 1.996; 25:78-106.

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