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Background
Posttransplantation lymphoproliferative disorders (PTLDs) are a well-known complication of organ transplantation. The overall risk varies according to the type of organ transplanted and the immunosuppressive regimen, ranging from less than 1% for renal transplantation, to 2% to 4% for liver transplantation, and up to 10% for combined heart-lung transplantation. The incidence is usually greatest in the year following transplantation. The risk and nature of PTLDs in pediatric transplant patients, and following pediatric liver transplantation in particular, are less well studied than in their adult counterparts. Nonetheless, several reports have described the clinicopathologic findings in this population and suggest that children are at higher risk than adults for developing PTLD.
Posttransplantation lymphoproliferative disorders are frequently, but not always, associated with the Epstein-Barr virus (EBV), and pretransplantation EBV seronegativity has been suggested as a primary risk factor for the development of PTLD.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION TRANSPLANTATION, NONMYELOABLATIVE ALLOGENIC STEM CELL Posttransplant lymphoproliferative
disorder following
nonmyeloablative
allogeneic stem cell transplantation.
Snyder MJ, Stenzel TT,
Buckley PJ, Lagoo AS,
Rizzieri DA, Gasparetto C,
Vredenburgh JJ, Chao NJ,
Gong JZ.
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Am J Surg Pathol. 2004 Jun;28(6):794-800. Abstract quote
Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of conventional bone marrow/stem cell and solid organ transplantation. However, not much is known about PTLD following the more recently introduced nonmyeloablative allogeneic stem cell transplantation (NMST).
This study reports the findings from two cases of PTLD following NMST and compares them to the one previously reported case. The donor origin of the PTLD was determined using short tandem repeat analysis, and B- and T-cell clonalities were evaluated by polymerase chain reaction. Two cases of PTLD evolved in a total of 70 patients who have undergone NMST at our institution from 1999 to 2003.
Both patients received conditioning with Fludarabine/Cytoxan/Campath 1H (alemtuzumab, anti-CD52 antibody) and T-cell-depleted donor cells with Campath-1H. Both PTLDs were EBV positive (by immunohistochemistry and in situ hybridization) with diffuse large B-cell lymphoma morphology. Our findings indicate the incidence of PTLD following NMST is 3% (2 of 70 patients from our institution and 1 of 30 from the previously reported case). All three PTLDs arose 6 to 7 months after NMST and were rapidly fatal.
The pathology of the PTLD in all cases was donor origin, EBV positive, diffuse large B-cell lymphoma.UMBILICIAL CORD BLOOD TRANSPLANTATION
- Posttransplant Lymphoproliferative Disorder After Umbilical Cord Blood Transplantation in Children.
Gong JZ, Bayerl MG, Sandhaus LM, Sebastian S, Rehder CW, Routbort M, Lagoo AS, Szabolcs P, Chiu J, Comito M, Buckley PJ.
Departments of *Pathology and daggerPediatrics, Duke University Medical Center, Durham, NC Departments of double daggerPathology and section signPediatrics, M.S. Hershey Medical Center, Hershey, PA parallelDepartment of Pathology, University Hospitals of Cleveland, Cleveland, OH. Dr. Routbort's current affiliation is Division of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX.
Am J Surg Pathol. 2006 Mar;30(3):328-336. Abstract quote
Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients received UCBT, including 1 patient who received multiple units and 1 transplanted under nonmyeloablative condition. The time interval from UCBT to PTLD averaged 4 months (range, 2 weeks to 9 months).
Patients typically presented with high-stage disease with visceral organ involvement. Histology of the PTLDs showed monomorphic morphology in 5 cases and polymorphic morphology in the remaining 2 cases. Bone marrow biopsies were performed in 3 cases and were negative for PTLD. Epstein-Barr virus (EBV) was detected in the PTLD in all 7 patients by in situ hybridization. Evidence of past EBV infection was found in the recipients, but the EBV genome was not detected in the donor cord blood samples, suggesting that donor cord blood was not the source of EBV infection. The origin of the PTLD was investigated in 5 cases. PTLD was of host origin in 2 patients who failed engraftment and of donor origin in the remaining 3 patients who had complete engraftment. Four of 5 patients with monomorphic PTLD failed to demonstrate significant responses to rituximab and/or reduction of immunosuppression and died within 1 month after diagnosis. The remaining 2 patients with polymorphic PTLD showed complete response to therapy.
One patient was alive 35 months after transplant, and the other patient died of infection 6 months after transplant. It is concluded that PTLD arising after UCBT in children occurs early after transplant and represents a serious EBV-related complication. PTLD may be of donor or recipient origin depending on engraftment status.
Both monomorphic and polymorphic histology may be seen, and monomorphic histology appears to predict an unfavorable prognosis.
PATHOGENESIS CHARACTERIZATION B CELL PHENOTYPE
Louis Novoa-Takara, MD, etal.
We immunohistochemically defined the histogenesis of posttransplantation lymphoproliferative disorders (PTLDs; B-cell phenotype) occurring after allogeneic T cell–depleted hematopoietic stem cell transplantation (HSCT; n = 15) or solid organ transplantation (SOT; n = 11) to determine whether transplantation type or morphologic subtype of PTLD affected the histogenetic subtype.
Immunohistochemical stains using histogenetic markers for germinal center (GC) B cells, late GC and post-GC B cells, and post-GC B cells were performed on paraffin-embedded samples. Morphologically, 14 cases were polymorphic; 12 were monomorphic. Histogenetic marker expression was as follows: 1 monomorphic case (4%), GC phenotype expressing bcl-6 and CD10; 17 cases (65%; polymorphic, 9; monomorphic, 8), late GC–early post-GC phenotype expressing MUM1/IRF4; 8 cases (31%; polymorphic, 5; monomorphic, 3), post-GC phenotype expressing MUM1/IRF4 and CD138 but not bcl-6. PTLD cases after HSCT more frequently were post-GC phenotype than after SOT (7/15 vs 1/11, respectively; P = .040) and were independent of morphologic subclassification. Results suggest that most PTLDs are late GC–early post-GC phenotype with a minor group of post-GC phenotype and rare cases of GC phenotype.
Findings also suggest a correlation between histogenetic phenotype of B-cell PTLD and type of transplantation.CYTOGENETIC CHANGES
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized.
We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)-like lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein-Barr virus infection status, and clinical outcome.
Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM-like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome.
We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD.EPSTEIN-BARR VIRUS
*Department of Pathology, Divisions of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, PA daggerTransplantation and Hepatic Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
The heterogeneity of the posttransplant lymphoproliferative disorders (PTLDs) is well recognized. However, in contrast to other immunodeficiency-associated lymphomas or diffuse large B-cell lymphomas in general, studies of the histogenetic spectrum of the large category of monomorphic B-cell cases have been more limited, produced conflicting results, and have paid little attention to the impact of Epstein-Barr virus (EBV).
Therefore, 30 monomorphic B-cell PTLD from 27 patients were analyzed using EBER in situ hybridization for EBV and a panel of antibodies directed against CD20, CD3/bcl-6, CD10, MUM-1/IRF4, CD138, and bcl-2. The results were correlated with the histopathologic features and clinical outcome. All PTLD were CD20 with 23% CD10, 53% bcl-6, 67% MUM-1/IRF4, 13% CD138, 83% bcl-2 and 67% EBV. 30% of the PTLD had a germinal center (GC) profile (CD10, bcl-6, MUM-1/IRF4, CD138), 53% a "late GC/early post-GC" profile (CD10, bcl-6, MUM-1/IRF4, CD138), 13% a post-GC profile (CD10, bcl-6, MUM-1/IRF4, CD138) and 3% an indeterminate profile (all markers negative). EBV positivity was associated with MUM-1/IRF4 expression (P=0.005) and with a non-GC phenotype (P=0.01). All CD138 cases were EBV. The cases with a GC phenotype were the most likely to resemble transformed GC cells (P=0.023). No statistically significant survival differences could be documented between those with a GC versus non-GC phenotype.
These results highlight the broad histogenetic spectrum of monomorphic B-cell PTLD. They demonstrate the association of EBV positivity with a non-GC phenotype and suggest that EBV PTLD are more like lymphomas that arise in immunocompetent individuals. The lack of a demonstrable correlation with survival may relate to the relatively small number of cases studied.N Engl J Med 1992;327:1710–1714
- Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder following lung transplantation is more commonly of host origin.
Peterson MR, Emery SC, Yung GL, Masliah E, Yi ES.
Department of Pathology, University of California, Medical Center, San Diego, CA 92103-8720, USA.
Arch Pathol Lab Med. 2006 Feb;130(2):176-80. Abstract quote
CONTEXT: Posttransplantation lymphoproliferative disorder (PTLD) in patients who have undergone solid organ transplantation is thought to be mostly of host (ie, transplant recipient) origin, as opposed to being predominantly of donor origin, which is observed in patients who have undergone bone marrow transplantation. Donor-origin PTLDs reportedly follow a more indolent course than host-origin PTLDs.
OBJECTIVE: To determine the origin of PTLD and its clinical implications in patients who have undergone lung transplantation.
DESIGN: Patients' medical records were reviewed for clinical data. We performed a molecular study to determine the origin of abnormal lymphoid cells in 4 PTLD cases identified from our autopsy files. Each case underwent restriction fragment length polymorphism analysis using polymerase chain reaction-based genotyping for CYP2D6. Epstein-Barr virus (latent membrane protein 1) immunostaining and polymerase chain reaction analysis were performed on PTLD-involved tissues.
RESULTS: Three of 4 PTLD cases were of host origin, and the remaining case was of donor origin. Epstein-Barr virus was detected by immunohistochemical and polymerase chain reaction methods in all PTLD-involved tissues that were examined. There was no apparent difference in clinical manifestations between host-origin and donor-origin PTLD cases in our study.
CONCLUSIONS: The PTLDs in our patients who had undergone lung transplantation were Epstein-Barr virus-positive and mostly of host origin, without any notable clinical difference from donor-origin PTLD.
Frequent expression of the tumor necrosis factor receptor–associated factor 1 in latent membrane protein 1–Positive posttransplant lymphoproliferative disease and HIV-associated lymphomas
Paul G. Murray, PhD
Lode J. Swinnen, MD
Joanne R. Flavell, BSc
Margaret V. Ragni, MD
Karl R.N. Baumforth, PhD
Siobhan M. Toomey
Alexandra H. Filipovich, MD
Derek Lowe, PhD
Carrie S. Schnell, BA
Jewel Johl, BA
Margaret Gulley, MD
Lawrence S. Young, PhD
Richard F. Ambinder, MD, PhDHum Pathol 2001;32:963-969 Abstract quote
The tumor necrosis factor receptor–associated factor 1 (TRAF1) participates in the signal transduction of various members of the tumor necrosis factor receptor (TNFR) family, including TNFR2, CD40, CD30, and the Epstein-Barr virus (EBV)–encoded latent membrane protein 1 (LMP1). In vitro, TRAF1 is induced by LMP1, and previous studies have suggested that expression of TRAF1 is higher in EBV-associated tumors than in their EBV-negative counterparts.
To determine whether this was the case in posttransplant lymphoproliferative disease (PTLD) and related disorders, we used immunohistochemistry to analyze expression of TRAF1 in a total of 42 such lesions arising in a variety of immunosuppressive states. The specimens consisted of 22 PTLD lesions, 18 acquired immunodeficiency syndrome–associated lymphomas, including 6 primary central nervous system lymphomas, and 2 cases of Hodgkin disease.
The presence of latent EBV infection was determined by EBER in situ hybridization, and expression of EBV-LMP1 was detected by immunohistochemistry. Latent EBV infection, as determined by a positive EBER signal, was detected in 36 of 42 tumors.
Of the EBER-positive specimens, 30 of 36 also expressed LMP1. Twenty-four of 30 LMP1-positive tumors, including both Hodgkin disease specimens, expressed TRAF1, compared with only 3 of 12 LMP1-negative tumors. This difference was statistically significant (P < .005).
These results show frequent expression of TRAF1 at the protein level in LMP1-positive PTLD and related disorders and suggest an important role for LMP1-mediated TRAF1 signaling in the pathogenesis of EBV-positive tumors arising in immunosuppressive states.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION VARIANTS CNS Primary Central Nervous System Posttransplant Lymphoproliferative Disorders
Amilcar A. Castellano-Sanchez, MD, Shiyong Li, MD, PhD, Jiang Qian, MD, PhD, Anand Lagoo, MD, PhD, Edward Weir, MD, and Daniel J. Brat, MD, PhDAm J Clin Pathol 2004;121:246-253 Abstract quote
Posttransplant lymphoproliferative disorders (PTLDs) represent a spectrum ranging from Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV+ or EBV– malignant lymphomas. Central nervous system (CNS) PTLDs have not been characterized fully.
We reviewed the clinical, radiologic, and pathologic features of 12 primary CNS PTLDs to define them more precisely. Patients included 10 males and 2 females (median age, 43.4 years) who were recipients of kidney (n = 5), liver (n = 2), heart (n = 2), peripheral blood stem cells (n = 2), or bone marrow (n = 1). All received immunosuppressive therapy. CNS symptoms developed 3 to 131 months (mean, 31 months) after transplantation. By neuroimaging, most showed multiple (3 to 9) intra-axial, contrast-enhancing lesions. Histologic sections showed marked expansion of perivascular spaces by large, cytologically malignant lymphoid cells that were CD45+, CD20+, EBV+ and showed light chain restriction or immunoglobulin gene rearrangement.
In distinction to PTLDs in other organ systems, CNS PTLDs were uniformly high-grade lymphomas that fulfilled the World Health Organization criteria for monomorphic PTLDs. Extremely short survival periods were noted for each CNS PTLD that followed peripheral blood stem cell transplantation. Survival of others with CNS PTLD varied; some lived more than 2 years.CTCL
- Primary cutaneous T-cell lymphoma occurring after organ transplantation.
Ravat FE, Spittle MF, Russell-Jones R.
Department of Dermatology, Addenbrooke's NHS Trust, Cambridge, United Kingdom.
J Am Acad Dermatol. 2006 Apr;54(4):668-75. Abstract quote
Lymphoma occurring after organ transplantation has been well described. The majority of cases are B-cell lymphomas and are usually associated with Epstein-Barr virus. Only a minority of posttransplant lymphomas are of T-cell origin, and primary cutaneous T-cell lymphoma (CTCL) is extremely rare.
In this article, we report a case of cutaneous peripheral T-cell lymphoma, pleomorphic CD30+ large-cell type, and review the literature relating to posttransplant primary CTCL. Of the 23 cases of posttransplant primary CTCL, 5 patients had erythrodermic disease, and 8 had primary cutaneous anaplastic large cell lymphoma. In addition, there are two cases of mycosis fungoides, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of CD30+ lymphomatoid papulosis, and 6 cases of peripheral T-cell lymphoma, of which 3 were CD30+ large cell lymphomas.
Seventeen cases had renal transplants and the majority received both cyclosporine and azathioprine. No consistent viral association was noted among these cases. The sex ratio was 18:5 (male/female), and the mean age at diagnosis was 53 years. Mean time from transplantation to diagnosis is 6.4 years and mean survival time from diagnosis is 14.5 months.
The prognoses normally associated with particular subsets of CTCL do not apply in the posttransplant setting.Posttransplant primary cutaneous T-cell lymphoma
Holly A. Ward,etal.
J Am Acad Dermatol 2001;44:675-80 Abstract quote
A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities.
Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms.
Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.
HYPOPHARYNX Epstein-Barr virus–associated extranodal NK/T-cell lymphoma, nasal type of the hypopharynx, in a renal allograft recipient: Case report and review of literature
Sylvia Stadlmann, MD
Falko Fend, MD
Patrizia Moser, MD
Peter Obrist, MD
Richard Greil, MD
Stephan Dirnhofer, MDHum Pathol 2001;32:1264-1268. Abstract quote
Posttransplant lymphoproliferative disorders (PTLPDs) are predominantly B-cell lymphoproliferations, whereas a T-cell origin is rarely observed. In contrast to B-cell PTLPD, T-cell PTLPDs show an inconsistent association with Epstein-Barr virus (EBV). Until now, only 13 cases of EBV-associated T-cell PTLPDs have been reported.
We describe a case of an EBV-associated T-cell PTLPD in a renal allograft recipient 2 years after transplantation. Histologic examination showed medium- to large-sized lymphoid cells with an angiocentric growth pattern and necrosis. The atypical cells showed a CD2+, CD3+, CD7+, CD43+, CD45R0+, CD56+, and CD4–, CD5–, CD8– F1- phenotype with expression of the latent membrane protein (LMP)-1 of EBV. In addition, EBV-specific RNAs (EBER 1/2) were identified by in situ hybridization. Molecular analysis of the T-cell receptor (TCR) chain by polymerase chain reaction (PCR) showed a polyclonal pattern. The morphologic, immunohistochemical, and molecular findings were consistent with a diagnosis of an EBV-associated extranodal natural killer (NK)/T-cell non-Hodgkin lymphoma (NHL) of nasal type.
To our knowledge, this is the first reported case of this rare entity in the posttransplant setting.
LIVER
A Report of Three Cases and a Review of the LiteratureJ. Dean Nuckols, M.D., Ph.D.; Pedro W. Baron, M.D.; Timothy T. Stenzel, M.D., Ph.D.; Babatunde A. Olatidoye, M.D., M.S.; Janet E. Tuttle-Newhall, M.D.; Pierre-Alain Clavien, M.D., Ph.D.; David N. Howell, M.D., Ph.D.
From Duke University Medical Center Departments of Pathology (J.D.N., T.T.S., B.A.O., D.N.H.) and Surgery (P.W.B., J.E.T.-N., P.-A.C.), and Durham Veterans Affairs Medical Center (D.N.H.).
Am J Surg Pathol 2000;24:733-741 Abstract quote Post-transplantation lymphoproliferative disease (PTLD) is a complication of solid organ transplantation that is typically of B-cell origin and associated with Epstein-Barr virus (EBV).
In patients receiving orthotopic liver transplantation (OLT) and treated with cyclosporin A, PTLD typically presents between 6 and 17 months post-transplantation as a systemic illness with involvement of the hepatic graft in a minority of cases. A small number of cases of biopsy-proven PTLD arising in the hepatic graft and limited to the liver and periportal structures have been previously reported.
This report describes three additional cases of liver-localized PTLD and reviews similar cases in the literature. The donor/host origin of PTLD may have prognostic significance because the two cases in this report that are of donor origin had different clinical and pathologic features compared with the case of host origin. A rapid PCR-based technique for determining the origin of PTLD is described.
Am J Surg Pathol 2001;25:324-330
Allograft liver biopsy specimens (n = 24) obtained in the clinical setting of primarily extrahepatic posttransplant lymphoproliferative disease (PTLD) were studied for histopathology, lymphocyte subsets, and Epstein-Barr virus (EBV)–encoded EBER RNA.
Acute rejection was found in 20 (83.3%) of 24 biopsy specimens and graded as indeterminate in 7 (35%) of 20 (35%), mild in 3 (15%) of 20, and moderate in 10 (50%) of 20 cases. EBV hepatitis was the primary diagnosis in two biopsy specimens and a secondary finding in six others. Four biopsy specimens showed nonspecific reactive hepatitis, and five showed recurrence of primary liver disease.
Immunoperoxidase staining showed primarily T cells. EBER RNA was detected in 14 (58.3%) of 24 biopsy specimens: 12 (60%) of 20 with and 2 (50%) of 4 without acute rejection.
Antirejection therapy resulted in complete or partial response in 4 (36.3%) of 11 and 7 (63.7%) of 11 treated cases, respectively, despite the presence of EBV-infected cells in some tissues. Subsequent follow-up showed early or late chronic rejection in 6 (25%) of 24 patients. Gamma glutamyl transferase, a marker for early or late chronic rejection, was greater than five times the upper limit of normal in 9 (37.5%) of 24 patients.
Conclusion:
Liver biopsy specimens in patients with PTLD show a spectrum of pathologic changes. Rejection may be treated even if EBV is concurrently present. Long-term graft is suboptimal, because low immunosuppression results in a tendency to develop chronic rejection.LUNG
Posttransplant lymphoproliferative disorders in lung transplant patients: the cleveland clinic experience.Ramalingam P, Rybicki L, Smith MD, Abrahams NA, Tubbs RR, Pettay J, Farver CF, Hsi ED.
Departments of Clinical Pathology (PR, MDS, NAA, RRT, JP, EDH), Anatomic Pathology (CFF), and Biostatistics (LR), Cleveland Clinic Foundation, Cleveland Ohio.
Mod Pathol 2002 Jun;15(6):647-56 Abstract quote PTLD is a well-recognized complication of organ transplantation. Large series of heart, renal, and liver transplants have been examined for the incidence and behavior of PTLD. However, reports of the incidence and characteristics of PTLDs in lung transplant (LTx) patients are few.
We report our experience with PTLDs in a large series of LTx recipients at a single institution and compare them to other solid organ transplant recipient PTLDs seen at our institution. Twenty-eight patients were found to have PTLD, of whom 8 were lung transplant recipients. We evaluated nine PTLD specimens from these 8 patients for their histology, immunophenotype (CD20, CD3, EBV-LMP1), EBER status by in situ hybridization, and clinical features. The incidence of PTLD was 3.3% (8/244 patients). The time to development of PTLD, after transplant, was short (median time, 7 mo). All were of B-cell lineage. Overall, EBV was demonstrated in 77.7% (7 of 9 specimens) of PTLDs. All specimens tested for clonality were found to be monoclonal. Five patients died, with a median time to death of only 4.6 months. PTLDs in LTx patients are EBV-associated B-cell, predominantly monoclonal lymphoid lesions similar to other solid organ transplant PTLDs. Compared with other solid organ transplant recipients with PTLD at our institution, PTLDs in LTx patients have a propensity to involve the transplanted organ (P =.001, Fisher's exact test), occur earlier after transplant (P =.003, Wilcoxon test), and have a shorter survival (P =.002, log rank test). Reasons for this may include the relatively higher level of immunosuppression required in these patients and limited options in decreasing it.
Although the incidence is low, careful early monitoring of lung transplantation patients is warranted because of the poor prognosis of patients developing this complication.
SKIN
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195-6100, USA.
Post-transplant lymphoproliferative disorder (PTLD) is a lymphoid proliferation that develops as a complication of solid organ or bone marrow transplants. Most cases usually present in the gastrointestinal tract, liver, kidney or lymph nodes. Plasmacytoma-like PTLD is an uncommon variant, and presentation in the skin is exceedingly rare.
We present a case of plasmacytoma-like PTLD presenting as a leg mass in a 58-year-old male. Biopsy from the lesion exhibited atypical plasmacytoid and plasmablastic cells that showed lambda light chain restriction and stained positive for CD138 and Epstain-Bar virus early RNA by in situ hybridization. These findings were diagnostic of plasmacytoma-like PTLD.
Only a few similar cases have been reported in the literature. The majority of these cases occurred in heart and kidney transplant patients. To our knowledge, this is the first reported case to occur in a lung transplant patient.
- Localized cutaneous posttransplant Epstein-Barr virus-associated lymphoproliferative disorder.
Capaldi L, Robinson-Bostom L, Kerr P, Gohh R.
Departments of Dermatology, Brown Medical School, Providence, Rhode Island 02903, USA.
J Am Acad Dermatol. 2004 Nov;51(5):778-80. Abstract quote
Localized cutaneous posttransplant lymphoproliferative disorder is a rare complication of solid organ transplantation.
Biopsies demonstrate diffuse dermal proliferations of atypical lymphocytes with variable Epstein-Barr virus latent membrane protein-1 expression. Extracutaneous involvement is absent.
Clinical and Pathological Features of Posttransplantation Lymphoproliferative Disorders Presenting With Skin Involvement in 4 Patients
David P. Beynet, MS ;Sue A. Wee, MD ;Steven S. Horwitz, MD ;Sabina Kohler, MD ;Sandra Horning, MD ;Richard Hoppe, MD ;Youn H. Kim, MD
From the Departments of Dermatology (Mr Beynet and Drs Wee and Kim), Medicine (Drs Horwitz and Horning), Pathology (Dr Kohler), and Radiation Oncology (Dr Hoppe), Stanford University School of Medicine, Stanford, Calif. The authors have no relevant financial interest in this article.Arch Dermatol. 2004;140:1140-1146. Abstract quote
Background Posttransplantation lymphoproliferative disorders (PTLDs) are lymphoid proliferations that can develop in recipients of solid organ or allogeneic bone marrow transplants. They are clinically and pathologically heterogeneous and range from polyclonal hyperplastic lesions to malignant lymphomas. Although extranodal involvement in PTLD is common, cutaneous presentation is rare, with only 19 cases reported previously.Observations We describe 4 patients with cutaneous presentations of PTLD. All patients had relatively late-onset PTLD (>1 year after transplantation) with a median of 8 years from organ allograft to tumor diagnosis. The extent, number, and anatomic location of skin lesions varied from a localized patch to widespread nodules. None of the patients exhibited systemic symptoms at the time of PTLD diagnosis. Pathological findings ranged from plasmacytic hyperplasia to monomorphic PTLD. In situ hybridization detected Epstein-Barr virus messenger RNA in all 3 cases with evaluable tissue. All patients underwent reduction in immunosuppressive therapy and received other individualized treatments. Median follow-up was 2.5 years. At the most recent follow-up, 3 patients were in complete remission and 1 had residual disease.
Conclusions In this study, PTLD lesions presenting in the skin responded to therapy. Despite their relatively late occurrence after transplantation, most of these cases were positive for Epstein-Barr virus. As observed with other cutaneous lymphomas, the PTLDs with predominant skin involvement had a relatively favorable outcome.
Post-transplant lymphoproliferative disorder limited to the skin.
Samolitis NJ, Bharadwaj JS, Weis JR, Harris RM.
Departments of Dermatology and Hematology-Oncology, University of Utah, Salt Lake City, USA.
J Cutan Pathol. 2004 Jul;31(6):453-7. Abstract quote
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a condition affecting immunosuppressed transplant patients and has a variety of clinical presentations. It is rarely found in the skin, and cases of PTLD in the skin are usually linked with lymph node or other organ involvement.
METHODS: We report a case of plasmacytoid PTLD that is limited to the skin. A 63-year-old man with a history of cardiac transplant presented with exophytic tumors involving the lower extremity. The diagnosis and classification of the various forms of PTLD are discussed.
RESULTS: Histology, immunohistochemical stains, and in situ hybridization revealed an aggressive plasmacytoid tumor that was Epstein-Barr virus positive. The patient's tumors resolved with decreased immunosuppression and localized radiation.
CONCLUSION: This case is unusual for several reasons including involvement limited to the skin, presentation 15 years following transplant, and plasmacytoid phenotype of the tumor. This disorder will likely be seen by dermatologists and dermatopathologists with the increasing use of immunosuppressive medications in the dermatologist's patient population.
HISTOLOGICAL TYPES CHARACTERIZATION General Semin Diagn Pathol 1997;14:8–14.
Workshop sponsored by the Society for Hematopathology, a classification scheme for PTLD was proposed that divides these lesions into 4 groups:
early lesions, polymorphic PTLD, monomorphic PTLD, and other types.Early lesions include lesions previously described as plasmacytic hyperplasia, atypical lymphoid hyperplasia, and infectious mononucleosis-like PTLD by others
This group is less clinically aggressive than other PTLD types and is characterized histologically by at least partial architectural preservation, although immunoblasts or small (EBV-positive) oligoclonal or monoclonal B-cell populations may be present.
The polymorphic PTLD group includes lesions previously designated as polymorphic B-cell hyperplasia, polymorphic B-cell lymphoma, and polymorphic PTLD by others
This group is characterized by architectural effacement in lymph nodes or extranodal sites by a population of cells that exhibits a full range of B-cell maturation, but necrosis, immunoblasts, and numerous mitotic figures may be present.
Monomorphic PTLDs resemble high-grade lymphoma histologically
An important feature in making the diagnosis of monomorphic PTLD is that the majority of cells are large and immature (blastlike), in contrast to the full range of maturation observed in polymorphic PTLD
Monomorphic PTLDs tend to behave more aggressively than other PTLD types.
VARIANTS CD30 POSITIVE
Department of Pathology, Weill Medical College Cornell University, New York, NY, USA.
Background: Post-transplant lymphoproliferative disease (PTLD) is a recognized complication of the immunosuppressive regimens associated with solid organ transplantation. The vast majority of these lesions represent monomorphic B-cell lymphoproliferative disease. Rarely, however, T-cell malignancies may emerge, the commonest being anaplastic large-cell lymphoma (ALCL).
Materials and methods: We describe two patients who developed a post-transplant ALCL several years after transplantation. Comprehensive phenotypic and molecular studies were conducted. The technique of capillary gel electrophoresis was employed.
Results: One patient died of unrelated causes, while the other patient did achieve clinical remission. The neoplastic cell populace was composed of CD4-positive cytotoxic T cells exhibiting CD30 positivity. There were very few B cells. Striking and prominent clonally restricted infiltrates were identified whereby there was both a heavy chain and T-cell beta gene rearrangement. There was no evidence of lytic Epstein-Barr virus (EBV) infection.
Conclusion: T-cell-associated PTLD does not appear to be directly attributable to EBV infection. Iatrogenic immune dysregulation may result in excessive T-cell proliferation to various antigenic stimuli, hence resembling other drug-associated cell lymphoproliferative conditions such as angioimmunoblastic lymphadenopathy. The dual rearrangement may have some implications regarding the cell of origin.Anaplastic Large Cell Lymphoma Associated With Epstein-Barr Virus Following Cardiac Transplant Pitman, Sean D MD*; Rowsell, Edward H MD, PHD*; Cao, Jeffrey D MD*; Huang, Qin MD, PHD†; Wang, Jun MD*
From the *Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, CA; and the †Department of Anatomic Pathology, City of Hope National Medical Center, Duarte CA
American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 410-415 Abstract quote Posttransplantation lymphoproliferative disorders (PTLDs) eventually occur in approximately 5% of all organ transplant recipients. Most of cases are B-cell proliferations associated with the Epstein-Barr virus (EBV). T-cell PTLDs are relatively rare, although some estimate that up to 14% of posttransplantation malignant lymphomas are T-cell lymphomas even though only a few of these cases are described in the literature.
A literature review found only 77 cases of T-cell PTLD, including 1 case following cardiac transplant, 15 cases associated with EBV, and only 1 case of anaplastic large cell lymphoma (ALCL). This single ALCL case followed a liver transplant, was of the T-cell phenotype, and was EBV negative. In this report, we describe a 14-year-old male who developed an EBV-positive, T-cell PTLD of the ALCL subtype after a period of 14 years following cardiac transplant. Immunohistochemical staining established the T-cell origin of the neoplasm with strong expression of CD45, CD3, CD43, and CD2 and also showed expression of CD30 consistent with the histologic features that suggested ALCL. EBER in situ hybridization detected the presence of the EBV. Polymerase chain reaction analysis for T-cell receptor-gamma gene rearrangements confirmed the T-cell lineage of this lymphoma.
To our knowledge, this is the first reported case of an EBV-positive T cell lymphoma of the anaplastic large cell subtype following organ transplant.
Posttransplant CD30+ (Ki-1) anaplastic large cell lymphoma: a case report and review of the literature.Lee LY, Harpaz N, Strauchen JA.
Mount Sinai Medical Center, Department of Pathology, New York, NY 10029, USA.
Arch Pathol Lab Med 2003 Mar;127(3):349-51 Abstract quote Posttransplant CD30(+) (Ki-1) anaplastic large cell lymphoma (ALCL) is rare. A review of the literature revealed only 3 such cases. All 3 cases were developed after single-organ transplantation.
We describe CD30(+) (Ki-1) ALCL in a dual-organ (liver and heart) transplantation recipient. The patient was a 68-year-old white female who underwent an orthotopic heart transplantation in 1999 and a liver transplantation in 2000. She presented with nausea and was found to have CD30(+) (Ki-1) ALCL by pathologic examination of the gastric antrum biopsy specimen.
To our knowledge, this patient represents the first reported case of posttransplant CD30(+) ALCL following a dual-organ transplantation.
EPSTEIN-BARR NEGATIVE Epstein–Barr Virus-Negative Post-Transplant Lymphoproliferative Disorders A Distinct Entity?
Beverly P. Nelson, M.D.; Michael A. Nalesnik, M.D.; David W. Bahler, M.D., Ph.D.; Joseph Locker, M.D., Ph.D.; John J. Fung, M.D., Ph.D.; Steven H. Swerdlow, M.D.
From the Departments of Pathology (B.P.N., M.A.N., D.W.B., J.L., S.H.S.) and Surgery (J.J.F.), University of Pittsburgh School of Medicine, Pittsburgh, PA; and the Department of Pathology (B.P.N.), University of South Alabama College of Medicine, Mobile, AL, U.S.A.
Am J Surg Pathol 2000;24:375-385 Abstract quote
Post-transplant lymphoproliferative disorders (PTLDs) are usually but not invariably associated with Epstein-Barr virus (EBV). The reported incidence, however, of EBV-negative PTLDs varies widely, and it is uncertain whether they should be considered analogous to EBV-positive PTLDs and whether they have any distinctive features.
Therefore, the EBV status of 133 PTLDs from 80 patients was determined using EBV-encoded small ribonucleic acid (EBER) in situ hybridization stains with or without Southern blot EBV terminal repeat analysis. The morphologic, immunophenotypic, genotypic, and clinical features of the EBV-negative PTLDs were reviewed, and selected features were compared with EBV-positive cases.
Twenty-one percent of patients had at least one EBV-negative PTLD (14% of biopsies). The initial EBV-negative PTLDs occurred a median of 50 months post-transplantation compared with 10 months for EBV-positive cases. Although only 2% of PTLDs from before 1991 were EBV negative, 23% of subsequent PTLDs were EBV negative (p <0.001). Of the EBV-negative PTLDs, 67% were of monomorphic type (M-PTLD) compared with 42% of EBV-positive cases (p <0.05). The other EBV-negative PTLDs were of infectious mononucleosis-like, plasma cell-rich (n = 2), small B-cell lymphoid neoplasm, large granular lymphocyte disorder (n = 4) and polymorphic (P) types. B-cell clonality was established in 14 specimens and T-cell clonality was established in three (two patients). None of the remaining specimens were studied with Southern blot analysis and some had no ancillary studies. Rearrangement of c-MYC was identified in two M-PTLDs with small noncleaved-like features, and rearrangement of BCL-2 was found in one large noncleaved-like M-PTLD. Ten patients were alive at 3 to 63 months (only three patients received chemotherapy). Seven patients, all with M-PTLDs, are dead at 0.3 to 6 months.
Therefore, EBV-negative PTLDs have distinct features, but some do respond to decreased immunosuppression, similar to EBV-positive cases, suggesting that EBV positivity should not be an absolute criterion for the diagnosis of a PTLD.
HODGKIN LYMPHOMA-LIKE
- Hodgkin Lymphoma-Like Posttransplant Lymphoproliferative Disorder (HL-Like PTLD) Simulates Monomorphic B-Cell PTLD Both Clinically and Pathologically.
Pitman SD, Huang Q, Zuppan CW, Rowsell EH, Cao JD, Berdeja JG, Weiss LM, Wang J.
Departments of *Pathology and Laboratory Medicine and daggerMedicine, Loma Linda University Medical Center, Loma Linda, CA double daggerDepartment of Anatomic Pathology, City of Hope National Medical Center, Duarte, CA.
Am J Surg Pathol. 2006 Apr;30(4):470-476. Abstract quote
Although Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder (HL-like PTLD) has been grouped with classic Hodgkin lymphoma type PTLD (HL-PTLD), controversy remains as to whether it is truly a form of HL or whether it should be more appropriately classified as a form of B-cell PTLD. Because only few cases of HL-like PTLD have been reported, their pathologic nature and clinical behavior have not been well defined.
This report characterized 5 cases of HL-like PTLD with respect to their immunophenotype, EBV status, clonality, and clinical outcome. All of the patients were male, with ages ranging from 1.5 to 55 years at diagnosis. PTLD developed from 4 months to 6 years following solid organ transplantation (3 hearts, 1 kidney, 1 liver), and involved both nodal and extranodal sites. All were EBV-related (EBER+) with the large neoplastic cells CD20/CD79a positive but CD15 negative. Immunoglobulin gene rearrangements were detected in 3 of 5 tested. All patients were managed by initial reduction/withdrawal of immunosuppression, with 2 also receiving chemotherapy for non-HL. Three patients died of progressive disease within 2 to 3 months after diagnosis, 1 is alive and well 2 years later, and the fifth was disease free but died of unrelated causes (graft coronary disease) 2 years later.
We conclude that, although HL-like PTLD morphologically simulates classic HL PTLD, there are important immunophenotypic, molecular genetic, and clinical differences, suggesting it is in fact most often a B-cell PTLD. Distinction between HL and HL-like PTLD may be important for clinical management and prognosis.
- Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder.
Semakula B, Rittenbach JV, Wang J.
Department of Pathology and Laboratory Medicine, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
Arch Pathol Lab Med. 2006 Apr;130(4):558-60. Abstract quote
Posttransplantation lymphoproliferative disorders (PTLD) are a heterogeneous group of monoclonal or polyclonal lymphoproliferative lesions that occur in immunosuppressed recipients following solid organ or bone marrow transplantation, including 4 categories: (1) early lesions (reactive plasmacytic hyperplasia, and infectious-mononucleosis-like PTLD), (2) polymorphic PTLD, (3) monomorphic PTLD (including B-cell neoplasms and T-cell neoplasms), and (4) Hodgkin lymphoma (HL) and HL-like PTLD in the current World Health Organization classification.
Although HL-like PTLD has been grouped with classic HL PTLD, controversy remains as to whether it is truly a form of HL or whether it should be more appropriately considered as a form of B-cell PTLD.
The current available literature data indicate the presence of important immunophenotypic, molecular genetic, and clinical differences between HL PTLD and HL-like PTLD, suggesting that HL-like PTLD is in fact most often a form of B-cell PTLD. Distinction from true HL may be important for clinical management and prognosis.LYMPHOMATOID GRANULOMATOSIS-LIKE
- Posttransplantation lymphoproliferative disease with features of lymphomatoid granulomatosis in a lung transplant patient.
Kwon EJ, Katz KA, Draft KS, Seykora JT, Rook AH, Wasik MA, Junkins-Hopkins JM.
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Am Acad Dermatol. 2006 Apr;54(4):657-63. Abstract quote
A 58-year-old lung transplant patient developed worsening shortness of breath and indurated erythematous plaques on the lower left leg. A skin biopsy specimen revealed a dense angiocentric and angioinvasive infiltrate in the mid to reticular dermis and panniculus containing large, atypical lymphocytes with convoluted nuclei and prominent nucleoli.
Immunohistochemical stains showed that the atypical cells were of B-cell origin, and that Epstein-Barr virus was present. Molecular studies demonstrated B-cell clonality. The patient was successfully treated with rituximab. The clinical and pathologic features in this case represent posttransplantation lymphoproliferative disease with features of lymphomatoid granulomatosis.
The case also highlights the importance of clinical and pathologic examination of cutaneous lesions in the evaluation of lymphoproliferative disorders for patients undergoing transplantation.PLASMACYTIC
Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder with monoclonal serum protein occurring in solid organ transplant recipients.
Sun X, Peterson LC, Gong Y, Traynor AE, Nelson BP.
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mod Pathol. 2004 Apr;17(4):389-94. Abstract quote
Post-transplant lymphoproliferative disorders are mostly Epstein-Barr virus-related, B-cell tumors that develop as a consequence of immunosuppressive therapy in recipients of solid organ or bone marrow transplants. These disorders range from reactive, polyclonal plasmacytic hyperplasia to those that are morphologically and genotypically indistinguishable from typical non-Hodgkin's lymphomas. Plasma cell myeloma occurring after solid organ transplantation is rare.
We report three plasma cell myeloma post-transplant lymphoproliferative disorder cases and one polymorphic, monoclonal post-transplant lymphoproliferative disorder case associated with a monoclonal serum protein. All three plasma cell myeloma post-transplant lymphoproliferative disorder cases had clinical, radiologic, and pathologic features of conventional plasma cell myeloma. The one polymorphic post-transplant lymphoproliferative disorder case was associated with an IgM monoclonal serum protein and was morphologically indistinguishable from a lymphoplasmacytic lymphoma. Three of the four cases, including the one polymorphic post-transplant lymphoproliferative disorder case, were positive for Epstein-Barr virus encoded small RNA by in situ hybridization. One patient died of plasma cell myeloma post-transplant lymphoproliferative disorder. The remaining three patients are alive: two are completely free of post-transplant lymphoproliferative disorder, and one has shown partial response to therapy.
We compare the clinicopathologic features of these cases with those in the literature.
Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.Dunphy CH, Galambos C, Polski JM, Evans HL, Gardner LJ, Grosso LE, Montone KT.
Division of Hematopathology, St Louis University Health Sciences Center, Mo, USA.
Arch Pathol Lab Med 2002 Mar;126(3):351-6 Abstract quote Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case.
We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.
T-CELL
- T-cell Posttransplant Lymphoproliferative Disorder Occurring in a Pediatric Solid-organ Transplant Patient.
Lundell R, Elenitoba-Johnson KS, Lim MS.
*Department of Pathology, University of Utah, and the daggerARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT.
Am J Surg Pathol. 2004 Jul;28(7):967-973. Abstract quote
Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication seen in transplant patients as a consequence of immunosuppressant therapy. Most cases are of B-cell origin and are commonly associated with Epstein-Barr virus (EBV) infection. T-cell PTLDs are rare and only 13 pediatric T-cell PTLDs with clinicopathologic correlation have been reported previously.
We present the histologic, immunophenotypic, and molecular features of a monomorphic PTLD (T-cell lymphoma) identified in a pediatric patient following orthotopic liver transplantation. The lymphoma was identified in the ileum, rectum, and mesenteric lymph nodes. In situ hybridization revealed numerous EBER-1-positive tumor cells.
A current review of the literature is also discussed. Of the 14 cases of pediatric T-cell PTLD reported in the literature, only 3 (21.4%) are described as being EBV positive. Most of the reported PTLDs are monoclonal, with 9 of 11 cases (82%) showing a clonal T-cell population by gene rearrangement studies. T-cell PTLD cases appear to have a poor prognosis (11 of 14 patients died of the disease), although patients with involvement of specific anatomic sites may have a better outcome.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS REMISSION
Initial Spontaneous Remission of Posttransplantation Epstein Barr Virus-related B-Cell Lymphoproliferative Disorder of the Skin in a Renal Transplant Recipient: Case Report and Review of the Literature on Cutaneous B-Cell Posttransplantation Lymphoproliferative Disease.Blokx WA, Andriessen MP, Van Hamersvelt HW, Van Krieken JH.
Am J Dermatopathol 2002 Oct;24(5):414-22 Abstract quote Primary cutaneous posttransplantation B-cell lymphoproliferative disorder is rare. The few previously reported patients were all treated with surgery, radiotherapy, or lowering of immunosuppression.
We describe a 65-year-old woman presenting with an intermammary skin ulcer 21 years after renal transplantation, proving on biopsy to be an Epstein Barr virus (EBV)-related posttransplantation B-cell lymphoproliferative disorder. A few weeks later, the skin ulcer showed complete clinical regression. Hematologic staging evaluation showed no evidence of extracutaneous involvement. Despite continuation of immunosuppression, the patient stayed free of disease until 18 months after initial diagnosis, when she developed a progressive hemiparesis and died of acute myocardial infarction. At autopsy, a recurrent B-cell posttransplantation lymphoproliferative disorder in the left side of the thalamus region (measuring 1 x 0.8 cm) was established. The long interval between the primary cutaneous lesion and the localized brain recurrence supports primary skin posttransplantation lymphoproliferative disorder, especially because the patient was not treated for her posttransplantation lymphoproliferative disorder.
Review of the literature on primary cutaneous posttransplantation B-cell lymphoproliferative disorder and this case gives the impression that cutaneous posttransplantation B-cell lymphoproliferative disorders of B-cell lineage behave in a more benign manner than identical lesions arising extracutaneously. Because of the rare occurrence of posttransplantation B-cell lymphoproliferative disorder primarily involving the skin, extracutaneous origin should be excluded. If B-cell lineage can be established, EBV is present, alterations in oncogenes or tumor suppressor genes associated with malignant lymphoma are absent, and bcl-6 gene mutation associated with progression is absent, initially aggressive treatment might be avoided.
However, long-term clinical follow-up with prolonged maintenance therapy (reduction of immunosuppression or antiviral therapy) for prevention of recurrent posttransplantation lymphoproliferative disorder seems indicated, as is demonstrated by the case reported in the current study.
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