Prsentation Clinique / Clinical Setting

Patient de 26 ans, admis pour détransplantation rnale. 

Histoire et Antécédents :   

Greffe de rein en juillet 97 (donneur vivant sa mre) suite un diagnostic de maladie de Berger et hémodialyse de 3 mois. Insuffisance rénale progressive suite une infection CMV, la biopsie rénale montrant une fibrose interstitielle et une GNFS. 

Sinusite. Infection CMV post greffe (7/97), pp65 (-), sérologie parvov B 19  (+). Epanchement pleural bilatral, foyer de comblement alvéolaire basal avec drain thoracique gauche. 

Epaississement nodulaire latéro-trachéal droit.Biopsie de la masse latéro-brachiale : matériel tumoral, compatible avec un lymphome malin grandes cellules B, CD 20 (+)

Hemothorax complicant la biopsie, motive une thoracotomie. Une biopsie chirurgicale est réalisée.

Patient 26 yo male admitted for kidney detransplantation. History of progressive renal failure, CMV infection, bilateral pleural effusion, chronic and lately a right tracheal nodular thickening. The biopsy, poorly representative was suggestive a large B-cell lymphoma.

Left hemothorax appeared after the biopsy, imposing a thoracotomy. a surgical biopsy is performed.

Imagerie / Radiology

Pathologie / Pathology

Microscopie / Microscopy

La lame montre montre un nodule sous-pleural, et le faible grossissement ses limites.

The slide shows a sub-pleural nodule, circumscribed on the low power.

La lésion est caractérisée par une atteinte alvéolaire et un infiltrat interstitiel avec dépot fibrineux.

The lesion is alveolar with fibrinous deposits, and an interstitial infiltrate.

L'infiltrat est leucocytaire polymorphe, prédominance lymphocytaire pléomorphe.

The infiltrate is polymorphic, with a lymphocytic predominance, pleomorphic.

L'infiltrat comporte une composante de grandes cellules, sternbergoides, et présente par place une atteinte parietale vasculaire.

The infiltrate discloses a large cell component, Sternberg-like, and in some areas vascular wall invasion is observed.

Infiltration parieto-vasculaire (Verhoeff) Vascular infiltration (Elastic Stain)

Immunohistochimie / Immunohistochemistry

Une expression des cellules aux marqueurs T et B est observée.

Positivity to T and B cell markers is noted.

Les grandes cellules sont positives au CD20 (membrannaire) et au CD30 (membrannaire, et Golgienne).

The large cells show membranous positivity to CD20 and to CD30 (membrane and Golgi apparatus)

Positivit l'antigéne nuclaire de l'EBV (EBNA2), et  négativité (non concluante) de la LMP-1.

Positivity to EBV nuclear antigen (EBNA2), and non conclusive negativity to LMP-1.

La bcl2 objective une positivit hétérogéne. La p53 est négative. Il s'y associe une large composante de cellules macrophagiques (KP1).

bcl2 discloses an heterogenous positivity. p53 is negative. Numerous macrophages are also part of the infiltrate (KP1)

Diagnostic propos / Proposed diagnosis

Lsion lymphoprolifrative post-transplantation, type polymorphe.

Post-transplant lymphoproliferative disease, polymorphous type.

Evolution: Arrét de l'immunosuppression aprés la dtransplantation. Controle radiologique apérs 2 mois, disparition des lésions.

Followup: Immunosuppresive therapy halted after removal of the kidney. After 2 months, MRI shows absence of lesions.

Selected Abstracts

Br J Surg 2001 Oct;88(10):1330-4

Rising incidence of post-transplant lymphoproliferative disease in kidney transplant recipients.

Libertiny G, Watson CJ, Gray DW, Welsh KI, Morris PJ.

Oxford Transplant Centre, Churchill Hospital, Headington, Oxford, UK. gabor.libertiny@surgery.oxford.ac.uk

BACKGROUND: The purpose of this study was to determine whether the incidence of post-transplant lymphoproliferative disease (PTLD) has been increasing in renal transplant recipients in this centre. METHODS: Prospectively gathered data were analysed to establish trends in the epidemiology of PTLD in 1537 patients. RESULTS: Overall, PTLD occurred in 2.3 per cent of renal transplant recipients. An increase in its incidence coincided with the introduction of cyclosporin in the 1980s. However, there was a further increase in the incidence of PTLD in the 1990s when the only change in immunosuppressive policy was the abandonment of pretransplantation blood transfusion. The latter increase was particularly pronounced in patients with early-onset PTLD in whom it presented within 600 days after transplantation. CONCLUSION: The incidence of PTLD has been increasing in renal transplant recipients. The recent increase appears to be independent of cyclosporin and may reflect the reduction in pretransplant blood transfusion. Changes in the incidence of PTLD may also mirror changes in the epidemiology of non-Hodgkin lymphoma in the general population.

Pediatr Transplant. 2001 Aug;5(4):235-8.

Post-transplant lymphoproliferative disease in children.

Collins MH, Montone KT, Leahey AM, Hodinka RL, Salhany KE, Kramer DL, Deng C, Tomaszewski JE.

Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. colv5q@chmcc.org

Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.

Haematologica 2001 Jul;86(7):715-21

Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study in a single center.

Domingo-Domenech E, de Sanjose S, Gonzalez-Barca E, Romagosa V, Domingo-Claros A, Gil-Vernet S, Figueras J, Manito N, Oton B, Petit J, Granena A, Fernandez de Sevilla A. Department of Clinical Hematology, Institut Catala d'Oncologia, Barcelona, Spain. 31577edd@comb.es

BACKGROUND AND OBJECTIVES: To study the incidence, clinical presentation, pathologic features and outcome of post-transplant lymphomas (PTL) during the past 20 years. DESIGN AND METHODS: We undertook a descriptive study of all biopsy-proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999. Risk ratios were estimated by comparing the incidence of PTL among transplanted patients with that of lymphoma observed in the general population of the region. Survival analysis was performed at the univariate level using the Kaplan Meier technique and at the multivariate level by Cox hazard models. RESULTS: Seventeen of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was calculated to be almost 8-fold higher than the risk of lymphoma in the general population. The risk was highest among those who had received a heart transplant (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/- 29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The majority of patients with allograft involvement died within the 2 months following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). INTERPRETATION AND CONCLUSIONS: Organ transplantation is a major risk factor for the development of lymphoma, a disease with a particularly bad prognosis when it develops at the site of the allograft. Early diagnosis and more specific treatment may improve PTL survival.

Pediatr Transplant 2001 Jun;5(3):198-203

Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplant recipients, 1988-97: a Canadian multi-centre experience.

Allen U, Hebert D, Moore D, Dror Y, Wasfy S; Canadian PTLD Survey Group--1998. Department of Pediatrics, Divisions of Infectious Diseases, The Hospital for Sick Children, University of Toronto, Canada. upton.allen@sickkidson.ca

The aim of this work was to obtain information on the magnitude of the problem, disease characteristics, and clinical practices relating to post-transplant lymphoproliferative disease (PTLD) in Canadian institutions. Adult and pediatric Canadian solid organ transplant groups were sent a questionnaire between July and October 1998. Analyzable data were obtained from 33 transplant groups. For the period 1988-97, 90 cases of PTLD were seen among 4283 solid organ transplant recipients. The incidence of PTLD varied from 0 to 14.6%, with the highest rates in children. Lymph nodes were the sites most frequently affected. Among the classifiable lesions, the majority were monoclonal. The lesions were of B-cell origin in 42.2% and of T-cell in 15.6%. The lesions were classified as monomorphic in 31.1%, polymorphic 18.9%, and hyperplastic in 1.1%. Tumors were reported as low grade in 26.7% and high grade in 10%. The majority of patients (71.1%) received reduced immunosuppression. Anti-viral agents were used in 52.2%. Chemotherapy was used in 27.8%, while immune globulin was used in 22.2%. Surgical resection was used in 20.0%, radiotherapy in 14.4%, and interferon-alpha therapy in 12.2%. The results showed that 48.9% of the patients had died, while 25.6% and 8.9% were regarded as having complete remission and partial remission, respectively. In conclusion, the incidence of PTLD varies widely across Canadian centres. Children are disproportionately affected and the mortality rate is high. Management practices vary significantly, and the need for information sharing was identified as one way of optimizing management.

Transpl Infect Dis 2001 Jun;3(2):70-8

Identifying the patient at risk for post-transplant lymphoproliferative disorder.

Cockfield SM. Division of Nephrology and Immunology, Department of Medicine, University of Alberta, Canada. sandra.cockfield@ualberta.ca

Post-transplant lymphoproliferative disorders (PTLD) are a recognized complication of the immunosuppression required to prevent allograft rejection, occurring in 1-20% of recipients of solid organ transplants. Several factors greatly increase the risk of developing PTLD early post-transplant in any individual recipient. Epstein-Barr virus (EBV) infection is critical in the pathogenesis of the majority of these cases. Pre-transplant EBV seronegativity increases the incidence of PTLD 10- to 75-fold over that of EBV-seropositive recipients. Other risk factors include very young recipient age, cytomegalovirus infection or mismatching (donor positive-recipient negative), aggressive immunosuppression with conventional biologic agents, and the type of organ transplanted. In contrast, the risk of developing PTLD late in the post-transplant course does not appear to be influenced by the type of immunosuppressive agents employed, but rather by the duration of any immunosuppression. The role of EBV in late PTLD is also less certain, as a greater proportion of lesions are not associated with evidence of EBV infection. As the understanding of these risk factors has expanded, opportunities exist to target those populations at highest risk for the development of PTLD for aggressive monitoring and pre-emptive or prophylactic therapy. It is hoped that implementation of such strategies will render early PTLD a preventable complication of transplantation.

Histopathology 2001 Feb;38(2):146-59

Lymphoproliferative disorders in children with primary immunodeficiencies: immunological status may be more predictive of the outcome than other criteria.

Canioni D, Jabado N, MacIntyre E, Patey N, Emile JF, Brousse N. Service d'Anatomie-Pathologique, Hopital Necker-Enfants Malades, Paris, France.

AIMS: Lymphoproliferative disorders (LPDs) are a severe complication in primary immunodeficiency and post-transplant patients. In primary immunodeficiency patients, LPDs are not well-known and, thus, we tried to evaluate their distinctive features and to determine prognostic factors predictive of clinical outcome by comparison with LPDs in post-transplant children. METHODS AND RESULTS: Clinical records and histopathology of 18 LPDs occurring in primary immunodeficieny children were compared with those of 10 LPDs in post-transplant children, together with results of in-situ hybridization for the detection of Epstein-Barr virus (EBV)-RNA and molecular biological techniques. LPDs were frequently extranodal, EBV-associated, and were more commonly pleomorphic in primary immunodeficiency than in post-transplant patients. A low T-cell count and abnormal T-cell function indicated bad prognosis in both groups. Polymorphic LPDs (PLPDs) were most frequent (n = 19), whereas lymphomas were rare (n = 7), and pseudo-tumoral lymphoid hyperplasias (n = 2) were observed only in primary immunodeficiency. Comparative p53/bcl-2 staining revealed a p53 overexpression in lymphomas compared with PLPDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expressed mainly CD20. TCR and IgH rearrangements did not help in distinguishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indicated poor prognosis, whereas oligoclonality by Southern blot regardless of PCR clonality and especially a polyclonal profile by Southern blot and PCR indicated a relatively good prognosis. CONCLUSIONS: This study documents the pleomorphism of LPDs in primary immunodeficiency compared to post-transplant children, even if some LPDs are similar in both groups (PLPDs). No criteria are useful enough to ascertain the diagnosis of malignancy in this series. Some molecular biological criteria help to predict the clinical outcome which, nevertheless, seems to depend more on the degree of immunosuppression and on T-lymphocyte presence and function.