Prsentation Clinique / Clinical Setting
Patient de 26 ans, admis pour détransplantation
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.
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 (+)
complicant la biopsie, motive une thoracotomie. Une biopsie chirurgicale
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.
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
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
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
Immunohistochimie / Immunohistochemistry
Une expression des cellules aux
marqueurs T et B est observée.
Positivity to T and B cell markers
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
bcl2 discloses an heterogenous positivity.
p53 is negative. Numerous macrophages are also part of the infiltrate
Diagnostic propos / Proposed diagnosis
Lsion lymphoprolifrative post-transplantation,
Post-transplant lymphoproliferative disease,
Evolution: Arrét de l'immunosuppression aprés
la dtransplantation. Controle radiologique apérs 2 mois, disparition
Followup: Immunosuppresive therapy halted
after removal of the kidney. After 2 months, MRI shows absence of
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
Oxford Transplant Centre, Churchill Hospital,
Headington, Oxford, UK. email@example.com
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
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.
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,
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. firstname.lastname@example.org
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
Cockfield SM. Division of Nephrology and Immunology,
Department of Medicine, University of Alberta, Canada. email@example.com
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.