Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?
OBJECTIVE
Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV.


METHODS
There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry.


RESULTS
The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01).


CONCLUSIONS
EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.
Leblond
V
V
Département d'Hématologie, Hôpital Pitié-Salpétrière, Paris, France. veronique.leblond@psl.ap-hp-paris.fr
Davi
F
F
Charlotte
F
F
Dorent
R
R
Bitker
M O
MO
Sutton
L
L
Gandjbakhch
I
I
Binet
J L
JL
Raphael
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000009:adverse effects; D017403:In Situ Hybridization; D008214:Lymphocytes / Q000737:chemistry; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000209:etiology* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015996:Survival Rate
C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D007136:Immunoglobulins; D012333:RNA, Messenger; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell