Infectious mononucleosis-like PTLD

2016-06-01   Ding-Bao Chen 

1.Department of Pathology, Peking University Peoples Hospital, Beijing 100044, Peoples Republic of China. chendingbao@21cn.com

Abstract

Post-transplant lymphoproliferative disorders (PTLDs) are serious, life-threatening complications of transplantation which represent a heterogeneous group of lymphoproliferative diseases and show a spectrum of clinical, morphologic, and molecular genetic features ranging from reactive polyclonal lesions to frank lymphomas. Infectious mononucleosis (IM)-like PTLD is a kind of early lesions, which shows characteristic clinic-pathological features and molecular involvement.

Clinics and Pathology

Disease

The term "post-transplant lymphoproliferative disorder" or disease (PTLD) was first introduced in 1984 by Starzl (Starzl et al.1984). PTLDs are serious, life-threatening complications of solid-organ transplantation (SOT) and bone marrow transplantation, and are associated with high mortality. PTLDs represent a heterogeneous group of lymphoproliferative diseases, which show a spectrum of clinical, morphologic, and molecular genetic features ranging from reactive polyclonal lesions to frank lymphomas.
PTLDs are classified into early lesions, polymorphic, monomorphic and classical Hodgkins lymphoma-like PTLD.
Infectious mononucleosis (IM)-like PTLD is a kind of early lesions, which shows characteristic clinicopathological features and molecular involvement. The early lesions are defined as lymphoid proliferations in an allograft recipient, characterized by architectural preservation of the involved tissue, with preservation of the nodal sinuses or tonsillar crypts, and residual or sometimes floridly reactive follicles in some cases. (Swerdlow et al. 2008; Mucha et al. 2010)

Phenotype stem cell origin

The majority (>90%) of PTLD in solid organ recipients are of host origin and only a minority of donor origin. Donor origin PTLD appear to be most common in liver and lung allograft recipients, and frequently involve the allograft. In contrast, the majority of PTLD in bone marrow (BM) allograft recipients are of donor origin, as would be expected, since successful engraftment results in an immune system that is nearly exclusively of donor origin. (Chadbum et al. 1995; Swerdlow et al. 2008)

Epidemiology

The incidence of PTLD ranges from 1-3 % in renal to 5-20 % in lung and intestinal transplantation, related to the type of transplanted organ, intensity of IS, age, and viral infection, etc. ( Opelz, 2003. Opelz,1993.) In contrast, the incidence of PTLD after BMT is about 1.0 % for recipients from HLA-compatible related donors (lower than that of SOT), but in up to 25 % for high-risk patients (Curtis, 1999). However, the field has evolved during the last decade. Hoegh-Petersen et al. found a frequency of 8.1 % among 307 allo-HSCT recipients who had also received ATG-based conditioning. Kamani et al. found an overall incidence of 2.3 % for post-transplant malignancy (most of which were PTLD) in patients receiving such transplant for primary immunodeficiency disorders. The highest subgroup, those patients with Wiskott-Aldrich syndrome, had a 3.3 % frequency.
In our hospital, it is 1.5 % (9/585) from August 2002 to October 2006 and about 1 % (9/857) from November 2006 to November 2009 after allo-HSCT, respectively. The incidence of PTLD was higher in mismatched or unrelated HSCT group than that of conventional one, 3.4 % (7/208), 2.3 % (1/44) versus 0/323. It was also higher in patients with conditioning regimen including ATG than those without, 3.4 % (9/262) vs. 0/323. (Swerdlow et al. 2008; Chen, 2013)

Clinics

The clinical features of PTLD differ from those of lymphomas observed in the general population. Symptoms may be mild, such as fever, mononucleosis-like syndrome, lymphadenopathy, recurrent infections or severe organ dysfunction. The variable manifestation of PTLD depends on many factors, such as the type of transplanted organ or IS used, histopathology and time elapsed since transplantation. The first year after transplantation is important, in lung recipients, more than 50 % of all PTLDs develop during the first post-transplant year. Our data showed that 88.2 % of patients (15/17) were diagnosed within 7 months after transplantation (1.5-7 months), and the median interval after transplantation to the diagnosis was 2.5 months (mean 4.7 months, range 1.5-19 months), shorter than that of SOT. The frequent sites of PTLD include GI (jejunum more often than colon), lymph nodes, and central nervous system, different from type to type of transplantation.
Early lesions mostly develop within 1 year after transplantation, and most patients with early lesions affected tonsils, Waldeyer ring, adenoids or lymph nodes. They often show spontaneous regression or regress following reduction in IS, and express EBER or EBV-LMP-1. IM-like PTLDs occur at a younger age than the other PTLD and are often seen in children or in adult solid organ recipients who have not had prior EBV infection. IM-like PTLDs can be fatal (Opelz, 2003; Swerdlow et al. 2008; Johnson, 2006).
Atlas Image
Figure 2. There is a polymorphic proliferation of immunoblasts, small lymophoid cells and plasma cells.
Atlas Image
Figure 3. Some cells are positive for CD20, and scattered B cells are shown.

Pathology

The underlying lymph node architecture is preserved, which shows hyperplasia of plasma cells and lymphocytes in interfollicular area, with paracortical expansion, scattered immunoblasts and reactive follicles
Atlas Image
Figure 4. Some cells are positive for CD3
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Figure 5. Foci of plasma cells are positive for CD38.
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Figure 6. The proliferation index of Ki 67 is 95%.
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Figure 7. EBER-positive cells are present (in situ hybridization)

Treatment

There is no consensus on the optimal treatment of PTLD. It is generally agreed that three major strategies should be applied: restoration of the recipients immunity (to limit the EBV infection), elimination EBV and removal of neoplastic B cells. Reduction of IS or even withdrawal remains the first-line treatment. With reduction of IS, virtually all early lesions regress and generally show good prognosis, whereas half of P-PTLD regress and some will progress, the majority of M-PTLDs do not regress . DLI was effectively used in EBV-associated PTLD after mismatched/haploidentical haematopoietic stem cell transplantation (HSCT). Patients with lymph node localization have a relatively good outcome, and disseminated disease in contrast has a poor prognosis. (Mucha 2010; Xu 2010)

Prognosis

The prognosis of PTLD is poor. The treatment of rejection episodes with OKT3 or ATG enhances the PTLD risk in patients who did not receive antibody induction, rejection therapy with OKT3 or ATG adds to the already increased lymphoma risk HLA matching is also a risk factor in the pathogenesis of PTLD, and HLA-B or HLA-DR mismatches especially seem to be critical. The number of HLA mismatches parallels with an increased risk of PTLD ( Opelz 2003; Opelz 2010)

Bibliography

Pubmed IDLast YearTitleAuthors
74953091995Post-transplantation lymphoproliferative disorders arising in solid organ transplant recipients are usually of recipient origin.Chadburn A et al
232551602013Clinicopathologic spectrum and EBV status of post-transplant lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation.Chen DB et al
104985901999Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study.Curtis RE et al
171225182006Impact of Epstein-Barr virus in monomorphic B-cell posttransplant lymphoproliferative disorders: a histogenetic study.Johnson LR et al
205767252010Post-transplant lymphoproliferative disorder in view of the new WHO classification: a more rational approach to a protean disease?Mucha K et al
201108572010Impact of HLA mismatching on incidence of posttransplant non-hodgkin lymphoma after kidney transplantation.Opelz G et al
79029001993Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients.Opelz G et al
61423041984Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.Starzl TE et al
212112112010[The efficacy and safety of donor lymphocyte infusion to treat Epstein-Barr virus associated lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation].Xu LP et al

Summary

Atlas Image
Figure 1. Infectious Mononucleosis-like PTLD: hyperplasia of plasma cells and lymphocytes in interfollicular area, with scattered immunoblasts and reactive follicles. (HE stain)

Citation

Ding-Bao Chen

Infectious mononucleosis-like PTLD

Atlas Genet Cytogenet Oncol Haematol. 2016-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1726/infectious-mononucleosis-like-ptld

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