PTLDs

Definition: 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 but some estimate that up to 14% of posttransplantation malignant lymphomas are T-cell lymphomas.

Case

 Case 189 (HPC:189)

Post-transplant lymphoproliferative disorders (PTLD) are a well-recognised and potentially life-threatening complication after solid organ transplantation. There is no universally accepted definition of the term PTLD but it is most commonly used to describe a wide spectrum of lymphoproliferative disorders after solid organ and haematopoietic cell transplantation that range from infectious mononucleosis and lymphoid hyperplasia to highly invasive malignant lymphoma. PTLD after solid organ transplantation nearly always originates from recipient lymphoid cells whereas after bone-marrow or stem cell transplantation, PTLD is usually of donor origin.

Most cases of PTLD after both solid organ and haematopoietic cell transplantation are associated with Epstein Barr virus (EBV) that leads to uncontrolled B cell proliferation and tumour formation. Although there are many similarities between PTLD after solid organ transplantation and after haematopoietic cell transplantation, only the former is considered further in this review.

PTLD is a relatively common malignancy after transplantation and is seen in up to 10% of all solid organ transplant recipients. It is the most common form of post-transplant malignancy in children and in adults it is the second most common malignancy after skin cancer.

In both children and adults it is the most common cause of cancer-related mortality after solid organ transplantation and the reported overall mortality for PTLD often exceeds 50%.

Types (WHO classification)

PTLD encompasses a wide spectrum of lymphoproliferative disorders with differing pathogenesis, histological appearance and clinical behaviour.

In Europe and the U.S., about 85% of PTLD are of B cell lineage and most of these (over 80%) are associated with EBV infection. Around 10–15% of PTLD are of T cell lineage, around 30% of which are associated with EBV.

Other haematopoietic cell lineages, such as natural killer cells, may very occasionally give rise to PTLD. In some parts of the world the proportion of T lymphocyte PTLD is markedly higher due to the prevalence of the oncogenic HTLV virus and in the Far East, for example, it may be as high as 40%.

 early PTLD

• plasmacytic hyperplasia and plasma cell-rich PTLDs (11860313)
• IMN-like PTLD (infectious mononucleosis-like PTLD)

 polymorphic PTLD (polymorphic B-cell hyperplasia)

• polyclonal polymorphic PTLD
• monoclonal polymorphic PTLD

 monomorphic PTLD

• B-cell monomorphic PTLD
  • diffuse large B-cell lymphoma (immunoblastic DLBCL, centroblastic DLBCL, anaplastic DLBCL)
  • marginal zone B-cell lymphoma
  • Burkitt lymphoma
  • Burkitt-like lymphoma
  • plasma cell myeloma
  • plasmocytoma-like lesions
  • small B-cell lymphoid neoplasm
  • anaplastic large cell lymphoma (ALCL) (15104308)

• Hodgkin lymphoma and Hodgkin-like PTLD

• T-cell PTLD
  • peripheral T-cell lymphoma (NOS)
  • large granular lymphocyte proliferations
    • large granular lymphocyte leukemia
    • large granular lymphocyte lymphoma

Variants

 polymorphic PTLDs
 monomorphic PTLDs

Lymphomas

• extranodal marginal zone lymphomas of the mucosa-associated lymphoid tissue (MALT-type lymphomas) (10632493)
• Epstein-Barr virus-associated nasal type NK/T-cell lymphoma (11727268)

Localization

 lymph nodes
 gastrointestinal tract (2158245)
 renal allograft (8619421)
 sites of previous surgical intervention (12698104)

Types (Knowles et al., 1995)

 plasmacytic hyperplasia and plasmacytic malignancy (11860313)
 polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma
 immunoblastic lymphoma and multiple myeloma

Cytogenetics

Cytogenetic abnormalities are identified in 72% of monomorphic B-cell PTLDs and in all T-cell PTLDs, but in only 15% of polymorphic PTLDs and in no early lesions. (16283619)

The most frequent clonal abnormalities in monomorphic PTLD are trisomy 9 and/or trisomy 11 , followed by 8q24.1 rearrangement, 3q27 rearrangement, and 14q32 rearrangement. (16283619)

MYC rearrangement (8q24.1) and T-cell-associated chromosomal abnormalities correlate with poor outcome and short survival. (16283619)

PTLD with trisomy 9 and/or trisomy 11 develope early after transplant, presenting as Epstein-Barr virus-positive large B-cell lymphoma with prolonged survival. (16283619)

Variants

 Epstein-Barr virus-negative post-transplant lymphoproliferative disorders (10716151)

See also

 EBV-associated tumors

• EBV-associated lymphoid tumors
  • EBV-associated lymphomas
  • EBV-associated B-cell lymphoproliferative disorders

References

 Djokic M, Le Beau MM, Swinnen LJ, Smith SM, Rubin CM, Anastasi J, Carlson KM. Post-transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities. Genes Chromosomes Cancer. 2006 Mar;45(3):313-8. PMID: 16283619

 Chadburn A, Chen JM, Hsu DT, Frizzera G, Cesarman E, Garrett TJ, Mears JG, Zangwill SD, Addonizio LJ, Michler RE, Knowles DM. The morphologic and molecular genetic categories of posttransplantation lymphoproliferative disorders are clinically relevant. Cancer. 1998 May 15;82(10):1978-87. PMID: 9587133

 Chadburn A, Cesarman E, Knowles DM. Molecular pathology of posttransplantation lymphoproliferative disorders. Semin Diagn Pathol. 1997 Feb;14(1):15-26. PMID: 9044506

 Knowles DM, Cesarman E, Chadburn A, Frizzera G, Chen J, Rose EA, Michler RE. Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood. 1995 Jan 15;85(2):552-65. PMID: 7812011