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Diagnosis: Polymorphic Post-transplant lymphoproliferative disorder (PTLD)

Post-transplant lymphoproliferative disorders (PTLD) are a serious complication after solid organ or allogeneic hematopoietic stem cell transplantation and include a range of diseases from benign proliferations to malignant lymphomas (Singavi AK, et al. Post-transplant lymphoproliferative disorders. Cancer Treat Res. 2015;165:305-27. [PubMed link]). Abnormal lymphoproliferation ranges from a polymorphic form characterized by premalignant hyperplasia to a monomorphic form pathologically indistinguishable from non-Hodgkin lymphoma. The distinction between polymorphic and monomorphic PTLD significantly affects therapeutic decisions because the monomorphic form is usually fatal. The diagnosis of PTLD requires evaluation of histopathologic appearance, cell phenotype, clonal status, and EBV status. Some suggest that the diagnosis of PTLD can be confirmed based on histologic evidence of invasive lymphoid hyperplasia along with positive tissue staining for EBV via either immunoperoxidase for latent membrane protein (LMP-1) or in situ hybridization for EBV-encoded messenger RNA (EBERs) (Scheinfeld NS. Posttransplantation Lymphoproliferative Disorders. In: eMedicine (consulted on May 25th 2017) [Link]).

PTLDs are categorized based on histopathological subtype and include the following:

- Early lesions: a. Hyperplastic (plasma cell hyperplasia) - b. Infectious mononucleosis–like

- Polymorphic polyclonal

- Polymorphic monoclonal

- Monomorphic (lymphomatous) a. B-cell lymphoma (diffuse large cell and Burkitt lymphoma–like) b. T-cell lymphoma.

- Other: Plasmacytoma, multiple myeloma, Hodgkin disease, T-cell-rich large B-cell lymphoma.

Early lesions, which include lesions with features of infectious mononucleosis (IM) and plasmacytic hyperplasia, show preservation of original tissue architecture. The name implies that these lesions show the first morphologic changes in the spectrum of PTLDs. These lesions are composed of a mixed cell population consisting primarily of small lymphocytes with scattered plasma cells and immunoblasts, that exhibit minimal, if any, cytologic atypia. Some IM-like PTLD lesions exhibit small clonal or oligoclonal B cell populations. EBV small terminal repeat genome analysis is typically polyclonal, but it may rarely have a monoclonal pattern. Early PTLD cases develop later than previously reported (median time from transplant 50 months), involved mostly tonsils and adenoids. The studies report excellent clinical response with reduction of immunosuppression alone. Polymorphic PTLD is composed of “polymorphic” cell populations, including small and medium sized lymphocytes, atypical immunoblasts, mature plasma cells and Reed-Sternberg (RS)-like cells. The infiltrate causes effacement and destruction of the underlying tissue architecture and may show malignant features, such as nuclear atypia, necrosis, and a high mitotic rate. Lesions are mostly monoclonal, and a small proportion (15 %) reveals clonal cytogenetic abnormalities. This is the most common subtype in the pediatric age group, and is mostly related to primary EBV infection (Al-Mansour Z, et al. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013;8(3):173-83. [PubMed link]).

In ouer case was essential for the diagnosis EBER in situ hibridization positivity in many infiltrating cells.

See the chapter: Kidney Transplantation Pathology of our Tutorial (only Spanish version).

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References

• Martínez-Calle N, Alfonso A, Rifón J, Herrero I, Errasti P, Rábago G, Merino J, Panizo Á, Pardo J, Prósper F, García-Muñoz R, Lecumberri R, Panizo C. First-line use of rituximab correlates with increased overall survival in late post-transplant lymphoproliferative disorders: retrospective, single-centre study. Eur J Haematol. 2017;98(1):38-43. [PubMed link]
• OʼRegan JA, Prendeville S, McCaughan JA, Traynor C, OʼBrien FJ, Ward FL, OʼDonovan D, Kennedy C, Berzan E, Kinsella S, Williams Y, OʼKelly P, Deady S, Comber H, Leader M, Conlon PJ. Posttransplant Lymphoproliferative Disorders in Irish Renal Transplant Recipients: Insights From a National Observational Study. Transplantation. 2017;101(3):657-663. [PubMed link]
• Scheinfeld NS. Posttransplantation Lymphoproliferative Disorders. In: eMedicine (consulted on May 25th 2017) [Link]
• Singavi AK, Harrington AM, Fenske TS. Post-transplant lymphoproliferative disorders. Cancer Treat Res. 2015;165:305-27. [PubMed link]
• Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013;8(3):173-83. [PubMed link]

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