PTLD

PTLD: Post-transplant Lymphoproliferative Disorders

PTLD: WHO (Jaffe, et al, 2001) –Lymphoid proliferation or lymphoma that develops as a consequence of immunosuppression in a recipient of a solid organ or bone marrow allograft. –PTLDs comprise a spectrum ranging from early EBV-driven polyclonal proliferations resembling infectious mononucleosis to EBV(+) or EBV(-) lymphomas of predominantly B-cell or less often T-cell type.

Post-transplant Lymphoproliferative Disorders- PTLD Early lesions Polymorphic PTLD Monomorphic PTLD (Classify according to lymphoma classification) Hodgkin lymphoma and Hodgkin-like PTLD

1. Early lesions Reactive plasmacytic hyperplasia Infectious Mononucleosis-like Possibly these are overlapping syndromes.

Infectious mononucleosis-like

Infectious mononucleosis-like, cont.

1. Early lesions: Characteristics Lymphoid proliferation with preservation of architecture of the involved tissue. Younger age, solid organ transplants EBV + (If negative should not call PTLD) Polyclonal. Tend to regress with reduction in immunosuppression Can be fatal!

2. Polymorphic PTLD 15 Y/O F 125 days post unrelated donor cord transplant for MDS now with GI symptoms and Acute GVHD. Jejunal Biopsy

2. Polymorphic PTLD, cont. EBER CD20

Polymorphic PTLD: Characteristics Destructive lesions composed of immunoblasts, plasma cells, and intermediate forms that efface the architecture. Full range of B-cell maturation. Clonal proliferations. EBV + Some will regress with reduction in immunosuppression.

3. Monomorphic PTLD B-cell neoplasms –Diffuse large B-cell lymphoma –Burkitt lymphoma –Myeloma –Plasmacytoma T-cell neoplasms –Peripheral T-cell lymphoma, NOS –Other types

3. Monomorphic PTLD: Case 1: DLBCL Pt. E.K.: 72 Male 8 mos. post renal transplant now with inguinal lymphadenopathy.

3. Monomorphic PTLD:DLBCL LMP1 CD20

Monomorphic PTLD: Case 2: DLBCL Pt R.E.: 46 Y/O M 34 months post liver transplant now with lung and mediastinal masses.

Case 2: DLBCL CD 20 LMP1

Case 3: Myeloma Pt. JS: 52 Y/O M 4 yrs post renal transplant now with pathologic fracture of left femur. Lambda LMP1

Monomorphic PTLD: Characteristics Can be diagnosed as lymphoma on morphologic grounds, and are classified accordingly (T- vs. B-cell). Most are EBV positive. Clonal proliferations. Tend to progress and require chemotherapy.

4. Hodgkin Lymphoma Mixed cellularity most common followed by Nodular sclerosis Lymphocyte depleted least common

Which PTLDs respond to reduction of immunosuppression? Morphology Immunophenotype EBV status Clonality Bcl-6 mutation: 3q27 t(3:22)(q27:q11) is associated with failure to regress in polymorphic and monomorphic PTLDs.