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.

Infectious mononucleosis-like, cont.

Infectious mononucleosis-like, cont.

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: DLBCLCD 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.