History

Now 17 year old male Velocardiofacial syndrome with

hypoplastic left heart Heart transplant at 13 weeks of age Multiple medical problems

6 years prior: post-transplant lymphoproliferativedisorder

6 months prior: acute rejection

History

Worsening fatigue and irritability

Physical Exam - unremarkable

Laboratory studies: Pancytopenia Acute renal failure

Current Hospitalization

Increasing fatigue, irritability

3.5 cm mass in right lobe of liver

Developed sepsis

CD30CD15

EBER

EBER

POST-TRANSPLANT LYMPHOPROLIFERATIVE

DISORDER (PTLD),

CLASSICAL HODGKIN LYMPHOMA TYPE

Diagnosis

Post-transplant lymphoproliferative disorder (PTLD)

A lymphoid or plasmacytic proliferation which develops consequent to immunosuppressionin recipients of solid organ, bone marrow or

stem cell transplants

Post-transplant lymphoproliferative disorder

Pathogenesis Epstein-Barr virus (EBV):

Up to 100% - Early lesionsMinority of cases EBV negative

Other viruses ?Possible candidate KSHV/HHV 8

Post-transplant lymphoproliferative disorders

2001 WHO Classification1) Early lesions

Plasmacytic hyperplasia Infectious mononucleosis-

like

2) Polymorphic

3) Monomorphic B-cell neoplasms T-cell neoplasms

4) Hodgkin lymphoma and Hodgkin lymphoma-like

Post-transplant lymphoproliferative disorders

2001 WHO Classification1) Early lesions

Plasmacytic hyperplasia Infectious

mononucleosis-like

2) Polymorphic

3) Monomorphic B-cell neoplasms T-cell neoplasms

4) Hodgkin lymphoma and Hodgkin lymphoma-like

2008 WHO Classification1) Early lesions

Plasmacytic hyperplasia Infectious mononucleosis-

like

2) Polymorphic

3) Monomorphic B-cell neoplasms T-cell neoplasms

4) Classical Hodgkin lymphoma-type

Hodgkin lymphoma-like PTLD

(HL-like PTLD)

vs

Classical Hodgkin lymphoma

type PTLD (cHL PTLD)

Classical Hodgkin lymphoma type PTLD Hodgkin lymphoma-like PTLD

CD45 CD20

CD30 CD15

Classical Hodgkin lymphoma type PTLD

CD45 CD20

CD30 CD15

Hodgkin lymphoma-like PTLD

Classical Hodgkin lymphoma type PTLD Hodgkin lymphoma-like PTLD

EBER EBER

Molecular Findings

Hodgkin lymphoma-like PTLD:

Clonality demonstrated by B-cell gene

rearrangement studies

Classical Hodgkin lymphoma type PTLD:

Clonality limited to single HRS cells

Post-transplant lymphoproliferative disorders

2001 WHO Classification1) Early lesions

2) Polymorphic

3) Monomorphic B-cell neoplasms T-cell neoplasms

4) Hodgkin lymphoma and Hodgkin lymphoma-like

2008 WHO Classification1) Early lesions

2) Polymorphic

3) Monomorphic B-cell neoplasms T-cell neoplasms

4) Classical Hodgkin lymphoma-type

cHL-PTLD vs. HL-like PTLD

cHL-PTLD HL-like PTLD

Morphology HRS cells in HRS cells in

background of small background of small

lymphocytes lymphocytes

cHL-PTLD vs. HL-like PTLD

cHL-PTLD HL-like PTLD

Morphology HRS cells in HRS cells in

background of small background of small

lymphocytes lymphocytes

Immunophenotype CD45-, CD20-, CD45+, CD20+,

CD30+, CD15+ CD30+/-, CD15-

cHL-PTLD vs. HL-like PTLD

cHL-PTLD HL-like PTLD

Morphology HRS cells in HRS-like cells in background of small background of smalllymphocytes lymphocytes

Immunophenotype CD45-, CD20-, CD45+, CD20+, CD30+, CD15+ CD30+/-, CD15-

EBV status EBER+ in EBER+ variable HRS cells only in HRS cells and

small bystander lymphocytes

cHL-PTLD vs. HL-like PTLDcHL-PTLD HL-like PTLD

Morphology HRS cells in HRS-like cells in background of small background of smalllymphocytes lymphocytes

Immunophenotype CD45-, CD20-, CD45+, CD20+, CD30+, CD15+ CD30+/-, CD15-

EBV status EBER+ in EBER+ variable HRS cells only in HRS cells and

small bystander lymphocytes

Molecular Difficult to Clonalitydemonstrate in whole tissue DNAclonality

Clinical & Prognostic Implications

HL-like PTLD Behaves like a non-Hodgkins lymphoma Rx: reduction of immunosuppression,

rituximab, and NHL chemotherapy cHL-PTLD

Is a true Hodgkins lymphoma Rx: reduction of immunosuppression, Hodgkin

lymphoma chemotherapy Rituximab?

Conclusion HL-like PTLD and cHL-PTLD are

morphologically similar

However, there are significant immunophenotypic and molecular genetic differences between the two entities

Distinction between cHL and HL-like PTLD may be important for their clinical management

Pitman SD, et al. Am J Surg Path.2006;30:470-476 and 2008 WHO book pp343-349

Acknowledgements

Dr. Jun Wang Dr. Craig Zuppan Dr. Jeffery Cao Dr. Katie Wilkinson

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