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Case 5A

A 16 year old female underwent renal transplant for a diagnosis of focal segmental glomerlulosclerosis (FSGS).

One year later she presented with symptoms of an acute abdomen and had jejunal perforation.

CD20

CD20

MIB-1

EBER

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Additional studies

• Infiltrating cells positive for CD20, CD30, CD45, with kappa light chain restriction

• Proliferative rate: moderate to high

• Focal staining for LMP-1

Dx: Post-transplant lymphoproliferative disease, polymorphic type

Rx: R-CHOP with CR

Follow-up: 4 years later presented with PTLD-plasmacytoma type, involving laryngeal mucosa

Case 5B

• 57 year old male presented with abdominal pain, 10 years after right kidney transplant for polycystic kidney disease and renal failure

• CT scan showed small bowel obstruction with ulceration, focal perforation

Small bowel ulceration

Focal extension to muscularis propria –mainly by small lymphocytes

Scattered atypical cells in a rich inflammatory background

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CD20

CD3

CD20

CD30 CD15

CD30

PAX5

Bcl-2MUM1

CD79a

EBER

LMP1

Polyclonal by PCR

Fr 2, Fr 3, IgK

Treatment & Follow up : 4x RituximabReduction of Mycophenolate acid from 720mg to 360mg No evidence of disease with 10 months follow-up

Diagnosis: EBV+ mucocutaneous ulcer, polymorphic post-transplant lymphoproliferative disorder (PTLD)-related

Comparison with 5A:

• Scattered HRS-like cells in a marked inflammatory background, numerous T-cells, histiocytes

• Atypical cells do not sheet out

• No evidence of clonality

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Mucocutaneous Ulcer (Dojcinov et al. AJSP 2010)

Sites: Oropharyngeal mucosa (70%); Skin (25%); GI tract (5%)

Median Age 77 (42-101)– Age related only, Med 79 (64-101)

– Age + iatrogenic immunosuppression, Med 72 (42-80)

• Waxing and waning clinical course, may regress spontaneously

• Clinical options, local radiation therapy, rituximab

• No disease related deaths

Mucocutaneous ulcerGingival Involvement common

85 y.o. male

EBV+ Mucocutaneous Ulcer

EBER

CD30

EBER

CD30CD15

PAX5 CD20

CD30 CD15

PAX5Phenotype often mimicsClassical Hodgkin lymphoma

Some cases probably misclassified as cutaneous CHL in the past

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Spontaneous resolution of MCU in a patient with RA on MTX over the course of 8 weeks following withdrawal of drug

75 y.o. femaleLesion of arm

CD15

CD30CD20

Curves for MCU & RH overlap at 100%

Age related EBV LPD – Dojcinov et al Blood 2011

• 7 cases in series of 70 transplant recipients

5 renal, 1 heart, 1 lung• Involved oral mucosa in 4 and GI tract in 3• Patients treated with reduced

immunosuppression or rituximab or both • No patient recurred or developed another

PTLD• Conservative management is sufficient

EBV-related Lymphoproliferative B-cell Disorders

• Infectious mononucleosis• Post-Transplant and other iatrogenic B-cell LPD’s• Lymphomatoid granulomatosis • EBV+ DLBCL with chronic inflammation • Burkitt lymphoma (subset)• Classical Hodgkin’s lymphoma

– Mainly Mixed cellularity and Lymphocyte depleted• Primary effusion lymphoma (HHV-8 & EBV)• Germinotropic B-LPD • Plasmablastic lymphoma• EBV + large B-cell lymphoma, NOS • Mucocutaneous ulcer – provisional entity in WHO 2016

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Patterns of reactive B‐cell hyperplasia

Aggressive B‐cell lymphoma

B‐LPD of varied malignant potential

Indolent B‐cell lymphoma   

Hyperplasia

Lymphoma

EBV+ B‐Cell Spectrum