1. Case 9 A 55 year old male presented with an enlarged axillary lymph node. Staging identified multiple enlarged lymph nodes, and B symptoms, including night sweats, weight loss

5. CD20

6. CD30

7. CD15

8. EBER

9. LMP1

10. MUM1/IRF4

11. CD3

12. Diagnosis – Case 9 EBV-positive Diffuse large B-cell lymphoma of the elderly –Differential includes classical Hodgkin’s lymphoma, mixed cellularity –Favoring EBV+ DLBCL Strong CD20 expression Range in tumor cell size and morphology

13. Age Related EBV+ Lymphoproliferation NCI Study Cohort (Dojcinov Blood 2011) 122 cases selected as Age Related EBV+ LPD Median age 75 (45-101) 67 Males; 55 Females Study period 16 years (1993 – 2009) Excluded: –Infectious mononucleosis –CAEBV –Other Lymphoma entities –Other sources of immunosuppression –Treatment for lymphoma –Autoimmune condition

14. Subclassification of Age-Related EBV-B-cell LPD Reactive Hyperplasia associated with EBV –All nodal Polymorphic B-cell lymphoma-like, nodal Polymorphic B-cell lymphoma-like, extranodal EBV-positive large B-cell lymphoma –Plasmablastic lymphoma

15. Clinical Presentation – Reactive Nodal Lesions (n=26) Age 67 (45-90) 13M 13F No = 31; 16 M 15 Fe Med Age 67; Range 45-90 65% localized 32% had some systemic symptoms, such as fever

16. Reactive: Pathology

17. Follicular 35% Interfollicular 65%

18. Clinical Presentation - Polymorphous Nodal No. = 30; 13 M 17 Fe Med age 73; Range 48-93 44% localized 17% multiple sites 39% generalized 35% B symptoms

19. Polymorphous Nodal: PathologyPTLD-like (plasmacytoid cells, immunoblasts)

20. CD20 CD30 PAX5 CD20 CD79a

21. No. = 21; Med Age 77.5 (Range 58-101) 9M 12F Presentation – Polymorphous Extranodal Note predominance Of Skin and Oropharyngeal

22. Mucocutaneous Ulcer – A Novel EBV Related Lesion Associated with Decreased Immune Surveillance (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

23. EBV+ Mucocutaneous Ulcer EBER CD30

24. CD20 CD15PAX5

25. CD30 CD15 EBER LMP1-

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

27. Mucocutaneous ulcer 85 y.o. male

28. EBV+ classical Hodgkin’s Lymphoma in the elderly has superior survival to EBV+ Large B-cell lymphoma of the elderly; Asano et al. Blood 2009 But - involvement of unusual extranodal sites in some cases of Classical Hodgkin’s lymphoma: skin, lung, GI tract

29. Presentation-DLBCL EBV+ No.= 30; Med Age 77; Range 59-90; 29M 11 Fe B Symptoms in 36% Localized 37%; Muliple sites or bulky disease 63% Lung, max. sinus, palate, tonsil, tongue, peritoneum, colon, stomach, skin, soft tissue, spleen, adrenal

30. EBV+ diffuse large B-cell Lymphoma of the elderly

32. CD30 EBER CD20PAX5

33. Curves for MCU & RH overlap at 100% Age related EBV LPD – Dojcinov et al Blood 2011