This document discusses the increased risk of lymphoma in patients with rheumatic disorders like rheumatoid arthritis and discusses three case studies. It notes that while TNF blockers are not intrinsically risky, rheumatoid arthritis itself increases lymphoma risk. The document also examines the proposed mechanisms for clonal B cell expansion in HCV-induced cryoglobulinemia and mixed cryoglobulinemia. It concludes that screening is important for high risk patients like those with Sjögren's syndrome and notes that rheumatic signs could indicate an underlying lymphoma.

1. Lymphoma in patients with rheumatic disorders Burkhard Möller, Bern

2. Contents Rheumaticdiseaseaslymphomariskfactor Treatingrheumaticdiseasesbylymphoablativetherapy Difficultdiagnoses

3. Rheumatoid arthritis

4. 2010 ACR / EULAR classification criteria ≥ 1 joint with definite clinical synovitis (swelling) not better explained by another disease and ≥ 6/10 points

5. J. Askling et al. ARD 2009;68: 648–53 Patient characteristics

6. Nointrinsicriskof anti-TNF, but of RA J. Askling et al. ARD 2009;68: 648–53

7. Comparisontoothertumorentities K. Hellgren et al. A&R 2010;62: 1252-8

8. Information for Healthcare Professionals: Tumor Necrosis Factor (TNF) Blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi) FDA ALERT [8/4/2009]: FDA is requiring the manufacturers of TNF blockers to update the Boxed Warning in the prescribing information to alert healthcare professionals of an increased risk of lymphoma and other malignancies in children and adolescents treated with TNF blockers.

9. Difficultdiagnoses LocoregionalWegener´sgranulomatosis versus extranodal NK-T celllymphomaof nasal type Loefgrensyndrome versus mediastinal lymphoma Cryoglobulinemia

10. Case 1: 43 years ♀, startswithchronicsinusitis….

11. Case 1: Destructionofthehardpalate

12. Case 1: ……..is ANCA negative

13. Case 1: … repeatedbiopsiesofthenoseHE 10x HE 20x

14. Biopsyfromthe nasal cavity Anti-CD3 Anti-CD56 Courtesyof Dr. Müller-Garamvölgyi ,Pathology University Bern

15. Case 2: ♀, 62 y, withWegener´s D. for XX years

16. Case 2: is ANCA-positive, hadseveralbiopsies

17. Case 3: Dg: Cryoglobulinemicvasculitis Illustrations: GG Hunder et al. Atlas ofRheumatology

18. Proposed Mechanism of Clonal B Cell Expansion in HCV-Induced Cryoglobulinemia ED Charles , LB Dustin: Kidney Int. 2009 ; 76(8): 818–824

19. HCV-associatedmixedcryoglobulinemiaand ML „Benign“ MC Symptoms Leukozytoklasticvasculitis Membranoprolif. GN Peripheralneuropathy Therapy pegylated interferon-α−2a/2b (pIFN) + ribavirin (RBV) Symptomatic: RTX (PDN) HCV associated ML immunocytoma splenic marginal zonelymphoma MALT lymphoma aggressive DLBCL Therapy HCV elimination Lymphoma-directed

20. Case 4 Dg: Acutesarcoidosis Illustrations: Uni Erlangen and Bern

21. Conclusions Significantriskofmalignant B celltransformationdespitemechanismsofanergy Sjögren (annualscreening) > SLE > RA RA Associationwithdiseaseseverity weakassociationwithuseofazathioprine Questionableriskby TNF blockade In lymphomapatients, lookforthesignsofperipheralarthritis (Loefgren) andvasculitis (cryoglobulinemia)