1. Evaluating Adenopathy: When to Worry and What to Do Kate Kolibaba, M.D. Northwest Cancer Specialists Vancouver, WA kathryn.kolibaba@usoncology.com

2. Adenopathy: Objectives Lymphatic system basics Causes of lymphadenopathy Evaluation

3. The Lymphatic System

4. What is the Lymphatic System? Network of organs, such as the tonsils, spleen, liver, bone marrow and lymphatic vessels that connect “ glands ”, the lymph nodes Lymph nodes located throughout the body Lymph nodes filter foreign particles out of the lymphatic fluid Contain B and T lymphocytes

5. Lymph Node - Normal Histology afferent lymphatic vessel capsule follicle (mainly B-cells) - germinal centre - mantle zone C cortex medulla paracortex efferent lymphatic vessel artery vein

6. Lymphatic Tissue Lymphocytes originate in bone marrow Lymphocytes undergo proliferation and differentiation in lymphoid tissue B-lymphocytes - tend to reside in lymph nodes & spleen T-lymphocytes - tend to circulate throughout the lymphatic system

7. Lymphocytes 20% of white blood cells are lymphocytes Most lymphocytes are in lymph nodes, spleen, bone marrow and lymphatic vessels T cells, B cells, natural killer cells B cells produce antibodies T cells help B cells produce antibodies and fight viruses

8. Lymphadenopathy Enlargement or change in texture of a lymph nodes Adenopathy Benign vs. malignant Require treatment Evaluation

9. Goals of Evaluation Identify the infrequent but serious causes of lymphadenopathy History, including exposures Age of patient Location

10. Differential Diagnosis MIAMI Malignancy Infection Autoimmune Miscellaneous-sarcoidosis, hyperthyroidism Iatrogenic-serum sickness, medications

11. Infectious Causes of Adenopathy Tuberculosis Bacterial Brucellosis, cat-scratch, STDs Viral HIV, hepatitis, CMV, EBV, rubella

12. Autoimmune Causes of Adenopathy Lupus erythematosis Rheumatoid arthritis Dermatomyositis Sjogren ’ s syndrome

13. Drugs Associated with Adenopathy allopurinol atenolol captopril carbamazepine gold hydralazine penicillins phenytoin primidone pyrimethamine quinidine Trimethoprim/sulfa- methoxizole sulindac

14. Likelihood of Malignancy Series of patients having biopsy: 21% in patients under 30 41% in patients 31-50 61% in patients over 50 Lee et al; J Surg Oncol 1980; 14: 53 – 60

15. Likelihood of Malignancy Lymphadenopathy that lasts one year with no size increase is unlikely to be neoplastic

16. Associated Symptoms Fever, night sweats, weight loss “ B ” symptoms, lymphoma Fatigue, malaise, fever Atypical lymphocytosis, mononucleosis Arthralgias, weakness, rash autoimmune

17. Physical Examination Supraclavicular most likely to be malignant 54-85% neoplastic in biopsy series

18. Axillary and Inguinal Adenopathy Drain extremities Often nonspecific, reactive Up to 2 cm can be normal

19. Nodal Character There is no specific size threshold that raises suspicion Hard, painless Malignant (metastatic) or granulomatous Rubbery Lymphoma

20. Evaluation of Adenopathy Results of initial assessment Benign or self-limited disease Autoimmune or serious infectious Malignancy Unexplained Bazemore and Smucker, Am Fam Physician 2002; 66: 2103-2110.

21. Evaluation of Adenopathy Empiric treatment Often antibiotics and/or corticosteroids are prescribed, but no data exists to support this approach

22. Benign or Self-Limited Disease Treatable Yes No Treat Reassurance, appropriately explain course of disease Offer follow-up for persistent or changing adenopathy

23. Suspected Autoimmune or Serious Infectious Disease Specific Testing Positive Negative Treat See appropriately “Unexplained”

24. Suspected Malignancy Biopsy Positive Negative Treat See appropriately “Unexplained”

25. Unexplained Adenopathy Review risk factors for malignancy If high risk, proceed with excisional biopsy

26. Unexplained Adenopathy Low Risk for Malignancy Generalized Regional Referral or Follow-up

27. Unexplained Generalized Adenopathy Consider miscellaneous causes Sarcoidosis Silicosis, berylliosis Storage diseases: Gaucher, Fabry ’ s Hyperthyroidism, hypertriglyceridemia Kawasaki syndrome

28. Unexplained Generalized Adenopathy Positive Negative Biopsy most abnormal node Treat CBC, RPR, PPD, HIV, HBsAg, ANA Positive Negative Follow-up

29. More About Biopsies FNA Core needle biopsy Excisional biopsy

30. Fine Needle Aspiration FNA - Fine Needle Aspiration Simple - 21-23 gauge needle,5-10 cc syringe Relatively atraumatic Sensitivity of 73-99% Ideal for simple cyst aspiration Can’t distinguish in-situ vs invasive cancer Can confirm relapse of known cancer

31. Core Needle Biopsy CNB - Core Needle Biopsy 14 - 20 gauge cutting needle greater trauma high sensitivity – 80-100% distinguishes between invasive and in-situ Diagnostic of many malignancies Non-diagnostic for lymphoma Avoid bone

32. Open Biopsy Open Biopsy (incisional or excisional) any suspicious finding clinical or radiologic finding with negative FNA or CNB atypia on FNA or CNB - 20-50% malignancy on open biopsy recurring cyst, enlarging node

33. Adequate Biopsy is Critical Open biopsy required to discern reactive (benign) from malignant lymphoid disorder Open biopsy required for lymphoma Diagnosis must be biopsy-proven before treatment is initiated Need enough tissue to assess architecture FNA is never adequate

34. Diagnosing Lymphoma Nodular (follicular)Diffuse small cell large cell IndolentAggressive

35. Lymph node biopsy – Follicular NHL

36. Questions? Kathryn.kolibaba@usoncology.com

37. A practical way to think of lymphoma CategorySurvival of untreated patients CurabilityTo treat or not to treat Non- Hodgkin lymphoma IndolentYearsGenerally not curable Generally defer Rx if asymptomatic AggressiveMonthsCurable in some Treat Very aggressive WeeksCurable in some Treat Hodgkin lymphoma All typesVariable – months to years Curable in most Treat

38. Relative Frequencies of Lymphoma Hodgkin Lymphoma 15% NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas 85% ~85% of NHL are B-lineage