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Evaluating Adenopathy: When to Worry and What to Do Kate Kolibaba, M.D. Northwest Cancer Specialists Vancouver, WA [email protected] Adenopathy: Objectives Lymphatic system basics Causes of lymphadenopathy Evaluation The Lymphatic System 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 Lymph Node - Normal Histology afferent lymphatic vessel capsule C follicle (mainly B-cells) - germinal centre - mantle zone artery efferent lymphatic vessel vein 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 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 Lymphadenopathy Enlargement or change in texture of a lymph nodes Adenopathy • Benign vs. malignant • Require treatment Evaluation Goals of Evaluation Identify the infrequent but serious causes of lymphadenopathy • History, including exposures • Age of patient • Location Differential Diagnosis MIAMI • • • • • Malignancy Infection Autoimmune Miscellaneous-sarcoidosis, hyperthyroidism Iatrogenic-serum sickness, medications Infectious Causes of Adenopathy Tuberculosis Bacterial • Brucellosis, cat-scratch, STDs Viral • HIV, hepatitis, CMV, EBV, rubella Autoimmune Causes of Adenopathy Lupus erythematosis Rheumatoid arthritis Dermatomyositis Sjogren’s syndrome Drugs Associated with Adenopathy allopurinol atenolol captopril carbamazepine gold hydralazine penicillins phenytoin primidone pyrimethamine quinidine Trimethoprim/sulfamethoxizole sulindac 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 Likelihood of Malignancy Lymphadenopathy that lasts < 2 weeks or > one year with no size increase is unlikely to be neoplastic Associated Symptoms Fever, night sweats, weight loss • “B” symptoms, lymphoma Fatigue, malaise, fever • Atypical lymphocytosis, mononucleosis Arthralgias, weakness, rash • autoimmune Physical Examination Supraclavicular most likely to be malignant • 54-85% neoplastic in biopsy series Axillary and Inguinal Adenopathy Drain extremities Often nonspecific, reactive Up to 2 cm can be normal Nodal Character There is no specific size threshold that raises suspicion Hard, painless • Malignant (metastatic) or granulomatous Rubbery • Lymphoma 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. Evaluation of Adenopathy Empiric treatment • Often antibiotics and/or corticosteroids are prescribed, but no data exists to support this approach Benign or Self-Limited Disease Treatable Yes Treat appropriately No Reassurance, explain course of disease Offer follow-up for persistent or changing adenopathy Suspected Autoimmune or Serious Infectious Disease Specific Testing Positive Treat appropriately Negative See “Unexplained” Suspected Malignancy Biopsy Positive Treat appropriately Negative See “Unexplained” Unexplained Adenopathy Review risk factors for malignancy If high risk, proceed with excisional biopsy Unexplained Adenopathy Low Risk for Malignancy Generalized Regional Referral or Follow-up Unexplained Generalized Adenopathy Consider miscellaneous causes • • • • • Sarcoidosis Silicosis, berylliosis Storage diseases: Gaucher, Fabry’s Hyperthyroidism, hypertriglyceridemia Kawasaki syndrome Unexplained Generalized Adenopathy CBC, RPR, PPD, HIV, HBsAg, ANA Positive Negative Biopsy most abnormal node Treat Positive Negative Follow-up More About Biopsies FNA Core needle biopsy Excisional biopsy 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 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 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 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 Diagnosing Lymphoma Nodular (follicular) Diffuse Indolent Aggressive small cell large cell Lymph node biopsy – Follicular NHL Questions? [email protected] A practical way to think of lymphoma Category NonHodgkin lymphoma Hodgkin lymphoma Survival of untreated patients Curability To treat or not to treat Indolent Years Generally not curable Generally defer Rx if asymptomatic Aggressive Months Curable in some Treat Very aggressive Weeks Curable in some Treat All types Variable – months to years Curable in most Treat Relative Frequencies of Lymphoma Non-Hodgkin Lymphomas 85% Diffuse large B-cell Hodgkin Lymphoma 15% NHL Follicular Other NHL ~85% of NHL are B-lineage