Evaluating Adenopathy:When to Worry and What to Do

Kate Kolibaba, M.D.Northwest Cancer Specialists

Vancouver, WAkathryn.kolibaba@usoncology.com

Adenopathy: Objectives

Lymphatic system basicsCauses of lymphadenopathyEvaluation

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 bodyLymph nodes filter foreign particles out of the

lymphatic fluid Contain B and T lymphocytes

Lymph Node - Normal Histology

afferent lymphatic vessel capsule

follicle (mainly B-cells)- germinal centre- mantle zone

C

cortex

medullaparacortex

efferent lymphatic vessel

artery

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 lymphocytesMost lymphocytes are in lymph nodes, spleen,

bone marrow and lymphatic vesselsT 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/sulfa-methoxizole

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 No

Treat Reassurance,appropriately explain course of disease

Offer follow-up for persistent or changing adenopathy

Suspected Autoimmune or Serious Infectious Disease

Specific Testing

Positive Negative

Treat Seeappropriately “Unexplained”

Suspected Malignancy

Biopsy

Positive Negative

Treat Seeappropriately “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

Positive Negative

Biopsy most abnormal node Treat

CBC, RPR, PPD, HIV, HBsAg, ANA

Positive Negative

Follow-up

More About Biopsies

FNACore needle biopsyExcisional 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

small cell large cell

Indolent Aggressive

Lymph node biopsy – Follicular NHL

Questions?

Kathryn.kolibaba@usoncology.comKathryn.kolibaba@usoncology.com

A practical way to think of lymphoma

Category Survival of untreated patients

Curability To treat or not to treat

Non-Hodgkin lymphoma

Indolent Years Generally not curable

Generally defer Rx if asymptomatic

Aggressive Months Curable in some

Treat

Very aggressive

Weeks Curable in some

Treat

Hodgkin lymphoma

All types Variable – months to years

Curable in most

Treat

Relative Frequencies of Lymphoma

HodgkinLymphoma 15%

NHL

Diffuse large B-cell

Follicular

Other NHL

Non-Hodgkin Lymphomas 85%

~85% of NHL are B-lineage