Approach to

Lymphadenopathy

Case

A.
B.
C.
D.

41 yo male school teacher presents to your office with right sided

cervical lymphadenopathy. His past medical history is significant
for hypertension and dyslipidemia. His medications include hctz
and simvastatin. NKDA. He noticed the lump in his neck last week.
He has not experienced any fevers, chills or weight loss. He denies
any sore throat, ear pain or dental problems. His vital signs are
stable. On physical exam he has a 2cm anterior cervical lymph
node which is firm, non-tender and mobile. His HEENT exam is
unremarkable. No skin lesions are evident. No other
lymphadenopathy is found. How should you proceed with this
patient?
Location and duration typical for viral etiology. Have your patient
follow up for annual physical next year.
Proceed to fine needle aspiration.
Check a CXR and cbc.
Have patient follow up in 3-4 weeks.

Learning Objectives

Provide an approach to the patient with

peripheral lymphadenopathy
Be able to differentiate between benign and
serious illness
Knowledgeable of nodal distribution and
anatomic drainage
Present a substantial differential diagnosis
Indications for nodal biopsy

Definition: Lymphadenopathy
Lymph nodes that are abnormal in
size, consistency or number
Generalized
Localized

Lymphatic System

Network that filters antigens from the interstitial fluid

Primary site of immune response from tissue
antigens
Lymphatic drainage in all organs of the body except
brain, eyes, marrow and cartilage
Flaccid thin walled channelsprogressive caliber
600 lymph nodes in body
Slow flow, low pressure system returns interstitial
fluid to the blood system

Secondary lymphoid tissue

Lymph nodes

Capsular shell
Fibroblasts and reticulin
fibers
Macrophages
Dendritic cells
T cells
B cells

Peripheral lymphadenopathy

Most cases benign, self limited illness

Primary or secondary manifestation of 100
illnesses
The CHALLENGE is to decide if it is
representative of a serious illness

Parameters to help
distinguish between
benign and serious
illness
Age
Character
Location

Malignancy much more

common in patients
greater 50 yrs of age
Not exactly

Epidemiology
Lee et al 1980 Referral centers 925
underwent a lymph node biopsy.
Age <30 79% benign 15% lymphomatous
6% carcinomas
Age >50 40% benign 16% lymphomatous
44% carcinomas
Age 30-50 indeterminate values

Dutch study Fijten 1988

0.6 annual incidence of generalized

lymphadenopathy
2,556 present with unexplained
lymphadenopathy
10% referred to subspecialist3.2% required
bx and of that 1.1% had a malignancy
40 yrs + 4% risk of cancer vs. 0.4% risk in pts
younger than 40

Lymph node character

Size
Site
Consistency
Pain with palpation

Size

Greater than one centimeter generally

considered abnormal
Exception inguinal area, lymph nodes
commonly palpated (>1.5 cm)
Size does not indicate a specific disease
process
Obese and thin population

Pain..

Indication of rapid increase in size: stretch of

capsular shell
NOT useful in determining benign vs
malignant state
Inflammation, suppuration, hemorrhage

Consistency

Stone hard: typical of cancer usually

metastatic
Firm rubbery: can suggest lymphoma
Soft: infection or inflammation
Shotty buckshot under skin
Suppurated nodes: fluctuant
Detect node from stroma
Matting

Location, location, location

Post cervical: scalp, neck skin of arms thorax cervical and axillary nodes (lymphoma, head/neck ca)

Supraclavicular Nodes

Drain the mediastinum and abdomen

Breast, GI, Lung Malignancies

Hodgkins/NHL
Chronic Fungal and mycobacterial

Axillary Nodes

Drain arm, breast, thorax and neck

Hodgkin, NHL
Melanoma (drains back of arm)
Staph/strep
Cat scratch
Silicone prosthesis

Inguinal lymphadenopathy

Drain the lower extremity, genitalia, buttocks,

abdominal wall

Normal
People who walk barefoot
Squamous cell carcinoma of penis or vulva
Venereal disease

Epitrochlear

Lymphoma/CLL
Mono
Historically associated with syphilis, rubella,
leprosy
Studies to indicate an association with early
HIV disease in sub-Saharan Africa, areas
with high prevalence of disease

Hilar, mediastinal, abdominal

>1 cm considered pathological

Pneumonia/inflammatory process can cause
unilateral hilar disease
Lymphadenopathy limited to abdomen likely
malignant

Highest rate of malignancy

Right Supraclavicular
Mediastinum
Lungs
Upper 2/3 esophagus

Left Supraclavicular
Virchow node
Testes/ovaries
Kidneys
Pancreas
Prostate
Stomach
Lower Esophagus

Famous nodes

Virchows
Left supraclavicular (abdominal or thoracic ca)
Sister Joseph
Para-umbilical (gastric adenoca)
Delphian node
Prelaryngeal (thyroid or laryngeal ca)
Node of Cloquet (Rosenmuller node)
Deep inguinal near femoral canal

Presentation of
lymphadenopathy

Unexplained
lymphadenopathy
3/4 presents with
localized
1/4 present with
generalized

Algorithm to evaluate
Lymphadenopathy
Attention to history and
physical exam
Confirmatory testing
Indication for biopsy

History
Localizing symptoms or signs to suggest a
specific site
Constitutional symptoms: B symptoms
(fever, night sweats, >10%body wt >6months)
Epidemiologic clues: occupation, travel, high
risk behavior
Medications

Creating a Differential
CHICAGO

Chicago

Cancer

Heme malignancies: Hodgkins, NHL, acute

and chronic leukemias, waldenstroms,
multiple myeloma (plastmocytomas)
Metastatic: solid tumor breast, lung, renal,
cell ovarian

icago

Hypersensitivity syndromes

Serum sickness
Serum sickness like
illness

Drugs
Silicone
Vaccination
Graft vs Host

Specific Medications

Cephalosporins
Atenolol
Captopril

Dilantin
Sulfonamides
Carbamazepine
Primodine
Gold
Allupurinol

Ch cago

Infections

Viral
Bacterial
Protozoan
Mycotic
Rickettsial (typhus)
Helminthic (filariasis)

VIRAL

EBVmono spot test

CMV.cmv titers, immunsuppresed,
transplant recipient, recent blood transfusion
HIVIV drug use, high risk sexual behavior
Hepatitis.IV drug use
Herpes Zoster.superficial cutaneous
nodules

Bacterial

Staph/strep: cutaneous source, lymphadenitis

Cat scratch: bartonella hensalae, two weeks
after inoculation
Mycobacterium: TB and non-tb, host
characteristics (HIV, foreign born, low
socioeconomic status, homeless)

Spirochete

Syphilis: Treponema pallidum Primary

localized inguinal lymph nodes and
secondary, non-treponemal, treponemal
Lyme disease

Protozoan
Toxoplasmosis: ELISA assay, intracellular
protozoan toxoplasmosis gondii.bilateral,
symmetrical, non-tender cervical adenopathy
consider undercooked meat, reactivation in
immuncompromised host

chi

cago

Connective Tissue Disease

Rheumatoid Arthritis
SLE
Dermatomyositis
Mixed connective tissue disease
Sjogren

chic

go

Atypical lymphoproliferative
disorders

Castlemans disease
Wegeners
Angioimmuonplastic lymphadenopathy with
dysproteinemia

Go

chica

Granulomatous

Histoplasmosis
Mycobacterial infections
Cryptococcus
Silicosis: coal, foundry, ceramics, glass
Berylliosis: metal, alloys
Cat Scratch

My cat Pigeon

OTHER.chicago

RARE
Kikuchi
Rosia Dorfman
Kawasaki
Transformation of germinal centers

Limited
Unexplained

Age

Location

History

Wait 3-4 weeks and reexamine

No indication for empiric antibiotics or steroids
Glucorticoids can be harmful and delay diagnosis
can obscure diagnosis due to lympholytic affect

Unexplained Generalized
lymphadenopathy

Always requires an evaluation

Start with CXR and CBC
Review Medications
PPD, RPR, Hepatitis screen, ANA, HIV
No yield on above test: Biopsy most
abnormal node

BIOPSY

Can be done by bedside, open surgery,

mediastinocopy or by needle aspiration*
FNA not recommended cannot distinguish
between lymphomas (nodal architecture
needs to be intact)
FNA reserved for established diagnosis and
to demonstrate recurrence

Diagnostic Yield

Ideally axillary and inguinal nodes are

avoided as often demonstrate reactive
hyperplasia
Preferred supraclavicular, cervical, axillary,
epitrochlear, inguinal
Complications include vascular and nerve
injury

Case

A.
B.
C.
D.

41 yo male school teacher presents to your office with right sided

cervical lymphadenopathy. His past medical history is significant
for hypertension and dyslipidemia. His medications include hctz
and simvastatin. He has no known drug allergies. He believes he
noticed the lump in his neck last week. He has not experienced
any fevers, chills or weight loss. He denies a sore throat, ear pain
or dental problems. His vital signs are stable. On physical exam he
has a 2cm anterior cervical lymph node which is firm, non-tender
and mobile. His HEENT exam is unremarkable. No skin lesions are
evident. No other lymphadenopathy is found. How should you
proceed with this patient?
Location and duration typical for viral etiology. Have your patient
follow up for annual physical next year.
Proceed to fine needle aspiration
Check a CXR and cbc
Have patient follow up in 3-4 weeks.

References

Uptodate Fletcher 2008 Evaluation of Peripheral Lymphadenopathy

Aster 2008 Castlemans Disease
Glazer. G. Normal Mediastinal Nodes AJR 144:261-265 Feb 1985
Ghirardelli, M. Diagnositc approach to lymph node enlargement. Haematologica
1999 84:242-247
Ferrer, R. Lymphadenopathy: Differential Diagnosis and Evaluation 1998
Haberman, T Lymphadenopathy Mayo Clinic Proc. 2000 75:723-732
Lee,Y. Lymph Node Biopsy for Diagnosis: A statistical study. Journal of Surgical
Oncology 14:53-60 1980
Skolnik, P Case 5-1999 37 yo male with fever and lymphadenopathy Volume
340: 545-554
Lichtman et al. (2006) Williams Hematology New York. McGraw-Hill
Parslow et al. (2001) Medical Immunology new York. McGraw-Hill
Malin, Ternouth (1994) Epitrochlear lymph nodes as a marker of HIV disease in
Subsaharan Africa BMJ 1994; 309 1550-1551
Bazemore and Smucker Lymphadenopathy and Malignancy AAFP 2002