Approach to

Lymphadenopathy
Case
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?
A. Location and duration typical for viral etiology. Have your patient
follow up for annual physical next year.
B. Proceed to fine needle aspiration.
C. Check a CXR and cbc.
D. 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..
Indicationof 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
 P ost cervical: scalp, neck ski n of arms thorax cervi cal and axill ary nodes (l ymphoma, 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

Peoplewho 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 Left Supraclavicular
Mediastinum Virchow node
Lungs Testes/ovaries
Upper 2/3 esophagus 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
 cH icago

Hypersensitivity syndromes
Serum sickness Drugs
Serum sickness like Silicone
illness Vaccination
Graft vs Host
Specific Medications
Cephalosporins Dilantin
Atenolol Sulfonamides
Captopril Carbamazepine
Primodine
Gold
Allupurinol
 i
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
 a
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
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?
A. Location and duration typical for viral etiology. Have your patient
follow up for annual physical next year.
B. Proceed to fine needle aspiration
C. Check a CXR and cbc
D. 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
Questions?