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Transcript
Lymphadenopathy
Soheir Adam , MD, MSc, MRCPath
The Lymphatic System

The body has approximately 600 lymph nodes, but
only those in the submandibular, axillary or inguinal
regions may normally be palpable in healthy
people.1 Lymphadenopathy refers to nodes that are
abnormal in either size, consistency or number.
There are various classifications of
lymphadenopathy, but a simple and clinically useful
system is to classify lymphadenopathy as
"generalized" if lymph nodes are enlarged in two or
more noncontiguous areas or "localized" if only one
area is involved.


Distinguishing between localized and
generalized lymphadenopathy is important in
formulating a differential diagnosis.
In primary care patients with unexplained
lymphadenopathy, approximately 3/4 of
patients will present with localized
lymphadenopathy and 1/4 with generalized
lymphadenopathy.
Lympahdenopathy

Findings from a Dutch study revealed a 0.6%
annual incidence of unexplained lymphadenopathy
in the general population.

Of 2,556 patients in the study who presented with
unexplained lymphadenopathy to their family
physicians, 256 (10 %) were referred to a
subspecialist and 82 (3.2 %) required a biopsy, but
only 29 (1.1 %) had a malignancy.
Lymphadenopathy
History


First, are there localizing symptoms or signs to
suggest infection or neoplasm in a specific site?
Second, are there constitutional symptoms such as
fever, weight loss, fatigue or night sweats to suggest
disorders such as tuberculosis, lymphoma, collagen
vascular diseases, unrecognized infection or
malignancy?
History


Third, are there epidemiologic clues such as
occupational exposures, recent travel or high-risk
behaviors that suggest specific disorders?
Fourth, is the patient taking a medication that may
cause lymphadenopathy? Some medications are
known to specifically cause lymphadenopathy (e.g.,
phenytoin ), while others, such as cephalosporins,
penicillins or sulfonamides, are more likely to cause
a serum sickness-like syndrome with fever,
arthralgias and rash in addition to lymphadenopathy.
Medications That May Cause Lymphadenopathy
Allopurinol (Zyloprim)
Atenolol (Tenormin)
Captopril (Capozide)
Carbamazepine (Tegretol)
Cephalosporins
Gold
Hydralazine (Apresoline)
Penicillin
Phenytoin (Dilantin)
Primidone (Mysoline)
Pyrimethamine (Daraprim)
Quinidine
Sulfonamides
Sulindac (Clinoril)
Adapted with permission from Pangalis GA, Vassilakopoulos TP, Boussiotis VA, Fessas P. Clinical approach to lymphadenopathy. Semin Oncol 1993; 20:570-82.
Physical Examination



Size.
Pain/Tenderness :The presence or absence of tenderness
does not reliably differentiate benign from malignant nodes.
Consistency: Stony-hard nodes are typically a sign of cancer,
usually metastatic. Very firm, rubbery nodes suggest
lymphoma. Softer nodes are the result of infections or
inflammatory conditions. Suppurant nodes may be fluctuant.
The term "shotty" refers to small nodes that feel like buckshot
under the skin, as found in the cervical nodes of children with
viral illnesses.
Physical Examination


Matting : can be either benign (e.g.,
tuberculosis, sarcoidosis) or malignant (e.g.,
metastatic carcinoma or lymphomas
Location : infectious mononucleosis causes
cervical adenopathy and a number of
sexually transmitted diseases are associated
with inguinal adenopathy
Physical Examination



Supraclavicular lymphadenopathy has the highest risk of
malignancy, estimated as 90 percent in patients older than 40
years and 25 percent in those younger than age.
Lymphadenopathy of the right supraclavicular node is
associated with cancer in the mediastinum, lungs or
esophagus.
The left supraclavicular (Virchow's) node receives lymphatic
flow from the thorax and abdomen, and may signal pathology in
the testes, ovaries, kidneys, pancreas, prostate, stomach or
gallbladder. Although rarely present
Evaluation of Suggestive S & S Associated with Lymphadenopathy
Mononucleosis-type
syndromes
Fatigue, malaise, fever, atypical
lymphocytosis
Epstein-Barr virus*
Splenomegaly in 50% of patients
Monospot, IgM EA or VCA
Toxoplasmosis*
80 to 90% of patients are
asymptomatic
IgM toxoplasma antibody
Cytomegalovirus*
Often mild symptoms; patients may
have hepatitis
IgM CMV antibody, viral
culture of urine or blood
Initial stages of HIV
infection*
"Flu-like" illness, rash
HIV antibody
Cat-scratch disease
Fever in one third of patients; cervical
or axillary nodes
Usually clinical criteria; biopsy
if necessary
Pharyngitis due to group A
streptococcus,
gonococcus
Fever, pharyngeal exudates, cervical
nodes
Throat culture on appropriate
medium
Tuberculosis lymphadenitis*
Painless, matted cervical nodes
PPD, biopsy
Secondary syphilis*
Rash
RPR
Hepatitis B*
Fever, nausea, vomiting, icterus
Liver function tests, HBsAg
Lymphogranuloma venereum
Tender, matted inguinal nodes
Serology
Chancroid
Painful ulcer, painful inguinal nodes
Clinical criteria, culture
Lupus erythematosus*
Arthritis, rash, serositis, renal, neurologic, hematologic
disorders
Clinical criteria, antinuclear antibodies,
complement levels
Rheumatoid arthritis*
Arthritis
Clinical criteria, rheumatoid factor
Lymphoma*
Fever, night sweats, weight loss in 20 to 30% of patients
Biopsy
Leukemia*
Blood dyscrasias, bruising
Blood smear, bone marrow
Serum sickness*
Fever, malaise, arthralgia, urticaria; exposure to antisera
or medications
Clinical criteria, complement assays
Sarcoidosis
Hilar nodes, skin lesions, dyspnea
Biopsy
Kawasaki disease*
Fever, conjunctivitis, rash, mucous membrane lesions
Clinical criteria
Less common causes of lymphadenopathy
Lyme disease*
Rash, arthritis
IgM serology
Measles*
Fever, conjunctivitis, rash, cough
Clinical criteria, serology
Rubella*
Rash
Clinical criteria, serology
Tularemiala*
Fever, ulcer at inoculation site
Blood culture, serology
Brucellosis*
Fever, sweats, malaise
Blood culture, serology
Plague
Febrile, acutely ill with cluster of tender nodes
Blood culture, serology
Typhoid fever*
Fever, chills, headache, abdominal complaints
Blood culture, serology
Still's disease*
Fever, rash, arthritis
Clinical criteria, antinuclear antibody,
rheumatoid factor
Dermatomyositis*
Proximal weakness, skin changes
Muscle enzymes, EMG, muscle biopsy
Amyloidosis*
Fatigue, weight loss
Biopsy
*--Causes of generalized lymphadenopathy.
EA=early antibody; VCA=viral capsid antigen; CMV=cytomegalovirus; HIV=human immunodeficiency virus; PPD=purified protein derivative; RPR=rapid plasma reagin; HBsAg=hepatitis B
surface antigen; EMG=electromyelography.
Unexplained Lymphadenopathy
Generalized Lymphadenopathy




almost always indicates a systemic disease is
present, proceed with specific testing as indicated.
If a diagnosis cannot be made, the clinician should
obtain a biopsy of the node.
The diagnostic yield of the biopsy can be maximized
by obtaining an excisional biopsy of the largest and
most abnormal node
The physician should not select inguinal and axillary
nodes for biopsy, since they frequently show only
reactive hyperplasia
Unexplained Lymphadenopathy
Localized Lymphadenopathy



The decision about when to biopsy is more difficult.
Patients with a benign clinical history, an unremarkable
physical examination and no constitutional symptoms
should be reexamined in three to four weeks to see if the
lymph nodes have regressed or disappeared.
Patients with unexplained localized lymphadenopathy who
have constitutional symptoms or signs, risk factors for
malignancy or lymphadenopathy that persists for three to
four weeks should undergo a biopsy.
Unexplained Lymphadenopathy
Localized Lymphadenopathy

Biopsy should be avoided in patients with
probable viral illness because lymph node
pathology in these patients may
sometimes simulate lymphoma and lead
to a false-positive diagnosis of
malignancy.
Lymphoma
Risk factors for NHL





immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents
ionizing radiation
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
Diagnosis requires an adequate
biopsy


Diagnosis should be biopsy-proven
before treatment is initiated
Need enough tissue to assess cells and
architecture
–
open bx vs core needle bx vs FNA
Staging of lymphoma
Stage I
Stage II
Stage III
Stage IV
A: absence of B symptoms
B: fever, night sweats, weight loss
Case: M.S.






25 year old woman
persistent dry cough
fever, NS, weight loss x 3 months
left cervical lymphadenopathy (2 cm)
left supraclavicular node (2 cm)
no splenomegaly
M.S. at presentation
M.S. at presentation
Case: M.S. differential diagnosis

lymphoma
–
–



Hodgkin
non-Hodgkin
lung cancer
other neoplasms: thyroid, germ cell
non-neoplastic causes less likely
–
sarcoid, TB, ...
What next?


Needle aspirate of LN: a few necrotic cells
Needle biopsy of LN: admixture of B- and Tlymphocytes. A few atypical cells.
Case: M.S. lymph node biopsy
Case: M.S. lymph node biopsy
Case: M.S. staging investigations




CT chest / abdo / pelvis
bone marrow
gallium scan
Blood work: normal
Staging Investigations



bone marrow normal
CT scan: L supraclavicular adenopathy; large
mediastinal mass; R hilum; no disease below
diaphragm
gallium avid
What is her diagnosis and stage?



nodular sclerosis HD
stage IIB
with bulky mediastinal mass