Transcript Lymphadenopathy

Lymphadenopathy
Differential Diagnosis
Steven W. Corso M.D.
12 march 2013
Lymphadenopathy
Outline and Objectives
 Brief overview of the Lymphatic System
 Anatomy
 Physiology
 Clinical approach to the patient with adenopathy
 Localized vs generalized
 Develop a Differential Diagnosis
 Examine common/important causes of
lymphadenopathy
Lymphadenopathy
Lymphatic System
 Anatomy
 A component of the
circulatory system
composed of:
 small caliber vessels
(lymphatic vessels)
 Lymph nodes
 We have hundreds
 Lymphoid tissue
 Spleen, thymus,
bone marrow,
lymphoid follicles
Lymphadenopathy
Lymphatic System
 Physiology
 Network of conduits and specialized tissue with
several key functions:
 Allows for return of fluid (lymph) to enter back into the
circulatory system
 Liters of plasma filtered out of the capillaries daily. Most
reabsorbed in blood vessels and returns via venous
circulation but several liters/day left in interstitial space
 Accessory route for this fluid to be returned to blood
 Immunologically important for mobilization of WBC
(lymphocytes) and filtering of antigens
Lymphadenopathy
Lymphatic System

Lymphatic fluid enters the lymph node in the afferent vessel, traverses the node
to exit via efferent vessel

Lymph is exposed to immunologically active cells throughout the node which
provide antigen processing/ presentation/recognition and proliferation of
effector B and T lymphocytes
Lymphadenopathy
Lymphatic System
Vascular System
Lymphatic System
Lymphadenopathy
Lymphatic System
 Normal immune
response leads to
proliferation and
expansion of cellular
components of lymph
nodes  lymph node
enlargement
 Children are constantly
undergoing exposure to
new antigens and
lymphadenopathy is the
rule not the exception
Lymphadenopathy
Introduction
 Common clinical finding
and often presents a
diagnostic dilemma
 Multiple etiologies
 Lymphadenopathy can be
caused by a vast array of
diseases and drugs

Some nodal
presentations suggest a
specific disease process

Some diseases present
predominantly with
adenopathy
Lymphadenopathy
Diagnostic Approach

History and Physical Examination

Etiology is often obvious after complete H&P

History

Age: cervical adenopathy in a child much less worrisome than 60 yo smoker

Symptoms of malignancy or infection: Fever, night sweats or weight loss

Duration: Acute (days) vs chronic (weeks-months)

Exposures associated with infection

Cat scratch (cat scratch disease)

Undercooked meat (toxoplasmosis)

Tick bite (Lyme disease)

Travel to endemic areas

High risk behavior (IV drugs or sexual behavior)

ROS for other systemic illnesses

Medications
Lymphadenopathy
Diagnostic Approach
 Medications
 A number of meds
can cause serum
sickness m/b fever,
arthralgias, rash and
generalized
adenopathy
 Phenytoin associated
with generalized
adenopathy in
absence of a serum
sickness reaction
Lymphadenopathy
Diagnostic Approach
 Physical Examination
 Evidence of local
infectious process
 Open wound or sore
 Pharyngitis/
vaginitis
 Focus on other signs
of systemic illness
 Splenomegaly
 Cutaneous findings
Lymphadenopathy
Diagnostic Approach
 Extent of Disease

Distinguishing between
localized and
generalized
lymphadenopathy can
help to formulate a
differential diagnosis

A clinically useful
approach is to classify
lymphadenopathy as
localized when it
involves only one
region such as the neck
or axilla, and
generalized when it
involves more than one
region
Lymphadenopathy
Diagnostic Approach

Physical Examination

Lymph nodes

Location - Localized

Cervical: commonly encountered due to high visibility and prevalence of
infections affecting head and neck region.

Inflamed nodes appearing over few days with fluctuation typically
staph/strep

Hard nodes in smoker is cancer till proven otherwise

Epitrochlear: never palpable so if present always represents pathologic
process

Supraclavicular: more often associated with malignancy

Axillary: drain multiple areas – cancer often found in absence of upper
extremity lesions


Also a common place for infectious process
Inguinal: frequent finding usually due to lower extremity infection, STD or
cancer
Lymphadenopathy
Diagnostic Approach
 Physical Examination

Lymph nodes
 Location – Generalized
 Predominant feature of a number of systemic illnesses. Some
common or especially important diseases include:

HIV: nontender nodes primarily involving the axillary
cervical and occipital nodes seen with initial infection

Mycobacterial infection: can present with adenopathy
alone – neck (scrofula); usually nontender and noted to
enlarge over weeks-months

Infectious mononucleosis: typically symmetric cervical
(posterior) nodes associated with fever and pharyngitis

Systemic lupus erythematosus: seen in 50% of patients;
typically non tender discrete cervical, axillary and
inguinal nodes
Lymphadenopathy
Diagnostic Approach

Physical Examination

Lymph nodes

Location

Size (Does matter)


< 1 cm rarely malignant

In one series, no patient with a lymph node smaller than 1 cm 2 had cancer, compared with 8 and 38 percent
of those with nodes 1 to 2.25 and greater than 2.25 cm 2

“Shotty” used to describe multiple small nodes but has no particular diagnostic significance
Consistency

Hard  post inflammatory fibrosis/sclerosis or solid tumors



Firm/rubbery  hematologic malignancy

Soft  inflammatory or infectious
Fixation: freely mobile or matted/fixed to surrounding tissue/nodes


Ex. Pancreatic and met breast cancer  hard and usually fixed nodes
Ex. Seen with met or neglected breast cancer
Tenderness: typical for inflammatory processes

Malignant nodes are rarely tender
Lymphadenopathy
Diagnostic Approach
 Diagnostic Tests
 Labs
 Confirm suspected diagnosis (Rapid Strep)
 Unknown diagnosis
 CBC
 Consider PPD, HIV, RPR, ANA
 Imaging studies
 Can define size and distribution more precisely
 CT, U/S, or MRI all useful at providing clues to Dx but
usually cannot replace biopsy
 CXR
Lymphadenopathy
Diagnostic Approach
 To Biopsy or Not To Biopsy: That is the Question!

Many review articles examining the approach to evaluation
and diagnosis of lymphadenopathy

Goal is to identify those patients most likely to benefit
from Bx (cancer, granulomatous diseases)

Hematology clinic - Greece
 study of causes of peripheral lymphadenopathy in 475
consecutive patients over the age of 14 followed for a
median of 69 months
 58% had nonspecific
 Specific findings included toxoplasmosis, lymphoma,
metastatic carcinoma, tuberculosis and infectious
mononucleosis
Vassilakopoulos TP, et al Medicine (Baltimore). 2000;79(5):338
Lymphadenopathy
Diagnostic Approach

When to perform biopsies of enlarged peripheral lymph nodes
in young patients. Slap GB et al; JAMA. 1984;252(10):1321.

123 patients (9-25 yo) who underwent biopsies of enlarged
peripheral lymph nodes

72 (58%) patients had biopsy results that did not lead to
treatment, and 51 (42%) had results that did lead to treatment

A predictive model was developed that assigned 95% of the
cases to the correct biopsy group based on:
 lymph node size;
 history of recent ear, nose, and throat symptoms
 chest roentgenogram.

When tested prospectively on new patients, the model
correctly classified 32 (97%) of 33 patients
Lymphadenopathy
Diagnostic Approach

Lymph Node Biopsy

Open biopsy
 Generally the best diagnostic test because histologic examination
of intact tissue provides information about both the presence of
abnormal cells (carcinoma, microorganisms) and abnormal node
architecture
 False negative results occur when the wrong node is taken, which
is not uncommon
 Outpatient procedure under local anesthesia
 Most abnormal node selected if multiple nodes are involved
 If no single node predominates, the choice in descending order of
preference is supraclavicular, neck, axilla, and groin

nonspecific result are greatest with axillary and inguinal nodes

complications of lymph node biopsy, infection and damage to the
neurovascular structures is higher in the groin and axilla
Lymphadenopathy
Diagnostic Approach
 Lymph Node Biopsy

Fine needle aspiration
 Cytology no
histology
 False negatives
common

Core needle Biopsy
 Increasingly utilized
when node not easily
accessible
 Improved ancillary
studies
Lymphadenopathy
Differential Diagnosis
 Infection

Bacterial


Mycobacterial


Lymphogranuloma venereum
Parasitic


Histoplasmosis, coccidiodomycosis
Chlamydial


Tuberculosis, leprosy
Fungal


Pyogenic bacteria, cat-scratch disease, syphilis, tularemia
Toxoplasmosis, trypanosomiasis, filariasis
Viral

EBV, CMV, rubella, hepatitis, HIV
Lymphadenopathy
Differential Diagnosis
 Infection
 Benign disorders of the immune system
 Rheumatoid arthritis
 SLE
 Serum sickness/ drug reactions
 Langerhans’ cell histiocytosis
 Kawasaki syndrome
 Kimura’s disease
Lymphadenopathy
Differential Diagnosis
 Infection
 Benign disorders of the immune system
 Malignant disorders of the immune system
 Lymphoma – Hodgkin’s and Non-Hodgkin’s
 Leukemia – chronic and acute
 Plasma cell dyscrasias – myeloma, Waldenstrom’s
macroglobulinemia
Lymphadenopathy
Differential Diagnosis
 Infection
 Benign disorders of the immune system
 Malignant disorders of the immune system
 Metastatic cancer (lung, breast, melanoma)
 Storage diseases (Gaucher’s and Niemann-Pick Disease)
 Endocrinopathies
(hyperthyroidism, adrenal insufficiency, thyroiditis)
 Miscellaneous: (sarcoidosis, amyloidosis)
Lymphadenopathy
Differential Diagnosis
 Most common causes in USA
 Unexplained
 Infection
 Drainage area of infection: pharyngitis with cervical
adenopathy
 Disseminated: mononucleosis
 Immune disorders: rheumatoid arthritis
 Neoplasms
 Hematologic
 Solid tumors
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Scenario 1
 10 y.o. with sore
throat and fever x 2
days during cold and
flu season

PE: Temp- 102.5
ill but non toxic
appearing, right
tender anterior
cervical LN
Oropharynx with
erythema and
exudate on tonsils
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 1 Cervical Lymphadenitis

Acute bilateral disease

Rhinovirus, EBV, CMV,
HSV, Adenovirus,
Enterovirus, Mycoplasma
pneumoniae, Group A
streptococcus, Influenza

Conservative management
recommended due to most
likely etiology (viral)

Follow up with further eval
if adenopathy persist or
progresses

Acute unilateral disease

Staphylococcus aureus, Group A
streptococcus, Anaerobic
bacteria

Further eval depends on severity
of symptoms and presenting
features

Exudative pharyngitis with
+ rapid strep test manage
with oral Abx

Ill/toxic child with
fluctuant node may require
FNA with oral/IV Abx
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Scenario 2
 20 yo college student
presents with fever,
malaise, and
posterior adenopathy
 PE: Temp-101 ill but
non toxic appearing
multiple non tender
bilateral cervical
nodes <1cm and
occipital adenopathy,
tender RUQ and mild
splenomegaly
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 2 Acute Bilateral Cervical Adenopathy
 Dx: Infectious mononucleosis presenting with classic triad
of fever, tonsillar pharyngitis and cervical adenopathy
 Pathogenesis: Epstein-Barr Virus = widely disseminated
herpes virus (90% of adults EBV+), spread by intimate
contact
 Dx Evaluation: CBC with lymphocytosis with atypical
lymphocytes on peripheral smear, CMP with elevated
AST/ALT, Monospot positive
 Treatment: Supportive
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Scerario 3

Otherwise healthy, 7 yo
girl with 2 week history
of a swelling behind her
left ear. She had no
systemic illness and
noted no improvement
with a course of
amoxicillin–clavulanate

PE: revealed a red,
tender, retroauricular
fluctuant lymph node
measuring 2 by 2 cm
behind her left earlobe.
No other lymph nodes
were enlarged.
Lymphadenopathy
Diff Dx – Cervical Adenopathy

Further History obtained
about recent exposure and
she reported having
regular contact with cats
and remembered being
scratched by one two
weeks earlier, shortly
before the mass appeared.
Diagnosis =
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 3 Cat Scratch Disease
 Cat scratch disease (CSD) is an infectious disease
characterized by self-limited regional
lymphadenopathy
 Epidemiology/Pathogenesis

Bartonella henselae is the etiologic agent responsible
for CSD. Cats serve as the natural reservoir and
transmitted via a cat scratch or bite (flea bite also
reported). Organism typically causes a local infection
that manifest as regional lymphadenopathy
 More commonly seen in children
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 3 Cat Scratch Disease
 Clinical
Manifestations
 Typically begins with
a cutaneous lesion at
the site of
inoculation; develops
3-10 days after the
bite/scratch and
evolves through
vesicular,
erythematous and
papular phases
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 3 Cat Scratch Disease
 Clinical Manifestations

Lymphadenopathy:
Regional adenopathy is
the hallmark of CSD.
Enlarged tender nodes
proximal to the site of
inoculation appear at
about 2 weeks. Very
commonly (85%)
present with solitary
node involved
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 3 Cat Scratch Disease

Clinical Manifestations

Visceral organ
involvement: liver-spleen

Constitutional: FUO,
weight loss

Ocular: neuroretinitis,
Parinaud’s
oculoglandular syndrome

Neurologic:
encephalopathy

Musculoskeletal:
Myalgias/arthralgias
Lymphadenopathy
Diff Dx – Cervical Adenopathy
Scenario 3 Cat Scratch Disease
 Diagnosis

Typical Hx and PE

Serology for B.
henselae
 Poor sens/spec
 IFA IgG titer > 1:256
strongly suggest
active or recent
infection

PCR or positive
Warthin-Starry stain
 Treatment

Most patients will have
gradual resolution
without intervention

Recommended to treat
with azithromycin x 5
days
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Scenario 4

24 yo female shooting a
movie in NC presents
to the ED with fever x 1
week and cervical
adenopathy. No prior
medical problems. Only
other complaint is
fatigue. She reports
uncle died of NHL and
he presented with fever
and adenopathy

PE: Healthy appearing,
Temp 100.9 normal
exam except for some
firm, nonfixed right
cervical nodes
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Diagnostic Evaluation
 Labs – normal except
for WBC-3500 and
atypical lymphocytes,
ESR-70, LDH -250
 Serology for EBV
HIV and CSD are
negative
 Imaging studies –
normal CT scan of
C/A/P; neck with
enlarged right
cervical nodes
Lymphadenopathy
Diff Dx – Cervical Adenopathy
 Scenario 4
 Biopsy performed
 FNA non diagnostic
 Excisional biopsy
reveals a histiocytic
cellular polyclonal
infiltrate with
preservation of
nodal architecture
Lymphadenopathy
Diff Dx – Cervical Adenopathy

Scenario 4

Diagnosis: Kikuchi’s
disease

Rare, benign condition of
unknown cause usually
characterized by cervical
lymphadenopathy and
fever

Most commonly seen in
young women

Diagnosis made by lymph
node biopsy and
excluding other causes

Self limited illness in
majority of patients

No effective treatment
May the odds be ever in your favor!
Lymphadenopathy
Dr. J Armitage Approach
1.
Does the patient have a know illness that causes lymphadenopathy?

2.
Is there an obvious infection to explain the lymphadenopathy?

3.
Perform a biopsy
Is the patient very concerned about a malignancy and unable to be
reassured that cancer is unlikely?

5.
Treat and monitor for resolution
Are the nodes very large and/or firm and thus suggestive of malignancy?

4.
Treat and monitor for resolution
Perform a biopsy
If none of the preceding are true, perform a CBC and if normal then
monitor with follow up in 2-6 weeks. Biopsy if progression noted or no
regression