600 lymph nodesSubmandibular, axillary, inguinal

regions Normally palpable in adults

Lymphadenopathy Nodes that are abnormal in either size,

consistency or numberGeneralized lymphadenopathy

defined as two or more sites with abnormal lymph nodes.

Lymph nodes Not generally palpable in the noenate Childhood:

▪ 1 cm cervical and axillary nodes▪ 5 mm epitrochlear lymphnodes▪ 1.5 cm inguinal nodes▪ Shotty adenopathy in the cervical, posterior auricular,

inguinal areas▪ Common▪ Often due to routine uncomplicated intercurrent

infections

In primary care patients with unexplained lymphadenopathy, ¾ of patients will

present with localized lymphadenopathy

¼ with generalized lymphadenopathy

Findings from a Dutch study revealed that only 10 percent of patients with unexplained adenopathy required referral to a subspecialist, and only 1 percent had a malignancy.

The cause of lymphadenopathy is often obvious: the child who presents with a sore throat,

tender cervical nodes and a positive rapid strep test,

the patient who presents with an infection of the hand and axillary lymphadenopathy.

In other cases, the diagnosis is less clear.

To present an approach to the diagnosis and management of patients who present with lymphadenopathy. Especially those whose diagnosis is “less

clear”.

HistoryAnd Physical Examination

Generalized LocalizedPossible SVC

syndrome

Duration Fever Weight loss Night sweats Inflammatory disease Neoplasia Sexual history Travel Recent

injuries/wounds/systemic infections/surgery/dental complications

pets

HistoryAnd Physical Examination

Generalized Localized Possible SVC syndrome

Age Size

2.5 cm cervical lymph nodes may be seen in intercurrent infections

Generalized: >2 non contiguous lymph node

groups Systemic disease

Localized Single set of nodes or contiguous

set of nodes Erythema Tenderness Warmth Fluctuance Dental disease Rashes Wounds Concomittant splenomegaly

HistoryAnd Physical Examination

Generalized Localized Possible SVC syndrome

Respiratory difficulties

Wheezing Facial swelling Plethora orthopnea

HistoryAnd Physical Examination

Generalized LocalizedPossible

SVC syndrome

HistoryAnd Physical Examination

Generalized LocalizedPossible SVC

syndrome

Generalized adenopathy

CBC, blood smear, ESR LDHUric acid, Renal and hepatic Function

Chest x-ray

None Simple viral illnesses

CBC abnormal white counts Anemia thromboctyopenia

PBS Atypical lymphocytes blasts

ESR Increases in infections +/- in malignancy

EBV titers Infectious

mononucleosis Mildly increased

transaminases Plus normal CBC

▪ Suggestive of viral illness

LDH Malignancies, hepatic

disease, hemolysis Uric acid, Phosphorus,

BUN, Calcium, K Chest xray

If with chest symptoms; Mediastinal adenopathy

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease or chronic inflammation

disease

Infection likely High risk for malignancy No Yes

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease or chronic inflammation

disease

Infection likely High risk for malignancy No Yes

Rhinitis Pharyngitis Malaise Headache Fever Ask:

TB exposure Sexual behavior Drug use Transfusion history

Weight loss (>10%) Malignancy Tuberculosis HIV

Nodes: Soft Tender Non-erythematous

Rash Hepatosplenomegaly

Mild to moderate Normal CBC or mild

leukopenia Atypical lymphos Normal uric acid ESR normal

Generalized adenopathy

Lab Exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vascular disease

or chronic inflammation disease

Infection likely

Consider: EBV Varicella Rubella Mumps Toxoplasmosis Measles Chlamydia HIV TB Syphillis Fungal infection Collagen vascular and

inflammatory disorders

Appropriate serology may be done if indicated

Appropriate bacterial and fungal studies

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease

or chronic inflammation disease

Infection likely

Yes NO

Suspicion of malignancy still persists?

Presumed viral illness Adenopathy continues to increase over a

2-week period or fails to resolve over a 6-week period

Other changes: Development of a more firm or matted

consistency of the nodes Supraclavicular adenopathy Weight loss Night sweats Respiratory distress

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease or chronic inflammation

disease

Infection likely

Yes NO

Suspicion of malignancy still persists?

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease or chronic inflammation

disease

Infection likely

Yes NO

Lymph node or BM biopsy

Suspicion of malignancy still persists?

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressivenode Enlargement

Abnormal labs

Suggestive of collagen vasular disease or chronic inflammation

disease

Infection likely

Yes NO

Lymph node or BM biopsy Treat/observe as appropriate

Suspicion of malignancy still persists?

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

Infection likely High risk for malignancy No Yes

RashArthralgiaArthritisChronic symptomsMedication use Increased ESRAbnormal renal function

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

No Yes

Anti-ds-DNA AntibodiesACE

Drug use

RASLE

SarcoidosisSerum sickness

Drug-induced lymphadenopathy

(+) ds-DNA RA SLE

Sarcoidosis Serum sickness

Phenytoin INH Hydralazine Dapsone Procainamide allopurinol

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

No Yes

Anti-ds-DNA AntibodiesACE

Drug use

RASLE

SarcoidosisSerum sickness

Drug-induced lymphadenopathy

treat diagnosis

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

Infection likely High risk for malignancy No Yes

R/O storage diseases

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

Infection likely High risk for malignancy No Yes

R/O storage diseases

Check for massive splenomegalyDo leukocyte assays for storage

diseasesBM biopsy for some diseasesDifferentials:

Gaucher Nieman-Pick

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

Infection likely High risk for malignancy No Yes

R/O storage diseases

Therapy: specific Storage disease

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless, progressive

node Enlargement Abnormal CBC, smear,

inc uric acid, inc LDH, abn CXR

Suggestive of collagen vasular disease or chronic inflammation

Infection likelyHigh risk for malignancy

No Yes

Generalized adenopathy

Lab exams

Flu-like symptoms

Weight loss, night sweats, bone pain, Painless

, progressivenode Enlargement

Suggestive of collagen vasular disease or chronic inflammation

Infection likelyHigh risk for malignancy

No Yes

Weight loss Night sweats Bone pain Painless, progressive node

enlargement Suprclavicular adenopathy Nodes rubbery and fixed

to skin/underlying tissues malignancy

Shotty adenopathy In ALL

Waxing and waning Hodgkin disease Apparent response to

antibiotic therapy Tuberculous node

May be firm, matted and fixed to surrounding confusion

Abnormal CBC Increased uric acid Inc LDH Abnormal Chest xray

Do LN bxBMA aspirateBM biopsyNa, K, ca, Mg, Phosphorus, BUN, creaChest xray

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressive

node Enlargement

Suggestive of collagen vasular disease or chronic inflammation

High risk for malignancy

InfectionOther inflammatory

states

Hodgkin diseaseNHL

LeukemiaTumpr lysis syndrome

Generalized adenopathy

Lab exams

Flu-like symptomsWeight loss, night sweats,

bone pain, Painless, progressive

node Enlargement

Suggestive of collagen vasular disease or chronic inflammation

High risk for malignancy

InfectionOther inflammatory

states

Hodgkin diseaseNHL

LeukemiaTumpr lysis syndrome

Differential dx for malignancy Hodgkin disease NHL Leukemia Neuroblastoma Rhabdomyosarcoma Histiocytici disroders Treatment: chemotherapy

HistoryAnd Physical Examination

Generalized LocalizedPossible SVC

syndrome

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Occipital Consider scalp

infections▪ Pediculosis capitus▪ Tinea capitis▪ Secondary infection of

seborrheic dermatitis

Rubella Roseola malignancy

Periauricular Cat scratch disease Eye infections Skin infections tularemia

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Cervical Streptococcal tonsilitis Viral infection URTI Acute adenitis EBV Malignancy

▪ ALL, NHL, neuroblastoma

▪ Hodgkin▪ Thyroid CA, NPCA,

fibrosarcoma

Kawasaki disease Toxoplasmosis Nonlymphoid masses

▪ Cystic hygroma▪ Giuter▪ Thyroid CA▪ Branchial cleft cysts▪ Sternocleidomastoid

tumors▪ Teratomas▪ Dermoid cysts▪ hemangiomas

Sinus histiocytosis TB

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Submaxillary Local infections of

the teeth and mouth

Acute lymphadenitis

Hodgkin disease NHL TB malignancy

Supraclavicular Very concerning Warrant biopsy Malignancy TB Histoplasmosis coccidioidomycosis

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Axillary Infections of the arm and

axilla Cat scratch disease Reactions to

immunizations malignancies

Mediastinal ALL NHL Hodgkin Neuroblastoma TB Fungal infection Teratoma Thyroid CA Thymoma Sarcoidosis

▪ Bilateral hilar LAD▪ Pulmonary parenchymal

infilteration, hypercalcemia▪ Incb ACE levels

Cystic fibrosis

Localized adenopathy

occipital

periauricular

cervical

submaxillary

supraclavicular

axillary

Mediastinal

abdominal

ilioinguinal

Abdominal NHL Hodgkin Mesenteric adenitis Other malignancies

Ilioinguinal Infections of

leg/groin Syphillis Lymphogranuloma

venereum plague

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

>1 cm in the cervical region Usually viral or bacterial Nodes decrease in 2-6 weeks

Persisting >6 weeks or continuing to increase for more than 2 weeks Do biopsy

Firm, nontender nodes Malignant

Tender, warm, erythematous, fluctuant, very mild anemia Infection

CBC Neutropenia, anemia, thromobocytopenia

LDH, phosphorus, uric acid

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Treatment: Trial of antibiotics Surgical drainage

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Observe for 2-6 weeks

Lab studies if questionnable diagnosis, progressively enlarging adenopathy, new symptoms or signs or failure to resolve after 6 weeks

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Do radiologic studies Ultrasound Xrays CT MRI Biopsy or excision

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Failure to improve, symptoms or laboratory findings suggestive of malignancy

Localized adenopathy

Assess all clinical data

Likely acute adenitis Or related to bacterial

infectionSuspected viral illness

Suspicious of malignancy

Non-lymphoid mass

Failure to improve, symptoms or laboratory findings suggestive of malignancy

Suspicious of malignancy Work-up discussed

previously▪ CBC▪ Blood smear▪ renal/hepatic fxn▪ LDH, uric acid, Ca, P▪ CXR▪ Possible CT

Early LN biopsy▪ Largest, most recently

enlarging lymph node▪ NOT always the

easiest/most accessible node