Approach to Lymphadenopathy PROF:AKMAL JAMAL FCPS;FRCSEd: 2013.

Approach to Lymphadenopathy

PROF:AKMAL JAMAL

FCPS;FRCSEd:

2013

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. 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

Objectives

Approach to Adenopathy Who to investigate When to investigate How to define risk for underlying malignancy

Definition: Lymphadenopathy

Lymph nodes that are abnormal in size consistency or number

Definitions

Pathologic Lymph Node >2cm in children is considered abnormal

Acute Lymphadenopathy < 2 weeks duration

Subacute Lymphadenopathy 2-6 weeks duration

Chronic Lymphadenopathy > 6 weeks duration

Classification: Lymphadenopathy

Generalized- if lymph nodes are enlarged in two or more noncontiguous areas

Localized- if only one area is involved.

Distinguishing between two is important in formulating a differential diagnosis.

3/4 of patients will present with localized lymphadenopathy

1/4 with generalized lymphadenopathy.

Why do lymph nodes enlarge?

Increase in the number of benign lymphocytes and macrophages in response to antigens

Infiltration of inflammatory cells in infection (lymphadenitis)

In situ proliferation of malignant lymphocytes or macrophages

Infiltration by metastatic malignant cells Infiltration of lymph nodes by metabolite

laden macrophages (lipid storage diseases)

The Lymphatic System

Normally palpable lymph nodes in healthy people?

The Lymphatic System Normally palpable lymph nodes in healthy people.

submandibular, axillary inguinal

Lymphatic System

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

Lymph nodes

Capsular shell Fibroblasts and reticulin

fibers Macrophages Dendritic cells T cells B cells

anatomy

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HISTOLOGYTWO ZONES:

A darkly staining cortexAnd a lightly staining medulla

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function

They are centers of lymphocyte production. Both B-lymphocytes and T-lymphocytes are produced here by multiplication of pre-existing lymphocytes.

Filter the products from lymph such as bacteria and other particulate matter and to prevent their entry into systemic circulation.

The antibodies produced by the B-Lymphocytes are carried to the circulation… and indirectly help in mounting an immune response.

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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

Algorithm to evaluate Lymphadenopathy

History

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

Medications That May Cause Lymphadenopathy

Allopurinol Atenolol (Tenormin) Captopril (Capozide) Carbamazepine Cephalosporins Gold Hydralazine

Penicillin Phenytoin Primidone Pyrimethamine Quinidine Sulfonamides Sulindac

Physical Examination

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 Matted

Location, location, location

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

Facial Papule with Adenopathy

Suppurative Lymphadenitis with Overlying cellulitis

Mycobacterial Lymphadenitis

Mycobacterial Lymphadenitis

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

Creating a Differential

CHICAGO

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Chicago

Cancer Heme malignancies: Hodgkins, NHL, acute

and chronic leukemias, waldenstroms, multiple myeloma (plastmocytomas)

Metastatic: solid tumor breast, lung, renal, cell ovarian

cHicago

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

Chicago

Infections

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

VIRAL

EBV…mono spot test CMV….cmv titers, immunsuppresed,

transplant recipient, recent blood transfusion HIV…IV 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

chicago

Connective Tissue Disease

Rheumatoid Arthritis SLE Dermatomyositis Mixed connective tissue disease Sjogren

chicago

Atypical lymphoproliferative disorders

Castleman’s disease Wegeners Angioimmuonplastic lymphadenopathy with

dysproteinemia

chicaGo

Granulomatous

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

OTHER…….chicago

RARE Kikuchi Rosia Dorfman Kawasaki Transformation of germinal centers

Non-Infectious Lymphadenopathy

Kawasaki Disease Lymphomucocutaneous Disease Five Characteristics of Disease (4/5 for

diagnosis) Fever >5 days Cervical lymphadenopathy (usually unilateral) Erythema and edema of palms and soles with

desquamation of skin Nonpurulent Bilateral Conjunctivitis Strawberry Tongue

Treatment IVIG and Aspirin

Systemic Manifestations of Kawasaki Disease

Kikuchi-Fujimoto disease Also known as necrotizing lymphadenitis Benign condition Affects young Japanese girls Associated Signs and Symptoms

Fever Nausea Weight loss Night Sweats Arthralgias Hepatosplenomegaly

Thought to have viral or autoimmune etiology The majority spontaneously regress within 6 months,

however some patients have recurrences

Rosai-Dorfman Massive, painless, bilateral cervical adenopathy Benign condition Generalized proliferation of sinusoidal histiocytes First decade of life with 2M:1F Associated signs and symptoms

Fever Neutrophilic leukocytosis Polyclonal hypergammaglobulinemia

Most patients will get a biopsy given the large adenopathy Characteristic biopsy showing sinus expansion with

histiocytes and phagocytosed lymphocytes (Foucar 1990) Treatment is supportive and most patients have

spontaneous regression

Rosai-Dorfman Lymphadenopathy

Langerhans Cell Histiocytosis Eosinophilic Granuloma

Solitary bone, skin, lung, or stomach lesions Hands-Schuller-Christian Disease

Diabetes Insipidus, Exophthalmos, Lytic bone lesions Letterer-Siwe disease

Life threatening multisystem disorder 50% 5 year survival

1/3 of patients will have background LAD Histopathology shows normal lymph node

architecture but increase sinusoidal Langerhans’ cells, macrophages, and eosinophils

Treatment with topical steroids, oral steroids, and even chemoradiation therapy

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Unexplained lymphadenopathy without signs or symptoms of serious disease or malignancy can be observed for one month, after which

specific imaging or biopsy should be performed

fine-needle aspiration, excisional biopsy remains the initial diagnostic procedure of choice.

Modern cross-sectional imaging modalities such as ultrasound(US), computed tomography (CT) and magnetic resonance (MR)

imaging allow reliable detection of cervical lymph nodes. However,the differentiation between benign and malignant lymph

nodes remains challenging

Alternative imaging modalities such as single photonemission computed tomography (SPECT) and positron emissiontomography (PET) can help to differentiate between benign and

malignant lymph nodes

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

Role of Ultrasound No radiation exposure Good for following the progress of an abscess Differentiate Reactive vs Malignant nodes

Reactive <1 cm Oval (S/L ratio <0.5cm) Normal hilar vascularity Low resistive index with high blood flow

Malignant >1 cm Round (S/L ratio >0.5cm) No echogenic hilus Cogaulative necrosis present High resistive index with low blood flow Extracapsular spread

Sensitivity 95% and Specificity 83% for differentiating reactive vs metastatic lymph nodes

The Role of FNA

Minimally invasive Low morbidity Not as reliable in children as in adults so you

can only trust FNA if it is positive (Twist 2000) Chau et al. 2003

Evaluated FNA of 289/550 patients referred with LAD

Sensitivity 49% and Specificity of 97% False negative rate of 45% 83% of false negatives were lymphomas

The Role of Excisional Biopsy

Still the gold standard for diagnosis Consider if FNA is inconclusive or if FNA is

negative but your suspicion for malignancy is high

You must excise the largest and firmest node that is palpable and must remove the node with the capsule intact (Twist 2000)

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

Unexplained Lymphadenopathy

Localized Lymphadenopathy

When to biopsy ?

Unexplained Lymphadenopathy

Localized Lymphadenopathy

Patients with benign clinical history, an unremarkable physical examination no constitutional symptoms should be reexamined in three to four weeks

to see if the lymph nodes have regressed or disappeared.

Unexplained Lymphadenopathy

Localized Lymphadenopathy

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.

Fine Needle Aspirate

Convenient, less invasive, quicker turn-around time

Most patients with a benign diagnosis on FNA biopsy do not undergo a surgical biopsy

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 cbcD. Have patient follow up in 3-4 weeks.