What’s in a node ?!Dr Hannes KoornhofDivision of Clinical HaematologyGroote Schuur Hospital

Overview• Definition • Causes• Approach• Take home messages

Definition of lymphadenopathy (LA)

• Lymph nodes (LNs) that are abnormal in size (>1cm), consistency or number.

• Localized or generalized

Causes (CHICAGO)

•Cancer

•Hypersensitivity

• Infections

•Collagen vascular diseases

•Atypical lymphoproliferative disorders

•Granulomatous disorders

•Other

Cancer• Haematological• Lymphoma, CLL, ALL, AML

• Solid tumors• Head & neck, breast, lung, GIT, prostate, cervix, melanoma etc.

Hypersensitivity reaction• Drugs• Phenytoin• Allopurinol• Carbamazepine• Atenolol• Bactrim• Penicillins• Quinine

• Serum sickness• GvHD

Infections• Viral• Infective mononucleosis, HIV, CMV, Hepatitis B&C,

Adenovirus, HSV, HZV, MMR• Bacterial• Strep (pharyngitis), Staph, TB, Syphillis (1° or 2°), Chlamydia

(LGV)• Cat scratch disease, Brucellosis, Leptospirosis

• Fungal• Histoplasmosis, Cryptococcus

• Rickettsia• Tick bite fever

• Parasites • Toxoplasmosis

Connective tissue diseases• SLE (50%)• Rheumatoid arthritis• Dermatomyositis• Sjogren’s disease

Atypical lymphoproliferative disorders

• Castleman’s disease• Rosai-Dorfman disease• Etc...

Granulomatous diseases• Sarcoidosis• Wegener’s granulomatosis• Crohn’s disease• Granulomatous infections• TB, fungi, Syphilis, Brucellosis

Other• Hypothyroidism• Addison’s • Storage diseases• Gaucher’s disease, Niemann-Pick disease

So how on earth do I approach this??!

• Back to 2nd year...• Often you just need common sense!

Which one is not supposed to look like this....??

HISTORY

History• Age• Study from a tertiary centre: <30y >>> 79% benign vs 60%

malignant if >50y• Probably a bit different at primary level, but point taken

• Onset of symptoms• Duration? Progressing?

• >4w or progressing: Chronic infections, malignancies, collagen vascular diseases

• <4w and not progressing (often localized): Most often infection e.g. Infectious mononucleosis, bacterial pharyngitis

History• Systemic symptoms (Guided by localization of LNs):• Specific systems e.g. Respiratory, Genitourinary, GIT,

musculoskeletal• General symptoms e.g. LOW, night sweats, fever, fatigue

History• Previous medical history• TB, HIV, Epilepsy, COPD, Previous malignancy & its treatment

• Previous surgical history• Medication• Family history• Malignancy, TB contact

• Social• Smoking• High risk behaviour (STI’s, HIV)• Travel• Pets

PHYSICAL EXAMINATION

Localization of nodes• Generalized• Systemic disease

• Cervical/submandibular• Viral (Infectious mononucleosis), Bacterial pharyngitis, Ear

infections, TB• Malignancies of head, neck & oral cavity• Lymphoma• Melanoma

Localization of nodes• Supraclavicular (High likelihood for malignant)• Right: Lung & breast Ca/implants, Lymphoma, TB, Esophageal Ca• Left: Lung & breast Ca/implants, Lymphoma, TB, Intra-abdominal

malignancy• Axilliary (Drains arms, breasts & thorax)• Skin infections• Melanoma• Breast Ca• Lymphoma

Localization of nodes• Epitrochlear• Lymphoma• Infectious mononucleosis• Local upper extremity infections• Sarcoidosis• Secondary syphilis• HIV

Localization of nodes• Inguinal (Up to 2cm can be normal; lowest diagnostic yield)• Cellulitis• Venereal disease• Lymphoma• Metastatic melanoma• Squamous cell carcinoma (metastatic from the penile or vulvar

regions)

Localization of nodes• Intra-abdominal• Suggestive of malignancy, chronic infection (especially if

retroperitoneal)• Splenomegaly• Infectious mononucleosis• Various haematological malignancies (Lymphoma, CLL, ALL, AML)• Tuberculosis• HIV• Collagen vascular disease• Sarcoidosis

Lymph node characteristics• Size• >1cm abnormal, especially >2cm

• Consistency• Hard (Carcinoma)• Firm & rubbery (Lymphoma)• Matted (TB, Ca)• Fluctuant (TB)

Lymph node characteristics• Tender• Suggest recent, rapid enlargement (capsule stretch)• Usually inflammatory

• Fixed• Ca, TB

JACCOLD• Jaundice:

• Hepatobiliary 1⁰ or 2⁰ malignancy, TB, Lymphoma, Viral hepatitis

• Anaemia: • Chronic disease, BM infiltration, GIT bleeding, haemolysis

• Clubbing: • Lung Ca

• Oedema• Lymphoedema, Venous thrombosis, SVC obstruction, low albumin

Systemic examination• As guided by symptoms and LN drainage• ?HSM

Supportive tests• Radiology• CXR, Abd U/S, CT scan

• Bloods• FBC&diff, smear• LDH, Uric acid, LFT’s• ESR• HIV & other virusses(e.g. Monospot test)• RPR, ANF, s-ACE

• Sputum for TB (Zn, culture, GeneXpert)• Throat culture

Impression after assessment• Generalized LA with non-diagnostic initial assessment • Localized LA with high suspicion of malignancy

• Investigation of choice = Excision biopsy

Impression after assessment• Localized LA with non-diagnostic work-up & low suspicion of

malignancy

= Observe for 3-4w & reassess!

If persistent, excision biopsy.

What about a fine needle aspiration?

• Haematologists generally want to ban the procedure…• But it probably has a role…• If done in the correct setting…• In the correct way…• With timeous follow-up of the result and subsequent lymph

node excision in the likely event of a non-diagnostic FNA…

Advantages of FNA• Quick, accessible• Cheap• Outpatient• You can do it yourself• Less risk of tumour seeding• No scar• Quick result/turnaround time….• High yield in carcinoma & TB (in the HIV setting)

Disadvantages of FNA• Operator dependent• Often leads to delays if inconclusive results• Not the procedure of choice if lymphoma suspected & patient

will likely need a excisional biopsy anyway

To improve the yield of FNA• Rapid on site evaluation (ROSE)• U/S guided e.g. to try and avoid necrotic areas• Experienced FNA clinics• Cultures• Flow cytometry• Molecular tests

• Preferences differ between institutions & health care levels

Most NB things to remember• Excisional bx is diagnostic procedure of choice in >90% of

literature for: • Undiagnosed generalized LA• Localized LA with suspicion of malignancy• Non-resolving localized LA

• FNA has a potential role in:• Pt’s with probable carcinoma or malignancy recurrence• HIV-negative patients with suspected TB

Most NB things to remember• Sample the largest or most abnormal LN• Avoid inguinal LNs if possible (lowest yield)• FNA cytology result should be available within 24-48h, so

follow-up result and reassess• Excisional preferred above trucut/core needle• Excisional biopsy results• Atypical lymphoid hyperplasia: Considered non-diagnostic

(not negative) >>> Close f/u and stronly consider repeat bx• Unrevealing bx in a pt with high risk of malignancy should

be considered non-diagnostic (not negative)

Most NB things to remember• Avoid empiric antimicrobial therapy and corticosteroids

• Obscure accurate diagnosis• Prognostic effects• Tumor lysis syndrome

• TB lymphadenopathy is supposed to go away with TB treatment (This includes disseminated TB diagnosed by way of abdo U/S)

Most NB things to remember• Keep in mind that a patient may occasionally have 2 diagnoses

e.g. • TB & Hodgkin’s lymphoma • HIV & lymphoma, infections, carcinoma• Dermatomyositis & carcinoma etc.

• When in doubt, ask a colleague.

References• BMJ best practice guidelines• Up-to-date• Some shared clinical experience• Fine-needle aspiration biopsy of lymph nodes – CME 2012 Prof

C Wright• Clinical approach to lymphadenopathy – JK-practitioner

2011, A Abdullah

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