What’s in a node ?! Dr Hannes Koornhof Division of Clinical Haematology Groote 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 Solid tumors Lymphoma, CLL, ALL, AML 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 Onset of symptoms 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 Previous surgical history Medication 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 Cervical/submandibular 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 Splenomegaly 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: Anaemia: Clubbing: Oedema 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 Bloods 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

Thanks for trying to listen!