Lymph Nodes & Lymphoedema

The lymphatic system runs as a silent parallel circulation to the venous system, and its surgical pathology spans congenital malformations, infection, oncological staging, and chronic limb swelling. This topic links surgical anatomy with oncology and is a recurrent source of NEET PG case scenarios on a swollen limb, a neck node for biopsy, or the sentinel node concept.

Lymphatic anatomy — the surgical essentials

Lymph is interstitial fluid (~2–4 litres/day) returned to the venous system via lymphatic capillaries → collecting vessels → lymph nodes → lymphatic trunks → the thoracic duct (drains into the junction of the left subclavian and left internal jugular vein) and the right lymphatic duct (drains the right head/neck, right arm, right hemithorax). Lymphatic capillaries are blind-ended, lack a basement membrane, and have overlapping endothelial "flap valves" that permit entry of large molecules and cells. There is no lymphatic drainage in the central nervous system (replaced by glymphatics), cartilage, cornea, and bone marrow.

High-yield: The thoracic duct drains everything below the diaphragm plus the left upper quadrant of the body. Injury during left neck/oesophageal surgery → chylous fistula / chylothorax.

Functions of lymph nodes: filtration of antigens, lymphocyte production, and an immunological barrier — which is exactly why nodes enlarge in infection and become the highway for cancer metastasis.

Lymphoedema — definition and classification

Lymphoedema is chronic, progressive swelling of a limb (or other region) due to failure of lymphatic transport, leading to accumulation of protein-rich interstitial fluid. The high protein content drives chronic inflammation, fibrosis, and adipose deposition, distinguishing it from low-protein oedema of cardiac/renal/hepatic origin.

Primary vs secondary

Feature	Primary lymphoedema	Secondary lymphoedema
Cause	Intrinsic developmental defect of lymphatics	Acquired obstruction/destruction
Commonest worldwide	—	Filariasis (Wuchereria bancrofti)
Commonest in developed world	—	Malignancy / post-surgery / radiotherapy (e.g. post-mastectomy arm)
Sex	More common in females	Depends on cause
Examples	Milroy, Meige, lymphoedema tarda	Filariasis, cancer, radiotherapy, recurrent cellulitis, trauma

Primary lymphoedema — by age of onset (classic clinical classification)

Type	Age of onset	Notes / eponym
Congenital	At birth / < 2 years	Includes Milroy disease (familial, autosomal dominant)
Lymphoedema praecox	Puberty to 35 yrs (most common type)	Includes Meige disease (familial); peaks around puberty, female predominance
Lymphoedema tarda	After 35 years	Rare; investigate to exclude underlying malignancy

High-yield: Lymphoedema praecox (Meige) is the commonest primary lymphoedema, presents around puberty, and is far more common in females.

Lymphangiographic / structural classification

• Aplasia — complete absence of collecting lymphatics.
• Hypoplasia — reduced number/size (commonest pattern in primary lymphoedema).
• Hyperplasia / megalymphatics (Type I, Allen) — dilated, varicose, valveless lymphatics; associated with chylous reflux and the worst prognosis surgically.

Milroy disease — the named entity

• Autosomal dominant, congenital lymphoedema present at or shortly after birth.
• Due to mutation in the VEGFR-3 (FLT4) gene → defective lymphangiogenesis.
• Typically bilateral lower limb swelling; may be associated with hydrocele and intestinal lymphangiectasia.

High-yield: Milroy disease = VEGFR-3 (FLT4) mutation, congenital, autosomal dominant. Meige = praecox variant at puberty.

Pathophysiology

Lymphatic transport failure → stasis of protein-rich fluid → chronic low-grade inflammation → fibroblast activation and collagen deposition → subcutaneous fibrosis and adipose hypertrophy. Recurrent attacks of cellulitis/lymphangitis accelerate destruction of remaining lymphatics, creating a vicious cycle. Long-standing skin changes produce the classic "peau d'orange", hyperkeratosis, and eventually fibrotic "woody" non-pitting oedema.

Stemmer sign positive = inability to pinch and lift a skinfold at the base of the second toe — a bedside hallmark of lymphoedema.

Staging of lymphoedema (ISL — International Society of Lymphology)

Stage	Features
0 (latent)	Subclinical; transport impaired, no visible swelling
I	Pitting oedema that reduces with elevation; early/reversible
II	Pitting that does not fully reduce with elevation; tissue fibrosis appears
III (elephantiasis)	Non-pitting, fibrotic, hyperkeratotic, papillomatous skin; irreversible

Clinical features

• Painless, progressive limb swelling, usually unilateral (filariasis/secondary) or bilateral (Milroy).
• Starts distally (dorsum of foot, toes) and ascends — the reverse of venous oedema which is gravity-dependent.
• Early: pitting, reduces on elevation. Late: non-pitting, brawny, "buffalo hump" on dorsum of foot, squaring of toes, loss of ankle contour.
• Stemmer sign positive, peau d'orange, warty hyperkeratosis.
• Recurrent attacks of cellulitis (commonly Streptococcus pyogenes).

High-yield: Lymphoedema characteristically spares relief on elevation only in early stages and produces a positive Stemmer sign with non-pitting late oedema — contrast with the soft, pitting, elevation-relieved oedema of venous/systemic causes.

Investigations

Investigation of choice / gold standard: Lymphoscintigraphy (radionuclide lymphangiography) using technetium-99m labelled colloid/antimony sulphide — it confirms lymphatic dysfunction, shows dermal backflow, delayed transit, and absent/reduced node uptake. It has largely replaced conventional contrast lymphangiography (which itself damages lymphatics).

Approach to a swollen limb →

1. History & examination (onset, laterality, Stemmer sign, skin changes) →
2. Duplex ultrasound to exclude venous/DVT cause →
3. Lymphoscintigraphy to confirm lymphoedema (IOC) →
4. MRI / CT to define soft-tissue pattern and exclude pelvic/abdominal malignancy in secondary or tarda cases →
5. Nocturnal peripheral blood smear for microfilariae if filariasis suspected.

Modality	Role
Lymphoscintigraphy	IOC — functional confirmation
Duplex USG	Exclude venous disease/DVT
MRI/CT	Anatomy, malignancy, "honeycomb" pattern
Indocyanine green (ICG) lymphography	Real-time mapping for surgical planning
Peripheral smear (midnight sample)	Filarial microfilariae

Management

Lymphoedema is generally incurable; goals are control, prevention of progression, and avoidance of cellulitis. Conservative (Complex/Combined Decongestive Therapy, CDT) is first-line for the vast majority.

Conservative — DLCM:

• Decongestive Lymphatic therapy: manual lymphatic drainage (MLD).
• Compression: multilayer bandaging, then graduated compression garments.
• Meticulous skin/foot care + exercise + limb elevation.
• Intermittent pneumatic compression pumps.
• Diuretics are NOT effective (protein-rich fluid) and may worsen — avoid as primary therapy.
• Prompt antibiotics (penicillin) for cellulitis; prophylactic penicillin for recurrent attacks.

High-yield: First-line management of lymphoedema is conservative — Complex Decongestive Therapy, NOT surgery. Diuretics have no role.

Surgical (reserved for failed conservative therapy / disabling disease):

• Physiological / bypass procedures: lymphovenous anastomosis (LVA), vascularised lymph node transfer (VLNT) — best in early disease with viable lymphatics.
• Excisional / reductive: Charles procedure (radical excision of skin and subcutaneous tissue with grafting — for gross elephantiasis), Homans procedure (staged subcutaneous excision under flaps), Sistrunk / Thompson buried dermal flap.
• Liposuction for fat-predominant late disease.

Procedure	Type	Use
Lymphovenous anastomosis (LVA)	Physiological	Early disease, patent lymphatics
Vascularised lymph node transfer	Physiological	Early–moderate disease
Charles procedure	Excisional (radical)	Gross elephantiasis (skin grafted)
Homans procedure	Excisional (staged, flaps preserved)	Moderate disease, better cosmesis
Liposuction	Reductive	Fat-dominant chronic limbs

Complications

• Recurrent cellulitis / lymphangitis (commonest; Strep pyogenes).
• Lymphangiosarcoma — Stewart–Treves syndrome: aggressive angiosarcoma arising in chronic lymphoedema, classically the post-mastectomy lymphoedematous arm; presents as bluish-red nodules/plaques; poor prognosis.
• Functional disability, recurrent ulceration, fungal infection, psychological morbidity.

High-yield: Stewart–Treves syndrome = lymphangiosarcoma in chronic (post-mastectomy) lymphoedema. A new violaceous nodule in a chronically swollen arm is sarcoma until proven otherwise.

Lymphangitis & filariasis

Acute lymphangitis — spreading infection along lymphatics, seen as red streaks (red lines) ascending a limb from a portal of entry, with tender regional nodes (lymphadenitis); commonest organism Streptococcus pyogenes (also Staph). Treat with rest, elevation, and penicillin.

Filariasis — Wuchereria bancrofti (transmitted by Culex mosquito) is the commonest cause of secondary lymphoedema worldwide. Adult worms live in lymphatics → recurrent lymphangitis → fibrosis → elephantiasis of legs, scrotum, and breast; chyluria from rupture of dilated lymphatics into the urinary tract. Diagnosis: nocturnal (midnight) peripheral blood smear for microfilariae; antigen card test. Treatment: diethylcarbamazine (DEC), ± albendazole/ivermectin in mass programmes; doxycycline targets Wolbachia endosymbiont.

High-yield: Filariasis microfilariae show nocturnal periodicity → take the blood sample at midnight. Drug of choice = DEC.

Lymph node biopsy — indications & sentinel node

A persistently enlarged lymph node needs evaluation. Lymphadenopathy red flags: size > 1 cm persisting > 4–6 weeks, hard/matted/fixed nodes, supraclavicular location, systemic "B symptoms" (fever, night sweats, weight loss), or no obvious infective cause.

Biopsy options:

• FNAC — first-line, quick; good for carcinoma metastasis, poor for lymphoma architecture.
• Core needle biopsy — preserves some architecture.
• Excisional biopsy — investigation of choice for suspected lymphoma (needs intact nodal architecture for subtyping); choose the largest, most central, deepest node (avoid inguinal nodes — often reactive).

High-yield: Excisional biopsy of the whole node is the IOC for lymphoma; FNAC is inadequate because it destroys architecture. For suspected metastatic carcinoma, FNAC is acceptable first.

Sentinel lymph node (SLN) concept

The sentinel node is the first node draining a tumour's lymphatic basin — if it is negative, downstream nodes are presumed negative, sparing the patient a full nodal dissection and its morbidity (notably lymphoedema). Mapping uses blue dye (isosulfan/methylene blue/patent blue V) + radiocolloid (Tc-99m) ± ICG, identifying the "hot and blue" node.

• Breast cancer: SLNB is standard for the clinically node-negative axilla; if SLN is positive in selected cases (per ACOSOG Z0011), completion axillary dissection may be avoided.
• Cutaneous melanoma: SLNB indicated for intermediate-thickness lesions (Breslow ~0.8–4 mm) to guide staging/prognosis.

High-yield: A negative sentinel node spares the patient axillary clearance, dramatically reducing the risk of arm lymphoedema. The classic mapping is "hot and blue" (radiocolloid + blue dye).

Key differentials of a swollen limb

Feature	Lymphoedema	Venous oedema	Lipoedema
Onset	Distal (toes/foot) ascending	Ankle, gravity-dependent	Symmetrical, bilateral legs
Foot involvement	Yes (buffalo hump, squared toes)	Usually	Spares feet (cut-off at ankle)
Stemmer sign	Positive	Negative	Negative
Skin	Peau d'orange, hyperkeratosis	Haemosiderin, ulcers, varicosities	Soft, tender, bruises easily
Elevation relief	Early only	Yes	No
Sex	F (primary)	Either	Almost always female

Also exclude systemic causes (cardiac, renal, hepatic, hypothyroid/myxoedema), DVT, and malignant pelvic/inguinal nodal obstruction (especially in lymphoedema tarda).

Recently asked / exam angle

• A young girl with bilateral leg swelling at puberty → lymphoedema praecox (Meige). Congenital at birth, AD, VEGFR-3 → Milroy.
• IOC for lymphoedema = lymphoscintigraphy.
• First-line treatment = conservative decongestive therapy; diuretics have no role.
• Bluish nodule in a chronically swollen post-mastectomy arm → Stewart–Treves (lymphangiosarcoma).
• Best biopsy for suspected lymphoma = excisional node biopsy (not FNAC).
• Sentinel node = first draining node; "hot and blue"; negative SLN avoids axillary dissection.
• Thoracic duct injury → chylothorax/chylous fistula (drains into left subclavian–IJV junction).
• Filariasis = commonest cause of secondary lymphoedema worldwide; midnight smear; DOC = DEC.
• Charles procedure = radical excision + skin graft for elephantiasis.
• Stemmer sign positive is the bedside clincher for lymphoedema.

Rapid revision

1. Thoracic duct drains all below diaphragm + left upper body → empties at left subclavian–IJV junction.
2. Primary lymphoedema: congenital (Milroy), praecox (Meige, commonest), tarda (>35 yrs, rule out cancer).
3. Milroy = VEGFR-3 (FLT4) mutation, autosomal dominant, congenital.
4. Commonest secondary cause worldwide = filariasis; in the West = malignancy/post-surgery/radiotherapy.
5. Lymphoedema is protein-rich, starts distally, gives a positive Stemmer sign, late oedema is non-pitting — diuretics don't work.
6. IOC = lymphoscintigraphy (Tc-99m colloid); duplex first to exclude venous disease.
7. First-line treatment = Complex Decongestive Therapy (MLD + compression + skin care + exercise).
8. Surgery: physiological (LVA, VLNT) for early; excisional Charles/Homans for late/elephantiasis.
9. Stewart–Treves syndrome = lymphangiosarcoma in chronic lymphoedema — poor prognosis.
10. Excisional biopsy is best for lymphoma; FNAC for suspected metastatic carcinoma.
11. Sentinel node = first draining node, mapped "hot and blue"; negative SLN spares nodal clearance and prevents lymphoedema.
12. Acute lymphangitis = red streaks + tender nodes, Strep pyogenes, treat with penicillin; filariasis DOC = DEC, midnight smear.