Lymphatic malformation

LM · cystic hygroma (historical, macrocystic) · lymphangioma (historical)

Lymphatic malformations (LMs) are congenital slow-flow vascular anomalies of dysplastic lymphatic channels. They are classified by ISSVA 2018 as macrocystic, microcystic, or mixed. The cutaneous manifestation — lymphangioma circumscriptum — is a superficial microcystic LM. Most are present at birth or appear in early childhood. Sirolimus (mTOR inhibitor) has transformed management of complex / refractory disease.

CurrentLast reviewed 16 May 2026

Classification (ISSVA 2018)

Macrocystic LM (cyst ≥1 cm): translucent fluid-filled swellings; common in neck, axilla, mediastinum.
Microcystic LM (cysts <1 cm): firm infiltrative tissue; oral / vulval / scrotal commonly.
Mixed: both.
Generalised lymphatic anomaly (GLA), Gorham-Stout disease, central conducting lymphatic anomaly — distinct entities under LM spectrum.

Genetics and biology

Sporadic somatic mosaic mutations:
- PIK3CA — most common; activating mutations within PI3K pathway.
- VEGFR3 / FLT4 — some primary lymphoedema overlap.
Defective lymphangiogenesis during embryonic period; abnormal lymphatic endothelial differentiation.
Markers: D2-40 (podoplanin), PROX1, LYVE-1 (lymphatic endothelium).

Clinical features

Macrocystic:
- Soft, translucent fluctuant swelling.
- Posterior neck, axilla, chest wall, abdomen, mediastinum.
- Acute enlargement with intralesional bleeding / infection.
Microcystic (lymphangioma circumscriptum):
- Frog-spawn-like vesicles, often haemorrhagic.
- Sites: oral cavity, tongue, vulva, scrotum, perineum, axilla.
- Lymphorrhoea, recurrent cellulitis.
Complications: airway compression, recurrent infection, lymphorrhoea, bleeding, lymphoedema, secondary cellulitis.

Workup

MRI with contrast: gold standard; T2-bright, septated; differentiates from venous malformation.
USS: differentiates cystic vs solid; flow Doppler distinguishes from haemangioma.
Fluid aspirate: chyle / clear lymph (vs blood of venous malformation).
Skin biopsy (rarely needed): D2-40 / PROX1 / LYVE-1 positive lymphatic channels.
Genetic biopsy from affected tissue: PIK3CA / VEGFR3 sequencing.

Management

Multidisciplinary vascular-anomaly team.
Sclerotherapy: doxycycline, OK-432 (Picibanil), bleomycin, ethanol — for macrocystic and mixed disease.
Surgical excision: for localised macrocystic disease; high recurrence in microcystic.
Laser: CO2 ablation for superficial microcystic / lymphangioma circumscriptum.
Sirolimus (mTOR inhibitor): transformative for complex / refractory cases (Adams 2016); 0.8 mg/m² BD with target trough 5-15 ng/mL.
Alpelisib (PI3K inhibitor) — emerging for PIK3CA-related disease.
Antibiotic prophylaxis for recurrent cellulitis; treat any cellulitis aggressively.
Compression for limb LM with lymphoedema component.

References

ISSVA classification of vascular anomalies. Boston: ISSVA; 2018.

Adams DM et al. Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics. 2016;137:e20153257.

Hammill AM et al. Sirolimus for the treatment of complicated vascular anomalies in children. Pediatr Blood Cancer. 2011;57:1018-1024.

Mulliken JB, Burrows PE, Fishman SJ. Mulliken and Young's Vascular Anomalies: Hemangiomas and Malformations. 2nd ed. Oxford: OUP; 2013.

Venot Q et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018;558:540-546.