Lymphatic Anomalies

The ISSVA (International Society for the Study of Vascular Anomalies) classification system, updated in 2014, divides lymphatic anomalies into lymphatic tumors and lymphatic malformations, with malformations further categorized as macrocystic, microcystic, combined, generalized lymphatic anomaly, Gorham-Stout disease, or central conducting anomalies.

The terms 'cystic hygroma' and 'lymphangioma' are outdated and should not be used; the correct term is 'lymphatic malformation' because it describes malformed embryologic lymphatic tissue.

Macrocystic lymphatic malformations have cysts large enough to be individually visualized (like a bunch of grapes), making them amenable to needle aspiration and sclerotherapy.

Microcystic lymphatic malformations have cysts too small to see individually, presenting as a soft tissue mass like a porous sponge, making sclerotherapy less practical.

Most lymphatic malformations are present at birth and visible at birth, though some may present later (e.g., at age 2) with sudden expansion of a previously undetected lesion.

Differential diagnosis for a 2-year-old with a new mass includes sarcomas, teratomas, and infectious lesions, not just lymphatic malformations.

Four general treatment options for lymphatic malformations are: observation/reassurance, microinterventional therapy (sclerotherapy), resective surgery, and pharmacological therapy.

For localized macrocystic lesions, sclerotherapy is preferred if one or two sessions can achieve a durable result without leaving a concerning scar; for very small lesions, minor resection may be preferred for a more durable outcome.

Very large macrocystic lesions extending from axilla to pelvis may warrant upfront surgical resection rather than multiple sclerotherapy sessions, because shrinking all cysts still leaves redundant skin and septa that may require eventual resection anyway.

EXIT (ex utero intrapartum treatment) procedures are not really necessary for lymphatic lesions, as they are soft and compressible and intubation is always achievable, unlike firm teratomas where EXIT plays a role.

Sirolimus (rapamycin) and everolimus are mTOR inhibitors that block the PIK3CA pathway, which is implicated in somatic mutations found in many lymphatic malformations.

A 2008 FDA-funded study at Boston Children's Hospital demonstrated that sirolimus improved quality of life, reduced pain, and decreased infection frequency in patients with complicated vascular anomalies with a lymphatic component.

Preoperative mTOR inhibitor therapy can soften lymphatic tissue, decrease lesion size, and make surgical debulking less extensive.

Dr. Fishman routinely operates on complex lesions (e.g., Klippel-Trénaunay syndrome) without stopping sirolimus preoperatively, finding that the tissue is softer and skin flaps more pliable, allowing more extensive resection with better closure.

Purely macrocystic lesions are unlikely to benefit from sirolimus therapy; the drug is more useful for microcystic and complex lesions.

Most lymphatic malformations do not spontaneously resolve, though rare cases of macrocystic lesions have deflated and remained quiescent for over a decade.

Dr. Fishman observed a massive cervical and mediastinal macrocystic lymphatic malformation detected prenatally that became undetectable on physical exam within less than a year after birth, without intervention.

Babies with congenital lymphedema of the lower extremities can have regression to the point of non-detection on physical exam, though this is uncommon.

For lesions not impinging on the airway or causing functional impairment, observation is a safe option, and the choice to intervene can be deferred.

Lesions impinging on the airway that could cause an emergency if infected or if they bleed internally should not be observed; early intervention is indicated.

Microcystic lesions on the face, tongue, or floor of the mouth are now treated very early in infancy, as early treatment likely yields better long-term results than delayed treatment.

Follow-up intervals for observed lymphatic malformations should be individualized: monthly initially for new parents, then extending to 3, 6, or 12 months as appropriate.

Ultrasound with Doppler is the first-line imaging modality for suspected lymphatic malformations, as it is least invasive and does not require sedation or anesthesia.

MRI is the next step if ultrasound is inconclusive.

'Burrows' rule' (named after interventional radiologist Pat Burrows) states that if a lesion is not classic on history, physical, and imaging, tissue biopsy is necessary to confirm diagnosis.

Dr. Fishman encountered a small leg lesion thought to be a vascular malformation that was ultimately diagnosed as synovial sarcoma on frozen section during resection; the tumor was metastatic and the patient did poorly.

Dr. Fishman was involved in a case of a newborn with what was thought to be multifocal hemangioma of the liver, which turned out to be metastatic neuroblastoma.

Sclerotherapy agents are chosen based on lesion type: doxycycline for macrocysts, bleomycin for microcysts (with monitoring for side effects), and sodium tetradecyl sulfate (STS) for venous components.

Venous sclerotherapy should almost always be performed under fluoroscopy to map venous drainage and prevent intravascular injection of sclerosant.

A small amount of ethanol injected systemically during venous sclerotherapy can cause sudden fatal pulmonary hypertension.

Large venous anomalies (e.g., in Klippel-Trénaunay syndrome) with direct macroscopic outflow to systemic veins can result in pulmonary embolism from clot induced by sclerotherapy; the outflow must be obliterated first using intravenous laser, titanium coils, glue, or guide wires.

Bleomycin is a cancer medicine that can cause pneumonitis if maximum dose limits are not observed during sclerotherapy.

Central conducting lymphatic anomalies can present with subcutaneous chyle, eroding bones, chylous ascites, chylothorax, and chyle dripping from the urethra, scrotum, vagina, or even from under toenails.

Combined overgrowth syndromes like Klippel-Trénaunay and CLOVES syndrome involve multi-system and multi-tissue involvement and do not have simple treatment answers; these patients benefit from expert consultation.