LYMPHATIC MALFORMATIONS

Arin K. Greene

A lymphatic malformation (LM) results from the abnormal development of the lymph system. The primary morbidity is psychosocial distress, because the lesion causes a deformity. LMs may also bleed, become infected, leak lymph fluid (lymphorrhea), and obstruct/destroy important structures. There are several phenotypes of LMs; many have a known causative mutation. Although LMs are present at birth, they may not be noted until childhood or adolescence. Lesions worsen particularly during puberty.

The management of LMs is based on the type of lesion. Macrocystic LMs have cysts greater than or equal to 5 mm that are large enough to be cannulated by a needle and treated with sclerotherapy. Sclerotherapy is the injection of a sclerosant (for example, doxycycline or ethanol) into a cyst, which causes irritation, shrinkage, and fibrosis of the lesion. Microcystic LMs with cysts less than 5 mm are typically not amenable to sclerotherapy. Microcystic lesions are managed with resection, bleomycin injection, carbon dioxide laser, radiofrequency ablation, and/or oral sirolimus. Combined LMs containing both macrocysts and microcysts can be treated with sclerotherapy. The cystic composition of LMs is determined by ultrasound examination. Primary lymphedema is managed with compression (custom-fitted garments, a pneumatic pump, and complex decongestive therapy); surgical intervention is reserved for severe overgrowth. Gorham-Stout disease and a generalized lymphatic anomaly affecting bone are treated with interferon and bisphosphonates; sirolimus also may reduce bone destruction and promote remineralization.

SURGICAL INDICATIONS

The treatment of LMs is not mandatory. Intervention is reserved for lesions that lower self-esteem, cause pain, bleed, or obstruct/destroy tissues. Resection and reconstruction should not leave a deformity worse than the LM. The primary variable that determines whether a lesion is resected is the type of LM; some can only be managed with excision, whereas others should be treated with sclerotherapy, carbon dioxide laser, radiofrequency ablation, or pharmacotherapy. Small, localized LMs are more amenable to resection, because they can potentially be removed for a cure.

Macrocystic LMs usually are managed best with sclerotherapy, because the treatment is more effective and safer than excision. This female was born with a large macrocystic LM of her right face and neck. She underwent resection of the lesion at an outside institution and suffered a facial nerve injury. Her appearance is shown at rest (A). An asymmetrical smile resulting from injury to her right marginal mandibular branch of the facial nerve is shown (B).

Macrocystic and combined LMs are managed with sclerotherapy, because this technique is safer and more effective than resection. Asymptomatic macrocystic lesions should generally be treated, because they are at risk of bleeding and infection. If a macrocyst has intralesional bleeding, the LM can be converted to microcysts, which are no longer amenable to sclerotherapy. Although sclerotherapy does not remove an LM, it effectively shrinks the lesion and improves symptoms. Resection of a macrocystic LM is reserved for:

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  Small lesions that may be completely removed for cure

  
  
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  Symptomatic LMs that can no longer be managed with sclerotherapy (all of the macrocysts have been treated)

MICROCYSTIC LYMPHATIC MALFORMATION

Asymptomatic microcystic LMs may be observed; intervention is reserved for problematic lesions. Generally first-line therapy is resection. Excision usually is subtotal, because microcystic LMs are often diffuse and involve multiple tissue planes. If a microcystic LM is in an unfavorable location for resection, other interventions are considered. Diffuse facial lesions may be improved by injecting bleomycin throughout the affected tissues. Extensive lesions of the skin can be managed with a carbon dioxide laser, cutaneous sclerotherapy, or cautery. Intraoral microcystic LMs may be improved with radiofrequency ablation. Recently oral sirolimus has shown efficacy for problematic LMs.

PRIMARY LYMPHEDEMA

Primary lymphedema is caused by hypoplastic lymphatic development. High-protein fluid is unable to be returned to the venous circulation, and pitting edema develops. Over time the fluid stimulates subcutaneous adipose deposition, which causes the area to enlarge. Ninety-five percent of patients managed in our lymphedema program can be treated conservatively with compression. Surgical intervention is reserved for individuals with subcutaneous adipose deposition that is causing lowered self-esteem, infections, and/or difficulty with the extremity.

TIMING OF INTERVENTION

LMs causing significant symptoms require intervention, regardless of the age of the child. If possible, treatment should be delayed until at least 6 months of age, because before this time the patient’s risk from anesthesia is greater than in an adult. In addition, a young infant is less able to tolerate a surgical procedure. If a large lesion is located on the scalp, removing it before 6 months of age should be considered to take advantage of scalp laxity that exists during infancy. Large, asymptomatic macrocystic LMs are treated prophylactically at 6 months of age, before the lesion bleeds or becomes infected, which would obviate future sclerotherapy.

If it is likely that a patient will require surgery to improve a deformity, I will commonly intervene between 3 and 4 years of age. Because long-term memory and self-esteem begin to form at approximately 4 years of age, removing an LM before this time will treat the deformity before it causes psychosocial distress; the patient will also likely not remember the procedure. Another period to intervene is during late childhood or early adolescence when the child is able to communicate whether he or she would like to have a procedure. If a patient has a minor deformity or a large lesion requiring significant reconstruction, the surgeon should wait until the child verbalizes the desire to have surgery. If the lesion is minor, it may be able to be removed with a local anesthetic by waiting until the patient is older. If the LM is significant, waiting until the child is a willing participant facilitates the process for the family and surgeon.

MACROCYSTIC LYMPHATIC MALFORMATION

Generally macrocystic/combined LMs should undergo sclerotherapy before resection because:

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  The lesion will be smaller.

  
  
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  Excision is facilitated, because cysts are converted to fibrotic tissue.

  
  
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  Peripheral vessels are permeated by the sclerosant, which theoretically reduces the recurrence rate.

Small lesions that can potentially be removed for a cure do not require preoperative sclerotherapy. Generally sclerotherapy is performed at 6-week intervals until the posttreatment ultrasound examination does not show that the remaining cysts are amenable to further injections.

Pure macrocystic LMs are most commonly located in the neck and axilla. These lesions can leave behind redundant skin after they have been deflated with sclerotherapy. In the axilla overresection of skin should be avoided to prevent a contracture. Large LMs can also have residual symptomatic microcystic disease after sclerotherapy, which may necessitate excision.

Most LMs are combined lesions containing both macrocysts and microcysts. These lesions should initially be managed with sclerotherapy to collapse the macrocysts. Usually the patient’s symptoms are adequately improved and resection is unnecessary. If the individual continues to have morbidity after sclerotherapy, extirpation of the area is facilitated.

Microcystic LMs are more difficult to manage compared with macrocystic lesions. Microcystic LMs usually involve the face and extremities. If the disease affects the integument, a patient may develop lymphatic vesicles that can bleed, become infected, and cause lymphorrhea. The best approach is to resect localized areas of skin involvement, which can recur along the scar. Larger regions of integument can be removed with serial excision. Diffuse lymphatic vesicles that are problematic to excise can be treated with a carbon dioxide laser. Alternatively, cutaneous vesicles can be managed with superficial sclerotherapy or cauterization. Intraoral lymphatic vesicles are best treated by radiofrequency ablation. This technique causes low-temperature tissue destruction, which reduces damage to adjacent structures. Compared with a carbon dioxide laser, there is less edema, which is particularly favorable in the oral cavity, because it minimizes the risk of airway obstruction.

Recent options to treat microcystic LMs are bleomycin sclerotherapy and oral sirolimus. Bleomycin can be diffusely injected throughout the tissues containing LM, and most patients will have a reduction in the size of the area and improvement in symptoms. Bleomycin is useful for patients with mild facial asymmetry, because the treatment may obviate the need for resection and a cutaneous scar. Individuals with diffuse, problematic microcystic LMs that have not responded to other interventions are candidates for sirolimus pharmacotherapy. Our center and others have had favorable outcomes with this medication; lesions have reduced size, bleeding, and lymphorrhea.

A large area of integument that has failed conservative therapies requires resection. Wounds are reconstructed by allowing them to heal secondarily, mobilization of local tissues, or skin grafts. Tissue expansion, regional muscle flaps, or free flaps are usually unnecessary. A recipient site containing a residual LM is more likely to accept a skin graft compared with a venous or an arteriovenous malformation. An underlying LM usually does not recur through the skin graft but may develop vesicles along the edges.

Localized LMs do not require preoperative imaging if only resection is planned. I prefer to obtain an MRI before I perform a resection of a large lesion to determine which surgical planes and anatomic structures are involved. Excision of an LM is associated with less bleeding compared with a venous or arteriovenous malformation. Blood loss is reduced by preoperative sclerotherapy and infiltrating the surgical area with epinephrine. If the volume of local anesthetic with epinephrine is limited by the amount of anesthetic that can be given based on the weight of the child, I will infiltrate an epinephrine-only solution to ensure maximum vasoconstriction of the surgical site (1 ml of 1:1000 epinephrine in 200 ml normal saline = 1:200,000 solution). The extirpation proceeds carefully by incising a localized area and controlling bleeding before continuing. Long, deep incisions should not be performed because of the risk of significant blood loss. None of the patients with an LM on whom I have operated has required a blood transfusion. I administer prophylactic intraoperative antibiotics to reduce the risk of postoperative infection, because LMs are predisposed to infection. If wide skin undermining is performed, drains should be placed, because tissues have a higher risk of lymph drainage.

Because most LMs are diffuse and involve multiple tissue planes, complete extirpation is rarely possible. Instead the goal is usually to alleviate symptoms and control the lesion. Despite subtotal and presumed “complete” extirpation, most LMs reenlarge. Patients and families are counseled that an LM is likely to recur after resection, and treatment may be needed in the future.

Surgical intervention for a diffuse facial LM should focus on improving the patient’s appearance or symptoms with localized, staged procedures without causing a significant deformity. Diseased tissue should not be removed if there is a risk of iatrogenic morbidity. Facial nerve dissections or parotidectomy generally should be avoided. When the lesion is throughout all structures of the face, strategies to improve the area include:

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  Excision of excess skin and subcutaneous tissue

  
  
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  Removal of the buccal fat pad

  
  
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  Contour burring of the zygoma

If overgrowth is located on the lateral cheek, a preauricular incision is used. Medial fullness is resected through a mesolabial incision. Alternatively, a circular excision can be used to access the overgrown tissue, and the purse-string closure can be revised at a second stage. Lip overgrowth is improved with a transverse mucosal resection along the keratinized and nonkeratinized border of the vermilion. Vertical resections of the lip should be avoided.

I typically do not use intraoral approaches to remove subcutaneous lesions. I prefer to make a cutaneous incision and remove abnormal subcutaneous tissues sharply under direct vision. I believe in the principle of trading scar for contour. Patients are most satisfied with achieving the best symmetry, which is noticed beyond conversational distance at the expense of a scar that can only be appreciated on close examination (similar to having a longer scar instead of a shorter scar and dog-ears at each end). Intraoral excision is more difficult and less predictable than direct cutaneous extirpation; there also is an increased risk of infection and facial nerve injury.

LYMPHEDEMA

There are two categories of procedures to treat lymphedema. Excisional procedures remove subcutaneous fibroadipose tissue; the two most common types are suction-assisted lipectomy (liposuction) and staged skin/subcutaneous excision. Physiologic surgeries attempt to improve lymphatic flow most often by lymphaticovenous anastomosis or vascularized lymph node transfer. My preferred surgical intervention for lymphedema is liposuction, because I think the technique gives the most consistent improvement and has minimal morbidity (see Video 8-1, Lymphatic Malformation).

Symptomatic patients who have failed conservative therapy undergo lymphoscintigraphy and an MRI before proceeding with suction-assisted lipectomy. Lymphoscintigraphy confirms the diagnosis of lymphedema and determines the severity of lymphatic dysfunction. An MRI documents subcutaneous fibroadipose overgrowth. Imaging of both extremities is necessary to compare the diseased limb with the contralateral side. If an MRI shows that the arm or leg is primarily enlarged because of fluid, the patient is not a candidate for the excisional procedure, and his or her compression regimen is maximized. It typically takes at least 6 years after the onset of edema for sufficient subcutaneous adipose tissue to be formed. If an MRI illustrates significant subcutaneous adipose tissue, the patient may have improvement with liposuction.

Individuals are counseled about risks of the procedure, including bleeding, infection, skin breakdown, and pulmonary emboli. Liposuction does not cure lymphedema, and patients are educated that they must continue their compression regimen after surgery to slow recurrence. Tumescent solution (50 ml of 1% lidocaine, 1 ml of 1:1000 epinephrine, and 1000 ml of normal saline solution) is injected into the subcutaneous compartment not to exceed 35 mg/kg of lidocaine. Tumescent or superwet technique is used, so that the volume of aspirate is equal to or less than the amount infused. Multiple 1 cm incisions are made along the extremity in relaxed skin-tension lines and natural creases (5 to 10 for the arm and 10 to 15 for the leg). Standard liposuction is used for the upper extremity with 3 to 5 mm cannulas. Power-assisted liposuction is typically incorporated for the lower extremity with 4 to 6 mm cannulas. Circumferential suctioning is performed, and the incisions are closed loosely to allow drainage. The limb is wrapped with gauze and elastic bandages and is changed within 1 week. Patients undergoing upper extremity liposuction are discharged on the day of the procedure. Depending on the severity of the lower extremity, procedures may be performed on an outpatient basis or patients may require inpatient recovery.

If a patient has bilateral lower extremity disease, only one leg is treated at a time to allow the individual to ambulate after surgery. The contralateral extremity is reduced 3 to 6 months later. Immediately after the procedure, the patient is encouraged to use the limb as much as possible and continue pneumatic compression for 1 to 2 hours a day. After the operative bandages are removed, patients wash the limb once a day and wrap the extremity with Ace wraps for 6 weeks until the limb has reached a steady-state volume. The individual is then fitted for a new custom-fitted garment.

Rarely, patients with primary lymphedema of the lower extremity and extreme overgrowth are managed best with staged skin/subcutaneous because:

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  Severe fibrosis of the subcutaneous tissue is less amenable to liposuction.

  
  
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  Significant skin excess requires resection.

Typically, a medial incision is made, skin flaps are raised one third the circumference of the extremity, and subcutaneous tissue, muscle fascia, and redundant skin are removed. Several months later, the procedure is repeated with a lateral incision. After staged skin/subcutaneous excision, patients can have significant improvement in the extremity function, but the procedure is more difficult and associated with greater morbidity compared with liposuction. Penile/scrotal lymphedema is not amenable to liposuction and requires staged skin/subcutaneous resection.

MACROCYSTIC LYMPHATIC MALFORMATION: RESECTION AFTER SCLEROTHERAPY

Patient A