Medical Professional Publications

Lymphatic Malformation: New Treatment Solutions in the Eye, Head and Neck

(From Pediatric Directions, Issue 38)

The interventional radiologists at Nationwide Children’s Hospital have created a program recognized internationally for providing successful minimally invasive treatment of lymphatic malformations (LM). For more than 16 years, the radiology team has been refining this process, especially in the eye, head and neck. LM is a common vascular malformation, representing approximately five percent of all benign tumors. For the first time, recurrence of cystic hygroma is non-existent and serious surgical complications can be avoided with definitive interventional radiological procedures developed at Nationwide Children’s Hospital.

Pictured above is author: William E. Shiels II, DO, chairman, Department of Radiology, Nationwide Children’s Hospital and president of the Children’s Radiological Institute.

Lymphatic Malformation Case Study: Kyla’s Story
October 2004 – A beautiful baby girl, Kyla, was born. However, at birth she had a puffy upper eyelid, which was thought to represent a blocked tear duct. At about one year, Kyla was fitted with eyeglasses. Her eye remained unchanged until April 2008.

April 2008 – At age 4, the swelling in Kyla’s left eye became worse. MRI showed orbital cysts interpreted to be an “orbital lymphangioma,” and she was monitored, and treated with an eye patch.

August 2010 – Kyla was getting ready to start Kindergarten. She was old enough to cheer for her brother’s little league football team, and her parents were expecting another baby. She was going to be a big sister. After years of eye patch treatment, now age 6, Kyla’s eye took a dramatic change. Kyla’s eye was very swollen and bruised, with the eyeball bulging out of the socket.

In addition to eye pain, the deformity changed a normal happy young 6-year-old cheerleader into a depressed girl who felt ugly and socially withdrawn. She was like a “turtle in a shell” according to her mother. In addition to withdrawing from school and cheerleading, the deformity haunted Kyla to the point of staying home from Halloween trick-or-treating. She even asked NOT to have a 6-year birthday party. “What 6-year-old doesn’t want to have a birthday party?” her mother asked. Her condition grew worse. Even after surgical drainage of the fluid collection behind her eyeball, Kyla was now unable to close her eye and required protective eye lubrication every two hours.

After contacting doctors in Iowa, Boston, Arizona, Mayo Clinic and Canada, the Vascular Malformation team at Iowa referred Kyla to Nationwide Children’s Hospital for a new treatment about which they had read. Kyla was treated at Nationwide Children’s Interventional Radiology Department for both macrocystic and microcystic elements of her retrobulbar orbital lymphatic malformation. The day Kyla went in for treatment at Nationwide Children’s, her mother was just two hours away, giving birth to her new baby sister. The next day, with a 5F drain in her orbit, Kyla looked up at her mother, smiling and giggling again, and said “Mom, my eye is fixed … now let me see my new baby sister.” After a few days, Kyla’s eye returned to a normal state.

The week after treatment, Kyla looked in the mirror and said, “Grandma, I am beautiful again!” One year later, with no recurrence, Kyla is “loud and proud” as a cheerleader, having great birthday parties, and was a Native American princess for Halloween 2011. (See 2a-2f for images of Kyla before, during and after treatment)

   

Figure 2a. 6-year-old female with severe proptosis due to massive intraorbital LM.
Figure 2b. Coronal MRI of left orbital mixed macro-and microcystic LM (arrow)encasing the optic nerve (arrowhead).
Figure 2c. Coronal MRI of the left orbit defining microcystic elements of the LM (arrowhead)
Figure 2d. 5F drainage catheter with contrast for drainage and ablation of the macrocystic element (arrowhead).
Figure 2e. Image during US guided microcyst treatment with 25G needle (arrowhead)in the leftmost of 2 microcysts, containing echogenic doxycycline foam(curved arrow). Straight arrow indicates the adjacent microcyst that will be treated next with echogenic doxycycline foam.
Figure 2f. Clinical photograph 10 months following treatment with resolution of proptosis and visual acuity improvement to 20/100.

Defining Lymphatic Malformation and the Pathology
Lymphatic malformation (LM), previously known as lymphangioma, is a common vascular malformation, representing approximately five percent of all benign tumors. More than half are recognized at birth and 90 percent before 2 years of age. Occasionally, LM may first manifest with a visible mass in early or late adulthood. An LM that is diagnosed at birth usually presents as a soft, spongy, non-tender mass. In older children and adults, a LM may present with rapid development of a firm painful mass, occurring as a result of hemorrhage into previously undiagnosed LM locules. LM is most frequently diagnosed in the head and neck, but can present in numerous other locations including the orbit, mediastinum, retroperitoneum, chest, abdomen, extremities, scrotum and penis. LM in the orbit may lead to severe disability, acute bradycardia, visual loss or complete blindness.

The pathology of LM is central to understanding the science and design of effective therapeutic interventional procedures. Pathologically, LM is a complex of multiple cysts lined with lymphatic vascular endothelium. The supporting matrix of the LM is a combination of fibrous tissue and smooth muscle with small feeding vessels and aggregates of lymphocytes in the interweaving septations. The cystic spaces may or may not communicate and contain serous or hemorrhagic fluid. Lesions can be classified as macrocystic (>1 cm), microcystic (< 1cm), solid (spongy), or mixed. When macrocystic disease predominates, pathologists refer to these cavernous lesions as the typical “Cystic Hygroma.”

Surgical resection has been considered standard treatment for these lesions, despite recurrences in 15 to 53 percent of reported clinical series. Significant complications in up to one-third of cases, including nerve paralysis, have been reported following operative resection. For the first time, recurrence of cystic hygroma is non-existent and serious surgical complications can be avoided with definitive interventional radiological procedures developed at Nationwide Children’s. Additionally, Nationwide Children’s offers the first available therapeutic option for percutaneous, minimally invasive treatment of microcystic LM.

Diagnostic imaging is best performed with a combination of MRI and sonography. MRI is the imaging modality of choice for global assessment of the extent of an LM. MRI may demonstrate LM extension in areas invisible to sonography, such as LM behind airway and boney structures. MRI and sonography together demonstrate LM to be a multiloculated cystic mass with variable appearance of the cyst fluid depending on the presence or absence of intracystic hemorrhage. Sonography may be the sole diagnostic imaging modality if the lesion is well localized in a superficial location, also providing definition of microcystic and solid elements, distinct from macrocystic elements. Sonography during a preoperative consultation facilitates pre-procedural mapping, as well as effective parent/patient education.

Radiological therapy is focused on selective ablation of vascular endothelium that lines LM cysts. Interventional radiological therapy has been attempted around the world over the past two decades using intralesional sclerotherapy with varying agents including bleomycin, doxycycline, ethanol, EthiblocTM, OK-432 and sodium tetradecyl sulfate, with excellent response in only 20 to 67 percent of patients A recent literature analysis of multiple sclerosant agents reported LM treatment requiring one to 23 treatment sessions with complete ablation of LM in 20 percent, and good response in 51 percent of patients. Previously, complications from sclerotherapy have been observed in 22 to 46 percent of patients, including nerve damage, persistent pain, skin ulceration, fever, airway obstruction and myoglobinuria. Prior to therapeutic discoveries at Nationwide Children’s, there was no percutaneous therapeutic regimen consistently delivering outcomes of 90 percent or greater success, without the above-described complications.

Percutaneous Therapy of Lymphatic Malformation
Patients who have undergone treatment for LM at Nationwide Children’s, range in age from 1-month to 60 of age. Locations of percutaneous treatment for LM include the orbit, ear, neck, head, arm, leg, hand, foot, axilla, mediastinum, chest wall, abdomen, scrotum and penis. Most procedures are performed as definitive first-line therapy, with occasional patients referred after surgical debulking or following surgical recurrence. Procedures are performed in the interventional radiology suite under deep intravenous anesthesia or general anesthesia. Treatment is divided into two therapeutic regimens, one for macrocystic disease and one for microcystic disease.
 
Macrocystic LM Treatment
Macrocyst (>1cm) access is most frequently performed with ultrasound guidance and placement of a 5-8F pigtail catheter system. Specific treatment of orbital macrocystic LM includes use of a new coaxial 5F pigtail catheter access system developed at Nationwide Children’s. In multilocular lesions, each macrocyst is treated with separate catheter placement. This technique of individual targeted cyst ablation has proven to be highly effective, with up to five catheters placed in a single child’s parotid LM and eight catheters placed in an abdominal LM. Following complete drainage of the macrocysts and contrast cystogram definition, macrocysts are treated with a novel dual-drug system developed at Nationwide Children’s. Cyst lining cells are first washed with detergent (sodium tetradecyl sulfate), which effectively removes cell membrane lipoproteins, thus increasing membrane permeability for intracellular delivery of ethanol for protein denaturation and cell death (within 15 minutes). Following aspiration of the ethanol, macrocysts are placed to suction drainage for three days prior to catheter removal.

Demonstrates the use of a pigtail catheter to drain a cyst, and the injection of solution to ablate the macrocyst. Also demonstrates the dual syringe method for aspirating and injecting doxycycline foam into LM microcysts.

This treatment is effective greater than 95 percent of the time, with the majority of patients (85 percent) responding in a single treatment. Patients with 5F pigtail catheters in the orbit, head and neck, report no pain from the indwelling catheter. This catheter based, dual-drug macrocystic treatment has been successful adjacent to optic, facial, phrenic and vagus nerves, without nerve injury.

Microcystic LM Treatment
Microcystic LM has been long considered to be untreatable using percutaneous treatments. Radiologists and scientists at Nationwide Children’s have successfully overcome this dilemma by developing the first successful minimally invasive “foam” treatment for microcystic LM. Patients may have hundreds of microcysts in a large LM (see illustration, which demonstrates the dual-syringe method for aspirating and injecting doxycycline foam into LM microcysts). Treatment of this “field” of microcysts involves aspiration of each individual microcyst and injection of doxycycline as a foam. The foam changes the color of the microcyst on ultrasound from black to white, and defines the treated from untreated microcysts. Microcystic LM as small as 1 mm in the eye, head and neck are successfully treated with this procedure, usually accessed through the eyelid or eyebrow, leaving no scars. Microcystic LM components may be treated at the same time of macrocyst treatment, or after successful treatment of overlying macrocystic LM elements. Successful (>95%) microcystic treatment often reveals remaining solid LM elements that may prove unnecessary to treat surgically.
 
Clinical Response to Treatment
Most LM treatments are performed as outpatients, with extensive cases involving a one-night stay in the hospital for intravenous antibiotic therapy and fluid management. Macrocystic treatment is painless, with no cases of permanent nerve injury, muscle injury or other major complications. Macrocystic treatment of the orbit, especially massive orbital macrocystic LM surrounding the optic nerve, results in a temporary pupillary motor dysfunction that resolves in all cases within three months. Simple macrocystic neck LM (small or large) in adults is effectively treated as an outpatient, with no sedation or general anesthesia. In these cases, local anesthesia provides painless catheter based dual-drug treatment of the macrocystic LM. During the three days of catheter macrocyst drainage (after treatment), patients (including orbit LM) are fully ambulatory and functional, without pain. Patients undergoing microcystic treatment may experience mild pain for two to four hours, responsive to oral narcotic analgesic therapy. Following treatment, patients undergo annual follow-up ultrasound examination (minimum five years) to evaluate for new microcysts that may mature from remaining solid LM tissue. New microcysts, if any, that develop are readily treated with simple microcystic needle injection therapy as an outpatient. In the past 15 years, greater than 95 percent of patients respond with complete resolution of macrocystic and microcystic LM components.

Click the above image to view an animation of treatment for LM.

The following case studies provide before and after clinical images of patients with LM:
Lymphatic Malformation of the Orbit

   

Figure 3a. MRI of 13-year-old male with proptosis due to retrobulbar lymphatic malformation (arrows). Note the optic nerve (arrowhead) that is encased by the LM.
Figure 3b. 5F drainage catheter in position for drainage and ablation (arrow)
Figure 3c. Contrast cystogram defining the orbital cystic mass (arrowhead) prior to ablation.
Figure 3d. MRI 2 years following treatment demonstrates normal globe, optic nerve, and orbital contents.
Lymphatic Malformation of the Neck

   

Figure 4a.13-month-old female with massive LM of the left neck.
Figure 4b.Coronal MRI demonstrates the LM (arrows) extending from the neck into the superior mediastinum.
Figure 4c.Axial MRI demonstrating the LM (arrows) encasing the carotid sheath and extending into the retropharynx.
Figure 4d.Contrast cystogram during macrocystic (arrow) ablation treatment.
Figure 4e.MRI 4 years following treatment demonstrates no macrocysts or microcysts, and small amount of fibrofatty tissue (arrows) remaining after cyst ablation.
Figure 4f.Photograph at age 5 demonstrating no visible mass effect or scar in the left neck. The scar (arrows) on front of the neck was from plastic tracheostomy frame skin abrasions.
Lymphatic Malformation of the Neck

   

Figure 5a.47-year-old female; ultrasound demonstrates the large macrocystic LM (arrows) of the left neck.
Figure 5b.Ultrasound exam 6 months following treatment demonstrating normal neck soft tissues (arrow on normal carotid artery) and no evidence of cysts or scar from treatment.

Author: William E. Shiels II, DO, chairman, Department of Radiology, Nationwide Children’s Hospital and president of the Children’s Radiological Institute.

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