Cecilia Tran, M.D.
June 19, 2003
Lymphangiomas of the Head and Neck

Lymphangiomas are localized, congenital malformations of the lymphatic system that involve the skin and subcutaneous tissues. They are found most commonly in the head and neck as well as the axilla and abdomen. In 1828, Redenbacher is credited with describing a lymphangioma lesion and coined the term “ranula congenital.” In 1843, Wernher gave the first case report of a cystic hygroma. This term comes from the Greek word “hygroth” meaning fluid and “oma” meaning tumor. In 1965, Bill and Summer proposed that cystic hygromas and lymphangiomas are variations of a single entity and that its location in the head and neck determines its classification.

Lymphangiomas are benign tumors of lymphatic vessels. There are two theories for the origin of the lymphatic system in humans. One theory is that the lymphatic system develops during the sixth week of embryogenesis from five primitive sacs that arise from the venous system. In the early 1900s, Sabin proposed that in the head and neck, endothelial outpouchings from the jugular sac spread to form the peripheral lymphatic system. Godart, on the other hand, proposed that the lymphatic system developed from mesenchymal clefts in the venous plexus and spread centripetally toward the jugular sac. Lymphangiomas arise from incomplete development and obstruction of the normal lymphatic system during the sixth week of embryogenesis. Either the primordial lymphatic sacs fail to connect with the venous system. This incomplete canalization of the lymphatics causes obstruction of lymph flow and cyst development. The second theory is that lymph tissues are deposited in the wrong area during embryogenesis and subsequently fail to join the normal lymph system.

Cervical facial lymphangioma are relatively uncommon, representing fewer than 6% of benign tumors of childhood. Incidence has been reported to be 1.2 to 2.8 per thousand population. Most studies report an equal sex incidence among males and females. The lesions can become evident at any age but they usually appear in infancy. Studies agree that about 50% are seen at birth and more than 90% are clinically apparent within the first year of life. Lymphangiomas are associated with Turner’s, Klinefelter's and Noonan’s syndromes and exposure to alcohol during pregnancy. They can occur anywhere in the skin and the mucous membranes of the body, appearing in the head and neck about 70% of the time. The tongue is the most common intraoral site while those in the neck most commonly appear in the posterior triangle

Children usually present with a mass in the head and neck region. The most common presentation is a soft, painless mass that may enlarge with time or in response to trauma or a URI. Hemorrhage into the lesion can also cause sudden enlargement. The second and third most common presenting symptoms are respiratory obstruction and problems with feeding and failure to thrive. Physical exam demonstrates a soft, painless compressible mass often described as being doughy on palpation. Superficial tumors may be pink to reddish blue, while deeper lesions may show no surface changes or have stretched and atrophic skin. Regional lymph nodes are either normal or hyperplastic. Grossly, the lesions are ill-defined, diffuse, and spongy, having indiscrete margins. Often, it is actually much larger than it appears to be. Usually these lesions are asymptomatic and patients merely have a cosmetic deformity. Pain is not common unless infection is present. Suprahyoid disease tends to cause more breathing difficulties and dysphagia than does infrahyoid disease. Symptoms are related to the size, location and extent of the lymphangioma. Tongue involvement can lead to macroglossia, with drooling, dysphagia, and airway obstruction. Infiltration of the base of tongue or larynx may result in dysphonia, stridor, apnea, and cyanosis. Isolated laryngeal lymphangiomas are uncommon and almost always represent extension of cervical disease.

It is necessary to differentiate these lesions from other cervical congenital masses or malignancy. The cystic nature and the bluish hue frequently resemble characteristics of a hemangioma. Lesions in the floor of the mouth, particularly when they bulge in the submental region, may simulate a plunging ranula. Other differential considerations in the head and neck include a branchial cleft cyst, a thyroglossal duct cyst, and goiter.

As far as imaging, MRI is the study of choice. It can help outline the extent of disease and aid in planning a surgical approach. Lesions are typically hypointense on T1 weighted images and hyperintense on T2 weighted images. You often see fluid levels and septations. The mean single intensity is greater than that of muscle or fat. This MRI shows an extensive parapharyngeal lymphangioma. You can see how well defined the borders are. If possible, MRI should always be obtained; however, sometimes very young children will require heavy sedation and intubation and in this case, CT scan is an acceptable alternative. On CT, the lesion typically appears as a multi-loculated cyst with smooth septa. CT contrast is unpredictable because enhancement occurs in only 50% of cases. CAT scan offers excellent visualization of lesions extending into the mediastinum, deep neck structures and retropharynx. This CAT scan shows a large cystic mass in the posterior triangle of the right neck. This CAT scan shows a lymphangioma in the right parotid gland involving both the superficial and deep lobes. On ultrasound, you would see a cystic mass with smooth, thin, or irregular walls. Ultrasound can be useful in detecting recent hemorrhage; however, it is limited in its ability to determine mediastinal and retropharyngeal extension. Lesions occur as hypoechoic, multi-locular cystic masses.

Depending on the anatomic location of the lesion, other diagnostic studies may be helpful. Arteriography can help rule out a hemangioma or AV malformation. Lymphoscintigraphy can help identify the source of lymph flow but is often unavailable clinically. Laryngoscopy, bronchoscopy, and esophagoscopy can also be useful. Chest x‑ray may help rule out mediastinal extension or pleural effusion and barium swallow can assess esophageal compression. FNA will usually yield a straw colored fluid, not the cellular material necessary for histologic diagnosis. Tissue diagnosis is the best and most consistent confirmation of lymphangioma. What we see microscopically are cystic or multi-locular masses extending into tissue fascial planes. The cyst walls are very thin and contain clear to cloudy fluid. During surgery it is often easy to penetrate and decompress the cyst inadvertently.

Histologically, these tumors are composed of dilated lymphatic channels. This slide shows the large empty lymphatic channels that are lined by a flattened layer of endothelial cells. They contain proteinaceous fluid. The intervening stroma consists of fat, fibrous tissue and skeletal muscle. The dilated spaces can vary from microscopic to large and cystic. They vary in size depending on the location and surrounding tissues.

Landing and Farber were the first to divide these lesions into two major groups based on the size of these abnormal lymphatic vessels. When a lymphangioma is confined to rather dense tissue like the tongue it presents as a microcystic lesion, but generally when it develops in the relatively loose fascia of the neck a macrocystic lesion results. These arise from lymphatic tissue in areas where expansion can occur.

Microcystic lesions consist of multiple clusters of vesicles that contain clear lymph fluid. These vesicles represent dilated lymphatic vessels in the dermis that push upward against the overlying epidermis. The most common sites are the lips, tongue, cheek, and the floor of mouth. Macrocystic lesions are deeply seated in areas of areolar or loose connective tissue. They appear early in life as large, soft tissue masses usually on the axilla, neck, or groin. These lesions tend to grow extensively spreading along multi-tissue planes. They are multi-locular cysts filled with clear or yellow lymph fluid. When discovered in the first two trimesters of pregnancy, these are different from those discovered at birth or in early childhood. Those appearing early in gestation are associated with fetal hydrops, cardiac malformations, and chromosomal abnormalities. Fetal lesions can be visualized by transvaginal ultrasound as early as 10 weeks gestational age. A staging system has been developed for these lesions. It incorporates the variables of functional impairment, cosmesis, number of locations, and age at diagnosis. Functional impairment is defined as altered swallowing, speech, vision, or respiration. With higher T-stage there is more likelihood of a major complication and more surgical procedures necessary for complete excision.

Lymphangioma is not a fatal disease. There is a 3% mortality rate. These deaths are usually due to bronchospasm, atelectasis, or airway compromise from edema. There is no risk of malignant transformation. The growth rate is variable but most lesions tend to progress slowly. In light of this slow progression and minimal mortality how are we to treat this lesion? Options include observation, laser sclerotherapy, and surgery. Spontaneous regression has been reported in the literature to be approximately 15%. Dr. Kennedy in 2001 offered evidence that there is no difference in outcome between those with surgery at the time of diagnosis and those who delay surgery until the age of three. He recommended that when a mass was the only sign or symptom to observe it until the child was at least two years of age. This slide from his article depicts a cystic hygroma in a child at six months of age. This large multi-cystic lesion involved all regions of the left neck and extended to the floor of mouth and tongue. The family decided to defer treatment and the child remained asymptomatic. This same child is shown here at age nine with significant spontaneous regression. The drawback to observation is the potential risk of enlargement and complications. If the child were to develop aspiration, airway compromise, or failure to thrive, these would all be clear indications for immediate intervention. Radiation can cause malignant transformation or retardation of growth sites. Aspiration of the cystic contents has been used as a temporizing measure to relieve airway obstruction and provide emergency decompression but it can cause infection, recurrence, or hemorrhage.

Carbon dioxide laser therapy has been effective in debulking upper airway lesions, especially those of the larynx, tongue base, and intraoral vesicles. Tongue lesions involve the anterior two-thirds of the tongue 90% of the time. The advantages to laser therapy include less bleeding, edema, and less tissue trauma. Also, it is the best option and perhaps the only option for sites not easily accessible for surgery such as the base of tongue and larynx, but it is only temporary as patients will require multiple treatments when their symptoms recur. The recurrence rate is higher compared with surgery since it is impossible to completely eradicate the disease burden.

In 1986, Dr Okida in Japan first described using OK-432 to stimulate an inflammatory response and regression of these lesions. OK-432 is a mixture of a low virulent strain of Group A streptococcus pyogenes incubated with penicillin G. The antigenic stimulation of the streptococcus induces immunologic upregulation of cytochymes including Isle 1 and Isle 2. This then activates neutrophils, macrophages and natural killer cells. The endothelium becomes more permeable accelerating lymphatic fluid drainage and size reduction of the cyst. This picture is from Dr. Okida’s web site in Japan at the University of Kyoto. He published his first results in 1986. This picture is the MRI of a parapharyngeal lymphangioma before and after sclerotherapy. In a perspective multi-institutional trial here at the University of Iowa, 29 patients with lymphangioma located in the head and neck received a four-dose injection series of OK-432 scheduled six to eight weeks apart. 86% of the 22 patients had a successful outcome. Success was defined as reduction of at least 60% in lymphangioma size as determined by calculated lesion volumes on CT or MRI.

Macrocystic lymphangiomas of the infratemporal fossa or cervical area have the best response to therapy. The most frequently reported complications are erythema, swelling, discomfort, and fever. It can also cause fibrosis that may impair later surgical excision. OK-432 is still currently only available in America in experimental trials.

Laser sclerotherapy can be used for lesions without airway compromise. Obviously, tracheotomy must be performed to protect the airway when necessary. Surgery is the treatment of choice for deep microcystic lesions where laser therapy and sclerotherapy cannot be used. It is important during surgery to optimize function and cosmesis. A balance must be determined intraoperatively between incomplete resection and potentially risking cranial nerve injury or creating a significant cosmetic deformity. Vital structures should be protected. Some authors will recommend surgery at the age of two.

Excision should be delayed at least three months after an acute infection. Some lesions, due to their immense size, will require multiple operations and extensive preoperative planning. In children such as the one shown here, airway and nutrition must be addressed at birth. Often these children will require a tracheotomy/NG tube soon after birth. Auxiliary services may need to be involved. Those with a trach will require trach care, speech therapy, and dental care for hygiene. Lesions may be so large that they have visual or auditory complications that must be addressed. Children with large lesions such as these will require multiple operations, removing what is possible and then staging the next procedure when the child becomes symptomatic again.

Recurrence rates following complete excision range from 0 to 27% in various studies, and after partial excision the recurrence rate is reported to be between 50 to 100%. Most recurrences occur within the first year of resection, but delayed recurrences as long as 10 years after the initial operation have been reported. Often, removal of a part of the disease burden may lead to the enlargement of cysts in neighboring unresected areas. Risk factors for recurrence are initial diagnosis in patients younger than one year of age or with lymphangiomas involving certain anatomic sites. Those found to be non-encapsulated and infiltrative by intraoperative or histologic assessment are more likely to recur. At Minnesota, a study was done of all cases of lymphangioma of the head and neck region in children seen between 1986 and 1996. Sixty-seven children were identified. All but eight presented with an obvious mass and five required tracheotomy because of airway obstruction. The most common location for a lymphangioma in their series was the submandibular gland followed by the parotid gland. They found that lesions involving the lips, hypopharynx, larynx, tongue, and floor of mouth were more likely to have recurrent or persistent disease. They found that a younger age at diagnosis correlated with increased likelihood of recurrence and more operations required. After initial healing has occurred, a baseline MRI of the operative bed can be done. In light of the high recurrence rate, follow-up into early adulthood is recommended. The most common complication is incomplete resection and recurrence. Cranial nerve injury is approximately 20%. The marginal mandibular branch of the facial nerve is the most common neural deficit reported. The risk of intraoperative nerve injury is related to the size and extent of the lesion at time of surgery.

In the future, advances in molecular biology may provide more effective treatment. Cells derived from cystic hygromas have been found to be angiogenic with increased levels of factors such as fibroblast growth factor. The EGFC in the skin of transgenic mice causes lymphatic endothelial proliferation and vessel enlargement. These studies speculate that lymphangioma growth can be slowed by injecting agents that either block angiogenesis or selectively block the EGFC. These studies are currently underway.

In conclusion, these are rare congenital lesions that appear in the head and neck in more than 70% of cases. They are also diagnosed early in life by history and exam. MRI is the study of choice for imaging. Lesions then are classified based on the size of the normal lymph vessels. The low mortality and slow progression of this disease must be considered a treatment decision. Laser is particularly useful for lesions of the base of tongue or larynx, and sclerotherapy is best suited for macrocystic lesions. Recurrence is associated with young age at diagnosis, certain anatomic sites, and large or multiple lesions.

Case Presentation:

The patient is a 10-year-old Caucasian male with a left neck mass. His parents first noticed the mass at age two. It has slowly been increasing in size over the past eight years, with intermittent increases in size associated with viral upper respiratory infections. He has not had symptoms of airway obstruction, stridor, feeding difficulties, weight loss, infection of this mass, or changes in speech. His medical history is unremarkable, and there is no history of trauma. The patient was referred by his pediatrician for evaluation.

Physical exam demonstrated a soft, painless, compressible mass in the left anterior neck. There is no discoloration, tenderness, or pulsation. There are no overlying skin changes or lymphadenopathy. The mass has ill-defined, diffuse margins.

MRI with contrast shows a large macrocystic mass, 9 cm in greatest dimension. It abuts the carotid sheath and extends to the lateral pharyngeal wall. Diagnosis of a lymphangioma was made based on imaging, history, and exam.

Treatment options considered were surgical excision vs. sclerotherapy. After extensive discussions with the family, he underwent sclerotherapy with OK-432. Four injections were performed at six week intervals. After the first injection, a small hard lesion remained that was then injected three more times. At one year follow-up, the child is doing well. The mass has completely resolved with minimal evidence of residuum on exam.

Bibliography:

Alqahtani A, Nguyen LT, Flageole H. Twenty five years experience with lymphangiomas in children. J Pedi Surg 1999;34:1164-1168.

Claesson G, Kuylenstierna R. OK-432 therapy for lymphatic malformation. Int J Pedi Otorhinolaryngol 2002;65:1-6.

De Serres LM, Sie KCY, Richardson MA. Lymphatic malformations of the head and neck—a proposal for staging. Arch Otolaryngol Head Neck Surg 1995;121:577-582.  

Fageeh N, Manoukian J. Management of head and neck lymphatic malformations in children. J Laryngol Otol 1997;26:253-258.

Fliegelman LJ, Friedland D, Brandwein M, Rothschild M. Lymphatic malformation: Predictive factors for recurrence. Otolaryngol Head Neck Surg 2000;123:706-710.

Fung K, Poenaru D, Soboleski DA. Impact of magnetic resonance imaging on the surgical management of cystic hygromas. J Pedi Surg 1998;33:839-841.

Giguere CM, Bauman NM, Smith RJ. New treatment options for lymphangioma in infants and children. Ann Otol Rhinol Laryngol 2002;111:1066-1075.

Giguere CM, Bauman NM, Sato Y. Treatment of lymphangiomas with OK-432 sclerotherapy. Arch Otolaryngol Head Neck Surg 2002;128:1137-1144.

Goshen S, Ophir D. Cystic hygroma of the parotid gland. J Laryngol Otol 1993;107:855-857.

Greinwald JH Jr., Burke DK, Sato Y, Poust RI, Kimura K, Bauman NM, Smith RJ. Treatment of lymphangiomas in children: An update of OK-432 sclerotherapy. Otolaryngol Head Neck Surg 1999;121:381-387.

Hartl DM, Roger G, Denoyelle F, Nicollas R. Extensive lymphangioma presenting with upper airway obstruction. Arch Otolaryngol Head Neck Surg 2000;126:1378-1382.

Kennedy TL, Whitaker M, Pellitteri P. Cystic hygroma: A rational approach to management. Laryngoscope 2001;111:1929-1937.

Maddalozzo J, Hughes CA, Huang L. High angiogenic activity in cells isolated from cystic hygroma: Role of bFGF. Arch Otolaryngol Head Neck Surg 1999;125:45-48.

Mikhail M, Kennedy R, Cramer B, Smith T. Sclerosing of recurrent lymphangioma using OK-432. J Pediatr Surg 1995;30:1159-1160.

Ogita S, Tsuto T, Nakamura K, Deguchi E. OK-432 therapy for lymphangioma in children: Why and how does it work? J Pedi Surg 1996;31:477-480.

Ogita S, Tsuto T, Nakamura K, Deguchi E, Iwai N. OK-432 therapy in sixty-four patients with lymphangioma. J Pedi Surg 1994;29:784-785.

Orford J, Barker A, Thonell S. Bleomycin therapy for cystic hygroma. J Pediatr Surg 1995; 30:1282-1287.

Orvidas LJ, Kasperbauer JL. Pediatric lymphangiomas of the head and neck. Ann Otol Rhinol Laryngol 2000;109:411-421.

Papsin BC, Evans JN. Isolated laryngeal lymphangioma: A rare cause of airway obstruction in infants. J Laryngol Otol 1996;110:969-972.

Riechelmann H, Muehlflay G, Keck T. Total, subtotal, and partial surgical removal of cervicofacial lymphangiomas. Arch Otolaryngol Head Neck Surg 1999;12:643-648.

Smith RJ, Burke DK, Sato Y, Poust RI. OK-432 therapy for lymphangiomas. Arch Otolaryngol Head Neck Surg 1996;122:1195-1199.

Tasca RA, Myatt HM, Beckenham EJ. Lymphangioma of the tongue presenting as Ludwig’s angina. Int J Pedi Otorhinolaryngol 1999;51:201-205.

Tibesar RJ, Rimell FL, Michel E. Cystic hygroma of the skull base. Arch Otolaryngol Head Neck Surg 1999;125:1390-1393.

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