This newborn male infant was born to a 30 year old G1P1 mother at 40 weeks gestation via cesarean section. Prenatal ultrasonography performed at 32 weeks gestation revealed a 1 cm x 1 cm x 1 cm hypoechoic but nonseptated mass in the posterior neck. An encephalocele or meningocele were deemed unlikely and the infant was suspected of having a cystic hygroma (a type of lymphatic malformation). No evidence of fetal hydrops or other congenital anomalies were noted. The pregnancy is closely monitored with detailed serial ultrasounds for the duration of the pregnancy. At term, the hypoechoic lesion is 2 cm x 1 cm x 2 cm. While there is still no indication of hydrops fetalis by ultrasonography, a cervical cystic mass could obstruct a vaginal delivery and the mother is advised to undergo a cesarean section.

Upon delivery, Apgar scores are 8 and 9 at 1 and 5 minutes. VS T 37.5, HR 110, R 60, BP 51/25, weight 3.3 kg (50th %ile), length 51cm (50th %ile). His head is normocephalic with no evidence of additional cystic masses. Eyes, ears, nose and mouth are all normal. A 2 cm wide mass is noted in the posterior neck. Heart, lung, abdomen, extremity, skin and neurologic examinations are normal.

He begins to breast feed normally. Imaging studies fail to demonstrate any other cysts. Because nuchal cysts can grow to obstruct the trachea or esophagus, most of the cyst is surgically excised. Histology of the cyst shows only lymphatic tissue, confirming the diagnosis of a cystic hygroma. Because of its proximity to nerves, the cystic hygroma tissue could not be completely removed. By 12 months of age, local recurrence of the cystic hygroma is evident. Options for recurrent and unresectable lymphangiomas, such as drug sclerotherapy, were discussed with his parents. They are also informed of the possibilities of infection, hemorrhage, and continual recurrence despite treatment.

Lymphangiomas or lymphatic malformations (LM) are defined as isolated regions of lymphatic tissue which are thought to occur after the 6th week of gestation, when developing lymphatic tissue fails to properly anastomose (1,2,3). Lymphatic tissue can also improperly anastomose with capillaries, veins, and arteries (4). These isolated regions of lymphatic tissue function to absorb interstitial fluid and enlarge as lymph fluid continues to accumulate with time (3). Depending on their location and size, lymphatic malformations can be benign and asymptomatic or they can press against nerves, organs, or obstruct circulation (4). For example, lymphangiomas in the head and neck can cause airway obstruction, and alter speech and/or mastication (3).

The true incidence rate for lymphatic malformations is uncertain, since small ones may not be very evident. The most common lymphatic malformation, cystic hygromas, have an estimated incidence of 1:875 among miscarriages (3). By comparison, hemangiomas are much more common and occur in as many as 10% of 1 year olds (5). Lymphatic malformations are found equally in boys and girls (5). Lymphatic malformations are commonly diagnosed in infancy with more than half of the cases identified prenatally or postpartum and more than 90% diagnosed by the 2nd or 3rd year of life (4,6). Lymphatic malformations rarely regress after birth but can remain asymptomatic until later in life when trauma or infections can cause lymphatic malformations to rapidly grow and interfere with other structures (7).

Seventy-five percent of lymphatic malformations are found in the head and neck but lymphatic malformations can occur anywhere (1). Generally, the most common sites are in the head and neck, mediastinum, axilla, and abdomen (1). Lymphangiomas that are microcystic superficial lesions of the skin or mucous membranes have many names: lymphangioma simplex, lymphangioma circumscriptom, capillary lymphangioma and angiokeratoma circumscriptum (4,9). Deeper lymphangiomas can be either microcystic (cavernous lymphangiomas), macrocystic (lymphangioma cystoides, cystic hygromas, or cystic lymphangiomas), or mixed microcystic-macrocystic (4,9).

The etiology of lymphangiomas is unknown (10). However, cystic hygromas have been found to be associated with chromosomal abnormalities such as Turner syndrome and Down syndrome (2,3). Chromosomal abnormalities are usually associated with other congenital findings such as mental or developmental retardation, heart defects, or alterations in the development of sexual characteristics at puberty.

Diagnosis is principally made on the basis of clinical appearance and imaging. For example, capillary lymphangiomas or lymphangioma simplex are superficial white, purple, or red papules that appear wart-like (9). Such superficial lymphangiomas are usually asymptomatic but can become infected. They can occasionally bleed when the superficial lymphangioma is in communication with ruptured blood vessels. Lymphangioma circumscriptum are superficial clusters of papules that are said to look like frog eggs (9). Lymphangioma circumscriptum is also found in skin or mucous membrane but extend deeper into the dermis than lymphangioma simplex (9). Cavernous lymphangiomas usually involve the skin or mucous membranes but they extend deeper into muscle where they form small, thin-walled, lymph fluid filled spaces referred to as microcysts (9).

Cystic lymphangiomas or cystic hygromas are large, well-circumscribed, loculated, lymph fluid-filled spaces (macrocysts) (3,9). Large loculated cysts tend to occur in areas where expansion is possible such as the deep lymph vessels in the neck and head or near other organs. These deep lymphangiomas can be asymptomatic or they can present with signs and symptoms associated with serious complications. Cystic hygromas, usually identified prenatally or antenatally, are especially serious. Considerable lymphedema can accompany growing cystic hygromas which can sometimes lead to hydrops fetalis and intrauterine fetal demise (IUFD) or early perinatal neonatal death (early PND) due to circulatory failure (3). Additionally, the size and position of the cyst may complicate vaginal delivery (3).

When aspirated, the cystic space fluid includes proteinaceous fluid with few lymphocytes (1). MRI findings are important in distinguishing between lymphangiomas and other vascular malformations (1). Arterial or venous vascular malformations enhance with contrast during MRI contrast studies, while lymphatic malformations do not. CT scans can also help differentiate venous malformations from lymphangiomas as well as help identify hemorrhages. Plain film radiographs can identify associated skeletal deformities. Ultrasound imaging is particularly useful during the perinatal/neonatal period (4).

Specimen biopsies of superficial lesions show typical lymphatic vessels lined by well differentiated, flat, endothelial cells (3,8). Deeper lesions show dilated and interconnected lymph vessels that can form loculations (3).

The differential diagnosis includes lymphadenitis, other congenital vascular malformations (hemangiomas, branchial cleft cyst, cellulitis, dermoid cyst), and tumors. Bloody lymphangiomas are often easily confused with hemangiomas or Kaposi's sarcoma (4). Because of the variable location of lymphangiomas, the differential diagnosis should also include site-specific pathologies. For example, the differential diagnosis of a nuchal cystic hygroma should include encephalocele or meningocele, and tumors of the head and neck (3).

Small superficial lymphangiomas are generally left untreated if asymptomatic (1). Cystic hygromas identified in a fetus are especially concerning. The fetus is assessed for additional abnormalities that would increase the risk of fetal death or poor postpartum prognosis such as chromosomal abnormalities, hydrops fetalis, and large cyst volumes (2). These factors are important in whether or not the fetus is aborted or delivered vaginally or by cesarean section. In the U.S., deep lymphangiomas such as cystic hygromas and larger superficial lymphangiomas are surgically excised (1,3,6). However, surgical excision is difficult because of the delicate nature of thin-walled lymphatic tissue and the close proximity of lymphatic malformations to nerves, organs, and blood vessels (3,6). As a consequence, complete excision is possible in less than a third of the cases (6). Incomplete excision does eliminate the space occupying effects of the lesion but are complicated by a high risk of recurrence and infection (3).

In sclerotherapy, drugs including bleomycin, OK-432 (derivative of low virulence Group A streptococcus pyogenes), and fibrin adhesives are used to stimulate sclerosis and regression (6). In the U.S,. sclerotherapy is generally reserved for recurrent or unresectable lymphangiomas but, in some small studies, sclerotherapy agents have been used in place of surgical excision with good results (3,6). Sclerotherapy complications include ulcers, scarring, and recurrence of lyphangiomas (3,7). Other treatment options include interferon-alpha treatment (7), laser ablation or radiation treatment. Radiation treatment carries a number of complications and is usually reserved as a treatment of last resort (7).

Questions

1. Which of the following is NOT a kind of lymphangioma?
. . . . . a. lymphangioma simplex or circumscriptum
. . . . . b. capillary lymphangioma
. . . . . c. cavernous lymphangioma
. . . . . d. cystic hygroma
. . . . . e. subdural hygroma

2. Which two of the following choices are NOT characteristic of cystic hygromas?
. . . . . a. bluish color
. . . . . b. increases in size with dependent position
. . . . . c. if superficial, transilluminates brightly
. . . . . d. does not enhance with contrast in MRI
. . . . . e. large neck mass presenting at birth

3. True/False: The differential for a lymphatic malformation depends on its location.

4. In the U.S., primary treatment of lymphatic malformations can include all of the following EXCEPT:
. . . . . a. surgical excision
. . . . . b. no treatment if benign
. . . . . c. pharmacological sclerotherapy
. . . . . d. radiation therapy

5. Complications of cystic hygromas in the head and neck include all of the following EXCEPT:
. . . . . a. airway obstruction
. . . . . b. esophageal obstruction
. . . . . c. infection
. . . . . d. hydrops fetalis
. . . . . e. hemorrhage
. . . . . f. no exceptions (all above are correct)

References

1. Faul JL, Berry GJ, Colby TV, et al. Thoracic Lymphangiomas, Lymphangiectasis, Lymphangiomatosis, and Lymphatic Dysplasia Syndrome. Am J Resp Crit Care Med 2000;161:1037-1046.

2. Fujita Y, Satoh S, Nakayama H, et al. In utero Evaluation and the Long-Term Prognosis of Living Infants with Cystic Hygroma. Fetal Diagnosis and Therapy 2001;16:402-408.

3. Gallagher PG, Mahoney MJ, Gosche JR. Cystic Hygroma in the Fetus and Newborn. Sem Perinatol 1999;23(4):341-356.

4. Davies D, Rogers M. Morphology of Lymphatic Malformations: A Pictorial Review. Australian J Dermatol 2000;41:1-7.

5. Burns AJ, Kaplan LC, Mulliken JB. Is There an Association Between Hemangioma and Syndromes with Dysmorphic Features? Pediatrics 1991;88(5):1257-1267.

6. Giguere CM, Bauman NM, Sato Y, et al. Treatment of Lymphangiomas with OK-432 (Picibanil) Sclerotherapy. Arch Otolaryngol Head Neck Surg 2002;128:1137-1142.

7. Reinhardt MA, Nelson SC, Sencer SF, et al. Treatment of Childhood Lymphangiomas with Interferon-[alpha]. J Pediatr Hematol Oncol 1997;19(3):232-236.

8. Baer S, Davis JD. Cystic Hygroma Presenting in Adulthood. J Laryngol and Otol 1989;103:976-977.

9. Williams HB. Hemangiomas and Lymphangiomas. In: Maclean LD (ed). Advances in Surgery, volume 15. Chicago, Year Book Medical Publishers, Inc., 1981, pp. 317-349.

10. Breugem CC, van der Horst CMAM, Hennekam RC. Progress Towards Understanding Vascular Malformations. Plastic and Reconstructive Surg 2001;107(6):1509-1523.

Answers to questions

1.e. A subdural hygroma is liquefaction of a subdural hematoma.

2.a & b. These are indicative of venous malformations.

3.true

4.d. Radiation is reserved as a last resort.

5.f