Lymphangiomas are uncommon, hamartomatous, congenital malformations of the lymphatic system that involve the skin and subcutaneous tissues. The classification of lymphangiomas lacks a standard clear definition and universal application, in part because of the nature of lymphangiomas, which represent a clinicopathologic continuum. The classification most frequently used divides these lesions into 2 major groups based on the depth and the size of these abnormal lymph vessels. The superficial vesicles are called lymphangioma circumscriptum. The more deep-seated group includes cavernous lymphangioma and cystic hygroma. Many categorize cystic hygroma as a variant of cavernous lymphangioma. Note the image below.
View Image
A 16-year-old obese boy with large unilateral verrucous lymphangioma.
Lymphangiomas can occur anywhere in the skin and the mucous membranes. The most common sites are the head and the neck, followed by the proximal extremities, the buttocks, and the trunk. However, they sometimes can be found in the intestines, the pancreas, and the mesentery. Deeper cystic lesions usually occur in areas of loose and areolar tissue, typically the neck, the axilla, and the groin. Their skin involvement ranges from small, well-demarcated areas to large, diffuse regions with unclear borders.
Lymphangioma circumscriptum, the common form of cutaneous lymphangioma, is characterized by persistent, multiple clusters of translucent vesicles that usually contain clear lymph fluid (often compared with frog spawn).[1] These vesicles represent superficial saccular dilations from underlying lymphatic vessels that occupy the papilla and push upward against the overlying epidermis. Each skin lesion may range from a minute vesicle to a small bulla-sized lesion. These vesicles can be clear or vary from pink to dark red because of serosanguineous fluid and hemorrhage. These vesicles often are associated with verrucous changes, which give them a warty appearance.
In the case of lymphangioma circumscriptum, the underlying lesions constitute abnormal dilated lymph vessels involving the upper part of the dermis. The sites of predilection are the proximal extremities, trunk, axilla, and oral cavity, especially the tongue.[2] Involvement in other areas, such as the scrotum, is not uncommon. Lymphangioma circumscriptum has a high recurrence rate after excision because of its deep component (see Pathophysiology).
Cavernous lymphangioma are also uncommon and usually arise during infancy. The most common sites are the head and neck areas and, less frequently, the extremities. These lesions are seated deep in the dermis, forming a painless swelling or thickening of the skin, mucous membranes, and subcutaneous tissue. Unlike lymphangioma circumscriptum, the overlying skin usually is uninvolved. Occasionally, patients report pain when the involved area is pressed. The affected area may be 1 cm, it may be as large as several centimeters in diameter, or it may involve an entire extremity. Upon examination and palpation, lipomas or cysts can be mistaken for these lesions. Lymphangioma circumscriptum can occur in conjunction with cavernous lymphangioma and cystic hygroma.
Some authors categorize cystic hygroma or cystic lymphangioma as an independent entity. Many authors agree that cystic hygroma is a form of cavernous lymphangioma in which the degree of involvement and character is determined by its location. These congenital 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 are soft, vary in size and shape, and tend to grow extensively if not surgically excised. Typical lesions are multilocular cysts filled with clear or yellow lymph fluid. Usually, cystic hygroma is diagnosed clinically with its large size, location, and translucence.
Terminology for these lesions can be confusing.[3] Some lymphangiectasias have sometimes been called acquired lymphangiomas, secondary lymphangiomas and acquired lymphangioma circumscriptum.
In 1976, Whimster[4] studied the pathogenesis of lymphangioma circumscriptum. According to Whimster, the basic pathologic process is the collection of lymphatic cisterns in the deep subcutaneous plane. These cisterns are separated from the normal network of lymph vessels, but they communicate with the superficial lymph vesicles through vertical, dilated lymph channels.
Whimster postulated that these cisterns might arise from a primitive lymph sac that fails to connect with the rest of the lymphatic system during its embryonic development. A thick coat of muscle fibers that cause rhythmic contractions line these sequestered primitive sacs. Rhythmic contractions increase the intramural pressure, causing dilated channels to protrude from the walls of the cisterns toward the skin. He suggested that the vesicles seen in lymphangioma circumscriptum are outpouchings of these dilated projecting vessels.
Whimster's observations are supported by those of lymphangiographic and radiographic studies. These studies revealed that large multilobulated cisterns extend deep in the dermis and laterally beyond the obvious clinical lesions. These deep lymphangiomas show no evidence of communication with the adjacent normal lymphatics. The cause for the failure of these primitive lymph sacs to connect to the rest of the lymphatic system is not known.
Some lymphangiomas may represent vascular malformations during embryonic development rather than as true neoplasms.[5] Vascular endothelial growth factor (VEGF)–C and VEGF receptor-3 are active in the formation of lymphangiomas. Based upon their expression, superficial lymphangiomas more likely result from peripheral lymphatic dilatation than from a growth factor.
Fetal lymphangioma is presumably a result of failure in lymphatic drainage.[6]
The reason that these embryonic lymph sacs remain disconnected from the rest of the lymphatic system is not known. Fetal lymphangioma is presumably a result of failure in lymphatic drainage, documented on routine prenatal ultrasonographic studies.[6] Vulva lymphangioma circumscriptum may be secondary to pelvic lymphatic obstruction, linked in some patients to rectal adenocarcinoma, cervical carcinoma, or endometrial carcinoma.[7]
Lymphangiomas are rare. They account for 4% of all vascular tumors and approximately 25% of all benign vascular tumors in children.
Race
No racial predominance is reported for lymphangiomas.
Sex
Equal sex incidences are reported for lymphangiomas in most studies. Some groups have reported that lymphangioma circumscriptum is more common in females than in males, while others report a 3:1 male-to-female ratio.
Age
Lymphangioma can become evident at any age, but the greatest incidence occurs at birth or early in life. About 50% of lymphangiomas are seen at birth, and most lymphangiomas are evident by the time the patient is aged 5 years. It may be documented in fetuses too.[6]
Lymphangiomas are benign hamartomatous malformations instead of true neoplasms. The prognosis for lymphangiomas is excellent.
Rarely do cutaneous lymphangiomas interfere with the well-being of patients. Patients are expected to live a full healthy life, and they usually seek medical intervention because of cosmetic reason.
Lymphangiomas represent hamartomatous malformations with no risk of malignant transformation. In the case of cystic hygroma, total surgical excision is appropriate to prevent complications such as respiratory compromise, aspiration, and infections in critical areas, such as the neck. Lymphangiomas have a strong tendency for local recurrence unless they are completely excised. Recurrent episodes of cellulitis and minor bleeding are not uncommon.
Patients should receive reassurance. Lymphangiomas represent benign lymphatic malformations and not premalignant lesions. Patients should be aware of the risk of recurrence.
The typical history involves a small number of vesicles on the skin at birth or shortly after. In subsequent years, they tend to increase in number, and the area of skin involved continues to expand. Vesicles or other skin abnormalities may not be noticed until several years after birth. Usually, lesions are asymptomatic, but, occasionally, patients may have spontaneous episodes of minor bleeding and copious drainage of clear fluid from ruptured vesicles.
Cavernous lymphangioma
Typically, during infancy, a solitary rubbery nodule with no skin changes becomes evident in a single location, such as the face, trunk, or extremity. These lesions often have a fast growth phase similar to that of raised hemangiomas. No family history of prior lymphangiomas is described.
Cystic hygroma
Soon after birth, the infant is noted to have a deep subcutaneous cystic swelling, usually in the axilla, base of the neck, or groin. If these lesions are drained, they tend to fill up rapidly with lymph fluid. The lesions tend to grow and increase to a large size if they are not completely excised at surgery.
Lymphangiomas may affect a number of sites, including the scrotum. Multilocular lymphangiomatosis of the scrotum is unusual.[8] The site of a lymphangioma may determine its clinical signs and symptoms. For example, a lacrimal gland lymphangioma may result in acute proptosis and inferonasal displacement of an eye.[9]
Note the images below.
View Image
A 44-year-old woman with plaque on her forearm since birth that clinically appeared to be typical lymphangioma circumscriptum. Histologically, however....
View Image
Close-up demonstrating the clinical morphology to better advantage.
Lymphangioma circumscriptum
Lymphangioma circumscriptum involves small clusters of vesicles measuring about 2-4 mm. These clear vesicles can vary from pink to red to black secondary to hemorrhage.[1] Although it may appear localized to the dermis, this neoplasm frequently extends deeply and laterally. The lesions can have a warty appearance on their surface; as a result, they are often confused with warts. Shah et al report a lymphangioma presenting on the penis.[10]
Cavernous lymphangioma
Typically, cavernous lymphangiomas appear as subcutaneous nodules with a rubbery consistency. They may have large dimensions. The overlying skin has no lesions or changes. The area of involvement varies, ranging from lesions smaller than 1 cm in diameter to larger lesions that involve an entire limb.
Cystic hygroma
Cystic hygromas are usually larger than cavernous lymphangiomas, and they more commonly occur in the neck and parotid area. Often, deep cavernous lymphangiomas are not evident on superficial examination, but cystic hygromas are detected with ease because of their size and location. These large cystic lesions are soft and translucent. Congenital and acquired lymphangiomas of the vulva are rare.[11, 7] Diffuse lymphangiomas may go unnoticed, evident as asymptomatic, erythematous flat, indurated, or atrophic plaques with or without swelling with or without any surface changes.
Fetal lymphangioma
Fetal lymphangioma may involve fetal skin and occasionally mucosa and subcutaneous tissue, typically on neck or axilla.[6] The fetal chest wall cystic lymphangioma is rare.[12]
Lymphangioma circumscriptum may occur. Lymphangiomas circumscriptum is associated with minor bleeding, recurrent cellulitis, and lymph fluid leakage. Two cases of lymphangiosarcoma arising from lymphangioma circumscriptum have been reported. However, in both of the patients, the preexisting lesion was exposed to extensive x-ray therapy. Therefore, radiation therapy should be avoided in lymphangiomas.
In cystic hygroma, large cysts can cause dysphagia, respiratory problems, and serious infection if they involve the neck.
A cystic lymphangioma of the scrotum may present as an acute scrotum, owing to the rare complication of hemorrhage.[13]
A Dabska tumor may rarely arise within lymphangioma circumscriptum.[14]
MRI can help define the degree of involvement and the entire anatomy of the lymphangioma lesion. MRI can help prevent unnecessary extensive, incomplete surgical resection, because of the association with a high recurrence rate.
The scrotum is not a usual site, but a painless scrotal swelling was documented as a lymphangioma by typical sonography and MRI findings, followed by excision and pathologic confirmation.[22]
Immunohistochemical study is useful in differentiating lymphangiomas from hemangiomas in difficult cases. Test results with factor VIII – related antigen are positive for hemangiomas but negative or weakly positive in the endothelium of lymphangiomas. Immunohistochemical studies for laminin show the typical multilayered basal lamina of normal blood vessels and the discontinuous basal lamina in lymphangiomas.
Dermoscopic findings may aid in the diagnosis of cutaneous lymphangioma circumscriptum.[23, 24, 25] Nodules filled with clear fluid show light brown lacunas surrounded by paler septa. Those tinged with blood may have focal reddish areas inside the lagoons, pink diffuse coloration, and/or reddish to violaceous lacunar structures. In those lacunae that contained blood, it accumulated in the lowest part.[26] Thus, they are characterized by a lacunar pattern and with a marked hematic content may be indistinguishable from a hemangioma.
Microscopically, the vesicles in lymphangioma circumscriptum are greatly dilated lymph channels that cause the papillary dermis to expand. They may be associated with acanthosis and hyperkeratosis. These channels are numerous in the upper dermis and often extend to the subcutis. These deeper vessels seem to have a large caliber, and they often have a thick wall that contains smooth muscle. The lumen is filled with lymphatic fluid, but it often contains red blood cells, lymphocytes, macrophages, and neutrophils. These channels are lined by flat endothelial cells, which stain positive for Ulex europaeus agglutinin-I. The interstitium often has numerous lymphoid cells and shows evidence of fibroplasia.
Nodules in cavernous lymphangioma are characterized by large, irregular channels in the reticular dermis and subcutaneous tissue that are lined by a single layer of endothelial cells. An incomplete layer of smooth muscle often lines the walls of these malformed channels. The surrounding stroma consists of loose or fibrotic connective tissue with a number of inflammatory cells. These tumors often penetrate muscle.
Cystic hygroma is indistinguishable from cavernous lymphangiomas on histology.
No medical care has been proven effective for lymphangiomas. Lymphangioma is not responsive to radiation therapy or steroids. However, propranolol represents a potential option, which may be of benefit even for intractable diffuse lymphangiomatosis.[27] Sodium tetradecyl sulfate may be used with care for off-label treatment of lymphangioma circumscriptum.[28]
Antibiotics are given for secondary cellulitis.
In the case of lymphangioma circumscriptum, severe recurrent cellulitis may warrant inpatient care at times, especially in patients who are immunocompromised.
The preferred treatment for lymphangiomas is complete surgical excision.[29] On the basis of the Whimster hypothesis, the large subcutaneous cisterns should be removed to prevent the lesion from resurfacing.
Local recurrences are common in lymphangiomas. Adequate excision of lymphangiomas can be difficult and, at times, unfeasible. This problem is the main reason for the high recurrence rate. Tumors that are confined to the superficial dermis are more amenable to surgical excision, which is associated with a high rate of success.
The use of other treatment modalities has been advocated; these include cryotherapy, sclerotherapy, cautery, and radiofrequency therapy.[30, 31] Bleomycin sclerotherapy has been advocated for head and neck lymphangiomas.[32]
Lymphangioma circumscriptum may be treated with simple electrodessication. It does not always respond to use of the pulsed-dye laser.[33]
Vaporization with a carbon dioxide laser has been tried with good results.[34] Other lasers may also be used.[35] Intra-oral lymphangioma may be treated using fractional carbon dioxide laser.[36]
Another therapeutic option for lymphangioma circumscriptum is 23.4% hypertonic saline sclerotherapy.[37]
The use of intralesional OK432 (Picibanil) is a new and effective treatment for macrocystic lesions,[38] but the response of microcystic or cavernous lesions to OK-432 has been disappointing and surgery remains the most effective treatment for these microcystic and cavernous lesions.[39, 40]
Postoperative vacuum-assisted closure devices may decrease the risks of recurrence and infection.[41]
Patients with lymphangiomas should be monitored and treated for cellulitis, especially those with ruptured vesicles, which provide a portal of entry for infection. Regular skin examination should be included in the follow-up treatment to evaluate recurrence and the response to treatment.
Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School
Disclosure: Nothing to disclose.
Coauthor(s)
Geover Fernandez, MD, FAAD, Staff Physician, Department of Dermatology, Rutgers New Jersey Medical School
Disclosure: Nothing to disclose.
Specialty Editors
David F Butler, MD, Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic
Disclosure: Nothing to disclose.
Jeffrey J Miller, MD, Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Carrie L Kovarik, MD, Assistant Professor of Dermatology, Dermatopathology, and Infectious Diseases, University of Pennsylvania School of Medicine
A 16-year-old obese boy with large unilateral verrucous lymphangioma.
A 44-year-old woman with plaque on her forearm since birth that clinically appeared to be typical lymphangioma circumscriptum. Histologically, however, it had features of both hemangioma and lymphangioma.
Close-up demonstrating the clinical morphology to better advantage.
A 44-year-old woman with plaque on her forearm since birth that clinically appeared to be typical lymphangioma circumscriptum. Histologically, however, it had features of both hemangioma and lymphangioma.
Close-up demonstrating the clinical morphology to better advantage.
A 16-year-old obese boy with large unilateral verrucous lymphangioma.
){kind=link}
){kind=link}
){kind=link}