Are You Confident of the Diagnosis?
What to be alert for in the history
A rare condition, lymphangioma circumscriptum (LC) has been divided into two broad categories, each with its own typical presentation and history. These two categories are classical and localized. In the classical form, the condition’s hallmark vesicles are typically present at birth or develop shortly thereafter. For lesions of either type developing after birth, the patient might provide a history of localized swelling or edema prior to the eruption of vesicles at the same site.
Classical LC has a predilection for appearing in the proximal limbs, axilla, buttocks, trunk and tongue. The clustered vesicles characteristically cover a surface area greater than a square centimeter, and it is uncommon for vesicular areas to form plaques or undergo verrucous changes.
The localized type is less confined by age at presentation or body distribution. The vesicles can appear at any age, and 25% of patients are greater than 45 years old at first presentation. Localized type characteristically covers a surface area of less than a square centimeter and may form thick plaques or undergo verrucous changes.
Unlike its classical counterpart, localized type can appear nearly anywhere on the body. Despite classical LC’s affinity for certain body regions, both types have been described appearing in the oral cavity, on the penis, vulva and scrotum, and even within the peritoneum, mesentery and bone.
Though LC is often asymptomatic, vesicles are prone to rupture with weeping and crusting, and a history of recurrent bacterial infection is common. This is particularly true if the lesions are itchy or irritating, as excoriations allow a portal for bacterial entry. Though the clustered vesicles may be painful, they should not undergo rapid change or growth. Any such history should raise suspicion of other conditions.
Characteristic findings on physical examination
On clinical examination, LC is best described as clustered thin-walled and translucent vesicles, most often less than 5mm in diameter. The vesicles contain clear lymphatic fluid, though hemorrhage can tint the fluid pink, red, brown or black. Their clustered appearance on smooth skin often draws comparisons to frog spawn (Figure 1). The vesicles may slowly grow larger and rupture, leading to crusting, weeping or bleeding, and thick, hyperkeratotic plaques with a verrucous appearance may form in adjacent skin. Localized swelling is often palpable surrounding the lesions.
Dermatoscopic inspection demonstrates septated lacunae filled with clear fluid that can be tinted pink, red, brown or black by the presence of erythrocytes. If there is extensive hemorrhage into the lymphatic channels, the brilliant red appearance of fresh blood can make LC indistinguishable from a hemangioma under the lens of a dermatoscope.
The rarity, varying appearance and distribution of LC can make for a challenging differential diagnosis, which includes the following:
– Cutaneous metastases of internal malignancy (particularly carcinoma telangiectoides). Malignancy is typically associated with a history of cancer near the site of cutaneous involvement, unexpected weight loss, or a family history of cancer. Biopsy of the lesion can identify malignant proliferation.
– Lymphangiosarcoma, a malignant neoplasm derived from lymphatic tissue and rarely arising from LC itself, can be distinguished from LC by biopsy.
– Lymphangiectasias: These have the same clinical appearance but are derived from obstructed normal lymphatic channels and can be distinguished by their appearance at sites of trauma, surgical incision or radiation therapy.
– Hemangioma: May have identical appearance under a dermatoscope, but a biopsy can distinguish the two.
– Warts: LC may undergo verrucous plaque formation making clinical appearance similar, particularly in the genital region, but tissue biopsy can delineate between the two entities.
– Molluscum contagiosum: LC can appear in the genital region with an appearance similar to molluscum, but again, biopsy will establish the diagnosis.
– Angiokeratoma (identified on biopsy).
Expected results of diagnostic studies
Obviously, tissue sample and histologic examination are critical to establishing diagnosis and treatment modalities. Under the microscope, numerous dilated lymphatic channels are observed in the papillary dermis underlying a thinned epidermis, though hyperkeratosis or acanthosis may be noted superficial to the lymphatics. The channels typically extend to the reticular dermis or subcutaneous tissue where they branch from deep smooth muscle-lines lymphatic cisterns of larger diameter.
The lymphatic spaces may contain varying numbers of red or white cells, depending on the degree of hemorrhage into them. Capillary tufts may be present within the tissue sample (Figure 2, Figure 3).
While imaging does not share a role in establishing the diagnosis of LC, magnetic resonance imaging (MRI) does have utility in planning treatment. Effective surgical treatment of LC necessitates excision of the deep lymphatic cisterns, which feed the surface vesicles. MRI can demonstrate the location and extent of these often deeply subcutaneous structures and allow for the construction of well-informed surgical margins.
Who is at Risk for Developing this Disease?
Though the most common of the cutaneous lymphangiomas, LC is rare. Well constructed epidemiologic studies determining the incidence of LC do not appear to exist, but lymphatic malformations occur in approximately 1.2 to 2.8 of every 1,000 live births in the United States. LC represents only a small percentage of these cases; 90% of patients who will get LC have it by the age of 2 years, and half of these individuals will have been born with the condition.
Despite these numbers, LC can appear in a patient of any age, even into late adulthood. Studies have not revealed any patterns of familial transmission, but more research into the epidemiology of this uncommon condition is needed. No specific risk factors for developing LC have been identified.
What is the Cause of the Disease?
Despite its superficial manifestations, LC is a problem of abnormal lymphatic vessels in the deep subcutaneous tissues. There, large dilated and abnormal lymphatic cisterns branch smaller channels that travel upward through the skin to blind endings in the papillary dermis.
These cisterns and their aberrant channels form a closed, fluid-filled system that does not communicate with normal lymphatics in the region. The deep cisterns have thick walls lined by smooth muscle fibers that contract, transmitting fluid pressure to the superficial channels. The increasing pressure dilates the superficial channels, which eventually protrude through the skin forming the typical thin-walled vesicles. Excision without removing the deep cisterns will result in recurrence, as the cisterns will sprout and feed new superficial channels.
The origin of the deep lymphatic cisterns is not known, but many propose they are an isolated remnant of primitive embryonic lymph sacs. During normal development, these sacs, which most commonly form at the site of limb buds, grow to confluence forming the normal lymphatic channels responsible for recirculating interstitial fluid. Failure to merge with the rest of the early lymphatic system may cause one of these sacs to form an isolated cistern and its closed system of channels leading to LC. The location of primitive lymph sac development at sites of limb buds would account for classical LC’s preferential presentation at the proximal limbs.
Systemic Implications and Complications
The most common complications for LC are bleeding and recurrent bacterial infection. Staphylococcus aureus is the most common causative organism of infection and can be treated with oral antibiotics. LC has been reported to occasionally occur concurrently with other lymphatic malformations such as cystic hygroma or cavernous lymphangioma, and these conditions can be detected with routine physical examination.
Case reports exist describing rare progression to certain malignancies, including Dabska tumors, squamous cell carcinoma and lymphangiosarcoma. Lymphangiosarcoma has been most commonly reported as arising from LC following radiation therapy. Lymphangioma circumscriptum, or the site of surgical excision of LC, should be observed by a physician for any rapid change or growth. Biopsy should be performed if any suspicion of malignancy arises. Radiation therapy is never recommended as a treatment for LC to minimize any risk of progression to lymphangiosarcoma
Treatment options for LC are summarized in Table I.
|Medical Treatment||Surgical Treatment||Physical Modalities|
|Antiobiotics for recurrent infectionDicloxacillin 500mg orally twice a day to 4 times a day for 10 daysCephalexin 500mg orally twice a day to 4 times a day for 10 daysor if MRSA is suspected,Doxycycline 100mg orally twice a day for 10 days||Full thickness surgical excision to deep fascia with 1cm margins. Closure dependent on size of defect. Anything over 3cm I will refer to plastic surgery. Preoperative MRI is helpful to fully characterize the size and depth of the region involved.Highest cure rates.||SclerotherapyHypertonic saline 23.4% full strength or cut in half to 11.7% to decrease the pain associated with injection. Sodium tetradecyl sulfate from 0.25% to 0.5%.Polidocanol 0.5% ( 2mg/kg is the maximum dose)None of these are FDA approved for LC.|
|CO2 laser ablationSettings: 1mm spot size, 5 Watts on continous wave mode. Many other settings exist.|
|Electrocautery – only for the most superficial of lesions|
|Cryotherapy – again for superficial lesions, not that successful|
|Radiation should be avoided.|
All therapies have a high rate of recurrence. This should be communicated to the patient before attempting any removal.
Optimal Therapeutic Approach for this Disease
Treatment for LC is not usually necessary, as the growths are benign with a very low probability of malignant transformation. In uncomplicated cases, observation is acceptable. In cases where the lesions are unsightly, are painful, are persistently leaking, or repeatedly become infected, treatment may be warranted.
Surgical excision has been demonstrated to be superior to other treatment modalities and is effective in removing the primary lesion and preventing recurrence in about 75% of cases. To successfully prevent recurrence, the deep lymphatic cisterns that feed the superficial dilated channels must be removed. Thus, the excision must include the full thickness of the skin, down to deep fascia. Since the channels can spread laterally under the skin, wide margins are recommended. Excised tissue should be sent for frozen section to assess margins in the lateral and deep planes.
MRI can effectively demonstrate the full extent of lateral and deep involvement, as well as identify the deep cisterns. The images can aid in constructing adequate surgical margins, minimizing the risk of recurrence.
In severe cases with involvement of a large surface area, excision may require grafting to close the surgical defect. Special consideration may also be necessary based on anatomic location. Excision of lesions affecting the genitals may require other specialties such as plastic surgery to achieve maximally efficacious treatment and an acceptable cosmetic end point.
Should the lesion recur after surgical excision, it is highly likely that one or more of the causative deep lymphatic cisterns was not properly excised. Re-excision should be attempted with the intent of fully removing the deep structures, which may lie deeper than the plane of excision or outside of the surgical margins. The margins should be reconsidered to optimize success. If the resected tissue was sent for frozen section, histopathology can guide the surgeon at reoperation. MRI can be utilized to pinpoint the location of the deep cisterns.
For patients in whom surgery is not an option, cauterization, sclerotherapy, cryotherapy and carbon dioxide lasers have been identified as acceptable alternatives for palliative treatment. Sclerotherapy may involve hypertonic saline or the sclerosing agent OK-432. The latter has been more extensively studied as a presurgical adjunct with good results. For all of these modalities, patients should be informed that recurrence is common and should be expected most likely within a year.
Laser ablation has been reported to have an elevated risk of keloid formation.
Patients should be informed of the natural history of LC. The condition is a benign lymphatic malformation with very low risk of malignant transformation. The possibility of recurrent infection should be explained as well. Despite the benign course of this disease, the physician should be sensitive to patients’ perceptions of the lesions. They may find the growths unsightly, irritating, or could be frustrated with recurrent infection and desire treatment to remove the affected areas.
As such, treatment should be tailored to the patient’s goals. Some may prefer the less invasive approaches of sclerotherapy or liquid nitrogen cryotherapy, despite the high probability of recurrence and need for periodic retreatment. Others may choose more invasive surgery with its low rate of recurrence. For all methods of treatment, patients should be counseled on the probability of lesions returning. Should the lesions recur after surgical excision, subsequent excision may yield better results.
Imaging studies or re-operation after microscopic examination of excisional margins may reduce recurrence rates. Utilizing sclerotherapy prior to surgical excision could increase efficacy. For patients with problematic recurrent cellulitis, antibiotic prophylaxis may be necessary to prevent reinfection.
Unusual Clinical Scenarios to Consider in Patient Management
Reports exist associating LC with certain syndromes. These include Proteus syndrome, Cobb syndrome, Maffucci syndrome and epidermal nevus syndrome. All these conditions are quite uncommon, and LC has been reported to only rarely occur in association with them.
What is the Evidence?
Fox, T, Fox, TC. “On a case of lymphangiectodes with an account of the histology of the growth”. Trans Pathol Soc London . vol. 30. 1878. pp. 470-6. (The sentinel article describing what is now called lymphangioma circumscriptum.)
Whimster, IW. “The pathology of lymphangioma circumscriptum”. Br J Dermatol. vol. 94. 1976. pp. 473(The widely accepted and first account of the pathophysiology of lymphangioma circumscriptum, with implications and management.)
Patel, GA, Schwartz, RA. ” Cutaneous lymphangioma circumscriptum: frog spawn on the skin”. Int J Dermatol . vol. 48. 2009. pp. 1290-5. (An excellent review of lymphangioma circumscriptum, including descriptions and clinical findings, histopathology, pathophysiology, epidemiology, differential diagnosis and treatment.)
Heller, M, Mengden, S. “Lymphangioma circumscription”. Dermatol Online J. vol. 15. 2008. pp. 14-27. (A concise review of lymphangioma circumscriptum including a case report of a patient presenting to the dermatology clinic at the Bellevue Hospital Center.)
Vlastos, AT, Malpica, A, Follen, M. “Lymphangioma circumscriptum of the vulva: a review of the literature”. Obstet Gynecol. vol. 101. 2003. pp. 946(A literature review detailing the pathophysiology, clinical findings and treatment options for lymphangioma circumscriptum with special considerations for involvement of the vulva. Includes a case report and in depth discussion of treatment modalities and recurrence rates in a small series.)
Swanson, DL. “Genital lymphangioma with recurrent cellulitis in men”. Int J Dermatol. vol. 45. 2006. pp. 800(A retrospective series of six patients and one case report of penile lymphangioma circumscriptum with recurrent infection. Patients were successfully prophylaxed against future infection with oral antibiotics. Though the series is too small to base standard of care decisions upon, in patients ineligible for surgery complicated by troublesome recurrent infections, prophylaxis is beneficial.)
Browse, NL. “Surgical management of lymphangioma circumscriptum”. Br J Surg. vol. 73. 1986. pp. 585(A series of 29 patients with lymphangioma circumscriptum treated with surgical excision and followed for 2 to 8 years, demonstrating excellent success rates. The authors did not perform any excisions so large as to require grafting, opting instead to leave affected skin behind in large lesions to permit primary closure. Success rates may have been improved by performing larger excisions with grafting. The article also lends support to Whimster's hypothesis on the pathogenesis of lymphangioma circumscriptum.)
Lapidoth, M. “Treatment of lymphangioma circumscriptum with combined radiofrequency current and 900nm diode laser”. Derm Surg. vol. 32. 2006. pp. 790(Six patients were treated with a combination of radiofrequency and pulse laser. Four patients rated outcomes as excellent, and two as good. Follow-up was only 2 months. The technique needs to be studied more but may be useful as a palliative therapy. The study's short follow-up is inadequate to determine recurrence rates.)
Bikowski, JB, Dumont, AMG. “Lymphangioma circumscriptum: treatment with hypertonic saline sclerotherapy”. J Am Acad Dermatol. vol. 53. 2005. pp. 442(An informative case report with good background detail on lymphangioma circumscriptum, discussing the use of hypertonic saline as a palliative agent.)
Peachey, RD, Lim, CC, Whimster, IW. ” Lymphangioma of skin: A review of 65 cases”. Br J Dermatol. vol. 83. 1970. pp. 519-27. (A study of 65 patients with the first widely accepted categorization of lymphangioma circumscriptum into two groups, classical and localized.)
Shim, JH, Lee, DW, Cho, BK. “A case of Cobb syndrome associated with lymphangioma circumscriptum”. Dermatology. vol. 193. 1996. pp. 45-7. (A case report describing a patient with Cobb syndrome and concurrent LC.)
Child, FJ, Werring, DJ, Vivier, AW. “Proteus syndrome: diagnosis in adulthood”. Br J Dermatol. vol. 139. 1998. pp. 132-6. (A case report of an adult patient diagnosed with Proteus syndrome after suffering its symptoms over the course of her life. The patient was also diagnosed as having LC.)
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