Are You Confident of the Diagnosis?
What you should be alert for in the history
The history is marked by congenital hemangioma that is fully or near-fully developed at birth and grows as the child grows, slight male predominance, and failure to involute spontaneously by the first year of life.
Characteristic findings on physical examination
Characteristic findings include a blue-violet mass or plaque that is well circumscribed and erythematous, which can have overlying telangiectasias or a surrounding pale rim. It occurs most often on the head and neck, favoring the mandible.
Expected results of diagnostic studies
Histopathology reveals a large central vessel with surrounding lobules of smaller, thin-walled vessels lined by “hobnail” endothelial cells, and dilated, abnormal interlobular veins. Gglucose transporter protein-1 (GLUT-1) is negative; Wilms tumor protein-1 (WT-1)
Among imaging studies, ultrasound can usually pick up NICH in the second and third trimesters of pregnancy. Magnetic resonance imaging (MRI) reveals a lobulated soft-tissue mass with flow voids, and high-flow vessels
The differential diagnosis includes infantile hemangioma (precursor lesion present at birth followed by rapid, postnatal growth; GLUT-1 [+] and rapidly involuting congenital hemangioma (rapid involutes within the first year of life).
Who is at Risk for Developing this Disease?
The risk ractors for hemangiomas apply to NICH as well. These include
-Low birth weight
-Chorionic villus sampling during pregnancy
-Multiple gestations, advanced maternal age
What is the Cause of the Disease?
The etiology is unknown.
The pathophysiology includes aberrant angiogenesis driven by local and systemic pro-angiogenic factors such as VEGF and angiopoeitin-2. The mechanisms behind resistance to involution are unknown.
Systemic Implications and Complications
Ulceration is the most common complication (10%). The incidence is proportional to the size of the lesion. Bleeding occurs mostly secondary to ulceration and can usually be controlled with firm pressure. Other complications include infection; pain; and high-output cardiomyopathy, a rare but potential fatal complication; risk proportional to the size of the lesion.
Surgical excision is usually curative and can be considered early in disease management if secondary complications become unmanageable. Medical management of secondary complications is performed appropriate. Pulsed-dye laser therapy and topical becaplermin have shown benefit in ulcerated infantile hemangiomas. High-output cardiomyopathyrequires medical management with cardiology consultation early on; consider early surgical intervention.
There is a possible role for systemic angiogenesis inhibitors but, given NICH’s rarity, clinical trials will be difficult to conduct. There are no studies to date regarding the use of propranolol for NICH. Although propranolol could be prescribed under extenuating circumstances, the presumption is that it would not be effective as the lesion does not involute naturally. Other ssuggested treatments include Bevacizumab (antibody against VEGF) and Sirolimus (MTOR inhibitor).
Optimal Therapeutic Approach for this Disease
Surgical excision is the optimal treatment. Intraoperative arterial embolization can help to manage the risk of hemorrhage, although not absolutely. NICH shows little risk of recurrence, approaching zero percent at 6 months.
Patients should be monitored for at least 1 year to allow for possible spontaneous involution. Until that time, management centers mainly around assessing the extent and flow-characteristics of the lesion as well as managing complications (ulceration, bleeding, infection) appropriately. If after 14-18 months the lesion is determined to be a NICH, surgical excision is the preferred treatment, as it carries little risk of complications.
With large lesions, there is a risk of potentially fatal high-output cardiomyopathy. Medical management with cardiology consultation early on and possible surgical intervention are key.
Unusual Clinical Scenarios to Consider in Patient Management
During the 14-18 months of observation, NICH can present challenges in medical management, including risks for ulceration, bleeding and infection. Clinicians should exert caution in addressing these issues preemptively by discussing them with caregivers and coming up with an action plan. The risk of potentially fatal high-output cardiomyopathy with large lesions should prompt cautious medical management with cardiology consultation early on if necessary and possible surgical intervention. Once the NICH determination has been made, surgical excision with or without intraoperative arterial embolization is often curative with little risk of complication or recurrence.
What is the Evidence?
Baker , C, Kelly , R, Bolognia , JL, Jorizzo , JL, Rapini , RP. “Other vascular disorders”. Dermatology. 2008. pp. 1615-25. (An excellent textbook summary with good clinical and pathologic images on a variety of vascular disorders, including NICH.)
Lawley , LP, Cerimele , F, Weiss , SW, North , P, Cohen , C, Kozakewich , HP, Mulliken , JB, Arbiser , JL. “Expression of Wilms tumor 1 gene distinguishes vascular malformations from proliferative endothelial lesions”. Arch Dermatol . vol. 141. 2005. pp. 1297-1300. (The authors were able to show that lack of immunohistochemical staining for WT-1 reliably distinguished vascular malformations from other vascular tumors with high specificity.)
Shirazi , F, Cohen , C, Fried , L, Arbiser , JL. “Mammalian target of rapamycin (mTOR) is activated in cutaneous vascular malformation in vivo”. Lymphat Res Biol . vol. 5. 2007. pp. 233-6. (This article argues for mTOR as a reasonable drug target in vascular malformations and suggests a role for mTOR inhibition in a variety of other vascular tumors.)
Hammill , AA, Wentzel , M, Gupta , A, Nelson , S, Lucky , A, Elluru , R. “Sirolimus for the treatment of complicated vascular anomalies in children”. Pediatr Blood Cancer. vol. 57. 2011. pp. 1018-1024. Together with reference 3, this article demonstrates in vivo the efficacy of mTOR inhibition by sirolimus in complicated vascular tumors and argues for further study of sirolimus and other mTOR inhibitors in the treatment of vascular lesions.
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