Clinical, molecular features aid worrisome birthmark recognition

"With new information about morphological and molecular prognostic features, we are getting smarter about subclassifying congenital nevi, hemangiomas and port wine stains. As a result, we are better able to reassure parents when there appears to be a good prognosis and know which children need further evaluation and monitoring," says Dr. Shwayder, director of pediatric dermatology, Henry Ford Hospital, Detroit.

Regarding congenital melanocytic nevi, there is some updated information from the ongoing New York University prospective study on the risks associated with large lesions. According to the latest data, the lifetime risk of melanoma associated with large lesions (those estimated to reach ≥20 cm in diameter in adulthood) appears to be about 2.5 percent to 3.5 percent.

However, as reported by Marghoob et al. in 2004, when a large congenital nevus involves the posterior axis and is accompanied by multiple satellite melanocytic nevi, there is an elevated risk of neurocutaneous melanocytosis. In that setting, MRI is indicated to identify meningeal involvement.

"The MRI should be interpreted by a radiologist who has expertise reading images from infants and looking for this entity," Dr. Shwayder says.

Hemangioma research Research focusing on identifying markers for differentiating subtypes of hemangiomas has yielded results that are helpful for subclassifying lesions and for shedding light on developmental mechanisms. Just a few years ago, MiltonWaner, M.D., and colleagues reported that high endothelial immunoreactivity for glucose transporter-1 protein (GLUT1) was a marker for common infantile hemangiomas. Studies of other tissue specimens showed GLUT1 expression was absent in various vascular lesions, while in normal tissue, its expression was restricted to microvessels with blood-tissue barrier function (ie., from the CNS or placenta).

Researchers proposed that hemangiomas might arise from embolized placental cells that reach the skin in the developing fetus by circulating through the patent ductus arteriosus.

"That hypothesis helps to explain why hemangiomas are more common after chorionic villus sampling and in premature infants," Dr. Shwayder says.

Immunostaining for GLUT1 has also been found useful for enabling diagnosis of non-involuting congenital hemangioma (NICH) and rapidly involuting congenital hemangioma (RICH). In contrast, to common infantile hemangiomas, RICH develop in utero, are fully formed at birth, and are negative for GLUT1. NICH appear initially like regular hemangiomas, but they do not regress or do so very slowly, leaving a large, fibro-fatty residual mass. NICH are also GLUT1 negative.

Red flags Among hemangiomas, certain segmental lesions should raise a red flag because of their potential association with extracutaneous anomalies. Hemangiomas with a large segmental facial distribution are potentially worrisome because they may be a feature of the PHACE syndrome. Other manifestations of the PHACE syndrome include posterior fossa malformations, arterial anomalies, coarctation of the aorta, cardiac defects, eye abnormalities and sternal and thyroid defects. PHACE hemangiomas are also GLUT1 negative.