Melanoma Gene Expression Markers for Surveillance of Epidermolysis Bullosa Nevi Malignant Transformation | Cancer Biomarkers | JAMA Dermatology | JAMA Network
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May 2016

Melanoma Gene Expression Markers for Surveillance of Epidermolysis Bullosa Nevi Malignant Transformation

Author Affiliations
  • 1Washington University in St Louis School of Medicine, St Louis, Missouri
  • 2Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
JAMA Dermatol. 2016;152(5):584-586. doi:10.1001/jamadermatol.2015.5702

The evaluation of malignant changes in epidermolysis bullosa (EB) nevi remains a challenge for clinicians; herein, we introduce the idea of employing melanoma gene expression markers to aid in thorough histopathologic examination of suspicious EB nevi lesions.

Report of a Case

A young girl with epidermolysis bullosa simplex (EBS) initially came under our care at age 4 years. Two years after her first presentation, she developed an irregular brown-black patch on her left lateral ankle. The lesion was a 3.6 × 3 cm triangular hyperpigmented, asymptomatic patch consisting of confluent mottled black and brown macules and several satellite lesions consistent with an EB nevus.

The patient returned at age 9 years and the parents noted slow but progressive growth of the hyperpigmented patch on her left ankle. On examination, several brown macules coalescing into a 5.5 × 5-cm patch with surrounding satellite lesions was seen on her lateral ankle (Figure 1A). Biopsy was performed of a representative area, showing a compound nevus with large nested melanocytes and bridging at the dermal-epidermal junction consistent with an atypical compound nevus (Figure 1B).

Figure 1.  Epidermolysis Bullosa Nevus at 9 Years of Age
Epidermolysis Bullosa Nevus at 9 Years of Age

A, A large, dark brown patch consisting of coalescing macules and satellite lesions is seen. B, Compound melanocytic proliferation is observed, demonstrating appropriate maturation, as is random atypia with large nested cells characterized by prominent nucleoli and heavy pigmentation (original magnification × 200).

The patient was seen for follow-up every 6 months. The atypical nevus remained unchanged until age 12 years, when 2 discrete areas of regression were noted (Figure 2A). On dermoscopy, discontiguous and irregular homogenous blue, brown, and gray areas with gray-brown structureless areas and a negative pigment network were observed, suggestive of malignant transformation. No induration was palpated except at the previous biopsy site.

Figure 2.  Epidermolysis Bullosa Nevus at 12 Years of Age
Epidermolysis Bullosa Nevus at 12 Years of Age

A, The patch shows areas of regression on the medial and left upper borders. B, Compound melanocytic proliferation is observed marked by random nuclear atypia and broad areas of regressive fibrosis (original magnification ×100).

Repeated biopsy of the areas of clinical regression showed atypical nevus with areas of dermal fibrosis (Figure 2B). Gene expression testing for 23 melanoma genes was performed yielding a melanoma gene expression test (Myriad myPath; Myriad Genetics) score of −7.1, where scores from −16.7 to −2.1 are consistent with a benign nevus. The score, in combination with the histopathologic findings, indicated that the changes seen on the clinical examination were benign. Therefore, we managed the lesion with conservative observation.


Epidermolysis bullosa nevi in patients with EBS have been largely thought to be of low malignant potential despite their alarming mimicry of melanoma. However, with the recent report of a malignant transformation of a melanocytic nevus in a patients with EBS, malignant potential of EB nevi has been reevaluated, and active surveillance of EB nevi in patients with EBS is warranted.1

Examination of melanocytic nevi is recommended every 6 months, along with biopsy and histopathologic examination of any suspicious changes.2 Given EB nevi’s striking baseline resemblance of melanoma, clinical evaluation is challenging. As EB nevi tend to be large, have a rapid, continuous growth phase, and occasionally regress over time, regular histopathologic evaluation of the nevi seems impractical, especially in pediatric patients who may not tolerate large, frequent biopsies.3,4 Even the histopathologic evaluation of EB nevi continues to be a challenge for the clinician, as blistering conditions can lead to pseudomelanomatous features that simulate melanomas.1,3

With the use of melanoma gene expression markers, smaller biopsy samples can differentiate malignant transformations from benign lesions with high sensitivity and specificity.5 Employing such gene expression markers can be especially helpful in cases of atypia seen on histopathologic examination because the markers can aid in distinguishing pseudomelanomatous changes from true malignant transformations. With the use of melanoma markers in combination with traditional histopathologic analysis, clinicians may also identify subtler changes of a malignant transformation earlier, ultimately leading to decreased morbidity and mortality of patients.

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Article Information

Corresponding Author: Tor Shwayder, MD, Division of Dermatology, Henry Ford Hospital, 3031 W Grand Blvd, Ste 800, Detroit, MI 48202 (

Published Online: February 10, 2016. doi:10.1001/jamadermatol.2015.5702.

Conflict of Interest Disclosures: None reported.

Additional Contributions: We are grateful to the patient and her family for participation in this study and for granting permission to publish this information.

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