Continuing Education Activity

A dysplastic nevus is also referred to as an atypical or Clarks nevus and has been the topic of much debate in dermatology and dermatopathology. It is an acquired mole demonstrating a unique clinical and histopathologic appearance that sets it apart from the common nevus. These moles appear atypical clinically, often with a fried-egg appearance, and are commonly biopsied by providers due to the concern for melanoma. This activity reviews the cause and pathophysiology of dysplastic nevus and highlights the interprofessional team's role in its management.

Objectives:

• Identify the etiology of dysplastic nevi.

• Interpret the presentation of dysplastic nevi.

• Differentiate the management options available for dysplastic nevi.

• Communicate interprofessional team strategies for improving care coordination and outcomes in patients with dysplastic nevi.

Introduction

A dysplastic nevus is also referred to as an atypical or Clark nevus and has been the topic of much debate in dermatology and dermatopathology. It is an acquired mole demonstrating a unique clinical and histopathologic appearance that sets it apart from the common nevus. These moles appear atypical clinically, often with a “fried-egg” appearance, and are commonly biopsied by providers due to the concern for melanoma. A clinical diagnosis of atypical nevi is based upon the presence of at least 3 of the following features: diameter greater than 5 mm, ill-defined borders, irregular margins, and lesional color variation. Individuals with these nevi have an increased risk for melanoma, but contrary to some individual beliefs, these are considered banal nevi.[1][2][3]

Etiology

The etiology of dysplastic nevi is not entirely clear. The phenotypic expression of dysplastic nevi has been determined to be related to environmental and genetic factors. Factors such as sun sensitivity, fair skin tone, light eye and hair color, and freckling propensity are inherited traits that strongly predict the development of nevi. Also, ultraviolet (UV) sunlight exposure has been shown to accentuate the expression of the dysplastic nevi phenotype. A higher incidence of the dysplastic nevus syndrome phenotype has been demonstrated in epidemiologic studies in children with a history of greater exposure to UV light.[4][5][6]

A sequential progression model for dysplastic nevi as the intermediate between banal nevi and melanoma has been proposed in the past by Clark and is still a supported model by many dermatologists. However, this model suggests that mutations in the nevi would be shared with melanoma, which has not been demonstrated in the literature. Also, approximately 25% of melanomas are estimated to arise in pre-existing nevi, and 75% arise de novo. One study demonstrated the risk of a dysplastic nevus evolving into melanoma is 0.0005% for people younger than 40 years. Dysplastic nevi tend to be stable over time. 

Epidemiology

Dysplastic nevi may exist in approximately 2% to 18% of the population. Individuals with these nevi are at increased risk for melanoma. In White race individuals in the United States, the lifetime risk of developing melanoma is less than 1%, whereas, in patients with dysplastic nevi, the risk is greater than 10%. The risk of melanoma increases significantly to 50% in individuals with a family history of dysplastic nevus syndrome. Dysplastic nevi are relatively uncommon in the Japanese population. The incidence of dysplastic nevi in the pediatric population is very low.

Pathophysiology

The pathophysiology of dysplastic nevi is not well understood. The inheritance pattern is complicated, as it occurs more commonly than autosomal dominant inheritance. Unlike patients with familial melanoma, who often demonstrate a CDKN2A gene mutation, dysplastic nevi do not commonly display this mutated gene. Recent studies noted that dysplastic nevi are clonal like common nevi, and some have BRAF, p16, or p53 alterations in expression. Also, dysplastic nevi were found to have higher proliferative rates than common nevi, as measured by proliferative markers Ki-67 and cyclin D1.[7][8][9]

Histopathology

Histopathologically, dysplastic nevi have 4 characteristic features that help distinguish them from other nevi or melanoma. These features include intraepidermal lentiginous hyperplasia of melanocytes, cytological atypia of melanocytes, lamellar and concentric fibroplasia (stromal response), and architectural atypia. Compound dysplastic nevi often have a “shoulder sign” in which the epidermal component extends beyond or “shoulders” the dermal component.[10]

The cytological atypia is random and includes enlarged dark nuclei with large nucleoli. This atypia is often graded from mild to severe. However, this is subjective, based on the dermatopathologist reading the slides. Cytological atypia is not exclusive to dysplastic nevi and may be seen in any nevus. Many studies have examined inter- and intra-observer concordance between dermatopathologists in diagnosing dysplastic nevi concerning cytological atypia grading. The results have been mixed and may vary widely from 1 dermatopathologist to another, but it is speculated that an individual dermatopathologist’s grading likely remains constant.[10]

History and Physical

Dysplastic nevi tend to be larger than the ordinary nevi, measuring approximately greater than 5 mm in diameter. They often contain multiple colors, including light brown, dark brown, and pink. They often appear as a “fried egg” with a darker papular central lesion and surrounding macular lighter shade. This clinical appearance is atypical, and they often follow the ABCDE guidelines for melanoma, including asymmetry, border irregularity, color variation, diameter (greater than 6 mm), and evolving lesion. Most of these atypically-appearing nevi are biopsied as they are a cause of concern for atypical moles or melanoma.[6] Dysplastic nevus syndrome involves patients with 50 or more dysplastic nevi. These patients develop atypical nevi in adolescence and adulthood. A patient is said to have dysplastic nevus syndrome if they have 5 or more atypical melanocytic nevi. A variant of dysplastic nevus described in the early 1990s is known as the lentiginous dysplastic nevus of the elderly. Some regard this as nevoid lentigo maligna or evolving or early melanoma in situ of the elderly. These nevi appear in elderly individuals older than 60 and tend to arise on the back in males and the legs in females. Rarely, dysplastic nevi can present in an eruptive form, primarily seen in immunosuppressed patients.

Evaluation

A lesion suspicious clinically for dysplastic nevus should be excised completely, whether by shave, punch, or excisional biopsy. The complete removal of the lesion is so the dermatopathologist may evaluate the entire lesion for symmetry and appreciate the shoulder sign, characteristic of dysplastic nevi. For this reason, an incisional biopsy is not recommended.[11][12] Dermoscopy is a tool dermatologists use to evaluate pigment patterns and secondary features, such as vascularity in suspicious skin lesions. Clear and well-studied dermoscopic features are characteristic of certain neoplasms, such as basal cell carcinoma, seborrheic keratosis, and melanoma. However, no dermoscopic criteria currently distinguish dysplastic nevi from melanoma in situ.[13]

Treatment / Management

The treatment of dysplastic nevi is controversial and varies from provider to provider. A survey of physicians in the American Academy of Dermatology organization reported that approximately two-thirds of the respondents prefer to re-excise dysplastic nevi if margins are reported to be positive in the initial biopsy. The reasoning for this could be if the incompletely excised nevus grew back in the biopsy scar, it may clinically and histologically be indistinguishable from melanoma. This is referred to as the “pseudo-melanoma” phenomenon. 

Many authors agree that most dysplastic nevi do not need to be re-excised after the initial biopsy. An extensive review concluded that dysplastic nevi are “fundamentally variants of common nevi.” However, if a provider worries about how a lesion appears clinically, this should trump what is reported histopathologically, and the lesion should be completely excised. It is also agreed upon that a dysplastic nevus with severe atypia or 1 that cannot be distinguished histologically from melanoma should be re-excised with appropriate margins (typically at least 5 mm margins).[13] Patients with a history of dysplastic nevi are recommended to wear sun protection.[13]

Differential Diagnosis

The differential diagnosis for dysplastic nevi includes the following:

• Blue nevi
• Basal cell carcinoma
• Cutaneous melanoma
• Dermatofibroma
• Lentigo
• Melanocytic nevi
• Spitz nevus
• Seborrheic keratosis

Prognosis

The prognosis for patients with dysplastic nevi is excellent. However, those with a history of dysplastic nevi have an increased risk of developing melanoma. Therefore, recommendations are for regular skin check-ups with a dermatologist. Management of mildly dysplastic nevi can entail nothing more than regular observation. However, severely dysplastic nevi require surgical removal. Based on the degree of clinical abnormality, moderately atypical nevi can be managed with close observation if there are many or surgical removal if there are only a few.[14][4]

Complications

As with any mole, patients need to be vigilant for the potential development of melanoma. Both patients and their healthcare providers must be alert for changes in the dysplastic nevi. A severely dysplastic nevus is indistinguishable from early melanoma. 

Deterrence and Patient Education

Patients need to be counseled to avoid UV light, including from the sun and tanning beds. When outdoors in the sun, they should use sunscreen and cover their exposed skin as much as is practical with long sleeves, broad-brimmed hats, and other protective garments.

Enhancing Healthcare Team Outcomes

A dermatologist primarily manages dysplastic nevi. However, most patients present with an abnormal skin lesion to their primary care provider. It is important for these healthcare workers to consult with a dermatologist first when they suspect a dysplastic nevus. A lesion suspicious clinically for dysplastic nevus should be excised completely, whether by shave, punch, or excisional biopsy. The complete removal of the lesion is so the dermatopathologist may evaluate the entire lesion for symmetry and appreciate the shoulder sign, characteristic of dysplastic nevi. For this reason, an incisional biopsy is not recommended. Dermoscopy is a tool dermatologists use to evaluate pigment patterns and secondary features, such as vascularity in suspicious skin lesions. There are clear and well-studied dermoscopic features characteristic of certain neoplasms, such as basal cell carcinoma, seborrheic keratosis, and melanoma. However, no dermoscopic criteria currently distinguish dysplastic nevi from melanoma in situ.