Dysplastic Nevi


Article Author:
Dana Baigrie


Article Editor:
Laura Tanner


Editors In Chief:
William Gossman


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
1/20/2019 9:47:29 AM

Introduction

A dysplastic nevus is also referred to as an atypical or Clark’s nevus and has been the topic of much debate in the fields of dermatology and dermatopathology. It is an acquired mole demonstrating a unique clinical and histopathologic appearance which 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 concerned 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 to occur 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 would suggest that mutations in the nevi would be shared with melanoma, and this has not been clearly demonstrated in the literature. Also, approximately 25% of melanomas are estimated to arise in pre-existing nevi, and 75% of melanomas arise de novo. One study demonstrated the risk of a dysplastic nevus evolving into a melanoma is 0.0005% for people younger than 40 years. Dysplastic nevi tend to be stable over time.

Epidemiology

Dysplastic nevi may be present in approximately 2% to 18% of the population. Individuals with these nevi have been shown to be at increased risk for melanoma. In Caucasian individuals in the United States, the lifetime risk of developing a 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 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 they occur 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][7][8][9][8]

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.

The cytological atypia is random and includes enlarged dark nuclei with large nucleoli. This atypia is often graded from low to severe. However, this is very 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 been performed looking at inter- and intra-observer concordance between dermatopathologists in diagnosing dysplastic nevi concerning grading of cytological atypia. The results have been mixed and may vary widely from dermatopathologist to dermatopathologist, but it is speculated that individual dermatopathologist’s grading will likely remain constant over time.

History and Physical

Dysplastic nevi tend to be larger than the ordinary nevi, measuring approximately greater than 5 mm in diameter, and often contain more than one color within them 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 which includes: asymmetry, border irregularity, color variation, diameter (greater than 6 mm), and evolving lesion. Most of these atypically-appearing nevi are biopsied as they are concerning for atypical moles or melanoma.

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 five or more atypical melanocytic nevi.

There is a variant of dysplastic nevus described in the early 1990s known as the lentiginous dysplastic nevus of the elderly. This is regarded by some to be nevoid lentigo maligna or evolving or early melanoma in situ of the elderly. These nevi appear in elderly individuals older than 60 years and tend to arise on the back in males and the legs in females.

Rarely, dysplastic nevi can present in an eruptive form which is primarily seen in immunosuppressed patients.

Evaluation

A lesion suspicious clinically for dysplastic nevus should be excised completely, whether it be by shave, punch, or excisional biopsy. The reason for complete removal of the lesion is so the dermatopathologist may evaluate the entire lesion for symmetry and appreciate the shoulder sign, which is characteristic of dysplastic nevi. For this reason, incisional biopsy is not recommended.[10][11]

Dermoscopy is a tool used by dermatologists to evaluate pigment patterns and secondary features such as vascularity in suspicious skin lesions. There are clear and well-studied dermoscopic features that are characteristic for certain neoplasms such as basal cell carcinoma, seborrheic keratosis, and melanoma. However, there are currently no dermoscopic criteria that distinguish dysplastic nevi from melanoma in situ.

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. 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. In fact, an extensive review concluded that dysplastic nevi are “fundamentally variants of common nevi.” However, if a provider is worried 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 one that cannot be distinguished histologically from melanoma should be re-excised with appropriate margins (typically at least 5 mm margins). 

It is recommended that patients with a history of dysplastic nevi wear sun protection.

Enhancing Healthcare Team Outcomes

The management of a dysplastic nevi is primarily done by a dermatologist. However, most patients first present to the primary care provider or nurse practitioner with an abnormal skin lesion. It is important for these healthcare workers to first consult with a dermatologist when they suspect a dysplastic nevi.

A lesion suspicious clinically for dysplastic nevus should be excised completely, whether it be by shave, punch, or excisional biopsy. The reason for complete removal of the lesion is so the dermatopathologist may evaluate the entire lesion for symmetry and appreciate the shoulder sign, which is characteristic of dysplastic nevi. For this reason, incisional biopsy is not recommended.

Dermoscopy is a tool used by dermatologists to evaluate pigment patterns and secondary features such as vascularity in suspicious skin lesions. There are clear and well-studied dermoscopic features that are characteristic for certain neoplasms such as basal cell carcinoma, seborrheic keratosis, and melanoma. However, there are currently no dermoscopic criteria that distinguish dysplastic nevi from melanoma in situ.


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Dysplastic Nevi - Questions

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Which of the following is a histopathologic feature of a dysplastic nevus?



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A 7 mm pink and brown papule with irregular borders is noted on the lower back of a 45-year-old male patient during his routine skin exam. This lesion is asymptomatic and has not been noticed by the patient before this exam. What is the next best step in management?



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What is the most common location of dysplastic nevi in men?



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Which of the following is not included in the ABCDs of atypical and dysplastic nevi and melanoma?



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Dysplastic Nevi - References

References

Strazzulla LC,Li X,Zhu K,Okhovat JP,Lee SJ,Kim CC, Clinicopathologic, misdiagnosis and survival differences between clinically amelanotic melanomas and pigmented melanomas. Journal of the American Academy of Dermatology. 2019 Jan 14;     [PubMed]
de Unamuno Bustos B,Sahuquillo Torralba A,Moles Poveda P,Pérez Simó G,Simarro Farinos J,Llavador Ros M,Palanca Suela S,Botella Estrada R, Telomerase Expression in a Series of Melanocytic Neoplasms. Actas dermo-sifiliograficas. 2018 Dec 24;     [PubMed]
Salmi S,Siiskonen H,Sironen R,Tyynelä-Korhonen K,Hirschovits-Gerz B,Valkonen M,Auvinen P,Pasonen-Seppänen S, The number and localization of CD68 and CD163 macrophages in different stages of cutaneous melanoma. Melanoma research. 2018 Nov 5;     [PubMed]
Bsirini C,Smoller BR, Histologic mimics of malignant melanoma. Singapore medical journal. 2018 Nov;     [PubMed]
Colebatch AJ,Scolyer RA, Trajectories of premalignancy during the journey from melanocyte to melanoma. Pathology. 2018 Jan;     [PubMed]
Tan SY,Strazzulla LC,Li X,Park JJ,Lee SJ,Kim CC, Association of clinicopathological features of melanoma with total naevus count and a history of dysplastic naevi: a cross-sectional retrospective study within an academic centre. Clinical and experimental dermatology. 2018 Jul;     [PubMed]
Winkelmann RR,Farberg AS,Glazer AM,Cockerell CJ,Sober AJ,Siegel DM,Leachman SA,High WA,Markowitz O,Berman B,Pariser DM,Goldenberg G,Rosen T,Rigel DS, Integrating Skin Cancer-Related Technologies into Clinical Practice. Dermatologic clinics. 2017 Oct;     [PubMed]
Madigan LM,Treyger G,Kohen LL, Compliance with serial dermoscopic monitoring: An academic perspective. Journal of the American Academy of Dermatology. 2016 Dec;     [PubMed]
Raghavan D, Cutaneous manifestations of genitourinary malignancy. Seminars in oncology. 2016 Jun;     [PubMed]
Rosendahl CO,Grant-Kels JM,Que SK, Dysplastic nevus: Fact and fiction. Journal of the American Academy of Dermatology. 2015 Sep;     [PubMed]
Perkins A,Duffy RL, Atypical moles: diagnosis and management. American family physician. 2015 Jun 1;     [PubMed]
Winkelmann RR,Rigel DS, Management of dysplastic nevi: A 14-year follow-up survey assessing practice trends among US dermatologists. Journal of the American Academy of Dermatology. 2015 Dec;     [PubMed]
Valdebran M,Bandino J,Elbendary A,Gad A,Arudra KC,de Feraudy S,Elston DM, Nuclear and cytoplasmic features in the diagnosis of Clark's nevi. Journal of cutaneous pathology. 2018 Mar;     [PubMed]

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