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Dermatology Diagnosis

Diagnosing An Irregular, Darkly-Pigmented Lesion On The Dorsolateral Forefoot Of A Patient With Previous Skin Cancer

A 50-year-old female with a history of type 2 diabetes mellitus and prior skin cancer presented with a chief concern of a painful “growth” on her right foot, which had been present for one year. She believed it was a wart and was seeking treatment. 

However, the physical exam revealed an irregular, darkly-pigmented, four to five mm lesion on the dorsolateral forefoot that was not related to her primary concern. The patient was unsure as to the duration of this other lesion. She was unable to relate what type of skin cancer she had previously other than stating that it was not melanoma. The lesion on the plantar forefoot that originally brought her into the office was a nucleated callus and I shaved the callus down.

Although the lesion on the dorsal forefoot was not painful and not the reason she presented to the office, due to the patient’s history of an unknown skin cancer and the lesion irregularity, I recommended a biopsy to rule out malignancy. 

Employing local anesthesia consisting of lidocaine with epinephrine, I obtained a four mm punch biopsy. The pathology exam revealed “an intra-epidermal proliferation of nested and solitary, intermediate-sized melanocytes, which are predominantly located along the dermal-epidermal junction.” It also showed minimal scatter of melanocytes within the spinous layer of the epidermis, minimal nuclear atypia and a positive Melan-A immunohistochemical stain. Additionally, solitary melanocytes predominated over nests in the pathology report.

Key Questions To Consider

1. What is the diagnosis? 

2. What are the key characteristics of this condition?

3. What more concerning pathology is in the differential diagnosis?

4. What are the treatment recommendations for this condition?

Answering The Key Diagnostic Questions

1. Dysplastic nevus with mild atypia

2. Asymmetry, irregular borders, size greater than five mm, heterogenous coloration but minimal nuclear atypia

3. Melanoma

4. Monitoring and excising the lesion if it recurs

What The Podiatrist Should Know About Dysplastic Nevi

Dysplastic nevi share many of the same characteristics as melanoma: asymmetry, irregular borders, size greater than five mm and heterogeneous coloration. However, they are not cancerous. In fact, the lifetime risk of a nevus developing into melanoma is quite low. In a study of nevus-associated melanoma by Kim and colleagues in 2017, they found that out of 467 moderately dysplastic nevi with positive histological margins, none developed into melanoma.1 However, 100 patients in the study developed melanoma at another site. According to Pampena and team, 29.1 percent of melanomas are associated with nevi while 70.9 percent arise de novo. Those melanomas that are associated with nevi usually arise from acquired nevi (77.4 percent) rather than congenital nevi.2

While the risk of a nevus, even a dysplastic one, developing into melanoma is low, the presence of an atypical nevus does increase the risk of developing melanoma somewhere else, and the reverse is true as well. According to Halpern and Quigley, individuals with an atypical nevus have a three- to 20-fold increased risk of melanoma.3 However, they also found that while the prevalence of atypical nevi in fair skinned individuals ranges from two to 10 percent, that number increases to 30 to 60 percent in patients with a history of melanoma. Clearly, the two entities are related but an atypical nevus should not arouse immediate or significant concerns about melanoma.

As I mentioned previously, atypical nevi display many of the same characteristics as melanoma, such as diameter (greater than five mm), asymmetry, irregular borders and even variegated colors (pink, tan, dark brown). Note that blue, red or whitish discoloration is not typical of nevi, and suggests melanoma instead. Atypical nevi mostly develop on the trunk and extremities, and rarely develop on the sun-exposed areas of the face and hands. This is because genetics plays the biggest part in the development of nevi although UV exposure does play an important modifying role. 

Dermoscopy is helpful in the diagnosis of atypical nevi because it aids in differentiation from melanoma, which has such defining characteristics as a multicomponent pattern, asymmetry, blue-gray veil and color variety.4 In a patient with multiple or many nevi, the nevi will usually look similar. Any nevi that looks strikingly dissimilar to all the rest of the nevi (the “ugly duckling” sign) is more likely to be melanoma.3 One should biopsy this and/or manage it accordingly.

The most frequent histopathological features of atypical nevi include absent or inconspicuous nucleoli, an estimated nuclear cytoplasmic ratio greater than 4:1 and the presence of solid hyperchromasia. Mitotic figures, pleomorphism with enlarged nuclei, notching, multiple nucleoli, a peppered moth nuclear pattern, flattened adjacent nuclei, single prominent nucleoli and vesicular nucleus with single rounded nucleoli all favor melanomas. In fact, in one study, the combination of pleomorphism with enlarged nucleus and notching had a specificity of 96 percent, a sensitivity of 94 percent and overall accuracy of 95.1 percent in diagnosing melanoma.5 The presence of mitotic figures with pleomorphism and notching showed a specificity of 99 percent, sensitivity of 94 percent and overall accuracy of 96.7 percent in the diagnosis of melanoma over dysplastic nevus.5

Keys To The Diagnostic Workup And Treatment Of Dysplastic Nevi

Given the aforementioned statistic regarding increased likelihood of melanoma in individuals with atypical nevi, the management of dysplastic nevi involves a full body examination to rule out melanoma in other areas. One should instruct patients to examine their own skin completely and frequently, and bring up any suspicious lesions with their doctor. Patients should follow up with a dermatologist at least annually or more frequently if they are at higher risk, or if one is monitoring a suspicious lesion closely. 

Medical histories should include questions about personal and family history of atypical moles or melanoma, sun exposure habits, and any changes in moles.

If one finds an atypical/dysplastic nevus during the physical exam, one should perform an excisional biopsy with two to three mm margins. This makes complete excision with negative margins more likely. Once the pathology report shows negative margins, even if the extent of atypia is moderate or severe, no re-excision is necessary and simple monitoring for recurrence is all that is necessary.

On the other hand, if the pathology report shows positive margins, treatment guidelines are less clear. Most dermatologists will re-excise the lesion with the same clear margin (two to three mm) if the atypia is moderate or severe. 

A consensus statement from members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group recommended that “mildly or moderately dysplastic nevi biopsied with clear histologic margins following initial biopsy do not need re-excision, and mildly dysplastic nevi with positive histologic margins following biopsy without evidence of clinically residual pigmentation may be safely observed. Observation may be a reasonable option for management of moderate dysplastic nevi with positive histologic margins without clinical residual pigmentation, although more data are needed to make a definitive recommendation.”6 

A systematic review in 2018 by Vuong and colleagues supports this treatment algorithm.7 They examined the clinical outcome of atypical nevi that were re-excised or observed. Follow-up ranged from two weeks to 30 years. Of the 2,673 atypical nevi of all grades of histologic atypia, 11 (0.4 percent) developed melanoma at the site of the biopsy, of which five (0.44 percent) were in the re-excision group and six (0.39 percent) were in the observation group. This indicates that the risk of melanoma developing at the site of a biopsied atypical nevus is generally low. However, one could argue that patients with moderate to severe atypia and positive margins may benefit from re-excision to exclude melanoma.

In Summary

Dysplastic nevi mimic melanoma in their appearance but pathology can accurately differentiate the two. In other words, a biopsy is not only helpful but frequently necessary in managing these conditions. With clear margins on pathology, monitoring for recurrence is all that is necessary. However, with positive margins and more severe atypia, re-excision may be necessary to rule out melanoma although the risk of melanoma developing at the biopsy site is quite low. 

Dr. Vella completed a fellowship in podiatric dermatology and is in private practice in Glendale, Ariz.

Dermatology Diagnosis
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By Joseph Vella, DPM
References

1. Kim CC, Berry EG, Marchetti MA, et al. Risk of subsequent cutaneous melanoma in moderately dysplastic nevi excisionally biopsied but with positive histologic margins. JAMA Dermatol. 2018;154(12):1401-1408.

2. Pampena R, Kyrgidis A, Lallas A, Moscarella E, Argenziano G, Longo C. A meta-analysis of nevus-associated melanoma: Prevalence and practical implications. J Amer Acad Dermatol. 2017;77(5):938-945.

3. Halpern A, Quigley E. Atypical (dysplastic) nevi. Available at: https://www.uptodate.com/contents/atypical-dysplastic-nevi . Updated Nov 6, 2018. Accessed October 25, 2019.

4. Emiroglu N, Cengiz FP, Hofmann-Wellenhof R. Dermoscopic and clinical features of trunk melanomas. Postepy Dermatol Alergol. 2014;31(6):362-367.

5. Valdebran M, Bandino J, Elbendary A, et al. Nuclear and cytoplasmic features in the diagnosis of Clark’s nevi. J Cutan Path. 2018;45(3):204-207.

6. Kim CC, Swetter SM, Curiel-Lewandrowski C, et al. Addressing the knowledge gap in clinical recommendations for management and complete excision of clinically atypical nevi/dysplastic nevi: Pigmented Lesion Subcommittee consensus statement. JAMA Dermatol. 2015;151(2):212-218.

7. Vuong KT, Walker J, Powell HB, Thomas NE, Jonas DE, Adamson AS. Surgical re-excision vs. Observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes. Br J Dermatol. 2018;179(3):590-598

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