Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?

BACKGROUND/OBJECTIVES: Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions. METHODS: We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded. RESULTS: Sixty-six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high-grade dysplastic nevi, and 50% (n: 33) were low-grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high-grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17-12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15-13.2), and total colour count (OR = 3.21, 95% CI, 1.2-8.5) were significant predictive factors for the lesions with high-grade dysplasia and melanomas. CONCLUSIONS: To avoid the underdiagnosis of both melanomas and high-grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1-year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high-grade dysplasia.

Survey on the Management of Dysplastic Nevus by Dermatologists in the Center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV). / Encuesta sobre el manejo del nevus displásico por los dermatólogos de la sección Centro de la Academia Española de Dermatología y Venereología (AEDV).

BACKGROUND AND OBJECTIVES: There are no clinical guidelines on the management of dysplastic nevus (DN). The aims of this study were to determine the percentage of dermatologists in the center-Spain section of the Spanish Academy of Dermatology and Venereology (AEDV) who would manage a histologically confirmed DN with a watch-and-wait approach or with wider surgical margins and to investigate whether their attitudes would vary depending on whether or not the patient had a personal and/or family history of melanoma. MATERIAL AND METHODS: We collected data from an anonymous survey sent to 738 dermatologists between June 15 and July 31, 2022. The independent variables were degree of dysplasia (low vs. high), margin status (positive vs. negative), and a personal or family history of melanoma (yes vs. no in both cases). The dependent variables were attitude towards management (watch-and-wait vs. re-excision with a surgical margin of 1 to 4mm or re-excision with a surgical margin of 5 to 10mm). RESULTS: We obtained 86 responses to the questionnaire. When pathology indicated a low-grade DN, 60.5% of dermatologists stated they would obtain a surgical margin of 1 to 4mm if the first margins were positive, and 97.7% would watch and wait if the report described negative margins. For high-grade DNs, 1.2% of dermatologists would watch and wait to manage DN with positive margins; 68.8% would use this approach for negative margins. A family or personal history of melanoma had no influence on most of the dermatologists' attitudes. CONCLUSIONS: Management strategies for DN among dermatologists from the center-Spain section of the AEDV varied, particularly when faced with low-grade DN with positive margins and high-grade DN with negative margins. A family or personal history of melanoma did not influence clinical attitudes in most cases.

A novel surgical margin (1 cm) might be from benefit for patients with dysplastic nevi, thin melanomas, and melanoma in situ: Analysis based on clinical cases.

Malignant melanoma is an oncologic disease, whose current management among others includes surgical and immunological therapy. According to the current recommendations of the American Joint Committee on Cancer, the surgical excision of the primary tumor should be performed in two operative sessions, which has several consequences. The following paper will present and discuss six cases of pigmented lesions and the advantages of the one-step melanoma surgery in their management.

Negative predictive value of biopsy margins of dysplastic nevi: A single-institution retrospective review.

BACKGROUND: Biopsies of dysplastic nevi processed by bread-loafing allow for limited margin assessment; however, reported biopsy margins often influence management. OBJECTIVE: To evaluate the negative predictive value of biopsy margins of dysplastic nevi. METHODS: A retrospective search of a single academic institution's pathology database was conducted to identify all biopsy specimens of dysplastic nevi between January 1, 2015, and December 31, 2017. Biopsy specimen margin assessments were compared with excision pathology reports to calculate negative predictive value and to assess the frequency of residual nevus on excision after positive biopsy margins. RESULTS: A total of 1245 dysplastic nevi from 934 patients were identified. Clear biopsy margins had a negative predictive value for the absence of residual nevus on excision of 87.3% for dysplastic nevi of moderate atypia or greater. Residual nevus was identified on excision in 29.41% of cases of dysplastic nevi of moderate atypia or greater when initial biopsy margins were positive. LIMITATIONS: This was a retrospective, single-institution study. The calculations likely overestimate the true negative predictive value of biopsy margins because of processing of excision specimens by bread-loafing. CONCLUSIONS: This study provides additional evidence that reported biopsy margins are not representative of true margin status.

CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients.

BACKGROUND: Cyclin dependent kinase inhibitor 2A gene (CDKN2A) germline mutations have recently been associated with poor survival in patients with melanoma. Despite the high mutation rate in our cohort (up to 10% in patients with apparently sporadic melanoma), information on the impact of CDKN2A on survival in this cohort is lacking. OBJECTIVE: To investigate whether poor survival associated with CDKN2A germline mutations was confirmed in a high mutation-prevalence cohort of Italian patients with melanoma undergoing a mutation-based follow-up. METHODS: A total of 1239 patients with cutaneous melanoma were tested for CDKN2A mutational status and then assigned to a follow-up scheme according not only to family history but also to CDKN2A mutational status, as follow-up intervals were more frequent for CDKN2A germline mutation-positive (MUT+) patients. From this cohort, we selected 106 MUT+ patients (with familial melanoma or apparently sporadic melanoma) and 199 CDKN2A germline mutation-negative (MUT-) patients with sporadic melanoma who were matched by age and sex and had a similar tumor stage distribution. RESULTS: We found no difference in overall survival (hazard ratio, 0.85; 95% confidence interval, 0.48-1.52; P = .592,) or melanoma-specific survival (hazard ratio, 0.86; 95% confidence interval, 0.38-1.95; P = .718,) between MUT+ and MUT- patients. MUT+ patients were more likely to develop multiple melanomas and to undergo surgical excision of dysplastic nevi than were MUT- patients. LIMITATIONS: Retrospective study. CONCLUSION: CDKN2A mutations were not associated with survival in our cohort.

Risk of Subsequent Cutaneous Melanoma in Moderately Dysplastic Nevi Excisionally Biopsied but With Positive Histologic Margins.

Importance: Little evidence exists to guide the management of moderately dysplastic nevi excisionally biopsied without residual clinical pigmentation but with positive histologic margins (hereafter referred to as moderately dysplastic nevi with positive histologic margins). Objective: To determine outcomes and risk for the development of subsequent cutaneous melanoma (CM) from moderately dysplastic nevi with positive histologic margins observed for 3 years or more. Design, Setting, and Participants: A multicenter (9 US academic dermatology sites) retrospective cohort study was conducted of patients 18 years or older with moderately dysplastic nevi with positive histologic margins and 3 years or more of follow-up data collected consecutively from January 1, 1990, to August 31, 2014. Records were reviewed for patient demographics, biopsy type, pathologic findings, and development of subsequent CM at the biopsy site or elsewhere on the body. The χ2 test, the Fisher exact test, and analysis of variance were used to assess univariate association for risk of subsequent CMs, in addition to multivariable logistic regression models. To confirm histologic grading, each site submitted 5 random representative slide cases for central dermatopathologic review. Statistical analysis was performed from October 1, 2017, to June 22, 2018. Main Outcomes and Measures: Development of CM at a biopsy site or elsewhere on the body where there were moderately dysplastic nevi with positive histologic margins. Results: A total of 467 moderately dysplastic nevi with positive histologic margins from 438 patients (193 women and 245 men; mean [SD] age, 46.7 [16.1] years) were evaluated. No cases developed into CM at biopsy sites, with a mean (SD) follow-up time of 6.9 (3.4) years. However, 100 patients (22.8%) developed a CM at a separate site. Results of multivariate analyses revealed that history of CM was significantly associated with the risk of development of subsequent CM at a separate site (odds ratio, 11.74; 95% CI, 5.71-24.15; P < .001), as were prior biopsied dysplastic nevi (odds ratio, 2.55; 95% CI, 1.23-5.28; P = .01). The results of a central dermatopathologic review revealed agreement in 35 of 40 cases (87.5%). Three of 40 cases (7.5%) were upgraded in degree of atypia; of these, 1 was interpreted as melanoma in situ. That patient remains without recurrence or evidence of CM after 5 years of follow-up. Conclusions and Relevance: This study suggests that close observation with routine skin surveillance is a reasonable management approach for moderately dysplastic nevi with positive histologic margins. However, having 2 or more biopsied dysplastic nevi (with 1 that is a moderately dysplastic nevus) appears to be associated with increased risk for subsequent CM at a separate site.

Automated decision support in melanocytic lesion management.

An automated melanocytic lesion image-analysis algorithm is described that aims to reproduce the decision-making of a dermatologist. The utility of the algorithm lies in its ability to identify lesions requiring excision from lesions not requiring excision. Using only wavelet coefficients as features, and testing three different machine learning algorithms, a cohort of 250 images of pigmented lesions is classified based on expert dermatologists' recommendations of either excision (165 images) or no excision (85 images). It is shown that the best algorithm utilises the Shannon4 wavelet coupled to the support vector machine, where the latter is used as the classifier. In this case the algorithm, utilising only 22 othogonal features, achieves a 10-fold cross validation sensitivity and specificity of 0.96 and 0.87, resulting in a diagnostic-odds ratio of 261. The advantages of this method over diagnostic algorithms-which make a melanoma/no melanoma decision-are twofold: first, by reproducing the decision-making of a dermatologist, the average number of lesions excised per melanoma among practioners in general can be reduced without compromising the detection of melanoma; and second, the intractable problem of clinically differentiating between many atypical dysplastic naevi and melanoma is avoided. Since many atypical naevi that require excision on clinical grounds will not be melanoma, the algorithm-in contrast to diagnostic algorithms-can aim for perfect specificities without clinical concerns, thus lowering the excision rate of non-melanoma. Finally, the algorithm has been implemented as a smart phone application to investigate its utility in clinical practice and to streamline the assimilation of hitherto unseen tested images into the training set.

Margin Assessment for Punch and Shave Biopsies of Dysplastic Nevi.

INTRODUCTION: Biopsies of atypical melanocytic nevi are among the most commonly performed procedures by dermatologists. Margin assessment is often used to guide re-excision, but can be a point of confusion as negative margins reported in the planes of sections examined do not always reflect complete removal of a lesion. This study investigates the rates of false negative margins after both punch and shave biopsies. METHODS: We performed a retrospective analysis of 50 consecutive punch and shave biopsy specimens (1) diagnosed as DN, and (2) reported as having clear margins in the planes of section examined. Identified specimen blocks were then sectioned through to examine true margin involvement. RESULTS: Of the 50 specimens identified, 20% (n = 10) were found to have positive margins upon additional sectioning. We found no difference between the groups with respect to biopsy technique, type of nevus, degree of atypia, or gender. CONCLUSION: This study observed false negative peripheral margin status in a sizeable proportion of biopsy specimens, which did not vary significantly based on biopsy technique or pathologic characteristics. This finding reflects a limitation of standard tissue processing, in which a limited proportion of the true margin is evaluated, and may be of note to many dermatologists who base their decision to re-excise on the reporting of margin involvement. J Drugs Dermatol. 2018;17(7):810-812.

Biodynamic excisional skin tension lines for surgical excisions: untangling the science.

Objective There remains confusion between Langer's lines and wrinkle lines with respect to the optimal orientation of elliptical excisions on the trunk. This study sought to determine the directions of wound closure that would result in least wound tension after skin lesion excisions. Materials and methods Some 1181 consecutive skin lesion excisions were investigated (age range 13-95 years, median 64 years) using a tensiometer to determine directions of least wound tension. These lines were mapped. Skin tension measurements were taken during the procedure and analysed. The clear majority of excisions were for skin cancer and the others were for cysts or dysplastic naevi. Lesions such as lipomas, which entail incisional rather than excisional surgery (i.e. where overlying skin was not excised) were excluded. All lesions were cut out in a circular fashion following tension measurements. Closure was undertaken in the direction of least tension (biodynamic excisional skin tension line) and this was illustrated. This process was repeated in all cases where body site and direction of closure was mapped. Statistical analyses were undertaken on a series on the scalp and lower limb. Results Biodynamic excisional skin tension lines have a clear directional preference: scalp-coronal direction, limbs--vertical orientation of ellipses and trunk - mostly horizontal except oblique at the shoulder and scapular regions. Discussion Skin cancer excisions often end up with poor cosmetic results, owing to inconsistency in identifying the correct excisional wound closure lines. This has not been helped by the (hitherto) lack of large in vivo biomechanical studies, and because incisional lines and excisional lines have not been considered separately in surgical practice. Orientating ellipses or wound closures using biodynamic excisional skin tension lines offers a guide to reducing wound tension and minimising wound complications or scarring after cutaneous surgery.

The management of dysplastic naevi: a survey of Australian dermatologists.

BACKGROUND/OBJECTIVES: The management of dysplastic naevi based on histopathological grading is a contentious issue. Comprehensive management guidelines are lacking and the approach taken varies between clinicians. The authors sought to understand how Australian dermatologists approach the management of biopsy-proven dysplastic naevi, and the impact of grading of dysplasia upon this management. METHODS: In total, 547 Fellows of the Australasian College of Dermatologists were surveyed and 218 responses were collected (40% response rate). RESULTS: Although all dermatologists surveyed would re-excise an incompletely removed severely dysplastic naevus, opinion was divided over whether to treat such a lesion as an in situ melanoma or a dysplastic naevus, with 55% of respondents using a 5-mm margin and the remainder opting for narrow margin re-excision. When the same lesion was reported to be clear of margins by 1 mm after biopsy and the clinical suspicion for melanoma was high, 44% would re-excise with a 5-mm margin. CONCLUSIONS: The approach of Australian dermatologists to the management of dysplastic naevi varies between clinicians, reflecting the problems raised by the validity of histopathological grading.

A prospective study evaluating the utility of a 2-mm biopsy margin for complete removal of histologically atypical (dysplastic) nevi.

BACKGROUND: Complete removal of individual dysplastic nevi (DN) is often accomplished by a second surgical procedure after the initial biopsy. The choice to perform the second procedure is strongly influenced by histopathologic margin status of the initial biopsy specimen. OBJECTIVE: To evaluate the clinical and histopathologic outcomes of in toto biopsy of DN using a predetermined margin of normal skin. METHODS: We conducted a prospective study of a saucerization method using a defined 2-mm margin in patients undergoing biopsy of a pigmented skin lesion. RESULTS: We performed 151 biopsies in 138 patients. Overall, 137 of 151 lesions subjected to biopsy (90.7%) were melanocytic: 86 DN (57.0%), 40 nevi without atypia (26.5%), and 11 melanomas (7.3%). Of 78 DN, 68 (87.2%) were removed with clear histopathologic margins (8 DN were excluded because of inadequate processing). There was no clinical evidence of recurrence at any of the biopsy sites that were simply observed (i.e., not re-excised) over a median of 16.9 months. LIMITATIONS: There were few biopsies performed on the face. CONCLUSIONS: The complete histopathologic removal of nearly 9 of 10 DN using a peripheral margin of 2 mm of normal skin and a depth at the dermis and subcutaneous fat junction has the potential to decrease second procedures at DN biopsy sites, thereby decreasing patient morbidity and saving health care dollars.

Dysplastic nevi with severe atypia: Long-term outcomes in patients with and without re-excision.

BACKGROUND: Dysplastic nevi with severe atypia (severely dysplastic nevi [SDN]) are frequently re-excised because of the concern that these lesions may in fact represent early melanoma. Data on long-term follow-up of these patients are limited. OBJECTIVE: We sought to determine the rate of subsequent melanoma development in patients with SDN who underwent re-excision versus those who did not and to determine factors associated with decision to re-excise. METHODS: A retrospective single institutional study was conducted with 451 adult patients (mean age 41.3 years) with SDN biopsied between November 1994 and November 2004, with clinical follow-up of at least 5 years. RESULTS: In 451 patients with SDN, re-excision was performed on 36.6%. Two melanomas were diagnosed in the re-excision specimens. Subsequent metastatic melanoma developed in 7 patients, all of whom had a history of melanoma. Margin comments influenced decision to re-excise. LIMITATIONS: This was a retrospective study at a single institution. CONCLUSION: Re-excision of all SDN may not be necessary.

Reexcision Perineural Invasion and Epithelial Sheath Neuroma Possibly on a Spectrum of Postinjury Reactive Hyperplasia Mediated by IL-6.

Epithelial sheath neuroma is a rarely recognized but established entity in the medical literature. First described in 2000 by Requena et al, there have only been 7 published cases to date, mostly in female patients and presenting as symptomatic solitary lesions on the back without a known history of trauma. In 2006, Beer et al described and reviewed a dozen cases in which epithelial sheath neuroma-like features were seen in the advent of a surgical procedure, which was termed "re-excision perineural invasion" and attributed to possible eccrine duct implantation during surgery. Our case is a 66-year-old male patient who underwent an excision of a melanocytic neoplasm in which a reactive epithelial sheath neuroma was incidentally discovered in the excision specimen, adjacent to the biopsy site cicatrix. Histologically, there was benign cutaneous nerve hyperplasia with a proliferation of squamous epithelium in intimate apposition to the nerve bundles in the superficial dermis. We postulate that the process active in the formation of re-excision perineural invasion is the same as in epithelial sheath neuroma and that minor trauma not appreciable on histologic examination is responsible in the latter entity. We performed IL-6 staining and documented that IL-6 was upregulated at the interface of the nerve and reactive epithelium, but was absent in nerves distant from the site of surgery, suggesting that IL-6 may be essential to the lesion's development. The recognition of reactive epithelial sheath neuroma including the subcategory of re-excision perineural invasion is crucial for the dermatopathologist to prevent mislabeling this reactive entity as a perineural squamous cell carcinoma, which has clinical consequences for the patient such as wider re-excision and radiation treatment. Additionally, we have identified a potential pathophysiologic basis for this lesion.