Faculty Bibliography

Background: During their lifetime about 8% of patients with single primary cutaneous melanoma (SPM) will develop multiple primary melanomas (MPM), which are associated with significantly higher mortality compared to patients with SPM. Based on the evidence that the immune system plays a role in regulating melanoma progression we explored whether germline genetic variants controlling the expression of immunomodulatory genes (immunomodulatory quantitative trait loci, eQTLs) discern risk of MPMcompared to patients with SPM or healthy controls.
Method(s): Previously, we identified 50 eQTLs significantly associated with the expression of 265 immunomodulatory genes using the MuTHer twin cohort. These 50 SNPs were genotyped in 837 SPM and 104MPM individuals using MassARRAY system. 1047 healthy controls were obtained from a publically available GWAS on CMascertained at MDAnderson (phs000187.v1.p1). We employed multivariate logistic regression to test the association of SNPs withMPM vs cancer-free controls andMPMvs SPM.
Result(s): When comparing MPMvs SPM, rs2071304, previously linked to expression of SPI1 in MuTHer data, showed a strong association with reduction ofMPM risk (OR=0.60; 95% CI=0.45-0.81; p=0.0007). Intriguingly, this variant also trended toward significance when comparing MPM vs controls (OR=0.61; 95% CI: 0.44-0.85; p=0.003). Finally, our most significant association when comparingMPM to controls was for rs2276645 (OR=0.60; 95% CI=0.45-0.81; p=0.0008), an eQTL associated with Zap-70 expression.
Conclusion(s): Our data, for the first time, indicate that the inherited host immunity impacts risk ofMPMin individuals with SPM, highlighting an importance of immune involvement in melanoma progression. The MPMrisk-predicting genetic variants identified here or in expanded efforts, currently underway, may eventually lead to a diagnostic tool allowing for enhanced screening and clinical management of patients at risk of MPM, hence reducing elevated MPM-associated mortality. Additionally, our results further support thatMPM and SPM may have different genetics underpinnings and should be treated as separate clinical entities

This article, co-authored by a patient diagnosed with acral melanoma, discusses the patient's experience of being diagnosed with and treated with surgery for this disease. The physician discusses the epidemiology, genetics, diagnosis, treatment, and prognosis of acral melanoma. Follow-up care plans are also discussed.

INTRODUCTION/BACKGROUND: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/CONCLUSIONS: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.

BACKGROUND:Patients with thick primary melanomas (≥4 mm) have highly variable survival outcomes. Cell proliferation marker Ki-67 has been identified as promising biomarker in thick melanoma but has not been evaluated since the wide spread adoption of sentinel lymph node biopsy. We revisit its prognostic relevance in the sentinel node era. METHODS:We studied patients with thick (≥4 mm) primary melanoma prospectively enrolled in a clinicopathological biospecimen database from 2002 to 2015, and evaluated the prognostic value of Ki-67 expression while controlling for features included in the existing staging criteria. RESULTS:We analyzed 68 patients who underwent lymph node sampling and who had an available tumor for Ki-67 immunohistochemical (IHC) staining. The median tumor thickness was 6.0 mm; the median follow-up was 2.6 years. In multivariable analysis including nodal status and primary tumor ulceration, Ki-67 expression was an independent predictor of worse recurrence-free survival (HR 2.19, P = 0.024) and overall survival (HR 2.49, P = 0.028). Natural log-transformed tumor thickness (ln [thickness]) was also significantly associated with worse OS (HR 2.39, P = 0.010). CONCLUSION/CONCLUSIONS:We identify Ki-67 and ln (thickness) as potential biomarkers for patients with thick melanoma who have undergone nodal staging. If validated in additional studies, these biomarkers could be integrated into the staging criteria to improve risk-stratification.

Purpose/UNASSIGNED:variants predicted melanoma risk independently of at-risk phenotypic characteristics. Materials and methods/UNASSIGNED:gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype. Results/UNASSIGNED:in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%). Conclusion/UNASSIGNED:genotype.

An interview with dermatologist David Polsky and Bio-Rad's Digital Biology Group's Director for Scientific Affairs about the role of droplet digital (DD) polymerase chain reaction (PCR) in melanoma care is presented. Topics mentioned include the limitations of DDPCR technology, liquid biopsy, and the steps for validating molecular diagnostic tests for melanoma

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.