This online-only bonus feature is an ongoing review of past peer reveiw journal articles with significant impact on dermatology.
Melissa Hoffman, MD
Rethinking Surgical Margins for Melanoma in Situ
The benefits of Mohs micrographic surgery (MMS), including high rates of complete excision, low local recurrence rates and maximal tissue conservation, are well known. Using this surgical technique for melanoma in situ (MIS) has predominately focused on the head and neck due to the demand for tissue conservation in this region. Recent reports have shown that MIS in these locations have variable tumor extensions and may require margins of 1 cm of greater. Due to the paucity of studies on surgical management of MIS on the trunk or extremities, less is known about appropriate surgical management of these sites. Recently, a retrospective study at a single-institution evaluated 882 MIS cases on the trunk or proximal extremity, treated with with MMS. Margins of 6 mm cleared only 83% of MIS patients, while 9 mm margins were needed to achieve 97% clearance. The remaining 3% required margins of 12 mm or more. While there was no significant difference in the necessary margins based on location, there was a trend towards increased margins for larger diameter lesions. There was only 1 local recurrence in this study, compared to the traditionally reported rates of 7-20%, highlighting the role for complete margin evaluation in treating MIS. This study contributes to the growing body of literature that traditional margins of 5 mm may be inadequate for MIS, independent of size, location, or subtype. These recent reports, which propose 1.0 cm margins for wide local excision of MIS, will likely have surgeons rethinking their standard surgical treatment of patients with MIS.
Stigall LE, Brodland DG, Zitelli JA. The use of Mohs micrographic surgery (MMS) for melanoma in situ (MIS) of the trunk and proximal extremities. J Am Acad Dermatol. 2016 Nov;75(5):1015-1021.
Landmark Study on the Peripheral Conversion of Testosterone in Skin
In memory of the recently passed Dr. Ronald Reisner, this article highlights the contributions Dr. Reisner made to our understanding of the pathogenesis of acne. Prior to this study it was known that circulating levels of testosterone in individuals with and without acne were the same. The data at the time supported that dihydrotestosterone (DHT) was the active form of testosterone at the cellular level. The theory of “end organ sensitivity” had been postulated to explain the role of testosterone, and its conversion to DHT, in the pathogenesis of acne. In this landmark study, 62 biopsies were obtained patients with and without acne from affected and unaffected areas. They found that DHT was one of the major metabolites of testosterone in the skin. Furthermore, acne bearing skin produced 2 to 20 times more DHT than did normal skin and normal facial skin produced more DHT than normal back skin. In general, normal male skin showed higher rates of conversion of testosterone to DHT than did female skin from corresponding sites. While this initial study was small, the authors later went on to evaluate larger populations and studied DHT levels in patients before and during treatment of their acne. The importance of Dr. Reisner’s contribution to our understanding of hormonal influences on acne is highlighted throughout today’s dermatology textbooks, which discuss DHT as the principal androgen mediating sebum production.
Sansone G, Reisner RM. Differential rates of conversion of testosterone to dihydrotestosterone in acne and in normal human skin--a possible pathogenic factor in acne. J Invest Dermatol. 1971 May;56(5):366-72.
Vismodegib for Advanced Basal Cell Carcinoma
Alternations in hedgehog signaling, leading to aberrant pathway activation and uncontrolled proliferation of basal cells are implicated in the pathogenesis of almost all basal-cell carcinomas (BCC). The most common mutation is loss of function mutation in patched homolog 1 (PTCH1) gene, which normally inhibits the signaling activity of smoothened homologue (SMO). Vismodegib, a small-molecule inhibitor of SMO, offers a pharmacologic method to inhibit this aberrant pathway activation involved in BCC. In a landmark, multicenter, international two-cohort study of patients with metastatic or locally advanced BCC who were not surgical candidates, patients received 150 mg of oral vismodegib daily. The majority of patients in both cohorts had tumor shrinkage. In 33 patients in the metastatic BCC group, independently assessed response rate was 30%, and in the 63 patients with locally advanced BCC, response rate was 43%. Furthermore, 54% of patients with locally advanced BCC had no residual disease in biopsy specimens obtained while on therapy. The most common adverse events, which occurred in 30% of patients, were muscle spasms, alopecia, dysgeusia, weight loss and fatigue. The authors also noted 7 deaths during treatment but the relationship to the drug was unknown. This study led to the 2012 FDA approval for vismodegib for treatment of patients with metastatic BCC or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. It also led to the use of Vismodegib for the treatment and prevention of BCC in patients with basal-cell nevus syndrome. While often used for this indication, many practitioners question the end point when using this medication and have to weigh its benefit versus the adverse effects which may not be tolerated by some patients.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366(23):2171-9.
