Merkel Cell Carcinoma, the Impact of Clinical Excision Margins and Mohs Micrographic Surgery on Recurrence and Survival: A Systematic Review

Abstract

BACKGROUND When treating Merkel cell carcinoma (MCC), the relation between wide local excision (WLE) margin and recurrence or survival is unclear. Mohs micrographic surgery (MMS) is an alternative surgical option for MCC, but it is unknown whether the local recurrence rate differs between MMS and WLE. OBJECTIVE To systematically assess the available literature to determine the recurrence and survival rates when treating MCC with MMS and different clinical excision margins. MATERIALS AND METHODS The MEDLINE, EMBASE, and CENTRAL databases were searched. Two independent reviewers selected studies that defined clear excision margins and either recurrence or survival. When possible, individual cases were extracted from case series and included in the analyses. Other studies were reviewed narratively. RESULTS Overall, 1108 studies were identified; of which, 19 case series (168 cases) and 12 cohort studies were eligible. None of the cohort studies showed significant differences in recurrence or survival for either excision margins or MMS. Equally, logistic and Cox regression analyses of the case series revealed no significant differences in recurrence or survival between different excision margins and MMS. CONCLUSION Synthesis of the available data does not indicate differences in recurrence and/or survival rates for MCC between different clinical excision margins and MMS.M erkel cell carcinoma (MCC), first described by Toker 1 in 1972, is a rare and potentially lethal skin cancer with a possible neuroendocrine origin. Worldwide, the annual incidence has been increasing, and currently, it is estimated to affect 0.19 to 0.82 per 100,000 people. [2][3][4][5] Merkel cell carcinoma also has the propensity for rapid growth and metastasis, 2 with low 5year survival rates of approximately 60%. [2][3][4] Treatment modalities vary depending on tumor stage, comprising surgery, radiotherapy, chemotherapy, and/or immunotherapy. 6,7 For primary excision, wide local excision (WLE) or Mohs micrographic surgery (MMS) are usually recommended. 8-10 However, there is uncertainty about the optimal clinical excision margin for WLE, with recommendations varying from 1 to 3 cm, and how this relates to recurrence and survival. 9,11 Given the classic presentation of MCC as a sharply circumscribed and nodular lesion, it can be argued that an excision margin of 1 cm is sufficient; by contrast, its rapid growth and high risk of metastasis supports the case for a wider excision margin.Excision may also be performed by MMS, which, using frozen sections, allows for intraoperational assessment of 100% of the peripheral and deep histological margins. Using this technique, the surgeon can continue to excise tissue until all margins are free of tumor, ensuring radical excision with minimal margins and preferable cosmetic results. However, it remains unclear whether MMS and WLE produce different recurrence or survival rates. 12 A systematic review on this subject could contribute to international guidelines for the surgical strategy to treat MCC.The objec...

Considerations Regarding Mohs Surgery for Early-Stage Merkel Cell Carcinoma—Reply

“…A systematic review of 31 studies (retrospective and case series) comparing WLE and MMS for MCC did not show a difference in outcomes. 2 A recent NCDB analysis of early-stage MCC during an overlapping period (2004-2014 vs 2004-2018 as in the current study 1 ) failed to detect a survival advantage with MMS. 3 The present study 1 was larger than the prior NCDB analysis and required pathologic nodal staging.…”

“…In Reply We appreciate the interest in our article 1 by Faries and Venna et al as well as their comments on the analysis. 2 While we agree that there are inherent limitations to retrospective studies of survival outcomes using registry data, we believe that it is prudent to glean what insights we can from these datasets given the lack of large-scale studies of rare cancers, such as Merkel cell carcinoma (MCC), in the existing literature.…”

“…Up to half of the deaths in patients with MCC are due to non-MCC causes. 2 Second, MCC-related deaths, when they do occur, almost always occur within about 4 years of diagnosis. 3 The difference in OS observed in the NCDB data only emerges after 4 years, making it very likely that it was due to causes of death other than MCC.…”

Characteristics of Hispanic patients with nonmelanoma skin cancer undergoing Mohs micrographic surgery: a review of the literature

“…Additionally, there was no data regarding the use of MMS for melanoma in Hispanic patients, although it is the third most common type of skin cancer among all racial groups with significantly lower survival rates in non‐whites 38,39 . Other rare cutaneous malignancies such as dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC) were not discussed, although it is important to understand these entities may have different presentations and outcomes in patients with skin of color 33,40–43 …”

“…38,39 Other rare cutaneous malignancies such as dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC) were not discussed, although it is important to understand these entities may have different presentations and outcomes in patients with skin of color. 33,[40][41][42][43] Outreach efforts are critical to educate patients regarding the risk of skin cancer regardless of race or ethnicity. Although Hispanics are commonly categorized as Fitzpatrick skin types IV to VI, ethnic skin colors can include a broad spectrum of skin phototypes.…”