Wide local excision of melanoma generally provides clear margins around a primary melanoma. In the case, however, of invasive melanoma or MIS at the margins of a wide excision, reexcision to clear margins is indicated; failure to do so can result in invasive recurrences, as highlighted by the histories of patients 1 and 3.
Our routine practice when there is MIS or invasive melanoma at margins of a wide excision is to reexcise the entire scar, with an additional 1-cm margin when original margins were positive. Additionally, when margins demonstrate AMH related to an MIS or invasive melanoma, reexcision to clear margins is indicated. Simple reexcision is adequate in most cases, especially those patients with disease at just one margin. Likewise, if the reexcision specimen demonstrated positive margins, most patients undergo adequate reexcision, with the second reexcision planned in a similar fashion. We do not propose that the punch biopsy technique be used routinely, even in the case of positive margins on second reexcisions.
We do recommend the proposed technique, however, in select cases. As illustrated in this report, when there is extensive MIS throughout the specimen or at numerous margins without pigmentation or other clinical findings to guide further reexcision, there is no standard approach to ensure clear margins with minimal morbidity. In cases where there is extensive sun damage and associated pathological changes, there is no standard approach to sample the field and to obtain a map of which areas have concerning pathology (such as AMH, MIS, or malignant melanoma) versus benign skin changes (such as melanocytic hyperplasia). In these clinical scenarios, we would recommend that this punch biopsy technique be considered. Stronger consideration would be recommended in anatomic locations where minimizing the size of resection is critical, as illustrated by patients 1 and 3 in this report. The face may in fact be an appropriate location, as the punch biopsy sites heal rapidly and scar minimally.
The present report illustrates a skin mapping technique that enables definitive resection of extensive occult melanoma at surgical margins. Mapping may enable definition of the appropriate margin when the extent of MIS or atypia may be unclear clinically. In all three cases, adequate margins were obtained in a single definitive resection, sparing the patient multiple additional procedures. This technique uses simple 2-mm punch biopsies and standard histological examination. This provides several advantages: low morbidity outpatient procedure, rapid healing, simultaneous evaluation at multiple distances from the original excision, and no requirement for specialized training or technology.
There are other alternatives to consider in managing difficult cases such as those presented here. These include systemic and local therapies.1,8–10
High-dose interferon alfa is the only approved adjuvant treatment for melanoma; however, it has not been evaluated for local control of radial growth phase melanoma and has clinically important morbidity.11–15
Radiotherapy has been used for intransit metastases, nodal disease, and palliation, though limited data exist to guide its use as an adjuvant for incomplete surgical excision of local disease.16
Topical imiquimod cream, an immune stimulator acting as a Toll-like receptor 7 agonist, has been reported to cause regression of MIS.10
In the cases described, however, use of topical imiquimod would have been problematic without histologic mapping of the extent of tumor to guide the application. Furthermore, where there is clinically invisible MIS or invasive melanoma, there is no way to be confident of the success of imiquimod treatment without biopsy.
Surgical options include Mohs micrographic surgery and modified Mohs procedures. Although traditional Mohs surgery in some experienced centers has been reported to provide excellent margin control in melanoma,17,18
its widespread use is limited by the training and expertise required of the dermatopathologists and Mohs surgeon. Its role in management of melanoma is also generally debated.
Variants of the Mohs technique—“slow Mohs”19
and other similar staged excision techniques20–22
—have been developed to aid in treatment. These approaches address the challenge of the important background of junctional melanocytic hyperplasia in chronically sun-damaged skin23
by allowing for evaluation of tissue fixed in formalin. Further modifications to the “slow” or staged Mohs technique have been described as the “perimeter technique”6
and the “square” procedure.7
These approaches enable sampling of the entire margin, but use a substantially more invasive initial procedure than in our mapping approach and leave a greater defect, pending definitive resection. Additionally, in these methods, only a single margin width is evaluated with each procedure, potentially requiring a greater number of procedures. One series reported up to four staging procedures before definitive reexcision.6
No technique is perfect, and the punch biopsy technique does not evaluate the entire margin; there is a limit to the extent of mapping that is realistic. In cases of non-continuous field cancerization, the punch biopsy technique may miss small areas of troubling pathology. In cases of continuous disease or near-continuous disease, however, the punch biopsy technique permits sampling of multiple areas at various distances from the original lesion in a single procedure with low morbidity.
Another approach uses confocal laser scanning microscopy to diagnose excised lesions24
or in vivo tumor margins25
as a means of distinguishing benign from malignant tissue. Ex vivo accuracy rate is reported to be >90%.24
This is a useful approach but requires special expertise and capabilities that are not widely available. It does not include direct histology assessment.
Use of punch biopsies for mapping melanoma in combination with ultraviolet (UV) imaging has been reported previously.1
The UV light permits identification of melanin in the dermal layer and preliminarily suggests the border of the melanocytic lesion. In experienced hands, UV imaging seems to be useful, and the punch biopsies aid in histologic confirmation of margins. Some melanomas, however, are not pigmented and therefore may not be highlighted by UV light. In patients with extensive melanocytic changes independent of melanin production, such as patient 2 described above, the extent of melanin production may not correspond to the extent of tumor. Thus, we propose that punch biopsy mapping can be useful independent of specialized imaging technology.
We have found that the described melanoma mapping approach is very well tolerated, definitive, and consistent with standard management approaches for definitive therapy of primary melanoma. This technique is simple to perform and is based on a standard punch biopsy technique. It does not require specialized equipment or experience and may be helpful to surgeons and dermatologists to add to their armamentarium for management of selected cases. We hope that the experience of others with this technique will further define its role.
In our clinical experience, this punch biopsy technique has proven useful in defining the extent of disease in patients with extensive melanoma that is not clinically distinguishable on examinations. Punch biopsies were performed in the outpatient setting with minimal morbidity. We did not analyze frozen sections, and we would not recommend them for these 2-mm punch biopsies. The subsequent surgical resection can use the precise landmarks created by the biopsy sites, maximizing the opportunity to obtain disease-free margins and minimizing patient morbidity in selected patients with extensive radial growth phase melanoma extending to margins of excision.