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BACKGROUND Staged excision with rush-processed paraffin-embedded tissue sections (Slow-Mohs) is an effective treatment for periocular melanoma. Although there is no consensus on initial margins of excision, narrower margins in the eyelids have the functionally and cosmetically important consequence of smaller postoperative wounds.
OBJECTIVES To report early cure rates for periocular melanoma using Slow-Mohs surgery with en-face margin sectioning.
METHODS Retrospective, multicenter, noncomparative case series. Slow-Mohs surgery in 14 patients with periocular melanoma from 2000 to 2006.
RESULTS Fourteen patients underwent 14 Slow-Mohs procedures for eight lentigo maligna, one nodular, and one superficial spreading melanoma, and four lentigo maligna, 12 primary, and two recurrent tumors. The most common site was the lower eyelid (8/14, 57.1%). Breslow thickness ranged from 0.27 to 1.70 mm, with four cases less than 0.76 mm and one case greater than 1.5 mm. Five cases were a Clark level II or greater. Complete excision was achieved with one level (6 cases) or two or three levels (8 cases), with 2- to 3-mm margins at each level in all but one case. With median follow-up of 36 months, there were two local recurrences (2/14, 14.3%).
CONCLUSION Slow-Mohs with en-face sections achieves similar early cure rates to previously published margin-controlled excision techniques. Narrow margins of excision can optimize tissue preservation without compromising outcome.
Malignant melanoma (MM) of the eyelid is rare but has the highest mortality of all primary skin tumors.1 The commonest subtype of periocular melanoma, lentigo maligna melanoma (LMM), and its precursor lentigo maligna (LM) are often large at presentation and have a propensity for subclinical extension beyond the clinically apparent margin.2,3
The difficulties in accurately interpreting the morphology of melanoma in frozen tissue section in standard Mohs micrographic surgery (MMS) are well documented,4–6 and have been overcome with a variety of modified Mohs surgery techniques using rush-processed paraffin-embedded tissue sections (Slow-Mohs).4,7–10 These techniques differ primarily in the way in which the margins of permanent sections are cut and examined—as en-face horizontal sections 11–14 or radial vertical sections (mapped serial excision (MSE)).4,7
Although there is no consensus on the initial margins of excision that should be used during staged Slow-Mohs excisions for periocular MM, several reports suggest that the majority of periocular MM are thin (≤1 mm thick) at presentation and that initial margins of excision of 5 mm or greater result in acceptably low recurrence and metastatic rates.4,7,9,11 More recently, the use of narrower margins of 2 to 3 mm at each level of excision has been reported, resulting in smaller mean postoperative defects and comparable recurrence rates with series using wider margins.15
We report early cure rates in a series of 14 patients with in situ or invasive periocular MM treated with Slow-Mohs with en-face sections in which complete excision with low recurrence rates was achieved in the majority of patients with initial margins of 2 to 3 mm and a comparable number of levels of excision to previous series.
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Reports on outcomes after margin-controlled excision of periocular MM are few because of the rarity of this tumor. This large series adds to the body of evidence that staged excision with rush-processed paraffin-embedded permanent tissue sections (Slow-Mohs) and conservative margins is an effective treatment for this aggressive tumor, ensuring complete excision with low recurrence rates. Our results also suggest that narrower margins of excision can be safely employed with comparable number of levels of excision with other series, achieving smaller postoperative defects without compromising early cure rates or cost or convenience to the patient.
Standard excision margins for melanoma may not be necessary in the context of periocular disease. The potential disadvantages of wide excision are unnecessary loss of periocular tissue and incomplete excision. The majority of periocular melanomas are LM or LMM.2,3 They are often thin (<1 mm) on presentation and have a tendency to unpredictable subclinical extension beyond the visibly pigmented and Wood's light margins.16 Furthermore, a number of studies have demonstrated that standard margins may be inadequate for the complete excision of more than 30% of LM and LMM7,17,18 and are associated with recurrence rates of 9% to 20%.2,19 Zitelli reported that an average of 1.8 cm more of normal skin is preserved with MMS than with standard excisional surgery. This is critical in the eyelid, whose total length is approximately 3 cm.20
Standard Mohs micrographic surgery uses en-face horizontally cut frozen tissue sections that allow examination of 100% of the lateral and deep margins, but the morphology of melanoma at these margins is difficult to interpret on frozen tissue sections. Problems with frozen sections include freeze artefact, fat tears, and relatively thick sections. These features can make it difficult to determine the peripheral margins of melanomas, particularly in the presence of scar tissue, a dense inflammatory infiltrate, or on chronically sun-damaged skin (which contains prominent single melanocytes with large, hyperchromatic nuclei).5
It may be particularly challenging to identify the periphery of LM, which may be represented only by single melanocytes, albeit with marked atypia.5,19
The use of melanocyte-specific immunohistochemical stains, with monoclonal antibody to HMB-45, S-100, Melan-A, Mel-5, and MART-1 proteins, may improve the diagnostic accuracy and facilitate margin evaluation in MMS frozen sections.12–14 HMB-45 does not distinguish benign from malignant melanocytes but has been reported as useful in demonstrating single atypical melanocyte proliferation in MMS for melanoma in situ.9 MART-1 has been reported to be more sensitive than HMB-45 in MMS frozen sections of invasive and in situ melanoma,14 although as has been previously pointed out,5,19 immunohistochemical methods can yield false negatives due to alteration or loss of the marker antigen or technical error, which means that lack of staining does not always exclude atypical melanocytic proliferations.
In common with the frozen section procedure, Slow-Mohs surgery involves the excision and orientation of the tumor with marker dyes and color-coded diagrams. Techniques differ in the manner in which the margins of specimens are sectioned for histologic examination. En-face sectioning, as used in our series, is the most commonly described and used.11,8–10 More recently, a technique known as MSE has been described for LM and LMM.4,7,15 This involves radial and vertical sectioning of the entire specimen, usually in 1-mm slices, before paraffin embedding. The advantages of radial and vertical sections over en-face sections include the ability to follow the evolution of tumor architecture from the center to the periphery. This in turn can increase the accuracy of identification of single or small nests of melanoma cells at the true periphery of LM. It may also assist in detecting invasive disease and allow measurement of tumor thickness throughout the specimen. A disadvantage of MSE is that is much more labor intensive, requiring experienced staff to process and interpret multiple sections.
Local recurrence of MM is strongly correlated with tumor thickness, widely regarded as the most important single predictor of survival in early (Stage 1) tumors.2,3 Local recurrence is uncommon in tumors of 1 to 2 mm thick or less, which account for the majority of periocular MM in most series.2,7,12 In a retrospective review of 44 cases of periocular MM (mean follow-up of 34 months), Esmaeli and colleagues reported a 50% recurrence rate in tumors 2 mm thick or thicker, compared with 6.3% recurrence in tumors 1 mm thick or less.21 The majority (7/9, 77.8%) of invasive lesions with a recorded Breslow thickness in our series were also thin (≤1 mm). The two cases of recurrence occurred in primary LMM with Breslow thicknesses of 1.70 and 0.30 mm, respectively.
Local recurrence is an important indicator of adequacy of surgical margins. Although there is no consensus on the margins that should be used for periocular MM, many margin-controlled techniques use initial excision margins of 5 mm or more and report acceptably low rates of local recurrence and regional or distant metastases.2,4,6,7,9–11
The study described above by Zalla and colleagues12 retrospectively reported the practice of surgeons managing 44 cases of eyelid MM throughout Europe, the United Kingdom, and the United States. Although no mention was made of the methods of excision used, the majority of lesions were 1 mm thick or less (43.1%) and had been excised with 5-mm margins or less (67%). As a consequence of their higher local recurrence rates, they recommended a margin of excision of at least 5 mm for tumors 1 mm or less and wider margins for thicker tumors.
Chan and colleagues2 reviewed 29 cases of periocular MM (the majority of invasive MM being less than 1.5 mm thick) managed with standard excision or margin-controlled excision with standard or modified MMS. The majority (79.3%) were excised with total margins of 5 to 10 mm. Subsequent median follow-up was 3 years, with local recurrence rates reported in 17.2% and distant metastases in 13.8%.
Malhotra and colleagues7 examined 27 cases of periocular LM and LMM (the majority of LMM being <1 mm thick) treated with MSE using 5-mm excision margins at each level. Most (55.6%) were completely excised with one level (5-mm margin), whereas the remainder required 2 to 3 levels (10- to 15-mm margins). Local recurrence rates were 7.4%, with a mean follow-up of 32 months.
Although there is clearly evidence to support the safety of 5-mm margins during staged excision of periocular MM, there is no evidence that refutes the use of narrower margins. In the eyelids, every millimeter of tissue loss is significant, and narrower margins have the functionally and cosmetically important consequence of smaller postoperative wounds.
In a retrospective review of 59 patients with cutaneous LM and LMM, the majority of which were in the head and neck (including 3 periocular cases), Bub and colleagues15 reported the long-term outcomes after treatment with MSE using 2- to 3-mm margins of initial excision. Despite narrower margins, complete excision was achieved with an average of 1.7 levels of excision. This is comparable with previous series using 5-mm margins or greater, where number of levels of excision ranged from 1.9 to 2.3,10,11,18 for lesions of similar size. In addition, the overall postoperative defect sizes were smaller than those previously reported. This was attributed to the narrower margins excised at each level, and they maintained low recurrence rates of 5% with a mean follow-up of 57 months.
Our data support the use of narrow margins of excision (<5 mm) through the use of Slow-Mohs surgery for periocular MM. The majority of lesions (10/14, 71.4%) were completely excised using 2- to 4-mm margins at each level, with an average of 1.64 levels for histologic clearance. A significant proportion of lesions (6/14, 42.9%) required only one level of excision. The majority of lesions (8/14, 57.1%) were cleared with two or three levels, using 2-mm margins at each level in all but one case. The significance of this was that the total margin of excision was 4 to 6 mm, rather than the 10 to 15 mm that would have resulted if 5-mm margins had been used. The only thick tumor (>1 mm) in this series was excised in one stage with a 3-mm margin. Our mean postoperative defect size (2.8 × 3.8 cm) is comparable with that of Bub and colleagues15 (2.5 × 3.3 cm) and therefore also smaller than those previously reported of 4.2 × 4.5 cm.18 Our recurrence rate of 14.3% was comparable with those of other series.
In conclusion, we report a large series of periocular MM treated with Mohs surgery using rush-processing of paraffin-embedded en-face sections (Slow-Mohs). Although the retrospective nature and relatively short follow-up of this series are significant limitations, our results emphasize that staged margin-controlled surgery should be the criterion standard of treatment for periocular MM. They also suggest that, where accurate histologic control is available, narrow margins of excision can be employed at each level of excision to optimize preservation of tissue without compromising outcome.