Review of Tumor Margins for Lentigo Maligna with Staged Surgical Excision and Permanent Section en face Processing

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METHODS
identify biopsy-proven primary or recurrent LM.Inclusion criteria consisted of pathology reports with a diagnosis of LM, while exclusion criteria eliminated cases of MIS subtypes or invasive melanoma.
All staged excisions were performed with an initial 5 mm margin.Excised tumor was examined by dermatopathologists using permanent section en face processing with hematoxylin and eosin (H&E) staining.In cases where margins showed residual LM, re-excision with 5 mm margins of tumoraffected areas and the same section processing was performed until a negative margin was achieved.If requested by the dermatopathology team, immunostaining with Microphthalmia transcription factor (MITF) was performed.Wounds were mapped with hatch marks and corresponding 5-0 Polypropylene sutures, and a xenograft was secured with 5-0 Poliglecaprone 25 while awaiting dermatopathology results.Data on age, sex, tumor site, preoperative size, the number of excisions, and the total margin required for clearance were collected.
A linear regression model was applied.The outcome variable, Total Margin Before Clearance (TMBC), was log-transformed for analysis.Correlation coefficients were calculated to assess the relationship between TMBC, preoperative size, and age.This study was conducted with the approval of the University of Texas Medical Branch Institutional Review Board.
Fifty-eight patients (89.2%) had clear margins after the initial excision.Of the seven patients requiring more than one excision, three patients needed two, two required three, one required four, and one underwent five.The mean preoperative tumor size of cases requiring multiple staged excisions was 2.4 ± 1.2 cm, with four located on the face, one on the scalp, one on the ear, and one on the trunk; One of these tumors was a recurrent LM, while the remaining six were primary tumors.
MITF immunostaining was requested for four tumors (6.2%).Of these four, three were primary tumors, and one was recurrent.Additionally, two of the four had clear margins after the initial excision, while the remaining two required three excisions.MITF was utilized by dermatopathology to diagnose the initial biopsy in eight (12.3%)patients but not on their SE.Findings are summarized in Table 2.2][3][4] This ongoing debate extends to determining the efficacy of SE and MMS techniques and their associated section specimens in accurately identifying margin positivity for LM.

DISCUSSION
][7][8][9][10][11][12] Among these studies, the mean margin size required for clearance ranges from 6.6 mm to 13 mm, and the margins necessary to achieve a 97% clearance vary from 11 mm to 25 mm.In comparison, two studies evaluating margin requirements for the resection of LM by MMS and frozen section processing reveal clearance rates of 79% with 6 mm margins and 69% with 6-10 mm margins, with the former reporting a minimum margin size of 12 mm to achieve a 97% clearance rate. 2,135][16] In the present study, 58 patients (89.2%) had clear margins after initial excision with a 5 mm margin.This clearance percentage deviates from margin sizes reported in previous literature.The authors speculate that these differences could be attributed to variations in section processing, staining techniques, and elements associated with greater subclinical spread.
Variations in processing techniques may partly explain the discrepancies in margin sizes for clearance between existing literature and the present study.Permanent sections have historically been favored for evaluating melanocytic lesions due to their preservation of pericytoplasmic vacuolization, which enhances melanocyte identification. 3However, the increased processing time required for permanent sections may offset this advantage.In contrast, frozen sections permit immediate microscopic examination of excision margins.Critics of frozen sections, however, highlight the potential for false positives due to freeze artifacts, tissue folding, and keratinocyte vacuolization resembling melanocytes. 1,3munohistochemical stains like MITF, melanoma antigen recognized T cells (MART-1, melan-A), human melanoma black-45 (HMB-45), S-100, and Mel-5 have been developed to address the challenges associated with frozen sections and better differentiate melanocytes from surrounding keratinocytes. 17While studies have shown immunostained frozen sections and permanent sections to be comparable, skepticism remains due to reports of false positives in the setting of actinic damage, as sun-damaged skin makes distinguishing benign melanocytes from malignant melanocytes challenging. 3,18,19This may inadvertently result in more extensive margin requirements and overtreatment of tumors.Notably, studies comparing the accuracy of frozen and permanent sections have shown conflicting outcomes.One study showed a diagnostic discrepancy as high as 40% for melanocytic lesions when comparing these two techniques. 20nversely, another study indicated an 86% agreement between immunostained frozen sections and permanent paraffin sections assessing margins of LM. 4 In reviewing variations in margin requirements for tumor clearance across studies utilizing different tissue sectioning and immunostaining methods, the authors suspect that the present study's utilization of permanent sections with en face processing and occasional immunostaining, as opposed to frozen section processing with immunostaining for each section, may have minimized events of overstaining or sections affected by artifacts, thereby reducing the number of false positives.
The degree of subclinical spread may further explain discrepancies in margin sizes.Areas that have been associated with subclinical spread include tumors of the head, neck, acral sites, and pretibial leg. 21,22In the present study, approximately 86% (six of seven) of our patients requiring additional excisions had tumors located on the head or neck, a consistency observed in earlier studies. 21,22Additional factors that have been reported to be associated with subclinical spread are tumors exceeding 1 cm in diameter and patients being aged 60 years or older, although another study found that neither the patient's age nor preoperative tumor size was predictive of surgical margins. 16In the present study, no significant relationship between margin requirements, age, and preoperative tumor size was observed, indicating the need for further investigation.
Part of the discussion concerning permanent and frozen sections involves considering whether subclinical spread might be overlooked when assessing permanent H&E stains.In a study evaluating 37 cases, discrepancies emerged in seven cases where the dermatopathologists initially deemed the margins clear while the Mohs surgeons identified positive margins after the first stage. 4Following an external pathologist review, one case was reclassified as concordant, and another was excluded due to incomplete slides, leaving five cases with an undetermined status.While recognizing the need for further investigation on this topic, the present study's authors acknowledge this limitation, as exemplified by cases where our dermatopathologists obtained MITF immunostain in instances where the first excision had ill-defined margins on H&E examination.
Our findings may offer insights for dermatology clinics without an on-site Mohs surgeon.When comparing studies assessing the geographical distribution of Mohs surgeons to those of general practicing dermatologists, it becomes evident that the former have less geographic coverage across the United States than their general dermatology counterparts. 23,24Given their broader geographic distribution, staged excision with 5 mm margins and permanent section en face processing is a viable treatment option for general dermatologists to consider, especially for patients in regions where Mohs surgeons are not readily available.Practicing dermatologists can employ a tissue-sparing technique to achieve clearance of LM without an immediate need for a Mohs surgeon.In doing so, this can help minimize the need for extensive reconstruction that may follow treatment by a conventional approach of wide local excision.Notably, while the findings in the present study provide evidence for the utilization of SE with 5 mm margins and permanent section en face processing, the authors acknowledge the ongoing inconsistencies within existing literature and the need for further research before a clear margin guideline can be established.
In conclusion, our study demonstrates a slightly higher percentage of tumors cleared with 5 mm margins than reported in existing literature.We suspect that this may be due to a reduced number of false positives resulting from the primary use of permanent section en face processing of tissue and the selective utilization of immunostaining in cases with unclear margins.Strengths of the present study include the focused analysis distinguishing LM from MIS and invasive melanoma and consistency in our analysis of resections performed.The single-center approach may limit the generalizability of our findings.Additional limitations include the retrospective design and small sample size, which pose challenges in drawing definitive conclusions.As such, future studies should further investigate the concordance between SE utilizing en face permanent paraffin sections and MMS utilizing immunostained frozen sections and disparities in accurately identifying the subclinical spread of LM.

Table 1 .
Patient and Tumor Characteristics.