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10.1245/s10434-006-9240-4
Annals of Surgical Oncology 14:893-898 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Method of Biopsy and Incidence of Positive Margins in Primary Melanoma

Virginia H. Stell, BA1, H. James Norton, PhD2, Kevin S. Smith, MD3, Jonathan C. Salo, MD1 and Richard L. White, Jr., MD1

1 Division of Surgical Oncology, Department of General Surgery, Carolinas Medical Center, Blumenthal Cancer Center, 1025 Morehead Medical Drive, Suite 600, Charlotte, NC 28204, USA
2 Department of Biostatistics, Carolinas Medical Center, Charlotte, NC, USA
3 Department of Pathology, Carolinas Medical Center, Charlotte, NC, USA

Correspondence: Address correspondence and reprint requests to: Richard L. White Jr., MD; E-mail: Richard.White{at}carolinashealthcare.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The staging of patients with primary melanoma is dependent on adequate sampling of the tumor thickness. Initial biopsies with a positive deep margin suggest inadequate sampling, potentially limiting accurate staging and affecting treatment decisions.

Methods: To determine the efficacy of shave biopsy to adequately sample the tumor, we retrospectively reviewed our pathology database for original pathology reports of primary melanomas accessioned between 01/01/04 and 6/30/05. The biopsies were evaluated by technique, the presence of tumor at the margins of the specimen, and specimen thickness.

Results: We identified 240 cases of primary melanoma; 223/240 were analyzable. The specimens were divided by biopsy technique (excisional, n = 51; punch, n = 44; and shave, n = 128). Shave and punch specimens had a significantly higher percentage of positive margins than excisional specimens (50, 68, and 16%, respectively; P < 0.0001). Shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (22, 7, and 2%, respectively; P = 0.0009). For melanomas ≤1 mm, shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (17, 0, and 0%, respectively; P = 0.0014). There was a significant difference in specimen thickness (P = 0.0005), with shave specimens being the thinnest.

Conclusions: The presence of tumor at the lateral margin of punch biopsies is an expected result, since this method is often used to diagnose lesions with a large diameter. The presence of positive deep margins in 22% of shave biopsy specimens compromises the ability of this technique to properly stage patients.

Key Words: Melanoma • Biopsy • Margins • Staging


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Both the National Comprehensive Cancer Network (NCCN) and the American Academy of Dermatology (AAD) recommend excisional biopsy with narrow margins as the preferred method of biopsy for the diagnosis and evaluation of primary cutaneous melanoma. However, both organizations consider an incisional biopsy technique acceptable for very large lesions, when excision is impractical, or when the likelihood for melanoma is low.1,2 Shave biopsy is reported to be a suitable technique for accurate determination of Breslow thickness, particularly in the case of "thin" melanomas.3

Appropriate treatment decisions, including the size of surgical margins of the definitive excision and inclusion of a sentinel lymph node biopsy, depend on the accurate staging of patients with primary melanoma. Breslow thickness is the most important prognostic indicator in primary melanoma and is given the most weight in the revised American Joint Committee on Cancer (AJCC) staging guidelines.4,5 Initial biopsies with positive deep margins raise questions about the accuracy of the measured Breslow thickness, complicating surgical treatment decisions and impairing appropriate patient counseling regarding prognosis for recurrence and survival. The corresponding pathology reports may or may not address margin status in the context of a shave biopsy.6 Our primary objective was to determine the accuracy of the shave biopsy method in determining the Breslow thickness of primary melanomas. A secondary objective was to determine how often an unspecified margin status yielded a positive deep margin on further review.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We retrospectively reviewed our pathology database for initial biopsy reports of primary melanomas accessioned between 01/01/04 and 06/30/05. This database includes pathology specimens submitted by physicians affiliated with our hospital system as well as specimens reviewed in consultation. The database contains specimens obtained by physicians in the region and nationally. Patients with melanoma in situ or patients whose only evidence of melanoma diagnosis was from a wide local excision (WLE) specimen were excluded. Institutional Review Board approval and waiver of informed consent were obtained for this retrospective study.

The diagnostic biopsies were categorized by technique (excisional, punch, and shave). The status of the margins was determined from the original pathology report. Retrospective review was performed by a single dermatopathologist (KSS) in a subset of cases where the margin status was uncertain (lateral vs. deep vs. both). Absolute thickness of the biopsies retrospectively reviewed was also evaluated by measuring the maximum thickness from the epidermal surface to the base of the specimen. Specimens in which the technique could not be ascertained were excluded. Other features analyzed included ulceration, growth type, tumor location (grouped by head/neck, trunk, upper extremity, and lower extremity), age, and gender.

The pathology database was searched for the WLE specimens that corresponded with each diagnostic biopsy. Each WLE was assessed for the presence of residual tumor. Comparisons were made between the Breslow thickness of tumor in the WLE specimen and that of the original biopsy to determine which specimen had the greatest tumor thickness. If tumor in the WLE was of a greater thickness, it was further analyzed to see if the increase in Breslow thickness was great enough to upstage the T stage of the melanoma. Guidelines from the 6th edition AJCC were used for staging purposes.7 Residual tumor consisting of only melanoma in situ was classified as less deep than the invasive tumor present in the original biopsy.

Statistical comparisons were made using the {chi}2 test (or Fisher’s exact test when appropriate) for nominal data and analysis of variance (ANOVA) for interval data. Descriptive statistics, including means and standard deviations, or counts and percentages were calculated. A P value of <0.05 was considered to be statistically significant. All statistical analyses were performed using SAS® software version 8.2 (SAS Institute, Inc., Cary, NC, USA).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
We identified 240 primary melanoma specimens; the method of biopsy could not be determined in 16. Of the remaining 224 specimens, 167 had the margin status stated on the pathology report. Reports with unevaluated margins or an unspecified positive margin (n = 57) were reviewed to determine margin status. The slides for one punch biopsy specimen were unavailable, leaving 56 reviewed cases (excisional, n = 4; punch, n = 18; and shave, n = 34). A total of 223 specimens were included in the entire pathologic analysis (excisional, n = 51; punch, n = 44; and shave, n = 128). Figure 1Go summarizes the procedure used for inclusion in the pathologic analysis.


Figure 1
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  		FIG. 1. Biopsy specimens included in this analysis.

 
Shave and punch biopsies had a significantly higher percentage of positive margins compared with excisional biopsies (P < 0.0001; Table 1Go). Shave biopsies had a significantly higher percentage of positive deep margins than punch or excisional biopsy specimens (P = 0.0009; Table 1Go). Three shave biopsy specimens could not be oriented as to the deep margin and were excluded from this portion of the analysis. For melanomas with a Breslow thickness ≤1 mm, shave biopsies again had a significantly higher percentage of positive deep margins than punch or excisional biopsy specimens (P = 0.0014; Table 2Go). Of the 18 shave biopsy specimens with a positive deep margin in this thin group of melanomas, 72% (n = 13) were T1a (nonulcerated and Clark level II or III) tumors less than 1 mm in thickness. Of the remaining specimens, 4/18 were Clark level IV and 1/18 was ulcerated.


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  		TABLE 1. Incidence of positive margins by biopsy technique for 223 specimens
 

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  		TABLE 2. Incidence of positive deep margin in thin melanomas (≤1 mm) by biopsy technique for 167 specimens
 
In univariate analysis, there was no significant difference in the method of biopsy when analyzed by gender, mean age, tumor location, growth type, or ulceration (Table 3Go). When Breslow thickness was stratified, thin melanomas were significantly more likely to be diagnosed by the shave technique (P = 0.0005; Table 3Go).


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  		TABLE 3. Demographic and other tumor characteristics
 
Specimens from the corresponding WLE or other definitive surgical procedure were available for 72% of the biopsy specimens (total, n = 161; excisional, n = 35; punch, n = 34; and shave, n = 92). Residual tumor was present in the WLE specimen in four specimens originally diagnosed by excisional biopsy (11%), 19 originally diagnosed by punch biopsy (56%), and 18 originally diagnosed by shave biopsy (20%). The residual tumor had a deeper Breslow thickness in none of the WLE specimens from excisional biopsies, in 26% of WLE specimens from punch biopsies (n = 9), and in 4% of WLE specimens from shave biopsies (n = 4). The residual tumor was deep enough to change the T stage of the tumor in 12% of punch biopsies (n = 4) and 2% of shave biopsies (n = 2). There was a significant difference in the presence of residual tumor, the thickness of residual tumor, and T upstaging among excisional, punch, and shave biopsies (P < 0.0001, P < 0.0001, and P = 0.0175, respectively). There was no significant difference in these three categories when comparing excisional to shave biopsies (P = 0.2790, P = 0.5747, and P = 1.0000, respectively).

Specimens retrospectively reviewed (n = 56) revealed the deep margin was positive in 18/34 (53%) of shave biopsy specimens. A positive deep margin was seen in 3/15 (20%) of punch biopsy specimens with unevaluated margins. In this subset of cases, there was a significant difference in biopsy thickness among the three methods (P = 0.0005), with shave specimens being the thinnest (Fig. 2Go).


Figure 2
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  		FIG. 2. Mean biopsy thickness by biopsy technique for 56 specimens.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The presence of tumor at the margins of punch biopsy specimens is an expected result, since this method is often used to diagnose lesions with a large diameter. Although the deep margin is rarely positive (7%), 26% of WLE specimens following punch biopsy were found to have a deeper Breslow thickness than that measured in the biopsy specimen. The punch biopsy technique may be necessary when the lesion is large or in a cosmetically sensitive area. NCCN guidelines recommend the biopsy should be of the "clinically thickest portion" of the lesion.1 However, clinicians should be aware that even with a negative deep margin, the biopsy may not be representative of the true Breslow thickness.

In the context of a suspected melanoma a shave biopsy should attempt to remove the entire lesion. The presence of positive margins in 50% of shave biopsy specimens, however, indicates that the entire lesion is often incompletely removed. This is supported by the evidence that 20% of melanomas diagnosed by the shave technique had residual melanoma present in the WLE specimen. Furthermore, 22% of patients whose diagnosis was made by the shave technique had positive deep margins on the biopsy specimen, potentially compromising accurate staging and appropriate treatment recommendations. Although there was a significant association between thinner melanomas and the use of the shave biopsy technique, 17% of melanomas with a Breslow thickness ≤1 mm diagnosed by shave biopsy had a positive deep margin, suggesting that even these thin lesions may have been sub-optimally staged. While only 2% of melanomas diagnosed by the shave technique were upstaged based on the residual tumor in the WLE specimen, the inherent difficulty in assigning an accurate Breslow thickness to a previously biopsied tumor8,9 argues that this percentage is misleadingly low. In addition, the rate of detection of residual tumor in the WLE specimen may be decreased if thermal cautery is used for wound treatment after biopsy. Indeed, absence of detectable tumor in the WLE specimen does not imply that there is no microscopic tumor present.

When considering treatment recommendations, thin melanomas with a positive deep margin present a particularly difficult issue. Current guidelines provided by the NCCN recommend the consideration of a sentinel lymph node biopsy (SLNB) for all melanomas ≥1 mm or for melanomas <1 mm with either ulceration or a Clark level of IV or V.1 A nonulcerated, Clark level II or III melanoma with a Breslow thickness of slightly less than 1 mm with a positive deep margin raises the question of whether or not a SLNB is indicated. In this study, 72% of T1 lesions with positive deep margins did not have other features (ulceration, Clark level IV or V) that would have otherwise generated a recommendation for a SLNB. While other factors can affect this decision (high mitotic rate,10,11 vertical growth phase,11,12 regression,13 younger age,10,14) there is little substitute for accurate primary tumor staging. Although a SLNB can be performed after WLE,15–19 concerns about disrupted lymphatic flow altering accurate identification of the sentinel lymph node after WLE have raised questions about the validity of performing a delayed SLNB.20–22 In addition to maximizing the likelihood of accurately identifying the sentinel lymph node, we maintain that performing the SLNB prior to WLE is the preferred method to spare the patient the increased costs and risks associated with multiple separate operations and potentially inaccurate staging.

Knowledge of the margin status of a melanoma is clearly of value to the physician for both devising a treatment plan and for counseling a patient regarding prognosis. A positive deep margin has more serious implications than does a positive peripheral margin. NCCN guidelines include peripheral and deep margin status among the minimal elements to be reported on a pathology report.1 Current College of American Pathologists (CAP) guidelines for reporting of melanoma of the skin, however, state that a comment on margin status in a "biopsy" specimen can be made if clinically indicated, but is necessary only for excisional biopsies or formal resections.6 In our study, positive deep margins were present in a substantial percentage of retrospectively reviewed cases in which the margins were designated as involved, but not further specified as to peripheral or deep in location. In the case of punch biopsy specimens, where the peripheral margins are often expected to be positive and therefore the margins are "not evaluated", 20% of punch biopsies with unevaluated margins had a positive deep margin on further review. This data suggests that one cannot make an assumption about either the peripheral or deep margin status when the pathology report language is nonspecific. Language on the pathology report that addresses the peripheral and deep margins is helpful in guiding management decisions.

Ongoing issues of interest include local recurrence and in-transit, regional, and distant disease rates stratified by margin status at the initial biopsy. Given the nature of this study (retrospective pathology database review), these matters cannot be addressed here.

The ability of physicians to accurately diagnose melanoma by physical exam is disappointingly poor,23–25 with the incidence of both false negatives and false positives limiting the accurate diagnosis of melanoma. Histologically benign lesions often clinically mimic melanoma, and lesions that clinically appear to be benign or non-melanoma skin cancer can be diagnosed as malignant melanoma on pathologic evaluation. These quandaries regarding clinical diagnoses support the notion that biopsy and subsequent pathological evaluation remain the gold-standard in obtaining accurate diagnoses of skin lesions. While the NCCN and the AAD guidelines state that excisional biopsy should be used on lesions clinically suspected to be melanoma,1,2 in our study, the shave method is the predominant technique by which melanomas were biopsied. We suspect that the predominance of shave biopsies is due to the relative ease and rapidity of the technique, literature reports suggesting the shave method is a suitable diagnostic technique,3 and the allowance by the NCCN and AAD guidelines of methods of biopsy other than the excisional technique.1,2 It is always preferable to have a pathologically confirmed diagnosis of any suspicious skin lesion, and if the options faced by the clinician are to perform a shave biopsy versus no biopsy at all, we accept that the shave technique has some value. However, the importance of having an adequate sample to make a diagnosis26 and having clear deep margins in the case of melanoma, make the shave technique a less-than-ideal method of biopsy. Punch biopsy is a potentially more valuable technique, as it rarely transects the base of a melanoma. Punch biopsy is also an accepted diagnostic technique in certain situations in accordance with NCCN guidelines.1 However, given the limitations of punch biopsy (removing only a limited portion of the lesion), discrepancies in the final lesion depth are to be expected. Based on these data, we encourage the use of an excisional biopsy technique for all skin lesions where melanoma is in the differential diagnosis when excision is feasible.


   ACKNOWLEDGMENTS
 
The authors would like to thank Cissy Moore-Swartz, medical editor for the Department of General Surgery, for her assistance in preparing the figures and editing the manuscript; Barbara Penny, Senior Application Analyst of the Department of Information Services—Laboratory, for facilitating the search of the pathology database; and Ellen Abercrombie, Operations Manager of Pathology Associates Services Laboratory, for facilitating the use of PAS consultation cases to be used in this study.

Received for publication August 8, 2006. Accepted for publication August 8, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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