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Frequency of and risk factors for tumor upstaging after wide local excision of primary cutaneous melanoma
Frequency of and risk factors for tumor upstaging after wide local excision of primary cutaneous melanoma Jeremy R. Etzkorn, MD,a John M. Sharkey, BA,a John W. Grunyk, BA,b Thuzar M. Shin, MD, PhD,a Joseph F. Sobanko, MD,a and Christopher J. Miller, MDa Philadelphia, Pennsylvania Background: Detecting a more advanced stage of the primary melanoma after wide local excision and reconstruction can complicate patient counseling about prognosis, management of surgical margins, and indications for sentinel lymph node biopsy. Objective: To identify the frequency of and risk factors associated with upstaging after wide local excision of primary melanoma. Methods: Retrospective, single center, cross-sectional study of 1332 consecutive in situ to stage T4a melanomas treated with wide local excision. Results: The overall rate of upstaging of melanoma was 3.9% (52/1332). After multivariate analysis, the greatest risk factor for upstaging was anatomic location on the head, neck, hands, feet, genitals, or pretibial leg (odds ratio [OR] 7.06, P \ .001) followed by extension of the melanoma to the base of the biopsy specimen (OR 3.42, P \ .001); the need for multiple preoperative scouting biopsies (OR 1.89, P = .004); older age (OR 1.03 per year, P = .002); and nonlentigo maligna histologic subtype (OR 3.6, P = .002). Limitations: This was a single-site, retrospective observational study. Conclusions: Clinicopathologic characteristics, particularly anatomic location on the head, neck, hands, feet, genitals, or pretibial leg and subtotal diagnostic biopsies, identify melanomas with an increased risk for upstaging. ( J Am Acad Dermatol 2017;77:341-8.) Key words: conventional excision; guidelines; melanoma; Mohs surgery; prognosis; reconstruction; sentinel lymph node biopsy; upstaging; wide local excision.
W
hen residual melanoma remains after the diagnostic biopsy, upstaging (defined as an increase in the T stage designated by the American Joint Committee on Cancer [AJCC] classification system for melanoma)1 might be detected after wide local excision in 5%-22% of cases.2-11 Upstaging might complicate patient counseling about prognosis and surgical management of melanoma. AJCC tumor stage is a powerful predictor of prognosis, with 10-year survival ranging from 93%
for T1a melanoma to 39% for T4b melanoma.1 Patients who are counseled about an excellent
From the Department of Dermatology, University of Pennsylvania Health System, Philadelphiaa; and Perelman School of Medicine, University of Pennsylvania, Philadelphia.b Funding sources: Drs Etzkorn and Sobanko are supported by a Dermatology Foundation Clinical Career Development Award in Dermatologic Surgery. Conflicts of interest: None declared. Accepted for publication March 16, 2017. Reprints not available from the authors.
Correspondence to: Jeremy R. Etzkorn, MD, Mohs and Reconstructive Surgery, Division of Dermatologic Surgery, University of Pennsylvania Health System, 3400 Civic Center Blvd, Philadelphia, Pennsylvania 19104. E-mail: jeremy.etzkorn@uphs. upenn.edu. Published online June 8, 2017. 0190-9622/$36.00 Ó 2017 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2017.03.018
Abbreviations used: AJCC: AUC: CI: LM: OR: SLNB:
American Joint Committee on Cancer appropriate use criteria confidence interval lentigo maligna odds ratio sentinel lymph node biopsy
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prognosis before surgery might be surprised and the cohort. Nonexcisional biopsy methods (shave, confused to learn of a worse prognosis if the tumor punch, or incisional) to diagnose melanoma are upstages after a wide local excision. more common than excisional biopsy in many Surgical management might also be complicated patient populations24,26,28 and have been noted to by upstaging because the Breslow depth, ulceration increase the risk for inaccurate microstaging.11,27 status, and mitotic rate from the diagnostic biopsy of This study adds to the work of previous authors a primary cutaneous melanoma dictate the surgical by examining the impact on upstaging of the widest excision margins and the inreported array of clinicodications for sentinel lymph pathologic risk factors in a CAPSULE SUMMARY node biopsy (SLNB).12 First, large cohort of melanomas diagnosed with a blend of if an inaccurate diagnostic Tumor upstaging after wide local excisional and nonexcisional biopsy leads to undertreatexcision complicates surgical preoperative biopsies, which ment with narrower surgical management of melanoma. might be more generalizable margins than those recomRisk factors for upstaging include tumor to many patient populamended by consensus guidelocation in cosmetically or functionally tions.24,26 The principal aims lines, patients might need sensitive areas, partial preoperative additional surgery either to of this study were to describe biopsies, older patient age, and clear the tumor or to comply the rate of upstaging after nonlentigo maligna histologic subtype. with wider margins recomwide local excision of mended for the upstaged tucutaneous melanoma and to The possibility of upstaging should be mor. Neither the randomized evaluate clinical and pathoconsidered during patient counseling trials that inform guidelines logic risk factors associated and surgical planning. for surgical management of with upstaging. Secondarily, primary cutaneous melawe aimed to describe how noma nor consensus guidelines address surgical frequently consensus recommendations for surgical margins after upstaging.12-18 Second, 1.3%-10% of management differ for discrepant tumor stages before and after wide local excision. upstaged tumors will meet criteria for SLNB.2,5,6,11 While some case series have demonstrated that SLNB can be performed after reconstruction, especially METHODS after linear repairs, with good sensitivity and rare Experimental design false negatives,19-21 the accuracy of SLNB after flap This retrospective cross-sectional study was and graft reconstruction remains uncertain.12,22,23 approved by the institutional review board at the Clarifying risk factors for upstaging is important to Hospital of the University of Pennsylvania. Inclusion help clinicians improve preoperative counseling criteria for this study were age $18 years, pathologic about prognosis and surgical management, particuT stage on diagnostic biopsy of in situ to T4a (T4b larly when deciding whether or not to delay were excluded because they have no risk for reconstruction for final staging of the wide local upstaging), biopsy-proven melanoma whose excision specimen.6 Current data about upstaging diagnostic biopsy and excision specimens were must often be gleaned from reports that focus interpreted by a board-certified dermatopathologist primarily on surgical technique2-4,6-9 or biopsy at the University of Pennsylvania from January 1, method.11,24-27 2008, through December 31, 2013, and initial Factors other than surgical technique and biopsy treatment with conventional wide local excision by method might independently increase the risk for a University of Pennsylvania Health System provider. upstaging. One previous study correlated microWide local excision was defined as excision of a staging accuracy with biopsy method as well as biopsy-proven melanoma with a margin of several other clinicopathologic factors.27 Compared clinically normal skin and immediate reconstruction, with excisional biopsy, punch and shave biopsy had followed by microscopic margin assessment via a significantly increased risk for inaccurate formalin-fixed, paraffin-embedded bread loaf tissue microstaging.27 Among partially biopsied lesions, sections. Eligible cases were identified via a search of tumor thickness (increased risk for thicker tumors) the Dermatopathology database for ‘‘melanoma’’ was the only clinicopathologic factor that and ‘‘lentigo maligna’’ (LM), which resulted in the significantly affected microstaging accuracy after identification of 7657 pathology reports containing multivariate analysis. However, these results might either term in the line diagnosis. Review of the not be generalizable because excision was the medical record identified 1332 melanomas that met method of biopsy in a high percentage (78.6%) of inclusion criteria for this study. Each melanoma d
d
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included in the study accounted for 2 (1 pathology report for the diagnostic biopsy and 1 for the wide local excision) of the 7657 reports. In addition, some melanomas had multiple preoperative biopsies and some pathology reports were from re-excisions for positive or equivocal margins. Most remaining cases were excluded because either the diagnostic biopsy or the wide local excision specimen was interpreted by a physician outside of the Penn health system. No a priori study size calculation was performed to determine the desired sample size. Data collection All data were recorded in a de-identified fashion in a RedCap database before statistical analysis. After verifying patient eligibility for this study, clinical notes and pathology reports from the diagnostic biopsies and wide local excisions for each patient were reviewed. The following data were recorded from the clinical notes and pathology reports: biopsy method, anatomic location, patient age at biopsy, personal history of melanoma, prior history of treatment, and histopathologic characteristics of the melanoma (presence or absence of residual melanoma in the excision specimen, invasive versus in situ disease, Breslow depth, mitotic rate, ulceration, regression, LM subtype versus other subtypes). If multiple pre-excision scouting biopsies had been performed, the number of scouting biopsies was recorded, and the tumor was classified according to the most advanced tumor stage. Data analysis Each case of melanoma was assessed for the presence of upstaging (defined as an increase in the T stage in the AJCC classification system for melanoma)1 after histopathologic evaluation of the wide local excision specimen. The frequency of upstaging was correlated with patient demographic characteristics, history of prior treatment, anatomic location (trunk and proximal extremities vs head, neck, hands, feet, genitals [including the nipple and areola], and pretibial leg), histopathologic characteristics of the melanoma (regression, ulceration, invasive vs in situ disease, and LM histologic subtype vs other subtypes), biopsy method (excisional vs other), and biopsy specimen margin positivity (lateral or deep) as assessed by histopathology. Anatomic locations were classified according to consensus guidelines for appropriate use criteria (AUC) of Mohs micrographic surgery: AUC-appropriate (head, neck, acral sites, genitalia [including nipple and areola], and pretibial leg) versus AUC-uncertain (trunk and proximal
extremities).29 Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Univariate logistic regression was used to identify potential risk factors for upstaging. Multivariate stepwise logistic regression with a prespecified cut off value of P $ .200 was then performed to reduce confounding. With each iteration of the stepwise regression analysis, the risk factor with the highest P value was sequentially removed from the multivariate model until no variables remained with a P value $ .200. All data analyses were performed using STATA version 13 (StataCorp, College Station, Texas).
RESULTS Table I shows the demographic and clinicopathologic features of the melanomas included in this study. Residual tumor and upstaging Upstaging was observed in 3.9% (52/1332) of melanomas overall and in 11.3% (52/460) of lesions with residual microscopic melanoma (in situ or invasive) in the wide local excision specimen. Residual invasive melanoma was seen in 12.8% (170/1332) of wide local excision specimens. Of these, 49% (83/170) had a deeper Breslow depth than the pre-excision diagnostic biopsies. Risk factors that were significantly associated with an increased risk for upstaging after multivariate analysis included anatomic location on the head, neck, hands, feet, genitals, or pretibial leg; multiple preoperative diagnostic biopsies; extension of melanoma to the base of the diagnostic biopsy; increasing patient age; and non-LM histopathologic subtype (Table II). Raw frequencies for upstaging were 12% (5/41) on the hands or feet and 12% (25/207) on the head or neck. Prior treatment and extension to the lateral margin of the diagnostic biopsy specimen were associated with an increased frequency of upstaging on univariate analysis but failed to remain significant predictors of upstaging after multivariate analysis. Statistically significant differences in rates of upstaging were not associated with excisional versus nonexcisional biopsy, sex, personal history of melanoma, regression, or in situ versus invasive disease. Specific changes in pathologic T staging that resulted in upstaging are shown in Table III. Of the melanomas with upstaging, 21% (11/52) became candidates for SLNB. Three additional melanomas did not change T stage but qualified for SLNB because of an increase in Breslow depth from \0.76 mm to 0.76-1 mm. Thus, of the 1019 melanomas with a Breslow depth of #0.75 mm
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Table I. Demographic data and clinicopathologic characteristics of melanomas included in this study Characteristics
Totals
Age, y Range 18-94 Mean 60.8 Median 62 Sex, % (n/total) Male 57.6 (767/1332) Female 42.4 (565/1332) Diagnostic biopsy T stage,* % (n/total) TIS 34.5 (459/1332) T1a (#1.0 mm without ulceration 37.0 (493/1332) or mitosis) T1b (#1.0 mm with ulceration 12.9 (172/1332) or mitosis) T2a (1.01-2.0 mm without 7.3 (97/1332) ulceration) T2b (1.01-2.0 mm with ulceration) 1.9 (25/1332) T3a (2.01-4.0 mm without 3.4 (45/1332) ulceration) T3b (2.01-4.0 mm with ulceration) 2.2 (29/1332) T4a ([4 mm without ulceration) 0.9 (12/1332) Location, % (n/total) Trunk and proximal extremity 79.2 (1055/1332) Pretibial leg 1.9 (25/1332) Head and neck 15.5 (207/1332) Hands and feet 3.1 (41/1332) Genitals 0.3 (4/1332) Total biopsies, n Range 1-7 Mean 1.09 Median 1 Residual melanoma present on wide local excision pathology, % (n/total)* Yes 34.2% (456/1332) In situ 63.4% (289/456) Invasive 36.6% (167/456) No 65.8% (876/1332) *T stage was based on the American Joint Committee on Cancer 7th edition.
noted on the diagnostic biopsy, 1.4% (14/1019) became candidates for SLNB. Of these 14 melanomas, 64% (9/14) were on the head, neck, hands, feet, genitals, or pretibial leg; 79% (11/14) had melanoma extending to the base of the diagnostic biopsy; 93% (13/14) had melanoma extending to the lateral margin of the diagnostic biopsy; and 29% (4/14) had multiple preoperative scouting biopsies. Of the melanomas with upstaging, 62% (32/52) had a T stage that warranted wider surgical margins than those recommended for the pre-excision tumor stage. Thus, of the 1246 in situ or stage T1 or T2 invasive melanomas, 2.6% (32/1246) upstaged to a T stage that warranted wider surgical margins than those recommended for the pre-excision tumor
stage. For these 32 melanomas, 56% (18/32) were on the head, neck, hands, feet, genitals, or pretibial leg; 59% (20/32) had melanoma extending to the base of the diagnostic biopsy; 91% (29/32) had melanoma extending to the lateral margin of the diagnostic biopsy; and 19% (6/32) were biopsied with multiple scouting biopsies.
DISCUSSION This study evaluated 1332 melanomas treated with wide local excision to correlate the risk for upstaging with the largest reported array of clinicopathologic risk factors. Compared with the diagnostic biopsies, wide local excision specimens were more likely to contain a higher tumor stage when cutaneous melanomas had the following independent risk factors: anatomic location on the head, neck, hands, feet, genitals, or pretibial leg; multiple preoperative diagnostic biopsies; extension of melanoma to the base of the diagnostic biopsy; increasing patient age; and non-LM histopathologic subtype. These findings are helpful to guide preoperative prognostic counseling and surgical management of melanoma. Despite National Comprehensive Cancer Network guidelines recommending narrow excision with 1-3 mm margins as the preferred method to biopsy lesions suspicious for melanoma,12 only 10% of cases in our cohort had a preoperative excisional diagnostic biopsy. This low rate of excisional biopsies is consistent with previously published cohorts.24,26 Biopsy method (ie, excision versus nonexcision) was not significantly associated with an increased frequency of upstaging in our cohort (P = .068, 95% CI 0.87-51.7). However, extension of the melanoma to the base of the biopsy and multiple diagnostic scouting biopsies, factors that indicated a subtotal biopsy, were significant predictors of an increased risk for upstaging after multivariate analysis. Extension of melanoma to the lateral aspect of the pre-excision biopsy specimen was a significant predictor in univariate analysis, but it failed to remain a significant predictor after multivariate analysis, possibly because of confounding with these other markers of subtotal biopsies. Our data indicate that subtotal biopsy, regardless of the biopsy method or number of scouting biopsies, has an increased risk for upstaging. This finding is consistent with prior studies that showed a correlation between partial sampling of a lesion and higher rates of upstaging.11,27 Anatomic location on the head, neck, hands, feet, genitals, or pretibial leg was the strongest predictor of upstaging (OR 7.06, 95% CI 3.77-13.25). A logical supposition might be that the more than 7-fold
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Table II. Clinical and histopathologic characteristics associated with upstaging
Risk factors
Frequency of upstaging (%)
Location Head, neck, hands, feet, genitals, 12 (33/277) or pretibial leg Trunk and proximal extremities 1.8 (19/1055) Sexz Male 4.3 (33/767) Female 3.4 (19/565) Personal history of melanomaz Yes 3.6 (12/337) No 4.0 (40/995) Previously treated Yes 15 (3/20) No 3.7 (49/1312) Number of preoperative biopsies No cut off N/a Age No cut off N/a In situ or invasive melanomaz Invasive 4.1 (36/873) In situ 3.5 (16/459) Lentigo maligna type Yes 3.2 (9/280) No 4.0 (43/1065) Regressionz Present 3.4 (7/205) Not present 4.0 (45/1127) Extends to base of biopsy specimen Yes 8.2 (32/389) No 2.1 (20/943) Extends to lateral margin of biopsy specimenz Yes 4.5 (45/990) No 2.0 (7/342) Biopsy type Nonexcisional 4.2 (51/1201) Excisional 0.8 (1/131)
Multivariate analysis with stepwise regression
Univariate analysis OR
95% CI
P value*
7.37
4.12-13.2
\.001
1.00y
-
1.29 1.00y
0.73-2.30 -
0.88 1.00y
OR
95% CI
P value*
7.06
3.77-13.25
\.001
1.00y
-
.383
-
-
-
0.46-1.70 -
.707
-
-
-
4.55 1.00y
1.29-16.0 -
.018
-
-
-
2.13
1.41-3.23
\.001
1.89
1.23-2.93
.004
1.03
1.01-1.05
.003
1.03
1.01-1.06
.002
1.19 1.00y
0.65-2.17 -
.568
-
-
0.78 1.00y
0.38-1.62 -
.504
0.28 -
0.12-0.64 -
0.85 1.00y
0.38-1.91 -
.694
-
-
-
4.13 1.00y
2.34-7.33 -
\.001
3.24 1.00y
1.76-5.96 -
\.001
2.28 1.00y
1.02-5.10 -
.045
-
-
-
5.77 1.00y
0.79-42.1 -
.084
6.12 -
0.81-37.8 -
-
.002
.080 -
CI, Confidence interval; N/a, not applicable; OR, odds ratio. *Logistic regression P value. y Reference category for comparison to calculate odds ratios. z Removed from multivariate analysis because of low significance (P [ .2) during stepwise logistic regression analysis.
increased odds of upstaging occurred because excisional biopsies were less common or less practical in these locations, excisional biopsy was actually slightly more prevalent (11%, 31/278) on the head, neck, hands, feet, genitals, or pretibial leg than on the trunk and proximal extremities (9.7%, 103/1067) in our cohort. However, excisional biopsies were less likely to have negative margins (both deep and lateral) for melanomas on the head, neck, hands, feet, genitals, or pretibial leg (26%, 8/31) versus those on the trunk and proximal extremities (54%, 54/100). The increased risk for upstaging, whatever the method of biopsy, adds to
the well-documented challenges of positive margins30-33 and local recurrence16,33-46 after wide local excision of melanomas on the head, neck, hands, feet, genitals, or pretibial leg. An explanation for the significance of the risk factors old age (OR 1.03, 95% CI 1.01-1.06, P = .002) and non-LM histopathologic subtype (OR 0.28, 95% CI 0.12-0.64, P = .002) is unclear. More severe background actinic damage with older age might increase the difficulty of discerning the most aggressive portion of a melanocytic tumor by clinical examination. LM melanomas might be more likely to have a more uniform Breslow depth compared with
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Table III. Changes in T staging that resulted in upstaging Initial T stage
T0 (in situ)
T1a
T1b T2a
T2b
T3a
Final T stage
N
Increase in recommended surgical margin
Upstaged to candidacy for SLNB
T1a T1b T4b T1b T2a T4a T2a T3a T2b T3a T4a T3a T3b T4b T3b T4a T4b
12 3 1 3 4 1 7 3 2 4 4 2 1 1 1 2 1
12 3 1 0 0 1 0 3 0 4 4 2 1 1 N/a N/a N/a
2 0 1 2 2 1 2 1 N/a N/a N/a N/a N/a N/a N/a N/a N/a
N/a, Not applicable; SLNB, sentinel lymph node biopsy.
other histologic subtypes, but these explanations remain purely speculative and merit further study. Of the 52/1332 (3.9%) upstaged melanomas in our cohort, 62% (32/52) warranted wider recommended surgical margins than those for the pre-excision tumor stage, and 21% (11/52) become candidates for SLNB. For melanomas at high risk for upstaging, delaying reconstruction until after histopathologic evaluation of the excisional specimen might be prudent to ensure that appropriate surgical margins are excised before definitive reconstruction. Delaying reconstruction with local flaps or skin grafts might also be judicious because the validity of SLNB after these reconstructions remains uncertain.12,22,23 Patients at high risk for upstaging might also benefit from preoperative counseling about alternative surgical approaches, such as undergoing a complete excisional biopsy before definitive excision and reconstruction or Mohs surgery with frozen-section bread loaf sectioning of the debulking specimen, which permits accurate and timely identification of upstaging before tissue rearrangement.6 Limitations of our study include the single-center, retrospective nature of our cohort. Our data are from a tertiary academic center, where patients often receive SLNB, which likely has a skewed sample with more invasive melanomas compared with the general population. The observed frequency of excisional biopsy in our cohort was 10%, which might not reflect the percentages seen at other institutions or in other regions. We were unable to assess the presence or absence of clinically visible residual lesions before excision or the percentage of the clinically visible lesions that was sampled with
the diagnostic biopsies. Finally, there exists inherent variability in the microscopic tumor staging of melanoma given that frequency of discordance between expert pathologists regarding the diagnostic and prognostic attributes of melanocytic lesions.47,48 Identifying patients at high risk for upstaging is important to improve preoperative counseling about prognosis and surgical management. The 2 greatest risk factors for upstaging of melanomas were location on the head, neck, hands, feet, genitals, or pretibial leg and subtotal diagnostic biopsies. Patients with melanomas at high risk for upstaging might benefit from preoperative counseling that prognosis and surgical management might change after complete microscopic tumor staging. REFERENCES 1. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-6206. 2. Iorizzo LJ 3rd, Chocron I, Lumbang W, Stasko T. Importance of vertical pathology of debulking specimens during Mohs micrographic surgery for lentigo maligna and melanoma in situ. Dermatol Surg. 2013;39(3 Pt 1):365-371. 3. Huilgol SC, Selva D, Chen C, et al. Surgical margins for lentigo maligna and lentigo maligna melanoma: the technique of mapped serial excision. Arch Dermatol. 2004; 140(9):1087-1092. 4. Cohen LM, McCall MW, Zax RH. Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. A follow-up study. Dermatol Surg. 1998;24(6):673-677. 5. Somach SC, Taira JW, Pitha JV, Everett MA. Pigmented lesions in actinically damaged skin. Histopathologic comparison of biopsy and excisional specimens. Arch Dermatol. 1996;132(11): 1297-1302.
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6. Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72(5):840-850. 7. Bub JL, Berg D, Slee A, Odland PB. Management of lentigo maligna and lentigo maligna melanoma with staged excision: a 5-year follow-up. Arch Dermatol. 2004;140(5): 552-558. 8. Mahoney MH, Joseph M, Temple CL. The perimeter technique for lentigo maligna: an alternative to Mohs micrographic surgery. J Surg Oncol. 2005;91(2):120-125. 9. Zalla MJ, Lim KK, Dicaudo DJ, Gagnot MM. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg. 2000;26(8):771-784. 10. Gardner KH, Hill DE, Wright AC, et al. Upstaging from melanoma in situ to invasive melanoma on the head and neck after complete surgical resection. Dermatol Surg. 2015; 41(10):1122-1125. 11. Karimipour DJ, Schwartz JL, Wang TS, et al. Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma. J Am Acad Dermatol. 2005;52(5):798-802. 12. Melanoma 2016. Available from: URL: http://www.nccn.org/ professionals/physician_gls/pdf/melanoma.pdf. Accessed January 15, 2016. 13. Veronesi U, Cascinelli N. Narrow excision (1-cm margin). A safe procedure for thin cutaneous melanoma. Arch Surg. 1991; 126(4):438-441. 14. Ringborg U, Andersson R, Eldh J, et al. Resection margins of 2 versus 5 cm for cutaneous malignant melanoma with a tumor thickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group. Cancer. 1996;77(9):1809-1814. 15. Khayat D, Rixe O, Martin G, et al. Surgical margins in cutaneous melanoma (2 cm versus 5 cm for lesions measuring less than 2.1-mm thick). Cancer. 2003;97(8):1941-1946. 16. Balch CM, Soong SJ, Smith T, et al. Long-term results of a prospective surgical trial comparing 2 cm vs 4 cm excision margins for 740 patients with 1-4 mm melanomas. Ann Surg Oncol. 2001;8(2):101-108. 17. Thomas JM, Newton-Bishop J, A’Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med. 2004;350(8): 757-766. 18. Gillgren P, Drzewiecki KT, Niin M, et al. 2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial. Lancet. 2011;378(9803):1635-1642. 19. Kelemen PR, Essner R, Foshag LJ, Morton DL. Lymphatic mapping and sentinel lymphadenectomy after wide local excision of primary melanoma. J Am Coll Surg. 1999;189(3): 247-252. 20. Ariyan S, Ali-Salaam P, Cheng DW, Truini C. Reliability of lymphatic mapping after wide local excision of cutaneous melanoma. Ann Surg Oncol. 2007;14(8):2377-2383. 21. Gannon CJ, Rousseau DL Jr, Ross MI, et al. Accuracy of lymphatic mapping and sentinel lymph node biopsy after previous wide local excision in patients with primary melanoma. Cancer. 2006;107(11):2647-2652. 22. Karakousis CP, Grigoropoulos P. Sentinel node biopsy before and after wide excision of the primary melanoma. Ann Surg Oncol. 1999;6(8):785-789. 23. McCready DR, Ghazarian DM, Hershkop MS, Walker JA, Ambus U, Quirt IC. Sentinel lymph-node biopsy after previous wide local excision for melanoma. Can J Surg. 2001;44(6): 432-434.
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24. Egnatios GL, Dueck AC, Macdonald JB, et al. The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma. Am J Surg. 2011;202(6):771-777. discussion 777-778. 25. Zager JS, Hochwald SN, Marzban SS, et al. Shave biopsy is a safe and accurate method for the initial evaluation of melanoma. J Am Coll Surg. 2011;212(4):454-460. discussion 460-462. 26. Kaiser S, Vassell R, Pinckney RG, Holmes TE, James TA. Clinical impact of biopsy method on the quality of surgical management in melanoma. J Surg Oncol. 2014;109(8):775-779. 27. Ng JC, Swain S, Dowling JP, Wolfe R, Simpson P, Kelly JW. The impact of partial biopsy on histopathologic diagnosis of cutaneous melanoma: experience of an Australian tertiary referral service. Arch Dermatol. 2010;146(3):234-239. 28. Tadiparthi S, Panchani S, Iqbal A. Biopsy for malignant melanomaeare we following the guidelines? Ann R Coll Surg Engl. 2008;90(4):322-325. 29. Ad Hoc Task Force. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012;67(4):531-550. 30. Christophel JJ, Johnson AK, McMurry TL, Park SS, Levine PA. Predicting positive margins in resection of cutaneous melanoma of the head and neck. Laryngoscope. 2013;123(3): 683-688. 31. Mangold AR, Skinner R, Dueck AC, Sekulic A, Pockaj BA. Risk factors predicting positive margins at primary wide local excision of cutaneous melanoma. Dermatol Surg. 2016;42(5): 646-652. 32. Hou JL, Reed KB, Knudson RM, et al. Five-year outcomes of wide excision and Mohs micrographic surgery for primary lentigo maligna in an academic practice cohort. Dermatol Surg. 2015;41(2):211-218. 33. Berdahl JP, Pockaj BA, Gray RJ, Casey WJ, Woog JJ. Optimal management and challenges in treatment of upper facial melanoma. Ann Plast Surg. 2006;57(6):616-620. 34. Rawlani R, Rawlani V, Qureshi HA, Kim JY, Wayne JD. Reducing margins of wide local excision in head and neck melanoma for function and cosmesis: 5-year local recurrence-free survival. J Surg Oncol. 2015;111(7):795-799. 35. Fisher SR, Seigler HF, George SL. Therapeutic and prognostic considerations of head and neck melanoma. Ann Plast Surg. 1992;28(1):78-80. 36. Harish V, Bond JS, Scolyer RA, et al. Margins of excision and prognostic factors for cutaneous eyelid melanomas. J Plast Reconstr Aesthet Surg. 2013;66(8):1066-1073. 37. Jones EL, Jones TS, Pearlman NW, et al. Long-term follow-up and survival of patients following a recurrence of melanoma after a negative sentinel lymph node biopsy result. JAMA Surg. 2013;148(5):456-461. 38. Bogle M, Kelly P, Shenaq J, Friedman J, Evans GR. The role of soft tissue reconstruction after melanoma resection in the head and neck. Head Neck. 2001;23(1):8-15. 39. Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical margins and prognostic factors in patients with thick ([4mm) primary melanoma. Ann Surg Oncol. 1998;5(4): 322-328. 40. Ravin AG, Pickett N, Johnson JL, Fisher SR, Levin LS, Seigler HF. Melanoma of the ear: treatment and survival probabilities based on 199 patients. Ann Plast Surg. 2006;57(1):70-76. 41. Gibbs P, Robinson WA, Pearlman N, Raben D, Walsh P, Gonzalez R. Management of primary cutaneous melanoma
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of the head and neck: the University of Colorado experience and a review of the literature. J Surg Oncol. 2001;77(3):179-185. discussion 186-187. 42. Neades GT, Orr DJ, Hughes LE, Horgan K. Safe margins in the excision of primary cutaneous melanoma. Br J Surg. 1993; 80(6):731-733. 43. Agnese DM, Maupin R, Tillman B, Pozderac RD, Magro C, Walker MJ. Head and neck melanoma in the sentinel lymph node era. Arch otolaryngol Head Neck Surg. 2007;133(11): 1121-1124. 44. Moehrle M, Kraemer A, Schippert W, Garbe C, Rassner G, Breuninger H. Clinical risk factors and prognostic significance of local recurrence in cutaneous melanoma. Br J Dermatol. 2004;151(2):397-406.
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45. Cohn-Cedermark G, Mansson-Brahme E, Rutqvist LE, Larsson O, Singnomklao T, Ringborg U. Outcomes of patients with local recurrence of cutaneous malignant melanoma: a population-based study. Cancer. 1997;80(8):1418-1425. 46. Sullivan SR, Liu DZ, Mathes DW, Isik FF. Head and neck malignant melanoma: local recurrence rate following wide local excision and immediate reconstruction. Ann Plast Surg. 2012;68(1):33-36. 47. Brochez L, Verhaeghe E, Grosshans E, et al. Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions. J Pathol. 2002;196(4):459-466. 48. Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol. 1996;27(6):528-531.
W
hen residual melanoma remains after the diagnostic biopsy, upstaging (defined as an increase in the T stage designated by the American Joint Committee on Cancer [AJCC] classification system for melanoma)1 might be detected after wide local excision in 5%-22% of cases.2-11 Upstaging might complicate patient counseling about prognosis and surgical management of melanoma. AJCC tumor stage is a powerful predictor of prognosis, with 10-year survival ranging from 93%
for T1a melanoma to 39% for T4b melanoma.1 Patients who are counseled about an excellent
From the Department of Dermatology, University of Pennsylvania Health System, Philadelphiaa; and Perelman School of Medicine, University of Pennsylvania, Philadelphia.b Funding sources: Drs Etzkorn and Sobanko are supported by a Dermatology Foundation Clinical Career Development Award in Dermatologic Surgery. Conflicts of interest: None declared. Accepted for publication March 16, 2017. Reprints not available from the authors.
Correspondence to: Jeremy R. Etzkorn, MD, Mohs and Reconstructive Surgery, Division of Dermatologic Surgery, University of Pennsylvania Health System, 3400 Civic Center Blvd, Philadelphia, Pennsylvania 19104. E-mail: jeremy.etzkorn@uphs. upenn.edu. Published online June 8, 2017. 0190-9622/$36.00 Ó 2017 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2017.03.018
Abbreviations used: AJCC: AUC: CI: LM: OR: SLNB:
American Joint Committee on Cancer appropriate use criteria confidence interval lentigo maligna odds ratio sentinel lymph node biopsy
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prognosis before surgery might be surprised and the cohort. Nonexcisional biopsy methods (shave, confused to learn of a worse prognosis if the tumor punch, or incisional) to diagnose melanoma are upstages after a wide local excision. more common than excisional biopsy in many Surgical management might also be complicated patient populations24,26,28 and have been noted to by upstaging because the Breslow depth, ulceration increase the risk for inaccurate microstaging.11,27 status, and mitotic rate from the diagnostic biopsy of This study adds to the work of previous authors a primary cutaneous melanoma dictate the surgical by examining the impact on upstaging of the widest excision margins and the inreported array of clinicodications for sentinel lymph pathologic risk factors in a CAPSULE SUMMARY node biopsy (SLNB).12 First, large cohort of melanomas diagnosed with a blend of if an inaccurate diagnostic Tumor upstaging after wide local excisional and nonexcisional biopsy leads to undertreatexcision complicates surgical preoperative biopsies, which ment with narrower surgical management of melanoma. might be more generalizable margins than those recomRisk factors for upstaging include tumor to many patient populamended by consensus guidelocation in cosmetically or functionally tions.24,26 The principal aims lines, patients might need sensitive areas, partial preoperative additional surgery either to of this study were to describe biopsies, older patient age, and clear the tumor or to comply the rate of upstaging after nonlentigo maligna histologic subtype. with wider margins recomwide local excision of mended for the upstaged tucutaneous melanoma and to The possibility of upstaging should be mor. Neither the randomized evaluate clinical and pathoconsidered during patient counseling trials that inform guidelines logic risk factors associated and surgical planning. for surgical management of with upstaging. Secondarily, primary cutaneous melawe aimed to describe how noma nor consensus guidelines address surgical frequently consensus recommendations for surgical margins after upstaging.12-18 Second, 1.3%-10% of management differ for discrepant tumor stages before and after wide local excision. upstaged tumors will meet criteria for SLNB.2,5,6,11 While some case series have demonstrated that SLNB can be performed after reconstruction, especially METHODS after linear repairs, with good sensitivity and rare Experimental design false negatives,19-21 the accuracy of SLNB after flap This retrospective cross-sectional study was and graft reconstruction remains uncertain.12,22,23 approved by the institutional review board at the Clarifying risk factors for upstaging is important to Hospital of the University of Pennsylvania. Inclusion help clinicians improve preoperative counseling criteria for this study were age $18 years, pathologic about prognosis and surgical management, particuT stage on diagnostic biopsy of in situ to T4a (T4b larly when deciding whether or not to delay were excluded because they have no risk for reconstruction for final staging of the wide local upstaging), biopsy-proven melanoma whose excision specimen.6 Current data about upstaging diagnostic biopsy and excision specimens were must often be gleaned from reports that focus interpreted by a board-certified dermatopathologist primarily on surgical technique2-4,6-9 or biopsy at the University of Pennsylvania from January 1, method.11,24-27 2008, through December 31, 2013, and initial Factors other than surgical technique and biopsy treatment with conventional wide local excision by method might independently increase the risk for a University of Pennsylvania Health System provider. upstaging. One previous study correlated microWide local excision was defined as excision of a staging accuracy with biopsy method as well as biopsy-proven melanoma with a margin of several other clinicopathologic factors.27 Compared clinically normal skin and immediate reconstruction, with excisional biopsy, punch and shave biopsy had followed by microscopic margin assessment via a significantly increased risk for inaccurate formalin-fixed, paraffin-embedded bread loaf tissue microstaging.27 Among partially biopsied lesions, sections. Eligible cases were identified via a search of tumor thickness (increased risk for thicker tumors) the Dermatopathology database for ‘‘melanoma’’ was the only clinicopathologic factor that and ‘‘lentigo maligna’’ (LM), which resulted in the significantly affected microstaging accuracy after identification of 7657 pathology reports containing multivariate analysis. However, these results might either term in the line diagnosis. Review of the not be generalizable because excision was the medical record identified 1332 melanomas that met method of biopsy in a high percentage (78.6%) of inclusion criteria for this study. Each melanoma d
d
d
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included in the study accounted for 2 (1 pathology report for the diagnostic biopsy and 1 for the wide local excision) of the 7657 reports. In addition, some melanomas had multiple preoperative biopsies and some pathology reports were from re-excisions for positive or equivocal margins. Most remaining cases were excluded because either the diagnostic biopsy or the wide local excision specimen was interpreted by a physician outside of the Penn health system. No a priori study size calculation was performed to determine the desired sample size. Data collection All data were recorded in a de-identified fashion in a RedCap database before statistical analysis. After verifying patient eligibility for this study, clinical notes and pathology reports from the diagnostic biopsies and wide local excisions for each patient were reviewed. The following data were recorded from the clinical notes and pathology reports: biopsy method, anatomic location, patient age at biopsy, personal history of melanoma, prior history of treatment, and histopathologic characteristics of the melanoma (presence or absence of residual melanoma in the excision specimen, invasive versus in situ disease, Breslow depth, mitotic rate, ulceration, regression, LM subtype versus other subtypes). If multiple pre-excision scouting biopsies had been performed, the number of scouting biopsies was recorded, and the tumor was classified according to the most advanced tumor stage. Data analysis Each case of melanoma was assessed for the presence of upstaging (defined as an increase in the T stage in the AJCC classification system for melanoma)1 after histopathologic evaluation of the wide local excision specimen. The frequency of upstaging was correlated with patient demographic characteristics, history of prior treatment, anatomic location (trunk and proximal extremities vs head, neck, hands, feet, genitals [including the nipple and areola], and pretibial leg), histopathologic characteristics of the melanoma (regression, ulceration, invasive vs in situ disease, and LM histologic subtype vs other subtypes), biopsy method (excisional vs other), and biopsy specimen margin positivity (lateral or deep) as assessed by histopathology. Anatomic locations were classified according to consensus guidelines for appropriate use criteria (AUC) of Mohs micrographic surgery: AUC-appropriate (head, neck, acral sites, genitalia [including nipple and areola], and pretibial leg) versus AUC-uncertain (trunk and proximal
extremities).29 Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Univariate logistic regression was used to identify potential risk factors for upstaging. Multivariate stepwise logistic regression with a prespecified cut off value of P $ .200 was then performed to reduce confounding. With each iteration of the stepwise regression analysis, the risk factor with the highest P value was sequentially removed from the multivariate model until no variables remained with a P value $ .200. All data analyses were performed using STATA version 13 (StataCorp, College Station, Texas).
RESULTS Table I shows the demographic and clinicopathologic features of the melanomas included in this study. Residual tumor and upstaging Upstaging was observed in 3.9% (52/1332) of melanomas overall and in 11.3% (52/460) of lesions with residual microscopic melanoma (in situ or invasive) in the wide local excision specimen. Residual invasive melanoma was seen in 12.8% (170/1332) of wide local excision specimens. Of these, 49% (83/170) had a deeper Breslow depth than the pre-excision diagnostic biopsies. Risk factors that were significantly associated with an increased risk for upstaging after multivariate analysis included anatomic location on the head, neck, hands, feet, genitals, or pretibial leg; multiple preoperative diagnostic biopsies; extension of melanoma to the base of the diagnostic biopsy; increasing patient age; and non-LM histopathologic subtype (Table II). Raw frequencies for upstaging were 12% (5/41) on the hands or feet and 12% (25/207) on the head or neck. Prior treatment and extension to the lateral margin of the diagnostic biopsy specimen were associated with an increased frequency of upstaging on univariate analysis but failed to remain significant predictors of upstaging after multivariate analysis. Statistically significant differences in rates of upstaging were not associated with excisional versus nonexcisional biopsy, sex, personal history of melanoma, regression, or in situ versus invasive disease. Specific changes in pathologic T staging that resulted in upstaging are shown in Table III. Of the melanomas with upstaging, 21% (11/52) became candidates for SLNB. Three additional melanomas did not change T stage but qualified for SLNB because of an increase in Breslow depth from \0.76 mm to 0.76-1 mm. Thus, of the 1019 melanomas with a Breslow depth of #0.75 mm
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Table I. Demographic data and clinicopathologic characteristics of melanomas included in this study Characteristics
Totals
Age, y Range 18-94 Mean 60.8 Median 62 Sex, % (n/total) Male 57.6 (767/1332) Female 42.4 (565/1332) Diagnostic biopsy T stage,* % (n/total) TIS 34.5 (459/1332) T1a (#1.0 mm without ulceration 37.0 (493/1332) or mitosis) T1b (#1.0 mm with ulceration 12.9 (172/1332) or mitosis) T2a (1.01-2.0 mm without 7.3 (97/1332) ulceration) T2b (1.01-2.0 mm with ulceration) 1.9 (25/1332) T3a (2.01-4.0 mm without 3.4 (45/1332) ulceration) T3b (2.01-4.0 mm with ulceration) 2.2 (29/1332) T4a ([4 mm without ulceration) 0.9 (12/1332) Location, % (n/total) Trunk and proximal extremity 79.2 (1055/1332) Pretibial leg 1.9 (25/1332) Head and neck 15.5 (207/1332) Hands and feet 3.1 (41/1332) Genitals 0.3 (4/1332) Total biopsies, n Range 1-7 Mean 1.09 Median 1 Residual melanoma present on wide local excision pathology, % (n/total)* Yes 34.2% (456/1332) In situ 63.4% (289/456) Invasive 36.6% (167/456) No 65.8% (876/1332) *T stage was based on the American Joint Committee on Cancer 7th edition.
noted on the diagnostic biopsy, 1.4% (14/1019) became candidates for SLNB. Of these 14 melanomas, 64% (9/14) were on the head, neck, hands, feet, genitals, or pretibial leg; 79% (11/14) had melanoma extending to the base of the diagnostic biopsy; 93% (13/14) had melanoma extending to the lateral margin of the diagnostic biopsy; and 29% (4/14) had multiple preoperative scouting biopsies. Of the melanomas with upstaging, 62% (32/52) had a T stage that warranted wider surgical margins than those recommended for the pre-excision tumor stage. Thus, of the 1246 in situ or stage T1 or T2 invasive melanomas, 2.6% (32/1246) upstaged to a T stage that warranted wider surgical margins than those recommended for the pre-excision tumor
stage. For these 32 melanomas, 56% (18/32) were on the head, neck, hands, feet, genitals, or pretibial leg; 59% (20/32) had melanoma extending to the base of the diagnostic biopsy; 91% (29/32) had melanoma extending to the lateral margin of the diagnostic biopsy; and 19% (6/32) were biopsied with multiple scouting biopsies.
DISCUSSION This study evaluated 1332 melanomas treated with wide local excision to correlate the risk for upstaging with the largest reported array of clinicopathologic risk factors. Compared with the diagnostic biopsies, wide local excision specimens were more likely to contain a higher tumor stage when cutaneous melanomas had the following independent risk factors: anatomic location on the head, neck, hands, feet, genitals, or pretibial leg; multiple preoperative diagnostic biopsies; extension of melanoma to the base of the diagnostic biopsy; increasing patient age; and non-LM histopathologic subtype. These findings are helpful to guide preoperative prognostic counseling and surgical management of melanoma. Despite National Comprehensive Cancer Network guidelines recommending narrow excision with 1-3 mm margins as the preferred method to biopsy lesions suspicious for melanoma,12 only 10% of cases in our cohort had a preoperative excisional diagnostic biopsy. This low rate of excisional biopsies is consistent with previously published cohorts.24,26 Biopsy method (ie, excision versus nonexcision) was not significantly associated with an increased frequency of upstaging in our cohort (P = .068, 95% CI 0.87-51.7). However, extension of the melanoma to the base of the biopsy and multiple diagnostic scouting biopsies, factors that indicated a subtotal biopsy, were significant predictors of an increased risk for upstaging after multivariate analysis. Extension of melanoma to the lateral aspect of the pre-excision biopsy specimen was a significant predictor in univariate analysis, but it failed to remain a significant predictor after multivariate analysis, possibly because of confounding with these other markers of subtotal biopsies. Our data indicate that subtotal biopsy, regardless of the biopsy method or number of scouting biopsies, has an increased risk for upstaging. This finding is consistent with prior studies that showed a correlation between partial sampling of a lesion and higher rates of upstaging.11,27 Anatomic location on the head, neck, hands, feet, genitals, or pretibial leg was the strongest predictor of upstaging (OR 7.06, 95% CI 3.77-13.25). A logical supposition might be that the more than 7-fold
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Table II. Clinical and histopathologic characteristics associated with upstaging
Risk factors
Frequency of upstaging (%)
Location Head, neck, hands, feet, genitals, 12 (33/277) or pretibial leg Trunk and proximal extremities 1.8 (19/1055) Sexz Male 4.3 (33/767) Female 3.4 (19/565) Personal history of melanomaz Yes 3.6 (12/337) No 4.0 (40/995) Previously treated Yes 15 (3/20) No 3.7 (49/1312) Number of preoperative biopsies No cut off N/a Age No cut off N/a In situ or invasive melanomaz Invasive 4.1 (36/873) In situ 3.5 (16/459) Lentigo maligna type Yes 3.2 (9/280) No 4.0 (43/1065) Regressionz Present 3.4 (7/205) Not present 4.0 (45/1127) Extends to base of biopsy specimen Yes 8.2 (32/389) No 2.1 (20/943) Extends to lateral margin of biopsy specimenz Yes 4.5 (45/990) No 2.0 (7/342) Biopsy type Nonexcisional 4.2 (51/1201) Excisional 0.8 (1/131)
Multivariate analysis with stepwise regression
Univariate analysis OR
95% CI
P value*
7.37
4.12-13.2
\.001
1.00y
-
1.29 1.00y
0.73-2.30 -
0.88 1.00y
OR
95% CI
P value*
7.06
3.77-13.25
\.001
1.00y
-
.383
-
-
-
0.46-1.70 -
.707
-
-
-
4.55 1.00y
1.29-16.0 -
.018
-
-
-
2.13
1.41-3.23
\.001
1.89
1.23-2.93
.004
1.03
1.01-1.05
.003
1.03
1.01-1.06
.002
1.19 1.00y
0.65-2.17 -
.568
-
-
0.78 1.00y
0.38-1.62 -
.504
0.28 -
0.12-0.64 -
0.85 1.00y
0.38-1.91 -
.694
-
-
-
4.13 1.00y
2.34-7.33 -
\.001
3.24 1.00y
1.76-5.96 -
\.001
2.28 1.00y
1.02-5.10 -
.045
-
-
-
5.77 1.00y
0.79-42.1 -
.084
6.12 -
0.81-37.8 -
-
.002
.080 -
CI, Confidence interval; N/a, not applicable; OR, odds ratio. *Logistic regression P value. y Reference category for comparison to calculate odds ratios. z Removed from multivariate analysis because of low significance (P [ .2) during stepwise logistic regression analysis.
increased odds of upstaging occurred because excisional biopsies were less common or less practical in these locations, excisional biopsy was actually slightly more prevalent (11%, 31/278) on the head, neck, hands, feet, genitals, or pretibial leg than on the trunk and proximal extremities (9.7%, 103/1067) in our cohort. However, excisional biopsies were less likely to have negative margins (both deep and lateral) for melanomas on the head, neck, hands, feet, genitals, or pretibial leg (26%, 8/31) versus those on the trunk and proximal extremities (54%, 54/100). The increased risk for upstaging, whatever the method of biopsy, adds to
the well-documented challenges of positive margins30-33 and local recurrence16,33-46 after wide local excision of melanomas on the head, neck, hands, feet, genitals, or pretibial leg. An explanation for the significance of the risk factors old age (OR 1.03, 95% CI 1.01-1.06, P = .002) and non-LM histopathologic subtype (OR 0.28, 95% CI 0.12-0.64, P = .002) is unclear. More severe background actinic damage with older age might increase the difficulty of discerning the most aggressive portion of a melanocytic tumor by clinical examination. LM melanomas might be more likely to have a more uniform Breslow depth compared with
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Table III. Changes in T staging that resulted in upstaging Initial T stage
T0 (in situ)
T1a
T1b T2a
T2b
T3a
Final T stage
N
Increase in recommended surgical margin
Upstaged to candidacy for SLNB
T1a T1b T4b T1b T2a T4a T2a T3a T2b T3a T4a T3a T3b T4b T3b T4a T4b
12 3 1 3 4 1 7 3 2 4 4 2 1 1 1 2 1
12 3 1 0 0 1 0 3 0 4 4 2 1 1 N/a N/a N/a
2 0 1 2 2 1 2 1 N/a N/a N/a N/a N/a N/a N/a N/a N/a
N/a, Not applicable; SLNB, sentinel lymph node biopsy.
other histologic subtypes, but these explanations remain purely speculative and merit further study. Of the 52/1332 (3.9%) upstaged melanomas in our cohort, 62% (32/52) warranted wider recommended surgical margins than those for the pre-excision tumor stage, and 21% (11/52) become candidates for SLNB. For melanomas at high risk for upstaging, delaying reconstruction until after histopathologic evaluation of the excisional specimen might be prudent to ensure that appropriate surgical margins are excised before definitive reconstruction. Delaying reconstruction with local flaps or skin grafts might also be judicious because the validity of SLNB after these reconstructions remains uncertain.12,22,23 Patients at high risk for upstaging might also benefit from preoperative counseling about alternative surgical approaches, such as undergoing a complete excisional biopsy before definitive excision and reconstruction or Mohs surgery with frozen-section bread loaf sectioning of the debulking specimen, which permits accurate and timely identification of upstaging before tissue rearrangement.6 Limitations of our study include the single-center, retrospective nature of our cohort. Our data are from a tertiary academic center, where patients often receive SLNB, which likely has a skewed sample with more invasive melanomas compared with the general population. The observed frequency of excisional biopsy in our cohort was 10%, which might not reflect the percentages seen at other institutions or in other regions. We were unable to assess the presence or absence of clinically visible residual lesions before excision or the percentage of the clinically visible lesions that was sampled with
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