Analysis of sentinel lymph node positivity in patients with thin primary melanoma

doi:10.1016/j.jaad.2012.08.045

Journal of the American Academy of Dermatology

Volume 68, Issue 4, April 2013, Pages 560-567

https://doi.org/10.1016/j.jaad.2012.08.045 Get rights and content

Background

A minority of patients with T1 melanoma will have a positive sentinel lymph node (SLN) biopsy (SLNB) finding. Identifying who will develop metastatic disease is important in determining prognosis and treatment.

Objective

We sought to identify clinical and histologic features predictive of a positive SLNB result and determine its prognostic significance in patients with T1 melanoma.

Methods

Clinical and histologic parameters were evaluated in 484 patients with T1 melanoma for their ability to predict a positive SLNB result. The impact of various factors on SLN positivity was evaluated. SLN status was examined as a predictor of overall survival.

Results

In all, 34 patients had a positive SLNB finding. Four factors predicted a higher risk of SLN positivity: age 43 years or younger, Breslow depth 0.8 mm or greater, tumors on the lower extremity and trunk, and tumor-infiltrating lymphocyte level. By multivariate analysis, low tumor-infiltrating lymphocytes (P = .0015) and decreasing age (P = .0058) independently predicted SLN positivity. If 0 to 2 of these factors were present, the rate of a positive SLNB result was 3%; this increased to 15% with 3 factors present and to 30% if all 4 factors were present (P < .002). SLN-positive patients had significantly decreased survival (P = .003), and SLN status was the most powerful predictor of survival (P = .009).

Limitations

Our data analysis includes patients from 1994 to 2007 and therefore information on mitotic rate, a recently defined T1b criterion, is not recorded for all patients.

Conclusions

Combining clinical and histologic prognostic factors may help identify subgroups of T1 patients at higher risk of SLN positivity. SLN status has significant prognostic impact in patients with thin melanomas.

Section snippets

Methods

This analysis was approved by the institutional review board at the University of California, San Francisco. From 1994 to 2007, patients referred to the University of California, San Francisco/Mount Zion Melanoma Center who had thin melanomas (defined as ≤1.0 mm) and high-risk histologic features were offered SLNB in addition to standard re-excision of the primary site. The following histologic features were recorded and evaluated: Breslow depth, Clark level, ulceration, MR, tumor vascularity,

Results

Table I shows the characteristics of the 484 patients included in our analysis. Of the 484 patients with T1 melanoma, 52.1% were T1a, 40.7% T1b, and 7.2% not classifiable. The mean age of the cohort was 52.2 years, with a mean Breslow depth of 0.80 mm, and a mean follow-up of 4.53 years. The majority of the melanomas were located on the trunk (43.8%), followed by the head and neck (19.6%), lower extremity (19.8%), and upper extremity (16.7%). Ulceration was present in 10.7% of primaries. Of the

Discussion

The revised AJCC staging classification for melanoma now includes MR as a T1b-defining feature (along with ulceration), and has replaced Clark level.¹⁷ T1b melanomas have a decreased survival, so a discussion about SLNB may ensue with the patient. In thin melanomas, the prevalence of SLN metastasis has been reported in the range of 0% to 8.3%,10, 18, 19, 20, 21, 22, 23, 24 with T1b lesions accounting for the majority, but certainly not all, SLN-positive cases. Therefore, it is important to

Conclusion

Our analysis identified 4 factors predictive of an increased risk of SLN metastasis. These results highlight the importance of TILs within the primary melanoma as a predictor of SLN status. There is a steady body of evidence showing the importance of TILs for melanoma prognosis at all stages of disease and in the treatment of late-stage melanoma. We propose that TIL level also be included in the synoptic report of all primary melanomas. Data presented in this format can then be studied in a

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Cited by (53)

Predictors of sentinel lymph node positivity in thin melanoma using the National Cancer Database
2019, Journal of the American Academy of Dermatology
Citation Excerpt :
Our finding that patients <60 years of age with thin melanomas are more likely to have positive SLN are in accordance with a recent study evaluating regional lymph nodes in patients from the NCDB.13 Several other studies have also found an inverse correlation between patient age and SLN positivity.14-18 Male sex was associated with a higher risk of SLN positivity among the NCDB cohort and some previous studies.
Sentinel lymph node biopsy (SLNB) specimens are often obtained from patients for further staging after these patients have undergone melanoma excision. Limited data regarding predictors of SLNB positivity in thin melanoma are available.
We sought to evaluate predictors of SLNB positivity in thin melanoma.
Patients with cutaneous melanoma with a Breslow thickness ≤1.00 mm who received a SLNB were identified from the National Cancer Database between 2004 and 2014 (n = 9186). Predictors of SLNB positivity were analyzed using logistic regression.
In a multivariate analysis, patients <60 years of age (P < .001) and Breslow thickness >0.8 mm (P = .03) were at increased risk for positive sentinel lymph node (SLN). Moreover, on multivariate analysis, the presence of dermal mitoses increased the odds of SLN positivity by 95% (odds ratio [OR] 1.95 [95% confidence interval {CI} 1.53-2.5], P < .001), ulceration by 63% (OR 1.63 [95% CI 1.21-2.18], P < .001), and Clark level IV to V by 48% (OR 1.48 [95% CI 1.19-1.85]). Patients without ulceration but with dermal mitoses had 92% (OR 1.92 [95% CI 1.5-2.48], P < .001) increased SLN positivity.
Limited survival data are available.
Younger age, a Breslow thickness >0.8 mm, the presence of dermal mitoses, ulceration, and Clark level IV to V are positive predictors of positive SLN. While the new American Joint Committee on Cancer system has removed dermal mitotic rate from staging, continued evaluation of dermal mitotic rate could be valuable for guiding surgical decision making about SLNB.
Guidelines of care for the management of primary cutaneous melanoma
2019, Journal of the American Academy of Dermatology
Citation Excerpt :
The WG recommends discussion of SLNB in patients with T1b CM, defined per the eighth edition of the AJCC staging system as less than 0.8 mm with ulceration or 0.8 to 1.0 mm with or without ulceration, although overall rates of SLN positivity in this subset of patients are still relatively low (≤10%). Rates of SLN positivity in T1a CM (<0.8 mm without ulceration) are generally less than 5%.151,152 Therefore, the WG does not recommend SLNB for patients in the T1a subgroup unless other histologic adverse features are evident.2,153,154
The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer–related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.
Current controversies in early-stage melanoma: Questions on management and surveillance
2019, Journal of the American Academy of Dermatology
Citation Excerpt :
While the prognosis for patients with early-stage melanoma is excellent, ≤5% of patients with minimally invasive (<0.8 mm) stage I disease will ultimately develop distant metastatic disease,8 and such cases are responsible for the majority of deaths from melanoma.45-47 As a prognostic test, the SLNB identifies patients with a higher risk of death from thin melanoma.48-50 However, SLNB may not be predictive for patients who develop metastasis through hematogenous spread not involving the regional lymph nodes.
There are a number of controversies and uncertainties relating to the management and surveillance of patients with early-stage, localized (ie, stage 0, I, and II) cutaneous melanoma. While tumor stage is a critical predictor of clinical outcome and guides treatment, accurate determination of stage may be affected by the biopsy technique used and the method of sectioning before histologic review. A new molecular prognostic test is available but has not been formally incorporated into staging or treatment guidelines. There are no randomized controlled clinical trials to support guidelines for surveillance following the treatment of early-stage melanoma. In the second article in this continuing medical education series, we review the controversies and uncertainties relating to these issues. The questions we address are controversial because they speak to clinical scenarios for which there are no evidence-based guidelines or randomized clinical trials with the consequence of considerable variability in clinical practice. Our goal is to provide the clinician with up-to-date contextual knowledge to appreciate the multiple sides of each controversy and to suggest pathways to resolution.
Mitotic rate is associated with positive lymph nodes in patients with thin melanomas
2018, Journal of the American Academy of Dermatology
Citation Excerpt :
Most notably, 1 single-center study of 1764 melanomas did observe a significant association between tumor mitotic rate and overall survival in unadjusted analyses.22 Other studies have failed to observe statistically significant associations between mitotic rate and lymph node positivity among thin melanomas; however, these were likely underpowered, as the largest had only 484 cases.14,23-25 Our study included more than 17,000 patients with thin melanoma who underwent a SLNB and had data on mitotic rate, finding a strong correlation between mitotic rate and lymph node positivity.
The American Joint Commission on Cancer will remove mitotic rate from its staging guidelines in 2018.
Using a large nationally representative cohort, we examined the association between mitotic rate and lymph node positivity among thin melanomas.
A total of 149,273 thin melanomas in the National Cancer Database were examined for their association of high-risk features of mitotic rate, ulceration, and Breslow depth with lymph node status.
Among 17,204 patients with thin melanomas with data on Breslow depth, ulceration, and mitotic rate who underwent a lymph node biopsy, there was a strong linear relationship between odds of having a positive lymph node and mitotic rate (R² = 0.96, P < .0001, β = 3.31). The odds of having a positive node increased by 19% with each 1-point increase in mitotic rate (odds ratio, 1.19; 95% confidence interval, 1.17-1.21). Cases with negative nodes had a mean mitotic rate of 1.54 plus or minus 2.07 mitoses/mm² compared with 3.30 plus or minus 3.54 mitoses/mm² for those with positive nodes (P < .0001).
The data collected do not allow for survival analyses.
Mitotic rate was strongly associated with the odds of having a positive lymph node and should continue to be reported on pathology reports.
Sentinel lymph node biopsy in cutaneous melanoma: An update and controversies
2018, Piel
Computer-assisted measurement of primary tumor area is prognostic of recurrence-free survival in stage IB melanoma patients
2017, Modern Pathology
Current staging guidelines are insufficient to predict which patients with thin primary melanoma are at high risk of recurrence. Computer-assisted image analysis may allow for more practical and objective histopathological analysis of primary tumors than traditional light microscopy. We studied a prospective cohort of stage IB melanoma patients treated at NYU Langone Medical Center from 2002 to 2014. Primary tumor width, manual area, digital area, and conformation were evaluated in a patient subset via computer-assisted image analysis. The associations between histologic variables and survival were evaluated using Cox proportional hazards model. Logistic regressions were used to build a classifier with clinicopathological characteristics to predict recurrence status. Of the 655 patients with stage IB melanoma studied, a subset of 149 patient tumors (63 recurred, 86 did not recur) underwent computer-assisted histopathological analysis. Increasing tumor width (hazard ratios (HR): 1.17, P=0.01) and digital area (HR: 1.08, P<0.01) were significantly associated with worse recurrence-free survival, whereas non-contiguous conformation (HR: 0.57, P=0.05) was significantly associated with better recurrence-free survival. The novel histopathological classifier composed of digital area, conformation, and baseline variables effectively distinguished recurrent cases from non-recurrent cases (AUC: 0.733, 95% confidence interval (CI): 0.647–0.818), compared to the baseline classifier alone (AUC: 0.635, 95% CI: 0.545–0.724). Primary tumor cross-sectional area, width, and conformation measured via computer-assisted analysis may help identify high-risk patients with stage IB melanoma.

View all citing articles on Scopus

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: Conflicts of interest: None declared.

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Original articleAnalysis of sentinel lymph node positivity in patients with thin primary melanoma

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Methods

Results

Discussion

Conclusion

Cancer statistics, 2007

CA Cancer J Clin

Cancer staging handbook

Final version of 2009 AJCC melanoma staging and classification

J Clin Oncol

Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma

J Clin Oncol

Primary cutaneous melanoma: optimized cutoff points of tumor thickness and importance of Clark's level for prognostic classification

Cancer

Impact of ulceration in stages I to III cutaneous melanoma as staged by the American Joint Committee on Cancer staging system: an analysis of the German central malignant melanoma registry

J Clin Oncol

Prognostic factors of thin cutaneous melanoma: an analysis of the central malignant melanoma registry of the German Dermatological Society

J Clin Oncol

Thin melanomas: predictive lethal characteristics from a 30-year clinical experience

Ann Surg

The prognostic importance of sentinel lymph node biopsy in thin melanoma

Ann Surg Oncol

Sentinel-node biopsy or nodal observation in melanoma

N Engl J Med

Vascular involvement in the prognosis of primary cutaneous melanoma

Arch Dermatol

Tumor vascularity in the prognostic assessment of primary cutaneous melanoma

J Clin Oncol

Cancer staging handbook

Learning and understanding the Kruskal-Wallis one-way analysis-of-variance-by-ranks test for differences among three or more independent groups

Phys Ther

Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system

J Clin Oncol

Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database

J Clin Oncol

Incidence of sentinel node metastasis in patients with thin primary melanoma (< or = 1 mm) with vertical growth phase

Ann Surg Oncol

Role of sentinel lymph node biopsy in patients with thin (<1 mm) primary melanoma

Ann Surg Oncol

Sentinel lymph node biopsy in patients with thin melanoma

Arch Dermatol

Prediction of sentinel lymph node micrometastasis by histologic features in primary cutaneous malignant melanoma

Arch Dermatol

Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas

Ann Surg Oncol

Predictors of sentinel lymph node metastasis in melanoma

Can J Surg

Prognostic factors associated with sentinel lymph node positivity and effect of sentinel status on survival: an analysis of 1049 patients with cutaneous melanoma

Melanoma Res

Thin primary cutaneous malignant melanoma: a prognostic tree for 10-year metastasis is more accurate than American Joint Committee on Cancer staging

J Clin Oncol

Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales central cancer registry and the Sydney melanoma unit

Cancer

Original article
Analysis of sentinel lymph node positivity in patients with thin primary melanoma