Prognostic Significance of Periadnexal Extension in Cutaneous Melanoma and its Implications for Pathologic Reporting and Staging

Tumor thickness is the strongest predictor of outcome for clinically localized melanoma. Therefore, accurate assessment is critical for appropriate staging, reliable estimation of prognosis, and management. When melanoma extends alongside skin adnexal structures more deeply than the main tumor mass (periadnexal extension), it is currently unknown whether the prognosis is more accurately reflected by the deepest point of periadnexal tumor extension or the main tumor mass. This study sought to address this question. Survival outcomes of 257 primary cutaneous melanoma patients with periadnexal extension diagnosed between 2005 and 2015 and managed at Melanoma Institute Australia were identified and compared with a control cohort of 514 patients who were matched for tumor thickness, sex, age, mitotic rate, ulceration status, and year of diagnosis but lacked periadnexal extension. The incidence of periadnexal extension at Melanoma Institute Australia was 1.5% (257/16,692 cutaneous melanomas diagnosed between 2005 and 2015). The patient characteristics between the 2 groups were otherwise very similar; median Breslow thickness was 0.9 mm for the periadnexal group and 1.0 mm for the control group. The median extension beyond the Breslow thickness in the tumors with periadnexal extension was 0.45 mm (mean, 0.4 mm). Median follow-up was 46 months for the periadnexal group and 44 months for the control group. Measures of clinical outcomes all showed trends for improved survival in the periadnexal extension group; these were melanoma-specific survival (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.44, 1.38), overall survival (HR, 0.91; 95% CI, 0.59, 1.41), disease-free survival (HR, 0.68; 95% CI, 0.45, 1.03), and distant disease-free survival (HR, 0.69; 95% CI, 0.4, 1.17), although none were statistically significant. There was a higher rate of sentinel lymph node (SLN) metastasis in the periadnexal group versus the control group in patients whose tumors were >1 mm thick (24/100=24% vs. 23/187=12.3%). Periadnexal extension was significantly associated with SLN metastasis on univariate logistic regression analysis (odds ratio [95% CI], 2.25 [1.20, 4.24], P=0.01). If the periadnexal extension had been included in the measurement of tumor thickness, 42.8% of patients would have been upstaged to a higher American Joint Committee on Cancer T category. The findings of this study indicate that periadnexal involvement that extends more deeply than the thickness of the main tumor mass increases the risk of SLN metastasis in tumours >1 mm thick, however, does not worsen clinical outcomes overall, and tumor thickness measurements should not include deeper foci of periadnexal tumor. J.F.T. is supported by the Melanoma Foundation of the University of Sydney. T.J.D. is supported by the Jani Haenke Melanoma Pathology Fellowship through the BB and A Miller Foundation and MIA. R.A.S. is supported by an Australian National Health and Medical Research Council Fellowship. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Richard A. Scolyer, MD, FRCPA, FRCPath, Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW 2050, Australia (e-mail: richard.scolyer@health.nsw.gov.au). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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