Kalady MF, White RR, Johnson JL et al.Thin melanomas: predictive lethal characteristics from a 30-year clinical experience.. Ann Surg 238:528-537

Department of Surgery, Duke University Medical Center Durham, North Carolina 27710, USA.
Annals of Surgery (Impact Factor: 8.33). 10/2003; 238(4):528-35; discussion 535-7.
Source: PubMed


To guide treatment and clinical follow-up by defining the natural history of thin melanomas and identifying negative prognostic characteristics that may delineate high-risk patients.
In following > 10,000 patients with cutaneous melanoma over the past 30 years, our institution has observed nodal or metastatic disease in approximately 15% of patients with a thin (<1 mm) primary lesion.
A database query of patients with cutaneous melanoma returned 1158 patients with primary lesion < or = 1 mm thick and who received their initial treatment at a single institution. Median follow-up was 11 years (range, 1 to 34 years). Patient and melanoma characteristics as well as outcomes were recorded and statistically analyzed.
6.6% of patients had nodal or distant disease at presentation. Over time, an additional 9.4% developed metastases, including nodal and distal recurrences. Overall incidence of advanced disease was 15.3%. Univariate analysis identified male gender (P = 0.01), advanced age (>45 years; P = 0.05), and Breslow thickness (>0.75 mm; P = 0.008) as significant negative prognostic characteristics. Of patients with these 3 high-risk characteristics, 19.7% developed advanced disease (likelihood ratio 6.3; P = 0.007 versus nonhigh-risk patients). This group had more than twice the incidence of nodal recurrences. Patients with recurrence had significantly decreased 10-year survival (82% versus 45%; P < 0.0001). Surprisingly, neither ulceration nor Clark level predicted advanced disease.
Thin melanomas are potentially lethal lesions. Long-term follow-up identified a high-risk population of older males with tumors between 0.75 mm and 1.0 mm whose risk of recurrent disease approaches 20%. Traditionally accepted negative prognostic factors such as ulceration and discordant Clark levels are not predictive for metastasis in this population. Given the poor prognosis associated with recurrent disease, we recommend close clinical evaluation and follow-up to maximize accurate staging and therapeutic options.

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    • "About 3–5% of patients with thin melanoma (≤1.0 mm) develop distant metastases (Kalady et al, 2003). Additional prognostic markers could be valuable to enable more accurate stratification of such patients with regard to survival, clinical management and follow-up regimens (Murali et al, 2012). "
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    ABSTRACT: Background: Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients. Methods: TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion. Results: A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P=0.005 and 0.01, respectively), increased Breslow thickness (Spearman's rho test, P<0.001) and the presence of ulceration (Mann–Whitney test, P=0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P-value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups. Conclusion: High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.
    Full-text · Article · Mar 2013 · British Journal of Cancer
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    • "On the one hand, the ramatic mismatch between increases in detection and mortality rates (report, 2010) may suggest significant overcalling (Glusac, 2011; Swerlick and Chen, 1996). On the other hand, nearly one in ten patients with thin melanomas (<1 mm) and no initial evidence of metastases develops recurrences (Kalady, White et al. 2003) – and there are no good markers to suggest which ones. Melanin chemistry is a natural biomarker of melanocyte activity, and is a promising marker to differentiate benign, dysplastic, and malignant pigmented lesions (Sealy et al, 1982; Lazova and Pawelek, 2009; Marchesini et al, 2009; Biesemeier et al, 2011). "
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    ABSTRACT: Pump-probe microscopy non-destructively differentiates eumelanin and pheomelanin and can be used to quantify melanin distributions in thin biopsy slices. Here we have extended that work for imaging eumelanin and pheomelanin distributions on a sub-cellular scale, allowing elucidation of characteristics of different cell types. The results show that melanin heterogeneity, previously found to be characteristic of melanomas, persists on the sub-cellular scale. We have also found spectral changes associated with melanin located in melanophages, which could potentially differentiate invasive pigmented melanocytes from melanophages without immunohistochemical staining.Journal of Investigative Dermatology accepted article preview online, 25 January 2013;doi:10.1038/jid.2013.37.
    Preview · Article · Jan 2013 · Journal of Investigative Dermatology
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    • "Well-characterized clinical prognostic markers such as tumor thickness and ulceration only partly explain the variability in the clinical course of melanoma. Patients with thin melanoma <1 mm, characterized as having a favorable prognosis, have reported rates of metastasis ranging from 3-22% [1]. Conversely, patients with thicker lesions not uncommonly have extended periods of disease-free survival. "
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    ABSTRACT: Increased levels of cryptic collagen epitope HU177 in the sera of melanoma patients have been shown to be associated with thicker primary melanomas and with the nodular histologic subtype. In this study, we investigate the association between HU177 shedding in the sera and clinical outcome in terms of disease-free survival (DFS) and overall survival (OS). Serum samples from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (mean age = 58, mean thickness = 2.09 mm, stage I = 136, stage II = 41, stage III = 32, median follow-up = 54.9 months) were analyzed for HU177 concentration using a validated ELISA assay. HU177 serum levels at the time of diagnosis were used to divide the study cohort into two groups: low and high HU177. DFS and OS were estimated by Kaplan-Meier survival analysis, and the log-rank test was used to compare DFS and OS between the two HU177 groups. Multivariate Cox proportional hazards regression models were employed to examine the independent effect of HU177 category on DFS and OS. HU177 sera concentrations ranged from 0-139.8 ng/ml (mean and median of 6.2 ng/ml and 3.7 ng/ml, respectively). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. Higher HU177 serum level was associated with an increased rate of melanoma recurrence (p = 0.04) and with increasing mortality (p = 0.01). The association with overall survival remained statistically significant after controlling for thickness and histologic subtype in a multivariate model (p = 0.035). Increased shedding of HU177 in the serum of primary melanoma patients is associated with poor prognosis. Further studies are warranted to determine the clinical utility of HU177 in risk stratification compared to the current standard of care.
    Full-text · Article · Feb 2010 · Journal of Translational Medicine
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