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

ArticleinAnnals of Surgery 238(4):528-35; discussion 535-7 · October 2003with23 Reads
Source: PubMed
Abstract
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.
    • "Vice versa, the prognostic value of the current dataset is enhanced by the fact that all patients underwent surgery at least once for histologic confirmation of brain metastasis. Thin T1 melanomas have an excellent prognosis; the range of melanoma associated deaths reported in the literature however is substantial (1–8% at 10 years [7,[16][17][18]). In addition, many studies regarding melanoma recurrence and survival are reported with end points of 5 to 10 years. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Brain metastasis is a common endpoint in patients suffering from malignant melanoma. However, little is known about factors that predispose to brain metastases. Objective: We performed a retrospective clinical and pathological investigation of melanoma patients with brain metastases in order to better characterise this patient population. Methods: 193 melanoma patients with brain metastasis histologically diagnosed between 1990 and 2015 at the University Hospital Zurich were retrospectively identified and further specified for sex, age at diagnosis and detection of brain metastasis, and localisation. In addition, data were extracted regarding the subtype of primary melanoma, Breslow tumour thickness, Clark Level, mutation status, extent of metastatic spread and history of a second melanoma. Results: We found a significant male predominance (n = 126/193; 65%; p < 0.001). Breslow tumour thickness showed a wide range from 0.2 to 12.0 mm (n = 99; median 2.3 mm). 14 of 101 melanomas (14%) were classified as T1, thereof 11 (79%) were found in men. In 32 of 193 patients (17%), the primary melanoma was unknown. Conclusions: Of special interest in our series is the high incidence of male predominance (79%) in cases of thin metastasing melanoma (14%), implicating genetic or epigenetic (hormonal) gender differences underlying tumour progression. Additionally, the high percentage of unknown primary melanoma (17%), at least partly representing completely regressed melanomas, indicates the importance of immune surveillance in melanoma progression.
    Full-text · Article · May 2016
    • "Melanoma has long been recognized as a highly heterogeneous disease910. It has been shown that approximately 50% of patients develop metastases within 15 years after treatment of the primary melanoma, and the occurrence rate of metastasis is 15% in patients with a thin (<1 mm) melanoma after their initial treatment [11]. However, the currently used AJCC (American Joint Committee of Cancer) staging system, which is based on clinical and histological parameters, although highly useful as a general guideline for prognostication, cannot precisely define such metastasis/mortality risks in many cases. "
    [Show abstract] [Hide abstract] ABSTRACT: Primary melanoma, a highly aggressive malignancy, exhibits heterogeneity in biologic behaviors, clinical characteristics, metastasis potential and mortality. The present study sought to identify the molecular signatures that define a subgroup of primary melanomas with high risks of metastasis and mortality. First, we identified the markers that best differentiated metastatic melanomas from primary melanomas by examining the expression of seven previously reported biomarkers (BRAF, Dicer, Fbw7, KAI1, MMP2, p27 and Tip60) in a training cohort consisting of 145 primary melanomas and 105 metastatic melanomas. KAI1 and p27, both tumor suppressors, emerged as best candidates. Loss of both tumor suppressors occurred in the majority (74.29%) of metastatic melanomas. Further, a subset (metastatic like, or “ML”, 33.10%) of primary melanomas also lost these two tumor suppressors. Kaplan-Meier analysis indicated that ML subgroup of primary melanoma patients had much worse 5 year survival compared with other primary melanoma patients (P = 0.002). The result was confirmed in an independent validation cohort with 92 primary melanomas (P = 0.030) and in the combined cohort with 237 melanoma patients (P = 3.00E-4). Additionally, compared to KAI1 and p27 as an individual prognostic marker, the combined signature is more closely associated with melanoma patient survival (P = 0.025, 0.264 and 0.009, respectively). In conclusion, loss of both KAI1 and p27 defines a subgroup of primary melanoma patients with poor prognosis. This molecular signature may help in metastatic melanoma diagnosis and may provide information useful in identifying high-risk primary melanoma patients for more intensive clinical surveillance in the future.
    Full-text · Article · Jul 2015
    • "Except for stage 0 patients, in which surgery ensured healing and postoperative surveillance, it was only required to catch the event of a new MM occurrence (a risk of 3-5%), all the other patients with invasive MM might develop metastases, the greater the percentage, the more advanced the stage at diagnosis. The worry lies however in the fact that 5-15% of the patients with thin MM (tumor thickness < 1mm) develop metastases [5,6]. Recent data support the hypothesis that MM has a simultaneous lymphatic and hematogenous spread, with the potential to metastasize in any organ, but in different percentages. "
    [Show abstract] [Hide abstract] ABSTRACT: Malignant melanoma (MM) is the cutaneous neoplasia with the greatest mortality rates and one of the malignancies with the highest potential of dissemination. The prognosis of patients with metastatic MM is grim, with a 5-years survival rate between 5-19%, and is dictated by the location and the number of metastases. We aimed to estimate the survival of patients with metastatic MM from our study and find out if the metastasis' location influences survival. Between 2008 and 2013, 155 patients with cutaneous MM were diagnosed in our clinic. All the patients were staged according to 2009 AJCC staging system. The median follow-up period was of 24 months. Survival was calculated by using the Kaplan-Meier method with a confidence level of 95%. 40.5% of the patients developed metastases in different organs, especially the brain. 80.6% of those with metastases died during the study. The median overall survival, estimated for the entire group of patients who developed metastases, was of 5.3 months. The influence of metastases distribution on the overall survival was examined and it was noticed that there were statistically significant differences between the risks of death of various groups of patients, depending on metastasis topography. Thus, the death probability of a patient with brain metastases is twice that of a patient with digestive metastasis, about 7 times higher than that of a patient with lung metastasis (p = 0.0004) and 12 times higher than the death risk of a patient with extra-regional lymph nodes or subcutaneous metastasis (p = 0.0000).
    Full-text · Article · Oct 2014
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