Comparing survival of patients with single or multiple primary melanoma in The Netherlands: 1994- 2009
Laura PardoR.J.T. ven der LeestElisabeth G.E. de VriesIsabelle SoerjomataramTamar NijstenLoes M. Hollestein
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Abstract:
There is conflicting literature as to whether the survival of patients with multiple melanoma is worse that this of single melanoma cases. We used extended Cox-proportional hazard models to estimate hazard-ratios (HR) of patients with multiple melanomas against single melanomas. Data from the nationwide Dutch Cancer Registry was used to retrieve cutaneous melanoma cases between 1994 and 2009 and linked with municipal records to assess the vital status. To account for the longer survival in the multiple melanoma cases we modelled multiple melanoma as time-varying variable, as well as Breslow thickness, histological subtype and nodal/distant metastasis. In total, 42,733 melanoma cases were identified, of which 1210 (3%) developed a new primary melanoma during a total follow-up of 11 years. The adjusted HR for multiple melanoma was 1.32 (95 %CI: 1.17-1.50) adjusting for age, sex, Breslow thickness, histological subtype and presence of nodal and distant metastasis . Our study showed that patients with multiple melanomas have an increased risk of dying when compared with single melanoma cases, and suggests that the improved survival of patients with multiple melanoma shown in previous studies was an artefact due to survival bias. Based on our findings we advise, within the guideline of five years of follow-up, to focus on high-quality patient-education about skin self-examination and the risks of subsequent melanomas.Keywords:
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Patients who are already diagnosed with cutaneous melanoma are at increased risk of developing another primary melanoma. The occurrence of multiple primary melanoma is a rare phenomenon, varying in frequency, with an estimated incidence ranging from 0.2% to 8.6%. The authors are presenting data on the patients with multiple primary melanoma from the Croatian Referral Melanoma Centre. The clinical, histological and epidemiological characteristics of 36 (3.6%) patients, identified from 991 patients with histologically confirmed melanoma, are analyzed in this study. Twenty-eight of the patients (78%) had two primary melanomas, six had three melanomas (16.7%) and two (5,6%) had four melanomas. Diagnosis was established synchronously in 11 patients (30%) and, in the rest of the patients, time interval between the diagnosis of the first and second melanoma varied from 1 month to the longest interval of 16 years. However, the majority of subsequent melanomas were removed within 2 years of the initial operation. The mean Breslow's thickness of the first melanoma was significantly higher than the mean Breslow's thickness of the second primary melanoma. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Therefore, we emphasize the importance of regular follow-up as well as the education in regular self--skin examinations in melanoma patients in order to detect subsequent primary melanomas in the early phase.
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There is conflicting literature as to whether the survival of patients with multiple melanoma is worse that this of single melanoma cases. We used extended Cox-proportional hazard models to estimate hazard-ratios (HR) of patients with multiple melanomas against single melanomas. Data from the nationwide Dutch Cancer Registry was used to retrieve cutaneous melanoma cases between 1994 and 2009 and linked with municipal records to assess the vital status. To account for the longer survival in the multiple melanoma cases we modelled multiple melanoma as time-varying variable, as well as Breslow thickness, histological subtype and nodal/distant metastasis. In total, 42,733 melanoma cases were identified, of which 1210 (3%) developed a new primary melanoma during a total follow-up of 11 years. The adjusted HR for multiple melanoma was 1.32 (95 %CI: 1.17-1.50) adjusting for age, sex, Breslow thickness, histological subtype and presence of nodal and distant metastasis . Our study showed that patients with multiple melanomas have an increased risk of dying when compared with single melanoma cases, and suggests that the improved survival of patients with multiple melanoma shown in previous studies was an artefact due to survival bias. Based on our findings we advise, within the guideline of five years of follow-up, to focus on high-quality patient-education about skin self-examination and the risks of subsequent melanomas.
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Introduction: Melanoma is a malignant tumor of melanocytes and it is the most malignant tumor of skin and mucous membranes. We do not have any data about incidence and characteristics of skin melanoma in Bosnia and Herzegovina. Aim: We aimed to analyze hospital records on skin melanoma cases from the region of Tuzla during the 5-year period in order to obtain preliminary data about melanoma incidence and clinical characteristics. Patients and methods: This retrospective study included all patients surgically treated at the University Clinical Center Tuzla, from January 2001 to December 2005, who were initially diagnosed with skin melanoma. Results: Most of pathologically verified skin melanoma, disregarding primary tumor (T), were presented in both genders at stage T4 (41.67 %) and T2 (28.33 %). Histological analysis showed that the majority of observed skin melanoma were diagnosed in Clark level III (36.36 %) and Clark level IV (33.33 %) stage. The average tumor thickness of the examined sample, according to Breslow’s classification, was found to be over than 4.0 mm. Conclusion: Our findings are similar to those reported in other countries in the region. Further studies are necessary in order to asses the burden of the disease in the national level. A national melanoma register is of great importance for further surveilance.
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Introduction
In Sweden, the incidence of cutaneous malignant melanoma rises yearly with 5.5% for men and 5.2% for women and has now reached world standard rates of 17.6 for men and 18.8 for women per 100,000 population. Over the past decades, the incidence of melanoma has been higher in Western Sweden than the national average. Previous international studies have shown that melanoma patients have an elevated risk of developing a new separate primary melanoma. This study aimed at describing multiple primary melanomas (MPMs) in Western Sweden with focus on the number of tumours detected, tumour characteristics and the time to diagnosis of a subsequent melanoma.
Methods
Data was extracted retrospectively from the Swedish Melanoma Registry and provided information on all invasive and in situ melanoma cases in Western Sweden (1.6 million inhabitants) from 1990 to 2013.
Results
Within the studied period, 12,152 patients developed 13,291 melanomas. 11,254 of the patients developed only a single primary melanoma. In total, 898 patients (7.4% of all melanoma patients) developed 2,037 MPMs. Preliminary results show that the median Breslow thickness for all invasive melanomas was below 1 mm. The median Breslow thickness for the MPMs was slightly thinner for the second and third invasive melanoma as compared to the first invasive melanoma. Further, there was a higher percentage of in situ tumours among the subsequent melanomas. The median time to diagnosis of a subsequent melanoma was approximately 3 years.
Discussion
Subsequent primary melanomas in Western Sweden are most commonly diagnosed with a somewhat thinner Breslow thickness than the first primary melanoma. The comparatively high percentage of melanoma survivors developing MPMs and the short median time to diagnosis of a subsequent melanoma stresses the importance of follow-up for melanoma patients, particularly during the first years.
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Given the specific melanin-associated paramagnetic features, the Electron Spin Resonance (ESR, called also Electron Paramagnetic Resonance, EPR) analysis has been proposed as a potential tool for non-invasive melanoma diagnosis. However, studies comparing human melanoma tissues to the most appropriate physiological counterpart (nevi) have not been performed, and ESR direct correlation with melanoma clinical features has never been investigated. ESR spectrum was obtained from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non-melanoma tissues and an endogenous ESR signal (g = 2.005) was found in human melanoma cells and in primary melanoma tissues explanted from mice, while it was always absent in non-melanoma samples. These characteristics of the measured ESR signal strongly suggested its connection with melanin. Quantitative analyses were then performed on paraffin-embedded human melanoma and nevus sections, and validated on an independent larger validation set, for a total of 112 sections (52 melanomas, 60 nevi). The ESR signal was significantly higher in melanomas (p = 0.0002) and was significantly different between "Low Breslow's and "High Breslow's" depth melanomas (p<0.0001). A direct correlation between ESR signal and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001). The eu/pheomelanin ratio was found to be significantly different in melanomas "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas "High Breslow's depth". Finally, ROC analysis using ESR data discriminated melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In the present study we report for the first time that ESR signal in human paraffin-embedded nevi is significantly lower than signal in human melanomas suggesting that spectrum variations may be related to qualitative melanin differences specifically occurring in melanoma cells. We therefore conclude that this ESR signal may represent a reliable marker for melanoma diagnosis in human histological sections.
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Abstract Background Melanomas can arise from naevi or appear de novo . The frequency or the effect of their origin on prognosis is still debated. Mitotic rate (MR) and ulceration of melanomas have been proposed as further new prognostic indexes. Aim To determine the different prognostic factors in melanomas de novo and melanomas from pre‐existing naevi and whether these two melanoma groups have different MR or presence of ulceration. Methods All patients with confirmed primary melanomas observed in our clinic from 1996 to July 2013 were included. The distinction between the two groups of melanomas was histologically based. We compared Breslow's thickness, the number of mitosis/mm 2 and the presence of ulceration between the naevus‐associated melanoma and de novo melanoma group. Results Of the 873 melanomas, 626 (71.8%) have a de novo melanoma, 247 (28.2%) a naevus‐associated melanoma. Breslow's thickness was not significantly different in the two groups (0.77 ± 1.47 mm vs. 0.59 ± 1.35 mm). The number of patients with presence of ulceration and MR ≥1 mitosis/mm 2 was not significantly different in the two groups (19.6% vs. 16.3%). In thicker melanomas (Breslow's thickness ≥ 1 mm), the number of patients with ≥6 mitosis/mm 2 was significantly higher (26.6% vs. 7.9%; P < 0.05) in the de novo melanoma group. Conclusions When mitosis ≥ 1 mm/mm 2 , the results obtained do not show a better or worse prognosis based on Breslow's thickness, ulceration and MR in melanomas associated with naevus vs. melanomas de novo . When ≥6 mitosis/mm 2 are considered, the number of patients in the de novo melanoma group with thick melanoma is highly more represented. The debate about the cut‐off value of mitosis ≥1 mm 2 is open.
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Although acral lentiginous melanoma is the most common subtype of malignant melanoma in acral locations, the term acral melanoma (AM) has to be differentiated from the histopathologic description.To characterize the clinical and pathologic features of patients with a primary AM and to elucidate whether the prognosis of patients with AM differs from that of those with melanoma at other sites (nonacral melanoma; NAM).Over a 20-year period, a series of 822 consecutive patients with melanoma were recorded in the database. Clinical and follow-up data were retrieved from the melanoma register and prospectively analyzed.Eighty-nine patients had a malignant melanoma located on the acral sites of extremities. Breslow thickness and Clark level were found to be related to specific and disease-free survival. Breslow thickness greater than 4 mm was associated with greater risk of recurrence, and amelanosis and age of 60 and older were significantly associated with greater risk of death. Comparison of survival of patients with AM with that of those with NAM clearly showed that disease-free survival and overall survival were significantly lower in the former.Survival differences between patients with AM and NAM are due to differences in already known prognostic factors, probably as a consequence of a delay in the diagnosis in these locations.
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There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma.The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes.Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database.The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma.This study is a retrospective, single-center design.Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.
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Some dermatopathological parameters are recognized as dominant indicators of high metastatic potential in melanoma, especially Breslow thickness, ulceration, Clark's level of invasion and mitotic rate. Because NM23 protein is the product of a melanoma metastasis suppressor gene, the aim of this study was to compare such dermatopathological indicators of melanoma prognosis with NM23 protein expression in primary cutaneous melanoma.The immunohistochemical NM23 expression was semiquantitatively assessed in 30 primary cutaneous melanomas. Ten dermatopathological parameters were evaluated and compared with NM23 expression.A significant inverse correlation was found for NM23 expression in comparison with Breslow thickness (p < 0.01), ulceration (p < 0.05), Clark's level (p < 0.01), mitotic rate (p < 0.05), and vertical growth phase (p < 0.05). By contrast, no significant correlation was found for NM23 expression in comparison with cell morphology, presence of adjacent nevus, pigmentation, tumor-infiltrating lymphocytes, and regression was impossible to evaluate.The expression of NM23 protein in primary cutaneous melanoma is significantly inversely correlated with dermatopathological parameters currently recognized as powerful indicators of melanoma prognosis. NM23 may be therefore considered in the dermatopathological evaluation of primary cutaneous melanoma.
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