Breslow thickness and clark level in melanoma: support for including level in pathology reports and in American Joint Committee on Cancer Staging

BACKGROUND: Thickness is known to be an important survival prognosticator for cutaneous melanoma, but controversy exists as to whether Clark level of invasion retains prognostic significance once thickness has been accounted for. A recent proposal to eliminate Clark level from the staging system for melanoma of the American Joint Committee on Cancer (AJCC) prompted the authors to investigate whether level adds useful prognostic information to Breslow thickness. They used the data base of the New York University Melanoma Cooperative Group (NYU-MCG) Registry. METHODS: The analysis was based on 919 patients with AJCC Stage I or II melanomas diagnosed between 1972 and 1982 and followed for an average of 10.9 years. Melanoma thicknesses were divided into 4 categories (< or = 0.75, 0.76-1.50, 1.51-4.00, and >4.00 mm). Patients were cross-classified according to tumor thickness and Clark level (II-V). For each combination of thickness and level, the Kaplan-Meier survival curve and 10-year survival proportion were computed, using death from melanoma as the outcome. The impact of Clark level on survival was evaluated for each of the thickness categories. The Cox proportional hazards model was used to assess the simultaneous effect of thickness and level on survival while controlling for other important prognostic factors, i.e., age, tumor location, and presence or absence of ulceration. RESULTS: Level of invasion was a significant predictor of death from melanoma in each of the four thickness categories. Likewise, in the Cox analyses, level was a significant prognostic variable, even after thickness was included in the model and regardless of whether thickness was treated as a categoric or a continuous variable. CONCLUSIONS: These results confirm that both tumor thickness and level of invasion are important independent prognostic factors in AJCC Stage I and II melanomas. The authors recommend that Clark levels be kept as criteria in the AJCC staging system and be included in pathology reports. [See editorial on pages 491-6, this issue.] Copyright 2000 American Cancer Society.     

No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm

In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it is relevant to perform the SN procedure - seems to depend on the Breslow thickness of the primary tumour. However, a Breslow thickness cut-off point has not yet been established. We evaluated a melanoma population that had undergone an SN procedure to determine this point, so that the procedure can be restricted to a smaller group of patients in future. In a total of 348 patients with proven American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of preoperative visualization of the lymph channels from the initial site of the melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval 0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31 months. Our data suggest that this procedure need no longer be indicated for almost a quarter of the patient population, because the cut-off point for nodal involvement appears to be a Breslow thickness of 0.90 mm.     

Sentinel node biopsy for thin melanomas: which patients should be considered?

BACKGROUND: As the incidence of melanoma increases, thin melanomas are being diagnosed at an increasingly frequent rate. Currently available prognostic factors are limited in their ability to reliably discriminate which patients will manifest regional nodal metastasis and would be identified early through sentinel node biopsy. METHODS: We summarized our experience with sentinel node biopsy for patients with cutaneous melanomas less than 1.00 mm in Breslow thickness, with evaluation of Clark level as a predictor of positive sentinel node metastasis. RESULTS: Among the 409 patients identified, micrometastases were found in the sentinel node in 20 patients, for an overall incidence of nodal progression of 4.9%. A total of 252 (62%) were Clark level II or III (11 of whom had a positive sentinel node) and 157 (38%) were Clark level IV (9 of whom had a positive sentinel node). We reviewed the literature to identify reliable indicators that might be helpful in determining which patients with "thin melanomas" would be likely to manifest regional progression to warrant routinely undergoing a preoperative lymphoscintigraphy followed by a sentinel node biopsy. CONCLUSIONS: Based on available data, patients with melanomas between 0.75 and 1.00 mm are appropriate candidates to be considered for sentinel node biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy (including the risk of a false-negative result), and the lack of proven survival benefit from any form of surgical nodal staging.     

Linear discriminant analysis of dermoscopic parameters for the differentiation of early melanomas from Clark naevi

As a first step to develop a screening system for pigmented skin lesions, we performed digital discriminant analyses between early melanomas and Clark naevi. A total of 59 cases of melanoma, including 23 melanoma in situ and 36 thin invasive melanomas (Breslow thickness < or =0.75 mm), and 188 clinically equivocal, histopathologically diagnosed Clark naevi were used in our study. After calculating 62 mathematical variables related to the colour, texture, asymmetry and circularity based on the dermoscopic findings of the pigmented skin lesions, we performed multivariate stepwise discriminant analysis using these variables to differentiate melanomas from naevi. The sensitivities and specificities of our model were 94.4 and 98.4%, respectively, for discriminating between melanomas (Breslow thickness < or =0.75 mm) and Clark naevi, and 73.9 and 85.6%, respectively, for discriminating between melanoma in situ and Clark naevi. Our algorithm accurately discriminated invasive melanomas from Clark naevi, but not melanomas in situ from Clark naevi.     

Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 and type 2 in stage I malignant melanoma

The urokinase-type plasminogen activator (uPA) and its inhibitors type 1 (PAI-1) and type 2 (PAI-2) are considered to have a key role in the process of invasion and metastasis. We investigated the differences in uPA, PAI-1 and PAI-2 concentrations in primary cutaneous melanoma and normal skin and correlations with well-established melanoma prognostic factors. The study was performed on 43 patients (19 men, 24 women; mean age 57 years) with histologically confirmed primary melanomas <1.5 mm thick. The uPA concentrations were determined in 36 pairs of triton extracts, and the PAI-1 and PAI-2 concentrations in 43 pairs of cytosols prepared from the tumour and adjacent normal tissue samples (matched pairs). The uPA, PAI-1 and PAI-2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Significantly higher concentrations of both uPA and PAI-1 were measured in melanomas than in normal surrounding skin (uPA: 1.08 vs 0.48 ng/mg total protein (mgp), p<0.001; PAI-1: 14.07 vs 2.07 ng/mgp, p<0.001). The melanoma uPA, PAI-1 and PAI-2 concentrations correlated significantly (p<0.05) with normal skin (r=0.73, 0.54, 0.38 respectively). The uPA concentrations positively correlated with those of PAI-1 measured in melanomas (r=0.45, p<0.01). PAI-1 values were significantly lower (p<0.001) in the melanomas of Breslow thickness < or =0.75 mm, Clark invasion 0.75 mm, Clark invasion of > or =II and < or =III, with microscopic ulceration and vascular invasion (22.25, 17.67, 27.67, 37.77, respectively). Determination of uPA and PAI-1 can provide significant additional prognostic information for melanoma patients.     

Adjuvant reactivity predicts survival in patients with “high-risk” primary malignant melanoma treated with systemic BCG

We report the prognostic importance of strength of reaction to BCG, tumor histology and clinical factors in patients with previously untreated high-risk (Clark, III, IV and V) primary malignant melanoma. One hundred and one such patients received high-dose BCG (1 × 10⁸ viable units) by Heaf gun as an adjuvant to standardized primary surgery according to EORTC Protocol 18741. Univariate analysis of disease-free interval (DFI) indicates that the degree of maximum reaction to BCG (p = 0.0003), Breslow thickness (p = 0.0003) and Clark level (p = 0.002) are highly significant prognostic factors. When a multivariate model using Cox's proportional hazard regression was used for DFI, the degree of maximum reaction to BCG and Breslow thickness were by far the most significant criteria. A prognostic equation was obtained to predict DFI from maximum BCG reaction and Breslow thickness. From analysis of the “scores” calculated in this way it appears that the two variables act independently. This technique permits the determination of values that are predictive of DFI and discriminate between subgroups of patients with different DFI characteristics (5 groups, p< 0.0001). This exercise was repeated for survival and similar results were obtained. The degree of a patient's immune reaction to BCG administered therapeutically is of paramount importance in determining the likelihood of survival. This factor and the Breslow thickness can be integrated to produce a mathematical equation which accurately predicts survival for appropriately treated melanoma patients.     

Estrogen receptor-alpha methylation predicts melanoma progression

The role of estrogen receptor alpha (ER-alpha) in melanoma is unknown. ER-alpha expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-alpha hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-alpha methylation status in tumor (n = 107) and sera (n = 109) from American Joint Committee on Cancer (AJCC) stage I to IV melanoma patients was examined by methylation-specific PCR. The clinical significance of serum methylated ER-alpha was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-alpha methylation in AJCC stage I, II, and III primary melanomas were 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. Methylated ER-alpha was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-alpha was methylated more frequently in metastatic than primary melanomas (P = 0.0003). Of 109 melanoma patients' sera in AJCC stage I, II, III, and IV, methylated ER-alpha was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-alpha was detected more frequently in advanced than localized melanomas (P = 0.03) and was the only factor predicting progression-free [risk ratio (RR), 2.64; 95% confidence interval (95% CI), 1.36-5.13; P = 0.004] and overall survival (RR, 2.31; 95% CI, 1.41-5.58; P = 0.003) in biochemotherapy patients. Hypermethylated ER-alpha is a significant factor in melanoma progression. Serum methylated ER-alpha is an unfavorable prognostic factor.     

Can sentinel node biopsy be safely omitted in thin melanoma? Risk factor analysis of 1272 multicenter prospective cases

BackgroundThe indication to sentinel node biopsy (SNB) for thin melanomas (Breslow <1 mm) is still subject to controversies. The aim of this paper is to review all SNB performed for thin melanoma and to analyze factors related to lymphatic metastasis. Moreover, the diagnostic performance of the 5th, 6th, 7th and 8th AJCC classifications for cutaneous melanoma were investigated.MethodsAll sentinel node biopsies performed for thin melanomas were selected from a multicentre prospectively-collected database. For each patient the following was collected: age, sex, date of treatment, site of primary melanoma, histopathologic features (Breslow, Clark, number of mitoses/mm², presence of ulceration) and the results of the sentinel node biopsy.ResultsFrom 1998 to 2017 were performed a total of 1272 SNB for thin melanoma. Mean age was 51years with 48.7% of male patients. Overall, 5.6% positive SNB were found. At univariate and multivariate analyses, Breslow thickness and ulceration were related to the presence of lymphatic metastasis. We compared the four versions of the AJCC classification: among pT1a patients there were respectively 5.32%, 5.63%, 3.72% and 3.49% of positive SNB.Conclusionsin thin melanoma Breslow thickness and ulceration were the only factors related to a positive SNB. Although convincing improvements resulted from the implementation of AJCC classifications with a reduction of positive biopsies among pT1a, a 10.71% rate among all positive nodes remains in the low-risk group. No recommendations can be drawn from this research and adjunctive evidences are needed to better identify patients at risk of nodal metastasis.     

Should all melanoma patients undergo sentinel lymph node biopsy?

PURPOSE OF REVIEW: It is now well established that sentinel lymph node biopsy is a powerful test to predict prognosis for melanoma patients. Controversy exists, however, regarding the appropriate selection of patients for sentinel lymph node biopsy, especially among patients with thin melanomas (< 1 mm Breslow thickness), thick melanomas (> 4 mm Breslow thickness), or locally recurrent melanoma. RECENT FINDINGS: The majority of the studies in the past 2 years regarding sentinel lymph node biopsy have been concerned with identifying factors that can better predict regional nodal metastasis and survival. Other studies have proposed a better risk stratification model, which includes these factors, to best select those patients at increased risk of nodal positivity. SUMMARY: Although much research has been done to select appropriate patients for sentinel lymph node biopsy based on multiple prognostic factors, further studies are necessary to completely define the indications for this procedure in patients with thin, thick and locally recurrent melanomas.     

Invasive cutaneous malignant melanoma in Sweden, 1990-1999. A prospective, population-based study of survival and prognostic factors

BACKGROUND: The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. METHODS: Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. RESULTS: There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. CONCLUSIONS: During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits; however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.     

KIT receptor is expressed in more than 50% of early-stage malignant melanoma: a retrospective study of 261 patients

The c-kit gene encodes a transmembrane receptor (KIT) with tyrosine kinase activity which is a specific target for anti-cancer therapy. We investigated KIT expression in a group of patients with early-stage malignant melanoma. Primary tumour specimens obtained from 261 radically resected patients with stage I and II malignant melanoma were examined for KIT expression. Formalin-fixed, paraffin embedded tissues were stained with the polyclonal rabbit anti-human anti-KIT antibody (Dako Cytomation Inc., Carpenteria, California, USA). Patients were classified into four groups according to the level of expression (0%, <30%, 30-60% and >60%). Univariate and multivariate analyses examining the impact of KIT expression, Breslow thickness, Clark level and microscopic ulceration on disease-free survival were performed. Within the population of 261 patients with early-stage melanoma with 62 recurrences during a follow-up of 64 months, KIT expression was found in 144 cases (55%). KIT was expressed in more than 60% of cells in 20 patients (8%), in 30-60% of cells in 64 patients (24%) and in less than 30% of cells in 60 patients (23%). KIT expression was not found in 117 patients (45%). In univariate analyses, the influence of KIT expression on disease-free survival was not proven (P=0.4956; log-rank test). Increasing Breslow thickness, a higher Clark level, the presence of microscopic ulceration and a higher stage were significantly associated with a shorter disease-free survival (P<0.0001; log-rank test in all cases). In multivariate analysis, Breslow thickness, stage and KIT expression were significant negative prognostic factors for a shorter disease-free survival (P<0.0001, P=0.0028, P=0.0488, respectively; stepwise Cox regression model). It can be concluded that KIT is expressed in more than one-half of early-stage malignant melanoma. KIT may serve as an additive prognostic factor to Breslow thickness and stage within the tested population. The therapeutic impact of KIT expression in malignant melanoma is uncertain. Results of ongoing pilot phase II studies may validate the efficacy of imatinib mesylate in malignant melanoma expressing KIT.     

Should all patients with melanoma between 1 and 2 mm Breslow thickness undergo sentinel lymph node biopsy?

BACKGROUND:

Sentinel lymph node (SLN) biopsy generally is recommended for patients who have melanoma with a Breslow thickness ≥1 mm. Most patients with melanoma between 1 mm and 2 mm thick have tumor‐negative SLNs and an excellent long‐term prognosis. The objective of the current study was to evaluate prognostic factors in this subset of patients and determine whether all such patients require SLN biopsy.

METHODS:

Patients with melanoma between 1 mm and 2 mm in Breslow thickness were evaluated from a prospective multi‐institutional study of SLN biopsy for melanoma. Disease‐free survival (DFS) and overall survival (OS) were evaluated by Kaplan‐Meier analysis to compare patients with melanoma that measured from 1.0 mm to 1.59 mm (Group A) versus patients with melanoma that measured from ≥1.6 mm to 2.0 mm thick (Group B). Univariate and multivariate analyses were performed to evaluate factors predictive of tumor‐positive SLN status, DFS, and OS.

RESULTS:

The current analysis included 1110 patients with a median follow‐up of 69 months. SLN status was tumor‐positive in 133 of 1110 patients (12%) including 66 of 762 patients (8.7%) in Group A and 67 of 348 patients (19.3%) in Group B (P < .0001). On multivariate analysis, age, Breslow thickness, and lymphovascular invasion were independently predictive of a tumor‐positive SLN (P < .05). DFS (P < .0001) and OS (P = .0001) were significantly better for Group A than for Group B. When tumor thickness was treated as either a continuous variable (P < 0.0001) or a categorical variable (P < .0001), it was significantly predictive of DFS and OS. On multivariate analysis, Breslow thickness, age, ulceration, histologic subtype, regression, Clark level, and SLN status were significant factors predicting DFS; and Breslow thickness, age, primary tumor location, sex, ulceration, and SLN status were significant factors predicting OS (P < .05). A subgroup of patients who had tumors <1.6 mm in Breslow thickness, had no lymphovascular invasion, and were aged ≥59 years had a low risk (5%) of tumor‐positive SLN.

CONCLUSIONS:

The current findings indicated that there is significant diversity in the biologic behavior of melanoma between 1 mm and 2 mm in Breslow thickness. SLN biopsy is recommended for all such patients to identify those with lymph node metastasis who are at the greatest risk of recurrence and mortality. Cancer 2010. © 2010 American Cancer Society.     

Increased incidence of brain metastases in cutaneous head and neck melanoma

The incidence of cutaneous melanoma is increasing, and 10-20% of these melanomas are located in the head and neck region. The incidence of brain metastases, risk factors and outcome were analysed for melanomas originating in the head and neck region. During the period 1965-2000, 324 patients [152 females (47%), 172 males (53%)] were treated for cutaneous melanoma of the head and neck. The patients were staged according to the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system. A matched control analysis was performed in order to identify the risk factors for the occurrence of brain metastases. The analysis was performed using cross-tabulations, chi-squared test and the logistic regression method. Twenty six (8%) head and neck patients, compared with 5.2% of extremity/truncal patients, developed brain metastases (confidence interval, 0.058-0.108; P<0.05). The 26 head and neck patients (four Stage I, 10 Stage II and 12 Stage III) had a median age of 46 years (range, 16-79 years) and developed brain metastases after a median follow-up of 24 months (range, 4-75 months). The median Breslow thickness was 3.3 mm (range, 0.7-12 mm). The patients were treated with steroids, surgery, radiation, chemotherapy, or a combination of these. The median survival after the development of brain metastases was 2.4 months (range, 0.2-64.3 months), with a 1-year overall survival of 15%. Risk factors identified for the development of brain metastases from head and neck melanoma were a younger age, male gender, Breslow thickness greater than 4 mm and increased mitotic rate. The incidence of brain metastases is significantly higher in patients with cutaneous melanoma of the head and neck (8%) compared with those with extremity/truncal melanoma (5.2%). The prognosis is still extremely poor with current therapies.     

P21 and Bax expression in cutaneous malignant melanomas: correlation with histologic prognostic parameters

In response to DNA damage, p53 accumulates and regulates expression of several genes, including cyclin-dependent kinase inhibitor p21. Cells then undergo p21 dependent cell cycle arrest, which allows DNA damage repair and apoptosis. Bax is a death promoter member of the bcl-2 family which plays a central role in the regulation and commitment to programmed cell death. Breslow thickness is the most important factor in predicting prognosis for cutaneous malignant melanoma. In order to define the role of cyclin dependent kinase inhibitors and apoptosis regulators in invasion of malignant melanoma we investigated the expression of p21 and bax proteins. We observed that significant high p21 expression was associated with increasing Breslow thickness (Spearman correlation analysis, p=0.01). Additionally, Clark level I and II tumours expressed significantly lower p21 positivity than Clark level III, IV and V (p=0.006). Similarly, thick tumors showed a higher bax expression (p=0.012). Our results suggested that the role of p21 expression is more complicated in melanocytic skin cancers and abnormal regulation or abnormal function of cell cycle regulators occurred in the development and progression of malignant melanoma. In order to understand the role of bax expression in thick malignant melanomas and invasion biology, comparative analytic studies with other apoptosis regulators are needed.     

Prognostic variables and prognostic groups for malignant melanoma. The information from Cox and Classification And Regression Trees analysis: an Italian population-based study

The common way to analyse the prognostic role of selected variables in cutaneous melanoma patients is by means of Cox proportional hazard model. The prognostic effect of the simultaneous presence of more than one independent variable in the same patient is, however, difficult to establish. This hampers the possibility of tailoring a survival expectance for a selected patient as well as to communicate it to the patient himself/herself. The objectives of the study were to compare information on cutaneous melanoma prognosis from multivariate Cox proportional hazard model and from Classification And Regression Trees analysis. Classification And Regression Trees analysis is an automatic method that splits data by means of a binary recursive process creating a 'tree' of groups with different profiles according to the analysed outcome, for example, the risk of death. This approach automatically produces data that is easily interpreted by clinicians. A total of 1403 invasive cutaneous melanoma patients, 1110 from the Tuscan Cancer Registry and 293 from the Reggio Emilia Cancer Registry, Italy, were included. Cases were incident during 1996-2001 and followed up at the end of 2003. Cox proportional hazard model and Classification And Regression Trees analysis were applied to the following variables: age, sex, Breslow thickness, Clark level, registry, subsite and morphologic type. The Classification And Regression Trees analysis identified 10 categories with statistically different survival; this results were summarized into six classes of different risks based on Breslow thickness, age and sex. The best prognostic group (5-year observed survival, 98.1%) included those subjected with Breslow less than 0.94 mm and age 19-44 years. The same thickness but an older age (50-69 years) was associated with a statistically significant different prognosis (5-year observed survival, 92.8%). The Cox proportional hazard model found sex, age, Breslow thickness, Clark and morphologic type to have a significant independent prognostic value. In conclusion, compared with the conventional approach based on Cox hazard model, Classification And Regression Trees analysis produces data closer to the clinical need of defining the prognostic profile of a specific patient. This may help the clinician both in the communication of risk and in the follow-up strategy.     

Prognostic factors for melanoma in children and adolescents

BACKGROUND:

Cutaneous melanoma in childhood is rare; therefore, its prognostic factors and biologic behavior and the effectiveness of adjuvant diagnostic techniques in this group remain mostly unknown.

METHODS:

The authors conducted a retrospective, observational study on the prognostic significance of clinical and pathologic findings from 137 cutaneous and mucosal melanomas in patients aged <18 years that were reviewed by the pathology department of a large cancer center during the period from 1992 to 2006.

RESULTS:

Univariate analysis indicated that there was a significantly greater risk of metastases for patients who had previous nonmelanocytic malignancies, nodular histologic type, fusiform or spitzoid cytology, high Breslow thickness, vertical growth phase, high dermal mitotic activity, ulceration, and vascular invasion. Adjacent nevus and radial growth phase were associated with a better prognosis. Twelve patients (10.3%) died during follow‐up. Decreased overall survival was related significantly to age >10 years, previous nonmelanocytic malignancy, high Breslow thickness, high Clark level, and the presence of metastases at diagnosis. All patients who died were aged ≥11 years, and 8 of those patients had metastases at diagnosis. In multivariate analysis, higher Breslow thickness predicted an increased risk of metastases, whereas age >10 years and the presence of metastases at diagnosis were associated with decreased survival.

CONCLUSIONS:

Similar to adults, the detection of metastases at diagnosis in children with melanoma was 1 of the main factors that influenced overall survival. Melanomas that were detected in children aged <11 years appeared to have a less aggressive behavior than those detected in adults. Cancer 2010. © 2010 American Cancer Society.     

Review of the 2001 AJCC staging system for cutaneous malignant melanoma

The American Joint Committee on Cancer (AJCC) staging system for melanoma has recently been revised and published. The previous staging system had not been substantially modified since the late 1980s. In a series of papers, the staging system for melanoma was critically analyzed, and many shortcomings were identified. Many well-established prognostic factors were not used in the staging system. This assessment has led to a substantially modified staging system for cutaneous melanoma in 2001 that is a considerable improvement over past staging systems, albeit more complex. The following modifications are the most important: 1) The primary determinant of tumor (T) staging is tumor thickness as measured in millimeters. The Clark level of invasion is now used only for defining T1 (< or = 1mm) melanomas; 2) The cutpoints for tumor thickness are less than or equal to 1 mm, 1 to 2 mm, 2 to 4 mm, and greater than 4 mm; 3) Ulceration has been added in describing the primary tumor; 4) Local recurrence, satellite disease, and in-transit metastases have similar prognosis and are now all classified together as regional stage III disease; 5) Size of lymph node as prognostic factor has been eliminated and replaced with the number of positive nodes; 6) The presence of an elevated serum lactic dehyrogenase level is used in the metastasis (M) category. This revised staging system more precisely defines prognosis and will improve the stratification of patients in future clinical trials.     

Up-to-date survival estimates and historical trends of cutaneous malignant melanoma in the south-east of The Netherlands.

BACKGROUND: We present survival outcomes of patients registered in the Dutch population-based Eindhoven Cancer Registry (ECR). PATIENTS AND METHODS: Data on patients diagnosed with a melanoma between 1980 and 2002 were obtained from the ECR. Data on vital status up to 1 January 2005 were obtained, up-to-date survival rates were calculated using period analysis. Multivariate analyses were carried out using Cox proportional hazards model. RESULTS: Ten-year crude survival rates were 82% for women and 60% for men (P < 0.05). Thin melanomas (Breslow thickness 74%, for melanomas >4.0 mm these rates were <65% (P < 0.05). In the early 1980s, 5-year relative survival rates were 84% and 62% for young (<60 years) women and men, and 66% and 69%, respectively, for the elderly (aged 60+). In the period 2000-2002, these rates had improved to >90% for females and to >72% for males. Multivariate analyses showed increased hazard ratios with increasing age and Breslow thickness, being male, having a melanoma on the trunk or unknown sites and having a nodular melanoma. CONCLUSIONS: Despite the absence of improvements in treatment options for melanoma, survival improved significantly, except for elderly males.     

So‐called “malignant blue nevus”

BACKGROUND:

Melanomas that arise in association with or that resemble blue nevi are extremely rare and have been termed “malignant blue nevi.” The authors report on a single‐institutional clinicopathologic study of “blue nevus‐like melanomas” (BNLMs).

METHODS:

Twenty‐six patients were identified with a “malignant blue nevus” over 29 years at the Sydney Melanoma Unit. Twenty‐three patients were included in the current study after pathologic review. Clinical outcomes of those patients were compared with the outcomes in a matched control group of patients with melanoma (matched for age, sex, Breslow thickness, Clark level, ulceration, and anatomic site).

RESULTS:

The median patient age was 44 years, and men comprised 65% of the patients. The tumors were distributed evenly among skin sites, and their median Breslow thickness was 5.5 mm. After a median follow‐up of 36.5 months, there was no difference in survival (P = .702) between patients with BNLM and patients in the control group.

CONCLUSIONS:

BNLMs tended to present at a more advanced stage, with thicker primary tumors, but had a metastatic pattern comparable to and was not more aggressive in behavior than other types of melanoma. The authors concluded that BNLMs should be treated in the same way as any other melanoma variants based on clinical staging and pathologic prognostic indices. Cancer 2009. © 2009 American Cancer Society.     

Prognostic factors in head and neck melanoma. Effect of lesion location

Cutaneous malignant melanomas of the head and neck are prognostically engimatic. In addition to known prognostic determinants of stage and lesion microstage, lesion location also appears to have prognostic importance. The authors have reviewed a series of 83 microstaged head and neck melanoma patients in order to analyze the relative importance of these factors. There were 36 males and 47 females with a median age of 56 years. Eighty-one percent had pathologic Stage I disease, 7% were Stage II, and 12% were Stage III. The primary location was face in 32 patients, neck in 18, ear in 12, and scalp in 21 patients. The actuarial 5-year survival according to lesion thickness was 86% for melanoma less than 1.0 mm, 56% for 1 to 2 mm thick lesions, 47% for 2.1 to 4 mm thick lesions, and 25% for melanomas greater than 4.0 mm. The 5-year survival according to lesion location was 78% for facial and 58% for neck melanomas; for ear and scalp, the respective survivals were 33% and 37%. Median thickness was 2.0 mm for facial and 1.85 mm for neck lesions. It was 2.7 mm for ear and 2.0 mm for scalp lesions (differences not significant). There were no microstage factors that correlated with the adverse prognosis seen with scalp and ear melanomas. Multivariate analysis in the entire series (all clinical stages) showed the following to be significant: stage, thickness, and location of the primary melanoma (all less than 0.0002). In clinical Stage I melanoma, the significant prognostic factors were location (P = 0.035), thickness (P = 0.008), level (P = 0.024), and ulceration (P = 0.035). The prognosis of head and neck melanoma is uniquely influenced by location of the primary lesions in addition to stage, thickness, level, and ulceration, as observed with other cutaneous melanomas at other sites. Ear and scalp melanomas are high-risk lesions whose poor prognosis is not readily explained by any of the microstage factors reviewed.