Identification of higher risk thin melanomas should be based on Breslow depth not Clark level IV

BACKGROUND: There is good prognostic correlation for the two microstaging systems, Breslow depth and Clark level, commonly used to stage melanomas. Many investigators have reported that Breslow depth is the superior microstaging method. Although Clark level has been dropped from most of the proposed American Joint Committee on Cancer (AJCC) melanoma staging system, the AJCC system still includes Clark Level IV as a criterion for upstaging thin melanomas. The authors sought to determine whether this is appropriate, based on melanoma patient data in the Duke Comprehensive Cancer Center database. METHODS: Of the 8833 patients registered between January 1, 1970 and December 31, 1995, complete data on Breslow depth and Clark level was available for 4560 patients who were without nodal or metastatic disease at presentation. Ten-year survival was measured from the date of excision of the primary tumor until death from melanoma and analyzed using Kaplan-Meier and Cox proportional hazard methodologies. RESULTS: When analyzed separately, both increased Breslow thickness and Clark level correlated with shorter survival times. During subgroup analysis, Breslow thickness remained a significant prognostic indicator of survival at Clark Levels III and IV. Conversely, at narrow levels of Breslow thickness (i.e., 0-0.75 mm, > 0.75 -1.0 mm, > 1.0-1.5 mm) survival times were indistinguishable between Clark Levels III and IV. For the broader Breslow thickness interval of 0-1.0 mm, a barely significant difference between Clark Levels III and IV could be obtained. However, for this thickness range, even greater differences in survival could be obtained by merely comparing Breslow subgroups (i.e., < or = 0.8 mm vs. > 0.8-1.0 mm, < or = 0.9 mm vs. > 0.9-1.0 mm). CONCLUSION: The authors' data suggested that, after controlling for Breslow depth, Clark level was not a good prognostic indicator for survival. If the AJCC's objective is to design a classification system that will reliably predict the higher risk melanomas, then the system should be based on tumor thickness, which is clearly a better prognostic indicator, and should not be modified because of Clark level.     

Differentiation between pigmented Spitz naevus and melanoma by digital dermoscopy and stepwise logistic discriminant analysis

Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.     

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.     

Dermoscopic criteria for melanoma in situ are similar to those for early invasive melanoma

BACKGROUND: Dermoscopy is a noninvasive technique that increases the diagnostic accuracy of pigmented skin lesions, particularly improving the diagnosis of patients with cutaneous melanoma in situ (CMIS) and early invasive melanoma. To establish reliable and reproducible dermoscopic criteria for the diagnosis of CMIS, the authors conducted a retrospective clinical study of 37 patients with CMIS and 53 patients with invasive cutaneous melanomas (ICM). METHODS: The 37 patients with CMIS were divided into three groups: those with CMIS lesions measuring < or = 5 mm in greatest dimension (8 patients), those with CMIS lesions measuring from > 5 mm to < or = 10 mm in greatest dimension (20 patients), and those with CMIS lesions measuring > 10 mm in greatest dimension (9 patients). The 53 patients with ICM were divided into two groups according to Breslow index: those with ICM lesions measuring < or = 0.75 mm in tumor thickness (19 patients) and those with ICM lesions measuring > 0.75 mm in tumor thickness (34 patients). Lesions were examined with a dermatoscope and were photographed at a magnification of x10. Dermoscopic criteria were evaluated from examination of the photomicrographs. RESULTS: Blue-whitish veil, gray-blue areas, black dots, and irregular extensions and branched streaks were the most relevant dermoscopic criteria for CMIS and were present in 78%, 76%, 73%, and 62% of lesions, respectively. Brown globules, irregular pigment network, pseudopods, and depigmentation were present in 57%, 54%, 54%, and 51% of CMIS lesions, respectively. White scar-like areas and linear and/or dotted vascular patterns, two criteria that are associated frequently with ICM, were not found in our patients with CMIS. No clinically significant differences were observed between the three groups of CMIS patients. CONCLUSIONS: Dermoscopic criteria for CMIS were similar to those for ICM, although white scar-like areas and linear and/or dotted vascular patterns were observed only in patients with ICM. Dermoscopic criteria appeared to be independent of CMIS lesions size.     

Early detection of melanoma: an educational campaign in Padova, Italy

To evaluate a public campaign for the early referral and treatment of cutaneous melanoma, an educational programme based on self-selection by subjects was organized in Padova, Italy in 1991. In the period from 1991 to 1996, 90,000 leaflets containing information on naevi, melanoma and skin self-examination were mailed to each household, reaching a population of 243,000 subjects. A total of 2050 individuals requested a skin check as a result of the leaflet. Most were at low risk, the majority being female (68%) and aged under 40 years (51.6%), with no risk factors (58.3%). One hundred and ninety subjects were referred for surgery for pigmented and non-pigmented suspect lesions. Histological diagnoses, obtained for all lesions, comprised 13 melanomas, 17 dysplastic naevi, 17 basocellular carcinomas, 140 pigmented benign lesions and three lesions of other types. The percentage of thin melanomas (< 1.50 mm) was 92.3%. Three hundred and fifty patients considered at risk at the first skin examination attended regular follow-up examinations. The sensitivity and predictive positive value of the visual examination were 92.8% and 6.8%, respectively. The impact of this campaign was evaluated in the Local Health District of Padova, comparing data from the pre-campaign period (1987-1990) with those from the campaign period (1991-1996); a trend towards a lower stage was observed (mean thickness 2.0 mm versus 1.50 mm; P < 0.02).     

Computer image analysis of pigmented skin lesions

To assist in the distinction of melanoma from benign pigmented lesions, an imaging system was developed, comprising a frame grabber, a microcomputer, a colour video camera and flash lighting with red, green and infrared filters. Over an 18-month period, video images of 70 unselected pigmented lesions for which complete diagnostic data were available, were successfully captured using the camera. Analysis software extracted features relevant to the size, colour, shape and boundary of each lesion, and these features were correlated with clinical and histological characteristics on which standard diagnoses of skin tumours are based. For discriminant analysis based on image analysis measurements, equal probabilities were assigned to three specified diagnostic groups, namely melanoma, naevi and 'other', and four of five melanomas were correctly classified when infrared data were included. However when infrared measurements were omitted, all five melanomas were correctly classified, and the overall accuracy of classification of pigmented lesions was 71%. This system holds promise as an aid in the clinical distinction of melanoma from benign pigmented skin lesions.     

Clinical whole‐body skin examination reduces the incidence of thick melanomas

Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence‐based assessments do not recommend population screening. We aimed to assess whether clinical whole‐body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). We conducted a population‐based case‐control study of all Queensland residents aged 20–75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%). Whole‐body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75 mm) (OR = 0.86, 95% CI = 0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76–1.49 mm was reduced by 7% (OR = 0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50–2.99 mm (OR = 0.83, 95% CI = 0.65, 1.05) and by 40% for melanomas ≥3 mm (OR = 0.60, 95% CI = 0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (≤0.75 mm) (OR = 1.38, 95% CI = 1.22, 1.56). This is the strongest evidence to date that whole‐body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.     

Non-invasive analysis of melanoma thickness by means of dermoscopy: a retrospective study

Epiluminescence microscopy (ELM), or dermatoscopy, is a non-invasive technique for the diagnosis of cutaneous melanoma that may play a role in the non-invasive, preoperative assessment of melanoma thickness. This study investigated the correlation between the frequency of appearance of some standard ELM criteria and the histological thickness of melanomas. In addition, the possible role of the total dermoscopic score (TDS) according to ABCD rule of dermoscopy as a predictor of melanoma thickness was analysed. The dermoscopic images of 84 cutaneous melanomas were retrospectively investigated to evaluate the presence of 10 standard ELM criteria, and for each lesion the TDS was established (with observers blinded as to the tumour thickness). A statistically significant association was found between the presence of an irregular pigment network and melanomas with a Breslow index equal to or lower than 0.75 mm (positive predictive value of 68%); in contrast, radial streaming, atypical vascular pattern and grey-blue areas were associated with melanomas > 0.75 mm (positive predictive values of 77%, 65% and 70%, respectively). Of the melanomas thinner than 0.76 mm, 82% showed a TDS lower than 6.80 (optimized cut-off point), while 79% of melanomas thicker than 0.75 mm had a TDS higher than 6.80 (chi2 = 30.815, P < 0.001); the positive predictive value of a TDS > 6.80 in the detection of lesions thicker than 0.75 mm was 79%. In conclusion, a statistically significant correlation does exist between some dermoscopic features and melanoma thickness. Both the mostly used dermoscopic methods (standard ELM pattern analysis and the ABCD rule of dermatoscopy) may provide useful information in the non-invasive assessment of melanoma thickness. However, their diagnostic performance is far from 100%; further studies are needed to investigate whether the combination of dermoscopy with other non-invasive approaches (e.g. sonometry) may result in an overall improvement in the diagnostic performance.     

Evidence and interdisciplinary consense-based German guidelines: diagnosis and surveillance of melanoma

Melanoma is a malignant tumor that arises from melanocytic cells and primarily involves the skin. The most important exogenous etiological factor is exposure to ultraviolet irradiation. Diagnosis of melanoma is based primarily on its clinical features, and the A-B-C-D rule is useful in identifying pigmented lesions, which are suspicious for melanoma (Asymmetry, Border irregular, Color inhomogeneous and Diameter more than 5 mm). Dermoscopy is very helpful in clarifying the differential diagnosis of pigmented lesions. About 90% of melanomas are diagnosed as primary tumors without any evidence for metastasis. The tumor-specific 10-year survival for all such tumors is about 75-85%. The most important prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen, presence of histopathologically recognized ulceration, invasion level (Clark level) and identification of micrometastases in the regional lymph nodes via sentinel lymph node biopsy. The current tumor node metastasis classification for the staging of primary melanoma is based on these factors. Melanomas can metastasize either by the lymphatic or by the hematogenous route. About two-thirds of metastases are originally confined to the drainage area of regional lymph nodes. A regional metastasis can appear as satellite metastases up to 2 cm from the primary tumor, as intransit metastases in the skin between the site of the primary tumor and the first lymph node and as regional lymph node metastases. In the stage of regional metastasis, the differentiation between micrometastasis and macrometastasis and the number of lymph nodes involved are crucial. As soon as distant metastasis develops, prognosis depends on the site of the metastasis and on the lactate dehydrogenase levels in the blood. The frequency and extent of follow-up examinations is based on the initial tumor parameters. In thin primary melanomas up to 1-mm tumor thickness, clinical examinations at 6-month intervals are sufficient and in thicker primary melanomas, at 3-month intervals. Lymph node sonography as well as determination of the tumor marker protein S100beta are recommended. Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually.     

In vivo evaluation of melanoma thickness by multispectral imaging and an artificial neural network. A retrospective study on 250 cases of cutaneous melanoma

AIMS AND BACKGROUND: Noninvasive diagnostic methods such as dermoscopy, sonography, palpation or combined approaches have been developed in an attempt to preoperatively estimate melanoma thickness. However, the clinical presentation is often complex and the evaluation subjective. Multispectral image analysis of melanomas allows selection of features related to the content and distribution of absorbers, mainly melanin and hemoglobin, present within the lesion. Hence, it is reasonable to assume that the same features might be useful to predict melanoma thickness. METHODS: A multispectral image system was used to analyze in vivo 1939 pigmented skin lesions. The lesion selection was based on clinical and/or dermoscopic features that supported a suspicion for melanoma. All the lesions were then subjected to surgery for the histopathological diagnosis, and 250 were melanomas. From the multispectral images of the melanomas, we selected 12 features, seven of which were used to train and test an artificial neural network on 155 and 95 melanomas, respectively. RESULTS: Sensitivity (i.e., melanoma > or = 0.75 mm thick correctly classified) and specificity (i.e., melanoma < 0.75 mm thick correctly classified) evaluated from the receiving operating characteristic curves ranged from 76 to 90% and from 91 to 74%, respectively. CONCLUSIONS: Our approach provides results similar to those obtained with other methods and has the advantage that it is not related to the expertise of the clinician. In addition, the physical interpretation of the selected features suggests a possible role of spectrophotometry as an objective method to study the natural history of the early phases of the disease.     

TTC4, a novel candidate tumor suppressor gene at 1p31 is often mutated in malignant melanoma of the skin

A novel candidate tumor suppressor gene, TTC4, on chromosome 1p31 has been described recently. Since aberrations in this region have been detected in malignant melanoma, we investigated DNA of paraffin-embedded sections from 16 typical naevi, 19 atypical naevi, 32 primary melanomas (15 superficial spreading melanomas, 17 nodular melanomas) and 25 metastases and DNA from four melanoma cell lines by PCR and direct sequencing analysis for mutations in all exons of TTC4. Tumors comprised a wide range of thickness (Breslow index) and Clark levels. No mutations could be detected in typical or atypical naevi, but we found seven different point mutations in the tumor samples, six of them causing an amino acid change. Ten melanoma samples belonging to nine patients showed one or more of these mutations. In detail, in six of 25 metastases, in two of 17 nodular melanomas and in two of 15 superficial spreading melanomas point mutations could be detected. In two cell lines, a loss of a whole exon could be demonstrated and in one cell line we found a point mutation. In addition, three polymorphisms were found. Our findings indicate that TTC4 may participate in the pathogenesis of malignant melanomas of the skin.     

Pitfalls in frozen section diagnosis of malignant melanoma

The importance of obtaining an intraoperative diagnosis and measurement of thickness of a malignant melanoma has emerged since the change in the surgical approach towards thin melanomas (0.75 mm). In experienced centers, both diagnosis and thickness, can be established on frozen section. Eighty-four pigmented lesions were examined on frozen section. Thirty of 31 were correctly diagnosed as malignant melanomas. The one not diagnosed was a regressing melanoma. The frozen section diagnosis of a regressing melanoma is difficult, and this should be deferred until paraffin sections are examined. In 29 consecutive skin melanomas thickness was measured on frozen section and was found to be 0.1-0.4 mm more than that measured on paraffin sections of the same specimens. It is therefore suggested that tumors measuring up to 0.85 mm on frozen section should be included in the group of thin melanoma.     

Clinicopathological features of melanocytic skin lesions in Egypt.

Although melanocytic skin lesions have been recognized since antiquity, their literature was limited to Caucasians. To date, the clinicopathologic features of these lesions in Egyptians are still unknown. To define these features, diagnostic records of the melanocytic skin lesions received at the Pathology Department, Assuit University Hospitals (1989-2004) were reviewed. The lesions examined included 12 benign naevi (BN), 10 dysplastic naevi (DN), and 21 cutaneous malignant melanomas (CMMs). The DN and CMMs were more common in men than in women (2 : 1 and 1.5 : 1, respectively) while BN were more common in women (2 : 1). The average age incidence was 33+/-5, 38+/-7 and 54+/-3 years, for BN, DN and CMM, respectively. The lower limb (13/21, 62%), head and neck (7/21, 33%) were the most common sites for CMMs. The average size (mm) was 2+/-0.3, 4+/-0.6 and 21+/-0.3 for BN, DN and CMMs, respectively. Recurrence occurred in 10% of CMMs. Histologically, CMMs were of nodular type and composed of epithelioid (7/21, 33%), spindle cells (1/21, 5%), or mixed cells (13/21, 62%). The mean tumour thickness (Breslow) was 6+/-0.5 mm. CMMs included two of 21(9%), three of 21(14%), six of 21(38%), and 10 of 21(38%) with Clark level II, III, IV and V. In Egypt, CMM is the third most common cutaneous neoplasm following squamous and basal cell carcinomas. Compared with Western societies, melanoma has a male sex predilection, similar histological features but different topographical distribution and rare incidence. The striking difference from Western series is the incidence of nodular melanoma - in the West this represents 15-30% of melanomas, with superficial spreading being the majority. Another key difference from the West is the 'sun-bed' culture of the West and the desire to have suntans. This is the first study that reports the clinicopathologic features of melanocytic skin lesions in Egypt.     

Melanoma with benign melanocytic naevus components: reappraisal of clinicopathological features and prognosis

The clinicopathological features and prognosis of primary cutaneous malignant melanoma with benign melanocytic naevus (BMN) components are still under debate. The purpose of this study was to characterize further the clinical and histopathological features of naevus-associated melanomas, with emphasis on the BMN components, and to examine their prognosis based on a large series. Following a histopathological review of 667 consecutive cases of primary cutaneous melanoma, 148 melanomas with BMN components (22.1%) were identified for further study. A control group of 519 melanomas without BMN components seen in a similar period were also studied. Clinically, patients with melanomas containing BMN components (n = 148; age range 25-86 years, mean age 54 +/- 16 years; male to female ratio 1:1.02) presented with tumours located mainly on the trunk (34.5%), followed by the upper extremities (24.3%), lower extremities (20.3%), and head and neck (14.2%). Compared with tumours without BMN components (n = 519; age range 19-89 years, mean age 57 +/- 15 years; male to female ratio 1:1.3), melanomas with BMN components occurred in slightly younger individuals (P = 0.027). Histopathologically, BMN components mainly showed features of acquired naevi (total 87 cases; dysplastic, 80 cases; banal, seven cases) or congenital naevi (total 57 cases; superficial, 56 cases; deep, one case), but a minority of these lesions (four cases) could not be further subcategorized. Generally, melanomas containing BMN components were relatively thinner than melanomas without BMN components (mean Breslow index 0.95 +/- 0.83 mm and 1.3 +/- 1.6 mm, respectively) (P = 0.015). The follow-up data available in 69 patients with naevus-associated melanomas consistently revealed a relatively good outcome (5 year metastasis-free survival rate 93.75%), although no statistical difference in prognosis was observed between this group and a subset of 283 melanomas patients without BMN components stratified by tumour thickness. We conclude that BMN components in naevus-associated melanomas constitute a heterogeneous group morphologically, consisting mainly of dysplastic and superficial congenital naevi. This finding indicates a more important role for superficial congenital naevus as a precursor lesion of naevus-associated melanomas than presently recognized. Patients with naevus-associated melanomas generally show a good clinical outcome, reflecting their small Breslow index.     

Time trends of cutaneous melanoma in Queensland, Australia and Central Europe

BACKGROUND: The objective of this study was to describe recent developments in cutaneous melanoma from the German speaking countries in Europe (Germany, Austria, and Switzerland) and from Queensland, Australia. METHODS: All incident invasive cutaneous melanoma cases recorded between 1986 and 1996 by the Queensland Melanoma Register and by the Central Malignant Melanoma Registry of the German Dermatological Society were included in the analysis. Weighted linear trend analyses were performed to assess significant changes over the years using yearly sample sizes as weights. RESULTS: In Central Europe, the median tumor thickness decreased from 1.2 mm in 1986 to 0.8 mm in 1996 (P < 0.001), whereas it varied insignificantly between 0.5 mm and 0.6 mm in Queensland. The percentage of patients with Clark Level II invasion increased significantly in Queensland (P < 0.001; 1996, 61.1%) and in Central Europe (P = 0.041; 1996, 24.5%). The percentage of superficial spreading melanomas rose in Central Europe (P = 0.043; 1996, 64.4%), whereas it decreased slightly in Queensland (P = 0.032; 1996, 75%). In Queensland and in Central Europe, younger people and women presented more frequently with thinner melanomas (相似文献   

Frequency and characteristics of melanomas missed at a pigmented lesion clinic: a registry-based study

To ensure the removal of all melanomas at an early phase, a number of benign lesions are currently excised for diagnostic evaluation. Nevertheless, little is known about the frequency of melanomas missed (neither recognized nor excised for diagnostic verification) by early detection practices. This study aimed to investigate the diagnostic performance of a specialized pigmented lesion clinic (PLC) through linkage with a local cancer registry. In 1997, 1741 individuals resident in the area of Florence and Prato, Italy, the catchment area of the Tuscany Cancer Registry (RTT), were consecutively examined at a specialized PLC that has been running since 1992 at the Department of Dermatology of Florence. The outcomes of dermatological consultations retrieved from PLC case notes were compared with all the diagnoses of both in situ and invasive melanoma recorded by the RTT until 31 December 1999. The performance of the PLC in detecting cutaneous melanoma was evaluated in terms of sensitivity, specificity and predictive values, with the RTT data as the gold standard. In the population examined at the PLC, 15 newly incident melanomas, all histologically demonstrated, were recorded by the RTT. In 13 of the 15 cases, excision of the lesion had been recommended by PLC staff, while two melanomas, one in situ and one level II 0.60 mm thick invasive, were missed and were subsequently excised 586 and 824 days, respectively, after the first PLC examination. The clinical and dermoscopic features of the invasive lesion were in agreement with a 'featureless' melanoma, and lacked the well-established parameters of malignancy. A total of 67 benign pigmented skin lesions were excised for diagnostic evaluation. Thus the PLC showed a sensitivity in detecting cutaneous melanoma of 86.7% (95% confidence interval [CI] 85.1-88.3%), a specificity of 95.4% (95% CI 94.3-96.3%), a positive predictive value of 13.7% (95% CI 12.1-15.3%) and a negative predictive value of 99.9% (95% CI 99.7-100.0%). The ratio of melanomas to benign skin lesions excised was 1:5.1. In conclusion, specialized examination of pigmented skin lesions at the PLC offered good level of diagnostic performance, with an acceptable cost in terms of benign lesions removed and overall a low risk of missing melanomas.     

Kinetic model of progression of cutaneous melanoma population

A kinetic model for progression of a population of cutaneous melanomas through categories defined by the range of Breslow thickness, with melanomas in situ (MIS) in category 0, and melanomas with Breslow thickness > or =2 mm in category 3, is described. The model assumes that all melanomas start out in category 0; this category is further subdivided into indolent and progressing melanomas. Steady-state solutions for the distributions of excised melanomas were found. Depending on the proportion of indolent MIS, these solutions predict very different distributions of excised melanomas and melanoma mortality, when either frequency of examinations by physicians or sensitivity to melanoma is changed. Although it is not currently possible to differentiate between indolent and progressing MIS either clinically or histologically, solutions of this kinetic model can be used to determine the proportion of such indolent lesions in a population-based study. The steady-state solutions of the kinetic model can be used to analyze melanoma progression in any stable patient population, in which the total number of melanomas detected per year is either stable or varies slowly. As an example, melanoma progression is analyzed using the American Cancer Society estimates of melanoma incidence and mortality. For a fixed incidence rate, melanoma mortality and melanoma treatment cost in the USA could be significantly reduced by increasing the biopsy sensitivity of physicians to in-situ and thin-invasive melanomas.     

Association between germ cell tumours, large numbers of naevi, atypical naevi and melanoma

Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple pigmented cutaneous spots. Forty-nine patients bearing a great number of naevi or atypical naevi were included in the study. Two thin cutaneous melanomas were discovered in two patients. In addition, a third patient had had a conjunctival melanoma since treatment of the GCT. Our study confirms the presence of atypical naevi in a subgroup of GCT patients, who are shown to be at high risk of developing melanoma. Patients harbouring multiple pigmented spots should be referred for a skin examination aimed at early detection of curable melanomas, and should be advised to protect themselves from sun exposure.     

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.     

A Retrospective Multicenter Evaluation of Cutaneous Melanomas in Turkey

Background: We defined melanoma distribution in a large series of Turkish patients and evaluated theprognostic parameters of melanomas. Materials and Methods: A total of 1574 patients’ data was retrospectivelycollected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametreswere evaluated based on sentinel lymph node involvement. Results: Mean age was 56.7 (4-99) years. While 844(53.6%) cases were male, 730 (46.4%) cases were female. One thousand four hundred forty-seven (92%) caseswere invasive melanoma and 127 (8%) cases were in-situ melanoma. The most common histopathological formwas the superficial spreading melanoma (SSM) which was found in 549 patients (37.9%). It was followed bynodular melanoma in 379 (26.2%), acral lentiginous melanoma (ALM) in 191 (13.2%) and lentigo malignamelanoma in 132 (9.1%), respectively. On univariate analysis, lymphovascular invasion (p<0.001), tumorthickness (p<0.001), histopathological subtype (p<0.001), Clark level (p=0.001), ulceration (p<0.001), ≥6/mm2mitosis (p=0.005), satellite formation (p=0.001) and gender (p=0.03) were found to be associated with sentinellymph node positivity. Regression was associated with sentinel lymph node negativity (p=0.017). According tomultivariate analysis, lymphovascular invasion and tumor thickness were significant independent predictivefactors of SLN positivity. Patient age, tumor localization, precursor lesions, lymphocytic infiltration andneurotropism were not related with sentinel lymph node involvement. Conclusions: In this retrospective analysis,it was found that the prevalence of SSM is at a lower rate while the prevalence of ALM is at a higher rate whencompared to western countries. According to Breslow index; most of the melanoma lesions’ thickness weregreater than 2 mm, corresponding Clark IV. Vascular invasion and tumor thickness are the most importantfactors for sentinel lymph node involvement.