Comparison between lentigo maligna melanoma and other histogenetic types of malignant melanoma of the head and neck. Scottish Melanoma Group.

A study of 953 invasive cutaneous malignant melanomas of the head and neck was performed to determine differences between lentigo maligna melanoma and other histogenetic types with regard to patients and sites affected; prognosis was analysed in 595 of these cases. The cases studied comprised all head and neck melanomas registered with the Scottish Melanoma Group between 1979 and 1992, apart from the 3% of cases that were unclassifiable or rare histogenetic types. The histogenetic types of melanoma were 498 (52%) lentigo maligna melanoma (LMM), 237 (25%) superficial spreading melanoma (SSM) and 218 (23%) nodular melanoma (NM). All types increased in incidence throughout the study period. Patients with LMM (mean age 73 years) and NM (mean 68 years) were significantly older than those with SSM (mean 57 years). There were significant anatomical subsite differences related to sex of patients and histogenetic type of melanoma; melanomas on the face were more frequent in females and 90% of LMM occurred at this site, whereas melanomas on the scalp, neck and ears were more frequent in men. Kaplan-Meier estimates of the probability of survival were produced for the 595 of these 953 patients with 5 year follow-up details. In this group of patients the prognostic significance of tumour thickness, Clark level of invasion, ulceration, histogenetic type of melanoma and number of mitoses were studied using stepwise variable selection of procedures. Each of these possible prognostic factors attained individual significance but the tumour thickness was the dominant risk factor in the proportional hazards analysis. When patients were divided into four sex/ulceration subgroups (male/ulcerated, female/ulcerated, male/non-ulcerated, female/non-ulcerated) and analysed by proportional hazards analysis, no variable other than the tumour thickness had any further prognostic effect. Histogenetic type did not remain an independent prognostic variable at this stage. Despite sex and subsite differences, the prognosis for invasive lentigo maligna melanoma does not differ from that for other histogenetic types after controlling for tumour thickness.     

Factors related to the presentation of thin and thick nodular melanoma from a population‐based cancer registry in Queensland Australia

BACKGROUND:

Worldwide, the incidence of thick melanoma has not declined, and the nodular melanoma (NM) subtype accounts for nearly 40% of newly diagnosed thick melanoma. To assess differences between patients with thin (≤2.00 mm) and thick (≥2.01 mm) nodular melanoma, the authors evaluated factors such as demographics, melanoma detection patterns, tumor visibility, and physician screening for NM alone and compared clinical presentation and anatomic location of NM with superficial spreading melanoma (SSM).

METHODS:

The authors used data from a large population‐based study of Queensland (Australia) residents diagnosed with melanoma. Queensland residents aged 20 to 75 years with histologically confirmed first primary invasive cutaneous melanoma were eligible for the study, and all questionnaires were conducted by telephone (response rate, 77.9%).

RESULTS:

During this 4‐year period, 369 patients with nodular melanoma were interviewed, of whom 56.7% were diagnosed with tumors ≤2.00 mm. Men, older individuals, and those who had not been screened by a physician in the past 3 years were more likely to have nodular tumors of greater thickness. Thickest nodular melanoma (4 mm+) was also most common in persons who had not been screened by a physician within the past 3 years (odds ratio, 3.75; 95% confidence interval, 1.47‐9.59). Forty‐six percent of patients with thin nodular melanoma (≤2.00 mm) reported a change in color, compared with 64% of patients with thin SSM and 26% of patients with thick nodular melanoma (>2.00 mm).

CONCLUSIONS:

Awareness of factors related to earlier detection of potentially fatal nodular melanomas, including the benefits of a physician examination, should be useful in enhancing public and professional education strategies. Particular awareness of clinical warning signs associated with thin nodular melanoma should allow for more prompt diagnosis and treatment of this subtype. Cancer 2009. © 2009 American Cancer Society.     

Cutaneous malignant melanoma in Swedish children and teenagers 1973-1992: a clinico-pathological study of 130 cases

To assess whether there has been a change in histological features and prognostic factors of primary cutaneous malignant melanoma (CMM) in young individuals in Sweden, an unselected, population-based study was undertaken; 177 cases of primary CMM in persons below 20 years of age were reported to the Swedish National Cancer Registry between 1973 and 1992. In 87% of the cases, original tumor tissue was available for histo-pathological review. The original diagnosis was verified in 88% (n = 126) of these cases. All tumors had histological features similar to adult CMM; 17% had an associated precursor lesion. Superficial spreading melanoma (SSM) was the most common sub-type, constituting 20/36 cases in the first decade and 59/90 in the second. Corresponding figures for nodular melanoma (NM) were 11/36 and 23/90. Only 5 melanomas in situ were diagnosed. In girls, the mean thickness of SSM decreased from 1.5 to 0.6 mm (p < 0.001). Overall mortality was 10%, 22% in the group with CMM diagnosed 0-15 years of age and 8% in individuals 15-19 years. Fatal CMM cases diagnosed below 15 years of age (n = 4) were NM > 1.6 mm thick and in subjects 15-19 years (n = 9) 44% of fatal tumors were NM with a mean thickness of 2.2 mm. Breslow index was the single most important prognostic factor. However, when known prognostic factors were adjusted for in a Cox regression analysis, young age remained an independent risk factor, with a relative death rate of 0.21 for individuals aged 15-19 compared with children < 15 years of age.     

Malignant melanoma in Taiwan: a prognostic study of 181 cases

This study was performed to determine the characteristics and clinical outcome of patients with cutaneous malignant melanoma in Taiwan. The medical records of patients with primary cutaneous melanoma between 1992 and 2001 at Chang Gung Memorial Hospital (CGMH) were retrieved from the cancer registry. Survival was analysed by the Kaplan-Meier method. Univariate and multivariate analyses of factors associated with survival were performed using the Cox proportional hazard model. One hundred and eighty-one cases were retrieved from the cancer registry of CGMH. The male to female ratio was 1 : 1.13. The most common age of onset was the sixth decade. The median age of onset was 61 years (2-95 years). There were 105 cases (58%) of acral lentiginous melanoma (ALM), 55 cases (30.4%) of nodular melanoma (NM), 19 cases (10.5%) of superficial spreading melanoma (SSM) and two cases (1.1%) of lentigo maligna melanoma. The median survival of the 181 patients was 3.71 years, and the 5-year survival rate was 45.63%. Five-year survival rates of patients with stages I, II, III and IV disease were 84.39%, 56.03%, 34.7% and 0%, respectively. Sex, Breslow thickness, Clark's level, pathological type and age were significant prognostic factors. There were no survival differences between ALM and NM. Both ALM and NM were associated with a poor prognosis when compared with SSM. In conclusion, ALM is the most common type of cutaneous malignant melanoma in Taiwan. The prognostic factors in Taiwan are similar to those in melanoma-prevalent countries.     

Etiological differences between subtypes of cutaneous malignant melanoma: Western Canada Melanoma Study

From newly incident cases in Western Canada, 415 patients with superficial spreading melanoma (SSM), 128 with nodular melanoma (NM), and 56 with lentigo maligna melanoma (LMM) were interviewed, with age- and sex-matched controls chosen from the general population. The associations of these 3 subtypes with pigmentation, skin reaction to sun, different types of sun exposure, sunburn, and suntan were assessed. Compared to the other types, LMM occurred in older patients, and 75% of lesions occurred on the head and neck: It was less strongly related to pigmentation factors, intermittent sun exposure, and skin reaction to sun. The associations of SSM and NM with pigmentation, chronic sun exposure, skin reaction, and suntan were very similar: Both were associated with intermittent sun exposure, but SSM was more strongly related to vacation exposures than was NM. These results were compared with those from a similar Australian study. While LMM appears different in its etiology from SSM and NM, there is no strong evidence of major etiological differences between SSM and NM.     

Changes in the presentation of nodular and superficial spreading melanomas over 35 years

BACKGROUND.

Nodular melanoma (NM) may be biologically aggressive compared with the more common superficial spreading melanoma (SSM), with recent data suggesting underlying genetic differences between these 2 subtypes. To better define the clinical behavior of NMs, the authors compared their clinical and histopathologic features to those of SSMs at their institution, a tertiary referral center, over 3 decades.

METHODS.

A total of 1684 patients diagnosed with 1734 melanomas were prospectively enrolled. Of these, 1143 patients (69% SSM, 11% NM, 20% other) were diagnosed between 1972 and 1982; 541 patients (54% SSM, 23% NM, 23% other) were diagnosed between 2002 and the present. Differences between the features of NM and SSM within each time period as well as changes over time were analyzed.

RESULTS.

The authors found that SSMs are now diagnosed as thinner lesions (P < .0001) with a low incidence of histologic ulceration (P < .0001), whereas there was no significant change in the median tumor thickness or ulceration status of NMs over time (P = .10, P = .30, respectively). The median age at diagnosis of NM, however, did significantly increase over time (51 years to 63 years, P < .01). The median duration of NMs was reported to be only 5 months compared with 9 months in SSM patients.

CONCLUSIONS.

The authors' data suggest that improvements have been made in the early detection of SSM but not NM. Modifications of current screening practices, including increased surveillance of high‐risk patients with an emphasis on the “E” for “evolution” criterion of the ABCDE acronym used for early detection of melanoma, are thus warranted. Cancer 2008. © 2008 American Cancer Society.     

Anorectal melanoma: surgical management guidelines according to tumour thickness

Management of patients with anorectal melanoma is still controversial. To reach a rationale therapeutic approach, we reviewed our experience obtained over the past decade. In all, 19 consecutive patients with the diagnosis of anorectal melanoma were included in this retrospective survey. Details of the patients' presentation, symptoms, tumour size and histology and tumour state were recorded, and the primary therapeutic procedures were evaluated in detail. The size of the tumours ranged between 0.5 and 7 cm in diameter. The median tumour thickness was 10 mm (range 0.6-40 mm). At diagnosis, six of 19 patients already presented with either regional or distant metastases. The remaining 13 patients were treated with curative intend, either by abdomino-perineal resection (APR) or wide local excision (WLE). The form of operative therapy, however, had no impact on overall survival. Nevertheless, the incidence of local recurrences was lower after APR even for patients with less favourable tumours. In conclusion, WLE alone is not sufficient for local tumour control of thick anorectal melanoma.     

Delay in the diagnosis of cutaneous melanoma: an analysis of 233 patients

Knowledge of factors associated with the detection of cutaneous malignant melanomas and reasons for delay in diagnosis are essential for the improvement of secondary prevention of cutaneous melanoma. For this reason, the extent and consequence of patient and professional delay in diagnosis and treatment was investigated in 233 patients with histologically proven primary cutaneous melanomas seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University, Munich, Germany, between January 1999 and January 2001. Personal interviews were conducted by two physicians to obtain information on patients' knowledge of melanoma symptoms, sun behaviour, delay in seeking medical attention, professional delay and related factors. The main component of delay was patient related. Nearly one-third (29.2%) of all patients reported a delay interval of more than 12 months from the onset of an observed change in a pigmented lesion or first detection of a pigmented lesion to the first visit to a physician. The delay interval from the first visit to a physician to surgical treatment was shorter (< 1 month) in most of our patients (74.7%). The predominant symptoms of melanoma detected by patients were a change in colour and an increase in size or elevation. Most patients had obtained knowledge about cutaneous melanomas from television and magazines. A delay in diagnosis and a history of many sunburns and outdoor leisure time activities were not associated with a greater tumour thickness. However, fairer skin types, lower education levels and lack of knowledge about cutaneous melanoma were associated with a greater tumour thickness. Further efforts are necessary to improve public and medical education about early detection and prompt surgical treatment, which is known to be the most effective treatment modality for cutaneous melanomas.     

Skin characteristics and risk of superficial spreading and nodular melanoma (United States)

Objective: To assess the risk for melanoma associated with moles and pigmentary characteristics. Methods: Representative melanoma cases (773) among non-Hispanic white residents under age 65 occurring between 1 June 1978 and 1 December 1983 in Los Angeles County were compared to controls (752) matched to cases by age, sex, race and neighborhood of residence. Factors considered include hair, eye, and skin color; numbers of freckles and moles; and propensity to burn and tan obtained during an in-person interview. Results: Five hundred and fifty-one cases were classified as superficial spreading melanoma (SSM) and 110 as nodular melanoma (NM). For SSM, the important risk determinants were hair and skin color, freckling, and mole prevalence. Light skin and more freckles were found to be more highly associated with SSM for younger compared to older subjects, whereas the associations between SSM and both hair color and moles remained independent of age. NM showed patterns of risk similar to SSM with the exception of skin color. NM showed no evidence of increasing risk with lighter skin, as compared to the strong association seen for SSM. Conclusion: Hair and skin color, freckling and, especially, numbers and size of moles are important determinants of melanoma risk.     

Associations between childhood height and morphologically different variants of melanoma in adulthood

Aim of the studyMelanoma subtypes have different aetiological characteristics. Child height is positively associated with adult melanoma; however, a clarification of associations with specific melanoma variants is necessary for an improved understanding of risk factors underlying the histologic entities. This study investigated associations between childhood height and future development of cutaneous melanoma variants.MethodA cohort study of 316,193 individuals from the Copenhagen School Health Records Register, with measured heights at ages 7–13 years who were born from 1930 to 1989. Melanoma cases were identified via linkage to the national Danish Cancer Registry and subdivided into subtypes. Cox proportional hazards regressions were performed.ResultsA total of 2223 cases of melanoma distributed as 60% superficial spreading melanoma (SSM), 27.5% melanoma not otherwise specified (NOS), 8.5% nodular melanoma (NM), and 2% lentigo maligna melanoma (LMM). The remaining rare melanoma forms were not analysed. Childhood height was positively and significantly associated with SSM, melanoma NOS, and NM, but not LMM, in adulthood. Per height z-score at age 13 years, the hazard ratios were 1.20 (95% confidence intervals [CI]: 1.13–1.27) for SSM, 1.19 (95% CI: 1.09–1.29) for melanoma NOS, and 1.21 (95% CI: 1.04–1.41) for NM. Further, growth patterns were linked to the melanoma variants with persistently tall children having an increased risk of developing SSM, melanoma NOS, or NM.ConclusionChildhood height is positively associated with the majority of the melanoma variants. These results suggest that the underlying processes contributing to childhood height and growth patterns interconnect early-life events with the predisposition to melanomagenesis in adulthood.     

Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.     

Differential clinical significance of alpha(v)Beta(3) expression in primary lesions of acral lentiginous melanoma and of other melanoma histotypes

Despite its potential clinical relevance, alpha(v)beta(3) expression has been analyzed only in a limited number of melanoma lesions, mostly nodular melanoma (NM) and superficial spreading melanoma (SSM). Therefore, in the present study, we have correlated alpha(v)beta(3) expression in 33 acral lentiginous melanomas (ALMs), 6 lentigo maligna melanomas, 7 mucosal melanomas, 12 NMs and 9 SSMs with their antigenic profile, with their histo-pathological characteristics and with the clinical course of the disease. Furthermore, we have compared alpha(v)beta(3) expression in ALM lesions with that in NM and SSM lesions since this information helps to clarify the relationship of the latter 2 histotypes with ALM. Such a relationship is uncertain since ALM has a clinical course similar to that of NM and SSM despite different antigenic profiles and biological characteristics. The level of alpha(v)beta(3) expression in primary lesions was not correlated with that of high-m. w. melanoma-associated antigen and intercellular adhesion molecule-1, with lesion thickness and with disease recurrence in ALM but was significantly correlated with these 4 parameters in the other melanoma histotypes analyzed. Therefore, alpha(v)beta(3) expression appears to have a differential clinical significance in ALM and in the other histotypes of melanoma we have analyzed since it appears to play a significant role in the progression of the disease only in non-ALM histotypes.     

Evolving concepts in melanoma classification and their relevance to multidisciplinary melanoma patient care

In the initial period after melanoma was recognised as a disease entity in the early 1800's, it was subclassified on the basis of its presumed origin (from a precursor naevus, from a melanocytic precursor lesion acquired during adult life or in previously blemish-fee skin). In 1967 the eminent American pathologist, Dr Wallace Clark, proposed a histogenetic classification for melanoma in which the disease was subdivided predominantly on the basis of histopathological features of the intra-epidermal component of the tumour adjacent to any dermal invasive component. The subtypes were superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM) and nodular melanoma (NM). Whilst additional entities, including acral lentiginous melanoma, mucosal melanoma, desmoplastic melanoma and naevoid melanoma have since been recognised, SSM, LMM and NM remain in the latest (2006) version of the WHO melanoma classification. Clark's histogenetic classification has been criticised because the criteria upon which it is based include clinical features (such as the site of the melanoma) and non-tumourous histopathological features (such as the character of the associated epidermis and the degree of solar elastosis) and also because of overlap in defining features, lack of an independent association with patient outcome and minimal relevance as a determinant of clinical management. However, such criticisms fail to acknowledge its importance in highlighting the myriad of clinical and histological guises of melanoma, which if not recognized by clinicians and pathologists will inevitably lead to a delay in diagnosis and a concomitant adverse clinical outcome. Recently, mutually exclusive oncogenic mutations in melanomas involving NRAS (15-20%), BRAF (50%), CKIT (2%), and GNAQ/GNA11 (50% of uveal melanomas) have been identified. This might herald the beginning of a new molecular classification of melanoma in which the biologically distinct subsets share a common oncogenic mechanism, behave clinically in a similar fashion and require similar clinical management. These discoveries are already being successfully exploited as therapeutic targets in clinical trials of metastatic melanoma patients with promising activity. Whilst there remains much to be discovered in this rapidly evolving field, there is already great optimism that more rational and effective therapies for melanoma patients will soon be widely available.     

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.     

Importance of tumour thickness measurement in prognosis of tongue cancer

Eighty-one patients who underwent surgery for cancer of the tongue were retrospectively studied to evaluate the influence on survival of some clinical and pathologic parameters. These parameters and data on the patient's current status were gathered by the study of tissue sections, using haematoxylin-eosin staining, and from medical records. The 5-year survival rate was 68.5%. Univariate analysis showed that the parameters influencing survival were: T (P<0.01), pathologic T (P<0.01), N (P<0.05), pathologic N (P<0.05), extracapsular nodal spread (P<0.05), locoregional recurrence (P<0.01), and tumour thickness (P<0.05). Multivariate analysis showed that tumour thickness had the greatest influence on survival. Patients with tumour thickness of < or = 3 mm had a 5-year survival of 85.7%, significantly greater (P<0.05) than the rates of 58.3 and 57% for patients with tumour thickness of 4-7 mm and >7 mm, respectively. Wider studies are required to unify criteria for the measurement of this important prognostic parameter.     

Patients' and doctors' delay in the diagnosis and treatment of cutaneous melanoma

Factors involved in patients' and doctors' delay in the diagnosis and treatment of primary or metastatic cutaneous melanoma were studied in an inquiry of 284 patients in 12 hospitals. The most important patients' delay factors were: unawareness of the danger of the earliest and to a lesser extent the late signs and symptoms in the evolution of melanoma. Age and socio-economic status were of negligible importance in this respect. When the primary melanoma was easily visible, patients noticed the first signs of the developing melanoma significantly earlier than when the primary was not visible; nevertheless visibility had no impact on tumor thickness. This again shows that the early signs were not experienced as signs that required a visit to a doctor. Patients who showed their melanoma as a secondary complaint while they visited the doctor for another condition, had a more favorable tumor thickness than those who only came for their melanoma. The most important factors in doctors' delay were lack of suspicion (often due to amelanosis), and the performance of an incisional or punch biopsy and treatment without histopathology. Melanomas discovered by chance during a physical examination while the patient was totally unaware of the lesion had a most favorable tumor thickness. These observations indicate that a better education of the general public and of the medical profession is warranted, in order to improve the prognosis of cutaneous melanoma.     

Familial melanoma by histology and age: Joint data from five Nordic countries

BackgroundWe aimed to estimate lifetime cumulative risk of melanoma (CRM) in relatives of patients with melanoma by histology and age at diagnosis in patients and relatives.MethodsA population-based cohort of 238 724 first-degree relatives of 46 091 melanoma patients diagnosed in 1955–2010 in Nordic countries was followed for cancer incidence.FindingsThe CRM (0–79 years) in first-degree relatives of a patient with superficial spreading (SSM), nodular (NM), or lentigo maligna melanoma was quite similar, ranging from 2.5% to about 3%, which represents about 2-fold increase over the general population risk. When one melanoma patient in the family was diagnosed before age 30, the CRM was about 3%. When there were ⩾2 melanoma patients diagnosed before age 30 in a family, CRM for relatives was about 14%, 6% for diagnoses at age 30–59, and 5% for diagnoses at age 60 or older. Depending on age at diagnosis of same-sex twins (not known whether monozygotic/dizygotic), their CRM was about 7–21%. Although no familial case of concordant histological types of acral lentiginous/desmoplastic/compound nevus/spindle cell melanomas or malignant blue nevus was found, familial risks of discordant histological types of melanoma were interchangeably high for most of the types, e.g. higher risk of SSM when a first-degree relative had NM [standardized incidence ratios (SIR) = 2.6, 95% confidence interval (CI) = 2.1–3.3, n = 72] or acral lentiginous (4.0, 95%CI = 1.5–8.8, n = 6) and vice versa. There was a tendency toward concordant age at diagnosis of melanoma among relatives of melanoma patients.InterpretationFindings of this study may help clinicians to find subjects at high melanoma risk for the genetic counseling. The risk was highest when melanoma occurred in a same-sex twin, one first-degree relative diagnosed at young age (<30), or ⩾2 first-degree relatives. Histological type of melanoma does not seem to play an important role in familial melanoma.FundingThis work was supported by the Nordic Cancer Union, Swedish Council for Working Life and Social Research, and German Cancer Aid.     

Risk of ocular melanoma in relation to cutaneous and IRIS naevi

A case-control study was set up to assess the risk of eye melanoma in relation to the number and type of cutaneous melanocytic naevi and pigmented lesions of the iris. Cases comprised 211 unselected ocular melanoma patients attending the Ocular Oncology Clinic at Moorfields Eye Hospital, London, during November 1990 to October 1991 and diagnosed after August 1986. Hospital and general practice controls (416) were recruited in the North East Thames Region of the UK. Cutaneous naevi greater than or equal to 2 mm in diameter were counted on the skin. Clinically atypical and congenital naevi were recorded separately. Pigmented lesions of the iris were counted. The relative risk for ocular melanoma increased with numbers of atypical naevi and numbers of common naevi. Ten percent of cases but 3% of controls had at least 100 naevi of 2 mm or greater diameter. Seven percent of cases and 0.4% of controls had 4 or more atypical naevi. Pigmented lesions of the iris were significantly more common in cases than controls. Nine percent of cases had the Atypical Mole syndrome (AMS) phenotype compared with 1% of controls. Six cases had concurrent cutaneous melanoma primaries. We conclude that atypical and iris naevi are important risk factors for eye melanoma and that patients with eye melanoma are at increased risk of cutaneous melanoma. Dermatological examination for the AMS phenotype and cutaneous melanoma should be recommended in eye melanoma patients with large numbers of pigmented lesions of the skin or family history of melanoma.     

Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.     

Prognosis of stage I melanoma of the skin. Who collaborating centres for evaluation of methods of diagnosis and treatment of melanoma

Prognosis of stage I melanoma of the skin was evaluated in 747 previously untreated patients observed by the WHO Collaborating Centres for Evaluation of Methods of Diagnosis and Treatment of Melanoma from September 1967 to September 1975. The mean follow-up period of these patients was 8.9 years. Sex, maximum diameter of melanoma, elevation on skin surface, histologic type, levels of invasion and maximum tumor thickness were found to be significantly related to survival when considered one by one. However, multifactorial analysis showed that sex and maximum thickness only had a significant impact on survival of stage I melanoma patients. The effect of sex was not evident in patients with maximum tumor thickness not exceeding 2 mm (81 % 5-year survival for males and 87% for females and a p value >0.05), while females did significantly better (p <10^?4) when maximum thickness of primary was over 2 mm.