A profile of invasive cutaneous malignant melanoma in Malta: 1993–2002

BACKGROUND: The incidence of malignant melanoma of the skin has risen in every part of the world where reliable cancer registration data are found. OBJECTIVE: Our study aims to describe the changing incidence of and survival from invasive cutaneous malignant melanoma in Malta, by analysing the data from the 211 cases that were registered at the Malta National Cancer Registry between 1993 and 2002. RESULTS: The age standardized incidence rates for invasive cutaneous malignant melanoma rose from 3.7 per 100,000 population per year for males and 5.1 for females in the first 5-year period, to 8.0 per 100,000 population per year for males and 5.9 for females in the second 5-year period. In both sexes, numbers of thin (< or = 1.0 mm) invasive melanomas increased significantly between 1993 and 2002; males also registered a significant increase in intermediate-thickness (1.01-4.0 mm) melanomas. The increase in numbers of thin and intermediate-thickness melanomas between the two 5-year periods was greatest in patients aged 60 years and over. The overall absolute 5-year survival rate for the first period was 74% and for the second period 92%. CONCLUSION: Numbers of reported cases of invasive cutaneous malignant melanoma in Malta have more than doubled during the 10-year study period. This is mostly due to a marked rise in the diagnosis of thin melanomas in both sexes, occurring mainly in patients aged 60 years and over. As thin melanomas are of low metastasizing potential, this has resulted in an increase in survival between the two 5-year study periods.     

皮肤黑色素瘤诊治的误区

目的揭示皮肤黑色素瘤诊断和治疗的误区，探讨合理诊断和治疗黑色素瘤的方法。方法结合有关文献，并对15例足部皮肤黑色素瘤的病程和治疗进行分析。结果大多数患者没有及时就医以及医疗单位病检取材不合理。结论正确取材活检，明确切除范围，及时手术以及一期修复组织缺损是有效防止癌肿扩散，提高生存率的关键。     

Comparison of diagnostic accuracy for cutaneous malignant melanoma between general dermatology,plastic surgery and pigmented lesion clinics

BACKGROUND: Since the 1980s there have been dedicated pigmented lesion clinics (PLCs) in the U.K. Important considerations when comparing the efficacy of the PLC with other referral clinics include diagnostic accuracy. OBJECTIVES: To compare the false-negative rate of clinical diagnosis (FNR) in the PLC with that in the other clinics of primary referral of malignant melanoma (MM) in the same geographical area. We have previously shown that certain clinical features are risk factors for diagnostic failure of MM. A further aim of this study was to correct for any differences in frequency of these factors in the melanoma populations between clinics and to estimate the false-positive diagnostic rate (FPR) in the PLC. METHODS: To compare the FNR between clinics, the case notes of all patients presenting with histologically proven cutaneous MM in Leicestershire between 1987 and 1997 were examined retrospectively. A false-negative diagnosis was defined as documentation of another diagnosis and/or evidence in the case notes that the diagnosis was not considered to be MM. The FNR was estimated as the number of false-negative clinical diagnoses/number of true-positive histological diagnoses. To estimate the diagnostic FPR, which was defined as the number of false-positive clinical diagnoses of MM/total number of positive clinical diagnoses, in the PLC, the outcome of 500 consecutive patients attending the PLC was surveyed. RESULTS: The case notes of 731 patients were available, of whom approximately two-thirds initially attended the PLC, one-fifth the General Dermatology clinics (D) and the remainder were divided approximately equally (one-twentieth each) between Plastic Surgery clinics (P), other clinics (O) and the surgery of the general practitioner (GP). The last was regarded as the primary referral clinic if the lesion were excised there prior to any referral. The FNR was lowest for the PLC, at 10%, compared with 29% (D), 19% (P), 55% (O) and 54% (GP) (P < 0.0001). Lesions with risk factors for diagnostic failure were under-represented in the PLC (P < 0.0001), the mean frequencies of the risk factors being 20% (PLC), 25% (D), 22% (P), 31% (O) and 30% (GP). Differences were not large but still could partially explain the lower FNR of the PLC. However, when the FNR was estimated for lesions exhibiting each of these risk factors, the PLC was found to have the lowest rate in every case (PLC vs. all clinics combined, P = 0.04 to P < 0.0001). The mean FNR for the risk factors combined was 18% (PLC), 45% (D), 50% (P), 68% (O) and 71% (GP). Also on logistic multivariable analysis of the PLC vs. all the other clinics on FNR and the above factors, the higher FNR of the other clinics retained significance (odds ratio 5.9, P < 0.0001). In the 500 patients surveyed separately in the PLC, the MM pick-up rate on biopsy was 32% and the diagnostic FPR was 41%. CONCLUSIONS: The FNR of MM was lower in the PLC than in the other clinics, while the pick-up rate for MM on biopsy and the FPR were acceptably low.     

Clinicopathologic and prognostic significance of SATB1 in cutaneous malignant melanoma

Background

Special AT-rich sequence-binding protein-1 (SATB1), a new type of gene regulator, has been reported to be expressed in several human cancers and may have malignant potential. However, no data on SATB1 expression and its relationship to tumor progression in cutaneous malignant melanoma (CMM) has yet been reported.

Objective

We examined the immunohistochemical expression of SATB1 in CMM to determine whether it could serve as a prognostic marker.

Methods

A total of 97 samples of primary CMM and controls were immunostained for SATB1. The following clinicopathologic variables were evaluated: age, gender, subtype, SATB1 expression, Breslow thickness, Clark level, presence of ulceration, lymph node metastasis, distant metastasis, and survival. Statistical analyses were performed to assess for associations. Several parameters were analyzed for survival using the Kaplan-Meier method and Cox proportional-hazards model.

Results

Forty cases (85.1%) of CMM showed positive staining for SATB1 by immunohistochemistry. The intensity of SATB1 staining was significantly higher in CMM than in nevus NV and normal skin (NS) (P < 0.01). High SATB1 expression was significantly correlated with Breslow thickness, Clark level, mortality, presence of ulceration, and lymph node metastasis (P < 0.01). Moreover, Kaplan-Meier analysis revealed that SATB1 overexpression was significantly associated with worse survival (P < 0.01). Further univariate analysis and multivariate regression analysis indicated that SATB1 expression was an independent prognostic marker for CMM (P = 0.03).

Conclusions

The overexpression of SATB1 correlated with metastatic potential of CMM and is a novel independent prognostic marker for predicting outcome.     

Dermoscopy of cutaneous melanoma metastases: A color‐based pattern classification

Dermoscopic studies about cutaneous metastases of malignant melanoma (CMMM) are few. Our objective was to analyze the dermoscopic features of CMMM and propose a new dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features. A retrospective evaluation of 150 dermoscopic images of CMMM taken from 40 patients was performed. One hundred CMMM images were individually evaluated by six dermatologists in order to classify them according to four dermoscopic patterns: (i) blue pattern; (ii) pink pattern; (iii) brown pattern; and (iv) mixed pattern. One hundred and fifty dermoscopic images including 50 CMMM and 100 benign lesions were evaluated by five dermatologists to calculate the accuracy of these patterns in the recognition of CMMM. An intra‐ and interobserver reproducibility agreement study between all different dermoscopic pattern classifications was performed. Seventy‐five percent of our cases of CMMM showed a monochromatic pattern. Light brown pigmented halo, peripheral gray spots and polymorphic atypical vessels were the most significant focal dermoscopic structures. The reproducibility of the color‐based dermoscopic pattern classification was superior to previous dermoscopic pattern classification. In summary, a dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features may be useful in recognizing early cutaneous melanoma metastasis. Multicentric studies are recommended in order to lower the impact of interobserver variability.     

The time from diagnostic excision biopsy to wide local excision for primary cutaneous malignant melanoma may not affect patient survival

BACKGROUND: The surgical management of primary cutaneous malignant melanoma usually involves an excision biopsy of the suspected lesion followed by wide local excision. No study has addressed whether a delay between these two surgical procedures influences patient outcome. OBJECTIVES: To determine if the surgical interval (SI) between the diagnostic excision biopsy and wide local excision for primary cutaneous malignant melanoma affects recurrence or survival outcome. METHODS: A cohort of 986 patients who had a diagnostic excision biopsy followed by wide local excision was identified from those registered on a specialist database that records the clinicopathological features, surgical treatment and follow-up information of all patients with malignant melanoma in Scotland. The cohort was divided into five arbitrary groups determined by the length of the SI as follows:< or =14 days, 15-28 days, 29-42 days, 43-91 days and > or = 92 days. Overall survival, disease-free survival and recurrence-free interval between the groups were compared univariately and multivariately. RESULTS: The mean age at excision biopsy was 47.4 years and the median period of follow-up was 5 years (range 27 days to 20.7 years). The median SI was 30 days (range 1-468 days). The SI was: (i)< or =14 days for 130 (13%); (ii) 15-28 days for 320 (33%); (iii) 29-42 days for 262 (27%); (iv) 43-91 days for 251 (25%); and (v) > or = 92 days for 23 (2%) patients. The latter group was older, had thinner melanomas, a higher percentage of lesions on the head and neck, fewer superficial spreading malignant melanomas and ulceration present less often compared with patients treated earlier. Univariately, there was no significant difference in overall survival (P = 0.60) or disease-free survival (P = 0.24) between the groups. Although there was a statistically significant difference in the percentage of recurrence-free patients between the groups (P = 0.011), the better recurrence-free rates occurred in the 29-42 and 43-91 day groups. After adjusting for age, sex, tumour thickness, site, histology, ulceration and mitotic activity using Cox's proportional hazards model, there was no statistically significant difference in overall survival, disease-free survival and recurrence-free percentages between the surgical groups (P = 0.88, P = 0.44 and P = 0.084, respectively). CONCLUSIONS: There was no evidence that survival outcome or recurrence was related to the time interval between the diagnostic excision biopsy and wide local excision of melanoma.     

A retrospective observational study of primary cutaneous malignant melanoma patients treated with excision only compared with excision biopsy followed by wider local excision

BACKGROUND: For primary cutaneous malignant melanoma the guidelines recommend an excision biopsy of the suspected lesion followed by wider local excision; the diagnosis can then be confirmed and excision margins planned. OBJECTIVES: To compare retrospectively the clinicopathological features, surgical margins and survival of patients from the Scottish Melanoma Group database whose tumour was removed by excision only (one-stage) or excision biopsy followed by wider local excision (two-stage) surgery. METHODS: The Scottish Melanoma Group database records the clinicopathological features, surgical treatment and follow-up information of all patients with malignant melanoma in Scotland. From this 1595 patients were identified over a 19-year interval from 1979 to 1997 with follow-up until the end of December 1999. Overall survival, disease-free survival and recurrence-free interval were examined with univariate and multivariate statistical methods. RESULTS: The patients in the one-stage excision group (n = 547) were statistically significantly older (P < 0.001), had thicker melanomas (P < 0.001), a higher proportion of lentigo maligna melanomas (P < 0.001), head and neck (P < 0.001), and ulcerated lesions (P < 0.003) compared with the two-stage group (n = 1048). The margins of excision were significantly narrower in the one-stage compared with the two-stage group (P < 1 x 10(-5)). Fifty-two percent of all one-stage excisions were performed with a margin < 1 cm compared with 20% of the two-stage group. The excision margin was more positively correlated with the Breslow thickness for the two-stage over the one-stage group (Spearman rho = 0.38, P < 0.001; and 0.27, P < 0.001, respectively). Overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RF) were all statistically significantly better in the two-stage compared with the one-stage excision group, P < 1 x 10(-5), P < 1 x 10(-5) and P = 0.001, respectively (log rank test). After adjusting for the prognostic factors of age, sex, tumour thickness, site, histology and ulceration, OS, DFS and RF were still significantly better in the two-stage compared with the one-stage group [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.61-0.92, P = 0.006; HR 0.75, CI 0.62-0.90, P = 0.002; and HR 0.78, CI 0.62-0.99, P = 0.04, respectively]. CONCLUSIONS: This study showed that one-stage excisions were more common in patients with poorer prognostic features and that excision with margins narrower than those suggested by current guidelines was more likely. Patient survival was statistically significantly better with the two-stage procedure, although the reasons for this were unclear.     

Acral cutaneous melanoma in caucasians: clinical features, histopathology and prognosis in 112 patients

BACKGROUND: Acral lentiginous melanoma (ALM) is the fourth distinct variant of cutaneous melanoma. The histological diagnosis and prognosis of ALM are still controversial. OBJECTIVES: To review the features of a large series of patients with ALM, and confirm the validity of the histological criteria for this type of melanoma. METHODS: A collection of 2642 patients with cutaneous melanoma was recorded during the period 1986-97, among these 187 were located on acral sites. Histological specimens were reviewed in 112 acral melanomas; the following study is based on this subgroup. RESULTS: Histological examination revealed acral lentiginous melanomas predominantly in palmoplantar and subungual locations (60%), while superficial spreading melanomas (SSM) were found mainly on the dorsal aspects of hands and feet (30%). Nodular melanomas (NM) (9%) occurred in all acral sites. The histological re-examination confirmed the characteristics of ALM as described by Reed in 1976. With increasing tumour thickness nesting of tumour cells and upward migration to the cornified layer was similarly observed. The 5-year survival rate for patients with primary acral melanoma without recognizable metastasis was 82%. ALM differed significantly in survival from SSM (P = 0.001) and lentigo maligna melanoma (P < 0. 001), but survival rates were similar to NM (P = 0.9). CONCLUSIONS: ALM, as diagnosed by current histological criteria, occur on the palms, soles and subungual sites, and have a poor prognosis.     

A case of pedunculated malignant melanoma of the vaginal mucosa.

We report an 84-year-old Japanese woman who presented with a pedunculated malignant melanoma of the vaginal mucosa. Mucosal melanoma is believed to be more common in Japan than other countries, but such tumors of the vulvovaginal region are quite unusual. In our patient, three tumors were connected by a narrow pedicle. Three black tumors measuring 5-10 mm in diameter with a common pedicle were seen on the vaginal mucosa at five o'clock from the cervix. The tumors were hanging from the narrow pedicle. On histologic examination, they were diagnosed as malignant melanoma. Resection was done with a distal margin of 3 cm from the tumors and a margin of 1 cm from the cervix. The patient has had no evidence of local recurrence or distant metastasis. In our patient, the three main tumors had a common pedicle, which seems to be a unique finding. Since pedunculated malignant melanomas are rare, making a clinical diagnosis is difficult. Although pedunculated melanomas are recognized as having a high malignant potential because these lesions are generally thick, a relatively good outcome is sometimes reported. In our patient, there was no tumor infiltration into the dermis of the pedicle, and this may be one reason for the good outcome at present. There has been no previous report of a mucosal melanoma consisting of three tumors like those in the present patient.     

A rational approach to melanoma follow-up in patients with primary cutaneous melanoma. Scottish Melanoma Group

From the Scottish Melanoma Group database for south-east Scotland we evaluated 5-year follow-up in patients with cutaneous malignant melanoma excised between 1979 and 1994 and devised an 'evidence-based' review protocol. Of the 1568 with stage I melanoma, 293 (19%) developed a recurrence, 32 had a second primary melanoma and 97 had an in-situ melanoma. The disease-free interval shortened progressively with increasing tumour thickness. Overall, 80% of recurrences were within the first 3 years, but a few patients (< 8%) had recurrences 5 or 10 years after the initial surgery. In-situ melanomas did not recur. Almost half (47%) the recurrences were noted first by the patient, and only 26% were detected first at a follow-up clinic. One hundred and thirty-nine patients (89%) were still under review when their recurrences were detected, and 102 (65%) had been seen within the previous 3 months. Questionnaires were completed by 120 patients: sun protection and avoidance, and mole examination were more likely after melanoma excision. We recommend 3-monthly review of patients with invasive lesions for the first 3 years. Thereafter, those with lesions >/= 1.0 mm need two further annual reviews. Patients with in-situ lesions should be reviewed once, to confirm adequate excision (0.5 cm margins) and to give appropriate education. Surveillance beyond 5 years is only justified if there are special risk factors.     

Malignant melanoma in HIV: Epidemiology,pathogenesis, and management

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV‐infected people is 2.6‐fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV‐negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV‐positive patients regardless of their CD4⁺ count and the use of standard surgical margins for re‐excision procedures. In case of diagnosis of melanoma in HIV‐positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV‐positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow‐up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint‐based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.     

Epidemiology of cutaneous malignant melanoma in Reunion Island

IntroductionThe incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. The aim of this study was to evaluate the epidemiology of CMM in Reunion Island, a French overseas department whose population is characterized by high ethnic diversity and high exposure to ultraviolet radiation.MethodsThis cross-sectional study examined all cases of in situ CMM and invasive CMM diagnosed between 1 January and 31 December 2015 in the Reunionese population.ResultsOne hundred and three new cases of CMM were recorded in Reunion Island in 2015: 33 cases of in situ CMM and 70 cases of invasive CMM. The sex ratio of men to women was 1.3 and 80% of patients had a fair skin phototype (Fitzpatrick skin phototype ≤ III). Age-standardized incidence rates of invasive CMM for all skin phototypes combined were 6.7/100,000 person-years (PY) in women and 5.3/100,000 PY in men. Crude incidence rates of invasive CMM for fair skin phototypes were estimated to be over 21/100,000 PY in women and over 25/100,000 PY in men.ConclusionsIn Reunion Island, the incidence of CMM in the population with fair skin phototype is very high. Primary and secondary prevention measures should be reinforced and tailored to the local context.     

恶性黑素瘤的诊治进展

皮肤恶性黑素瘤(cutaneous malignant melanoma,CMM)是黑色素细胞的恶性肿瘤,本文对CMM的发病情况、临床分期及目前的治疗方法进行了综述。     

Efficacy of positron emission tomography and computed tomography in clinical staging of cutaneous malignant melanoma

Accurate staging is very important for determining the prognosis and appropriate treatment for malignant melanoma (MM). The aim of this study is to determine the effectiveness of positron emission tomography and computed tomography (PET/CT) imaging in staging MM. Patients diagnosed with MM who then underwent PET/CT metastasis before treatment were assessed retrospectively. For each patient, the following variables were recorded: Breslow thickness, Clark's level, number of mitoses, the presence of ulceration detected in the pathology report, and the presence of lymph nodes and/or distant metastases detected by PET/CT. The pathology and PET/CT reports of 139 patients (79 female and 60 male) were retrospectively evaluated for staging after MM diagnosis. Patients with a Breslow thickness greater than 3.4 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with regional lymph node metastasis after PET/CT scans. Patients with Breslow thickness greater than 2.85 mm and Clark's level of 4 to 5 were found to be statistically significantly higher with distant metastasis after PET/CT scan. The results of our study suggest that PET/CT imaging for metastasis scanning, starting with T2 patients, may be used in MM staging to reduce the need for sentinel lymph node (SLN) biopsy and lymph node dissection.     

The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. OBJECTIVES: We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. METHODS: Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. RESULTS: Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. CONCLUSIONS: Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms.     

Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases

Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100‐positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre‐existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun‐exposed areas (mainly head and neck region) in elderly patients associated with S100‐positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non‐melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors.     

原发皮肤恶性黑色素瘤细胞分子遗传学研究进展

本文综述了原发皮肤恶性黑色素细胞分子遗传学改变，染色体上的非随机改变主要发生在1、6、9、7及10号染色体上。