Trauma and melanoma formation: a true association?

BACKGROUND: Little is known about the role of mechanical trauma in the pathogenesis of malignant melanoma. In individual patients, traumatic events have been discussed as a causative factor for the induction of melanoma and diagnosis of melanoma following trauma may raise medico-legal questions. OBJECTIVES: To evaluate the relationship between traumatic single or recurrent events and melanoma characteristics. METHODS: Retrospective questionnaire in 369 melanoma patients. RESULTS: A large number of patients (337 of 369; 91.3%) denied an association between a possible traumatic event and melanoma formation. Thirty-two of 369 patients (8.7%) considered an association of trauma and melanoma formation likely. Of these 32 patients, 22 patients (13 men, nine women) reported a single event, and 10 patients (four men, six women) a persisting irritation. An irritation of a pre-existing melanocytic naevus was reported by two patients with histologically confirmed melanoma on acquired or congenital naevus. CONCLUSIONS: As most of the patients who mentioned a trauma in this study suffered from acral melanoma, or melanoma located on the extremities, a history of trauma should be expected more frequently at these body sites. A review of epidemiological, clinical and scientific research indicates that there seems to be no evidence for single or persistent traumatic events as a causative factor for melanoma formation.     

Melanoma and tumor thickness: challenges of early diagnosis

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.     

Time to diagnosis of melanoma: same trend in different continents

BACKGROUND: Patients and physicians both play an important role in the diagnosis of malignant melanoma. OBJECTIVE: The purpose of this study was to assess important factors of delay in diagnosis at different centers and on three continents. METHODS: Between October 2001 and October 2002, patients with histologically confirmed invasive melanoma were included in the study and given an established questionnaire. Recorded patients and tumor characteristics included age, sex, anatomic location, Breslow thickness, patients' awareness of the lesion and time with suspicion, and physicians' time (delay) before the operation. RESULTS: The study included 985 patients (486 males, 499 females): 253 from Germany, 464 from Sweden, 58 from Brazil, and 210 from Australia. More females detected their lesions by themselves. The change to a darker color (21%) and enlargement of the area of the lesion (19%) were the major signs. The highest knowledge among patients that early detection may improve the outcome was found in Sweden and Australia. At each center, the media (newspaper, magazine, radio, and television) provided the best sources of information about melanoma. Twenty to 33% of all physicians initially consulted missed the melanoma diagnosis, independent of their specialty. CONCLUSIONS: There are still factors for the delay in melanoma diagnosis in different countries and continents, but the differences are rather small. The results should be included in planning prevention campaigns in this specific field and in the education of medical students, physicians of all specialties, and other health professionals.     

肢端恶性黑素瘤100例临床和病理分析

目的 探讨肢端恶性黑素瘤的临床、病理特点和外伤在发病中的意义以及现行分型方法的有效性。方法 选取最近诊断的具有完整临床、病理资料的100例肢端恶性黑素瘤，对其临床、病理数据进行统计分析。结果 原发于手28例，其中拇指甲下14例；足72例，足掌跖29例，足跟18例，拇趾甲下12例。31例原发部位有外伤史。40例肢端恶性黑素瘤难以用目前的分型方法分型，依据现行病理分型方法，肢端雀斑样痣性、结节性、浅表扩散性黑素瘤在肿瘤浸润深度、临床分期等方面差异无显著性。结论 足部是肢端恶性黑素瘤的好发部位，外伤是发病的重要诱因，现行分型方法的临床意义尚需进一步研究。     

Clear cells in acral melanoma

Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.     

早期诊断黑素瘤的无创方法

黑素瘤作为一种高度恶性的皮肤肿瘤,经早期诊断和治疗能够获得较高的存活率.目前黑素瘤的诊断无疑仍依赖于组织病理学方法,然而活检或手术切除是病理学诊断的必要条件.黑素细胞性皮肤病中,良性病变占绝大多数,如能通过其他方法早期鉴别,则可减少不必要的组织创伤.皮肤自我检查、皮肤镜、远程皮肤镜、激光共聚焦显微镜等无创方法均可用于鉴别良、恶性黑素性皮肤病,缩短以往诊断黑素瘤所需要的时间、简化其繁琐的过程.概述几种主要的无创方法早期诊断黑素瘤.     

黑素瘤发病机制相关蛋白的研究进展

黑素瘤是高死亡率的皮肤肿瘤,鉴定出与黑素瘤发病及进展相关的蛋白质有助于阐明黑素瘤的发病机制,临床上应早期诊断以提高疗效.近年来,比较蛋白组学、蛋白质表达谱等多种蛋白质组学研究方法应用于黑素瘤发病机制的研究,有助于明确相关细胞信号通路蛋白的功能,阐明肿瘤耐药机制、发现可能的肿瘤标记物以利于早期诊断、判断疗效和预后.     

Factors of delay in the diagnosis of melanoma

Delay in the diagnosis of melanoma was defined as the interval in months from the patient's report of first noticing a suspected lesion to the date of the removal of a histologically confirmed melanoma. 216 patients were included in our study. Total delay was subdivided in three components: patient, medical and referral delay. The major component of delay is due to the patient and the most important cause of it was lack of concern. Lesions in men were detected more frequently by family members, while in women melanomas tended to be self-detected. Nodular melanoma had lower delay but higher thickness. Amelanotic melanomas had a higher delay principally due to the physicians. A significative positive correlation between Breslow thickness and patient delay was observed. The visibility of the tumor and the educational or socio-economic status did not seem to improve early diagnosis. The observation about the shorter delays in thicker tumors lead us to think that educational campaigns should be more focused on recognition of changing or growing lesions than other signs of the ABCD rule and that nodular melanomas are quite different from superficial spreading melanomas.     

PLANTAR MALIGNANT MELANOMA

Among 51 cases of malignant melanoma seen at the Department of Dermatology, Tohoku University School of Medicine, from 1966 to 1978, 16 cases had had the primary lesion on the sole. The average age of these 16 cases was 63 and the sex ratio (M:F) was 11:5. The common sites of involvement on the sole were the heel (in 9 cases) and the toes and metatarsal region (in 5 cases). In 14 cases the lesions arose on the right sole; furthermore, 6 cases had had histories of trauma before or after the development of tumor and 7 cases had received insufficient excisions of their lesions, all of which showed a recurrence and/or lymph node metastasis within a year. These data suggest that traumatic stimulation may have some effect up on the pathogenesis of plantar melanoma. The clinicopathological features of plantar malignant melanoma in Japan are also described.     

Concomitant traumas influence prognosis in melanomas of the nail apparatus

BACKGROUND: In nail apparatus melanomas (NAM), the role of standard melanoma prognostic factors is under discussion. The prognostic influence of traumas to the clinically apparent tumour has not been sufficiently examined. OBJECTIVES: To estimate the influence of traumas against the background of standard prognostic factors on the course of NAM. METHODS: In 33 patients (20 women, 13 men, median age 65.0 years) with NAM (median tumour thickness 3.5 mm), we retrospectively examined a detailed history of trauma to the affected extremity at first presentation. Histological or other standard prognostic factors and follow-up were studied prospectively using a standardized protocol. RESULTS: Of 33 patients, 21 had suffered injury to the clinically apparent melanoma primary between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy up to 3 months ahead of excision of the melanoma was not considered). Eight of these patients had undergone inadequate therapy procedures. In Kaplan-Meier analysis, trauma to the clinically apparent tumour and tumour thickness were found to be significant prognostic factors for recurrence-free survival, and trauma to the clinically apparent tumour, Clark level and tumour thickness were significant prognosis predictors for overall survival. In Cox's proportional hazards model, trauma to the clinically apparent tumour was found to be a significant and independent risk factor with regard to overall survival (hazard ratio 5.39; P = 0.029). An influence of trauma on the primary pathogenesis of NAM could not be confirmed. Only three patients reported trauma prior to the onset of tumour. CONCLUSIONS: From our data, trauma to the clinically apparent tumour might be a considerable risk factor in NAM. The diagnosis of NAM should be considered in lesions of the nail apparatus and further deterioration of the prognosis due to inadequate therapeutic attempts or injury to the NAM should be avoided.     

Dubreuilh melanoma: and epidemiologic and prognostic study

BACKGROUND: Lentigo maligna melanoma is a specific histoclinical type of melanoma. We studied the epidemiologic features of lentigo maligna melanoma (Dubreuilh's melanoma) and compared prognosis with other types of melanoma. PATIENTS AND METHODS: A retrospective review of 516 cases of cutaneous melanomas, seen from 1985 to 1997, identified 29 cases of lentigo maligna melanoma. Epidemiologic, clinical and prognostic data were collected using a common scoring system for all patients. The chi-squared test, univariate log rank analysis, Cox multiple regression model for multivariate analysis, and actuarial survival curves were applied. RESULTS: The 29 cases of lentigo maligna melanoma (16 women, 13 men) accounted for 5.9 p. 100 of all melanomas. Mean age at diagnosis was 73 years compared with 54 years for others melanomas. Predominant localization was head and neck. There was no prior history of nevi compared with 50 p. 100. Mean delay to diagnosis was 4 years versus 1 year. All patients have had an occupation with to sun exposure. Mean tumoral thickness was 2 mm. Survival was the same as for extensive superficial melanomas and better than for nodular melanomas. Multivariate analysis showed that prognosis was not better in case of lentigo maligna melanoma. Tumoral thickness was the main prognosis factor. DISCUSSION: Our findings confirmed the specific nature of lentigo maligna melanoma and suggested that sun exposure plays an important role. Multivariate analysis did not show that prognosis was any better in case of lentigo maligna melanoma than in other types of melanoma. The thickness of the tumor must be taken into account as for other melanomas.     

Never perform laser treatment of skin tumors with clinical “EFG” criteria

Laser treatment is a common procedure for the treatment of cosmetically troubling skin lesions but has the limitation that histopathologic diagnosis is usually not obtained prior to treatment. Laser treatment of melanomas with benign clinical features may delay or make more difficult the correct diagnosis of such tumors. A helpful tool to identify clinically innocent appearing melanomas is the “EFG” rule, summarizing the common clinical features as “elevated, firm skin lesions showing continuous growth”. We report a 42‐year‐old woman who presented with a recurrent and metastatic melanoma after laser treatment of a tumor which was apparently clinically innocent and highlight the clinical features of such benign‐looking melanomas.     

Effect of health care delivery models on melanoma thickness and stage in a university-based referral center: an observational pilot study

OBJECTIVE: To compare the effect of differing health care delivery models, specifically, gatekeeper (GK) vs direct access (DA) routes, on melanoma outcome as measured by tumor thickness and cancer stage at diagnosis. DESIGN: Retrospective medical record review of patients previously diagnosed as having cutaneous melanoma who were referred to a university-based clinic from January 1, 1996, through December 31, 2000. SETTING: Stanford Pigmented Lesion and Cutaneous Melanoma Clinic, Stanford, Calif. Patients Two hundred thirty-four patients with primary melanoma stratified according to health care access route (GK or DA). MAIN OUTCOME MEASURES: Differences in Breslow thickness, American Joint Committee on Cancer stage, histologic features, patient delay in seeking medical attention, and physician delay in diagnosis (time between initial physician visit and diagnostic biopsy procedure). RESULTS: Of 234 patients, 168 (72%) were referred through the DA route and 66 (28%) through the GK route. A significant association was found between physician delay and access route; patients in the DA group underwent biopsy sooner (< or =3 months vs >3 months) than those in the GK group (P<.001). No significant difference was observed in stage at diagnosis (predominantly stage IA), proportion of nodular melanoma (DA 4% vs GK 2%), patient delay, or median tumor thickness between DA and GK routes (0.42 mm vs 0.50 mm, respectively). A trend toward a greater proportion of histologically ulcerated melanoma was observed in the DA group compared with the GK group (12% vs 5%, respectively; P = .06). CONCLUSIONS: This pilot study demonstrated no difference in outcome between GK and DA routes as measured by melanoma thickness and stage, although patients in the DA group underwent diagnostic biopsy sooner than those in the GK group. The potential effect of health care models on melanoma outcomes merits further study.     

Calcaneal petechiae (black heel)

A pigmented lesion on the heel of a young person, due to trauma, may cause difficulty in diagnosis—distinguishing it from a wart or a malignant melanoma.     

Sex differences in survival from cutaneous melanoma

The matter of sex differences in survival from melanoma is more complex than generally recognized, and at least 6 factors, some of which appear to be interrelated, must be conisdered: location of the primary melanoma; stage of disease at presentation; endocrine factors; immunologic factors; pattern of metastatic spread (i.e., lymphogenic versus hematogenic), and environmental and behavioral characteristics. Extremity melanomas have a more favorable prognosis than axial melanomas, but, after allowance for tumor site, women still fare better than men. There appears to be a stage-by-stage difference in favor of women for survival. This applies to clinical stages (stage 1, local disease; stage 2, regional spread; and stage 3, distant metastases), as well as to pathologic microstages. Some authors have inferred that female advantage disappears once the disease has metastasized. No valid explanation for this observation has ever been advanced, and careful review of the literature reveals a female superiority in survival at stage 2 or stage 3 disease as well as stage 1. Many recent studies have confirmed the ancient impression that the incidence of metastatic disease at the time of diagnosis is higher in men. Men tend to have an equal or shorter history before treatment, yet they have more advanced disease at the time of diagnosis. They have an unfavorable outcome irrespective of lesion site, tumor thickness, histogenetic subtype, and clinical stage of disease. These data suggest that the disease develops more rapidly in men. Thus, the aggressiveness and metastatic potential of cutaneous melanoma is more distinct in the male sex. The exacerbation of melanoma during pregnancy may be due to the increase of estrogens or to the elevated androgen levels. The first possibility is unlikely. The elevation of follicle stimulating hormone, luteinizing hormone, and MSH levels may play a role. Several case-controlled studies have failed to reveal any overall relationship between prior history of oral contraceptive use and the development of melanoma. Because the role of estrogens (and hormones in general) in the course of melanoma is not yet satisfactorily established, oral contraceptives are best avoided. It is concluded that malignant melanoma may be a hormone-responsive tumor, despite the fact that the exact nature of such endocrine factors remains nebulous.     

Melanoma and melanocytic nevi in decorative tattoos: three case reports

Background: In response to the demands of style and fashion, the number of decorative tattoos has been increasing worldwide. This has been paralleled by a rising incidence of melanocytic proliferations, including melanoma. The coincidence of various dermatological diseases and skin tumors with tattoos has been documented with some frequency, but reports of melanoma associated with tattoos are exceedingly rare. To date, only 13 cases have been documented in the English language literature. The possibility of an association between melanocytic proliferations and tattoos remains an area for further study. Observations: This report presents two cases of melanocytic nevi and one of melanoma occurring in association with a decorative tattoos. Conclusions: At present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a photoallergic effect, or an inflammatory reaction may promote malignant transformation. Clinicians and histopathologists should be aware of the clinical and pathological features if they are to make a correct diagnosis. Varga E, Korom I, Varga J, Kohán J, Kemény L, Oláh J. Melanoma and melanocytic nevi in decorative tattoos: three case reports.     

恶性黑色素瘤选择性表达孕激素受体并与PCNA呈负相关性

目的探讨孕激素受体(PR)在恶性黑色素瘤(MM)中的表达情况及意义。方法以免疫组化法检测35例MM患者标本,8例痣细胞痣PR及增殖性细胞核抗原(PCNA)的表达,并结合临床及组织病理学资料进行分析。结果在MM中PR的阳性表达率为25.7%,在痣细胞痣中无表达。MM中PR表达与PCNA表达显著负相关。女性、年龄≤55岁、病程>1年、溃疡以及非肢端型组织亚型PR阳性比例增高,但均无统计学意义。结论PR在MM中选择性表达并可能具有抗增殖作用。     

STAT3与黑素瘤

信号转导与转录激活因子3(STAT3)既是一种胞质信号分子又是胞核转录因子,参与细胞的存活、增殖、转化及迁移等过程.它在肿瘤如黑素瘤的发病中起着非常重要的作用,通过调节基因表达促进黑素瘤细胞的生长而参与肿瘤细胞的存活与增殖;通过诱导基因的表达促进黑素瘤细胞转移和肿瘤血管生成,参与调节肿瘤免疫侵袭所致的肿瘤免疫耐受.通过向目的细胞内引人STAT3反义寡核苷酸、诱饵寡核苷酸或显性负相蛋白等阻断STAT3的功能,可抑制目的细胞的增殖,促进细胞的死亡.     

Diagnosis of blue nevus-like metastatic uveal melanoma confirmed by fluorescence in situ hybridization (FISH) for monosomy 3

Metastatic melanoma can on rare occasion simulate the appearance of a blue nevus clinically and/or histopathologically, which may lead to diagnostic confusion and delay in treatment. Given the known difficulty in recognizing a small dermal blue nevus-like melanoma metastasis by light microscopic findings alone, recent discoveries of unique cytogenetic aberrations in various types of melanomas have led pathologists to explore cytogenetic techniques as an ancillary diagnostic tool. Herein, we report a case of a 58-year-old man with a history of uveal melanoma, in which fluorescence in situ hybridization (FISH) analysis for monosomy 3 helped confirm a diagnosis of blue nevus-like uveal melanoma metastasis. The patient had presented clinically with a new small 1-mm dark blue-gray macule on the forehead. Histopathologically, a small dermal nodule of pigmented epithelioid melanocytes and melanophages was found with a rare mitotic figure. The pathologist's suspicion of a blue nevus-like melanoma metastasis was confirmed by FISH analysis: both the tumor cells of the patient's prior uveal melanoma and the melanocytes of the new dermal blue nevus-like nodule carried only one copy of chromosome 3. Furthermore, deletion of 1p36 and amplifications of 8q32 were also identified.     

Acquired periungual fibrokeratoma: a case report

Acquired periungual fibrokeratoma (APF) is an uncommon lesion located around the nail and related to acquired digital fibrokeratoma. Histologic features of APF include a core of thick collagen bundles oriented along the longitudinal axis of the tumor and a very characteristic pseudo-nail plate formation. Different terms have been used to describe these lesions, and there has been no consensus on the terminology for some years. It is now believed that trauma may play a role in the pathogenesis of these periungual lesions.