A ten-year analysis of demographic trends for cutaneous melanoma: analysis of 2501 cases treated at the University Department of Dermatology in Vienna (1990-1999)

BACKGROUND: The aim of the study is to provide recent demographic data on cutaneous melanoma in Austria. PATIENTS AND METHODS: Patients with primary cutaneous melanoma diagnosed between January 1, 1990 and December 31, 1999 were included in the analysis. Data were retrieved from the melanoma registry of the University Department of Dermatology in Vienna. RESULTS: In the observation period, 2501 cutaneous melanomas were diagnosed in 2427 patients (mean age: 55.4 yrs; 51.2% females). A total of 267 (10.7%) cutaneous melanomas were in situ, and 2234 (89.3%) were invasive. The median invasion thickness according to Breslow for invasive melanomas was 0.98 mm (25%-75% percentiles: 0.55-2.00 mm). We observed a significant trend towards thicker tumors with increasing age (p < 0.001). In patients less than fifty years of age, a significantly higher Breslow thickness was observed in men than in women (0.90 mm versus 0.80 mm, p = 0.03). The median Breslow thickness of invasive melanoma decreased from 1.20 mm in 1990 to 0.92 mm in 1999 (p for trend, < 0.001). Compared to women, men had melanomas more frequently on the back (43.8% versus 24.4%, p < 0.001). In women, melanomas were more frequently found on the lower legs than in males (21.5% versus 6.7%, p < 0.001). In a multivariate model, invasion thickness according to Breslow was the single most important predictor of survival. CONCLUSION: Our data confirm recent reports from other European countries with regard to the decline in tumor thickness of cutaneous melanoma. Our data also demonstrate a need for improving early diagnosis, particularly in certain subgroups of patients.     

Preoperative Measurement of Thickness of Cutaneous Melanoma Using High-Resolution 20 MHz Ultrasound Imaging: A Monocenter Prospective Study and Systematic Review of the Literature

Histologic measurement of the thickness of melanoma is a major prognostic factor and governs the size of the surgical excision (1cm for melanomas less than 1 mm thick, 2 cm for melanomas thicker than 2 mm and 3 cm beyond 4 mm). To determine whether high-resolution ultrasound can be used to predict surgical margins and, thus, to operate on patients in a single procedure avoiding further re-excision, we performed a systematic review of studies published from January 1987 to June 2007 and a prospective study. The systematic review selected 14 studies comparing histologic and ultrasound measurements and showing correlation coefficients generally greater than 0.9. Data available from 7 of the 14 studies (total 869 patients) showed predictive values of adequate margins in at least 72% of lesions using preoperative measurement of ultrasound thickness. The prospective study included 31 patients referred with a primary melanoma from March 2005 to March 2007. Ultrasound measurement of thickness was possible except for thin melanomas (<0.4 mm) in areas with marked photoaging, in the plantar zone, and in the case of very thick melanomas exceeding the explored depth (7.6 mm). The average thickness was 1.96 mm measured by ultrasound (SD: 2.15) and 1.95 mm by histology (SD: 2.62) and the Bland and Altman graph showed moderate agreement between ultrasound and histology. Limits of agreement were estimated at –1.4 and +1.8, corresponding to relative limits of agreement of –40 to +80%. Ultrasound predicted appropriate margins (1, 2 or 3 cm wide according to sonometric thickness) in 26 of the 31 subjects (84%, 95% CI 66–95). Preoperative high-resolution ultrasound is a noninvasive examination that can help in choosing appropriate surgical margins and should reduce the need of partial or excisional biopsy before surgery, and the need for further re-excision. (E-mail: machet@univ-tours.fr)     

Diagnosis and management of malignant melanoma

The incidence of malignant melanoma has increased in recent years more than that of any other cancer in the United States. About one in 70 people will develop melanoma during their lifetime. Family physicians should be aware that a patient with a changing mole, an atypical mole or multiple nevi is at considerable risk for developing melanoma. Any mole that is suggestive of melanoma requires an excisional biopsy, primarily because prognosis and treatment are based on tumor thickness. Staging is based on tumor thickness (Breslow's measurement) and histologic level of invasion (Clark level). The current recommendations for excisional removal of confirmed melanomas include 1-cm margins for lesions measuring 1.0 mm or less in thickness and 2-cm margins for lesions from 1.0 mm to 4.0 mm in thickness or Clark's level IV of any thickness. No evidence currently shows that wider margins improve survival in patients with lesions more than 4.0 mm thick. Clinically positive nodes are typically managed by completely removing lymph nodes in the area. Elective lymph node dissection is recommended only for patients who are younger than 60 years with lesions between 1.5 mm and 4.0 mm in thickness. In the Eastern Cooperative Oncology Group Trial, interferon alfa-2b was shown to improve disease-free and overall survival, but in many other trials it has not been shown to be effective at prolonging overall survival. Vaccine therapy is currently being used to stimulate the immune system of melanoma patients with metastatic disease.     

Three-dimensional ultrasound biomicroscopy for xenograft growth analysis

We reported the use of high-frequency ultrasound biomicroscopy (UBM) in the quantitative analysis of early tumor growth in mice bearing melanoma xenografts in a noninvasive longitudinal assay. Initially, measurements of tumor width, depth and length were obtained using on-screen UBM calipers in real time and tumor volume was calculated with the standard ellipsoid formula w d l pi/6. We were able to detect initiating minute tumor nodules, with the lower limit of detection at approximately 0.01 mm(3) in volume. Successive parallel cross-sectional UBM images (33 microm step) encompassing the complete length of these tumors were also obtained and reconstructed into 3-D representations. Subsequent segmentational volumetric analysis provided a measure of tumor volume. Volume measurements using the two techniques were highly correlated when all 33 xenografts were studied (r = 0.9813, p < 0.0001) and a lower degree of correlation was measured with a subset of early small tumors (r = 0.7973, n = 16, p = 0.0004). Further analysis demonstrated that 3-D segmentational volumetric analysis yielded volume estimates that were often smaller than the caliper-and-formula calculation for most early developing xenografts. Thus, 3-D UBM imaging and segmentation is expected to be especially valuable for small tumors that were observed to grow in irregular shapes other than ellipsoids.     

High-frequency sonography and color Doppler in the management of pigmented skin lesions

We aimed to evaluate high-frequency sonography (HFS) coupled with color Doppler in the management of pigmented skin lesions (PSL). HFS examination was performed in 111 patients with 130 PSL. A color Doppler study was conducted in 107 lesions, to assess intralesional vascularization. Imaging findings were compared with histologic diagnosis. In the case of melanoma, sonographic and histologic maximum thickness measurements were compared. HFS showed 114 of the 130 lesions. Among the detected lesions, HFS alone provided 100% sensitivity and 100% specificity in the distinction of melanoma/nevi from other lesions, and 100% sensitivity and 32% specificity in the distinction of melanomas from nonmelanoma lesions. Sonographic and histologic measurement of melanoma thickness strongly correlated (r > 0.96, p < 0.001). Color Doppler detection of intralesional vessels had a 100% specificity and 34% sensitivity in the distinction of melanomas from other PSL. HFS coupled with color Doppler is a simple, reliable tool for PSL management.     

Clinical epidemiologic data of malignant melanoma based on 1,368 patients of the Graz University Dermatology Clinic (1970-1989)]

Epidemiological and histological data of 1368 patients with invasive malignant melanoma treated at the Department of Dermatology between 1970 and 1989 were analysed retrospectively. Frequency of melanoma increased from 103 cases between 1970 and 1974 to 593 between 1985 and 1989. The male/female ratio was 1/1.5 and did not change during the study period. Mean age of patients at the time of primary operation was 56.1 years and was approximately the same for males and females (males 55.8, females 56.3 years). The predominant site was the trunk in males (58.7 per cent) and the lower leg in females (41.6 per cent). There was a relative increase of melanomas of the back in males and the lower leg in females at the expense of melanomas of the face. The Breslow index was significantly higher in males than in females. In patients older than 69 years, the proportion of thick melanomas was above average. During the study period, the frequency of thick melanomas (greater than 1.5 mm) showed an encouraging decrease in both sexes. In 1989, 50 per cent of all melanomas were thinner than 1.01 mm. This can be interpreted as a successful outcome of efforts in preventive medicine.     

Diagnosis and treatment of Basal cell and squamous cell carcinoma

Cutaneous malignant melanoma accounts for 3 to 5 percent of all skin cancers and is responsible for approximately 75 percent of all deaths from skin cancer. Persons with an increased number of moles, dysplastic (also called atypical) nevi, or a family history of the disease are at increased risk compared with the general population. An important tool to assist in the evaluation of potential melanomas for patients and health care professionals is the ABCDE mnemonic, which takes into account asymmetry, border irregularities, color variation, diameter, and evolution. Any suspicious pigmented lesion should be biopsied. Appropriate methods of biopsy can vary, and include deep shave, punch, and excisional biopsy. Regardless of the procedure selected, it is essential that the size of the specimen be adequate to determine the histologic depth of lesion penetration, which is known as the Breslow depth. The Breslow depth is the most important prognostic parameter in evaluating the primary tumor. Because early detection and treatment can lead to identification of thinner lesions, which may increase survival, it is critical that physicians be comfortable with evaluating suspicious pigmented lesions and providing treatment or referral as necessary.     

Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma

Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.     

结膜恶性黑色素瘤的手术治疗

目的探讨结膜恶性黑色素瘤的手术治疗方法。方法 1997年1月-2007年1月收治结膜恶性黑色素瘤48例,均为单眼。肿瘤范围：〈1/3眼睑长度及结膜14例,〉1/3眼睑长度,部分穹隆结膜受累19例,上下眼睑及内外眦大部分结膜受累者15例。采用单纯肿瘤切除术、单纯肿瘤切除联合液氮冷冻治疗、眼眶内容物剜除术3种治疗方法。结果所有患者均经病理学证实为结膜恶性黑色素瘤。术后48例进行9个月～5年随访,15例眶内容物剜除术,3例死于肺及颅脑转移;14例单纯扩大肿瘤切除联合液氮冷冻治疗,2例死于肝转移;19例单纯扩大肿瘤切除术,6例分别死于肝、肺及颅脑转移。结论早期诊断并选择积极有效的手术治疗是提高患者生存率,改善生存质量的重要手段。手术切除联合液氮冷冻法可有效降低肿瘤复发,避免影响患者视觉质量和外观,是治疗结膜恶性黑色素瘤的一种有效方法。     

Lymph node metastases arising from uveal melanoma

Since the eye lacks lymphatic vessels, uveal melanomas primarily metastasize hematogenously. Here we report the case of a patient with ciliary body ring melanoma who developed lymph node metastases after a fistulating glaucoma operation. A 40-year-old female Caucasian patient presented with unilateral pigment dispersion. Pigment dispersion glaucoma was diagnosed and since the intraocular pressure could not be managed with topical medication, transscleral cyclophotocoagulation and two trabeculectomies had to be performed. Due to enlargement of the pigmented iris mass and cell deposits in the chamber angle, a ciliary body ring melanoma was presumed and the eye enucleated. Histology confirmed the diagnosis of "ciliary body ring melanoma". Six months after enucleation the patient presented multiple metastases including ipsilateral preauricular and submandibular lymph node metastases. The patient died two months later. Lymph node metastases arising from ciliary body melanomas are very rare. Tumor seeding through the trabeculectomy site into the bleb and then via conjunctival lymphatic vessels might be the crucial factor for this pathway of metastases. Therefore, in cases of unilateral pigment dispersion, malignancy should be excluded before fistulating operations are performed.     

Primary noncutaneous melanoma

Primary noncutaneous melanomas are rare neoplasms that affect patients in an older age group than primary cutaneous melanomas. The prognosis is worse than primary cutaneous melanomas because of the advanced stage at the time of diagnosis, the rich vascular and lymphatic supply of mucosal sites, and the lack of clinical suspicion of the tumor because of its rarity. The initial treatment is surgical resection but the location may make it technically difficult to obtain complete tumor removal. Unlike cutaneous melanoma, sun exposure is not a risk factor for noncutaneous melanomas. Darker-skinned individuals may have a higher incidence of some noncutaneous melanomas, such as anorectal melanomas. It is important for clinicians and pathologists to recognize primary noncutaneous melanomas to provide early detection and optimum management.     

Cutaneous melanoma: update on prevention, screening, diagnosis, and treatment

Melanoma is an increasingly common malignancy, and it affects a younger population than most cancers. Risk factors for melanoma include white race, sun sensitivity, family history of melanoma, and melanocytic nevi. Sunburn and intermittent sun exposure appear to increase the risk of developing melanoma. The role of population-based screening for skin cancer remains unclear. Consistent screening results in the diagnosis of thinner melanomas, but there is no evidence that this leads to decreased mortality. The ABCDs--asymmetry, border, color, diameter--can be used as a guide to differentiate melanoma from benign lesions. Suspicious pigmented lesions should undergo full thickness biopsy. Treatment consists of surgical resection, lymph node evaluation, and systemic therapy for some patients. Prognosis depends on the stage at diagnosis. Patients with melanoma require dose follow-up because they are at risk for recurrence and diagnosis of a second primary tumor. Preventive strategies for melanoma should emphasize seeking shade when outdoors, wearing protective clothing, and avoiding exposure during the peak sunlight hours.     

99mTc标记硫胶体淋巴显像探测皮肤恶性黑色素瘤前哨淋巴结的价值

目的：探讨99mTc 标记硫胶体（99mTc-SC）淋巴显像探测皮肤恶性黑色素瘤前哨淋巴结（SLN）的临床应用价值和影响因素。方法选取99例Ⅰ、Ⅱ期皮肤恶性黑色素瘤患者,术前4-6 h在肿瘤病灶周围皮下注射显像剂99mTc-SC,行早期局部及延迟全身显像,结合显像进行体表定位。随后行前哨淋巴结活检术（SLNB）,对初诊患者加行原发病灶切除术,对SLN及原发病灶行详细病理检查。结果99mTc-SC的SLN总检出率为90.9%（90/99）,检出率与原发灶部位有关（P＜0.001）;区间淋巴结检出率为7.1%（7/99）;SLN转移阳性率为28.9%（26/90）,与肿瘤的病理组织学特点（Breslow厚度、Clark分级）呈正相关;假阴性率为3.7%（1/27）,灵敏度为96.3%（26/27）,特异度为98.4%（63/64）。结论99mTc-SC显像可准确显示SLN部位及淋巴引流情况,减少药物标记时间,进一步提高区域淋巴结检出,为恶性黑色素瘤区域淋巴结的诊治决策提供重要的临床依据。     

New prognostic factors and developing therapy of cutaneous melanoma

The multiple molecular alterations underlying the neoplastic process and clinical characteristics of cutaneous melanoma are currently under intensive investigation. Recent studies have demonstrated that the levels of melanoma-associated proteins in tumor tissue or in patient serum can serve as new markers to predict disease outcome. Similarly, the expression of thousands of genes in melanoma tumors can be surveyed simultaneously using DNA arrays, allowing molecular profiling of individual tumors, which gives the possibility of classifying melanomas based on their biological diversity. Large clinical studies have also identified multiple prognostic factors, such as tumor ulceration, and led to development of a new, more precise melanoma staging system, which emphasizes the biological characteristics of the primary disease. These new findings may have an important role in earlier measurement of the clinical response and provide a basis for tailored melanoma therapy, the development of which will also be discussed in this review.     

New prognostic factors and developing therapy of cutaneous melanoma

The multiple molecular alterations underlying the neoplastic process and clinical characteristics of cutaneous melanoma are currently under intensive investigation. Recent studies have demonstrated that the levels of melanoma-associated proteins in tumor tissue or in patient serum can serve as new markers to predict disease outcome. Similarly, the expression of thousands of genes in melanoma tumors can be surveyed simultaneously using DNA arrays, allowing molecular profiling of individual tumors, which gives the possibility of classifying melanomas based on their biological diversity. Large clinical studies have also identified multiple prognostic factors, such as tumor ulceration, and led to development of a new, more precise melanoma staging system, which emphasizes the biological characteristics of the primary disease. These new findings may have an important role in earlier measurement of the clinical response and provide a basis for tailored melanoma therapy, the development of which will also be discussed in this review.     

Isolated perfusion of extremities for metastatic melanoma from an unknown primary lesion

Since 1957, 822 patients with invasive malignant melanoma of the limbs were treated by regional perfusion at the Tulane Medical Center. Between 1958 and 1982, there were 32 patients with regional metastatic melanoma from an unknown primary site involving either the upper limb and axillary lymph nodes or lower limb and femoral or inguinal lymph nodes. This group represents 3.5% of patients with regional melanomas treated during this period. There were 16 patients with upper limb regional metastases and 14 patients with lower limb metastases. Sixteen patients had stage IIIB disease (ie, regional lymph node metastases), ten had stage IIIA disease (ie, satellitosis), and four had stage IIIAB disease. Six patients had a history of a suggestive limb lesion that had completely regressed and showed no residual tumor on biopsy. All 30 patients were treated by regional isolated perfusion and regional lymph node dissection, with surgical excision of in-transit disease when possible. The cumulative five-year survival for all patients is 50%. Interestingly, the patients with a history of a lesion that regressed had 85% cumulative five-year survival, and the patients with stage IIIB disease did almost as well, with 62% surviving for five years.     

A new ultrasound instrument for in vivo microimaging of mice

We report here on the design and evaluation of the first high-frequency ultrasound (US) imaging system specifically designed for microimaging of the mouse. High-frequency US or US biomicroscopy (UBM) has the advantage of low cost, rapid imaging speed, portability and high resolution. In combination with the ability to provide functional information on blood flow, UBM provides a powerful method for the investigation of development and disease models. The new UBM imaging system is demonstrated for mouse development from day 5.5 of embryogenesis through to the adult mouse. At a frequency of 40 MHz, the resolution voxel of the new mouse scanner measures 57 microm x 57 microm x 40 microm. Duplex Doppler provides blood velocity sensitivity to the mm per s range, consistent with flow in the microcirculation, and can readily detect blood flow in the embryonic mouse heart, aorta, liver and placenta. Noninvasive UBM assessment of development shows striking similarity to invasive atlases of mouse anatomy. The most detailed noninvasive in vivo images of mouse embryonic development achieved using any imaging method are presented.     

Advances in targeted therapy for melanoma

Metastatic melanoma remains an aggressive malignancy conferring a very poor prognosis, and standard chemotherapeutic and immunologic treatments have not demonstrated an overall survival benefit. No molecularly targeted therapy is approved for the treatment of advanced melanoma. Melanoma is a molecularly heterogeneous malignancy, and optimal treatment in a given patient is likely to depend on the presence of specific molecular abnormalities. Aberrations in components of signal transduction pathways have been identified that modulate melanoma proliferation and survival. Mutations that activate the mitogen activated protein kinase (MAPK) pathway via BRAF or NRAS are present in the majority of melanomas arising on skin intermittently exposed to the sun. Mutations that activate the KIT oncogene are more commonly present in melanomas arising from mucosal, acral, or chronic sun-damaged sites. Inhibitors of the MAPK pathway and of KIT are currently undergoing clinical investigation. In this article, we review advances in targeted strategies to treat different subgroups of patients with melanoma.     

国产UBM测量闭角型青光眼前段结构的准确性

目的探讨国产超声生物显微镜（UBM）对闭角型青光眼眼前段结构测量的准确性。方法应用BME-300型UBM对40例（80只眼）闭角型青光眼的角膜厚度、前房深度、晶状体厚度进行测量,计算校正值,并与A超测量结果进行比较。结果未进行校正之前,UBM与A超的角膜厚度、前房深度、晶状体厚度测量值之间均存在显著性差异（t=8.853～2.777,P〈0.01）。校正之后前房深度、晶状体厚度与A超测量结果比较,差异无统计学意义（P〉0.05）,但UBM所测角膜厚度明显大于A超所测结果（t=23.508,P〈0.01）。结论UBM测量所得眼前段数据应根据公式进行校正;在前房深度、晶状体厚度的测量中UBM与A超一致性较好,角膜厚度测量两者之间差异较大。