Andreas Blum

Prospective Evaluation of a Follow-Up Schedule in Cutaneous Melanoma Patients: Recommendations for an Effective Follow-Up Strategy

PURPOSE To prospectively examine and evaluate the results of follow-up procedures in a large cohort of cutaneous melanoma patients. PATIENTS AND METHODS This was a prospective study in 2,008 consecutive patients with stage I to IV cutaneous melanoma from 1996 to 1998 on the yield of stage-appropriate follow-up examinations according to the German guidelines. Documentation of patient and follow-up data comprised patient demography, primary tumor specifics, and any clinical and technical examinations performed. The detection of metastasis was classified as early or late, and the means of their detection and the resulting overall survival probabilities were examined. RESULTS A total of 3,800 clinical examinations and 12,398 imaging techniques were documented. Sixty-two second primary melanomas in 46 patients and 233 disease recurrences in 112 patients were detected during this time. In stage I to III disease, physical examination was responsible for the discovery of 50% of all recurrences. In the primary tumor stages, 21% of all recurrences were discovered by lymph node sonography, with the majority being classified as early detection. Forty-eight percent of the recurrences were classified as early detection, and these patients had a significant benefit of overall survival probability. CONCLUSION The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.

Epidemiology of Cutaneous Melanoma in Germany and Worldwide

Rising incidence rates of cutaneous melanoma have been observed during the last three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per 100,000 inhabitants and year were reported by the Saarland Cancer Registry in Germany. Other incidence studies from Germany in the 1990s even reported 10–12 cases per 100,000 inhabitants and year, which is more likely to be the representative melanoma incidence in Western Germany. In a worldwide comparison this is a medium incidence rate as compared to clearly higher incidence rates in the United States (10–20 cases per 100,000 inhabitants and year) and in Australia (40–60 cases per 100,000 inhabitants and year). In Europe the highest incidence rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants and year) and the lowest from the Mediterranean countries (about 5–7 cases per 100,000 inhabitants and year). Mortality rates likewise increased in Germany between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to 2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many other countries a leveling off of mortality rates was observed. 48,928 melanoma patients have been recorded by the Central Malignant Melanoma Registry from the German-speaking countries in the time period from 1983 to September 2000, and clinico-epidemiological analysis of cutaneous melanoma is based on this data material. While 2/3 of all melanoma patients in Germany were females in the 1970s, there is now a more balanced gender distribution with more than 45% of patients being males. Age distribution does not significantly change during the last three decades. Most melanomas are diagnosed in the age group between 50 and 60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear decrease of Breslow’s tumor thickness was found from the beginning of the 1980s to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower Breslow’s tumor thickness at first diagnosis of cutaneous melanoma has only been reported from Australia. This development indicates improved early recognition of cutaneous melanoma which is presently the main factor for a more favorable prognosis.

Malignant Melanoma S3-Guideline "Diagnosis, Therapy and Follow-up of Melanoma"

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years.

Digital image analysis for diagnosis of cutaneous melanoma. Development of a highly effective computer algorithm based on analysis of 837 melanocytic lesions.

Background  Digital image analysis has been introduced into the diagnosis of skin lesions based on dermoscopic pictures.

Ultrasound examination of regional lymph nodes significantly improves early detection of locoregional metastases during the follow-up of patients with cutaneous melanoma

In regional lymph node metastasis of cutaneous melanoma, the number and volume of involved lymph nodes are the most important prognostic factors. Several studies have revealed that palpation of the lymphatic drainage area(s) and regional lymph nodes has a high rate of false‐negative results during follow‐up. The aim of the current study was to assess the sensitivity and specificity of ultrasound versus clinical diagnosis in the detection of subcutaneous and regional metastases.

Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi.

Background  Based on the dermoscopic classification of acquired melanocytic naevi, six different dermoscopic types can be distinguished by morphology (globular, globular‐reticular, globular‐homogeneous, reticular, reticular‐homogeneous, homogeneous) and by pigment distribution (uniform, central hyperpigmentation, central hypopigmentation, peripheral hyperpigmentation, peripheral hypopigmentation, multifocal hyper/hypopigmentation). It has been suggested that most individuals harbour one predominant dermoscopic type among their naevi.

Surveillance of patients at high risk for cutaneous malignant melanoma using digital dermoscopy

Background  Dermoscopy has improved the sensitivity and specificity of clinical diagnosis of melanoma from 60% to over 90%. However, in order not to miss melanoma a certain percentage of suspicious but benign lesions has to be excised.

Time Required for a Complete Skin Examination With and Without Dermoscopy: A Prospective, Randomized Multicenter Study

OBJECTIVE To determine the time required to perform a complete skin examination (CSE) as a means of opportunistic screening for skin cancer both without and with dermoscopy. DESIGN Randomized, prospective multicenter study. SETTING Eight referral pigmented lesion clinics. Patients From June 2006 to January 2007, 1359 patients with at least 1 melanocytic or nonmelanocytic skin lesion were randomly selected to receive a CSE without dermoscopy or CSE with dermoscopy. For each patient, the total number of lesions and the duration of the CSE were recorded. A total of 1328 patients were eligible for analysis (31 were excluded because of missing data). MAIN OUTCOME MEASURES The median time (measured in seconds) needed for CSE with and without dermoscopy and according to total cutaneous lesion count. RESULTS The median time needed for CSE without dermoscopy was 70 seconds and with dermoscopy was 142 seconds, a significant difference of 72 seconds (P < .001). The use of dermoscopy increased the duration of CSE, and this increase was in direct proportion to the patients total lesion count. In contrast, the time required to perform a CSE without dermoscopy remained the same irrespective of whether the patients had few or many lesions. CONCLUSIONS A CSE aided by dermoscopy takes significantly longer than a CSE without dermoscopy. However, a thorough CSE, with or without dermoscopy, requires less than 3 minutes, which is a reasonable amount of added time to potentially prevent the morbidity and mortality associated with skin cancer.

Awareness and early detection of cutaneous melanoma: an analysis of factors related to delay in treatment

Factors associated with the detection of cutaneous melanomas and reasons for delay in diagnosis were investigated in 429 patients with histologically proven melanoma operated on between January 1993 and June 1996. Patients were interviewed using a standardized questionnaire. In 25% of patients, treatment was delayed for more than 1 year from the time they first noticed a suspicious pigmented lesion. Melanoma was detected by the patients themselves in 67% of women and 45% of men. The three predominant clinical symptoms of melanoma were change in colour (darker), increase in size and increase in elevation of a pigmented lesion. The role of sun exposure and of naevi as risk factors for melanoma, as well as the potential benefit of early treatment, were known by 87%, 66% and 82% of the patients, respectively. However, melanoma awareness had no impact on the time period between first observation of skin changes and treatment. Among the factors associated with delay in melanoma diagnosis, an initial incorrect diagnosis as a benign lesion by the physician first visited (in 18% of all cases) had the highest significance. Patients detecting their lesions themselves were treated significantly later than patients in whom others had remarked on changes in a naevus. Furthermore, melanomas of the head and neck were treated later than melanomas at other body sites. Further efforts to educate both the public and the medical profession are essential to ensure earlier treatment for cutaneous melanomas.

Dermoscopy of pigmented lesions of the mucosa and the mucocutaneous junction: results of a multicenter study by the International Dermoscopy Society (IDS).

OBJECTIVE To better characterize the dermoscopic patterns of mucosal lesions in relation to the histopathologic characteristics. DESIGN Retrospective and observational study. SETTING Fourteen referral pigmented lesion clinics in 10 countries. PATIENTS A total of 140 pigmented mucosal lesions (126 benign lesions, 11 melanomas, 2 Bowen disease lesions, and 1 metastasis) from 92 females (66%) and 48 males (34%) were collected from October 2007 through November 2008. MAIN OUTCOME MEASURES Scoring the dermoscopic patterns (dots, globules, or clods, circles, lines, or structureless) and colors (brown, black, blue, gray, red, purple, and white) and correlation with the histopathologic characteristics. RESULTS Based on univariate analysis and 2 diagnostic models, the presence of structureless zones inside the lesions with blue, gray, or white color (the first model) had a 100% sensitivity for melanoma and 92.9% sensitivity for any malignant lesion, and 82.2% and 83.3% specificity for benign lesions in the group with melanoma lesions and the group with malignant lesions, respectively. Based on the colors (blue, gray, or white) only (the second model), the sensitivity for the group with melanoma was 100% and for the group with any malignant lesion was 92.9%, and the specificity was 64.3% and 65.1%, respectively. Patients with malignant lesions were significantly older than patients with benign lesions (mean [SD] ages, 60.1 [22.8] years vs 43.2 [17.3] years, respectively). CONCLUSION The combination of blue, gray, or white color with structureless zones are the strongest indicators when differentiating between benign and malignant mucosal lesions in dermoscopy.