PRIMARY MALIGNANT AMELANOTIC MELANOMA ARISING FROM A VITILIGO PATCH OF AN AFRICAN TANZANIAN: CASE REPORT.

Skin cancer is rare in people of African origin while vitiligo occurs worldwide. The occurrence of primary malignant melanoma and vitiligo together is very rare. We present a rare case of primary malignant amelanotic melanoma arising from a depigmented patch of a patient with vitiligo. It was completely excised and followed for one year. No recurrence or metastases was noted during the follow up period.

[Special aspects of dermatologic surgery in children]. / Besonderheiten der Dermatochirurgie im Kindesalter.

This reviews gives suggestions how to meet the needs of our young patients, especially with reference to dermatologic surgery. With the right attitude, specific knowledge and appropriate preparation, a potential disruption can be transformed into a low-conflict routine or even a rewarding experience for all persons involved.

[Operative therapy of acral melanomas]. / Operative Therapie von akral lokalisierten Melanomen.

Acral lentiginous melanomas (ALM) represent 4-10% of cutaneous melanomas in white populations. Patients with ALM seem to have a poor prognosis, often due to late diagnosis. Micrographic surgery (3D-histology) is not seen as surgical procedure but more as histopathological technique. With micrographic surgery, continuously spreading ALM can be excised with smaller excision margins and good functional and cosmetic outcomes. In a recent study, 244 patients with ALM were compared using conventional histology versus 3D-histology. Clinical and surgical risk factors influence the prognosis of ALM. Tumor thickness and ulceration are the most important prognostic factors. 3D-histology with paraffin technique (optionally combined with immunohistological methods) can reduce excision margins and avoid local recurrences. Subungual melanomas represent only 2-3% of cutaneous melanomas in Caucasian and 20% in African or Asian skin type and are often clinically misdiagnosed. They are often localized on the thumb or great toe, which are most important for the function of the affected limb. The excision of subungual melanoma with 3D-histology and tumor-free excision margins including the nail matrix can be seen as a safe surgical strategy, which does not hazard the prognosis of the patient. Function and cosmesis of the finger or toe are preserved. Amputation in subungual melanoma is not recommended and should be reserved only for infiltrating melanomas with affection of the bone or joint.

[Sentinel node biopsy. What are the facts?]. / Sentinel-Node-Biopsie. Welche Aussagen sind gesichert?

Sentinel node biopsy (SNB) is increasingly being used as a minimally invasive staging procedure in patients with malignant melanoma. For decades elective lymph node dissection (ELND) was performed in many centers on patients at risk for lymph node metastasis but without clinically detectable lymph node involvement. Today, selective lymph node dissection (SLND) is offered only to patients with histologically proven metastasis in a SN (10-29%). A positive SN is one of the most important prognostic parameters. Ten years after the introduction of the technique, the role of SNB in the treatment of cutaneous melanoma still remains controversial. Issues include the usefulness of highly sensitive evaluation of SN using molecular biology or cytology techniques, as well as the therapeutic impact of the SNB per se and the associated combined surgical or medical adjuvant therapies.

Is sentinel lymph node biopsy of therapeutic relevance for melanoma?

INTRODUCTION: It is still unclear whether sentinel lymph node biopsy (SLNB) has an effect on the survival or recurrence-free survival of patients. It would be necessary to compare patients with SLNB (or with selective lymph node dissection in the case of positive SLNB) and patients without SLNB who received only a close clinical and sonographic follow-up. To date, no results from prospective, randomized studies of SLNB are available. MATERIAL AND METHODS: Patients with SLNB (n = 283) and patients in clinical stage I and II with close follow-up examinations only (n = 3,514) were studied retrospectively in this investigation with regard to prognostic factors established in the literature: sex, age, tumor thickness, histological tumor type, ulceration and localization. RESULTS: Multivariate analysis did not show an independent significant advantage with regard to survival when SLNB had been performed (p = 0.37). Compared with patients in clinical stage I and II with close follow-up only (n = 2,617),patients in stage I and II with negative SLNB (n = 238) had no significantly lower melanoma-related mortality (p =0.36) but significantly fewer recurrences in the regional lymph node area (p = 0.0015). With regard to survival without distant metastases and disease-specific survival, patients with positive SLNB (n = 33) did not significantly benefit by comparison with patients who developed lymph node metastasis identified clinically or sonographically later during follow-up examinations (n = 246; p =0.89 and p = 0.38, respectively). CONCLUSION: In the relatively short follow-up period after SLNB, patients for whom SLNB had been performed did not have - on the whole - a prognostic advantage over patients who were subject only to close follow-up monitoring. Patients for whom subclinical lymph node metastases had been removed as the result of a positive SLNB did not have a better prognosis than patients without SLNB who had developed lymph node metastases within the follow-up period [corrected]

[Taking responsibility for one's own health. Possibilities and limits using the example of malignant melanoma]. / Gesundheitliche Eigenverantwortung. Möglichkeiten und Grenzen am Beispiel des malignen Melanoms.

Because of the persistent shortage of health care resources, scientists and politicians are discussing ways to increase the patients' personal responsibility for their own health. Based on a philosophical analysis of the concept of responsibility, this article tries to assess strengths and limits of a personal responsibility for health, illustrated by the prevention of cutaneous melanoma. On the one hand, individuals bear prospective responsibility for their health status by adopting a healthy lifestyle and participating in prevention programs. On the other hand, individuals can--retrospectively--be held responsible for those conditions that result from the voluntary choice of health risks. Considering the tremendous practical and ethical problems associated with retrospective responsibility, prevention and public health policies should emphasize prospective personal responsibility for health.

[Sentinel lymph node in melanoma]. / Sentinel Lymph Node beim Melanom.

The procedure of sentinel node biopsy (SNB) has emerged as an important advance especially with respect to staging of malignant melanoma. Elective (prophylactic) lymph node dissection that had been practiced in primary melanoma with a suspected increased risk of (clinically occult) lymphatic metastasis has been replaced by SNB. Patients with proven metastatic involvement of the sentinel node (12-25%) can be specifically selected for regional lymph node dissection. Metastatic involvement of the sentinel node (SN) is a significant independent prognostic factor. The value of detecting metastasis by highly sensitive diagnostic tools such as RT-PCR is just as uncertain as is the therapeutic benefit of operative or conservative therapies in sentinel node-positive patients with respect to improving prognosis and is currently under study.

[The moat technique. A two-step surgical technique for extensive basal cell carcinomas of the lip]. / Wallgrabentechnik. Zweizeitige operative Versorgung von ausgedehnten Basalzellkarzinomen im Lippenbereich.

Surgery of large basal cell carcinomas (BCC) in problematic locations is sometimes challenging. A two-step surgical treatment of extensive BCC of the upper lip with the moat technique as an alternative to temporary wound closure will be illustrated using the example of two patients: In the first step, only the safety margin around the tumor is removed. After micrographic examination proves the lateral margins to be tumor-free, the tumor itself with all layers of the upper lip is removed in a second step. The defect is then closed with advancement flaps. If tumor resection does not involve all layers, the histopathologic interpretation of the base is first possible after complete surgical closure. The moat technique offers several advantages: The infection risk is minimized and the patient can eat and drink with an intact lip while resection margins are processed overnight. Tumor-free tissue is spared through the step-by-step procedure; the extent of plastic surgery is thus reduced and good functional and cosmetic results can be achieved. In addition, the perioperative period is less complicated.

Patients with lymphatic metastasis of cutaneous malignant melanoma benefit from sentinel lymphonodectomy and early excision of their nodal disease.

Early versus delayed excision of lymph node metastases is still being assessed in malignant melanoma. In the present retrospective, multicentre study, the outcome of 314 patients with positive sentinel lymphonodectomy (SLNE) was compared with the outcome of 623 patients with delayed lymph node dissection (DLND) of clinically enlarged lymph node metastases. In order to avoid the lead-time bias, survival was generally calculated from the excision of the primary tumour. Survival curves were constructed using the Kaplan-Meier product-limit estimate. Cox's proportional hazards model was used to perform a multivariate analysis of factors related to overall survival. Compared with SLNE and early performed complete lymph node dissection, DLND yielded a significantly higher number of lymph node metastases. Median and mean tumour thickness were nearly identical in the two therapy groups. The estimated 3-year overall survival rate was 80.1+/-2.8% (+/-standard error of the mean (SEM)) in patients with positive SLNs, and 67.6+/-1.9% in patients with DLND (5-year survival rates 62.5+/-5.5 and 50.2+/-5.4%, respectively). The difference between the two survival curves was statistically significant (P=0.002). Using multifactorial analysis, SLNE (P=0.000052), American Joint Committee on Cancer (AJCC) Breslow thickness category (P<0.000001), age (P=0.01) and gender (P=0.028) were independent predictors of overall survival. The location of the primary tumour (P=0.59) was non-significant. Considering only those centres with sufficient data for epidermal ulceration, this risk factor was also significant. In cutaneous malignant melanoma, early excision of lymphatic metastases, directed by the sentinel node procedure, provides a highly significant overall survival benefit.

[Prognostic parameters and surgical strategies for facial melanomas]. / Prognostische Faktoren und operative Strategien bei Melanomen des Gesichts.

BACKGROUND: In treated facial melanomas, the safety margins generally applied in other body sites cannot be achieved for functional and esthetical reasons. To date there are no controlled studies on safety margins for facial melanomas. Clinical parameters and surgical strategies influencing the prognosis of patients with a facial melanoma were evaluated in a retrospective study of melanoma patients in the Department of Dermatology of the University of Tuebingen (1980-1999). PATIENTS AND METHODS: The 368 melanomas of the face comprised 9.3% of 3960 primary stage I and II melanomas and 63% of the melanomas in the head and neck area. RESULTS: Multistep procedures, excisional biopsy for histological diagnosis followed by a subsequent resection of a clinical safety margin or re-excision when the tumor extended to the margin, were associated with a higher probability for recurrence-free survival (p = 0.0007), but had no statistical influence on overall survival. In a multivariate analysis, level of invasion (p = 0.0049), ulceration (p = 0.011), 3D-histology (p = 0.027) and defined safety margins (tumor thickness < or = 1.00 mm: 10 mm; > 1.00 mm 20 mm; lentigo maligna melanoma 5 mm with 3D-histology) (p = 0,033) were independent significant risk factors for recurrence-free survival. Level of invasion (p = 0.032), ulceration (p = 0.029), 3D-histology (p = 0.0047) were identified as independent significant risk factors for overall survival. Multivariate analysis did not show that the histological type of melanoma was of prognostic significance. CONCLUSION: Reduced safety margins can be employed in melanomas of the face. 3D-histology allows further reduction of safety margins, detects subclinical tumor strands and is correlated with an improved prognosis in patients with facial melanomas.

Is subungual melanoma related to trauma?

Subungual melanomas represent approximately 20% in dark-skinned and oriental populations compared to about 2% of cutaneous melanomas in white populations. UV exposure seems to be an important risk factor for cutaneous melanoma. However, UV radiation is unlikely to penetrate the nail plate. Another pathogenetic factor of subungual melanoma will be discussed. 406 subungual melanomas of the hands (n = 240) and feet (n = 166) of 74 patients from the melanoma registry of the Department of Dermatology, University of Tübingen, and of 332 patients from the literature were evaluated. The hypothesis of a uniform distribution of the occurrence of subungual melanoma on the fingers and toes had to be rejected (p < 0.001 using the chi(2)(4,0.95) test). There was a considerable predominance of subungual melanoma localized on the thumb (58% of all fingers) and the hallux (86% of all toes). Many patients report direct trauma related to the onset of subungual melanoma. This might be explained by coincidence, increased attention to a dark area under the nail, traumatic bleeding of a subclinical subungual melanoma or mutation of melanocytes during trauma-induced proliferation. Squamous cell carcinoma is known to occur in sites of chronic trauma. Trauma could be an etiologic factor in subungual melanoma as well.

Activity, expression, and transcription rate of the cathepsins B, D, H, and L in cutaneous malignant melanoma.

BACKGROUND: Increased activity of the protease cathepsin B has been demonstrated in many tumor cells. A correlation of cathepsin B activity and metastatic potential of melanoma has been well established. METHODS: The cathepsins B, D, H, and L were evaluated in normal skin, nevi, and melanoma samples to obtain information about their role and their regulation in melanoma. The authors localized specific proteolytic activity with histochemistry, cathepsin protein immunohistochemistry, and mRNA with in situ hybridization. RESULTS: Activities and immunoreactivities of the cathepsins B and L were found to be increased in all melanocytic lesions. However, the staining for the corresponding mRNA levels was elevated only in melanomas. Cathepsin D protein and mRNA were expressed to a higher degree only in the dysplastic nevus and in melanomas. The increase was due to tumor cells and cells of the surrounding tissue. Cathepsin H activity, immunoreactivity, and mRNA appeared to be correlated inversely with the invasive potential of the lesion. CONCLUSIONS: It may be relevant for the malignant potential of the lesion whether the increase in activity is accompanied by an increase in the mRNA level. Two different mechanisms-the existence of different mRNAs and the higher transcription rate of the cathepsin gene-have been proposed for the regulation of cathepsin B activity in tumor cells. The current data suggest that, depending on the thickness of the melanoma, cathepsin activity is regulated by different mechanisms. The up-regulation of cathepsin gene transcription appears to be characteristic for more invasive tumor cells.