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Die Wachterlymphknotenbiopsie gewahrleistet eine sehr zuverlassige Ausbreitungsdiagnostik des regionaren Lymphabflussgebietes fur Patienten mit primarem Melanom. Der histologische Status des Wachterlymphknotens ist von herausragender prognostischer Bedeutung. Innerhalb der histologisch positiven Patienten konnen anhand des Tumordurchmessers prognostische heterogene Gruppen identifiziert werden. Aufgrund der erhohten Sensitivitat zur Tumorzelldetektion kann durch die zusatzliche Durchfuhrung von RT-PCR-Untersuchungen eine Verbesserung der prognostischen Relevanz der Wachterlymphknotenbiopsie erzielt werden. The technique of sentinel lymph node biopsy is highly accurate in staging the regional lymph node basins in primary melanoma patients. The histological status of the sentinel lymph node is one of the most important prognostic factors for recurrence. In patients with positive histological status the extend of nodal tumour mass has been to shown to correlate with recurrence. Due to the increased sensitivity of tumour cell detection by molecular biological techniques the additional use of RT-PCR is able to improve the clinical impact of sentinel lymph node biopsy.

This report deals with a 15-year-old girl suffering from the verrucous type of Thomson's syndrome. Initial poikilodermatous skin changes developed on both cheeks at the age of 3 months. Subsequently, rapid generalization of typical skin findings was observed. The clinical heterogenity of this syndrome is discussed with reference to the existing literature and the present case. Up to now, very few comparable cases of associated neurological symptoms have been described.

Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique.

The technique of sentinel lymph node (SLN) biopsy has been demonstrated to be highly predictive for the detection of melanoma micrometastases in the regional lymph node basin. Therefore, the SLN was proposed to accurately reflect the lymph node status of patients with primary cutaneous melanoma. As the regional lymph node status is one of the most powerful predictors of survival in patients with primary melanoma, the histopathologic assessment is critically important for accurate staging. In approximately 20% (ranging from 9% to 42%) of patients with primary melanoma, the SLN was found to be tumor-positive by histopathology or immunohistochemistry. However, the true incidence of metastatic melanoma cells in (sentinel) lymph nodes is underestimated by histopathologic examination. Recently, the method of reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase mRNA has been used as a molecular marker for the presence of melanoma cells. Tyrosinase RT-PCR was demonstrated to significantly increase the detection of melanoma cells in SLNs as compared to histopathology. All lymph nodes positive by histopathology were shown to express tyrosinase by RT-PCR. Furthermore, tyrosinase transcripts were also detected in 36–52% of stage I and II melanoma patients with SLNs negative by histopathology. Importantly, the recurrence rate was significantly higher in patients with histologically negative SLNs who were found to be positive by RT-PCR than in patients with negative results by both techniques. These findings indicate that RT-PCR status of the SLN is more sensitive for detection of minimal melanoma disease than histopathology. Therefore, the RT-PCR status of the SLN may be suitable to improve melanoma staging and may serve as a prognostic factor in patients with primary cutaneous melanoma.

The technique of sentinel lymph node (SLN) biopsy has been demonstrated to be highly predictive for the detection of melanoma micrometastases in the regional lymph node basin. Therefore, the SLN was proposed to accurately reflect the lymph node status of patients with primary cutaneous melanoma. As the regional lymph node status is one of the most powerful predictors of survival in patients with primary melanoma, the histopathologic assessment is critically important for accurate staging. In approximately 20% (ranging from 9% to 42%) of patients with primary melanoma, the SLN was found to be tumor-positive by histopathology or immunohistochemistry. However, the true incidence of metastatic melanoma cells in (sentinel) lymph nodes is underestimated by histopathologic examination. Recently, the method of reverse transcription-polymerase chain reaction (RT-PCR) for tyrosinase mRNA has been used as a molecular marker for the presence of melanoma cells. Tyrosinase RT-PCR was demonstrated to significantly increase the detection of melanoma cells in SLNs as compared to histopathology. All lymph nodes positive by histopathology were shown to express tyrosinase by RT-PCR. Furthermore, tyrosinase transcripts were also detected in 36-52% of stage I and II melanoma patients with SLNs negative by histopathology. Importantly, the recurrence rate was significantly higher in patients with histologically negative SLNs who were found to be positive by RT-PCR than in patients with negative results by both techniques. These findings indicate that RT-PCR status of the SLN is more sensitive for detection of minimal melanoma disease than histopathology. Therefore, the RT-PCR status of the SLN may be suitable to improve melanoma staging and may serve as a prognostic factor in patients with primary cutaneous melanoma.

Conflicting results were obtained by various research groups using the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells circulating in peripheral blood. Whereas 100% positivity was initially reported for stage IV patients, more recent investigations reported positive detection rates between 30% and 50% in patients with disseminated melanoma. While the high detection rate initially reported in metastatic melanoma may be explained by contamination problems, methodological differences in different steps of the technical procedure of RT-PCR may account for the differences reported in more recent examinations. Major differences may result from the kind of blood preparation, the RNA isolation method, the kind of RT enzyme used, and the gene targeted by PCR primers. In our experience, blood purification by a Ficoll gradient increased melanoma cell detection rates compared to RNA extraction from total blood or after erythrocyte lysis. Amplification of MelanA in addition to tyrosinase resulted in a 30% enhanced sensitivity of melanoma cell detection compared to amplification to tyrosinase alone, whereas gp100/pMel17 and MUC18 gene products were already detected in blood from nonmelanoma patients. These findings are in agreement with those of other groups. Currently, an increase in the sensitivity for detection of circulating tumour cells to more than 50% of patients with disseminated melanoma seems to be unlikely. It is interesting that between 15% and 30% positive results and sometimes more have already been obtained from patients with primary melanoma. So far, there is no data for judging the prognostic significance of the detection of circulating tumour cells in patients without clinically recognisable metastases. Our limited experience shows that staging examinations in these patients reveal no proof of macrometastasis. Therefore, it is presently unclear whether these positive findings are associated with long-term prognosis or if they merely reflect false positive findings in this highly sensitive RT-PCR technique.

Bei primaren malignen Melanomen wird heute die Prognoseschatzung aufgrund der Parameter des Primartumors vorgenommen. Der wichtigste Faktor ist die Bestimmung der vertikalen Tumordicke am histologischen Praparat nach Breslow (Breslow, 1970). Als zweiter wesentlicher prognostischer Faktor gilt der Invasionslevel nach Clark, bei dem das Eindringen des Tumors anhand des anatomischen Aufbaus der Haut bestimmt wird (Clark et al. 1969). Diese Parameter erlauben statistische Voraussagen, das eine Tumorprogression und ein Versterben an dem Tumor mit einer bestimmten Wahrscheinlichkeit erfolgen wird. Sie erlauben aber keine Aussagen daruber, inwieweit der Einzelne betroffen sein wird oder nicht. Deshalb impliziert diese Art der Prognoseschatzung, das aufwendige diagnostische Masnahmen in der Tumornachsorge ebenso wie adjuvante Therapien bei einem Teil der Patienten durchgefuhrt wird, bei denen eine Mikrometastasierung und damit die Chance zur spateren Manifestation von Tumoren gar nicht vorliegt.

Previous studies have referred to the value of epiluminescence microscopy in the differential diagnosis of pigmented skin lesions and to the possibility of preoperative tumor thickness measurement in malignant melanoma by high-frequency ultrasound. Both noninvasive methods have been combined in this study. The question of improved diagnostic accuracy was discussed. Previously proposed epiluminescence microscopic characteristics of 508 melanocytic lesions and sonographic characteristics of 792 skin tumors were investigated for their sensitivity and specificity. The tumor thickness of 108 malignant melanomas was measured sonographically.Black dots, irregular pigment network, and grayish-blue areas have been shown to be the most sensitive characteristics, whereas pseudopods, grayish-blue areas, and a whitish veil have been shown to be the most specific epiluminescence microscopic features for malignant melanoma. Sonography alone cannot reliably distinguish between different skin tumors. Preoperatively, the tumor thickness of 85% of the melanomas was assessed correctly concerning the pT stage.A 20-MHz ultrasound, in addition to epiluminescence microscopy, may improve the diagnostic accuracy by delivering information about depth and topographic location of skin tumors, but cannot give highly specific information about tissue dignity. It is a reliable tool for tumor thickness measurement for surgical planning.

Die hochfrequente Ultraschall-Technik wurde hinsichtlich ihres Wertes in der Differentialdiagnose von Hauttumoren untersucht. Hierfur wurden sonographische Charakteristika von 792 Hauttumoren bezuglich ihrer Sensitivitat und Spezifitat beurteilt. Daruber hinaus wurde die Tumordicke von 108 kutanen malignen Melanomen praoperativ sonographisch bestimmt. Der hochfrequente Ultraschall kann die diagnostische Sicherheit durch Zusatzinformationen uber Vertikalinvasion und topographische Lokalisation eines Hauttumors erhohen, wenngleich spezifische Aussagen zur Gewebedignitat nur bedingt moglich sind. Die praoperative Tumordickenbestimmung, entsprechend der pT- Stadien, wurde in 85% (Durchschnitt) der malignen Melanome exakt eingestuft. Es handelt sich somit um ein zuverlassiges praoperatives Untersuchungsverfahren zur Tumordickenbestimmung, das die stadiengerechte chirurgische Therapieplanung sinnvoll erganzt.

This report deals with a 15-year-old girl suffering from the verrucous type of Thomson's syndrome. Initial poikilodermatous skin changes developed on both cheeks at the age of 3 months. Subsequently, rapid generalization of typical skin findings was observed. The clinical heterogenity of this syndrome is discussed with reference to the existing literature and the present case. Up to now, very few comparable cases of associated neurological symptoms have been described.