["Die grosse Barb" in the museum of the University of Marburg. An early documentation of acromegaly]. / Die grosse Barb im Marburger Universitätsmuseum. Eine frühe Dokumentation der Akromegalie.

The university museum for cultural history in the castle of Marburg has a portrait "Die grosse Barb", which represents a women suffering from acromegaly. She shows the typical pathologic alterations: thickening of the skin folds, thickening of the lips and the eyelids, growth of bones and cartilages, lengthening of the nose, enlargement of the ears, protrusion of the zygoma, mandible and the chin. Acromegaly is a consequence of enhanced secretion of growth hormone, which occurs also as a symptom of several syndromes, such as multiple endocrine neoplasia type 1, McCune-Albright-syndrome, and NAME syndrome (Carney complex type I). The most remarkable symptom of acromegaly is the gigantism. This occurs also in androgen-deficient states, such as the Klinefelter syndrome and some more genetic syndromes, of which the Simpson-Golabi-Behmel syndrome, the Sotos syndrome, the Marfan syndrome, the homocystinuria, and the fragile X-syndrome may be mentioned. Nothing is known on the further fate of the patient shown in the portrait. It is also unknown, whether she owes her position as a chambermaid to her gigantism, for it was a common use in courts to have people with abnormal body shapes in attendance.

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. OBJECTIVES: To develop a computer algorithm for the diagnosis of melanocytic lesions and to compare its diagnostic accuracy with the results of established dermoscopic classification rules. METHODS: In the Department of Dermatology, University of Tuebingen, Germany, 837 melanocytic skin lesions were prospectively imaged by a dermoscopy video system in consecutive patients. Of these lesions, 269 were excised and examined by histopathology: 84 were classified as cutaneous melanomas and 185 as benign melanocytic naevi. The remaining 568 lesions were diagnosed by dermoscopy as benign. Digital image analysis was performed in all 837 benign and malignant melanocytic lesions using 64 different analytical parameters. RESULTS: For lesions imaged completely (diameter < or = 12 mm), three analytical parameters were found to distinguish clearly between benign and malignant lesions, while in incompletely imaged lesions six parameters enabled differentiation. Based on the respective parameters and logistic regression analysis, a diagnostic computer algorithm for melanocytic lesions was developed. Its diagnostic accuracy was 82% for completely imaged and 84% for partially imaged lesions. All 837 melanocytic lesions were classified by established dermoscopic algorithms and the diagnostic accuracy was found to be in the same range (ABCD rule 78%, Menzies' score 83%, seven-point checklist 88%, and seven features for melanoma 81%). CONCLUSIONS: A diagnostic algorithm for digital image analysis of melanocytic lesions can achieve the same range of diagnostic accuracy as the application of dermoscopic classification rules by experts. The present diagnostic algorithm, however, still requires a medical expert who is qualified to recognize cutaneous lesions as being of melanocytic origin.

Micrometastasis of a sentinel lymph node in cutaneous melanoma is a significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) has been proposed as a minimally invasive procedure for the histopathologic staging of the regional lymph node basin. The aim of this work was to investigate the prognostic value of detection of micrometastasis by SLNB. METHODS: In the period from January 1996 to March 2000, a sentinel lymph node (SLN) was identified in 283 patients at the Department Dermatology, University of Tuebingen. In the case of 38 patients (13.4%) histopathologic examination led to the detection of micrometastasis in at least one SLN. The median follow-up period was 29 months. RESULTS: Thirty-one of 245 patients (12.7%) suffered a tumor recurrence following a negative SLNB, and 19 of 38 patients (50%) following positive SLNB. In the case of disease-free survival the remaining significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.011), ulceration (p=0.026), and the detection of micrometastasis in SLNB (p=0.021). With respect to distant-metastasis-free survival the significant independent prognostic factors of the multivariate analysis were tumor thickness (p=0.0022) and the SLNB results (p=0.0068). For overall survival the tumor thickness (p=0.013) and the SLNB results (p=0.034) were significant independent prognostic parameters in the multivariate analysis. CONCLUSION: The study examined patients with melanomas of all tumor thicknesses and SLNB for which the prognostic significance of SLNB was tested. Recurrences were more frequent in patients with a micrometastatic SLN. Patients with a negative SNLB are still at risk for tumor recurrence. The histopathologic result of SLNB is, after tumor thickness, the most significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

Clinical risk factors and prognostic significance of local recurrence in cutaneous melanoma.

BACKGROUND: True local recurrence (LR) means clinically detectable regrowth of parts of the tumour which were not completely excised. In the literature the term 'LR' has been used in a vague and inconsistent manner that may include satellite and in-transit metastasis. OBJECTIVE: The aim of this study was to establish clinical, histological and surgical risk factors for the manifestation of LR and to evaluate the prognostic significance of LR. STUDY DESIGN: Data from 3960 Stage I and II melanoma patients who visited the melanoma clinic of the Department of Dermatology at the University of Tuebingen from 1980 to 1999 were documented in a prospective manner. A retrospective comparative analysis of patients with and without LR was performed. RESULTS: Of all patients 1.4% had a LR as a first recurrence and 1.7% had a LR in the course of the follow-up period. LR were most frequent after previous clinical or histological misdiagnosis and inadequate therapy. In the univariate analysis significant risk factors for LR-free survival were age, tumour surface area, locality, tumour thickness, level of invasion, histological type, associated naevus, surgery (one step vs. multiple steps) and compliance with recommended excision margins. In the multivarate analysis the factors locality (P < 0.0001), tumour thickness (P = 0.0086) and compliance with recommendations on excision margins (P = 0.014) were significant independent risk factors for the manifestation of LR. The overall survival of patients with LR as first progression did not significantly differ from the overall survival of the other patients with melanoma (P = 0.60). CONCLUSION: True LR is a rare event for which tumour locality, tumour thickness and surgery are independent risk factors. The occurrence of LR might not impair the prognosis of melanoma patients. However, in the published literature numerous definitions of 'LR', including lymphogenic metastasis, complicate comparison.

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]

The dermoscopic classification of atypical melanocytic naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions.

BACKGROUND: The dermoscopic classification is a useful tool for handling patients with atypical naevi (Clark naevi). OBJECTIVES: To investigate if the dermoscopic classification of atypical naevi is of any value to discriminate benign from malignant melanocytic lesions. METHODS: Consecutive patients (n = 205) were included with 254 suspicious melanocytic lesions, confirmed by histopathology at the Pigmented Lesions Clinic of the Department of Dermatology, University Medical Center, University of Tuebingen, Germany. In this retrospective study, dermoscopic images of benign and malignant melanocytic lesions were classified according to the dermoscopic classification of atypical naevi (reticular, globular, homogeneous or combinations of two of these) and pigmentation (uniform, central hyper- or hypopigmentation, eccentric peripheral hyper- or hypopigmentation, or multifocal hyper- or hypopigmentation). The three-structure type (reticular, globular and homogeneous) was additionally defined. RESULTS: Reticular, homogeneous and reticular-homogeneous types were significantly more frequent in naevi than in melanomas, whereas the three-structure type was significantly more frequent in melanomas (P < 0.001). A sensitivity of 86.7%, specificity of 87.7% and diagnostic accuracy of 87.4% was obtained. Uniformly pigmented and centrally hyperpigmented types were significantly more frequent in naevi than in melanomas, whereas eccentric peripheral hyperpigmented and multifocal hyper- or hypopigmented types were significantly more frequent in melanomas (P < 0.001). CONCLUSIONS: The dermoscopic classification of atypical naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions. The three-structure type and eccentric peripheral hyperpigmentation were significantly more frequently found in malignant than in benign melanocytic lesions. The knowledge of these two dermoscopic types should be helpful for the management of patients presenting with multiple melanocytic lesions.

[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.

Metastatic pathways and time courses in the orderly progression of cutaneous melanoma.

BACKGROUND: It is known that two-thirds of patients who develop clinical metastases following treatment of a primary cutaneous melanoma initially present with locoregional metastases and one-third initially present with distant metastases. However, few reports in the literature give detailed figures on different metastatic pathways in cutaneous melanoma. OBJECTIVES: The aim of the present study was to perform a detailed analysis of the different metastatic pathways, the time course of the development of metastases and the factors influencing them. METHODS: In a series of 3001 patients with primary cutaneous melanoma at first presentation, 466 subsequently developed metastasis and were followed-up over the long term at the University of Tuebingen, Germany between 1976 and 1996. Different pathways of metastatic spread were traced. Associated risk factors for the different pathways were assessed. Differences in survival probabilities were calculated by the Kaplan-Meier method and evaluated by the log-rank test. RESULTS: In 50.2% of the patients the first metastasis after treatment of the primary tumour developed in the regional lymph nodes. In the remaining half of the patient sample the first metastasis developed in the lymphatic drainage area in front of the regional lymph nodes, as satellite or in-transit metastases (21.7%) or as direct distant metastases (28.1%). Anatomical location, sex and tumour thickness were significant risk factors for the development of metastasis by different pathways. The most important risk factor appeared to be the location of the primary tumour. The median intervals elapsing before the first metastasis differed significantly between the different metastatic pathways. The direct distant metastases became manifest after a median period of 25 months, thus later than the direct regional lymph node metastases (median latency period, 16 months) and the direct satellite and in-transit metastases (median latency period, 17 months). In patients who developed distant metastases the period of development was independent of the metastatic route. The time at which the distant metastases developed was roughly the same (between 24 and 30 months after the detection of the primary tumour), irrespective of whether satellite or in-transit metastases, lymph node metastases or distant metastases were the first to occur. CONCLUSIONS: The time course of the development of distant metastasis was more or less the same irrespective of the metastatic pathway; this suggests that in patients with in-transit or satellite metastasis or regional lymph node metastasis, haematogenic metastatic spread had already taken place. Thus, the diagnostic value of sentinel lymph node biopsy and the therapeutic benefit of elective lymph node dissection may be limited, as satellite and in-transit metastases or direct distant metastases will not be detected and haematogenous spread may already have taken place when the intervention is performed.

Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil.

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to be effective in transplant patients. Some case reports and pilot studies have suggested efficacy against systemic lupus erythematosus (LE), particularly in the case of lupus nephritis. Reports on MMF treatment of skin manifestations of LE are still anecdotal. We report two cases with extensive skin lesions owing to subacute cutaneous LE (SCLE). Both patients had been treated with azathioprine and antimalarials without effect. Finally both patients were given highly dosed glucocorticosteroids, which were also ineffective but led to vertebral fractures because of long-term steroid treatment in one patient and steroid-induced psychosis in the other. MMF 2 g daily caused the skin manifestations to disappear within a few weeks in both patients. One patient was followed up for more than 24 months, and showed good toleration of MMF treatment. The skin remained stable over this period when at least 1 g MMF per day was administered. In conclusion, MMF appears to be an attractive treatment option in skin manifestations of SCLE, and seems to be beneficial for patients with steroid-refractory lesions that are also resistant to treatment with immunosuppressants or antimalarials. The observations suggest that further evaluation of this route in randomized controlled trials is warranted.

Dermcidin: a novel human antibiotic peptide secreted by sweat glands.

Antimicrobial peptides are an important component of the innate response in many species. Here we describe the isolation of the gene Dermcidin, which encodes an antimicrobial peptide that has a broad spectrum of activity and no homology to other known antimicrobial peptides. This protein was specifically and constitutively expressed in the sweat glands, secreted into the sweat and transported to the epidermal surface. In sweat, a proteolytically processed 47-amino acid peptide was generated that showed antimicrobial activity in response to a variety of pathogenic microorganisms. The activity of the peptide was maintained over a broad pH range and in high salt concentrations that resembled the conditions in human sweat. This indicated that sweat plays a role in the regulation of human skin flora through the presence of an antimicrobial peptide. This peptide may help limit infection by potential pathogens in the first few hours following bacterial colonization.

Dermatoscopy turns histopathologist's attention to the suspicious area in melanocytic lesions.

BACKGROUND: Histopathologically, the diagnosis of nevus-associated melanoma or melanoma close to a common nevus can be missed if the specimen is cut in a nonrepresentative area or if the section shows only the associated common nevus. OBJECTIVE: To find out whether dermatoscopy of suspicious areas within a nevus can improve the histological diagnosis of malignant melanocytic lesions of the skin. MATERIALS: The study was based on dermatoscopic images of more than 2000 benign and 115 malignant pigmented lesions and a collection of corresponding histopathologic slides. METHODS: The dermatoscopic images and the corresponding histopathologic diagnoses were compared. In case of differences, the histopathologic findings were reevaluated and compared with the dermatoscopic findings. RESULTS: Three cases were identified in which melanoma could have been histopathologically missed as a result of improper sectioning. After the dermatoscopic findings were evaluated, the specimens were reembedded and further sections were obtained. Finally, nevus-associated melanoma or melanoma close to a common nevus was diagnosed. CONCLUSIONS: Specific dermatoscopic patterns of malignancy can be found in highly suspicious areas, eg, broadened networks, radial streaming, pseudopods, or dots located at the periphery. The dermatoscopic-histopathologic correlation can improve the diagnosis of melanoma. Therefore, the clinician should point to the most suspicious area with a drawing or image, and the suspected diagnosis of melanoma and the history of the lesion should be also mentioned.

[Stripping operations of the parva and magna saphenous veins. Long-term study in relation to pre- and postoperative dysfunction]. / Strippingoperationen der V. saphena magna und parva. Langzeituntersuchung in Beziehung zu prä- und postoperativen Funktionsprüfungen.

BACKGROUND AND OBJECTIVE: Little data is available on the log-term effects of stripping the greater and lesser saphenous veins in combination with pre- and post-operative function tests. The goal of this study was to record the long-term course after surgery based on the function data. PATIENTS/METHODS: Drain-off capability was measured preoperatively and postoperatively by light reflection rheography in 203 patients (58 men, 145 women) between 17 and 79 years. Questionnaires were used about 9 years after surgery to determine the nature of the post-operative complaints. RESULTS: Nine years after surgery 58% of the patients still had no discomfort, and 78% had fewer problems with venous ulcers. About 60% reported improvement of swelling and skin changes. The results tended to be better in men. Freedom of complaints was longer-lasting where venous drainage had been good before surgery. CONCLUSIONS: Stripping operations can produce long-lasting improvement of venous ulceration and the above-mentioned complaints in a high percentage of patients.

The dermatoscopic pattern of clear-cell acanthoma resembles psoriasis vulgaris.

BACKGROUND: Dermatoscopy (dermoscopy, epiluminescence microscopy) is used for the early detection of malignant tumors and avoidance of unnecessary excisions of benign skin tumors. OBJECTIVE: Description of the dermatoscopic pattern of clear-cell acanthoma. METHODS: Video dermatoscopy at 20-fold magnification of a clear-cell acanthoma and psoriasis vulgaris. RESULTS: Homogeneous, symmetrically or bunch-like arranged, pinpoint-like capillaries were seen in the clear-cell acanthoma and in psoriasis vulgaris. CONCLUSION: The dermatoscopic psoriasis-like pattern of clear-cell acanthoma is a diagnostic clue which may help the clinician to identify this benign epidermal tumor and to differentiate it from other benign and malignant tumors of the skin.

Detection of melanoma cells in sentinel lymph nodes, bone marrow and peripheral blood by a reverse transcription-polymerase chain reaction assay in patients with primary cutaneous melanoma: association with Breslow's tumour thickness.

BACKGROUND: Tyrosinase reverse transcription-polymerase chain reaction (RT-PCR) has been shown to be highly sensitive in detecting tumour cells in melanoma patients. OBJECTIVE: To assess whether the detection of minimal residual disease by RT-PCR is improved by concomitant analysis of sentinel lymph nodes (SLNs), bone marrow (BM) and peripheral blood (PB) in patients with primary melanoma. METHODS: Thirty-five SLNs, 41 BM samples and 26 PB specimens from 26 patients with primary cutaneous melanoma (tumour thickness > or = 0.75 mm) were examined by nested RT-PCR for tyrosinase and Melan-A. SLNs and BM samples were also analysed by histopathology. RT-PCR findings were related to tumour thickness of the primary melanoma. RESULTS: Overall, melanoma cells were detected by RT-PCR in 13 of 26 patients (50%). Seven patients had positive RT-PCR results in their SLNs (27%), including all patients (n = 4) with histologically positive SLNs, two patients had positive findings in their BM exclusively detected by RT-PCR (8%) and six patients in PB (23%). The presence of tumour cells detected by RT-PCR in SLNs was not related to the presence of melanoma cells in BM and/or PB. The incidence of RT-PCR-positive SLNs was significantly associated with greater tumour thickness (P = 0.004). Both patients with positive RT-PCR findings in their BM had a large tumour thickness (> or = 2 mm). No association between positive RT-PCR findings in PB and greater tumour thickness was observed. CONCLUSIONS: RT-PCR-positive SLNs were strongly associated with greater tumour thickness, underlining the prognostic significance of SLN positivity. Similar to certain epithelial malignancies, molecular investigation of the BM might provide complementary prognostic information in the early stages of melanoma. In contrast, no association between positive RT-PCR results in PB and increasing tumour thickness was found, implying that RT-PCR findings in PB are of doubtful clinical relevance in primary melanoma.

Hyperkeratosis lenticularis perstans (Flegel's disease)--lack of response to treatment with tacalcitol and calcipotriol.

Hyperkeratosis lenticularis perstans (HLP) or Flegel's disease is a rare dermatosis characterized by asymptomatic hyperkeratotic papules predominantly located on the lower extremities. Lesional and non-lesional epidermis samples were studied by light- and electron-microscopic examination. The main ultrastructural finding was the presence of structurally altered Odland bodies/membrane-coating granules. Different therapeutic options for HLP have been reported, but none of the treatments was shown to be consistently effective. Here, we report on a patient with Flegel's disease who did respond to topical 5-fluorouracil, whereas topical vitamin D(3) synthetics were ineffective.

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.

Does intensive histopathological workup by serial sectioning increase the detection of lymph node micrometastasis in patients with primary cutaneous melanoma?

Various histopathological techniques have been developed in order to improve the detection of micrometastasis in the regional lymph nodes of patients with malignant melanoma. Our standard histopathological examination of lymph nodes included haematoxylin and eosin (H & E) staining and immunohistochemistry (IH) using antibodies to HMB-45 and S-100 proteins of three paraffin sections at one level. In addition, lymph nodes were examined by molecular biological methods using tyrosinase reverse transcription-polymerase chain reaction (RT-PCR). In this study, we investigated the use of step sections and IH in lymph nodes regarded as negative by standard histopathology but positive by tyrosinase RT-PCR, suggesting the presence of tumour cells. In a series of 76 consecutive patients with stage I and II cutaneous melanoma, a total of 156 regional lymph nodes were examined by H & E staining, IH and tyrosinase RT-PCR. All lymph nodes were bisected along their long axis for separate evaluation. In 21 patients, at least one lymph node in the regional nodal basin reported as tumour-negative by standard histopathology was demonstrated to express tyrosinase (total number of nodes = 33). These 33 lymph nodes were re-examined by H & E and IH at 10 additional levels of the paraffin block. Only one lymph node from one patient had occult melanoma cells in deeper levels detected exclusively by IH. Six out of 20 patients with positive findings exclusively on tyrosinase RT-PCR developed tumour recurrences during a median follow-up of 34 months. We therefore conclude that additional step sectioning with IH does not significantly increase the detection of tumour-positive lymph nodes. Patients with melanoma cells detected exclusively by RT-PCR, however, were shown to be at increased risk for tumour recurrence.