Background: Conventional surgery for lentigo maligna melanoma (LMM) is based on normal histological evaluation. However, such evaluation leaves diagnostic gaps. In contrast, complete three-dimensional (3D) histology o...Background: Conventional surgery for lentigo maligna melanoma (LMM) is based on normal histological evaluation. However, such evaluation leaves diagnostic gaps. In contrast, complete three-dimensional (3D) histology of excision margins permits accurate detection of continuously spreading tumour strands like those of LMM. These can be specifically excised in tumour-positive areas with smaller excision margins, and better cosmesis and function. To date there have been no controlled studies of micrographic surgery of LMM. Objectives: Clinical parameters and surgical strategies influencing the prognosis of patients with LMM were evaluated in a prospective study of melanoma patients in the Department of Dermatology of the University of Tübingen (1980-99). Methods: The 292 LMMs comprised 7.4%of 3960 primary stage I and II melanomas treated during this period. One hundred and thirty-six patients in this group (46.6%) underwent surgery on the basis of 3D histology. Results: The geometric mean excision margins were significantly smaller in the 3D histology group (P < 0.0001). Patients with micrographic surgery had fewer recurrences. Multivariate analysis of clinical, histological and surgical variables was carried out, and tumour thickness and 3D histology proved to be independent, significant factors for the prognosis of recurrence-free survival (relative risk, RR 2.08, P < 0.0001 and RR 2.11, P = 0.0037, respectively). There were no melanoma-related deaths in the 3D histology group. All 16 melanoma-related deaths were observed among the 156 patients of the conventional histology group (10.3%). Conclusions: Excision of LMM using 3D histology resulted in a two fold lower probability of recurrence and two fold smaller excision margins. 3D histology is a valuable diagnostic tool and can be used in the management of LMM because of the latter’s pattern of continuous tumour spread.展开更多
Background: The ear’s specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. Objectives: The aim of this prospective study was to define prognostic fact...Background: The ear’s specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. Objectives: The aim of this prospective study was to define prognostic factors for melanoma of the ear and to evaluate surgical strategies for excision margins, histological evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better cosmetic and functional results. Patients and methods: One-hundred and sixty-one patients with stage I/II melanoma of the external ear were treated in the Department of Dermatology, University of Tuebingen, from March 1976 to March 2004 (median follow-up 62 months). Malignant melanoma of the external ear represented 3%of the stage I/II cutaneous melanomas and 20%of the stage I/II head and neck melanomas recorded in the Melanoma Registry of the Department of Dermatology at the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM) underwent conventional histological evaluation, 22 underwent complete three-dimensional histology of excision margins (3D histology) in a paraffin-technique, i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas thicker than 1.0 mm. Clinical, histological and surgical risk factors were evaluated by univariate and multivariate analysis. Results: The median thickness of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50 mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0 mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence-free survival rate was 83%. Tumour thickness and invasion level were the only risk factors significant for disease-specific survival. Tumour thickness, location of the tumour and extent of excision margins were independently significant risk factors for recurrence free survival. LMMs removed surgically with accompanying 3D histology were thicker than those examined by conventional histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology, i.e. micrographic surgery, made it possible to reduce the excision margins (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs were positive (6.9%). There were six preregional recurrences after negative SLNB and one after positive SLNB. None of the patients who underwent SLNB died of melanoma related causes during the observation period. Conclusions: This is the largest series of ear melanomas reported so far. The overall survival depended only on the tumour thickness and Clark level of invasion. Local recurrence was more frequent with smaller excision margins, but this did not influence the overall survival. Smaller excision margins under 3D-histological control did not carry an increased risk of local recurrence. Our results do not permit conclusions regarding the prognostic impact of SLNB for patients with melanoma of the ear.展开更多
Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cath...Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cathelicidins-are prod uced by keratinocytes primarily under inflammatory conditions. In contrast, derm cidin (DCD), a recently discovered AMP with broad-spectrum activity, is express ed in eccrine sweat glands and transported via sweat to the epidermal surface. O bjectives:To investigate whether DCD expression is induced under inflammatory c onditions in epidermal keratinocytes. Methods:Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by im munohistochemistry using a polyclonal anti-DCD antiserum. We also examined whet her DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. Results:Whereas DCD was constitutively expresse d in eccrine sweat glands of all skin biopsies, we found that, independent of th e type of the inflammatory skin lesion, DCD protein expression was not induced i n human epidermal keratinocytes. In contrast, β-defensin 2 was expressed in ep idermal keratinocytes of inflammatory human skin, but not in keratinocytes of he althy human skin. Upon stimulation of the cultured cells with 12-O-tetradecano yl-phorbol -13-acetate, tumour necrosis factor-α, lipopolysaccharide or H2O2,DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocyt es, but was detected in MeWo and SKMEL28 melanoma cells. Conclusions:These resu lts indicate that, unlike human cathelicidins and β-defensinswhichare inducibl e peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By m odulating surface colonization, DCD may help to prevent local and systemic invas ion of pathogens.展开更多
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...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. Objectives: To evaluate the dermoscopic changes and the rates of excision in benign melanocytic naevi and cutaneous malignant melanoma in long- term follow- up of high- risk patients using digital dermoscopy. Methods: Digital dermoscopic images of 2015 atypical melanocytic naevi in 196 high- risk patients were analysed retrospectively. Among others, the following data were collected for each naevus: changes in surface area, overall architecture, dermoscopic patterns and distribution of pigmentation. All tumours suspicious for melanoma or showing asymmetrical changes were excised. Results During a median follow- up time of 25 months 128 (6.4% ) of all naevi showed changes in size or architecture. Eighty- six per cent of all changes in patients who attended more than one visit were observed at the first follow- up visit. Thirty- three lesions showing changes were excised and two melanomas in situ and 31 melanocytic naevi were diagnosed. Conclusions: Follow- up examinations using digital dermoscopy revealed unchanged morphology in the large majority of melanocytic naevi. Excisions were only performed in cases of asymmetrical growth, asymmetrical changes of pigmentation, or development of dermoscopic features indicative of melanoma. The ratio of 33 lesions excised in order to identify two melanomas in situ seems reasonable and may be further reduced in future.展开更多
文摘Background: Conventional surgery for lentigo maligna melanoma (LMM) is based on normal histological evaluation. However, such evaluation leaves diagnostic gaps. In contrast, complete three-dimensional (3D) histology of excision margins permits accurate detection of continuously spreading tumour strands like those of LMM. These can be specifically excised in tumour-positive areas with smaller excision margins, and better cosmesis and function. To date there have been no controlled studies of micrographic surgery of LMM. Objectives: Clinical parameters and surgical strategies influencing the prognosis of patients with LMM were evaluated in a prospective study of melanoma patients in the Department of Dermatology of the University of Tübingen (1980-99). Methods: The 292 LMMs comprised 7.4%of 3960 primary stage I and II melanomas treated during this period. One hundred and thirty-six patients in this group (46.6%) underwent surgery on the basis of 3D histology. Results: The geometric mean excision margins were significantly smaller in the 3D histology group (P < 0.0001). Patients with micrographic surgery had fewer recurrences. Multivariate analysis of clinical, histological and surgical variables was carried out, and tumour thickness and 3D histology proved to be independent, significant factors for the prognosis of recurrence-free survival (relative risk, RR 2.08, P < 0.0001 and RR 2.11, P = 0.0037, respectively). There were no melanoma-related deaths in the 3D histology group. All 16 melanoma-related deaths were observed among the 156 patients of the conventional histology group (10.3%). Conclusions: Excision of LMM using 3D histology resulted in a two fold lower probability of recurrence and two fold smaller excision margins. 3D histology is a valuable diagnostic tool and can be used in the management of LMM because of the latter’s pattern of continuous tumour spread.
文摘Background: The ear’s specific anatomical and lymphatic characteristics impose special requirements on the treatment of melanoma of the ear. Objectives: The aim of this prospective study was to define prognostic factors for melanoma of the ear and to evaluate surgical strategies for excision margins, histological evaluation and sentinel lymph node biopsy (SLNB) in order to achieve better cosmetic and functional results. Patients and methods: One-hundred and sixty-one patients with stage I/II melanoma of the external ear were treated in the Department of Dermatology, University of Tuebingen, from March 1976 to March 2004 (median follow-up 62 months). Malignant melanoma of the external ear represented 3%of the stage I/II cutaneous melanomas and 20%of the stage I/II head and neck melanomas recorded in the Melanoma Registry of the Department of Dermatology at the University of Tuebingen. Twenty of 42 lentigo maligna melanomas (LMM) underwent conventional histological evaluation, 22 underwent complete three-dimensional histology of excision margins (3D histology) in a paraffin-technique, i.e. micrographic surgery. SLNB was performed in 28 patients with melanomas thicker than 1.0 mm. Clinical, histological and surgical risk factors were evaluated by univariate and multivariate analysis. Results: The median thickness of the tumours in the present study was 1.08 mm (mean 1.51 mm; range 0.18-8.50 mm), and the median excision margins were 11.0 mm (mean 12.61 mm; range 2.0-31.0 mm). The 3-year disease-specific survival rate was 98%, and the 3-year recurrence-free survival rate was 83%. Tumour thickness and invasion level were the only risk factors significant for disease-specific survival. Tumour thickness, location of the tumour and extent of excision margins were independently significant risk factors for recurrence free survival. LMMs removed surgically with accompanying 3D histology were thicker than those examined by conventional histology (median 0.93 mm vs. 0.83 mm). The use of surgery with 3D histology, i.e. micrographic surgery, made it possible to reduce the excision margins (median 5 mm vs. 10 mm) without an increased risk of recurrence. Two of 29 SLNBs were positive (6.9%). There were six preregional recurrences after negative SLNB and one after positive SLNB. None of the patients who underwent SLNB died of melanoma related causes during the observation period. Conclusions: This is the largest series of ear melanomas reported so far. The overall survival depended only on the tumour thickness and Clark level of invasion. Local recurrence was more frequent with smaller excision margins, but this did not influence the overall survival. Smaller excision margins under 3D-histological control did not carry an increased risk of local recurrence. Our results do not permit conclusions regarding the prognostic impact of SLNB for patients with melanoma of the ear.
文摘Background:Antimicrobial peptides (AMPs) are important effector molecules of innate immunity, protecting epithelial surfaces of multicellular organisms. In h uman skin two classes of AMPs-the β-defensins and the cathelicidins-are prod uced by keratinocytes primarily under inflammatory conditions. In contrast, derm cidin (DCD), a recently discovered AMP with broad-spectrum activity, is express ed in eccrine sweat glands and transported via sweat to the epidermal surface. O bjectives:To investigate whether DCD expression is induced under inflammatory c onditions in epidermal keratinocytes. Methods:Lesional skin of the inflammatory skin diseases atopic dermatitis, psoriasis and lichen planus was analysed by im munohistochemistry using a polyclonal anti-DCD antiserum. We also examined whet her DCD RNA expression is induced in cultured human keratinocytes, fibroblasts, melanocytes and melanoma cells. Results:Whereas DCD was constitutively expresse d in eccrine sweat glands of all skin biopsies, we found that, independent of th e type of the inflammatory skin lesion, DCD protein expression was not induced i n human epidermal keratinocytes. In contrast, β-defensin 2 was expressed in ep idermal keratinocytes of inflammatory human skin, but not in keratinocytes of he althy human skin. Upon stimulation of the cultured cells with 12-O-tetradecano yl-phorbol -13-acetate, tumour necrosis factor-α, lipopolysaccharide or H2O2,DCD mRNA expression was not detected in primary keratinocytes, fibroblasts and melanocyt es, but was detected in MeWo and SKMEL28 melanoma cells. Conclusions:These resu lts indicate that, unlike human cathelicidins and β-defensinswhichare inducibl e peptides that primarily function in response to injury and inflammation, DCD is exclusively part of the constitutive innate defence of human skin. By m odulating surface colonization, DCD may help to prevent local and systemic invas ion of pathogens.
文摘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. Objectives: To evaluate the dermoscopic changes and the rates of excision in benign melanocytic naevi and cutaneous malignant melanoma in long- term follow- up of high- risk patients using digital dermoscopy. Methods: Digital dermoscopic images of 2015 atypical melanocytic naevi in 196 high- risk patients were analysed retrospectively. Among others, the following data were collected for each naevus: changes in surface area, overall architecture, dermoscopic patterns and distribution of pigmentation. All tumours suspicious for melanoma or showing asymmetrical changes were excised. Results During a median follow- up time of 25 months 128 (6.4% ) of all naevi showed changes in size or architecture. Eighty- six per cent of all changes in patients who attended more than one visit were observed at the first follow- up visit. Thirty- three lesions showing changes were excised and two melanomas in situ and 31 melanocytic naevi were diagnosed. Conclusions: Follow- up examinations using digital dermoscopy revealed unchanged morphology in the large majority of melanocytic naevi. Excisions were only performed in cases of asymmetrical growth, asymmetrical changes of pigmentation, or development of dermoscopic features indicative of melanoma. The ratio of 33 lesions excised in order to identify two melanomas in situ seems reasonable and may be further reduced in future.
