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Clark Level (clark + level)
Selected AbstractsFine-needle aspiration biopsy of metastatic malignant melanoma resembling a malignant peripheral nerve sheath tumorDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008Svetoslav Bardarov M.D. Abstract We report a case of metastatic malignant melanoma resembling a malignant peripheral sheath tumor, which posed a significant diagnostic challenge. The patient is a 76-year-old male, who presented in the emergency room with bilateral chest pain exacerbated by inspiration. The pain was present for 3 week and was not exacerbated by physical exercise. The diagnostic workup revealed bilateral parenchymal pulmonary infiltrates. The CT-scan guided fine-needle aspiration and the core biopsies of the largest pulmonary lesion revealed high-grade spindle cell neoplasm with individual cell apoptosis and necrosis. The immunohistochemical profile on the cell block showed that the cells are positive for Vimentin. The S-100 stain showed only focal positivity. The immunohistochemical stains for HMB45, Melan A, pancytokeratin, and smooth muscle actin were negative. Five years ago the patient was diagnosed with melanoma on the back with Clark level of IV. The melanoma was excised with clear margins and sentinel lymph nodes were negative. Careful examination of patient's previous slides revealed an area of spindle cell melanoma adjacent to a nodular type melanoma. Based on the patient's previous history, current clinico-pathologic presentation and immunohistochemical profile, the diagnosis of metastatic malignant melanoma resembling peripheral nerve sheath tumor was favored over the diagnosis of metastatic malignant spindle cell neoplasm of unknown primary site, which by itself is very rare clinical scenario. Diagn. Cytopathol. 2008;36:754,757. © 2008 Wiley-Liss, Inc. [source] Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanomaHISTOPATHOLOGY, Issue 7 2007F Piras Aims:, Survivin is expressed in neoplastic cells and appears to be associated with resistance to therapy and shorter survival in various types of tumours. The aim of the present study was to determine whether nuclear or cytoplasmic expression of survivin is related to disease recurrence and overall survival of patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Methods and results:, Immunohistochemistry was performed on formalin-fixed paraffin-embedded sections of primary cutaneous melanoma from 50 patients. Survival rates were estimated using the Kaplan,Meier method and compared using the log rank test. Association of clinical variables (gender, age, tumour location, thickness, Clark level and AJCC stage) with survivin expression was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for survivin had an increased risk of disease recurrence during the first three postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic immunoreactivity was not correlated with either survival or clinical variables. Conclusions:, Nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with Stage I and II melanoma. [source] Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasmsJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005Michael L. Cohn Recent studies have suggested that some metastatic solid tumors lack claudin expression. It is unknown whether claudins play a role in cutaneous melanoma. Immunohistochemical studies were performed on tissue microarrays containing 19 benign melanocytic nevi (BN), 21 dysplastic nevi (DN), 23 primary malignant melanomas (MMs), and 31 metastatic melanomas (MMMs) using a polyclonal anti-claudin-1 antibody. Immunoreactivity in tumor cells and associated vessels was graded by intensity and by percentage of reactive cells. Normal epidermis served as internal control (3+ labeling). Cases with at least 2+ labeling in more than 25% of the cells were considered positive. Claudin-1 expression was present in 37% of BN, 24% of DN, 26% of MM, and 3.2% of MMM. Tumor-associated vessels showed the following results: 11 of 19 (58%) in BN, 14 of 21 (67%) in DN, 17 of 23 (74%) in MM, and 6 of 31 (19%) in MMM. A significant loss of expression was noted between MMM and all other lesions in tumor cells and associated vessels. There was no significant difference between BN, DN, and MM. Within primary melanomas, there was a significant correlation between expression of claudin in tumor cells and Clark level/Breslow thickness. Also significant was a decreased expression of claudin in tumor vessels of lesions with higher Breslow thickness or Clark level. These data suggest that loss of claudin-1 may play a significant role in the acquisition of metastatic phenotype in cutaneous melanoma. [source] Osteopontin as a molecular prognostic marker for melanomaCANCER, Issue 1 2008Javier Rangel MD Abstract BACKGROUND. Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined. METHODS. Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS. High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062). CONCLUSIONS. The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis. Cancer 2008. © 2007 American Cancer Society. [source] Clinicopathologic significance of dysadherin expression in cutaneous malignant melanomaCANCER, Issue 8 2005Immunohistochemical analysis of 115 patients Abstract BACKGROUND The E-cadherin,mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti,cell-cell adhesion function and down-regulates E-cadherin. METHODS Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors. RESULTS Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001). CONCLUSIONS Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma. Cancer 2005. © 2005 American Cancer Society. [source] Expression of lumican, a small leucine-rich proteoglycan with antitumour activity, in human malignant melanomaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2007S. Brézillon Summary Background., The family of small leucine-rich proteoglycans (SLRPs), which includes decorin, lumican, biglycan and fibromodulin, constitutes an abundant component of the skin extracellular matrix. We previously demonstrated that human lumican inhibits melanoma growth and progression in a mouse experimental model, by regulating cell migration, proliferation and apoptosis. Aim., The aim of this study was to investigate the expression of lumican and decorin in human malignant melanoma and adjacent peritumoral tissue, to understand better their role in the control of growth and invasion of human melanoma. Methods., Expression of both proteoglycans was studied by immunohistochemistry using specific antibodies in 34 malignant melanomas, 12 Hutchinson's melanotic freckles and 4 cutaneous metastatic melanomas. Results., We showed that lumican and decorin are located in the dermis and in the peritumoral stroma of malignant melanoma, but are not found in melanoma cells or dense tumour tissue. In the healthy dermis, distant from the tumour, the increasing ratio of lumican to decorin was inversely correlated with the proliferation of the tumour cells (P = 0.035). The comparison of the level of expression of lumican protein in superficial vs. nodular subtypes of malignant melanomas showed a decrease of lumican but not decorin in the peritumoral stroma of nodular subtypes. In the peritumoral stroma, the level of expression of lumican but not decorin decreased significantly (P = 0.016) with increasing Clark levels. In addition, immunocytochemical and reverse transcription PCR analyses of malignant melanoma cell lines (A-375, HT-144) and of MRC-5 and dermal fibroblasts from healthy donors in vitro confirmed that dermal fibroblasts are responsible for lumican and decorin synthesis in skin. Conclusions., Lumican may regulate vertical progression of human malignant melanoma, but further study is necessary to clarify the antitumour mechanism and the downstream signal transduction pathways involved. [source] Cutaneous melanoma: estimating survival and recurrence risk based on histopathologic featuresDERMATOLOGIC THERAPY, Issue 5 2005David E. Elder ABSTRACT:, The prognosis of melanoma is best understood in terms of a model of tumor progression, in which most melanomas may evolve through two major phases of progression: from a lesion that is nontumorigenic and has little or no capacity for metastasis; to a more advanced lesion that is tumorigenic and may have capacity for metastasis. The likelihood of metastasis varies with a number of attributes of the primary melanoma, including the phase of progression, the Breslow tumor thickness, mitotic rate, and host response to the tumorigenic compartment of the lesion, Clark's level of invasion, and other factors. When distant metastasis has occurred, the prognosis for the patient is very poor. In this monograph, the focus will be the discussion of factors related to the prognosis of melanomas that at diagnosis are clinically localized to the primary site. [source] Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanomaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2003N. Jonjic Summary Depth of invasion and stage of the disease are well known prognostic indicators in cutaneous melanoma (CM). However, the role of other parameters, such as the variations in cytomorphology of melanocyte tumours, mitotic activity and angiogenesis is still open to question. The aim of this study was to analyse proliferation by mitotic activity index (MAI) and immunostaining of proliferating cell nuclear antigen (PCNA), and the intensity of neovascularization (microvessel density; MVD) in CM clinical stage I in relation to epithelioid, spindle and nevoid cell type, histological type (superficial spreading melanoma and nodular melanoma), Clark's level and Breslow thickness. Finally, the role of all parameters in the prognosis of CM was evaluated. Statistical analysis demonstrated that cytological characteristics of CM correlate only with Clark's level, while histological types correlate with MAI, PCNA and MVD. MAI and PCNA also showed correlation between groups according to Clark's level and Breslow thickness. Finally, tumour cell PCNA was found to correlate with MVD. Survival of patients with CM correlated significantly with MAI. These results suggest that cytological variation, histological type, PCNA and MVD alone are not independent prognostic parameters, whereas MAI is a potentially important prognostic marker in CM. [source] |