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Primary Cilium Depletion Typifies Cutaneous Melanoma In Situ and Malignant Melanoma  [PDF]
Jinah Kim, Salma Dabiri, E. Scott Seeley
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027410
Abstract: Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.
Primary Cutaneous Melanoma Arising in a Long-Standing Irradiated Keloid  [PDF]
Lindsay M. Fish,Lisa Duncan,Keith D. Gray,John L. Bell,James M. Lewis
Case Reports in Surgery , 2012, DOI: 10.1155/2012/165319
Abstract: Ionizing radiation has been used therapeutically for a variety of clinical conditions, including treatment of hypertrophic keloids. Keloids may rarely be associated with malignancy, but the use of low-dose ionizing radiation is associated with an increased risk of cutaneous malignancies. We describe a case in which a primary desmoplastic melanoma arose in a long-standing, previously irradiated keloid. 1. Introduction Historically, ionizing radiation has been used to treat a variety of clinical conditions including tinea capitis and for treatment of prominent keloids [1]. Over time, however, people who have been treated with radiation for cutaneous lesions have been shown to be at an increased risk of developing cutaneous malignancy in the treated field. 2. Case Presentation A 57-year-old man with an extensive life-time history of sun exposure and long-term smoking was evaluated for a recurrent cutaneous chest wall keloid. The keloid initially developed secondary to a varicella zoster infection as a child. At age 9, the keloid was treated with low-dose external beam irradiation and essentially resolved. Many years later and over a period of eighteen months prior to clinician reevaluation in 2009, the lesion began to grow in size. Corticosteroid injections failed to induce regression and a punch biopsy was performed. Pathology from the punch biopsy revealed a primary desmoplastic melanoma, at least 5.0?mm thick with positive margins arising within a keloid. The patient’s review of systems revealed vague muscle and rib pains, right-sided headaches, abdominal pain, and a forty-five-pound weight loss. Staging workup was completed to investigate these symptoms and revealed no evidence of metastatic disease. Clinically, it was impossible to differentiate keloid from desmoplastic melanoma. Thus, a two-stage surgical procedure was performed with initial resection of the primary site including the entire keloid with 2?cm margins and bilateral axillary sentinel node biopsy (Figures 1, 2, and 3). Temporary coverage of the primary resection defect was performed with porcine dermal substitute (not pictured) to ensure a margin free resection prior to reconstruction, since it was difficult to determine how deep the melanoma had invaded macroscopically. Figure 1: Keloid appearance at presentation. (methylene blue injection for sentinel lymph node biopsy). Figure 2: Surgical defect measuring 145?cm 2. Figure 3: Axillary sentinel lymph node biopsy. Final pathology revealed desmoplastic melanoma occurring in the keloid with clear radial margins and a deep margin within
Clinical Characteristics of Cutaneous Melanoma and Second Primary Malignancies in a Dutch Hospital-Based Cohort of Cutaneous Melanoma Patients  [PDF]
Haike M. J. van der Velden,Michelle M. van Rossum,Willeke A. M. Blokx,Jan B. M. Boezeman,Marie-Jeanne P. Gerritsen
Dermatology Research and Practice , 2009, DOI: 10.1155/2009/479183
Abstract: The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy. In conclusion, 48 patients developed a subsequent malignancy. As nonmelanoma skin cancer is the most frequent second malignancy, our results subscribe to the necessity of follow-up by a dermatologist.
Biology of Human Cutaneous Melanoma  [PDF]
Elias G. Elias,Joanne H. Hasskamp,Bhuvnesh K. Sharma
Cancers , 2010, DOI: 10.3390/cancers2010165
Abstract: A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.
Primary cutaneous melanoma: an 18-year study
Anger, Moris;Friedhofer, Henri;Fukutaki, Marina Fussae;Ferreira, Marcus Castro;Landman, Gilles;
Clinics , 2010, DOI: 10.1590/S1807-59322010000300004
Abstract: background: primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. objectives: this study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. methods: using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. results: the melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. in addition to breslow's thickness and ulceration (p = 0.043 and p < 0.001, respectively), the mitotic rate per mm2 also correlated with worse patient outcome (p = 0.0007). the sum of ulceration (0 when absent or 1 when present), the breslow index (1 when <1 mm, 2 when >1 mm and <4 mm, 3 when >4 mm) and the mitotic index (0 when absent or 1 when >1 per mm2) allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7%) patients had systemic disease. the 5-year survival was approximately seventy percent. conclusion: because american join committee of cancer staging will update the classification of malignant tumors (tnm) staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. additional studies are necessary to confirm the importance of a prognostic score as proposed herein.
Primary Cutaneous Melanoma Arising in a Long-Standing Irradiated Keloid
Lindsay M. Fish,Lisa Duncan,Keith D. Gray,John L. Bell,James M. Lewis
Case Reports in Surgery , 2012, DOI: 10.1155/2012/165319
Abstract: Ionizing radiation has been used therapeutically for a variety of clinical conditions, including treatment of hypertrophic keloids. Keloids may rarely be associated with malignancy, but the use of low-dose ionizing radiation is associated with an increased risk of cutaneous malignancies. We describe a case in which a primary desmoplastic melanoma arose in a long-standing, previously irradiated keloid.
Differential diagnosis in primary and metastatic cutaneous melanoma by FT-Raman spectroscopy
Oliveira, Andrea Fernandes de;Santos, Ivan Dunshee de Abranches Oliveira;Cartaxo, Sidney Bandeira;Bitar, Renata Andrade;Enokihara, Mílvia Maria Sim?es e Silva;Martinho, Herculano da Silva;Martin, Airton Abrah?o;Ferreira, Lydia Masako;
Acta Cirurgica Brasileira , 2010, DOI: 10.1590/S0102-86502010000500009
Abstract: purpose: to qualify the ft-raman spectral data of primary and metastatic cutaneous melanoma in order to obtain a differential diagnosis. methods: ten normal human skin samples without any clinical or histopathological alterations, ten cutaneous melanoma fragments, and nine lymph node metastasis samples were used; 105, 140 and 126 spectra were obtained respectively. each sample was divided into 2 or 3 fragments of approximately 2 mm3 and positioned in the raman spectrometer sample holder in order to obtain the spectra; a monochrome laser light nd:yag at 1064 nm was used to excite the inelastic effect. results: to differentiate the three histopathological groups according to their characteristics extracted from the spectra, data discriminative analysis was undertaken. phenylalanine, dna, and amide-i spectral variables stood out in the differentiation of the three groups. the percentages of correctly classified groups based on phenylalanine, dna, and amide-i spectral features was 93.1%. conclusion: ft-raman spectroscopy is capable of differentiating melanoma from its metastasis, as well as from normal skin.
An Attempt at a Molecular Prediction of Metastasis in Patients with Primary Cutaneous Melanoma  [PDF]
Melanie Gschaider, Friederike Neumann, Bettina Peters, Florian Lenz, Michael Cibena, Malgorzata Goiser, Ingrid Wolf, J?rg Wenzel, Cornelia Mauch, Wolfgang Schreiner, Stephan N. Wagner
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049865
Abstract: Background Current prognostic clinical and morphological parameters are insufficient to accurately predict metastasis in individual melanoma patients. Several studies have described gene expression signatures to predict survival or metastasis of primary melanoma patients, however the reproducibility among these studies is disappointingly low. Methodology/Principal Findings We followed extended REMARK/Gould Rothberg criteria to identify gene sets predictive for metastasis in patients with primary cutaneous melanoma. For class comparison, gene expression data from 116 patients with clinical stage I/II (no metastasis) and 72 with III/IV primary melanoma (with metastasis) at time of first diagnosis were used. Significance analysis of microarrays identified the top 50 differentially expressed genes. In an independent data set from a second cohort of 28 primary melanoma patients, these genes were analyzed by multivariate Cox regression analysis and leave-one-out cross validation for association with development of metastatic disease. In a multivariate Cox regression analysis, expression of the genes Ena/vasodilator-stimulated phosphoprotein-like (EVL) and CD24 antigen gave the best predictive value (p = 0.001; p = 0.017, respectively). A multivariate Cox proportional hazards model revealed these genes as a potential independent predictor, which may possibly add (both p = 0.01) to the predictive value of the most important morphological indicator, Breslow depth. Conclusion/Significance Combination of molecular with morphological information may potentially enable an improved prediction of metastasis in primary melanoma patients. A strength of the gene expression set is the small number of genes, which should allow easy reevaluation in independent data sets and adequately designed clinical trials.
Cutaneous Melanoma: Taiwan Experience and Literature Review  [PDF]
John Wen-Cheng Chang
Chang Gung Medical Journal , 2010,
Abstract: Malignant melanoma is a rare disease in Taiwan with anincidence rate of 0.65/100,000. Excessive exposure to ultravioletradiation is not associated with most Taiwanese melanomacases. Acral lentiginous melanoma comprises 58% of cutaneousmelanoma. Advanced disease is seen in 50% of cases.Surgery, including resection of the primary melanoma, sentinellymph nodes that may harbor microscopic metastasis, clinicallyabnormal lymph nodes, and selected distant metastases, isthe most important treatment. Lymphatic mapping and sentinellymph node biopsy has changed the clinical stage in 22.2% ofour patients. Adjuvant high-dose interferon significantly prolongsprogression-free survival. However, its use in Taiwan islimited by its substantial toxicity. The prognosis of metastaticdisease remains poor with a median survival of 12 months. Inthe past, chemotherapy alone was the most common treatmentmodality for metastatic disease. Recently biochemotherapy hasbeen more commonly utilized to treat patients with metastatic melanoma.
Primary cutaneous nocardiosis: A case study and review  [cached]
Inamadar A,Palit A
Indian Journal of Dermatology, Venereology and Leprology , 2003,
Abstract: BACKGROUND: Primary cutaneous nocardiosis is an uncommon entity. It usually occurs among immunocompetent but occupationally predisposed individuals. AIM: To study clinical profile of patients with primary cutaneous nocardiosis in a tertiary care hospital and to review the literature. METHODS: The records of 10 cases of primary cutaneous nocardiosis were analyzed for clinical pattern, site of involvement with cultural study and response to treatment. RESULTS: All the patients were agricultural workers (nine male) except one housewife. The commonest clinical type was mycetoma. Unusual sites like the scalp and back were involved in two cases. Culture was positive in six cases with N. brasiliensis being commonest organism. N. nova which was previously unreported cause of lymphocutaneous nocardiosis, was noted in one patient, who had associated HIV infection. All the patients responded to cotrimaxazole. CONCLUSION: Mycetoma is the commonest form of primary cutaneous nocardiosis and responds well to cotrimoxazole.
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