Genetic alterations in melanocytic tumors.
ABSTRACT In the last decade, significant progress has been made in our understanding of the genetic alterations in melanocytic tumors. The most exciting finding is the discovery of oncogenic BRAF mutations in both malignant melanoma and melanocytic nevi. This finding indicates that activation of the mitogen-activated protein kinase pathway may be a critical initiating step of melanocytic neoplasia, and that the fundamental difference between melanoma and nevi may lie in the inhibitory machinery for this oncogenic signaling. In addition, different genetic alterations identified in melanomas at different sites and with different levels of sun exposure have been shown, indicating that there are several distinct genetic pathways in the development of melanoma. Different patterns of genetic alterations have also been identified among different kinds of melanocytic nevi. While acquired nevi and small congenital nevi show a high frequency of BRAF mutations regardless of their anatomic localization, the mutations were rare in medium-sized congenital nevi and giant congenital nevi. Spitz nevi show no BRAF mutations, while a subset of cases show HRAS mutations, often associated with a copy number increase of chromosome 11p. The clear differences in genetic aberration patterns have significant clinical implications in the diagnosis and treatment of melanocytic tumors.
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ABSTRACT: Pseudoepitheliomatous hyperplasia (PEH), a histological mimic of squamous cell carcinoma, is an exuberant reactive epithelial proliferation that may be induced by a variety of infectious, traumatic, inflammatory and neoplastic conditions of the skin and mucous membranes. PEH has been described in association with Spitz nevi and intramucosal nevi but not with oral malignant melanoma. A case of PEH in malignant melanoma of the palate in a 46-year-old female patient has been described. A search of the English literature did not disclose any previously reported case of such event. PEH associated with oral malignant melanoma is apparently very rare and most likely originates from the surface epithelium. This is in contrast with PEH in cutaneous melanoma where follicular or eccrine units have been suggested to be the origin.Journal of Cutaneous Pathology 05/2006; 33(4):331-3. DOI:10.1111/j.0303-6987.2006.00454.x · 1.56 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the clinical, pathological, and therapeutic experience of a group of patients with primary oral malignant melanoma (OMM) in Amsterdam, The Netherlands. Fourteen patients (5 males, 9 females, mean age 57.9 years) with histopathologic diagnosis of OMM were treated at the Department of Oral and Maxillofacial Surgery/Oral Pathology of the Vrije University Medical Center in Amsterdam between 1978 and 2005. A pigmented, flat or swollen, irregularly bordered lesion of oral mucosa was detected in most patients during the first clinical examination. Pain was the most commonly referred symptom; the palate was the most frequently affected subsite. Following the mucosal melanoma microstaging system, all patients staged as stage I (T any N0M0) could be subclassified as microstage II (invasion up to the lamina propria), except for 1 patient microstaged as stage III (deep skeletal tissue invasion into skeletal muscle, bone, or cartilage). Where possible, surgery was the treatment of choice. Postoperative radiotherapy, using fractions of 6 Gy twice a week for a total dose of 30 Gy, was given to 3 patients. Three patients were treated primarily with radiotherapy alone. Five patients developed local recurrence within 4 to 72 months, and 10 patients developed distant metastases within 6 to 78 months. Ten patients died of their disease within an average interval of 40 months, with a range of 12 to 80 months. Of the 10 patients who qualified for evaluation of the 5-year-survival rate, 1 was alive with disease and 2 were alive without evidence of disease, resulting in a 5-year survival rate of 30%. However, all patients died of their disease before the end of the 10-year follow-up period. Our study confirms that OMM is a rare and aggressive malignancy with a low 5-year survival rate. An evidence-based protocol for the best therapeutic approach is not yet available.Journal of Oral and Maxillofacial Surgery 12/2007; 65(11):2181-6. DOI:10.1016/j.joms.2006.10.044 · 1.28 Impact Factor
Article: Molecular Nevogenesis[Show abstract] [Hide abstract]
ABSTRACT: Despite recent advances, the biology underlying nevogenesis remains unclear. Activating mutations in NRAS, HRAS, BRAF, and GNAQ have been identified in benign nevi. Their presence roughly correlates with congenital, Spitz, acquired, and blue nevi, respectively. These mutations are likely to play a critical role in driving nevogenesis. While each mutation is able to activate the MAP kinase pathway, they also interact with a host of different proteins in other pathways. The different melanocytic developmental pathways activated by each mutation cause the cells to migrate, proliferate, and differentiate to different extents within the skin. This causes each mutation to give rise to a characteristic growth pattern. The exact location and differentiation state of the cell of origin for benign moles remains to be discovered. Further research is necessary to fully understand nevus development given that most of the same developmental pathways are also present in melanoma.Dermatology Research and Practice 04/2011; 2011:463184. DOI:10.1155/2011/463184