RESUMEN
Nevus of Ota is an uncommon benign mesodermal melanosis that involves the first and second divisions of the trigeminal nerve. Primary non-cutaneous melanoma often involves distinct genetic mutations compared to cutaneous melanoma. In primary central nervous system (CNS) melanomas associated with nevus of Ota, somatic mutations most commonly occur at the Q209 and R183 residues of GNAQ and likely induce tumorigenesis through upregulation of the MAP kinase pathway. This case underscores the importance of elucidating neurologic symptoms early in patients with nevus of Ota, as a delayed presentation of CNS melanoma could portend a devastating outcome.
Asunto(s)
Neoplasias del Sistema Nervioso Central , Melanoma , Melanosis , Nevo de Ota , Neoplasias Cutáneas , Adolescente , Neoplasias del Sistema Nervioso Central/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Humanos , Melanoma/genética , Nevo de Ota/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genéticaRESUMEN
Nevus of Ota is a blue, hyperpigmented, benign dermatosis of the skin and mucosae that most often occurs unilaterally in the distribution of the ophthalmic (V1) and maxillary (V2) branches of the trigeminal nerve. Although uncommon, association with malignant melanoma is a complication that must be considered in the evaluation of patients with nevus of Ota. Mutations in the GNAQ and BAP1 genes in patients with nevus of Ota place them at higher risk for malignant melanoma and metastasis. We report the case of a 29-year-old woman with a long-standing history of nevus of Ota who presented acutely with an intracranial melanoma as an extension of a primary uveal melanoma.
Asunto(s)
Neoplasias Encefálicas , Melanoma , Nevo de Ota , Neoplasias de la Úvea , Adulto , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Humanos , Melanoma/complicaciones , Melanoma/genética , Melanoma/patología , Melanoma/terapia , Nevo de Ota/complicaciones , Nevo de Ota/genética , Nevo de Ota/patología , Nevo de Ota/terapia , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Neoplasias de la Úvea/complicaciones , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/terapiaAsunto(s)
Melanoma/genética , Melanoma/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Nevo de Ota/patología , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Adulto , Anciano , Femenino , Humanos , Nevo de Ota/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genéticaRESUMEN
Melanoma presents molecular alterations based on its anatomical location and exposure to environmental factors. Due to its intrinsic genetic heterogeneity, a simple snapshot of a tumor's genetic alterations does not reflect the tumor clonal complexity or specific gene-gene cooperation. Here, we studied the genetic alterations and clonal evolution of a unique patient with a Nevus of Ota that developed into a recurring uveal-like dermal melanoma. The Nevus of Ota and ulterior lesions contained GNAQ mutations were c-KIT positive, and tumors showed an increased RAS pathway activity during progression. Whole-exome sequencing of these lesions revealed the acquisition of BAP1 and TP53 mutations during tumor evolution, thereby unmasking clonal heterogeneity and allowing the identification of cooperating genes within the same tumor. Our results highlight the importance of studying tumor genetic evolution to identify cooperating mechanisms and delineate effective therapies.
Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Nevo de Ota/genética , Neoplasias Cutáneas/genética , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Adulto , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Nevo de Ota/patología , Neoplasias Cutáneas/patologíaRESUMEN
Meningeal melanocytomas are rare melanin-producing tumors that are often found to be benign. However, a small subset of these tumors can present as intermediate-grade melanocytomas (IGMs) that have histopathological features that are between those of benign melanocytomas and malignant melanomas. IGMs have the potential to recur and metastasize or progress to a more histologically high grade melanoma. Melanocytomas appear to differ from primary and metastatic melanoma by their prolonged clinical course and they appear to have different driver mutations (i.e. mutation of GNAQ gene). The association of a meningeal melanocytoma with nevus of Ota is extremely rare. To our knowledge, there have been only 10 reported cases of synchronous occurrence and only one of the cases involved an IGM. We report the second case of intermediate-grade meningeal melanocytoma that is associated with congenital nevus of Ota. Histopathological work-up confirmed the intermediate grade of the lesion and a driver GNAQ mutation was identified consistent with previous reports.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP/genética , Melanocitos/patología , Melanoma/genética , Neoplasias Meníngeas/genética , Nevo de Ota/genética , Adolescente , Adulto , Anciano , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Humanos , Masculino , Melaninas/biosíntesis , Melanoma/complicaciones , Melanoma/terapia , Neoplasias Meníngeas/complicaciones , Neoplasias Meníngeas/terapia , Persona de Mediana Edad , Nevo de Ota/patología , Adulto JovenRESUMEN
Nevus of Ota is a benign congenital melanocytic lesion found most commonly in people of Asian ancestry. It is associated with an increased risk of glaucoma and uveal melanomas. Most cases are sporadic and unilateral. We present the first reported case of a brother and sister with familial, bilateral nevus of Ota.
Asunto(s)
Neoplasias del Ojo/genética , Nevo de Ota/genética , Enfermedades de la Esclerótica/genética , Hermanos , Neoplasias Cutáneas/genética , Niño , Preescolar , Neoplasias del Ojo/patología , Femenino , Humanos , Masculino , Nevo de Ota/patología , Enfermedades de la Esclerótica/patología , Neoplasias Cutáneas/patologíaRESUMEN
Pigmentary changes in Asians are larger problems and more important features of aging than wrinkles. Melasma is a commonly observed epidermal hypermelanosis of the face in Asians. The altered dermal structures and impaired basement membrane are thought to have an influence on the development of epidermal hyperpigmentation of melasma. Dermal hyperpigmentary diseases are particularly common in Asians. Acquired bilateral melanosis of the neck is a characteristic dermal melanotic condition primarily of the neck in peri-menopausal women. It is characterized by marked accumulation of dermal pigment with perivascular lymphocytic infiltration. The cases seem to represent a continuum of Riehl's melanosis. Subclinical injury or inflammation may play a role as possible causative factors for the development of the pigmentation.
Asunto(s)
Trastornos de la Pigmentación/etnología , Envejecimiento/etnología , Pueblo Asiatico/genética , Membrana Basal/patología , Dermis/patología , Femenino , Humanos , Terapia por Láser , Linfocitos/patología , Masculino , Melaninas/metabolismo , Melanocitos/metabolismo , Melanocitos/patología , Melanosis/etnología , Melanosis/genética , Melanosis/patología , Melanosis/terapia , Cuello , Nevo de Ota/etnología , Nevo de Ota/genética , Perimenopausia , Trastornos de la Pigmentación/genética , Piel/irrigación sanguínea , Neoplasias Cutáneas/etnología , Neoplasias Cutáneas/genéticaRESUMEN
Nevus of Ota is a variant of congenital nevus, which is morphologically paucicellular and resembles a common blue nevus. Although nevus of Ota is a risk factor for uveal melanoma in white people, the development of cutaneous melanoma within nevus of Ota is a very rare occurrence with only a few reported cases. We present a case of a long-standing nevus of Ota, with radiologic imaging demonstrating a large retro-orbital mass and a biopsy showing melanoma. The histopathology of the eye exenteration specimen illustrated various stages of melanocytic progression including areas resembling a nevus of Ota, blue nevus, cellular blue nevus, and melanoma. There was heterogeneity in the overtly malignant sections with some areas displaying expansile nodules of blander appearing spindled cells, whereas other areas were composed of epithelioid cells with higher mitotic counts and zones of necrosis. The extensive lesion also infiltrated the soft tissue and bone. We performed gene mutation analysis for GNAQ, BRAF, NRAS, and KIT and fluorescence in situ hybridization (FISH) targeting commonly altered chromosomal loci in melanoma and comparative genomic hybridization (CGH). Copy number changes typical of melanoma were identified by both FISH and CGH in the morphologically malignant areas illustrating the relationship of tumor progression and the progressive acquisition of genetic aberrations.
Asunto(s)
Melanoma/patología , Nevo de Ota/patología , Nevo Azul/patología , Neoplasias Orbitales/patología , Hibridación Genómica Comparativa , Análisis Mutacional de ADN , ADN de Neoplasias/análisis , Progresión de la Enfermedad , Femenino , Humanos , Hibridación Fluorescente in Situ , Melanoma/genética , Melanoma/terapia , Persona de Mediana Edad , Nevo de Ota/genética , Nevo de Ota/terapia , Nevo Azul/genética , Nevo Azul/terapia , Evisceración Orbitaria , Neoplasias Orbitales/genética , Neoplasias Orbitales/terapia , Radioterapia Adyuvante , Resultado del TratamientoRESUMEN
The association of nevus flammeus with mongolian spot, nevus fuscoceruleus, nevus spilus and, with variable frequency, with nevus anemicus has been termed phacomatosis pigmentovascularis, a genodermatosis first described by Ota and co-workers. Four different combinations have been specified. Most cases are reported from the Japanese literature. Phacomatosis pigmentovascularis may constitute an exclusively cutaneous disorder, but overlapping with other syndromes like Klippel-Trenaunay syndrome or Sturge-Weber syndrome is also possible. We report a 30-year-old woman with nevus flammeus on the back and right arm associated with nevus fuscoceruleus on the back.
Asunto(s)
Síndrome del Nevo Displásico/genética , Síndrome de Hamartoma Múltiple/genética , Nevo de Ota/genética , Neoplasias Cutáneas/genética , Adulto , Biopsia , Diagnóstico Diferencial , Síndrome del Nevo Displásico/diagnóstico , Síndrome del Nevo Displásico/patología , Femenino , Síndrome de Hamartoma Múltiple/diagnóstico , Síndrome de Hamartoma Múltiple/patología , Humanos , Melanocitos/patología , Microscopía Electrónica , Fagocitos/patología , Piel/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
Uveal melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial uveal melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with uveal melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and melanoma syndrome. Nonrandom cytogenetic changes in uveal melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous melanoma predisposition gene, is probably not a uveal melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in uveal melanoma samples and the absence of germline mutations in familial uveal melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble uveal melanoma. We propose that uveal melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize uveal melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of uveal melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of uveal melanoma.