Nevi In Association Research Articles

Congenital Melanocytic Nevi and the Risk of Malignant Melanoma: Establishing a Guideline for Primary-Care Physicians

Objective: The objective of this review is to determine what size congenital melanocytic nevi (CMN) increases the risk of malignant melanoma in affected patients.Background: Congenital melanocytic nevi are benign proliferations of cutaneous melanocytes apparent at birth or in the first postnatal weeks. The Kopf system classifies nevi based on size: small, <1.5 cm in diameter; medium, 1.5–19.9 cm in diameter, and large, ≥20 cm in diameter. Great variability exists in quantifying the risk of malignant transformation from congenital nevi of different sizes. Evidence-based standard guidelines for clinical investigation need to be established. Methods: Literature search included studies on medium, large, and giant congenital nevi in association with melanoma.Results: Three studies pertaining to small, medium, and large congenital nevi are defined. The odds ratio of malignant transformation from small CMN was determined to be 20.9 by history and 10.5 by histology in 238 patients in the case-control study selected. No malignant transformation was found in a prospective study of 230 individuals with medium-sized melanocytic nevi. Finally, a 5% risk of malignant transformation was reported in a prospective study of patients with large congenital nevi.Conclusion: All patients should receive total body skin and mucosal surface exams. Patients with small CMN (<1.5 cm in diameter) and medium CMN (≥1.5 cm–19.9 cm in diameter) should be closely observed over their lifetimes and given the option of specialist referral. Finally, patients with large CMN (≥20 cm in diameter) should be referred to specialists upon initial presentation. More original data and follow-up are needed for maturation of evidence-based clinical recommendations.

Late onset epidermal nevus with hypertrichosis and facial hemihypertrophy

Epidermal nevus syndromes are rare conditions, characterized by different types of keratinocytic or organoid epidermal nevi in association with ocular, neurological, and skeletal manifestations. We present a case of late onset epidermal nevus with hypertrichosis and hemihypertrophy of face. Genetic analysis did not reveal presence of FGFR3 or PIK3CA mutations. The patient has features that cannot be categorized into the present well-known syndromes.

780 Bilateral Renal Artery Stenosis and Epidermal Nevus Syndrome in a Child

Epidermal nevus syndrome is a rare congenital sporadic neuro-ectodermic disorder, characterized by the presence of epidermal nevi in association with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular...

Bilateral renal artery stenosis and epidermal nevus syndrome in a child

Epidermal nevus syndrome is a rare congenital sporadic neuro-ectodermic disorder, characterized by the presence of epidermal nevi in association with various developmental abnormalities of the skin, eyes, nervous, skeletal, cardiovascular and urogenital systems. We describe a 5-year-old boy with conjunctival lipodermoid, cervical and facial sebaceous nevi who presented at 3 years of age with hypertension due to bilateral renal artery stenosis together with multiple vascular anomalies (aorta, celiac trunk, superior mesenteric artery) as shown by magnetic resonance angiography. Systemic arterial hypertension was difficult to control despite combined anti-hypertensive drugs and the surgical repair of the aortic coarctation.

Epidermal nevus syndrome associated with anterior scleral staphyloma and ectopic bone and cartilaginous intraocular tissue

Epidermal nevus syndrome encompasses a group of congenital neurocutaneous anomalies characterized by epidermal nevi in association with cerebral, ocular, and skeletal abnormalities. We report herein the case of a Japanese girl with epidermal nevus syndrome associated with complex ocular choristoma and discuss the histopathological findings. A mass lesion was noted on the left eyeball of a newborn Japanese girl. The lesion appeared to be a scleral staphyloma. Linear and diffuse acanthoses were also apparent on the face. Skin biopsy revealed an epidermal nevus. Histopathological examination of the enucleated left eyeball demonstrated that extremely thin sclera adjacent to the corneal limbus resulted in anterior staphyloma, and ectopic osteocartilaginous tissues were present in the posterior sclera. Epidermal nevus syndrome associated with complex ocular choristoma was diagnosed. The anterior staphylomatous lesion observed in this case has not been reported previously.

Epidermal nevus syndrome

Epidermal nevus syndrome is a group of congenital neurocutaneous disorders characterized by epidermal nevi in association with cerebral, ocular, skeletal, and sometimes cardiac and renal abnormalities. These nevi have been classified according to their predominant component. We described a child presenting with inflammatory linear verrucous epidermal nevus on the head, which is an uncommon location. He also encountered ocular and central nervous system structural disorders.

Pineal germinoma associated with multiple congenital melanocytic nevi: A unique presentation

Intracranial germ cell tumors are rarely seen and typically localize in the pineal or suprasellar region. The largest category of germ cell tumors is the germinoma. There have been reported associations of malignant tumors and chromosomal abnormalities in germ cell tumors. In this study, we present a 22-year-old man with multiple congenital melanocytic nevi in association with pineal tumor. Congenital melanocytic lesions greater than 2 cm were counted to be 54 in number, and those smaller than 1 cm in diameter were found to be 25 in number. The pathological diagnosis of the pineal tumors was germinoma, and the lesions located in the occipital region and trunk were compound congenital nevi. To our knowledge, a relationship between multiple congenital melanocytic nevi and germ cell tumors has not been reported before. The connection between them remains to be clarified.

Neurocutaneous melanosis.

Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the presence of large or multiple congenital melanocytic nevi in association with benign or malignant proliferation of melanocytes in the leptomeninges. NCM is believed to occur as a consequence of an error in morphogenesis in neural ectoderm in the developing embryo. Animal models suggest that aberrant expression of the hepatocyte growth factor/scatter factor (HGF/SF) may be involved in the pathogenesis in the NCM. While the majority of patients with NCM have large congenital melanocytic nevi in a posterior axial distribution, a significant proportion of patients present with multiple smaller nevi in the absence of a single larger lesion. Neurologic manifestations generally occur within the first two years of life, and are often related to increased intracranial pressure. Associated structural anomalies of the CNS have been reported in NCM, particularly the Dandy-Walker complex. The long-term clinical significance of characteristic magnetic resonance findings in neurologically asymptomatic patients is unclear. Approximately half of NCM patients develop CNS melanoma. The prognosis of symptomatic patients remains poor.

Analysis of N- and K-Ras Mutations in the Distinctive Tumor Progression Phases of Melanoma

Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the "intraepidermal" radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma.

Dysplastic changes in different types of melanocytic nevi. A unifying concept.

We observed histopathologic changes previously described in dysplastic melanocytic nevi in association with a dermal component characteristic of other types of melanocytic nevi or overlapping with features of other varieties of nevi. In order to determine the frequency of these changes, we studied 2,164 cases of compound melanocytic nevi that fulfilled the histopathologic criteria for the diagnosis of compound dysplastic nevus, including architectural pattern, cytologic features, and mesenchymal changes. Of the 2,164 compound dysplastic melanocytic nevi, 1,895 (87.6%) had the histopathologic characteristics previously described for dysplastic nevus, 179 (8.3%) showed a dermal component with a congenital pattern, 67 (3.1%) demonstrated epidermal and dermal characteristics of Spitz's nevus, 8 (0.3%) had features of a combined blue nevus, 13 (0.6%) had a halo phenomenon and 2 (0.1%) showed dermal neuronevus. By considering these nevi as variants of dysplastic nevi, one may apply a unified conceptual basis for their nomenclature. In order to completely describe the appearance of the nevus, we named them by adding the term "dysplastic", to their main histopathologic subtype. Accordingly, six different varieties of dysplastic nevi were identified: 1) dysplastic nevus (original); 2) dysplastic nevus with a congenital pattern; 3) dysplastic Spitz's nevus; 4) dysplastic combined blue nevus; 5) dysplastic halo nevus; and 6) dysplastic neuronevus. In summary, we conclude that the histopathologic criteria previously reported for the diagnosis of dysplastic nevi may be found in association with a dermal component characteristic of other types of melanocytic nevi or may have overlapping features with other variants of nevi.

Widespread eruptive dermal and atypical melanocytic nevi in association with chronic myelocytic leukemia: case report and review of the literature

Eruptive nevi have been associated with local skin trauma and immunosuppression, and atypical eruptive nevi preceding melanoma have been reported in immunocompromised transplant patients. We describe a 25-year-old man with widespread eruptive atypical and dermal melanocytic nevi in association with chronic myelocytic leukemia. Our patient's disease differs from earlier reports of eruptive nevi because his nevi appeared before induction chemotherapy. Eruptive nevi may have been a prodrome to leukemia in this patient. His nevi were histologically similar to eruptive atypical nevi observed in AIDS patients and may imply a link between systemic immunosuppression and melanocyte proliferation. We suggest that patients in whom eruptive nevi develop in association with immunosuppression should be carefully observed for the development of melanoma skin cancer.

Primary Leptomeningeal Melanoma

Primary malignant melanoma of the leptomeninges of the central nervous system is a rare and aggressive tumor in children. We report our experience from 1964 to 1990 with this tumor in eight children. The mean age at diagnosis was 4.9 years (range, 1.3 to 13 yr). Five children presented with signs and symptoms of raised intracranial pressure from hydrocephalus secondary to tumoral obliteration of the basal cisterns, but the time from the initial symptomatology to diagnosis was frequently delayed. Three patients in this series had hairy nevi in association with their leptomeningeal melanoma. Cerebrospinal fluid (CSF) analysis typically showed raised opening pressures, decreased glucose, and increased protein concentrations. Malignant melanoma cells were found in the CSF in three patients. Confirmatory radiographic examinations included air encephalography, myelography, and computed tomographic and magnetic resonance scanning. Four patients were treated with lumboperitoneal shunts, and one patient was treated with a ventriculoperitoneal shunt for hydrocephalus. Two patients underwent craniotomies and subtotal excisions of their tumors. In seven patients, a definitive diagnosis of leptomeningeal melanoma was made by pathological examination of tissues sent at surgery or at post mortem. In one case, the diagnosis was established by a detailed cytological analysis of the CSF. Four children died of fulminant disease and tumor spread before treatment could be instituted. The four children who received treatment had a combination of radiation therapy and chemotherapy. One child received intrathecal methotrexate. The two children with the longest survivals (2 and 3 yr, respectively) received cisplatinum and dimethyltriazenoimidazole carboxamide in addition to craniospinal irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)