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Neurocutaneous melanosis with intracranial malignant melanoma in an adult: a case report.

A 65-year-old female with congenital giant, hairy and pigmented nevus developed sudden onset of headache and consciousness disturbance. CT scan revealed a high density mass in the right temporal subcortical region. The high density area suggested hematoma. A right temporal craniotomy was performed. Hemorrhage was observed in a black colored tumor. Histologically, the tumor was malignant melanoma, while the skin tumor was benign intradermal nevi. This patient was diagnosed as neurocutaneous melanosis. Neurocutaneous melanosis belongs to unusual congenital syndrome, and an adult case is very rare. To our knowledge this is the oldest patient to be reported with this disease.

Aged↗

Treatment of nevus using medical tattooing.

Medical tattooing is used to color skin with a pigment loss. Currently, however, a trial-and-error scheme is employed to obtain the desired color appearance of tattooed skin because prediction of the color appearance is dependent on the experiences of medical doctors. We propose a method for predicting the color appearance of tattooed skin. Two trial dyes are first injected in the area of pigment loss, and the color appearance of a third dye to be injected can be predicted using measured spectrocolorimeter data and mathematical formula. The spectrocolorimeter measures the color appearances of the skin before and after tattooing using the first two dyes, and the mathematical formula calculates the color appearance of the tattooed skin using any third dye. In the derivation of the mathematical formula, light propagation in the skin has been modeled using the modified Lambert-Beer law considering the strong scattering of light by biological tissues. The proposed method was successfully validated by a preliminary tattooing of the skin to an area with pigment loss. Predicting the color appearance of tattooed skin significantly reduces the number of trial-and-error attempts required in the current methods. Medical tattooing using this method can also be applied to treat various skin color abnormalities such as leukoderma, intradermal nevi, and reconstructed nipples.

Colorimetry↗

On the occurrence of cysteinyldopa and dopa in melanocytes and benign nevi cells.

Previous studies have demonstrated a specific cytoplasmic fluorescence in human melanocytes, as well as in pigmented nevi and in malignant melanomas, when the formaldehyde histofluorescence method for visualization of certain catechol and indole derivatives was used. In malignant melanoma two fluorogenic substances, dopa and cysteinyldopa, were found previously. In human melanocytes and benign nevi cells the fluorogenic catechols have so far not been characterized, since chemical analyses are difficult to perform on skin, due to the small amounts of catechols present. However, using split thickness skin quantitative determinations are possible by sensitive fluorometric methods. The chemical analyses of cysteinyldopa showed that in human adult skin most or all was located in the superficial layers. The only specific fluorescence in the thin skin was found in dendritic melanocytes. The findings leave little doubt that cysteinyldopa is stored in melanocytes although the possibility of a concomitant occurrence of other thioethers is not excluded. Nevi and giant nevi were also similarly studied and we found considerable amounts of cysteinyldopa in the nevi. It seems as if the cysteinyldopa is stored in the fluorescent nevi cells. There was no consistent difference in the content of the catechol derivatives between intradermal and compound nevi.

Adolescent↗

Cyclin D1 overexpression in Spitz nevi: an immunohistochemical study.

The morphologic distinction between Spitz nevus and malignant melanoma can be difficult. Because cyclin D1 has been reported to be overexpressed in malignant melanomas, but not in common acquired nevi, we hypothesized that cyclin D1 might be a useful marker to distinguish Spitz nevi from malignant melanoma. Thus, we assessed for cyclin D1 expression in 11 Spitz nevi (10 compound and 1 intradermal) and 9 malignant melanomas (4 Clark stages I-III and 5 Clark stages IV-V) using an immunohistochemical method and routinely fixed and processed tissues. The cyclin D1 results were arbitrarily divided into three groups: 0% to 10%, >10% to 25%, and >25%. We confirmed the observations reported previously by others that cyclin D1 is expressed in malignant melanomas but not in common acquired nevi. Unexpectedly, a relatively high number of cyclin D1-positive cells (i.e., >10%) was also found in all cases of Spitz nevus. However, unlike malignant melanoma, the cyclin D1 positivity in Spitz nevi was present in a zonal pattern. In other words, the number of cyclin D1-positive cells decreased as the lesion extended more deeply, with the number of positive cells in the reticular dermis being less than that in the papillary dermis. Fluorescence in situ hybridization methods were used to assess amplification of 11q13, the locus harboring the cyclin D1 gene, in four cases of Spitz nevus; all were disomic. Using the antibody MIB-1, we compared cyclin D1 expression to the proliferation rate in Spitz nevi. Despite the high cyclin D1 positivity, all Spitz nevi had a relatively low number of MIB-1-positive cells (mean=3.2%), which was significantly lower than that of malignant melanomas (mean=15.3%) (p < 0.001). Thus, unlike malignant melanoma, there appears to be a dissociation between cyclin D1 overexpression and cell proliferation in Spitz nevi.

Carrier Proteins↗

[Nevus on nevus. Apropos of 7 case reports, 3 of them associated with other dysplasias, and 1 with an invasive malignant melanoma].

There is some doubt as to whether naevus pilus is identical with naevus-on-naevus or lentiginous naevus en mottes. The former could be classified together with Becker's naevus among the clinically progressive types of epidermal naevi, whereas the latter could be a truly melanocytic naevus of special expression which, for some authors, might become malignant. Seven cases of naevus-on-naevus with different sizes and locations are reported. In 3 cases the naevus was associated with other pathologies: pigmented sclerotic and kyphoscoliosis, verrucoid epidermal naevus, tuberous angioma and underlying muscular hypertrophy. In every case the diagnosis was confirmed by histological examination. An invasive malignant melanoma on superficial extensive melanoma coexisted with a retiform intradermal naevus pilosus. The hypothesis of complex neuro-ectodermic dysplasia and the histogenesis of malignant melanoma developed upon a naevus-on-naevus are discussed.

Adult↗

Differentiation-associated localization of nPKC eta, a Ca(++)-independent protein kinase C, in normal human skin and skin diseases.

The expression of nPKC eta, a Ca(++)-independent isoform of protein kinase C in normal human skin, and skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, nevus pigmentosus, and seborrheic keratosis, were examined by immunohistochemical staining using a polyclonal antibody raised against a synthetic peptide at a diverse region of the nPKC eta molecule. In normal epidermis, the strongest staining was observed in the uppermost granular layer with no staining of the spinous or basal layers. The inner layer of the intra-epidermal eccrine duct was also strongly stained. Weak staining was observed in several layers of the outer root sheath of the follicular infundibulum. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, intradermal eccrine duct, arrectores pilorum, melanocytes, Langerhans cells, fibroblasts, or blood vessels. In psoriatic skin, stained keratinocytes were distributed in the suprabasal layers with the most being observed in the uppermost layer and the least in layers closed to the basal layer. In squamous cell carcinoma, weak staining was observed in the keratotic cells around horny pearls. In the basal cell epithelioma and nevus pigmentosus, the cells were not stained, whereas in seborrheic keratosis, cells that stained were located in the granular layer. We conclude from the evidence presented above that nPKC eta is expressed in close association with epidermal differentiation in normal skin and skin diseases.

Adult↗

Spitz nevus (large spindle cell and/or epithelioid cell nevus). Age-related involvement of the suprabasal epidermis.

The Spitz nevus (large spindle and/or epithelioid cell nevus) is a benign acquired melanocytic tumour found predominantly in children and adolescents. Depending on the architecture (junctional, compound, dermal) and cytology (predominance of spindle or epithelioid cells, or presence of both cell types) several variants have been distinguished. A histological feature occasionally leading to diagnostic difficulties is the involvement of the suprabasal epidermis. The present study details the occurrence of intraepidermal involvement (pagetoid spread, nesting of cells, trans-epidermal elimination) according to the age of the patients. 89 cases of Spitz nevus were reviewed. There were 19 compound Spitz nevi with evidence of epidermal involvement, 56 cases of compound Spitz nevi without evidence of epidermal involvement and 14 cases of dermal Spitz nevi. The epidermal involvement mainly consisted of nesting of nevus cells above the basal cell layer, 9 cases clearly showing evidence of transepidermal elimination of cell nests. Upward spread of single melanocytes (pagetoid spread) was minimal and always associated with nesting or trans-epidermal elimination. The mean age of patients was significantly lower in the group of compound nevi with intraepidermal involvement (7.16 +/- 4.52 years), than in the group of compound nevi without epidermal involvement (13.18 +/- 8.88 years). The age of the latter group was significantly lower than the group of pure intradermal nevi (30.14 +/- 11.25 years). Thus, involvement of the suprabasal epidermis is not a feature of Spitz nevi in adults; in such a case the diagnosis of malignant melanoma should be considered.

Adolescent↗

Immunohistochemical demonstration of S100 protein in malignant melanoma and pigmented nevus, and its diagnostic application.

The presence of nervous tissue specific S100 protein was studied immunohistochemically in 47 cases of malignant melanoma and 25 pigmented nevi of various types of peroxidase-antiperoxidase immunoenzyme method on routine paraffin sections of the surgical specimens. Of 47 cases of malignant melanoma, 44 were positively stained for S100 protein. The intensity of S100 protein immunostaining was suggested to be inversely proportional to the amount of melanin pigment. In ten cases of 12 amelanotic melanomas, the immunoreaction for S100 protein in tumor cells was stronger than that of normal Bergmann glial cell in human cerebellum. Intradermal nevi and juvenile melanomas were strongly positive for S100 protein, but blue nevi contained little or no S100 protein. Our results suggest that S100 protein is widely distributed among melanotic tumors and is also a very useful diagnostic indicator for malignant melanoma, especially of the amelanotic type.

Histocytochemistry↗

Giant nevocellular nevi with rickets and brainstem tumor.

A boy, 9 years, 8 months of age, with hairy pigmented nevi over the trunk, upper extremities, and face with bone deformities characteristic of rickets was admitted because of general weakness and poor appetite for 3 weeks. Repeated examinations demonstrated marked brainstem dysfunction; a brainstem tumor was visualized by computed tomography. The patient died 14 days after admission despite supportive treatment. The relationship between giant intradermal nevocellular nevi and brain tumor is discussed.

Arachnoid Cysts↗

Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis.

A subset of Spitz nevi poses substantial diagnostic difficulty, even among experts, due to its resemblance to malignant melanoma. These lesions are termed atypical Spitz nevi/tumors and there is currently a lack of objective criteria for predicting their biologic behavior. We compared the expression of Ki-67, p21, and fatty acid synthase by immunohistochemistry in 10 atypical Spitz nevi, 28 typical Spitz nevi, 19 compound melanocytic nevi and 18 invasive malignant melanomas. There was a progressive increase in fatty acid synthase cytoplasmic expression with statistically significant differences observed between Spitz nevi and atypical Spitz nevi (P=0.003) and between atypical Spitz nevi and malignant melanoma (P<0.050). Ki-67 nuclear staining was lower in both typical and atypical forms of Spitz lesions than in malignant melanoma (P<0.001). The degree of P21 nuclear expression in atypical Spitz nevi was not significantly different than in Spitz nevi, but was significantly greater than expression in conventional nevi and approached significance after multiple comparisons corrections for malignant melanoma. Thus, a high level of P21 expression makes a tumor more likely to be a typical or atypical Spitz nevus than a malignant melanoma, especially when coupled with a low Ki-67 index and weak expression of fatty acid synthase. These immunohistochemical observations support the concept that atypical Spitz nevi are distinct lesions of borderline biologic behavior residing between Spitz nevi and malignant melanoma. The study also compared a large array of histologic features of 16 cases of typical Spitz nevi in children with 12 typical Spitz nevi in adults. The adult lesions were significantly more likely to be intradermal and to display dermal fibroplasia, but were histologically similar to their pediatric counterparts in all other respects.

Adolescent↗

"Pseudomelanoma" in a keloid.

A pigmented lesion resembling a superficial spreading malignant melanoma appeared in keloidal scarring resulting from partial excision of three closely set intradermal and compound nevi. Complete excision of nevi when feasible is recommended as the wisest course to obviate future uncertainty.

Adult↗

Treatment of congenital melanocytic nevi using the combined (normal-mode plus Q-switched) ruby laser in Asians: clinical response in relation to histological type.

Clinical response of congenital melanocytic nevus (CMN) to the combined normal-mode ruby laser (NMRL) and Q-switched ruby laser (QSRL) treatment method (ie, NM plus QS) was correlated with the histologic depth of nevomelanocytic nests to predict the efficacy rate and therapeutic outcome of the laser treatment. Thirty-four patients with CMN were treated using the combined (NM plus QS) ruby laser method. The clinical results of the laser treatment demonstrated that 20 had excellent response, 11 had good response, 3 had fair response, and there was no poor response. When correlated with the histologic type, the efficacy rate of the combined ruby laser was significantly higher in the superficial intradermal type than in the others. We conclude that combining the NMRL and QSRL with appropriate parameters to target both superficial and deep nevomelanocytic components provides a greater degree of penetration of laser light.

Adolescent↗

Combined cutaneous hamartoma encompassing benign melanocytic naevus, vellus hair cyst and epidermoid cyst.

We describe a combined cutaneous hamartoma in a 57-year-old man, which comprised a vellus hair cyst, an epidermoid cyst and an intradermal melanocytic naevus in a single facial tumour. The vellus hair cyst was filled with keratinous material with unusual slit-like lacunae. While numerous cases of epidermoid cyst have been reported in association with an intradermal melanocytic naevus, our case is a rare example of a lesion combining several hamartomatous elements.

Cysts↗

The histogenesis of acquired melanocytic nevi. Based on a new concept of melanocytic differentiation.

A new concept of melanocytic differentiation during normal development is presented, suggesting that 1) normally developing melanocytes and Wagner-Meissner bodies are both derived from primitive, pluripotential precursors in the perineural region of fetal cutaneous nerves; and 2) melanocytes, like keratinocytes and many other cell series, have a differentiation pathway with discrete stages. The proposed stages of the melanocytic differentiation pathway are: the nerve-sheath precursor stage, the dermal migratory stage, the junctional migratory stage, and the dendritic stage. This theory is consistent with current knowledge of human embryology, present understanding of the biology of cells derived from the neural crest, and modern concepts of stem cells and differentiation. Based on this concept, it is proposed that the commonly encountered types of acquired melanocytic nevi derive from pluripotential cells in the nerve-sheath precursor stage of the melanocytic differentiation pathway. As the progeny of these precursors attempt to mature along the pathway, they may produce various patterns that may be interpreted as caricatures of the stages in the pathway. In particular, maturation of most elements to the dendritic stage may produce the pattern of lentigo simplex; predominance of maturation to the junctional migratory stage may produce the pattern of junctional nevi; predominance of maturation to the dermal migratory stage may produce the pattern of intradermal nevi; and failure of progeny to mature along the melanocytic differentiation pathway may produce the pattern of neuroid nevi. This histogenetic model accounts satisfactorily for morphologic variations and clinicopathologic correlations in acquired melanocytic nevi.

Cell Differentiation↗

Pigmented terminal hair cysts within an intradermal melanocytic naevus.

The combination of melanocytic naevi and cysts of adnexal or epithelial origin has been described previously. Herein we describe a case of intradermal melanocytic naevus containing pigmented terminal hair cysts, a rare variant of epithelial cysts. Our observation suggests that pigmented follicular cysts and combined cystic-melanocytic lesions may be attributed to follicular occlusion.

Adult↗

Recurrent Spitz's nevi. A clinicopathologic investigation.

Spitz's nevi recur uncommonly following initial removal. A clinicopathologic investigation was performed on 16 such cases. The initial nevi in almost all cases extended to the margins of the sections. Otherwise, these lesions showed no unusual clinical or histologic features. The average recurrence time was 13 months, with a range from 2 months to 3 years. The recurrent lesions occasionally were mistaken clinically for keloids. Histologically, recurrent lesions were predominantly intradermal. Nests, fascicles, and individual spindle and/or epithelioid cells extended to the deep reticular dermis and occasionally into the subcutaneous fat. The surrounding stroma was densely fibrotic. Recurrent Spitz's nevi are different clinically and histologically from recurrent ordinary melanocytic nevi. They also often differ histologically and clinically from primary Spitz's nevi. Recurrent Spitz's nevi are similar histologically to the desmoplastic type of Spitz's nevus.

Adolescent↗

Image analysis cytometry of dysplastic nevi.

Computerized image analysis was used to assess nuclear atypia in 24 dysplastic nevi (DN), 19 CN (CN), and five thin melanomas. DN were selected for the study using architectural criteria alone. Feulgen-stained, 6-um sections were analyzed with a microTICAS cytometer. At least 100 nuclei were measured in each case. The standard deviation of nuclear area, mean nuclear roundness, standard deviation of nuclear roundness, mean ploidy, and standard deviation of ploidy were found to be significantly greater for DN than for CN. DNA histograms from DN showed an increased fraction above 2N, suggesting that DN are more proliferative than CN. No DN were aneuploid. All melanomas were aneuploid, and differed significantly from DN in mean nuclear area, standard deviation of nuclear area, mean ploidy, and standard deviation of ploidy. There were no significant differences between the junctional and intradermal populations of compound DN in any of the measured parameters, except that the intradermal nuclei were significantly rounder than the junctional nuclei. There were no significant differences between DN from patients with only a single DN and DN from patients with at least two dysplastic nevi.

Cell Nucleus↗