Acquired bilateral naevus of Ota-like macules: an immunohistological analysis of dermal melanogenic paracrine cytokine networks.

BACKGROUND: Acquired bilateral naevus of Ota-like macules (ABNOM) is similar to melasma with regard to their clinical features, including female predominance, acquired onset, and predominant involvement of the malar area. The similar clinical features suggest the possibility of a shared pathogenesis. Dermal factors including vascularity and melanogenic paracrine networks such as the stem cell factor (SCF)/c-kit pathway have recently been suggested to play an important role in the pathogenesis of melasma. However, the role of dermal factors in ABNOM remains unknown. OBJECTIVES: To provide a novel view on the pathogenesis of ABNOM, we studied the expression of melanogenic paracrine cytokines such as SCF/c-kit, and assessed dermal vascularity. METHODS: Thirty-seven patients with ABNOM and 20 patients with melasma were enrolled in this study. Skin samples were obtained from lesional and perilesional normal skin. Immunohistochemistry was performed. RESULTS: Solar elastosis was slightly more intense in the lesional skin of ABNOM. In contrast to dermal pigmentation and melanocytes, the amounts of epidermal pigmentation and melanocytes were not increased in the lesional skin of patients with ABNOM. The expression of dermal SCF and c-kit was increased; however, the expression of epidermal SCF and c-kit and dermal factor VIII-related antigen was not increased in the lesional skin of ABNOM. CONCLUSIONS: These results suggest that the increased expression of the SCF/c-kit pathway between dermal fibroblasts and dermal melanocytes may play an important role in the pathogenesis of ABNOM.

Expression of MCSP and PRAME in conjunctival melanoma.

BACKGROUND: To analyse the expression of melanoma chondroitin sulfate proteoglycan (MCSP) and the preferentially expressed antigen of melanoma (PRAME) in conjunctival melanoma (CoM), lymph node (LN) metastases of cutaneous melanoma (CM) and conjunctival nevi (CoN) by immunohistology. METHODS: Immunohistology was performed in 70 samples of CoM, 25 of LN metastases of CM and 12 of CoN, and assessed by an immunoreactive score (0-12 points). Statistical analysis was performed to disclose relevant differences in the expression pattern. The diagnostic value of the markers was tested by receiver operating characteristics (ROC) analysis. RESULTS: MCSP and PRAME were expressed at significantly higher levels in CoM and LN metastases of CM than in CoN (p<0.0001). Within CoM, an MCSP expression <9.0 points meant higher risk for recurrences (Cox HR=3.1) and a shorter recurrence-free survival (p=0.002) than an MCSP expression >9.0 points. ROC analysis showed an area under the curve of 91.3% for MCSP (p=0.0002) and 93.8% for PRAME (p<0.0001). CONCLUSIONS: MCSP and PRAME are differentially expressed in conjunctival melanomas and nevi. MCSP might have an impact on the risk for recurrence in being inversely correlated to the event. Both markers have high potential to discriminate CoM from CoN. The results indicate that immunohistological characteristics gain relevance in the assessment of CoM.

Melanotic schwannoma arising in association with nevus of Ota: 2 cases suggesting a shared mechanism.

Melanotic schwannoma is a rare markedly pigmented peripheral nerve sheath tumor comprising cells with prominent melanization and schwannian features. The psammomatous variety is associated with Carney complex, a multiple neoplasia syndrome with spotty skin pigmentation. We present the first 2 reported cases of melanotic schwannoma arising in patients with a history of nevus of Ota, a rare dermal melanosis believed to represent a failure of melanocyte migration to the epidermis during embryogenesis. Case 1 involves a 40-year-old woman with a 1.8-cm, deeply pigmented, trigeminal nerve mass and pigmentation of the maxillary sinus mucosa and bone. Case 2 involves a 53-year-old woman with a 1.5-cm mass adjacent to the clavicle. Microscopically, both masses consist of partially encapsulated epithelioid and spindle cells with abundant melanin pigment, arising in association with peripheral nerves. Morphological, immunohistochemical, and ultrastructural features support a diagnosis of melanotic schwannoma. No psammoma bodies are noted, and neither patient exhibits any additional features of Carney complex. Melanotic schwannoma is most often benign but has been associated with malignant behavior in some cases. Distinguishing this nerve sheath tumor from malignant melanoma can be difficult but is of great clinical importance due to differences in prognosis and treatment.

A role of SH-compounds in maturation of melanosomes in cells cultured from nevus Ota.

A role of SH-compounds such as cysteine and glutathione in melanogenesis in dermal melanocytes cultured from Ota's nevus tissue was demonstrated in relation to another substrate, dihydroxyphenylalanine (DOPA). Chemical analysis of eumelanin and pheomelanin was performed in addition to the conventional electron microscopic observation. Supplements of the culture medium with each of these compounds separately for two weeks gave rise to the formation of pre-pheomelanosomes and secondary lysosomes or myelinosome-like inclusions. When DOPA and glutathione were added to the medium together, the maturation of melanosomes was promoted. This was proven by the increase in electron-density of pre-melanosomes observed as well as by the content of pheomelanin and eumelanin. However, mature melanosomes were not formed when each of these chemicals was added to the medium individually for the same periods. The melanosome maturation seemed to occur via a process involving secondary lysosomes or myelinosomes, in which more electron-dense particles accumulated in the presence of both reagents. The pheomelanosomal process was also observed, but typical eumelanosome-related processes were not observed in this culture system.

Characterization of melanosomes and melanogenesis in cells cultured from Ota's nevus.

Cells from dermis and epidermis of Ota's nevus lesions were cultured to obtain the pigment producing cells that are specific epidermal and dermal melanocytes of nevus Ota. The following media were used: Eagle's minimum essential medium, fortified or not fortified with cholera toxin and phorbol ester. Both epidermal melanocytes and dermal melanocytes grew in the Eagle's minimum essential medium fortified with cholera toxin and phorbol ester. The melanocytes were characterized by 14C-tyrosine uptake and by identification of melanosomes and status of melanogenesis in comparison with those reported in dysplastic nevi and melanomas, as well as those found in Ota's nevus tissue in situ. Eumelanosomes, pheomelanosomes and secondary lysosomal melanosomes appeared in epidermal melanocytes. Pheomelanosomes and melanolysosomes, or myelinosiderosomes appeared predominantly in the dermal melanocytes. These melanosomes seemed to be related to the peculiar skin color of nevus Ota. Some of the abnormal types of melanosomes were very similar to those found in dysplastic nevi and melanomas.