Morphologic Changes and the Expression of Alpha-Melanocyte Stimulating Hormone and Melanocortin-1 Receptor in Melasma Lesions: A Comparative Study

Abstract

Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light- to dark-brown macules on sun-exposed skin areas. The literature shows few studies on its physiopathogeny. However, changes in α-melanocyte stimulating hormone (α-MSH) secretion and melanocortin-1 receptor (MC1-R) expression may play a role to trigger this condition. Biopsies were taken from both melasma skin and adjacent perilesional normal skin of 44 patients. The biopsies were submitted for hematoxylin and eosin and Fontana-Masson staining and immunohistochemistry with Melan-A, α-MSH, and MC1-R, and processed for transmission electron microscopy. In some cases, they were submitted to MC1-R gene expression analysis by real-time polymerase chain reaction. Increased lymphohistiocytic infiltrate and solar elastosis, higher epidermal melanin were observed in melasma skin. Electron microscopy revealed a greater number of mature melanosomes in keratinocytes and melanocytes, and more prominent cytoplasmic organelles in melasma skin. There was no difference in melanocyte number between areas. However, melanocytes were larger and more dendritic in melasma skin. Immunohistochemistry with α-MSH and MC1-R showed significant labeling in melasmic epidermis but MC1-R messenger ribonucleic acid (RNAm) did not show significant quantitative difference between melasma and normal skin.

Clues to the Pathogenesis of Melasma from its Histologic Findings

“…Fontana-Masson staining has shown that, the melanin content of melasma skin is higher in all layers of the epidermis, including the stratum corneum, than that in perilesional normal skin [7][8][9]. Image analysis of Fontana-Massonstained sections of skin from 22 patients with melasma showed a significant difference in the density of melanin between melasma skin (mean ± standard deviation [SD]: 0.37 ± 0.02) and perilesional normal skin (0.34 ± 0.02) (p<0.01) [10]. These findings indicate that the development of melasma involves accelerated melanin synthesis, increased levels of melanin transfer to the keratinocytes, and reduced melanin degradation.…”

“…In contrast, a study by Grimes et al [11] of 22 skin specimens from subjects with Fitzpatrick skin types IV-VI immunostained using Mel-5, did not find a significant increase in melanocyte numbers in melasma skin compared with perilesional normal skin. Moreover, in their study of 44 patients with melasma, Miot et al [10] did not find any differences in melanocyte numbers between melasma skin and perilesional normal skin sections labeled using a Melan-A antibody.…”

“…Electron microscopy has shown higher numbers of mature melanosomes in keratinocytes and melanocytes in melasma skin [10], and a significantly higher number of dendrites per keratinocyte in melasma skin (7.55 ± 2.53 dendrites per keratinocyte) than that in perilesional normal skin (5.28 ± 1.85 dendrites per keratinocyte) (p<0.05) [11]. Furthermore, electron microscopy demonstrated increased levels of activity within melanocytes in melasma skin, which was deduced from the presence of higher organelle numbers, including mitochondria, Golgi apparatuses, rough endoplasmic reticula, and ribosomes [7].…”

Current and New Strategies for Managing Non-Responders to Laser Toning in the Treatment of Melasma

“…[59][60][61] Melanocytes in the melasma lesion are larger and have more developed dendrites compared to those in the normal tissues. [59][60][61] The basement membrane is also damaged, presenting pendulous melanocytes that protrude into the dermis.…”

“…[59][60][61] Melanocytes in the melasma lesion are larger and have more developed dendrites compared to those in the normal tissues. [59][60][61] The basement membrane is also damaged, presenting pendulous melanocytes that protrude into the dermis. 62,63 Along with these findings, other noticeable histochemical characteristics include increased inflammatory cytokines, elevated levels of melanogenesis-associated proteins, and signs suggesting UV-induced skin damage.…”