Barysch Marjam Jeanette, Braun Ralph Peter, Kolm Isabel, Ahlgrimm-Siesz Verena, Hofmann-Wellenhof Rainer, Duval Christine, Warrick Emilie, Bernerd Francoise, Nouveau Stéphanie, Dummer Reinhard
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Department of Dermatology, University Hospital Salzburg, Salzburg, Austria.
Dermatopathology (Basel). 2019 Jan 3;6(1):1-11. doi: 10.1159/000495404. eCollection 2019 Jan-Mar.
Solar lentigines (SL) affect chronically UV-radiated skin. Treatment is often refractory. Deeper knowledge on its pathogenesis might improve therapeutic effects.
Morphological characterization of 190 SL was performed and epidermal thickness, pigment distribution, dendricity, and cornification grade were measured. Immunoreactivity was investigated using Melan A, Tyrosinase, MITF, p53, and CD20, as well as Notch1 using immunofluorescence.
We found 2 groups of histological patterns, i.e., either acanthotic or atrophic epidermis. Lesions with basket-woven cornification and atrophic epidermis were observed in 6 out of 9 and 14 out of 16 cases from the face, respectively. Consistency of areas with a high pigmentation was observed in 96-97% of the cases. Hyperpigmentation grade and acanthosis or cornification disorders correlated positively in 88.5% of the cases. Overexpressed of p53 was found in 19 out of 20 lesions, presenting in a scattered distribution. A significant correlation of p53 and acanthosis ( = 0.003) and cornification grade ( = 0.0008) was observed. Notch1 was expressed in all SL, with the highest immunoreactivity in atrophic facial lesions. Lesions from the hands expressed Notch1 mainly in acanthotic areas with elongated rete ridges and less compact cornification.
We suggest that Notch1-dependent keratinocytic malfunction causes the development of SL. Consequently, hyperpigmentation would be a result and not the primary cause of the pathogenesis. Confirmation of these findings might have clinical implications as hitherto treatment has mainly focused on melanocytes and pigmentation and not on the proliferation/differentiation balance of keratinocytes.
日光性雀斑（SL）影响长期受紫外线辐射的皮肤。其治疗往往难以奏效。对其发病机制更深入的了解可能会提高治疗效果。
对190个日光性雀斑进行形态学特征分析，并测量表皮厚度、色素分布、树枝状形态及角化程度。采用免疫荧光法，使用Melan A、酪氨酸酶、小眼畸形相关转录因子（MITF）、p53和CD20以及Notch1研究免疫反应性。
我们发现了两组组织学模式，即棘层肥厚型或萎缩型表皮。面部9例中有6例、16例中有14例分别观察到具有篮状角化和萎缩型表皮的病变。96% - 97%的病例中观察到色素沉着较高区域的一致性。88.5%的病例中色素沉着程度与棘层肥厚或角化紊乱呈正相关。20个病变中有19个发现p53过表达，呈散在分布。观察到p53与棘层肥厚（P = 0.003）和角化程度（P = 0.0008）有显著相关性。Notch1在所有日光性雀斑中均有表达，在萎缩性面部病变中免疫反应性最高。手部病变中Notch1主要在棘层肥厚区域表达，伴有延长的 rete 嵴且角化不那么紧密。
我们认为Notch1依赖的角质形成细胞功能障碍导致了日光性雀斑的发生。因此，色素沉着过多将是发病机制的结果而非主要原因。这些发现的证实可能具有临床意义，因为迄今为止的治疗主要集中在黑素细胞和色素沉着上，而不是角质形成细胞的增殖/分化平衡。
