Department of Dermatology, Rambam Medical Center, Haifa, Israel.
Department of Pathology, Rambam Medical Center, Haifa, Israel.
J Am Acad Dermatol. 2010 Jan;62(1):107-113. doi: 10.1016/j.jaad.2009.05.016.
Recent developments in molecular genetics may lead to re-examination of the histopathology of inherited palmoplantar keratodermas (PPKs) based on more precise groupings of the various entities and syndromes.
We sought to characterize the histopathological findings in PPKs associated with mutations in DSG1, which encodes desmoglein 1.
We studied the histopathology of 3 cases of keratosis palmoplantaris striata type I and one case of diffuse PPK, all associated with autosomal-dominant mutations in DSG1. Our cases for comparison included 4 cases with Mal de Meleda PPK associated with autosomal-recessive SLURP1 mutations, one case with pachyonychia congenita type II PPK associated with an autosomal-dominant KRT17 mutation, and one case with focal PPK associated with an autosomal-dominant KRT16 mutation.
The distinguishing histopathological features of the 3 keratosis palmoplantaris striata type I cases and the diffuse PPK case associated with DSG1 mutation were: varying degrees of widening of the intercellular spaces and partial disadhesion of keratinocytes in the mid and upper epidermal spinous cell layers, often extending to the granular cell layer. These findings, which are associated with haploinsufficiency of desmoglein 1, were not observed in any of the other 6 PPK cases. Mild perinuclear eosinophilic condensations and cytoplasmic vacuolizations were observed in the spinous cell layer keratinocytes of the pachyonychia congenita type II PPK and the nonspecified focal PPK cases.
There were a limited number of patients and control patients with hereditary PPKs.
Widening of the intercellular spaces and disadhesion of epidermal keratinocytes may serve as a histologic clue to PPKs caused by DSG1 mutations.
分子遗传学的最新进展可能导致基于各种实体和综合征的更精确分组重新检查遗传性掌跖角化过度症（PPK）的组织病理学。
我们旨在描述与 DSG1 基因突变相关的 PPK 的组织病理学发现，该基因编码桥粒芯糖蛋白 1。
我们研究了与 DSG1 常染色体显性突变相关的 3 例角化过度性掌跖条纹Ⅰ型和 1 例弥漫性 PPK 的组织病理学，所有这些都与常染色体隐性 SLURP1 突变相关。我们的比较病例包括 4 例伴 Mal de Meleda PPK 的病例，与常染色体隐性 SLURP1 突变相关，1 例伴常染色体显性 KRT17 突变的先天性厚甲症Ⅱ型 PPK 病例，以及 1 例伴常染色体显性 KRT16 突变的局灶性 PPK 病例。
与 DSG1 基因突变相关的 3 例角化过度性掌跖条纹Ⅰ型和弥漫性 PPK 病例的特征性组织病理学特征为：中上层棘层细胞的细胞间隙不同程度增宽，部分角蛋白细胞分离，常延伸至颗粒层。这些发现与桥粒芯糖蛋白 1 的单倍不足有关，在其他 6 例 PPK 病例中均未观察到。在先天性厚甲症Ⅱ型和未指定的局灶性 PPK 病例的棘层细胞角蛋白细胞中观察到轻微的核周嗜酸性凝聚和细胞质空泡化。
遗传性 PPK 的患者和对照患者数量有限。
细胞间隙增宽和表皮角蛋白细胞分离可能成为由 DSG1 突变引起的 PPK 的组织学线索。
