平滑肌瘤是源自平滑肌的良性肿瘤，可以影响所有器官，最常见于子宫。间羟基丁二酸合酶基因（FH）突变是一种常染色体显性遗传病，特征为肾脏肿瘤发生率增加，同时也伴随皮肤纤维瘤（CLs）和子宫肌瘤（ULs）。到目前为止，在FH非突变的ULs患者中是否存在皮肤肿瘤的发生率增加尚未得到证实。为此，比较了34例接受子宫肌瘤手术治疗的FH非突变患者（病例组）与37例连续配对的健康女性（对照组）之间的情况。评估了皮肤肿瘤的发生情况，包括CLs和表皮纤维瘤（DFs）。此外，还比较了FH非突变皮肤肿瘤和临床史中仅存在一种类型的皮肤肿瘤且无ULs的与之年龄匹配的人群（n = 70）的显微镜下特征。免疫组织化学和体外研究分析了TGFβ和维生素D受体的表达。FH非突变的ULs患者显示了较高的CLs和DFs发生率（p < 0.03和p < 0.001），但其他类型的皮肤肿瘤发生率并无显著增加。免疫组织化学显示ULs组中的CLs和DFs中维生素D受体（VDR）的表达较人群组低（p < 0.01），但TGFβ受体和SMAD3的分布相似。体外研究表明，TGFβ-1和维生素D3对皮肤纤维细胞和肌瘤细胞培养物中α-SMA、TGFβR2和VDR的表达具有相反作用。这种FH非突变的ULs患者中CLs和DFs发生率的增加，以及伴随维生素D缺乏，提示维生素D生物可用性在CLs和DFs的发生中可能具有潜在的致病作用。

Leiomyomas are smooth muscle-derived benign neoplasms that can affect all organs, most frequently in the uterus. Fumarate hydratase gene (FH) mutation is characterised by an autosomal dominant disease with increased occurrence of renal tumours, but also by cutaneous (CLs) and uterine leiomyomas (ULs). So far, an increased occurrence of skin tumours in non-mutated patients with ULs has not been verified. To this aim, a case-group of women who were FH non-mutated patients surgically treated for ULs (n = 34) was compared with a control-group (n = 37) of consecutive age-matched healthy women. The occurrence of skin neoplasms, including CLs and dermatofibromas (DFs), was evaluated. Moreover, the microscopic features of FH non-mutated skin tumours were compared with those of an age-matched population group (n = 70) who presented, in their clinical history, only one type of skin tumour and no ULs. Immunohistochemical and in vitro studies analysed TGFβ and vitamin D receptor expression. FH non-mutated patients with ULs displayed a higher occurrence of CLs and DFs (p < 0.03 and p < 0.001), but not of other types of skin tumours. Immunohistochemistry revealed a lower vitamin D receptor (VDR) expression in CLs and DFs from the ULs group compared with those from the population group (p < 0.01), but a similar distribution of TGFβ-receptors and SMAD3. In vitro studies documented that TGFβ-1 treatment and vitamin D3 have opposite effects on α-SMA, TGFβR2 and VDR expression on dermal fibroblast and leiomyoma cell cultures. This unreported increased occurrence of CLs and DFs in FH non-mutated patients with symptomatic ULs with vitamin D deficiency suggests a potential pathogenetic role of vitamin D bioavailability also for CLs and DFs.