Schei-Andersen Ane J, Schuurs-Hoeijmakers Janneke H M, van der Post Rachel, Mensenkamp Arjen R, Schieving Jolanda, Vos Janet R, Hoogerbrugge Nicoline
Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Radboud Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.
Clin Genet. 2025 Oct;108(4):400-411. doi: 10.1111/cge.14759. Epub 2025 Apr 28.
PTEN Hamartoma Tumor Syndrome (PHTS) is a rare hereditary syndrome. PHTS has a variable phenotype characterized by benign lesions and increased cancer risks. Clarifying the extent of the benign phenotype could facilitate early recognition of PHTS patients before cancer development. Therefore, we assessed the spectrum, frequency, and age of excerpt of pathology-confirmed benign lesions in PHTS patients. Pathology reports were collected for 379 patients with a pathogenic PTEN variant from the Dutch nationwide pathology databank (Palga). Benign lesions were classified as PHTS-related based on current clinical diagnostic guidelines and non-PHTS-related lesions by ICD-10 codes. Age of last follow-up was year of pathology request minus birth year. Analyses were stratified by sex and index status. Patients presented mainly with gastrointestinal (54%), skin (47%), thyroid (31%) and vascular lesions (26%). Males developed lipomas at an early age (9 years (5-34)). Females developed endometrial hyperplasia (16%) at an earlier age (41 years (35-49)) and uterine polyps (13%) more often than the general population. No significant differences were observed between sexes or index and non-index patients. The results are reflective of current diagnostic guidelines. Early-onset lipomas may be useful for early detection of PHTS patients. Additionally, uterine polyps should be considered for inclusion as a PHTS-related lesion.
PTEN错构瘤综合征（PHTS）是一种罕见的遗传性综合征。PHTS具有可变的表型，其特征为良性病变和癌症风险增加。明确良性表型的范围有助于在癌症发生前早期识别PHTS患者。因此，我们评估了PHTS患者经病理证实的良性病变的范围、频率和出现年龄。从荷兰全国病理数据库（Palga）收集了379例携带致病性PTEN变异的患者的病理报告。根据当前临床诊断指南，良性病变被分类为与PHTS相关，通过ICD - 10编码分类为非PHTS相关病变。最后一次随访年龄为病理申请年份减去出生年份。分析按性别和索引状态分层。患者主要表现为胃肠道病变（54%）、皮肤病变（47%）、甲状腺病变（31%）和血管病变（26%）。男性在早年（9岁（5 - 34岁））出现脂肪瘤。女性比普通人群更早（41岁（35 - 49岁））出现子宫内膜增生（16%）且更频繁出现子宫息肉（13%）。在性别之间以及索引患者和非索引患者之间未观察到显著差异。结果反映了当前的诊断指南。早发性脂肪瘤可能有助于早期发现PHTS患者。此外，子宫息肉应被考虑纳入与PHTS相关的病变。
