Abstract：
PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition. Genetic testing results and pathology reports were collected for patients tested for germline PTEN variants between 1997 and 2020 from the diagnostic laboratory and the Dutch nationwide pathology databank (Palga). The cancer spectrum and age of onset were assessed in patients with (PTENpos) and without (PTENneg) a germline PTEN variant. Histopathological cancer characteristics were assessed in a nested cohort. 341 PTENpos patients (56% females) and 2882 PTENneg patients (66% females) were included. PTENpos patients presented mostly with female breast (BC, 30%), endometrial (EC, 6%), thyroid (TC, 4%) or colorectal cancer (4%). PTENpos were significantly younger at cancer onset (43 vs. 47 years) and had more often (46% vs. 18%) a second BC than PTENneg. PTEN detection rates were highest for BC <40 years (9%), TC <20 years (15%) and EC <50 years (28%), and dropped to 6%, 4%, and 15% by age 60. Histopathological characteristics were similar between groups. No histopathological cancer characteristics were distinctive for PHTS. However, PTENpos were significantly younger at cancer onset. Therefore early-onset BC, EC, or TC warrants consideration of PHTS diagnostics either through a pre-screen for other PHTS features or direct germline testing.
摘要：
PTEN错构瘤综合征（PHTS）具有广泛的临床范围，包括诊断年龄不同的各种良性和恶性肿瘤。许多患者仍未被识别，没有意识到他们患癌症的风险增加。我们的目的是描述癌症谱，发病年龄和组织病理学癌症特征，以评估特定癌症特征是否可以提高PHTS识别。从诊断实验室和荷兰全国病理学数据库（Palga）收集了在1997年至2020年之间测试种系PTEN变异的患者的遗传测试结果和病理学报告。在有（PTENpos）和没有（PTENneg）种系PTEN变体的患者中评估了癌症谱和发病年龄。在嵌套队列中评估组织病理学癌症特征。包括341名PTENpos患者（56%女性）和2882名PTENneg患者（66%女性）。PTENpos患者主要表现为女性乳房(BC，30%),子宫内膜（EC，6%),甲状腺（TC，4%)或结直肠癌(4%)。PTENpos在癌症发作时明显年轻（43vs.47年)，并且更常见(46%与18%)一第二BC比PTENneg。PTEN检出率最高，BC<40年（9%），TC<20年(15%)，EC<50年(28%)，下降到6%，4%,到60岁时占15%。组之间的组织病理学特征相似。对于PHTS，没有组织病理学癌症特征。然而,PTENpos在癌症发作时明显年轻。因此早发性BC，EC,或TC保证通过预筛选其他PHTS功能或直接种系测试来考虑PHTS诊断。
