Reid Hadley W, Young Alexandria N, Yin Sophia H, Velez Isabela Covelli, Abel Mary Kathryn, Kolin David L, Ginsburg Elizabeth S, Yurgelun Matthew B, Feltmate Colleen, St Laurent Jessica D
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Massachusetts General Hospital, Boston, MA, USA.
Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, MA, USA.
Gynecol Oncol Rep. 2025 May 17;59:101768. doi: 10.1016/j.gore.2025.101768. eCollection 2025 Jun.
Provide evidence on fertility-sparing treatment for patients with Lynch Syndrome (LS) and early-stage low grade endometrioid endometrial cancer (EC) or endometrial intraepithelial neoplasia (EIN).
We conducted a retrospective chart review of patients with EC or EIN, LS pathogenic germline variant, and treatment with progestin therapy without upfront hysterectomy due to desire to preserve fertility. Demographic, clinical, and reproductive variables were collected.
Of the 273 patients who met criteria for LS with EIN (38) or EC (235) there were seven patients, three with an initial diagnosis of EIN and four with an initial diagnosis of EC who underwent fertility sparing treatment. The median age was 36 (range 31-44) at diagnosis with the following mutations (2), (1), (1) and (3). Four out of 7 (53%) patients responded to progestin therapy with a 33% (1/3) and 75% (3/4) regression rate for EIN and EC respectively. Two out of 4 patients (50%) subsequently recurred. There were three pregnancies and two live births. Five patients ultimately underwent hysterectomy. Two patients, both with mutant p53 expression on immunohistochemistry, had higher grade or stage pathology, one with stage 1A grade 2 EC and one with stage 1B grade 3 EC.
Fertility sparing management for LS patients with an EIN or EC diagnosis is uncommon. Progesterone response rates appear to be lower than those in sporadic cases, though similar clinical and histologic factors (age, BMI, and p53 expression pattern) may predict disease regression and fertility outcomes. A larger sample and standardized treatment paradigm are needed to provide more evidence on fertility sparing management for LS patients.
为林奇综合征（LS）合并早期低级别子宫内膜样腺癌（EC）或子宫内膜上皮内瘤变（EIN）的患者提供保留生育功能治疗的证据。
我们对患有EC或EIN、LS致病种系变异且因希望保留生育功能而未先行子宫切除术接受孕激素治疗的患者进行了回顾性病历审查。收集了人口统计学、临床和生殖变量。
在273例符合LS合并EIN（38例）或EC（235例）标准的患者中，有7例患者接受了保留生育功能治疗，其中3例初始诊断为EIN，4例初始诊断为EC。诊断时的中位年龄为36岁（范围31 - 44岁），有以下突变（2例）、（1例）、（1例）和（3例）。7例患者中有4例（53%）对孕激素治疗有反应，EIN和EC的消退率分别为33%（1/3）和75%（3/4）。4例患者中有2例（50%）随后复发。有3次妊娠和2例活产。5例患者最终接受了子宫切除术。2例患者免疫组化显示p53突变表达，病理分级或分期较高，1例为1A期2级EC，1例为1B期3级EC。
对于诊断为EIN或EC的LS患者，保留生育功能的管理并不常见。孕激素反应率似乎低于散发性病例，尽管相似的临床和组织学因素（年龄、BMI和p53表达模式）可能预测疾病消退和生育结局。需要更大的样本和标准化的治疗模式来为LS患者保留生育功能的管理提供更多证据。
