Two cases of successful pregnancies after hysteroscopic removal of endometrioid adenocarcinoma grade I, stage IA, in young women with Lynch syndrome

Abstract Background Endometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far. Case presentation The proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years. Conclusion This report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

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Fertility-sparing treatment in women with endometrial cancer

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2020.03629 ◽

2020 ◽

Vol 47 (4) ◽

pp. 237-244

Author(s):

Seyeon Won ◽

Mi Kyoung Kim ◽

Seok Ju Seong

Keyword(s):

Endometrial Cancer ◽

Young Women ◽

Eligible Patient ◽

Myometrial Invasion ◽

Definitive Treatment ◽

High Dose ◽

Low Grade ◽

Endometrioid Adenocarcinoma ◽

Fertility Sparing ◽

The Ideal

Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500–600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.

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Does mismatch repair (MMR) deficiency have prognostic significance in low-risk endometrioid endometrial cancers?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e17122 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e17122-e17122

Author(s):

Soyoun Rachel Kim ◽

Annick Pina ◽

Arianne Albert ◽

Jessica N. McAlpine ◽

Robert Wolber ◽

...

Keyword(s):

Lynch Syndrome ◽

Mismatch Repair ◽

Prognostic Significance ◽

Cox Proportional Hazards Model ◽

Low Risk ◽

Recurrence Rates ◽

Significant Difference ◽

Stage Ia ◽

Endometrial Cancers ◽

Mmr Deficiency

e17122 Background: Mismatch repair (MMR) deficiency is observed in 25-30% of all endometrial cancers. This can be detected by the absence of MMR protein staining on immunohistochemistry (IHC), and is used in many jurisdictions as a screen for an inherited mutation in one of the MMR genes (Lynch Syndrome). Only 10% of women with MMR deficiency (MMRd) have Lynch syndrome, but MMRd may still have prognostic significance. The objective of this study was to compare clinical outcomes between MMR deficient and proficient low-risk endometrioid endometrial cancers (stage IA, grade 1/2). Methods: This was a retrospective population-based cohort study of all low-risk endometrial cancers from Vancouver Coastal Health authority region from 2011 to 2016 that were assessed for MMR deficiency (MMRd). Primary outcome measures were recurrence rates expressed per person-years (py), progression free survival (PFS) and overall survival (OS) calculated using Kaplan-Meier method and log-rank tests. Cox proportional hazards model estimated the association between MMRd and recurrence and death after adjustment for covariates, expressed as hazard ratios (HR). Results: There were 475 low-risk patients, including 131 MMRd (27.6%) and 345 MMRp (proficient) patients. Women with MMRd tumors had higher recurrence rates (3.53p100py vs 1.21p100py) and worse PFS (p = 0.0082) compared to women with MMRp tumors. After adjustment for age, LVSI status, adjuvant therapy, and post-operative grade, MMRd status remained associated with a higher risk of recurrence (HR 2.99, 95% CI 1.27-7.04). There was no significant difference in OS between MMR groups (HR 1.38, 95% CI 0.57-3.33). Conclusions: In low-risk stage IA grade 1 or 2 endometrioid endometrial cancers, MMR deficiency is associated with a higher recurrence rate than in MMR proficient cases, after adjustment for covariates, implying that MMR deficiency reflects a different biology in endometrial cancer.

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Conservative management of young women with endometrial adenocarcinoma with grade 2-3 and/or superficial myometrial invasion.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5601 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5601-5601

Author(s):

Jeong-Yeol Park ◽

Dae-Yeon Kim ◽

Tae-Jin Kim ◽

Jae Weon Kim ◽

Jong-Hyeok Kim ◽

...

Keyword(s):

Young Women ◽

Endometrial Adenocarcinoma ◽

Myometrial Invasion ◽

Complete Response ◽

Endometrioid Adenocarcinoma ◽

Median Dose ◽

Recurrence Rates ◽

Day Range ◽

Progestin Treatment

5601 Background: To estimate the oncologic and pregnancy outcomes after progestin treatment of young women with endometrial adenocarcinoma with grade 2–3 and/or superficial myometrial invasion. Methods: Medical records of 48 young women with endometrioid adenocarcinoma of the uterus with grade 2–3 and/or superficial myometrial invasion who were conservatively managed with oral progestin were reviewed. Results: Fourteen patients (29.2%) received daily oral megestrol acetate (median dose, 160 mg/day; range, 40–240 mg/day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose, 500 mg/day; range, 80–1000 mg/day). The median treatment duration was 10 months (range, 3–20 months). Complete responses were observed in 37 patients (77.1%) and the median time to complete response was 17 weeks (range, 9–51 weeks). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with grade 2–3 without myometrial invasion (n=17), patients with grade 1 and superficial myometrial invasion (n=23), and patients with grade 2-3 and superficial myometrial invasion (n=8), respectively (P = 0.731). Their recurrence rates after a median follow-up time of 48 months (range, 7–136 months) were 23.1%, 47.1%, and 71.4%, respectively (P = 0.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy babies. Conclusions: Progestin treatment is safe for patients with grade 2–3 without myometrial invasion and patients with grade 1 and superficial myometrial invasion. However, it should be provided on an individual basis and must be applied cautiously in patients with grade 2–3 and superficial myometrial invasion.

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Carcinoma of the Lower Uterine Segment: A Newly Described Association With Lynch Syndrome

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.6296 ◽

2008 ◽

Vol 26 (36) ◽

pp. 5965-5971 ◽

Cited By ~ 131

Author(s):

Shannon N. Westin ◽

Robin A. Lacour ◽

Diana L. Urbauer ◽

Rajyalakshmi Luthra ◽

Diane C. Bodurka ◽

...

Keyword(s):

Endometrial Cancer ◽

Lynch Syndrome ◽

Endometrial Carcinoma ◽

Lower Uterine Segment ◽

Endometrioid Adenocarcinoma ◽

Clinicopathologic Characteristics ◽

Endocervical Adenocarcinoma ◽

Case Comparison ◽

Pathology Reports ◽

Clinical Records

Purpose Endometrial carcinoma in the lower uterine segment (LUS) is a poorly described cancer that can be clinically confused with endocervical carcinoma. We performed a case-comparison study to document the clinicopathologic characteristics of LUS tumors and their association with risk factors for endometrial cancer. Patients and Methods The clinical records and pathology reports from women who underwent hysterectomy at our institution for endometrial or endocervical adenocarcinoma over an 11-year interval were reviewed. The LUS group consisted of women with endometrial tumors that clearly originated between the lower uterine corpus and the upper endocervix. Immunohistochemistry and microsatellite instability and MLH1 methylation assays were performed. Results Thirty-five (3.5%) of 1,009 women had endometrial carcinoma of the LUS. Compared with patients with corpus tumors, LUS patients were younger, had higher stage tumors, and had more invasive tumors. Preoperative diagnosis of the LUS tumors more frequently included the possibility of endocervical adenocarcinoma. Seventy-three percent of the LUS tumors had an immunohistochemical expression pattern typical of conventional endometrioid adenocarcinoma. Ten (29%) of 35 women with LUS tumors were confirmed to have Lynch syndrome or were strongly suspected to have Lynch syndrome on the basis of tissue-based molecular assays. Conclusion The prevalence of Lynch syndrome in patients with LUS endometrial carcinoma (29%) is much greater than that of the general endometrial cancer patient population (1.8%) or in endometrial cancer patients younger than age 50 years (8% to 9%). On the basis of our results, the possibility of Lynch syndrome should be considered in women with LUS tumors.

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