Endometrial cancer in a young nulliparous woman: a case report.

A 27-year-old woman presented with severe anemia secondary to menorrhagia. She reported worsening lethargy, intermittent episodes of shortness of breath, palpitations, and a syncopal episode a few weeks prior to the visit, which affected her ability to work and perform household tasks. However, she had no fever, rashes, hypothyroid symptoms, or bleeding from the gastrointestinal system. Her diet was normal. She experienced menarche at the age of 12 years. Initially, her menstrual cycle was irregular, occurring every 2 to 3 months per cycle, without menorrhagia or dysmenorrhea. However, from the age of 15 years, she started to experience heavy and prolonged bleeding lasting >15 days per cycle. She did not seek any treatment and assumed a normal postmenarche pattern. Over the years, she developed recurrent episodes of symptomatic anemia, leading to multiple hospital admissions for blood transfusions over the past 7 years. Investigations conducted 6 years ago did not yield a diagnosis. She defaulted on her gynecological follow-up in 2020 during the COVID-19 (coronavirus disease 2019) pandemic and subsequently sought irregular treatment at private clinics, receiving only hematinic and tranexamic acid. She has been married since 2020 and has been attempting to conceive. Despite not using contraception, she did not conceive. His husband was healthy and did not have any chronic medical problems. On examination, the patient appeared pale. Her blood pressure was 132/76 mm Hg and her pulse rate was 86 beats per minute. The patient’s body mass index was 37 kg/m 2 . No incidences of jaundice, angular stomatitis, or mouth ulcers were noted. Cardiovascular, respiratory, and abdominal examination results were unremarkable. A transabdominal scan revealed an enlarged uterus measuring 9.5 cm×5.0 cm. A hyperechoic intrauterine mass with mixed echogenicity, measuring 6.4 cm×3.0 cm in size, arising from the posterior myometrial wall and extending to the lower part of the uterus was observed ( Figure 1 ). The endometrial thickness was 20 mm, and Doppler scan uptake increased. Both ovaries showed increased ovarian stroma, measuring 3 cm×3 cm. The cervix was 3 cm×2.5 cm in size with a regular endocervical canal. Her hemoglobin level was 6.0 g/dL; therefore, blood was transfused. The Pap smear result was negative for intraepithelial lesion or malignancy. Endometrial pipelle sampling revealed a well-differentiated endometrial endometrioid adenocarcinoma (FIGO grade 1) ( Figure 2 ). Hysteroscopy was performed, and HPE of the endometrial tissue was consistent with endometrial endometrioid carcinoma (type 1) ( Figure 3 ). Computed tomography (CT) showed an enlarged uterus with a 6.4 cm×3.2 cm intrauterine mass. Both ovaries are enlarged. No signs of liver or lung metastases were observed. Magnetic resonance imaging did not reveal endometrial invasion. She expressed concerns about conception. Consequently, the management focused on medical therapies for fertility preservation. A hormonal intrauterine device was inserted and high-dose oral progesterone was administered. Regular follow-ups were planned to monitor disease progression and prepare for future pregnancies. A written informed consent for the publication of this case report was obtained from the patient.

Prolonged heavy menstrual bleeding (menorrhagia) can result from structural (polyps, adenomyosis, leiomyoma, and malignancy), nonstructural (coagulopathy, ovulatory dysfunction, and endometrial disorders), iatrogenic, and nonclassified causes [ 1 , 2 ]. Menorrhagia is a clinical manifestation of endometrial hyperplasia, with the atypical form being a precursor to endometrial carcinoma [ 1 , 3 ]. According to the 2014 World Health Organization classification, endometrial hyperplasia is categorized into the following two groups: without atypia (usually non-neoplastic) and with atypia (neoplastic, also referred to as endometrial intraepithelial neoplasia [EIN]). EIN can progress to or coexist with endometrial carcinoma [ 3 ]. Endometrial carcinomas are broadly classified into types 1 and 2. Type 1 tumors are estrogen-dependent and occur in younger women [ 4 ]. They develop from EIN following prolonged exposure to unopposed estrogen, and generally have a more favorable prognosis than type 2 tumors, which are nonestrogen-dependent, occur in older women, and have a poorer prognosis [ 4 , 5 ]. According to the Malaysian National Cancer Registry, endometrial cancer is the fourth most common malignancy in women worldwide [ 6 ]. While 75% to 80% of cases occur in postmenopausal women, 14% to 20% are diagnosed in premenopausal women [ 5 ]. The risk factors include nulliparity, obesity, diabetes mellitus, and unopposed estrogen therapy [ 5 ]. The rising obesity rate, which is associated with an increased incidence of endometrial cancer in women aged <50 years, is of particular concern [ 7 ]. The youngest reported case of endometrial cancer worldwide was in a 13-year-old girl [ 8 ]. Endometrial cancer is diagnosed by clinical presentation and histopathological examination of endometrial tissue biopsy (HPE) [ 5 ]. The International Federation of Gynecology and Obstetrics (FIGO) staging and histopathological grading are used to stage endometrial cancer [ 5 ]. Although hysterectomy is the definitive management, fertility-preservation treatment is an option for young and premenopausal women [ 4 , 9 ]. The preservation of fertility requires careful disease control and prepregnancy planning before the ultimate treatment is undertaken.

In the first 2 years after menarche, up to 85% of adolescents experience irregular, anovulatory cycle; by fifth year ovulation occurs in 75% of adolescents [ 10 ]. Menstrual cycles exceeding 45 days, bleeding lasting >7 days, or the need for pad changes >1 every 1 to 2 hours require evaluation. In a normal menstrual cycle, the average blood loss is 30 to 40 mL (3–6 pads per day) [ 10 ], and chronic blood loss of >80 mL per cycle can cause anemia [ 2 ]. In assessing a patient with irregular and heavy menstruation, a detailed menstrual history, which includes the duration, frequency, volume of bleeding, symptoms of anemia, and family history of bleeding disorders, followed by abdominal and pelvic examinations should be performed. Pelvic ultrasonography is indicated if bimanual pelvic examination reveals abnormalities [ 1 ]. This patient initial result revealed no abnormalities; however, further evaluation was missed as she defaulted follow-up. The American College of Obstetricians and Gynecologists recommends endometrial biopsy for all women aged >45 years with abnormal uterine bleeding and in women aged <45 years with prolonged unopposed estrogen exposure, persistent bleeding, or unresponsive to medical therapy [ 11 ]. In adolescent, diagnostic hysteroscopy is essential for obtaining accurate tissue sample and should be performed using minimally invasive, hymen-sparing technique especially in those with intact hymen or cultural sensitive consideration [ 12 ]. The initial management of menorrhagia in the absence of structural and histological abnormalities is pharmacological, with the primary aim of reducing blood loss and addressing ovulatory dysfunction. Tranexamic acid and nonsteroidal anti-inflammatory drug can reduce menstrual blood loss up to 60% and 50% respectively [ 1 ]. The levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) is the most effective therapy, achieving up to 95% reduction in blood loss [ 1 ]. Oral progestins can reduce blood loss by approximately 87%, whereas combined oral contraceptive pill achieve up to 35%–69% reduction [ 1 ]. In the absence of ovulation, the corpus luteum fails to form, resulting in a lack of progesterone production. This leads to prolonged estrogenic stimulation of the endometrium, excessive proliferation, endometrial instability, and erratic bleeding. The interval between menarche and the establishment of regular ovulatory cycles represents a period of unopposed estrogen exposure, which is a known precursor of endometrial cancer. Endometrial hyperplasia develops due to exposure to continuous estrogen, unopposed by progestin [ 13 ]. This patient had been exposed to unopposed estrogen since menarche and did not receive proper treatment to control endometrial hyperplasia. Eventually, the hyperplasia progresses to endometrial carcinoma. Her obesity further increased the risk of developing endometrial cancer [ 3 , 5 , 7 , 13 ]. Endometrial hyperplasia without atypia has a low risk (<5% over 20 years) of progression to cancer, with most cases (81%) regressing spontaneously, 18% persisting, and only 1% progressing to malignancy. In contrast, atypical hyperplasia carries a significantly higher risk, with cancer rates of 8.0%, 12.4%, and 27.5% in 4, 9, and 19 years, respectively [ 14 ]. This may explain the prolonged interval from symptom onset to cancer in this patient, particularly given the missed follow-up appointments. The incidence of endometrial cancer in premenopausal women aged <40 years is only 5% [ 6 ]. Due to generally low risk, endometrial biopsy is warranted only in patients with risk factors or those fail to respond to conservative medical management [ 1 ]. Hysterectomy remains the definitive treatment for endometrial cancer [ 3 ]. However, fertility-preserving therapy is an option for women who meet the following criteria: age ≤40 years, strong desire for fertility, histopathological type 1 tumors without myometrial invasion, and no contraindication to progesterone therapy [ 4 , 9 ]. Progesterone acts on the endometrium and protects the cells from estrogen-driven growth and proliferation. It reverses endometrial hyperplasia via stromal decidualization, resulting in endometrial thinning. High-dose progesterone regimens, such as oral medroxyprogesterone acetate 250–500 mg daily or megestrol acetate at 160–320 mg daily, has 58%–89% complete response rate. LNG-IUSs are also recommended as maintenance therapy in young women with early-stage endometrial cancer [ 9 ]. Surveillance should include 3-monthly endometrial sampling and follow-up until complete response, followed by continued monitoring with pelvic examination, cancer antigen 125 levels, and thoracoabdominal imaging (CT or magnetic resonance imaging) for 3 to 6 months. The patient was treated with an LNGIUS combined with high-dose progesterone. If high-risk factors for recurrence emerge or if the treatment response is prolonged, hysterectomy is recommended [ 9 , 15 ]. Although endometrial cancer during pregnancy is uncommon, studies have reported a pregnancy rate of 26.7% and live birth rate of 20.5% in young women treated with progestin-based regimens [ 15 ]. Pregnancy should be planned as soon as a complete response is achieved, to minimize the risk of recurrence [ 15 ]. In this scenario, counseling patients on fertility potential and the importance of timely conception following medical remission is essential, with hysterectomy reserved for postchildbearing or disease recurrence. A local study showed that endometrial carcinoma in young women is associated with favorable prognostic factors, including endometrioid-type tumors, well-differentiated grades, early stage presentation, limited myometrial invasion, and absence of lymphovascular involvement [ 5 ]. Chronic menstrual irregularity, particularly in women with obesity and irregular ovulation, is a common early warning symptom of endometrial pathology. Since endometrial cancer can develop silently in high-risk individuals, clinicians must maintain a high index of suspicion when evaluating women with chronic irregular menstruation. These cases should never be missed; proper evaluation and regular follow-up are crucial. Primary care plays a vital role in preventive strategies, including early assessment of abnormal menstrual bleeding and weight reduction to minimize the risk of endometrial cancer. Hormonal therapy is essential for endometrial protection in at-risk patients. Conservative hormonal management can provide an opportunity for pregnancy in young women with endometrial cancer before proceeding with a definitive hysterectomy. In conclusion, menstrual disturbance in adolescents and young women is a potential risk factor for the development of endometrial hyperplasia, a precursor to endometrial cancer, if untreated. Early recognition, appropriate management, and sustained follow-up in primary care can prevent progression and preserve fertility. Increasing public awareness and clinical vigilance at the primary care level is a critical step toward improving outcomes.