Endometrial cancer is one of the most common malignancies affecting women, with around 9,700 new cases diagnosed in the UK every year (1). Whilst the exact prevalence of endometrial cancer in young women is equivocal, it has been estimated that up to 14% of cases occur in young women aged less than 40 years (2–4). Risk factors associated with the incidence of endometrial cancer in young women include higher body mass index, nulliparity and polycystic ovarian syndrome (3, 5, 6).

We present the unique case of a young woman diagnosed with both early endometrial and ovarian cancer that eluded full surgical treatment and developed complete spontaneous remission following pregnancy and childbirth.

The consensus recommendation was that the patient should be offered completion surgery, including total abdominal hysterectomy, left salpingo-oophorectomy, with omentectomy and lymphadenectomy. In light of the patient’s young age and nulliparity, she was also offered an alternative, fertility-sparing, hormonal treatment option with oral Megestrol acetate 160mg daily, and surveillance with subsequent hysteroscopy and laparoscopy 6-8 weeks later.

The patient was undecided on the type of therapeutic intervention she wished to receive and was due to travel abroad soon after being informed of her diagnosis. She was therefore prescribed the hormonal treatment and prophylactic enoxaparin sodium, with a plan to re-discuss definitive treatment on her return to the UK.

The patient remained abroad and absconded from treatment. After 2 months of unsuccessful attempts to make contact with the patient, she was subsequently discharged back to primary care. Eight months later, the patient re-presented to her GP and was urgently referred back to gynaecology clinic. On assessment, the patient reported that she had not received any medical treatments or alternative therapies in the previous eight months whilst abroad, and had stopped taking Megestrol acetate after 2 weeks due to intolerable side effects. The patient had conceived naturally and was 9 weeks pregnant at the time of assessment.

In line with the patient’s wishes, an MDT decision was made to postpone further investigation and treatment until the patient had delivered her baby, to avoid compromising her pregnancy. She declined VTE prophylaxis throughout her pregnancy.

Her pregnancy was followed up by the local high-risk obstetric team. All antenatal ultrasound scans were unremarkable with no abnormalities detected. The patient had an uncomplicated pregnancy and had a spontaneous vaginal delivery at term. Histological analysis of the placenta showed features of chorioamnionitis only.

The patient was re-assessed in outpatient gynaecology clinic at 7 weeks postnatal. She was amenorrhoeic and breastfeeding. Speculum examination demonstrated normal vulva, vagina and cervix. Transvaginal ultrasound was unremarkable, with an endometrial thickness of 3.9mm, and a normal appearing left ovary. An endometrial biopsy obtained by pipelle showed hyalinised decidua and inactive endometrium, with no evidence of hyperplasia or neoplasia. Repeat tumour markers including CA125 were normal.

Repeat hysteroscopy was unremarkable with no new polyps seen. Endometrial biopsy taken intra-operatively showed proliferative changes with no evidence of hyperplasia or malignancy. The gynaecological oncology MDT recommendation was for surveillance with repeat ultrasound, hysteroscopy and tumour markers at 8 months postnatal.

At 8 months postnatal the patient’s menstrual periods had recommenced, with no menstrual irregularities or intermenstrual bleeding. Repeat ultrasound showed a normal uterus with regular echotexture and an endometrial thickness of 8mm. The left ovary remained normal in appearance. Hysteroscopy was postponed on the basis of reassuring ultrasound findings.

The patient was reviewed again at 14 months postnatal. Repeat ultrasound showed a regular, homogenous endometrium with a thickness of 11mm. The left ovary appeared normal. Tumour markers were repeated and remained normal. Hysteroscopy revealed a normal appearing endometrium with no polyps. An endometrial pipelle biopsy showed a late proliferative endometrium with no hyperplasia or invasive malignancy.

Repeat diagnostic laparoscopy was considered to evaluate the left adnexa as part of ongoing surveillance. However, the patient wished to avoid further surgery unless indicated from other procedure findings.

To date, the patient remains on a 6-monthly surveillance plan consisting of pelvic ultrasound and tumour markers as routine. Indication for hysteroscopy will be evaluated during assessment. Laparoscopy will be recommended in instances of abnormal or inconclusive findings. The patient is considered to have had complete natural remission of her endometrial cancer following pregnancy.

Completion surgery, including a contralateral salpingo-oopherectomy and total abdominal hysterectomy, will be offered to the patient once her family is complete.

Table 1 summarises the relevant historical and current data from the episode of care.

Spontaneous regression has been acknowledged as a natural phenomenon in relation to many types of cancer, and has been discussed in medical literature as early as 1742 (9). More recently, a review of previous reports of tumour regression has identified a common association between spontaneous regression of cancers and acute infection, fever, and subsequent activation of the immune response (10). Whilst there are a small number of cases in which spontaneous regression of endometrial cancers has been observed, they describe cases of postmenopausal women, or those with advanced, distant metastatic disease (11–14). However, the spontaneous regression of endometrial cancer following pregnancy, in the absence of any comprehensive intervention, is extremely rare. A literature review failed to identify cases where the patient was diagnosed with endometrial cancer before conceiving, and whom their endometrial cancer resolved following pregnancy, without any substantial hormonal or surgical treatment.

The particularity of this case is that, apart from nulliparity, the patient lacked any recognisable risk factors for endometrial cancer, such as exposure to unopposed oestrogen, obesity, diabetes, polycystic ovarian syndrome, and use of tamoxifen (15). Whilst this patient’s age at menarche is unknown, endometrial cancer risk amongst nulliparous women is not thought to be associated with age at menarche (16). However, this patient was found to have multiple endometrial polyps. It is unclear how long she had uterine polyps before their detection, and whether this influenced their malignant transformation. Whilst endometrial cancer occurs in only 2-5% of women with endometrial polyps (17), the malignant potential of polyps in this case remains unclear.

The atypical occurrence of endometrial cancer in the absence of dysfunctional uterine bleeding must also be noted. Very few studies describe cases of endometrial cancer without abnormal bleeding, and such cases are exclusive to postmenopausal women (18, 19).

Various hypotheses for the protective effect of pregnancy on endometrial malignancy have been discussed. The persistently high progesterone levels occurring in pregnancy are thought to arrest mitotic activity and suppress carcinogenesis during this period (20). This may explain the remission observed in this case, and concurs with the rationale of progestin use in fertility-sparing treatment of endometrial cancers of the same grade. Others have proposed a physical “clearance” of premalignant and malignant cells or lesions during delivery (21), or tissue remodelling during postpartum involution of the uterus that limits growth of malignant tumours (22).

Synchronous endometrial and ovarian carcinomas are a rare occurrence, but accounts for the majority of synchronous female genital tract tumour combinations (23). Approximately 50-70% of these cases demonstrate endometrial and ovarian carcinomas both of endometrioid type, making a diagnosis of synchronous cancers difficult (23). Criteria for distinguishing synchronous tumours from metastatic deposits was first detailed by Ulbright and Roth (24), and further developed by Scully et al. (25). The histological findings in this case meet various minor criteria for synchronous tumours: ovarian tumour unilaterality; absence of lymphovascular emboli; no or only superficial myometrial invasion of endometrial tumour; and absence of evidence of distant spread (25, 26). Although it is uncertain, the endometrial and ovarian lesions diagnosed in this case could be classified as synchronous tumours on the basis that at least two criterion have been met.

There is also evidence to suggest increased rates of synchronous tumours in young women with endometrial cancer. A recent retrospective study identified a significantly higher rate of synchronous ovarian cancer in young women aged ≤40 years with endometrial cancer, compared to those aged 41-60 years (9.2% vs 0.7%, P<0.001) (5). This rate has previously been suggested to be as high as 19% in women aged less than 50 years (6). Moreover, synchronous endometrial and ovarian cancers generally have a better prognosis when compared to metastatic lesions (27, 28). The favourable outcome observed in this case further promotes the likelihood of synchronous cancers.

At present, surgical treatment for this patient’s ovarian and endometrial cancer is considered incomplete. However, the indication for further surgery without evidence of recurrence could be debated. Findings of a recent meta-analysis suggested that hysterectomy is associated with a lower risk of recurrence for FIGO stage I ovarian tumours (OR 0.23, P=0.0006), but an increased risk of death (due to disease or of any other cause) when compared to uterine-sparing surgery for borderline ovarian tumours (29). Without recurrence of this patient’s ovarian cancer, the risks associated with hysterectomy - besides loss of fertility - will need to be closely examined as part of future planning.

Contrastingly, the recurrence of FIGO stage I ovarian cancer during pregnancy and following salpingo-oopherectomy has been observed (30). Considering the clinical course in such cases, it has been suggested that minimal interaction occurs between the intrauterine and intrabdominal environments, and pregnancy may in fact initiate or accelerate recurrence. Whilst remission of ovarian cancer has occurred in this case, the risk of future recurrence is therefore unclear.

Based on The Cancer Genome Atlas 2013 molecular analysis of endometrial cancers, the carcinoma identified in this case can be categorised under the copy-number low/endometrioid subtype (31, 32). Analogous to this classification, the patient’s endometrial cancer is considered to be of low prognostic risk under the most recent European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) guidelines (33). Examining such molecular prognostic factors is particularly valuable in this instance, where atypical clinical factors may cause uncertainty regarding appropriate management.

Where the intrauterine conditions produced by pregnancy may equate to those occurring during progestin therapy, such molecular-level prognostic factors may also be applied to stratify the efficacy and favourability of fertility-sparing endometrial cancer treatment in the future.

The management of this case was strengthened by the comprehensive approach taken towards the patient’s diagnosis, taking into consideration important personal factors such as her age and her fertility wishes. In light of this, we devised a personalised treatment plan that provided the patient a choice of either fertility sparing conservative or radical surgical treatment.

A limitation of this case is the period during which the patient temporarily absconded from treatment. During this 8-month period, the patient did not have any repeat imaging – or any other form of disease surveillance. We are therefore unable to map out the exact course of her remission, and understanding of the exact disease process in this case remains unclear.

This unique case demonstrates a natural phenomenon, and highlights the potential for pregnancy to induce remission of gynaecological cancers. Whilst endometrial cancer is uncommon in young patients without abnormal bleeding, it is exceptionally rare to observe the complete, natural remission of endometrial cancer following pregnancy and childbirth. Natural remission of ovarian cancer under these circumstances is similarly extraordinary. In such cases, the aetiology may be related to the high progesterone-producing state of pregnancy. Further research is required to better understand the mechanism by which endometrial carcinogenesis may be arrested or reversed under the specific intrauterine conditions of pregnancy. How such conditions may affect extra-uterine gynaecological tumours must also be understood. In turn, the modification of current progestin therapy regimens - to achieve pregnancy levels of progesterone - may further enhance the prognostic benefit of this fertility-sparing treatment option for low-grade endometrial cancers. Such benefit may also be applicable to borderline or early-stage ovarian cancers in the future.

The patient declined to formally comment on her perspective on this episode of care.

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Acquisition of data: DD, RV, PS, SM, and VM. Manuscript writing: DD, PS, RV, and SM. Critical review of the manuscript: All authors. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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