Identification of a DICER1 mutation in a preeclamptic patient with ruptured ovarian Sertoli–Leydig cell tumor and renal allograft failure under hemodialysis: a case report

Abstract

Background

Patients with renal allograft failure undergoing hemodialysis may be associated with an increased risk of preeclampsia. Preeclampsia can present with systemic manifestations, including organ bleeding. In this case, a suspected placental abruption was eventually confirmed to be caused by the rupture of an ovarian Sertoli–Leydig cell tumor (SLCT). A DICER1 mutation was subsequently identified in the patient.

Case presentation

A 30-year-old primigravid woman with a history of thyroidectomy and renal allograft failure on maintenance hemodialysis presented at 29 weeks of gestation with a blood pressure of 180/110 mmHg and sudden onset of abdominal pain. She was diagnosed with preeclampsia. Due to suspected placental abruption and acute fetal distress, an emergency cesarean section was performed, resulting in the delivery of a healthy baby girl. During the operation, approximately 600 g of intraperitoneal blood clots were found, secondary to a ruptured ovarian cyst. Histopathological examination revealed a moderately to poorly differentiated ovarian SLCT. Targeted next-generation sequencing identified a new DICER1 variant (c.3175 dup: p.Tyr1059LeufsTer32 in exon 20 of chr14:95571502) in peripheral blood samples. The frameshift variant induces a premature termination classified as likely pathogenic based on ACMG criteria. Analysis of the family pedigree reveals a clustering of earlier-onset renal disease. During the 22-month follow-up period, following the decline of adjuvant chemotherapy, the patient experienced a second unintended pregnancy that required medical termination. No evidence of SLCT recurrence was observed.

Conclusions

This case report presents a unique pregnant patient with a history of thyroidectomy and living-renal allograft failure requiring hemodialysis, who developed preeclampsia and a ruptured ovarian SLCT. To our knowledge, this appears to be the first combination of a DICER1-mutation-associated ovarian SLCT in a pregnant patient with transplant failure. This highlights the pivotal need for systematic preconception counseling and effective contraceptive education in this population. A well-coordinated multidisciplinary team approach was imperative to secure optimal maternal and fetal outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12884-026-09019-y.

Background

DICER1, located on chromosome 14q32, encodes an RNase III endonuclease responsible for cleaving precursor microRNAs (pre-miRNAs) into active microRNAs (miRNAs). Mutations in DICER1 lead to aberrant cleavage of mature 5p miRNAs, resulting in dysregulated mRNA expression and an increased risk of developing various types of neoplasms [1]. DICER1 mutations are most commonly associated with pleuropulmonary blastoma (PPB), as well as thyroid, renal, and reproductive system tumors. Notably, approximately 60% of patients with ovarian Sertoli–Leydig cell tumors (SLCTs) harbor DICER1 mutations [2]. Pathogenic DICER1 variants are typically inherited in an autosomal dominant manner with incomplete penetrance, which has been reported to be around 15% for PPB. The estimated population prevalence of germline DICER1 variants ranges from 1 in 3,700 to 1 in 1,100 individuals [3]. The detection of a malignant ovarian cyst in our patient prompted genetic panel testing. Notably, ovarian tumor recurrence is associated with a high mortality rate. A recent cohort study of patients with SLCT demonstrated that those harboring germline DICER1 variants had significantly better recurrence-free and overall survival [4]. Therefore, identifying these variants can facilitate surveillance algorithms that enable early detection and management of DICER1-related malignancies, as well as cascade genetic testing for family members.

Variants in the DICER1 gene are frequently detected in thyroid nodules among pediatric and young adult patients, highlighting the necessity of thyroid monitoring during pregnancy [5]. Moreover, pathogenic DICER1 variants have been recognized as a significant genetic driver in the pathogenesis of cystic nephroma [6].

Pregnant patients with ESRD face a high risk of developing preeclampsia. When severe abdominal pain occurs in this population, it should be regarded as a critical warning sign prompting urgent evaluation for potentially life-threatening conditions such as placental abruption, HELLP syndrome, hepatic rupture, spontaneous hemoperitoneum, acute fatty liver of pregnancy or organ hemorrhage [7, 8].

This report describes the diagnostic and multidisciplinary management challenges encountered in this complex clinical setting and aims to enrich the literature regarding the phenotypic manifestations of DICER1 syndrome in the context of concurrent pregnancy, chronic immunosuppression, and severe preeclampsia.

Case presentation

The patient was a 30-year-old woman (married at 27, 155 cm, 47 kg, BMI 19.6 kg/m²). Due to irregular menstrual cycles, the pregnancy remained unrecognized until 14 weeks of gestation (See additional Fig. 1). At that time, she was on maintenance hemodialysis due to renal allograft failure. Before recognizing her pregnancy, she had irregularly taken 16 valsartan tablets (51 mg each) for hypertension. Upon confirmation, she sought medication advice from a pharmacist. With no obvious fetal abnormalities on ultrasound, the patient and her family elected to continue the pregnancy. The multidisciplinary team (MDT) engaged in risk clarification and collaborative decision-making.

Her past medical history included thyroidectomy for multinodular goiter (MNG) at the age of 19, followed by daily levothyroxine replacement therapy (150 µg/day). At the age of 22, she presented with fatigue and was diagnosed with end-stage renal disease (ESRD) for unknown reasons. At 24 years old, she underwent living-related kidney transplantation with her mother as the donor. However, at age 27, she experienced acute graft rejection following a high fever secondary to COVID-19 infection. The transplanted kidney lost all function within one year, after which the patient resumed regular hemodialysis and became anuric. Transplant nephrectomy was not performed following a thorough, individualized risk-benefit assessment. Timeline of the key medical events were show (See additional Fig. 2).

Despite graft failure, immunosuppressive therapy was continued due to persistent graft immunogenicity, including prednisone 5 mg once daily and tacrolimus 1 mg every 12 h. Her dialysis regimen was intensified to five sessions per week (Monday, Tuesday, Wednesday, Thursday, and Saturday), four hours each, totaling approximately 20 h of dialysis weekly during pregnancy. Her family history was notable for earlier onset of renal disease: one cousin (paternal uncle’s daughter) developed renal failure and underwent kidney transplantation at age 17, while another cousin (paternal aunt’s daughter) was diagnosed with nephrotic syndrome at age 30. Her parents were otherwise healthy. No detailed childhood renal imaging records, renal biopsy results, or specific histological diagnoses were available for the proband or her affected relatives.

The patient exhibited no signs of androgen excess. She attended regular prenatal visits and was admitted at 22 + 2 weeks’ gestation for lower abdominal tightness. Tocolytic therapy with the oxytocin antagonist atosiban was subsequently initiated to prevent preterm labor. Her pre-dialysis hypertension was controlled with oral labetalol (100 mg twice daily) and nifedipine (30 mg once daily), which were titrated as needed. Prophylactic therapy for preeclampsia included low-dose aspirin (75 mg daily) and calcium supplementation from the 14th week of pregnancy until preterm delivery. Moreover, her blood pressure was controlled through meticulous dry weight adjustment, with a gradual increase of approximately 0.3 kg per week during mid-late trimesters as recommended. Intravenous and oral iron, combined with erythropoietin, were administered to correct anemia. Ultrasound examinations revealed that the estimated fetal weight was consistent with gestational age, and no adnexal masses were detected. At 28 weeks of gestation, her blood pressure rose to 180/110 mmHg. She also reported episodic dizziness, prompting a clinical suspicion of superimposed preeclampsia. The laboratory workup revealed neither thrombocytopenia nor an increase in liver enzyme levels (See additional Table 1). She was subsequently started on intravenous nicardipine and attenuated dosing of magnesium sulfate for prompt stabilization.

At 29 weeks of gestation, the patient experienced sudden-onset lower abdominal pain during the night, accompanied by hypotension (97/60 mmHg) and fetal bradycardia (70 bpm). An emergency cesarean section was performed for suspected placental abruption and fetal distress, with a decision-to-delivery interval of 22 min. A well-developed, live female infant weighing 1,240 g was delivered with Apgar scores of 7 and 9 at 1 and 5 min, respectively.

Intraoperative findings revealed rupture of a right ovarian cyst measuring approximately 7 × 6 × 5 cm, with an actively bleeding 1 cm surface defect (Fig. 1). No peritoneal implants were observed and the tumor capsule is smooth. Cystectomy was performed for a presumed hyperreactio luteinalis due to the unavailability of frozen section analysis at night. The evacuation of approximately 600 g of intraperitoneal blood clots was performed. The subsequent drop in hemoglobin from 12.2 g/dL to 7.9 g/dL prompted transfusion of two units of PRBCs. The postoperative course was uneventful.

Fig. 1.

A ruptured Sertoli–Leydig cell tumor (SLCT) was encountered during cesarean section surgery

Final histopathology revealed a moderately to poorly differentiated Sertoli–Leydig cell tumor (SLCT) of the ovary (Fig. 2).Gene panel-based genetic testing revealed a pathogenic DICER1 variant of c.3175dup: p.Tyr1059LeufsTer32 (Fig. 3). Based on clinicopathological findings, the disease was classified as FIGO stage IC2 (tumor rupture before surgery).

Fig. 2.

Histopathological findings: Sertoli–Leydig cell tumor and multinodular goiter of the thyroid. A HE staining showing a low- to moderately-differentiated Sertoli–Leydig cell tumor (SLCT). B Tumor cells showing positive immunostaining for α-inhibin. C Positive nuclear staining for SF1. D Positive nuclear staining for WT1. E, F Histopathological features consistent with multinodular goiter of the thyroid

Fig. 3.

Pedigree and genetic analysis. A Pedigree reveals earlier onset of renal disease within the family (arrow indicates the proband). B, C The DICER1 frameshift variant (c.3175dup; p.Tyr1059LeufsTer32) and its genomic location. D Genetic analysis of the aborted fetus revealed no pathogenic mutations. MNG: Multinodular Goiter; SLTC: Sertoli–Leydig Cell Tumour; KT: kidney transplantation

The patient declined adjuvant chemotherapy due to concerns about side effects and financial constraints. Until now, she also refused genetic testing for her relatively healthy daughter and parents, citing anxiety and potential emotional distress that could arise from positive results. Chest X-rays of her daughter showed no abnormalities at birth or at 1 year of age. Although parental genotypes could not be confirmed, the family pedigree may suggest an earlier onset of renal disease (Fig. 3). Twenty-two months later, the patient experienced another unexpected pregnancy, which was medically terminated at 12 weeks of gestation using mifepristone and misoprostol, without curettage. Genetic testing of the aborted fetus revealed no DICER1 mutation. Follow-up chest computed tomography (CT) revealed no evidence of PPB or other thoracic masses. Abdominal CT showed no recurrence of the ovarian SLCT, and both native and transplanted kidneys remained stable (Fig. 4). To date, there has been no evidence of tumor recurrence during surveillance.

Fig. 4.

Representative imaging studies during the second pregnancy. A Chest CT showing no evidence of pleuropulmonary blastoma. B Second pregnancy demonstrating the intrauterine fetus. C Native kidneys showing bilateral atrophy. D Transplanted kidney with irregular morphology. E Right ovary appearing normal after recovery. F Left ovary showing its normal appearance

Discussion and conclusion

We discuss a rare case that raises important considerations for the optimal management of pregnancy complicated by end-stage renal disease (ESRD), preeclampsia, and a ruptured DICER1-associated ovarian tumor.

In this case, an ovarian Sertoli–Leydig cell tumor (SLCT) was incidentally discovered during an emergency cesarean section, prompting subsequent DICER1 genetic testing. SLCTs are rare mixed sex cord–stromal tumors that account for < 0.2% of all ovarian neoplasms and typically occur in the first two decades of life [9]. Our case shows that without first-trimester ultrasound, ovarian masses can be missed during pregnancy. Therefore, detailed adnexal assessment in later trimesters is crucial if early imaging was not performed. Expectant management is generally appropriate for asymptomatic, benign-appearing cystic ovarian lesions in pregnancy. However, aggressive surgical intervention should be considered for masses suspicious for or confirmed as malignant [10].

Current guidelines recommend adjuvant cisplatin-based chemotherapy for patients with SLCTs with adverse prognostic factors, such as FIGO stage > I, moderate-to-poor differentiation, or heterologous elements. A recent report described the successful treatment of a pregnant patient with a DICER1-mutated SLCT using surgery and adjuvant chemotherapy [11]. In the present case, the tumor displayed high-risk features that typically warrant adjuvant therapy. Although platinum-based regimens may be considered for kidney transplant recipients after individualized risk-benefit evaluation, their potential nephrotoxicity remains a concern [12]. For personal reasons, our patient declined chemotherapy after providing informed consent, diverging from the standard management approach. While emerging evidence indicates that DICER1 mutations may correlate with improved recurrence-free survival in SLCTs [4], fatal outcomes have also been reported in earlier case series [13].

DICER1 syndrome predisposes individuals to a range of benign and malignant tumors. Female carriers appear more frequently affected than males [14], a trend may consistent with our family pedigree. The patient was on hemodialysis during pregnancy due to renal allograft failure. In this population, cancer is the second leading cause of death after cardiovascular disease. Post-transplant cancer has multiple possible causes [15]. Immunosuppression may have worked together with the patient’s DICER1 mutation to increase risk, although there is no strong evidence linking specific immunosuppressant drugs to ovarian SLCT. DICER1 is involved in regulating molecules called miRNAs, and problems with this process are linked to kidney disease and certain kidney tumors [16]. Without complete genetic information, we cannot confirm a connection.

Pregnancy during dialysis is high‑risk, with higher rates of complications such as miscarriage, preeclampsia, preterm birth, low birth weight, and more need for newborn care. Thus, planning counseling before pregnancy is crucial for these patients—an area that was overlooked in our patient’s care. Various birth control options exist and should be chosen together with each patient [17]. In early-pregnancy ESRD patients, medical abortion is recommended to minimize complications. For patients who opt to continue the pregnancy, teratogenic medications such as ACE inhibitors and mycophenolate should be discontinued prior to conception [15].

As we know, preeclampsia was a major complication, linked closely to transplant failure and ESRD through shared mechanisms like endothelial dysfunction, fluid shifts during dialysis, and effects of immunosuppression [18, 19]. Low-dose aspirin prophylaxis should be initiated between 12 and 16 weeks of gestation in high-risk women [20]. In our case, hypertension was managed using a stratified approach: prophylaxis with aspirin and calcium supplementation, oral antihypertensives for mild hypertension, and intravenous nicardipine for severe hypertension, consistent with standard recommendations [21]. If available, an elevated sFlt-1/PlGF ratio could have strengthened the diagnostic confidence for superimposed preeclampsia [22].

Preeclampsia can lead to severe complications like placental abruption, HELLP syndrome, or hepatic rupture, though ovarian cyst rupture is very rare [23, 24]. In this case, the ruptured ovarian cyst initially resembled placental abruption, with symptoms including abdominal pain, hypotension, and fetal distress. Because timely delivery is crucial for perinatal outcomes, ruling out placental abruption in an emergency is often not feasible [25, 26]. The SLCT rupture likely resulted from the tumor’s inherent features. Pregnancy may promote tumor growth and rupture through hormonal effects and physical strain. Acute hemodynamic shifts during hemodialysis could also have contributed.

In patients with ESRD, correction of anemia along with intensified dialysis to improve uremic control, has been associated with improved pregnancy outcomes, including reduced prematurity and increased gestational age [27, 28]. Social and family support also play a crucial role in achieving favorable maternal–fetal outcomes.

To the best of our knowledge, this is a unique case of a pregnancy involving a DICER1 variant with concurrent multinodular goiter, hemodialysis for graft failure, and ovarian SLCT. Preeclampsia was the major comorbidity, and ovarian cyst rupture represented an obstetric emergency. Multidisciplinary coordination was essential to optimize outcomes.

Limitations: We recognize that preconception care could have been improved in this case. A notable limitation is the absence of comprehensive genetic testing and detailed renal phenotyping among affected family members. Nonetheless, this report offers meaningful phenotypic observations and points to a possible link between DICER1‑related tumor susceptibility and renal disease, which may inform subsequent mechanistic and population‑based studies.

Abbreviations

SLCT

Sertoli–Leydig cell tumor

MNG

Multinodular goiter

KT

Kidney transplantation

ESRD

End-stage renal disease

MDT

Multidisciplinary team

PPB

Pleuropulmonary blastoma

CT

Computed tomography

Authors' contributions

ZFZ and YL designed the research. ZFZ and YTZ collected patients’ information. YL, JHQ and ZFZ did the surgery. YL, JHQ, YTZ, WZ, and ZFZ managed the patient. ZFZ outlined the initial draft and made a collection of clinical images. All authors have read and approved the manuscript.

Funding

None.

Data availability

The datasets generated and/or analysed during the current study are available in the Genome Sequence Archive repository (GSA-Human: HRA016942), which is publicly accessible at https://ngdc.cncb.ac.cn/gsa-human.

Declarations

Ethics approval and consent to participate

The study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, and was conducted in accordance with the Declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Competing interests

The authors declare no competing interests.