Delayed diagnosis for DICER1-associated embryonal rhabdomyosarcoma in the cervix for a 15-year-old girl: a case report
Highlight box
Key findings
• A 15-year-old girl with a vulva mass was diagnosed with cervical embryonal rhabdomyosarcoma (ERMS) bearing DICER1 mutation by pathological examination.
• Vincristine + actinomycin D (KSM) + cyclophosphamide (CTX) combination chemotherapy is effective for cervical ERMS.
What is known and what is new?
• ERMS is a large subtype of rhabdomyosarcoma (RMS), which is an aggressive malignant embryonal tumour arising from mesenchymal stem cells. For female patients, the symptoms of ERMS in the cervix are non-specific thus it is uneasy to make a diagnosis in the early stage.
• The first presentation of ERMS in the cervix could be a prolapsed vulva mass. The tumor diagnosis should always be taken into consideration for any unexpected vulval mass for teenagers. Vincristine + KSM + CTX combination chemotherapy is effective for ERMS in the cervix.
What is the implication, and what should change now?
• The tumor diagnosis should always be taken into consideration for any unexpected vulval mass for teenagers.
• A multi-disciplinary team including a gynecologist, pediatrician, oncologist, radiologist, and pathologist could be a good choice to avoid such a pitfall of misdiagnosis.
Introduction
Embryonal rhabdomyosarcoma (ERMS) is a large subtype of rhabdomyosarcoma (RMS), which is an aggressive malignant embryonal tumour arising from mesenchymal stem cells (1). ERMS is composed of round or spindle-shaped cells and recapitulates the embryogenesis of skeletal muscle. Generally, it often presents as a well-circumscribed multinodular mass with gelatinous, gray-white cut surface (2). ERMS accounts for 50–70% of all RMS and the Annual Percent Change (APC) in overall incidence stayed stable between 1973 and 2014 (3). A bimodal age distribution was observed in ERMS, including a larger peak between ages 0–5 years and a smaller peak in adolescence (4). More male patients were affected during the second peak. ERMS tends to occur in the head, neck area, and genitourinary tract (GU). The GU is the second most common site for RMSs and 80% of them are ERMS (5,6). For female patients, tumors arise from the vulva, vagina, cervix, and uterus, present with non-specific symptoms, such as large protruding masses, vaginal bleeding, abdominal pain, or symptoms from mass effect (7). It is the non-specific symptoms make it difficult to make a diagnosis in the early stage for patients with ERMS in GU.
Treatments for ERMS mainly involve the use of chemotherapy, radiation and surgery. Generally, ERMS in GU responds well to chemotherapy. Thus, surgery taken out in a small group is only for biopsy, and organ preservation and avoids functional or cosmetic deformity (8-10). Thanks to multimodal approaches to treatments, the relative 5-year survival rates improved from 60.9% to 73.4% from 1976 to 1980. But it varied with age, the 5-year survival rate was estimated to be 71% for children younger than 15 years old while decreased to 54% for teenagers ages 15 to 19 years (11).
In this paper, we reported the diagnosis and therapeutic process of a 15-year-old girl with ERMS in the cervix. A vaginal mass stealthily emerged in the patient’s vaginal opening and the diagnosis was tricky in the beginning due to the general view of the mass resembling prolapsed cervix. The initial surgical plan was to explore the origin of the mass and cut it. The biopsy was not performed before surgery, which resulted in the delayed diagnosis and treatment until the pathological outcome. This case would remind us of the likelihood of the tumor for any vulval mass in a teenage girl. We present this article in accordance with the CARE reporting checklist (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-39/rc).
Case presentation
A 15-year-old female patient came to the clinic with a vulval mass stuck in the vaginal opening. The patient had a normal menstrual period every 28 days since she was 13 years old and the bleeding lasted 5 days. The mass prolapsed from the vagina during the menstrual period and then retracted for the last 3 months. At this visit, the mass would not retract anymore after a period. The patient was in good condition at the visit and walked into the clinic with her mother. After examination, the mass was at egg size and its surface was scattered with ulceration and pus. An opening-like structure was seen on the surface which was shown in Figure 1. On palpation, the mass was connected to the uterus with a spindly stalk tissue. Notably, no normal cervix was palpated inside the vagina. Thus, the mass was suspected to be a prolapsed cervix.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s mother for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Investigation
For evaluation, the serum tumor markers like carbohydrate antigen (CA)125, CA19-9, CA15-3, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) were all in the normal range. No other positive findings in the blood tests.
On ultrasonography, as shown in Figure 2, the total length from the internal cervical orifice to the surface of the mass was 7.6 cm. Regular endocervical echo and endocervical morphology were detected inside the extended cervical tissue and stopped at 1.0 cm above the mass. The external cervical os-like echo is not obvious on its surface. Blood flow signals extended from the cervix could be observed in the weak echo bulge. The ultrasonography indicated the vulval mass was a prolapsed extended cervix.

On magnetic resonance imaging (MRI) scanning, uneven high signal on T2WI and isointense signal on T1WI were seen on the mass with no obvious diffusion restriction, shown in Figure 3. The enhanced scanning showed obvious uneven enhancement. The mass was connected to the extended cervix. However, the cervix was not enlarged, and the cervical stromal ring was intact, which was contradictory to the ultrasound findings. The MRI scanning supported the idea the mass was a neoplasm which originating from the cervix.

Treatment
The vulval mass was suspected to be a prolapsed cervix. After a comprehensive discussion with the parents, surgery was opted to remove the mass. Once removed, the mass was found to be originated from the right part of the cervix, of which the left part was intact (Figure 1C). ERMS was diagnosed according to pathological examinations. The mass was composed of round or spindle-shaped cells and recapitulates embryogenesis of skeletal muscle, indicating the RMS-differentiation. Immunohistochemical studies were performed, and the tumor cells showed positivity for desmin, myogenin, MyoD1, myoglobin, CD10, CyclinA1 (partially), wild-type p53, and ki67 (80%). The immunohistochemical results are shown in Figure 4. In contrast, estrogen receptor (ER), progesteron receptor (PR), s-100 and CK-P were all negative (not shown). Sanger sequencing for DICER1 gene (NM_001271282) in the mass tissue revealed a heterogenous variation (c.5662A>C), resulting in the change of the 1813th amino acid from glutamic acid to alanine (E1813A) in the tumor cells. Since then, ERMS was finally made due to the pathological diagnosis.

Once diagnosed, the patient was transferred to Oncology department. She had received VAC (vincristine + actinomycin D + cyclophosphamide) combination chemotherapy for two cycles: vincristine (VCR) 2 mg intravenously guttae (ivgtt) + actinomycin D (KSM) 2 mg ivgtt + cyclophosphamide (CTX) 1,700 mg ivgtt. During the initial surgery, the tumor was resected but the margin of the resection tissue was observed with tumor cells. Then cervical conization was implemented to remove the residue of the tumor. No more tumor residue was found in the conization tissue according to the pathological report. Then the patient received the third cycle of VAC combination chemotherapy. No complications of surgery or chemotherapy were observed during the treatments.
Outcome and follow-up
The patient came back to the clinic every 3 months. Gynecological examination and blood tests for the tumor markers were routinely taken out. Clinical follow-up showed no evidence of recurrence or metastasis 12 months after the last chemotherapy. The timeline of presentation, diagnosis, treatment, and follow-up is shown in Figure 5.

Discussion
We reported a case of a 15-year-old girl who had a vulval mass stuck in the vaginal opening. The mass was thought to be a prolapsed cervix in the beginning but finally proved to be an ERMS tumor after excision and histopathological examination. The following chemotherapy and cervical conization ensured a good therapeutic effect and the patient remained disease free in the 12-month follow-up. Given the results of this case, we demonstrated a rare cervical ERMS case presented with a big mass prolapsed from the cervix and the initial diagnosis was confusing due to its appearance and ultrasonography results. We believe that it could remind medical professionals of the possible ERMS if they encountered a teenage girl with a mass prolapse from the vagina, as this knowledge will support them in making proper diagnostic and therapeutic decisions.
Cervical ERMS is a rare histological type of cervical sarcomas, and it usually presents as a cervical polyp or multiple polyps (12). The primary site is closely related to the age of the patient. Tumor entity is usually found in the vagina during infancy and early childhood and is more common in the cervix during the teenage stage (13). By analysis of 94 cases, irregular vaginal bleeding is the most common signs, followed by protruding vaginal mass, cervical polyp, or expelled tumor fragments per vagina (14). However, the early diagnosis in teenage girls is not easy for some reasons. Firstly, irregular vaginal bleeding is also common in teenage girls for the immaturity of the hypothalamic-pituitary-ovarian (HPO) axis. Secondly, the obsession with virginity in some areas impedes the examination or biopsy for vagina and cervix in these groups. Lastly, some girls are ashamed to confide their symptoms with even intimate persons. In this case, the patient started with protruding vulval mass during their menstrual period 3 months ago without telling others and finally resorted to her mother when the mass was continuously stuck in the vaginal opening. That’s to say, she could get a diagnosis as well as treatment three-month earlier once the vaginal mass appeared. The difficulty of early diagnosis for ERMS also happened in other hidden organs such as the prostate. One case of prostate ERMS case was misdiagnosed due to the non-specific presenting symptoms (15). Thus, doctors should always keep in mind the possibility of neoplasm in front of unusual mass. In this case, the ultrasonography of mass supported the initial diagnosis of a prolapsed cervix, however, the MRI images indicated a possible neoplasm originating from the cervix. Based on the efficiency of MRI in the diagnosis and evaluation of endometrial and cervical cancers, we suggested MRI scanning be a prior choice in front of any suspicious mass (16,17).
ERMS is normally regarded as a sporadic tumor, however, its development may also be associated with some various familial tumor predisposition syndromes, such as Li-Fraumeni syndrome (TP53), neurofibromatosis type 1 (NF1), Noonan syndrome (multiple genes), Costello syndrome (HRAS) and DICER1 syndrome (18). The DICER1 syndrome has been linked to pathogenic germline mutations of the DICER1 gene which encodes an endoribonuclease involved in the maturation of microRNAs (miRNAs) (19,20). The products of DICER1 gene are a key component of a highly conserved cellular pathway responsible for the generation of small RNAs (miRNAs and siRNAs), which could negatively regulate gene expression and appear to play critical roles in stem cell maintenance, organogenesis, cell cycle progression, and oncogenesis (21,22). Decreased DICER1 expression would weaken the down-regulation of oncogenesis pathway, which results in tumorigenesis like familial pleuropulmonary blastoma or ERMS (23). Patients with DICER1 gene mutations are predisposed to certain types of benign or malignant tumor. For individuals who harbor pathogenic DICER1 mutations, the risk to develop a neoplasm is 5.3% before the age of 10 years and 31.5% before the age of 60 according to a study on 207 carriers (24). In a study on 19 cases of uterine ERMS, 18/19 (95%) of them were detected with DICER1 mutations (25). In another study on 17 genitourinary ERMS, DICER1 mutations were found in all 9 uterine (four uterine corpus and five cervix) ERMS, while the rest 1 vaginal and 7 urinary tract tumors had wild-type DICER1 gene (18). In the same study, through analysis of the clinicopathologic and molecular analysis of DICER1 mutation status in the 17 cases, the authors proposed that DICER1-associated ERMS could be qualified as a distinct subtype in future classifications. Even though the incidence peak of ERMS is in children and teenagers, DICER1-associated ERMS are more frequently observed in older patients (18,25). In contrast, another study reported the median age of patients with DICER1-associated female genital ERMS at diagnosis was 16 years old (26). Those contradictory results are probably due to a selection bias. We consider that this clinicopathologic feature should be explored in a large cohort of patients. The relationship between DICER1mutation and the prognosis of cervical ERMS has not been elucidated yet, but a quite favorable prognosis with an event-free survival of over 50%, and an overall survival of around 90% were observed (27). In this case, one mutation of DICER1 gene (NM_001271282, c.5662A>C) was found in the patient’s tumor tissues, which led to the amino acid change (E1813A) in the protein products. This 1,813th amino acid site is located in an RNase III 1 domain, acting as a binding site for Mg-2 ions (28). However, the consequences of the amino acid change had not been reported yet, and the relationship between this mutation and cervical EMRS could not be concluded from this case. To get elucidated, a lot more cell experiments and animal experiments should be carried out in the future. Except for the gene sequencing for tumor cells, the circulating tumor DNA was also detected in the serum sample, which may be used as a biomarker for tumor heterogeneity, tumor resistance and inform potential targeted therapies in certain types of rhabdomyosarcoma (MRS) (29,30).
There are no guidelines or consensus regarding the treatments for this disease, the treatment plans should be fully discussed with gynecologist, oncologist, pediatrician and pathologist. Treatments for newly diagnosed ERMS patients often include surgery, radiation therapy, and chemotherapy, which one comes first dependent on the site, size and type of the tumor as well as the presence of metastasis. The goal of surgical treatments is to completely resect the tumor entity with a surrounding margin of normal tissue (31). Radiation therapy is an efficient approach to achieve local control of the tumor for patients with microscopic or gross residual disease after biopsy, initial surgical resection, or chemotherapy. Patients are divided into four groups (I, II, III and IV) according to the completeness of initial surgical resection and pathological review of the tumor specimens (32). The doses and volume of radiation therapy are determined by the classification of groups and the extent of primary tumors. Normally, Group II patient subsets (tumor was grossly resected with microscopic residuals) could benefit from the radiation therapy for local tumor control and a better event-free survival (33). Moreover, for adults with head and neck RMS, carbon-ion beam radiotherapy alone or combined with proton radiotherapy is also effective in local disease control (34). Chemotherapy is recommended for children’s RMS. The intensity and duration of the chemotherapy are dependent on the Risk Group assignment (35). According to their TNM stage, the clinical group, and the PAX/FOX01 fusion gene status, patients were divided into three risk groups, which helps doctors make treatment plans. The combination of VAC are the most commonly used for chemotherapy.
For genitourinary EMRS, fertility preservation should always be a consideration for all patients (22). The patient in this report was classified as stage 1 for clinical stage, Group II for surgical-pathological group system, and low risk for risk group according to the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (32). In the beginning, the protruding mass was deemed as a prolapsed cervix, thus the purpose of initial surgical treatment was to remove the abnormal cervix. The 3 cycles of VAC chemotherapy began soon once the pathological diagnosis of EMRS was made. To preserve the fertility, no radiation therapy was adopted. To achieve maximum therapeutic effect, a second surgery of cervical conization was taken out to remove the residue in the cervix. Actually, the second surgery was disputable because the microscopic residue was acceptable. Moreover, chemotherapy alone is an efficient way to keep local control (36). Notably, for Group II or Group III patients with genitourinary EMRS, conservative surgical intervention with primary chemotherapy and radiation results in excellent 5-year survival rates (37). Back to the beginning, if a diagnosis was made via biopsy, the second surgery could be largely avoided because the tumor entity together with partial cervix tissue could be excised in the initial surgery. The pitfall of this case was the appearance of the tumor was similar to the cervix, which was supported by the first ultrasound examinations. However, there was an indication of possible tumor mass according to the enhanced MRI scanning, which showed the mass was uneven enhancement. This case reminds us of the importance of a biopsy for any suspicious mass in every single patient.
Conclusions
Herein, we reported a rare case of cervical EMRS with DICER1 mutation. This tumor mass was misdiagnosed with a prolapsed cervix in the beginning due to the cervix-similar appearance and the ultrasound examinations. The diagnosis was corrected soon after the pathological examinations. Fertility-conserving surgery, followed by adjuvant chemotherapy was taken out under clinical evaluation by gynecologist, oncologist, pediatrician and pathologist. However, there existed some limitations in this study. First of all, it was a rare sporadic case. Secondly, the level of local health care varies all over the world. Thus, the diagnosis and treatment for this case could not be representative of all the cervical EMRS cases. Even though, we could still learn from this rare case tumor diagnosis should always be taken into consideration for any unexpected mass. A multi-disciplinary team could be a good choice to avoid such pitfall of misdiagnosis.
Acknowledgments
The authors thank Department of Radiology and Department of Ultrasonography in West China Second University Hospital for providing the MRI scanning pictures and ultrasonography pictures in this paper.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-39/rc
Peer Review File: Available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-39/prf
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-24-39/coif). X.T. serves as an unpaid editorial board member of Gynecology and Pelvic Medicine from October 2023 to December 2025. The other authors have no conflict of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient’s mother for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Liao H, Luo G, Liao G, Sun L, Tan X. Delayed diagnosis for DICER1-associated embryonal rhabdomyosarcoma in the cervix for a 15-year-old girl: a case report. Gynecol Pelvic Med 2025;8:4.