Ma HR, Zhang D, Li L, Qi L, Wang L, Li YT, Wang YR. Targeted maintenance therapy for a young woman with cervical rhabdomyosarcoma: A case report and review of literature. World J Clin Oncol 2025; 16(3): 101909 [DOI: 10.5306/wjco.v16.i3.101909]
Corresponding Author of This Article
Li Li, Department of Gynecologic Oncology, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Chengxi District, Xining 810000, Qinghai Province, China. 1215014711@qq.com
Research Domain of This Article
Oncology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Huan-Ran Ma, Dan Zhang, Li Li, Lin Qi, Yi-Tong Li, Ya-Ru Wang, Department of Gynecologic Oncology, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
Liang Wang, Department of Gastrointestinal Oncology Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
Author contributions: Ma HR and Zhang D co-worked on the manuscript and reviewed the literature, they contributed equally to this article, they are the co-first authors of this manuscript; Li L contributed to the article concept and design and revised and reviewed the manuscript; Qi L provides image data for this manuscript; Wang L provides help for polishing and submitting this manuscript; Li YT and Wang YR participated in the tabulation of this manuscript; and all authors have read and approved the final manuscript.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Li Li, Department of Gynecologic Oncology, Affiliated Hospital of Qinghai University, No. 29 Tongren Road, Chengxi District, Xining 810000, Qinghai Province, China. 1215014711@qq.com
Received: September 30, 2024 Revised: November 19, 2024 Accepted: December 5, 2024 Published online: March 24, 2025 Processing time: 112 Days and 21.6 Hours
Abstract
BACKGROUND
Rhabdomyosarcoma of the uterine cervix is a rare form of soft-tissue sarcoma predominantly affecting young women, with no established standard treatment protocol.
CASE SUMMARY
This report presents a case of a 17-year-old female patient presenting with intermittent, non-cyclical vaginal bleeding and associated lower abdominal pain. Pelvic magnetic resonance imaging and additional examinations led to the diagnosis of cervical rhabdomyosarcoma. The primary treatment options for uterine cervical rhabdomyosarcoma include surgery, with or without adjuvant chemotherapy and radiotherapy. This patient underwent surgery followed by a postoperative chemotherapy regimen of gemcitabine combined with docetaxel and bevacizumab. After 19 months of follow-up, the patient showed no signs of recurrence and maintained good overall health. Given the rarity of cervix rhabdomyosarcoma, this case is presented to provide insights into the diagnosis and treatment of this condition.
CONCLUSION
This suggests that bevacizumab may demonstrate potential efficacy in the treatment of cervical rhabdomyosarcoma. In the future, targeted therapy is expected to play an increasingly significant role in the management of rhabdomyosarcoma.
Core Tip: Rhabdomyosarcoma sarcoma is a malignant tumor originating from rhabdomyocytes or mesenchymal cells that differentiate toward rhabdomyocytes and is the most common type of soft-tissue sarcoma in children. This paper reports a case of a young female patient with cervical rhabdomyosarcoma who underwent radical surgery, followed by chemotherapy and targeted maintenance therapy, resulting in a favorable prognosis. Given the rarity of this case, we review previous literature and provide new insights into the diagnosis, treatment, and prognosis of uterine cervical rhabdomyosarcoma.
Citation: Ma HR, Zhang D, Li L, Qi L, Wang L, Li YT, Wang YR. Targeted maintenance therapy for a young woman with cervical rhabdomyosarcoma: A case report and review of literature. World J Clin Oncol 2025; 16(3): 101909
The incidence of cervical rhabdomyosarcoma (RMS) is low and clinically rare. There is currently no standard treatment. This case combines the experience of previous cases. Different chemotherapy regimens were used after surgical treatment. Patients have a better prognosis.
CASE PRESENTATION
Chief complaints
Vaginal bleeding lasting 4 months and sudden onset of lower abdominal pain for 6 hours.
History of present illness
Since October 2022, she had experienced intermittent non-cyclical vaginal bleeding, accompanied by dizziness, fatigue, and worsening symptoms over time, including a pronounced vaginal odor and increased vaginal watery discharge. On January 17, 2023, six hours before admission, she developed intense lower abdominal pain. A local gynecological ultrasound suggested abnormal echogenicity extending from the cervix to the vaginal opening, with suspected hymenal atresia and hemoglobin levels at 90 g/L. She was referred to our hospital for further evaluation.
History of past illness
She had no history of chronic diseases, trauma, surgery, blood transfusions.
Personal and family history
The patient reported menarche at 15 years, with typically irregular menstrual cycles (4-5 days in length, every 15-30 days) characterized by light flow, dark red color, no clots, and occasional abdominal pain. Her last menstrual period was unknown, no family history of cancer.
Physical examination
The patients were generally in good condition and no obvious abnormalities were found.
Laboratory examinations
Admission examination: Blood test revealed a red blood cell count of 3.09 × 1012 and hemoglobin of 65 g/L. Nuclear medicine testing showed elevated estradiol at 126.3 (reference range: 25.8-60.7) and prolactin at 52.74 (reference range: 4.79-23.3), with other hormone levels within normal ranges.
Imaging examinations
Transabdominal gynecologic ultrasonography suggested a hypoechoic area in the vagina, likely indicating blood accumulation. Imaging and diagnosis: Pelvic contrast-enhanced magnetic resonance imaging (MRI) (Figure 1A and B) revealed a vaginal mass extending to the cervix, suggestive of a malignant neoplastic lesion, possibly sarcoma, as well as a left ovarian cyst. Figure 1 illustrates the patient’s imaging examination, which includes preoperative and postoperative and the last follow-up.
Figure 1 Patient imaging examinations.
A and B: Preoperative magnetic resonance imaging (MRI) (January 19, 2023): Cervical signal abnormalities, vaginal enlargement, and cauliflower-like mixed signal shadow, diffusion-weighted imaging showed high signal, and the maximum cross-sectional range of the lesion was 8.29 cm × 7.42 cm; C and D: Postoperative MRI (March 10, 2023): The uterus and bilateral appendages were missing, showing changes after resection, and other abnormalities were not found; E and F: The last MRI (August 26, 2024): The uterus and bilateral appendages were missing, showing changes after resection, scar shadow under right abdominal wall, and other abnormalities were not found. Orange arrow: The location of the tumor.
FINAL DIAGNOSIS
On January 28, 2023, the final diagnosis was highly suggestive of cervical rhabdomyosarcoma.
TREATMENT
Preoperative pathological biopsy
On January 19, 2023, a preoperative pathological biopsy of the cervical mass, combined with immunohistochemistry and morphological analysis, suggested a malignant soft tissue tumor, consistent with an undifferentiated sarcoma. On January 20, 2023, the patient underwent a transabdominal extensive hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection under general anesthesia. Intraoperative findings revealed a uterus of normal size, with no abnormalities in the bilateral fallopian tubes and ovaries. Enlarged lymph nodes were observed bilaterally with a short diameter of approximately 1 cm, while the common iliac, internal iliac, and deep inguinal lymph nodes showed no significant enlargement. Postoperative examination of the specimen showed a uterine depth of 7 cm, with endometrial thickening of 5mm and no intrauterine masses. The cervical mass measured 8 cm × 8 cm × 8 cm, presenting as a friable, purplish-black, necrotic tissue resembling rotten flesh.
Postoperative pathological examination and other hospital consultation
On January 26, 2023, postoperative histopathological examination (Figure 2 and Figure 3) confirmed a malignant soft tissue tumor, identified as undifferentiated sarcoma based on immunohistochemistry and morphology, with AE1/AE3 expression and extensive areas of necrosis. No pelvic lymph node metastasis was detected. Although genetic testing was recommended to confirm the diagnosis further, the patient did not proceed with it due to financial constraints. Postoperative consultation slides from the First Affiliated Hospital of Air Force Military Medical University showed a high-grade sarcoma with extensive necrosis, with a strong likelihood of RMS based on morphology and immunohistochemistry. Additional immunohistochemical results showed diffuse positivity for CD56 and murine double minute 2, BOCR (+/-), cyclinD1 expression in a few cells (< 25%), and minimal weak positivity for progesterone receptor. Negative results were observed for CD10, estrogen receptor, PanTrk, and synuclein, while H3K27me3 showed no deleterious expression. On March 10, 2023, she was readmitted for MRI evaluation (Figure 1C and D) and other examinations, after which chemotherapy was initiated. On March 08, 2023, she received intravenous gemcitabine (1.3 g), followed by gemcitabine (1.3 g) and docetaxel (110 mg) on March 15, 2023. Due to chemotherapy-induced bone marrow suppression, subsequent doses were adjusted, with gemcitabine (1.3 g) and bevacizumab (0.4 g) administered on April 4, April 25, May 16, and June 6, 2023. Additional doses were given on April 11, April 25, May 23, June 13, June 27, and July 4, 2023, with a regimen of gemcitabine (1.3 g) and a reduced dose of docetaxel (73 mg). From July 28, 2023, to August 23, 2024, maintenance therapy with bevacizumab (400 mg) was administered every 21 days.
Figure 3 Hematoxylin and eosin staining at different magnifications showed that sarcoma cells could be seen.
A: Hematoxylin and eosin at 4 × 10; B: Hematoxylin and eosin at 10 × 10; C: Hematoxylin and eosin at 20 × 10; D: Hematoxylin and eosin at 40 × 10.
OUTCOME AND FOLLOW-UP
The patient’s condition was closely monitored with regular assessments of tumor markers, computed tomography, MRI and other examinations. After 19 months of follow-up, including 6 cycles of postoperative chemotherapy and 13 cycles of targeted maintenance therapy, the last MRI shown in Figure 1E and F, dated August 26, 2024, showed no evidence of disease progression, metastasis or recurrence. The treatment outcomes and progression are illustrated in Figure 4.
Figure 4 Evaluation of the effectiveness of the treatment process; the efficacy of the patients in the treatment and follow-up is shown in the above diagram, which is a state of continuous complete remission.
CR: Complete remission (refers to the complete disappearance of all previously detectable tumors after treatment, without any clinical and imaging evidence to prove the existence of the tumor).
DISCUSSION
Cervical RMS is classified as a carcinosarcoma, representing an extremely rare type of malignant cervical tumor. Historically regarded as a sarcoma, recent molecular studies have focused on the clonal relationship between the cancerous and sarcomatous components within cervical carcinosarcoma. Gotoh et al[1] showed that the sarcomatous element originates from the carcinoma component through transdifferentiation. Based on clonal studies, Berton-Rigaud et al[2] proposed that most cervical carcinosarcomas are actually metaplastic carcinomas. The incidence of this tumor type is estimated at about 4.5 cases per million people per year in individuals aged 0-20 years[3]. Among female genital RMS cases, only approximately 3.5% involve the cervix[4], making cervix RMS exceedingly rare. Clinically, the primary clinical manifestations include abnormal vaginal bleeding and cervical masses, which may present as exophytic or polypoid growths. Depending on the tumor size, additional symptoms may include urinary incontinence, constipation, lower abdominal pain, or pressure-related symptoms[5]. The average tumor size is approximately 5.75 cm (range 2.0 cm to 9.5 cm). Notably, these symptoms can easily mimic other cervical pathologies, such as cervical cancer, leiomyomas, or cervical polyps, necessitating careful differential diagnosis. In this case, postoperative examination of the specimen showed an exophytic cervical mass measuring about 8 cm × 8 cm × 8 cm. The tumor appeared fragile, purplish-black, and resembled necrotic tissue. The patient's main symptom was persistent vaginal bleeding, which, while consistent with previous cases, was not entirely typical. Therefore, distinguishing this condition from other cervical diseases is crucial for accurate diagnosis.
There is no highly specific imaging test for diagnosing and staging uterine rhabdomyosarcoma. MRI is the most commonly used imaging modality, with an approximate tumor detection rate of 83%[6]. MRI is particularly valuable for assessing the depth of tumor infiltration, lymph node metastasis, and other critical parameters, making it the preferred imaging tool for staging RMS and guiding treatment planning[7]. In this patient, pelvic MRI with contrast enhancement showed an abnormal cervical signal, vaginal dilatation with cauliflower-like mixed signals, high signal on diffusion-weighted imaging, and a lesion with a maximal cross-section of 8.29 cm × 7.42 cm. The imaging findings suggested a vaginal space-occupying lesion involving the cervix, with a high suspicion for a malignant sarcoma. Although MRI is effective in determining the localization and extent of the lesion, the histological diagnosis of RMS is still dependent on pathological biopsy and immunohistochemistry, considered the gold standard for confirmation. Michelagnoli et al[8] found that MyoD1 can also appear in other small round cell tumors, such as Ewing’s sarcoma and other non-RMS tumors, while myogenin expression is specific to rhabdomyosarcoma. However, in this case, the immunohistochemical results were inconclusive, with MyoD1(-), myogenin (weak +), and significant necrotic tissue, limiting the pathologist’s ability to make a definitive diagnosis.
Currently, there is no standardized treatment plan for cervical rhabdomyosarcoma, and the main clinical approach involves surgery, with or without adjuvant chemotherapy and radiotherapy[9]. The Intergroup Rhabdomyosarcoma Study clinical staging system is considered the best indicator for assessing prognosis[10]. In a systematic review of 137 patients with non-metastatic gynecological rhabdomyosarcoma, Elsebaie and Elsayed[11] concluded that surgery is the main method for achieving local tumor control. Retrospective studies and case reports, Table 1[12-15] and Table 2[7,16-22] show that all 36 patients underwent surgical treatment, with or without chemotherapy and radiotherapy before or after surgery, with survival times ranging from 3 months to 156 months. Results from the case series by Koukourakis et al[18] demonstrated a better prognosis for RMS patients in clinical group I. In addition, cases with no deep myometrial invasion, single polypoid tumors, and embryonic histological subtypes showed favorable outcomes following surgical treatment. Xu et al[22] suggested that for adults without fertility requirements, radical surgery followed by adjuvant chemotherapy after neoadjuvant treatment [vincristine, actinomycin D, and cyclophosphamide (VAC)] might be an effective strategy for treating large cervical rhabdomyosarcoma. Doxorubicin, either as monotherapy or in combination with ifosfamide and/or dacarbazine, is considered the standard first-line chemotherapy regimen[23,24]. However, some studies have shown that a 14-day cycle of gemcitabine-docetaxel chemotherapy is more effective and safer than the traditional 21-day regimen for patients with advanced soft tissue and bone sarcoma[25].
vincristine ifosfamide doxorubicin etoposide and CHT
Yes
Yes
60/NED
Recent years have seen increased interest in molecular targeted therapy for tumor treatment. Angiogenesis, a hallmark of cancer, is crucial for tumor growth and progression. Bevacizumab, a humanized monoclonal antibody targeting angiogenesis, binds to all circulating soluble vascular endothelial growth factor A (VEGF-A) subtypes and prevents its interaction with VEGF receptor. By inhibiting the activation of the VEGF signaling pathway, bevacizumab disrupts the pathway promoting neovascularization. Zhuang et al[26] have shown that bevacizumab inhibits vascular growth, induces the regression of newly formed blood vessels, and normalizes the vascular system, facilitating the delivery of cytotoxic chemotherapy while directly impacting tumor cells. In addition, recent studies have shown that VEGF signaling supports immunosuppression through a variety of mechanisms, including abnormal hematopoiesis, impaired maturation and function of dendritic cells and T cells, inhibition of activated T cell transport and survival, and promotion of immunosuppressive cells, such as regulatory T cells and myeloid-derived suppressor cells[27]. Targeting VEGF/VEGF receptor has been recognized as a strategy to enhance anti-tumor immunity, especially in combination with cancer immunotherapy. There is experimental evidence supporting the use of bevacizumab in rhabdomyosarcoma[28,29]. Previous evidence has suggested that bevacizumab exerts its anti-tumor effect by blocking the autocrine loop through its anti-angiogenic action[28] and mitigating the immunosuppressive effect of vascular endothelial growth factor[30]. Lindén et al[31] reported a case of embryonal RMS in the retromaxillary space, where the patient, resistant to conventional radiochemotherapy, was treated with bevacizumab and statins. The treatment, along with postoperative maintenance with bevacizumab, resulted in complete remission for two years after surgery. Further, reports have documented the use of bevacizumab in treating ovarian sarcoma. In one case, the patient’s ovarian sarcoma comprised primarily fibrosarcoma, with small amounts of chondrosarcoma and rhabdomyosarcoma. Treatment with cisplatin, paclitaxel, and bevacizumab led to improvement, with a short-term follow-up of 6 months[32]. Given the rarity of rhabdomyosarcoma, its high malignancy and recurrence rates, and the lack of a standard treatment plan, our patient underwent surgery followed by 6 cycles of chemotherapy. Instead of a VAC regimen, the chemotherapy included an initial cycle of gemcitabine (1.3 g) and docetaxel (110 mg). Due to myelosuppression, the dosage of docetaxel was reduced to 73 mg in the subsequent cycle, with bevacizumab (0.4 g) added. Anti-angiogenic targeted maintenance therapy with bevacizumab was subsequently implemented. At a 19-month follow-up, imaging and tumor marker-related examinations showed no disease progression, recurrence, or metastasis, and the patient remains in good health. Our case provides further clinical insights into the treatment of cervical RMS and suggests that postoperative combination chemotherapy and targeted maintenance therapy may be effective treatment options for managing this rare malignancy.
The prognosis for early-stage cervical RMS patients is relatively favorable, making early diagnosis and treatment essential for improving outcomes. Factors affecting prognosis include tumor stage, patient age, histological subtype, regional lymph node involvement, distant metastasis, and treatment methods[33]. Studies have shown that the 2-year overall survival rate for adult RMS patients receiving surgery and VAC chemotherapy is approximately 55%, with a disease-free survival rate of 64%[34]. However, the survival rate observed in a retrospective study by Gruessner et al[16] was lower than previously reported. This discrepancy may be attributed to underlying molecular and pathophysiological differences in the patients studied. In the present case, the patient was young, and intraoperative examination revealed a large cervix lesion, measuring approximately 8 cm × 8 cm × 8 cm, with deep cervical invasion. Bilateral obturator lymph nodes were enlarged, with a short diameter of 1 cm, though there was no evident enlargement in the common iliac, internal iliac, or deep inguinal lymph nodes. Therefore, an abdominal radical hysterectomy, bilateral salpingectomy, and pelvic lymph node dissection were performed. The patient has since received postoperative adjuvant chemotherapy and ongoing bevacizumab anti-angiogenic targeted therapy. Currently, the patient demonstrates a good prognosis.
CONCLUSION
Cervical RMS is rare in clinical practice due to its low incidence and atypical symptoms. Most reports on RMS are limited to case studies, and no standardized treatment protocol exists thus far. The primary treatment approach remains surgical resection, often combined with radiotherapy or chemotherapy. However, treatment selection must consider a variety of factors, including accurate assessment of the patient’s condition, surgical options, and individualized radiotherapy and chemotherapy plans. These plans should be tailored to the specific situation of the patient, rather than relying solely on clinical guidelines or case reports. Therefore, further exploration of optimized treatment methods for cervical RMS is urgently needed. In this case, the patient underwent surgery, followed by 6 cycles of chemotherapy with gemcitabine and docetaxel, along with 13 cycles of bevacizumab for targeted maintenance therapy. At the 19-month follow-up, imaging and tumor marker examinations showed no signs of disease progression, metastasis, or recurrence, and the patient remains in good health. This case suggests that bevacizumab may offer potential therapeutic benefits in the treatment of cervical rhabdomyosarcoma. In the future, targeted therapy is expected to become an important treatment method for rhabdomyosarcoma. However, due to the rarity of the disease, further long-term follow-up and studies on more patients are required to substantiate the efficacy of bevacizumab in treating cervical rhabdomyosarcoma.
ACKNOWLEDGEMENTS
The authors acknowledge and appreciate our colleagues for their valuable suggestions and assistance for this article.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade C
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade B
P-Reviewer: Ma WX S-Editor: Bai Y L-Editor: A P-Editor: Zhao YQ
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