Alveolar Vaginal Rhabdomyosarcoma in an Adult: A Rare Case Report and Comprehensive Literature Review

Department of Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Morocco

*Corresponding Author: Dr. Zineb Kabala, Department of Oncology, University Hospital Center Ibn Rochd, Faculty of Medicine and Pharmacy, University Hassan II, Morocco, Phone: 0615449640, Email: [email protected]

Received Date: April 25, 2025

Published Date: May 24, 2025

Citation: Kabala Z, et al. (2025). Alveolar Vaginal Rhabdomyosarcoma in an Adult: A Rare Case Report and Comprehensive Literature Review. Mathews J Case Rep. 10(3):207.

Copyrights: Kabala Z, et al. © (2025).

ABSTRACT

Rhabdomyosarcoma (RMS) is a rare and aggressive malignant tumour arising from mesenchymal tissue with skeletal muscle differentiation. Although it mainly affects children and adolescents, its presence in the female genital tract, particularly the vagina, is exceptionally rare. Among its histological subtypes, alveolar rhabdomyosarcoma (ARMS) is recognised for its aggressive nature, poor prognosis and distinct molecular features. Despite advances in multimodal treatment strategies, the prognosis and optimal management of vaginal RMS are still under investigation. Given its early non-specific symptoms and potential for rapid progression, early diagnosis is essential to improve patient outcomes. We report a rare case of a 58-year-old divorced woman, mother of one, with a family history of gastric cancer (maternal grandmother). The patient's symptoms began six years prior with recurrent episodes of scant metrorrhagia, which were initially neglected due to preserved general condition. The worsening of bleeding prompted medical consultation. A pelvic ultrasound revealed an enlarged uterus with a 5 cm intra-cavitary mass. A pelvic MRI showed a solid-cystic abdomino-pelvic mass measuring 82 x 85 mm, suspicious for a tumor of either peritoneal or ovarian origin. An exploratory laparoscopy was performed, with biopsy of a peritoneal mass and excision of a vaginal mass. Histopathological analysis confirmed a diagnosis of alveolar rhabdomyosarcoma of the vagina, an extremely rare malignancy in adults. Further staging with CT imaging revealed peritoneal carcinomatosis and pulmonary nodules, which were confirmed by biopsy to be metastatic in nature. A complete biological work-up was normal. The patient received two cycles of first-line chemotherapy (vincristine, dactinomycin, and cyclophosphamide), but unfortunately died 21 days after the second cycle due to rapid disease progression. This case highlights a rare and aggressive form of vaginal alveolar rhabdomyosarcoma in adults, characterized by late diagnosis, metastatic spread, and poor prognosis, despite appropriate therapeutic intervention.

Keywords : Alveolar Rhabdomyosarcoma, Vaginal Tumor, Soft Tissue Sarcoma, Genitourinary.

INTRODUCTION

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for approximately 4–6% of all pediatric malignancies [1]. It arise from primitive mesenchymal cells with the potential for skeletal muscle differentiation. RMS is classified into several histological subtypes, with embryonal and alveolar variants being the most common. While embryonal RMS is the predominant subtype in genitourinary tract tumors, alveolar rhabdomyosarcoma of the vagina is exceedingly rare and is typically associated with a more aggressive clinical course and poorer prognosis [2].

Given its rarity, vaginal alveolar rhabdomyosarcoma poses significant diagnostic and therapeutic challenges [3].

We present a rare case of vaginal alveolar rhabdomyosarcoma in a young patient, detailing the diagnostic process, therapeutic strategy, and clinical outcome.

The anatomical complexity of the female genital tract poses significant challenges in achieving complete surgical resection while preserving reproductive and sexual function. Multimodal treatment approaches, including surgery, chemotherapy, and radiotherapy, are often employed; However, the optimal therapeutic strategy remains undefined due to the paucity of cases and lack of standardized guidelines [4].

Moreover, the long-term sequelae of aggressive treatments, such as urinary and sexual dysfunction, significantly impact the quality of life of survivors. A recent qualitative study highlighted these concerns, emphasizing the need for comprehensive survivorship care that addresses both physical and psychosocial aspects [5].

Given these challenges, there is a critical need for increased awareness, early diagnosis, and the development of tailored treatment protocols to improve outcomes for patients with vaginal alveolar rhabdomyosarcoma.

CASE REPORT

We report the case of a 58-year-old divorced housewife with one daughter and a grandmother who died of stomach cancer.

Her history of the disease dates back 6 years to the onset of several episodes of metrorrhagia of low abundance, neglected by the patient in a context of conservation of general condition. The picture was marked by a worsening of the metrorrhagia, which prompted the patient to seek medical attention. A pelvic ultrasound performed on 12/10/2024 showed an enlarged uterus with an intra-cavity mass measuring 5cm, ovary not seen, and a cervical biopsy showed a morphological aspect in favour of suppuration necrosis. The work-up was completed by pelvic MRI showing a solid cystic mass of tumour origin measuring 82*85 mm, right abdomino-pelvic tissue mass of tumour origin, carcinosis mass? or ovarian origin?

Figure 1. Solid cystic mass of tumour origin measuring 82*85 mm, right abdomino-pelvic tissue mass of tumour origin.

Figure 2. Alveolar structures composed of roundish cells around a connective septa or vascular structures.

An exploratory laparoscopy was performed with biopsy of the peritoneal mass, and exeresis of the vaginal mass with anatomopathological evidence of malignant proliferation in favour of an alveolar rhabdomyosarcoma of the vagina Strong nuclear positivity for Myogenin and MyoD1, positivity of Desmin, CD56, Vimentin, Negativity of Cytokeratin, S100, CD45 (LCA).

The work-up was completed by a CAT scan which revealed a tumour process centred on the pelvis, associated with pulmonary involvement of probable secondary origin, peritoneal carcinosis.

The pulmonary nodules were biopsied, confirming their secondary origin.

A full biological work-up was carried out, with no abnormalities.

The patient was started on first-line chemotherapy consisting of vincristine, dactinomycin, and cyclophosphamide, receiving a total of two treatment courses. Despite this aggressive multimodal approach, the disease demonstrated relentless progression. Unfortunately, the patient’s condition rapidly deteriorated, and she succumbed just 21 days following the completion of the second chemotherapy cycle. This rapid clinical decline underscores the highly aggressive nature of vaginal rhabdomyosarcoma, which is known for its swift invasion and resistance to standard therapies in certain cases. The poor outcome in this case highlights the urgent need for early detection and the exploration of novel therapeutic strategies to improve prognosis in such aggressive presentations.

DISCUSSION

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, accounting for approximately 4–5% of pediatric malignancies [6]. Among its subtypes, alveolar rhabdomyosarcoma is distinguished by its aggressive nature and poor prognosis [7]. Vaginal ARMS, though exceedingly rare, represents a distinct clinical entity requiring a multidisciplinary treatment approach. Understanding its molecular biology, clinical course, and response to therapy is crucial for improving patient outcomes.

Vaginal rhabdomyosarcoma is most frequently diagnosed in children under the age of 5, with the embryonal subtype (botryoid variant) being the most common. However, alveolar rhabdomyosarcoma of the vagina tends to present in older children and adolescents. Alveolar vaginal rhabdomyosarcoma is exceedingly rare in adults, with the majority of cases occurring in the pediatric population [8,9]. The clinical presentation in adults may be atypical, leading to misdiagnosis or delayed detection [10]. Adult patients often present with persistent vaginal bleeding, pain, and an enlarging mass, which may be mistaken for benign gynecologic conditions such as fibroids or endometrial polyps [11,12]. Unlike pediatric cases, adult vaginal ARMS may exhibit a more aggressive disease course with higher rates of local invasion and distant metastases.Histologically, alveolar rhabdomyosarcoma is characterized by small, round cells with scant cytoplasm, arranged in a pattern resembling pulmonary alveoli. Immunohistochemical staining is essential for confirming the diagnosis, with tumor cells expressing markers such as desmin, myogenin, and MyoD1 [13]. A defining feature of alveolar rhabdomyosarcoma is its genetic translocations, most notably t(2;13)(q35;q14), which results in the PAX3-FOXO1 fusion gene, and t(1;13)(p36;q14), leading to PAX7-FOXO1 fusion [14]. These genetic alterations contribute to tumorigenesis by deregulating muscle differentiation pathways and enhancing cell proliferation [15]. Tumors with PAX3-FOXO1 fusions are associated with a more aggressive phenotype and poorer prognosis compared to those with PAX7-FOXO1.

The diagnostic workup for vaginal ARMS includes imaging studies such as ultrasonography, MRI [16], and PET scans to assess local invasion and distant metastases. Biopsy with histopathological examination and molecular testing is critical for confirming the diagnosis. The Intergroup Rhabdomyosarcoma Study (IRS) staging system is commonly used to classify RMS, guiding therapeutic decisions. Staging takes into account tumor size, lymph node involvement, and metastatic spread, with advanced-stage disease associated with significantly lower survival rates [17].

The management of vaginal alveolar rhabdomyosarcoma relies on a multimodal approach, incorporating surgery, chemotherapy, and radiotherapy [18]. Complete tumor surgical excision is the preferred approach whenever feasible. However, due to the anatomical constraints of the vagina and surrounding structures, organ-preserving surgery is often prioritized to maintain functional and cosmetic outcomes [19,20].

Systemic chemotherapy forms the cornerstone of treatment. Standard regimens include vincristine, actinomycin D, and cyclophosphamide (VAC protocol), which are effective in reducing tumor burden and preventing metastasis. In high-risk cases, additional agents such as irinotecan or temozolomide may be introduced [21,22].

Given the aggressive nature of ARMS, radiation therapy is often required, particularly for tumors that are unresectable or have positive surgical margins. However, in young children, the long-term risks of radiation, including secondary malignancies and impaired organ development, must be carefully weighed [23].

The prognosis of vaginal alveolar rhabdomyosarcoma depends on several factors, including tumor stage, genetic profile, and treatment response. Patients with localized disease who achieve complete remission have a relatively favorable prognosis, with a five-year survival rate exceeding 70% [24]. However, those with metastatic disease at diagnosis have a significantly worse outlook, with survival rates dropping below 30%. The presence of PAX3-FOXO1 fusion is associated with poorer outcomes due to increased metastatic potential and resistance to conventional therapies [25]. Relapse remains a major concern, often necessitating salvage chemotherapy or experimental treatments.

CONCLUSION

Vaginal alveolar rhabdomyosarcoma is a rare and aggressive malignancy requiring early diagnosis and a multimodal treatment approach. Despite current therapies, prognosis remains poor, particularly in cases with high-risk molecular features. Future perspectives include targeted therapies, immunotherapy, and molecularly guided treatments to improve survival and reduce treatment toxicity. Advances in genomics, biomarker discovery, and precision oncology could lead to more personalized management strategies. Multidisciplinary collaboration and continued research are essential to refine treatment approaches and enhance patient outcomes.

LIST OF ABBREVIATIONS

CT: Computed Tomography; MRI: Magnetic Resonance Imaging; RMS: Rhabdomyosarcoma.

CONSENT

Written informed consent is obtained from the patient for publication and any accompanying images.

ETHICAL APPROVAL

This study is exempt from ethical approval in our institution since it doesn't involve experimental treatment.

FUNDING

 This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CONFLICT OF INTEREST STATEMENT

None.

REFERENCES

1. Pappo AS, Anderson JR, Crist WM, Wharam MD, Breitfeld PP, Hawkins D, et al. (1999). Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group. J Clin Oncol. 17(11):3487-3493.
2. Malempati S, Hawkins DS. (2012). Rhabdomyosarcoma: review of the Children’s Oncology Group (COG) Soft-Tissue Sarcoma Committee experience and rationale for current COG studies. Pediatr Blood Cancer. 59(1):5-10.
3. Parham DM, Ellison DA. (2006). Rhabdomyosarcomas in Adults and Children: An Update. Archives of Pathology & Laboratory Medicine [Internet]. 130(10):1454-1465.
4. Messaoudi H, Benlghazi A, Elktaibi A, Belouad M, Moulay Mehdi E, Kouach J. (2024). A challenging diagnosis and treatment of embryonal rhabdomyosarcoma in the cervix of an adult woman: A surgical case report. Int J Surg Case Rep. 119:109742.
5. Saunders RA, Balthazar AK, Jaeger CD, Javidan-Nejad M, Chung CY, Vessey JA, et al. (2025). Long-Term Urinary and Sexual Outcomes in Pediatric Genitourinary Rhabdomyosarcoma Survivors: A Qualitative Study. J Urol. 213(4):494-503.
6. Sun X, Guo W, Shen JK, Mankin HJ, Hornicek FJ, Duan Z. (2015). Rhabdomyosarcoma: Advances in Molecular and Cellular Biology. Sarcoma. 2015:232010.
7. Jo VY, Fletcher CDM. (2014). WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 46(2):95-104.
8. Ferrari A, Dileo P, Casanova M, Bertulli R, Meazza C, Gandola L, et al. (2003). Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer. 98(3):571-580.
9. Sultan I, Qaddoumi I, Yaser S, Rodriguez-Galindo C, Ferrari A. (2009). Comparing Adult and Pediatric Rhabdomyosarcoma in the Surveillance, Epidemiology and End Results Program, 1973 to 2005: An Analysis of 2,600 Patients. Journal of Clinical Oncology. 27(20).
10. Park S, Lee J, Do IG, Jang J, Rho K, Ahn S, et al. (2014). Aberrant CDK4 amplification in refractory rhabdomyosarcoma as identified by genomic profiling. Sci Rep. 4:3623.
11. Odoi AT, Dassah ET, Darkey DE, Owusu-Afriyie O, Valkov AY. (2009). Advanced alveolar rhabdomyosarcoma of the uterus: a case report. Afr J Reprod Health. 13(1):167-173.
12. Emerich J, Senkus E, Konefka T. (1996). Alveolar Rhabdomyosarcoma of the Uterine Cervix. Gynecologic Oncology. 63(3):398-403.
13. Parham DM, Qualman SJ, Teot L, Barr FG, Morotti R, Sorensen PHB, et al. (2007). Correlation between histology and PAX/FKHR fusion status in alveolar rhabdomyosarcoma: a report from the Children’s Oncology Group. Am J Surg Pathol. 31(6):895-901.
14. Olanich ME, Barr FG. (2013). A call to ARMS: targeting the PAX3-FOXO1 gene in alveolar rhabdomyosarcoma. Expert Opin Ther Targets. 17(5):607-623.
15. Xia SJ, Pressey JG, Barr FG. (2002). Molecular pathogenesis of rhabdomyosarcoma. Cancer Biol Ther. 1(2):97-104.
16. Gardner CS, Sunil J, Klopp AH, Devine CE, Sagebiel T, Viswanathan C, et al. (2015). Primary vaginal cancer: role of MRI in diagnosis, staging and treatment. Br J Radiol. 88(1052):20150033.
17. Lawrence W, Anderson JR, Gehan EA, Maurer H. (1997). Pretreatment TNM staging of childhood rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study Group. Children’s Cancer Study Group. Pediatric Oncology Group. Cancer. 80(6):1165-1170.
18. Raney RB, Maurer HM, Anderson JR, Andrassy RJ, Donaldson SS, Qualman SJ, et al. (2001). The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS-I Through IRS-IV Studies as Background for the Current IRS-V Treatment Protocols. Sarcoma. 5(1):9-15.
19. Rosenberg AR, Skapek SX, Hawkins DS. (2012). The inconvenience of convenience cohorts: rhabdomyosarcoma and the PAX-FOXO1 biomarker. Cancer Epidemiol Biomarkers Prev. 21(7):1012-1028.
20. Cecchetto G, Bisogno G, De Corti F, Dall'Igna P, Inserra A, Ferrari A, et al. (2007). Biopsy or debulking surgery as initial surgery for locally advanced rhabdomyosarcomas in children?: the experience of the Italian Cooperative Group studies. Cancer. 110(11):2561-2567.
21. He W, Jin Y, Zhou X, Zhou K, Zhu R. (2020). Alveolar rhabdomyosarcoma of the vulva in an adult: a case report and literature review. J Int Med Res. 48(3):300060520905438.
22. Nakano K, Ae K, Matsumoto S, Takahashi S. (2020). The VAC regimen for adult rhabdomyosarcoma: Differences between adolescent/young adult and older patients. Asia Pac J Clin Oncol. 16(2):e47-e52.
23. Puranik RB, Naik S, Kulkarni S, Kulkarni MH. (2010). Alveolar rhabdomyosarcoma of vulva. Indian J Pathol Microbiol. 53(1):167-168.
24. Meza JL, Anderson J, Pappo AS, Meyer WH, Children’s Oncology Group. (2006). Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Children’s Oncology Group. J Clin Oncol. 24(24):3844-3851.
25. Gryder BE, Yohe ME, Chou HC, Zhang X, Marques J, Wachtel M, et al. (2017). PAX3-FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability. Cancer Discov. 7(8):884-899.