Primary Embryonal Rhabdomyosarcoma of the Breast: A Case Report and Literature Review

Abstract

Background

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, but primary RMS of the breast is exceptionally rare and diagnostically challenging. Imaging findings are nonspecific and can mimic benign adolescent lesions (e.g., fibroadenoma), making timely histopathologic confirmation crucial. Immunohistochemistry for muscle markers – particularly desmin and myogenin – supports definitive diagnosis of embryonal RMS (ERMS).

Case Presentation and Case Discussion

A 14-year-old Arab female presented with a rapidly enlarging left-breast mass and ipsilateral axillary lymphadenopathy. Core biopsy showed small round blue cells with rhabdomyoblastic differentiation; tumor cells were desmin- and myogenin-positive, consistent with ERMS. She received 6 cycles of mesna-doxorubicin-ifosfamide-dacarbazine (MAID) chemotherapy, followed by local recurrence; one cycle of ifosfamide-carboplatin-etoposide (ICE) achieved an approximately 50% partial response but was complicated by cystitis and rapid radiologic progression. After three cycles of vincristine-dactinomycin-cyclophosphamide (VAC), she underwent total mastectomy with lymph-node dissection. Restaging fluorodeoxyglucose positron emission tomography/computed tomography demonstrated local recurrence and nodal metastases (bilateral axillary, subpectoral, and internal mammary) with pulmonary nodules. Despite multimodal therapy, the disease remained refractory and the patient ultimately died from complications of metastatic disease. This case highlights the aggressive biology of primary breast ERMS in adolescents and the risk of early recurrence and dissemination despite intensive therapy. While standard management of RMS is multimodal – systemic chemotherapy with surgical resection and/or radiotherapy – responses can be transient, and treatment interruptions (e.g., toxicity-related delays) may jeopardize disease control. The diagnostic value of myogenin (highly specific for rhabdomyoblastic differentiation) and Desmin was pivotal here, while the clinical course underscores the limitations of currently available regimens (MAID, ICE, VAC) for refractory disease at this uncommon site.

Conclusion

This case illustrates the need for early biopsy of rapidly enlarging breast masses in adolescents, the central diagnostic role of muscle-specific immunohistochemical markers, and the importance of uninterrupted multimodal therapy in primary breast ERMS. It also underscores the limitations of currently available regimens in refractory disease and highlights the need for collaborative, guideline-based management, and clinical-trial enrollment when feasible.

Introduction

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents and represents the most frequent pediatric soft-tissue malignancy, with an estimated annual incidence of approximately 4.5 cases per one million children [1]. It predominantly affects children and young adults, with the highest incidence observed in individuals between 15 and 24 years of age [2]. The majority of RMS cases involve the soft tissues of the head and neck, followed by the genitourinary tract, trunk, and extremities, whereas primary involvement of the breast is exceptionally rare and represents a highly uncommon site of occurrence for this tumor [3, 4].

RMS has traditionally been classified into distinct histopathologic subtypes, including embryonal RMS (ERMS), alveolar RMS, spindle cell/sclerosing RMS, and pleomorphic RMS [5]. ERMS accounts for the majority of RMS cases in younger children and is generally associated with a more favorable prognosis, whereas alveolar RMS is characterized by a higher likelihood of metastatic spread and inferior outcomes [5, 6]. Despite advances in multimodal therapy, survival outcomes for patients with metastatic RMS remain poor, with event-free survival rates below 20%, particularly when excluding children under 10 years of age diagnosed with ERMS [6, 7].

The current standard-of-care treatment for RMS across risk groups relies on a multimodal approach, which typically includes a combination of systemic multi-agent chemotherapy, surgical resection when feasible, and/or radiotherapy, tailored according to tumor location, histologic subtype, and extent of disease [8]. This risk-adapted strategy has improved outcomes for patients with localized disease; however, prognosis remains dismal in the setting of refractory or relapsed RMS.

Given the extreme rarity of primary RMS of the breast, its radiologic and clinical features are not well defined and can easily mimic common benign lesions such as fibroadenoma in adolescents. Each additional case therefore provides incremental insight into potential diagnostic pitfalls, optimal sequencing of chemotherapy, surgery, and radiotherapy, and the impact of treatment interruptions or toxicity on outcome. In this report, we describe the clinical course of a 14-year-old girl with primary breast ERMS who experienced early local recurrence and rapid metastatic progression despite intensive multimodal therapy. By integrating our experience with the existing literature, we aim to highlight key warning signs that should prompt early biopsy, discuss management challenges in this rare presentation, and underscore the need for more effective treatment strategies.

Case Presentation

A 14-year-old Arab female presented to our department with a primary complaint of a left-breast mass. Diagnostic imaging initially revealed a large, 6 cm infiltrating and contrast-enhancing mass in the left breast alongside 6 enlarged ipsilateral axillary lymph nodes, with no evidence of distant disease. A subsequent biopsy was performed. Histopathological examination revealed hyperchromatic small round cells with scanty cytoplasm exhibiting solid-sheet and cord-like growth patterns. On IHC examination, these cells showed nuclear positivity for myogenin and desmin. The tumors were diagnosed as embryonal RMS (ERMS) based on histological and IHC findings.

Her treatment course was complex and marked by multiple setbacks. She was first initiated on six cycles of MAID chemotherapy (mesna, doxorubicin, ifosfamide, dacarbazine). Unfortunately, this regimen failed to achieve lasting control, and a local recurrence was observed. Therapy was then switched to one cycle of ifosfamide, carboplatin, etoposide (ICE), which resulted in an initial partial tumor response of approximately 50%. However, this treatment was complicated by cystitis, necessitating a 1-week delay. Shortly thereafter, a follow-up CT scan revealed significant disease progression with an increase in tumor size (Fig. 1–4).

Fig. 1.

Contrast-enhanced axial chest CT scan demonstrating a heterogeneously enhancing soft-tissue mass in the upper outer quadrant of the left breast, measuring approximately 1.7 cm in diameter. The lesion shows irregular margins and early invasion of surrounding breast parenchyma.

Fig. 4.

Axial contrast-enhanced CT image of the chest showing significant disease progression of the patient’s embryonal rhabdomyosarcoma. A large, necrotic mass (arrow) is seen within the left breast, measuring 8.24 cm in its longest dimension and 4.17 cm in the orthogonal dimension (L). This radiographic evidence of progression occurred after initial chemotherapy regimens and necessitated a change in the treatment plan.

Fig. 2.

Axial CT image showing a large infiltrative left-breast mass measuring approximately 10.8 × 3.5 cm, extending toward the pectoralis muscle and anterior chest wall, with associated skin thickening and subcutaneous edema – findings consistent with locally advanced disease progression.

Fig. 3.

Contrast-enhanced axial CT image at a lower thoracic level demonstrating multiple small pulmonary nodules in both lungs, highly suspicious for metastatic spread, along with postoperative and inflammatory changes in the left chest wall following mastectomy.

A third-line chemotherapeutic protocol with three cycles of vincristine, dactinomycin, cyclophosphamide (VAC) was administered. Following this, the patient underwent a radical surgical intervention involving a total mastectomy of the left breast and lymph node dissection (Fig. 5). Despite this aggressive multimodal approach, a restaging F-18 fluorodeoxyglucose positron emission tomography/computed tomography scan performed later demonstrated widespread hypermetabolic lesions consistent with local recurrence in the left-breast parenchyma and new metastatic involvement of lymph nodes in the bilateral axillae, left subpectoral region, and internal mammary chain. Concurrent CT imaging confirmed multiple large, necrotic masses in the left breast and noted the presence of small pulmonary nodules highly suspicious for metastatic spread. At her final follow-up in May 2025, the disease had progressed further, and she was referred for palliative radiation therapy. Despite all therapeutic efforts, the patient’s disease proved refractory to treatment, and she ultimately succumbed to complications of her metastatic rhabdomyosarcoma.

Fig. 5.

Clinical photograph of the patient’s left hemithorax following radical mastectomy and lymph node dissection.

Discussion

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, but its primary occurrence in the breast is exceedingly rare, accounting for a very small percentage of all RMS cases [7, 8]. This rarity, coupled with its aggressive nature, makes the diagnosis and management particularly complex. The initial presentation with a rapidly growing breast mass and associated axillary lymphadenopathy in an adolescent necessitates a broad differential diagnosis, including benign conditions common in this age group, such as fibroadenomas, as well as other malignant entities. Imaging, as performed in this case, revealed a peripherally infiltrating, contrast-enhancing mass with enlarged lymph nodes, raising suspicion for malignancy. Definitive diagnosis of RMS relies heavily on histopathological examination and immunohistochemical staining. In this patient, the biopsy confirmed ERMS, a subtype typically seen in younger children, though it can occur in adolescents [7]. The positive immunohistochemical staining for desmin and myogenin is crucial for confirming rhabdomyoblastic differentiation. Desmin is a general muscle marker, while myogenin is a highly specific marker for rhabdomyoblastic differentiation, making it invaluable in distinguishing RMS from other small round cell tumors and confirming the diagnosis of ERMS [9].

The management of RMS is typically multimodal, involving chemotherapy, surgery, and often radiation therapy [10]. Current risk-adapted protocols generally recommend initial systemic multi-agent chemotherapy, most commonly VAC-based regimens, combined with careful staging and response assessment. For primary breast RMS, this usually involves neoadjuvant chemotherapy followed by either breast-conserving surgery or mastectomy with appropriate axillary management, depending on tumor size, nodal involvement, and response to systemic therapy. Radiotherapy to the primary site and involved nodal basins is indicated when margins are positive, when resection is not feasible, or when there is residual microscopic or gross disease after surgery, with the goal of maximizing local control while limiting long-term toxicity in children and adolescents.

In our patient, the initial choice of mesna-doxorubicin-ifosfamide-dacarbazine (MAID) as first-line chemotherapy reflects an aggressive attempt to control what was already locally advanced disease. MAID is a regimen known to be active in various sarcomas, including rhabdomyosarcoma, particularly in advanced or metastatic settings [11]. However, despite this intensive first-line approach, local recurrence was observed, highlighting the inherent aggressiveness of primary breast RMS and the potential limitations of systemic therapy alone in achieving durable local control at this anatomical site.

Following the recurrence, the patient was switched to ifosfamide-carboplatin-etoposide (ICE) chemotherapy. ICE is a commonly used salvage regimen for recurrent or refractory sarcomas, including rhabdomyosarcoma, and has shown promising response rates in pediatric and adolescent populations [12, 13]. A partial tumor response of approximately 50% was initially achieved, suggesting some chemosensitivity. However, a critical challenge arose with the delay in treatment due to cystitis, a known side effect of ifosfamide. This delay likely contributed to the subsequent increase in tumor size observed shortly afterward, underscoring the importance of maintaining dose intensity and promptly managing adverse events in aggressive malignancies such as RMS.

The patient then received three cycles of vincristine-dactinomycin-cyclophosphamide (VAC) chemotherapy. VAC is considered a core regimen in the treatment of rhabdomyosarcoma, particularly in the upfront setting, and is a well-established combination for this disease [11–14]. Its use in this recurrent setting, following two other regimens, reflects a strategy of employing different active agents to overcome potential drug resistance or to consolidate response before definitive local therapy. Following chemotherapy, a total mastectomy of the left breast, along with lymph node dissection, was performed. Surgical resection plays a vital role in achieving local control in RMS, especially when the tumor is resectable [10, 14]. In cases of recurrent disease, surgical debulking or complete resection, if feasible, is often critical to improve outcomes. Despite these extensive efforts, as of the last follow-up in May 2025, local recurrence was again noted, highlighting the significant challenges in managing primary breast RMS, which often presents with advanced local disease and a high propensity for recurrence, even after aggressive multimodal therapy.

The ongoing local recurrence underscores the poor prognosis often associated with recurrent RMS, particularly in unusual primary sites like the breast. The patient’s referral for radiation therapy represents a crucial step, as radiotherapy is an integral component of RMS treatment, used for local control, especially in situations where complete surgical margins are difficult to achieve or in recurrent settings to reduce the risk of further local progression [9, 11, 15]. In parallel with conventional approaches, several innovative strategies are being explored for high-risk and relapsed RMS, including dose-intensified and maintenance chemotherapy, targeted agents, epigenetic and cell-cycle modulators, and, more recently, immunotherapeutic approaches. Although such options were not available in our setting and remain largely investigational, enrollment in cooperative-group or early-phase clinical trials should be considered whenever feasible for patients with refractory primary breast RMS, as this may provide access to novel agents and contribute to evidence generation in this rare subgroup. A review of the literature is summarized in Table 1.

Table 1.

Comparative analysis of primary rhabdomyosarcoma of the breast cases

Characteristic	Present case	Binokay et al. [16] (2003)	Bayramoglu et al. [17] (2018)	Attili et al. [18] (2007)	Bhosale et al. [19] (2013)	Dausse et al. [20] (2005)	Varshney et al. [21] (2021)	Malik et al. [22] (2024)	Zhu et al. [23] (2023)
Age, years	14	16	12	40	60	46	12	17	17
Sex	Female	Female	Female	Female	Female	Female	Female	Female	Female
Histologic subtype	Embryonal	Alveolar	Alveolar	Embryonal	Rhabdomyosarcoma (with infiltrating ductal carcinoma)	Embryonal	Alveolar	Embryonal	Embryonal
Laterality	Left	Right	Left	Right	Left	Left	Bilateral	Right	Right
Tumor size	Largest mass: 10 cm (CT)	10 × 6 cm	45 × 20 × 40 mm	4 × 3 cm	8 × 7 cm (breast), 18 × 8 cm (axilla)	80 mm (rapid growth to this size)	Right: 3.8 × 3.5 × 3.0 cm; left: history of mastectomy	Large, replaced entire breast	Very large, “too large to measure”
Lymph node involvement	Yes (bilateral axillary, internal mammary)	Yes (axillary)	Yes (axillary)	Yes (axillary)	Yes (axillary)	Not specified	Yes (axillary)	Not specified at presentation, but axillary recurrence later	Not specified
Treatment	MAID → ICE → VAC → mastectomy → radiation (for recurrence)	Modified radical mastectomy	VAC chemo → breast-conserving mastectomy + axillary dissection → radiation	Modified radical mastectomy → chemotherapy (VAC)	Modified radical mastectomy → chemotherapy	Neoadjuvant chemo (adriamycin/ifosfamide) → quadrantectomy → brachytherapy	Bilateral modified radical mastectomy	Mastectomy → adjuvant chemoradiotherapy → recurrence	Surgical resection only (adjuvant therapy refused)
Outcome	Deceased (due to refractory/metastatic disease)	Not specified	Disease-free (34 months)	Complete remission (1 year)	Disease-free (posoperative)	Complete remission (18 months)	Lost to follow-up	Recurrence (chest wall nodules)	Refused further work-up/adjuvant therapy; outcome unknown

Characteristic	Evans [24] (1953)	Mondal et al. [25] (2014)	Yuan et al. [26] (2017)	Nogi et al. [27] (2007)	Kim et al. [28] (2017)	Herrera and Lugo-Vicente [29] (1998)	Italiano et al. [30] (2005)
Age, years	41	49	34	13	17	13	46
Sex	Female	Female	Female	Female	Female	Female	Female
Histologic subtype	Not specified (pleomorphic features)	Pleomorphic (PRMS)	Not Specified	Alveolar	Alveolar	Embryonal	Embryonal
Laterality	Left	Right	Left	Left	Right	Right	Left
Tumor size	4 × 6 × 12 cm	7 × 6.5 cm	3.5 × 3.0 cm (recurrence)	13 × 8 cm	3.1 cm (initial)	6 × 4 cm	Not specified (rapidly growing)
Lymph node involvement	Not specified	No (0/17 nodes)	Not specified	Yes (9 nodes)	No (sentinel node negative, but later axillary recurrence)	No	Not specified
Treatment	Amputation → forequarter amputation (for recurrence)	Modified radical mastectomy (no adjuvant therapy)	Segmental mastectomy → mastectomy → chemo (THP/IFO/DTIC)	Excisional biopsy → modified radical mastectomy → chemo (VAI + doxorubicin)	Nipple-sparing mastectomy → VAC/IE chemo (at recurrence)	Simple mastectomy → chemo (VAC)	Neoadjuvant chemo (AI) → quadrantectomy → radiation (brachytherapy)
Outcome	Alive with disease (supraclavicular mass) at 4 years	Disease-free (12 months)	Disease-free (30 months)	Deceased (8 months post-op)	Stable disease post-chemotherapy	Disease-free (1 year)	Not specified (implied treatment for control)

Conclusion

This case underscores the highly aggressive and refractory nature of primary embryonal rhabdomyosarcoma of the breast. Despite intensive multimodal therapy, the disease progressed relentlessly, highlighting the profound limitations of current treatment strategies. This tragic outcome emphasizes the urgent need for earlier diagnosis and the development of novel, effective therapies to improve survival for this devastating malignancy.

Statement of Ethics

Ethics Committee at Damascus University does not require ethical approval for reporting individual cases or case series. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000550115).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Ahmad Al-Bitar: collected the patient’s clinical data, reviewed the medical history, and contributed to drafting the initial version of the manuscript. Mohammad Alaa Aldakak: participated in patient data collection, contributed to literature review, and initial manuscript preparation. Maher Saifo: supervised the overall case management and manuscript development, ensured scientific accuracy, and performed the final critical review before submission. All authors have read and approved the final version of the manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.