Perianal Rhabdomyosarcoma Mimicking Perianal Abscess: Case Report and Literature Review.

Introduction
Rhabdomyosarcoma [1] is a common soft tissue sarcoma in pediatrics that accounts for <1% of adult soft tissue malignancies [2]. Although the incidence of this condition decreases with increasing age, older age is associated with significantly poorer survival outcomes. RMS is histologically classified into four subtypes (embryonal, alveolar, spindle cell/sclerosing, and pleomorphic), each distinguished by its unique clinical presentation and molecular features [3]. Among RMS subtypes, embryonal rhabdomyosarcoma (ERMS) predominates in younger children and typically presents in head, neck, and genitourinary regions [4]. ERMS exhibits a bimodal age distribution, with a primary peak between birth and 5 years and a smaller secondary peak during adolescence [5]. However, primary involvement of the perianal/perineal region in adults remains rare, with only a few reported cases [6–8]. ERMS exhibits less aggressive clinical course than the alveolar subtype, but adults’ presentation of ERMS may still present significant diagnostic and therapeutic challenges [9]. Definitive diagnosis of RMS relies on histopathology and immunohistochemical (IHC) analysis [10]. Moreover, the absence of PAX3-FOXO1 fusion gene that is detectable by fluorescence in situ hybridization is a signature of alveolar subtype [11]. In this study, we aimed to present an adult patient with ERMS and explore the diagnostic challenges and surgical management considerations of primary perianal/perineal RMS in adults. This case report adheres to the CARE guidelines [12] (CARE checklist available as online suppl. material at https://doi.org/10.1159/000550387).

Presentation of Case
A 26-year-old Persian woman with a history of breast cancer presented with a perianal mass. The patient was unmarried, had no history of tobacco or alcohol use, and reported a negative family history for cancer. She had a BMI of 23 and did not mention any menstrual irregularity. Symptoms had begun 4 months prior, and she had undergone multiple drainage procedures for presumed perianal abscesses. However, due to the lack of improvement, she was referred to our institution for further evaluation. The patient was stable with vital signs within normal limits. A 7-cm wound lesion was observed, located from the 4 o’clock to the 9 o’clock position in the posterior perineum. The lesion exhibited purulent and bloody discharge, and several scars were noted in the perianal region. Importantly, the rectal mucosa and anal sphincters remained intact. The abdomen was soft and non-tender. The patient’s medical history was significant for breast cancer diagnosed 8 years prior. She had undergone a partial mastectomy followed by 8 cycles of chemotherapy and 32 courses of radiation therapy. Laboratory tests were performed as part of the initial workup and were mostly within normal limits, with the exception of mild hypochromic anemia.
To further investigate the lesion, a computed tomography (CT) scan was performed, which revealed a lobulated mass (105 × 84 mm) with soft tissue density in the perineal area (Fig. 1). Due to the refractory nature of the lesion, a biopsy was performed, and histopathological analysis revealed malignant small round cells consistent with alveolar rhabdomyosarcoma. Following the discussion of the case in multidisciplinary tumor board, the patient was treated with six cycles of neoadjuvant chemotherapy, which included vincristine 1.5 mg/m2 intravenous [7], dactinomycin (actinomycin D) 0.045 mg/kg IV, cyclophosphamide 1,500 mg/m2 IV. Preoperative magnetic resonance imaging revealed multiple nodules in the posterior perianal region, with the largest measuring 18 × 30 mm (Fig. 2). These nodules extended into the bilateral gluteal clefts and ischioanal spaces.
The patient underwent an extended local resection under general anesthesia. The 75 × 30 mm perianal mass (reduced from 105 × 84 following neoadjuvant chemotherapy), classified as TNM stage T2bN0M0 and Intergroup Rhabdomyosarcoma Study (IRS) group 1, located less than 1 cm from the anal verge at the 4 o’clock position, was excised in its entirety. All suspicious tissue, including the posterior aspect of the external anal sphincter, was resected and the circumferential resection margin was 1 cm, except at the 4 o clock position, where it was 2 mm. Intersphincteric plane was not entered (Fig. 3.). Pathological examination revealed clear surgical margins, with no evidence of perineural or lymphovascular invasion. Histologically, the tumor demonstrated the classic features of ARMS, characterized by nests of small round to oval cells with hyperchromatic nuclei and scant cytoplasm, separated by fibrous septa, giving an alveolar appearance. IHC staining was strongly positive for myogenin and MyoD1 (Fig. 4): Tumor cells display strong nuclear staining for myogenin and MyoD1, confirming rhabdomyoblastic differentiation consistent with alveolar rhabdomyosarcoma).
The patient was discharged on postoperative day 10. Due to the high risk of recurrence associated with RMS, 4 weeks after surgery, she underwent six cycles of adjuvant chemotherapy, consisting of vincristine (1.4 mg/m2), cyclophosphamide (1.5 g/m2), and dactinomycin (0.045 mg/kg). At the 6-month follow-up, the patient remained asymptomatic, with no evidence of disease recurrence on imaging.

Discussion
RMS is the most prevalent soft tissue sarcoma in pediatrics and adolescents, accounting for approximately 50% of all cases [2]. There is a sex disparity in RMS incidence, with males being more affected than females with a rate ratio of 1.37 [13]. Primary ERMS most commonly occurs in the head and neck, whereas primary ARMS typically arises in extremities [4]; however, the perianal region is a rare site of occurrence. In this study, we reviewed 24 case reports of adolescent and young adult patients with RMS (14 cases of ARMS and 10 cases of ERMS) in the perianal/perineal region (Table 1).
Although RMS exhibits morphological features characteristic of skeletal muscle, it can potentially occur in the sites where skeletal muscle is not normally found, supporting the notion that the cell of origin of RMS tumor is not completely identified [3]; however, it is suggested that disruption in the growth or differentiation of multipotent mesenchymal stem cells may be responsible for the development of this malignancy [5, 29]. Although RMS lacks a specific genetic pattern, studies have shown that ERMS tumor cells often exhibit allelic loss at chromosome 11p15.5, along with upregulation of PAX7 expression, a gene that is normally expressed by myogenic satellite cells [9, 11]. Furthermore, specific translocations at the loci of the PAX3 and/or PAX7 genes have been identified as being associated with the occurrence of ARMS [11]. Imataki et al. [16] presented a case of perineal ARMS who was positive for PAX3-FOXO4 fusion gene, although all of the other ARMS cases with genetic evaluation were positive for PAX3-FOXO1.
Adolescent and young adult [30] RMS outcomes are significantly worse than those in children [31]. A large recent study involving 1977 soft tissue sarcomas found 5‐year event‐free survival for AYAs of 44–53% versus 68–78% in children and 5‐year OS 52–57% versus 78% in children [32]. Poorer outcomes in older patients are associated with several adverse factors, including larger tumors (≥5 cm), alveolar histology (FOXO1 fusion-positive), nodal involvement, and metastatic spread [33, 34]. A. Ferrari et al. [32] reported that AYAs presented with metastatic disease at diagnosis in 24% versus 11% in children and more unfavorable histology (46% vs. 26%) [32]. These factors contribute to the increased risk of recurrence and reduced survival seen in this age group. Factors associated with poor prognosis in our case are advanced age, tumor size ≥5 cm, and alveolar histology; On the other hand, absence of lymph node involvement and metastasis are suggestive of better prognosis. Considering these prognostic factors, it is important to monitor this case closely for any potential recurrence.
RMS may be asymptomatic in early stages of disease or present as a painless mass. In symptomatic patients, clinical manifestations depend on the tumor’s location and are usually related to mass effect or secondary complications. Koivusalo et al. [7] reported cases that highlight how perianal RMS can initially mimic a perianal abscess, leading to delayed diagnosis and treatment.
Imaging studies are typically performed for further investigation of a primary tumor. Although RMS appears largely nonspecific in magnetic resonance imaging, cross-sectional imaging characterizes primary tumor and regional lymph nodes, which show intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-weighted images. Evaluation of pulmonary nodules in metastatic disease can be performed using CT scan [35]. Positron emission tomography [36] scan and F-18 fluorodeoxyglucose PET/CT have the ability to detect metastatic lesions and play an important role in staging and predicting outcomes in RMS patients [37].
Open biopsy or core needle biopsy provide tissue samples for histopathological and IHC analysis, which are widely used as valuable diagnostic tools. Under the light microscopy, malignant rhabdomyoblasts of ERMS appear spindle-shaped with eosinophilic cytoplasm and round to oval eccentric nuclei in a background of densely cellular areas adjacent to loose myxoid areas [2, 38]. ARMS histologically exhibits nests of cells with round nuclei separated by fibrous septa, giving it an alveolar appearance [39].
The number of IHC markers has increased due to a better understanding of disease pathophysiology, and these markers are essential for the diagnosis of RMS cases. MyoD1, a myogenic regulatory protein, has a sensitivity of 97% and a specificity of 91% for RMS [10]; However, Fulciniti et al. [40] reported a case of vulvar ARMS that was negative for MyoD1 and the diagnosis of ARMS was made based on positive IHC for vimentin, caldesmon, and desmin, along with cytopathologic findings. Similarly, myogenin, another intranuclear transcription factor, shows a sensitivity of 97% and a specificity of 90% for RMS [10].
With new treatment strategies, the outcomes of RMS patients have improved over the years; however, this improvement is mostly due to better outcomes in low-risk RMS. A combination of chemotherapy, surgical resection, and radiotherapy is performed for RMS patients. VAC (vincristine, actinomycin D, and cyclophosphamide) or IVA (isofosfamide, vincristine, and actinomycin D) remained the standard chemotherapy regimen for RMS in recent decades [36, 41]. A trial of metastatic RMS reported that high-dose chemotherapy led to more severe toxicities, although it failed to improve outcomes [1]. Complete resection of primary tumor is preferred, except there is a serious morbidity [42]. Radiotherapy is recommended for all patients with RMS, except those who have undergone a negative-margin resection [43]. Preoperative radiotherapy may also have some advantages, such as decreasing radiation exposure to the non-tumor tissues. Additionally, as irradiated tissue is subsequently resected, the risk of developing secondary malignancy in the area may be lower theoretically. However, preoperative tumor may be more resistant to radiotherapy [44]. As the tumor in our case was surgically resectable with clear margins, neoadjuvant radiotherapy was not included in her treatment protocol.

Conclusion
This case highlights the diagnostic challenges posed by perianal RMS, which can mimic more common benign conditions like perianal abscesses. Despite the tumor’s rarity, this case underscores the importance of maintaining a high index of suspicion in patients with refractory perianal lesions. Early biopsy and prompt treatment, including neoadjuvant chemotherapy and surgical excision with adequate margins, are essential for improving prognosis.

Statement of Ethics
This study was conducted in accordance with the Declaration of Helsinki. The study protocol was reviewed, and the requirement for ethics approval was waived by the Iran University of Medical Sciences (Firoozgar Hospital), Tehran, Iran. Written informed consent for publication of the clinical details and any accompanying images was obtained from the patient. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.

Conflict of Interest Statement
The authors declare no conflicts of interest.

Funding Sources
This case report is not funded.

Author Contributions
Conceptualization: M.S. and S.H.M. Methodology: S.H.M., and A.M. Investigation/data curation: M.S., A.A.G., B.M., and M.P. Pathology/validation: A.M. Surgery/resources: S.H.M. Visualization: A.M. and M.S. Writing – original draft: M.S. and B.M. Writing – review and editing: all authors. Supervision and guarantor: S.H.M.