Embryonal rhabdomyosarcoma at an unusual age and in an atypical site: a case report

Abstract

Background

Rhabdomyosarcoma is classified into histologic subtypes: embryonal, alveolar, pleomorphic, spindle, and mixed-type. Embryonal rhabdomyosarcoma is mainly a disease of children. It occurs rarely in adults. When rhabdomyosarcoma is found in adults, it usually exhibits worse outcomes than in pediatric patients.

Case presentation

We present a case report of a 20-year-old Arab woman who presented with generalized musculoskeletal pain, unintended weight loss, and excessive night sweats. There was no remarkable history of medications, diseases, or surgeries. A positron emission tomography scan showed multiple osteolytic lesions with metabolic activity, as well as pleural effusion and soft tissue mass around the thoracic area. Following this, a bone marrow biopsy was performed and showed metastatic embryonal rhabdomyosarcoma according to immunochemistry stainings. Chemotherapy was started with 3 doses of vincristine, actinomycin D, and cyclophosphamide regimen for 3 months, after which a positron emission tomography scan showed a total disappearance of the soft tissue mass, but revealed metabolic activity of new foci. Therefore, the patient took another 3 doses of the vincristine, actinomycin D, and cyclophosphamide regimen, and received a total of 30 Gy of radiotherapy on the new foci.

Conclusion

This paper describes a case of a patient diagnosed with adult rhabdosmyosarcoma at an uncommon age and in an uncommon site; therefore, it is important to consider rhabdomyosarcoma in the differential diagnosis of patients given an abnormal presentation and unexplained findings. Early detection of the disease, which is difficult with nonspecific symptoms, is crucial for improving outcomes.

Introduction

Rhabdomyosarcoma (RMS) is a prevalent soft tissue sarcoma among pediatric patients [1]. It has a comparatively rare occurrence in adults, constituting less than 1% of all malignancies and only 3% of adult soft tissue sarcomas. RMS is currently classified into embryonal RMS, alveolar RMS, and pleomorphic RMS [2]. Embryonal rhabdomyosarcoma (ERMS) is a primitive, malignant soft tissue tumor that mimics the phenotype and biology of embryonic skeletal muscle [3]. ERMS represents the most common type of RMS, accounting for 60% of all rhabdomyosarcomas and 4–6% of all childhood malignancies [4]. Prognosis of ERMS is determined by stage, histological classification, age, and site of origin [3]. Despite similar rates of regional and distant spread, adults with RMS consistently exhibit significantly worse outcomes than pediatric patients. Atypical presentation of adult RMS results in delayed diagnosis of the disease. About 15% of RMS cases are metastatic at diagnosis [5]. Furthermore, adult RMS tumors are more likely to be located in less favorable anatomic sites and to demonstrate different histological subtypes [6]. Symptoms of RMS can be local, which are caused by mass lesions. However, there are other diverse, nonspecific clinical manifestations that can lead to misdiagnosis [7]. The treatment of adult rhabdomyosarcoma is like that of pediatric rhabdomyosarcoma, but the prognosis is generally worse due to the advanced stage at which adult cases are often diagnosed [8]. Responses to the current treatment guidelines of the Intergroup Rhabdomyosarcoma Study Group (IRS) multimodal therapy (MMT) for children are less favorable in adults compared with children [9]. In this study, we describe a rare case of thoracic embryonal rhabdomyosarcoma in an Arab young adult, presenting with generalized musculoskeletal pain and systemic symptoms.

Case presentation

A 20-year-old Arab woman was admitted to our hospital; she was suffering from generalized musculoskeletal pain for 2 months. The pain, initially intermittent, became persistent, and was exacerbated with physical activity and relieved with analgesics. It was most severe in the lumbar spine, right shoulder, and middle of the sternum, spreading to the lower extremities with morning stiffness for about an hour. The complaint was accompanied by constitutional symptoms: unintended weight loss of about 10 kg within 2 months, along with excessive night sweats without fever or chills, and exertional dyspnea after approximately walking 100 m. There was no remarkable history of medications, diseases, or surgeries. On physical examination we noticed conjunctival pallor, palpated two nodules in the right breast—in the upper lateral quadrant and another in the upper inferior medial quadrant—and nodules of different sizes in the left breast. Along with tenderness in the lumbar vertebrae (L1–L5) and sternum, with the patient’s inability to comb her hair. Breath sounds were low in the left lung. Our patient upon admission was alert, responsive, and oriented; all vital signs were normal and laboratory tests upon admission are presented in Table 1. Abdomen and pelvic ultrasound (US) revealed hepatomegaly (19 cm) and splenomegaly (670 cm³) while breast US showed a suspicious soft mass between the left breast edge and thoracic wall in the medial inferior region, prominent from the thoracic wall (5 cm). The patient was further advised for computed tomography (CT) with intravenous contrast, which showed nodular densities in the right and left breasts, which may indicate fibroadenoma. In addition to left subclavicular lymphadenopathy (1.5 cm) and peri internal thoracic artery lymphadenopathy (1 cm). Osteolytic foci were observed in the middle of the sternum and in the body of many lumbar vertebra (Fig. 1). Lumbar magnetic resonance imaging (MRI) showed degenerative changes in the bodies of the lumbar vertebrae lumbar (L) vertebrae L1–L4 consistent with bone metastases (Fig. 2). A positron emission tomography (PET) scan displayed bilateral pleural effusion with multi osteolytic foci that showed a metabolic activity standardized uptake value (SUV) 7–3 with spindle shaped soft tissue mass around the anterior arch of left third rib (3 cm × 6 cm) and sternum, as well as a soft tissue mass around thoracic vertebra (T) T12 and T11. It also revealed nodules behind the diaphragm, retroperitoneal, and right ileum (20 mm) with activity SUV 6, along with hepatomegaly and splenomegaly without metabolic activity (Fig. 3). Bone marrow aspiration revealed hypercellularity of bone marrow owing to age. The marrow was infiltrated with monotonous cells with abundant blue cytoplasm containing vacuoles and fine chromatin—the three cell stains are suppressed. There were aggregates of some unspecified cells (metastatic, malignant small round blue cell tumor) (Fig. 4). Moreover, bone marrow biopsy was done owing to to bicytopenia, which showed metastatic embryonal rhabdomyosarcoma with immunochemical staining positive for myogenin and desmin, and negative for WT-1 and CD30. The patient’s karyotype showed a translocation between chromosome 2 and 15 46XX, t(2;15) (Fig. 5). Eventually, we performed flow cytometry to rule out an acute disease and also showed no evidence of leukemia or lymphoma in the peripheral blood. The patient was put on a polychemotherapy regimen (vincristine, actinomycin, and cyclophosphamide) (VAC regimen) according to Table 2, along with 4 g of mesna as a continuous intravenous infusion for 24 hours to reduce the risk of hemorrhagic cystitis related to cyclophosphamide. This regimen was given monthly for 3 continuous months, before a PET scan evaluation was done which showed almost total disappearance of the soft tissue mass and pleural effusion but also revealed metabolic activity of new foci (metabolic activity SUV 9–5) localized in the lower third of the right thigh, in addition to scattered foci in the body of the right thigh; the neck of the left thigh; the right ileum and the wing of the sacrum; thoracic (T) T12 and L5; and the right humeral head. So the patient completed another three doses of VAC regimen (one dose each month) before receiving a total of 30 Gy of radiotherapy for the left hip and right knee, with ten sessions dedicated to each area.

Table 1 Laboratory tests upon patient’s arrival

Fig. 1

Transverse computed tomography showing a swollen lytic focus in the middle third of the sternum with a slightly displaced fracture

Fig. 2

Lumbar magnetic resonance imaging showing degenerative changes in the bodies of the lumbar vertebrae consistent with bone metastases

Fig. 3

Positron emission tomography scan showing pathological metabolic activity with values ranging between 3 and 7 SUV with a fusiform shaped soft tissue mass around the anterior arch of the left third rib, extending 3 cm × 6 cm around the middle of the sternum

Fig. 4

Bone marrow aspiration showing infiltration by monotonous cells with abundant blue cytoplasm containing vacuoles and fine chromatin (small round blue cells)

Fig. 5

Patient’s karyotype 46, XX, t(2;15) 100%. The two red arrows indicate the translocation between chromosome 2 and chromosome 15

Table 2 Showing the process of giving the VAC regimen

Discussion and conclusion

RMS is primarily a pediatric disease. However, adult cases have been reported in the literature, but diagnosis is often delayed owing to atypical presentations [4, 10]. Predominant sites of origin for ERMS include the head and neck region and the genitourinary system [11]. ERMS can also arise in other anatomical sites, including the biliary tract, retroperitoneum, pelvis, perineum, and abdomen. Moreover, involvement of visceral organs, such as the liver, kidney, heart, and lungs, has been documented [3]. RMS is more likely to present with systemic symptoms and less likely to have a localized mass compared with pediatric cases [10]. Our patient first presented to the clinic with nonspecific systemic symptoms such as generalized musculoskeletal pain and weight loss.

On immunochemistry stainings, positivity of skeletal muscle differentiation markers is seen in ERMS. The most frequently used diagnostic marker is desmin. Other markers include myogenin and MYO-D1 [3]. Our patient’s immunochemistry staining of metastasis markers aligns with the diagnosis of ERMS. We avoided biopsy and surgical removal of the primary tumor (left third rib and sternum) owing to its sensitive anatomical location near the mediastinum.

RMS in adults has significantly worse 5-year overall survival rates than in children, and is more likely to be found in unfavorable sites [6].

Our case is rare, given our patient’s age and tumor site. The incidence of ERMS is 9% of all chest wall sarcomas [12]. A case of chest wall ERMS arising from the rib of an 8-year-old girl, with a good response to VAC (vincristine, actinomycin D, and cyclophosphamide) regimen chemotherapy, has been reported [13].The treatment of adult rhabdomyosarcoma is like that of pediatric rhabdomyosarcoma, but the prognosis is generally worse due to the advanced stage at diagnosis. Some studies describe more expression of multidrug-resistance proteins in adult RMS than in childhood patients [8]. Another case of sclerosing rhabdomyosarcoma (SRMS) in the chest wall of a 26-year-old woman has been described [14]. Some studies suggest a cytogenic link between SRMS and ERMS [15].

Intrabdominal and pelvic RMSs have also been reported in the literature as rare anatomical sites for adult EMRS [16,17,18].

Moreover, the differences in pathogenesis, in addition to the doubts of considering chemotherapy in the treatment of rhabdomyosarcoma contribute to the poor prognosis that is still seen in adult RMS [19]. Optimal management of RMS remains challenging. Standard treatments for RMS include chemotherapy, radiotherapy, and surgical removal of tumor. The standard chemotherapy regimen for the treatment of RMS is the combination of vincristine, actinomycin, and cyclophosphamide/ifosfamide [20]. Current guidelines align with the IRS MMT for children, which has significantly improved long-term survival [10]. Small studies suggest that chemotherapy responders have better metastasis-free survival [9]. Doxorubicin-based regimens and ifosfamide have shown reduced recurrence and improved prognosis in localized resectable soft-tissue sarcoma [21]. The VAC regimen that was used to treat our patient is the standard combination chemotherapy for pediatric RMS in adolescent/young adult (AYA) patients and older RMS patients [22]. This combination chemotherapy has no significant differences in response rates among AYA and older patients with RMS. In a randomized trial that compared the IVA (ifosfamide, vincristine, and actinomycin D) regimen with the VAC regimen, no significant differences in clinical outcomes were observed [10]. In the case of localized tumor, most cases can be cured, while the outcomes remain poor in patients with metastatic or recurrent disease. Our patient was put on VAC regimen (one dose monthly for 3 months) then a PET scan was performed, which revealed total disappearance of the soft tissue mass and but also showed metabolic activity of new foci; therefore, radiotherapy was added for another three VAC regimen doses.

RMS is rare in adults and has a less favorable response to treatment, compared with pediatric patients. Patients can present with misleading clinical signs and symptoms, as well as atypical tumor locations, which might result in misdiagnosis. This case report highlights the importance of considering rhabdomyosarcoma in the differential diagnosis of adult patients with unexplained musculoskeletal pain, systemic symptoms, and abnormal physical findings, even with the lack of clear risk factors. Early diagnosis and appropriate treatment are crucial for improving outcomes in this rare disease. Developing systemic treatments, which have better oncological outcomes with long-term safety, is crucial for patients with RMS.