Pleomorphic rhabdomyosarcoma with an impressive response to chemotherapy: case report and review of the literature



Pleomorphic rhabdomyosarcoma (RMS) represents a rare sarcoma subtype of the adult population. Due to its clinical characteristics, treatment is currently based on the guidelines for adult soft tissue sarcoma therapy. Hence, in the metastatic setting, doxorubicin-containing regimens are used in the sarcoma community, with limited treatment benefit. Scanty published data are available on the efficacy of systemic treatment. Whether treatment response and outcome of these patients could be improved by using pediatric protocols used typically in other RMS subtypes, like embryonal and alveolar RMS, is unclear. We report on an impressive effect of multiagent pediatric chemotherapy in an adult patient with metastatic pleomorphic RMS.


We present the case of a 70-year-old man with metastatic pleomorphic RMS of his left thigh. Systemic chemotherapy according to the VAC regimen (vincristine, actinomycin, cyclophosphamide) was initiated. Follow-up clinical and radiologic assessment demonstrated an impressive treatment response.


Sixteen months after primary diagnosis, computed tomography scan shows no signs of tumor progression.


Our case report emphasizes that multiagent systemic therapy according to pediatric protocols should be considered in adult patients with pleomorphic RMS.

Tumori 2016; 102(Suppl. 2): e57 - e60

Article Type: CASE REPORT



Attila Kollár, Rupert Langer, Codruta Ionescu, Jennifer L. Cullmann, Frank M. Klenke

Article History


Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.

This article is available as full text PDF.

Download any of the following attachments:


Rhabdomyosarcoma (RMS) accounts for approximately 3% of soft tissue sarcomas (STS) and is a common childhood malignancy. In contrast to the embryonal and alveolar variant, pleomorphic RMS occurs almost exclusively in the adult population (1). The prognosis of RMS in older patients appears to be worse. Reasons for these age-dependent differences seem to be multifactorial and include differences in the distribution of histopathologic subtypes and primary tumor sites, different chemosensitivity in older patients, and an increase in treatment toxicity with age (2).

Although the entity of pleomorphic RMS was questioned in the past due to confusing diagnostic criteria, the recent WHO classification has allocated it as a separate RMS subtype. The diagnosis is based on histomorphologic, immunohistochemical, and molecular characteristics, described by Fletcher and colleagues (3).

Pleomorphic RMS, which almost exclusively occurs in the adult population, is located most commonly at the extremities, the uterus, and in the paratesticular and head and neck regions. Further primary locations are of thoracic (thorax, heart, breast), intra-abdominal (kidney, adrenal gland, diaphragm, choledochus, liver), cutaneous, ocular, and cerebral origin. The age at diagnosis of adult pleomorphic RMS has been reported to range from 46 to 62 years and the tumors occurred predominately in males (4-5-6). In a retrospective case series by Furlong et al (6), the median age was 54 (21-81) years, 28 out of 38 patients (74%) were male, 55% of the tumors were located in the extremities, and the median tumor size at initial diagnosis was 6.8 cm (1.5-15 cm). The 5-year disease-free survival was 27%. Data on the usage of and response to chemotherapy were not reported.

The rarity of the disease and lack of clinical data makes it worthwhile to look into the clinical features, systemic treatment strategies, and disease outcomes in detail. We present a case of pleomorphic RMS of the left thigh treated according to a pediatric chemotherapy regimen. Due to multiple lung metastases, systemic therapy with vincristine, actinomycin D, and cyclophosphamide was initiated, resulting in a favorable response.

Case report

A 70-year-old man presented with a slowly growing mass of his left thigh in May 2014. Due to a minor trauma a few weeks earlier, a hematoma was suspected. His medical history included a malignant melanoma of the left calf in 1994 and an inguinal relapse 18 years later, both of which were resected, cholecystolithiasis, and dyslipidemia. Family history was negative for neoplastic diseases.

Magnetic resonance imaging (MRI) showed a large lesion of the left thigh (21 × 15 × 11 cm) with central necrosis (Fig. 1). The cranio-caudal dimension extended from the greater trochanter to the lateral retinaculum of the knee. The tumor involved multiple muscles including the vastus lateralis, the biceps femoris, and the semimembranosus. The tumor infiltrated the cutis and subcutis and invaded the femoral neurovascular bundle. Staging computed tomography scan of the chest revealed multiple bilateral pulmonary metastases. Biopsy results of the primary tumor and of one of the lung lesions showed no malignant melanoma cells, but a high-grade pleomorphic sarcoma with highly atypical spindly to polygonal cells. Positivity of immunohistochemical stains desmin, sm-actin, and myogenin confirmed the diagnosis of a pleomorphic RMS. The tumor showed a high proliferation rate of 60% assessed by Ki67 staining (Fig. 2).

Magnetic resonance imaging of left thigh (contrast-enhanced T1-weighted fatsat).

Hematoxylin & eosin and immunohistochemical staining for Ki-67 and desmin.

Due to the advanced stage of the disease and the high risk of skin perforation, systemic treatment according to the VAC regimen (vincristine, actinomycin, cyclophosphamide) was initiated immediately. Treatment consisted of 7 cycles, which were administered between June 2014 and November 2014. Overall, chemotherapy was tolerated well, clinically and hematologically; filgrastim was given as primary prophylaxis. Vincristine had to be stopped after the 4th cycle due to neurotoxicity. Due to progressing fatigue, systemic therapy was stopped after the 7th cycle. Clinical follow-up showed a rapid and marked decrease in tumor size at the primary tumor site within the first 10 weeks of treatment. The radiographic follow-up revealed a continuous response of the lung metastasis and delayed response of the primary tumor (Tab. I).

Radiologic follow-up according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Date of imaging Target lesions, cm Nontarget lesions (lung) New lesions Overall response
Primary tumor Lung metastasis Sum of target lesions
CR = complete remission; PD = progressive disease; PR = partial response; SD = stable disease.
May 2014 22 4.3 26.3 Non-CR/non-PD No -
August 2014 24 3.1 27.1 Non-CR/non-PD No SD
October 2014 20 2.6 22.6 Non-CR/non-PD No SD
January 2015 15 2 17 Non-CR/non-PD No PR

After 5 cycles of chemotherapy, the patient presented with symptoms of a grand mal epileptic seizure. Magnetic resonance imaging showed a small (1.5 cm), solitary right temporal lesion suggesting a solitary brain metastasis. Antiepileptic treatment with levetiracetam was initiated. Treatment consisted of stereotactic radiosurgery with 20 Gy applied in a single dose.

A follow-up scan in January 2015 showed a mixed response of the known lung lesions, but altogether a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (diagnosis of solitary brain lesion excluded in the RECIST evaluation) (Tab. I). Particularly, MRI of the right thigh showed a significant decrease in size of the necrotic main lesion, but an adjacent, new enhancing lesion of unknown etiology. In order to prevent further local complications in terms of immobilization and skin perforation, consolidation radiotherapy of the primary site was performed after completion of the chemotherapy. Radiotherapy was delivered in an intensity-modulated radiation therapy technique with a single fraction of 3 Gy up to a total dose of 45 Gy. After radiotherapy in early March 2015, follow-up scans of the chest and MRI of the right upper extremity were performed every 3 months. No new lesions could be verified thereafter. At the last radiologic follow-up in August 2015, 12 months after initiation of the treatment, no signs of progressive disease at the primary tumor site or the lungs were seen. The patient’s general condition remains good without tumor-associated symptoms.


To date, the existing clinical knowledge on pleomorphic RMS is mainly based on case reports and retrospective case series. The latter generally report on adult patients with RMS including clinical information on the pleomorphic variant with limited data (Tab. II) (4, 5, 7-8-9-10-11). There is only one retrospective case series, including 38 patients, which reports exclusively on clinical features and outcome of pleomorphic RMS, but excludes details on systemic therapy (6).

Retrospective series of adult/pleomorphic RMS

Reference RMS subtypes number of patients pleomorphic variant (n) median age (years) male gender (%) localized stage (%) Extremity location (%) Chemotherapy (%) Chemotherapy agent/regimen Overall response rate (%) 5-y-OS (%)
ACT = actinomycin; CYC = cyclophosphamide; DOD = dead of disease; DOX = doxorubicin; IFO = ifosfamide; MAID = mesna, doxorubicin, ifosfamide, dacarbazine; NED = no evidence of disease; RMS = rhabdomyosarcoma; VCR = vincristine.
Ferrari et al. 2003 (1) adult RMS 180 37 27 (all) 50 (pleo) 70 (pleo) 83 65 (pleo) 73 (all) 32 (pleo) nr 85 40 (all) 53.4 (pleo)
Stock et al. 2009 (4) adult RMS 57 16 62 (pleo) 56 93 65 61 DOX, VCR, CYC, IFO nr 33
Esnaola et al. 2001 (5) adult RMS 39 5 27 (all) 46 (pleo) 62 67 31 95 nr 82 31% (all) 26 (pleo)
Furlong et al. 2001 (6) pleo RMS 38 38 54 74 nr 55 nr nr nr 5-y-DFS 27%
Hawkins et al. 2001 (7) adult RMS 84 14 23 51 48 22 92 VCR, ACT, CYC, DOX, IFO nr 35
Little et al. 2002 (8) adult RMS 82 35 27 55 100 22 71 DOX or ACT with VCR, CYC 74 44
Simon et al. 2003 (9) adult RMS 39 14 45 59 95 39 56 VCR, ACT, CYC nr 35
Ogilvie et al. 2010 (10) adult RMS 11 7 49 73 55 72 100 DOX, IFO, VCR 86 55
Gerber et al. 2013 (11) adult RMS 138 16 28 57 68 22 91 VAC, DOX, VAdriCyclolfo, MAID nr 34

Accordingly, almost no data on chemotherapy sensitivity in pleomorphic RMS are available. In the pediatric population, collaborative clinical trials have shown a significant improvement in outcome when including chemotherapy in multimodality treatment concepts of localized RMS. In pediatric oncology group treatment protocols, 3-drug combination with vincristine, actinomycin, and cyclophosphamide (VAC) has been the backbone of RMS therapy. Although higher age at diagnosis seemed to be correlated with an adverse outcome in children, there is no evidence of limited treatment responsiveness to chemotherapy in adult RMS. Two studies reported an objective response rate to chemotherapy of up to 86% in adult RMS (5, 8). Ferrari and colleagues (1) reported on similar treatment response and outcome of adult RMS when treated according to pediatric regimens. However, differences in pharmacodynamics and pharmacokinetics between the adult and pediatric population often preclude adequate practicability, e.g., in terms of dosage of systemic therapy. So far, a single study has investigated the effect of chemotherapy on pleomorphic RMS in adults (10). Five patients out of 7 with pleomorphic RMS were treated with doxorubicin, ifosfamide, and vincristine in a neoadjuvant setting. Two patients had a complete response and 2 a partial response to this combined drug regimen. Nevertheless, due to limited data, no conclusions can be drawn about the ideal systemic therapy options in this sarcoma subtype. Considering the similarity of pleomorphic RMS to other STS in terms of biological characteristics and clinical behavior, chemotherapy regimens used for adult STS including doxorubicin and ifosfamide are used in the sarcoma community. This seems to be associated with a poor prognosis (5, 6). The present case report suggests that pediatric treatment protocols should be considered as a treatment option in pleomorphic RMS.

In conclusion, pleomorphic RMS represents an aggressive tumor entity of the adult population with a markedly dismal prognosis. Multidrug chemotherapy seems to be a possibility to improve treatment outcome. However, the optimal chemotherapy regimen remains to be defined.


Financial support: No financial support was received for this submission.
Conflict of interest: None of the authors has conflict of interest with this submission.
  • 1. Ferrari A Dileo P Casanova M et al. Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer 2003 98 3 571 580 Google Scholar
  • 2. Sultan I Qaddoumi I Yaser S Rodriguez-Galindo C Ferrari A Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients. J Clin Oncol 2009 27 20 3391 3397 Google Scholar
  • 3. Fletcher CDMBJ Hogendoorn P Mertens F eds. WHO Classification of Tumours of Soft Tissue and Bone (IARC WHO Classification of Tumours). 4th ed2013. Google Scholar
  • 4. Stock N Chibon F Binh MB et al. Adult-type rhabdomyosarcoma: analysis of 57 cases with clinicopathologic description, identification of 3 morphologic patterns and prognosis. Am J Surg Pathol 2009 33 12 1850 1859 Google Scholar
  • 5. Esnaola NF Rubin BP Baldini EH et al. Response to chemotherapy and predictors of survival in adult rhabdomyosarcoma. Ann Surg 2001 234 2 215 223 Google Scholar
  • 6. Furlong MA Mentzel T Fanburg-Smith JC Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. Mod Pathol 2001 14 6 595 603 Google Scholar
  • 7. Hawkins WG Hoos A Antonescu CR et al. Clinicopathologic analysis of patients with adult rhabdomyosarcoma. Cancer 2001 91 4 794 803 Google Scholar
  • 8. Little DJ Ballo MT Zagars GK et al. Adult rhabdomyosarcoma: outcome following multimodality treatment. Cancer 2002 95 2 377 388 Google Scholar
  • 9. Simon JH Paulino AC Ritchie JM Mayr NA Buatti JM Presentation, prognostic factors and patterns of failure in adult rhabdomyosarcoma. Sarcoma 2003 7 1 1 7 Google Scholar
  • 10. Ogilvie CM Crawford EA Slotcavage RL et al. Treatment of adult rhabdomyosarcoma. Am J Clin Oncol 2010 33 2 128 131 Google Scholar
  • 11. Gerber NK Wexler LH Singer S et al. Adult rhabdomyosarcoma survival improved with treatment on multimodality protocols. Int J Radiat Oncol Biol Phys 2013 86 1 58 63 Google Scholar



  •  Department of Medical Oncology, Inselspital, Bern University Hospital, Sarcoma Center, Bern - Switzerland
  •  Institute of Pathology, University of Bern, Bern - Switzerland
  •  Department of Radiation Oncology, Inselspital, Bern University Hospital, Sarcoma Center, Bern - Switzerland
  •  Institute for Diagnostic, Interventional, and Pediatric Radiology, Inselspital, University Hospital Bern, Bern - Switzerland
  •  Department of Orthopedic Surgery, Inselspital, Bern University Hospital, Sarcoma Center, Bern - Switzerland

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.