Rhabdomyosarcoma in childhood and adolescence: Clinical presentation, diagnostic evaluation, and staging
- M Fatih Okcu, MD, MPH
M Fatih Okcu, MD, MPH
- Professor of Pediatrics
- Baylor College of Medicine
- John Hicks, MD, DDS, PhD
John Hicks, MD, DDS, PhD
- Department of Pathology
- Baylor College of Medicine
- Section Editors
- Alberto S Pappo, MD
Alberto S Pappo, MD
- Section Editor — Pediatric Oncology
- Head of Solid Malignancies Program
- St. Jude Children's Research Hospital
- Thomas F DeLaney, MD
Thomas F DeLaney, MD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Radiation Oncology
- Harvard Medical School
Sarcomas are rare malignant tumors that can arise from mesenchymal tissue at any body site. The histopathologic spectrum of sarcomas is broad, presumably because the embryonic mesenchymal cells from which they originate have the capacity to mature into striated skeletal and smooth muscle, adipose and fibrous tissue, bone, and cartilage.
Rhabdomyosarcomas (RMS) are thought to originate from immature cells that are destined to form striated skeletal muscle; however, these tumors can arise in locations where skeletal muscle is not typically found (eg, the urinary bladder).
Undifferentiated sarcomas derive from mesenchyme that cannot be ascribed to a specific tissue lineage. As such, they are now grouped with non-rhabdomyosarcomatous soft tissue sarcomas  and will not be discussed further in this review.
The treatment of RMS has evolved considerably over the past several decades. Cure rates have risen, largely due to the increasingly intensive, multimodality therapeutic protocols that have been developed by large international cooperative groups, such as the Intergroup Rhabdomyosarcoma Study Group (IRSG). The IRSG has now become the Soft Tissue Sarcoma Committee of the Children's Oncology Group (COG), and the designation IRS is no longer used for cooperative group trials.
This topic review will cover the clinical presentation, diagnostic evaluation, staging, and risk stratification for purposes of treatment selection among patients with RMS. The epidemiology, pathology, molecular pathogenesis, and specific issues related to treatment are discussed elsewhere, as are primary tumors of bone and other soft tissue neoplasms arising in children as well as adults. (See appropriate topic reviews.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Fletcher CDM, Chibon F, MErtens F. Undifferentiated/unclassified sarcomas. In: WHO Classification of Tumours of Soft Tissue and Bone, Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (Eds), IARC, Lyons 2013. p.236.
- Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 1988; 61:209.
- Maurer HM, Gehan EA, Beltangady M, et al. The Intergroup Rhabdomyosarcoma Study-II. Cancer 1993; 71:1904.
- Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1995; 13:610.
- Stevens MC, Rey A, Bouvet N, et al. Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence: third study of the International Society of Paediatric Oncology--SIOP Malignant Mesenchymal Tumor 89. J Clin Oncol 2005; 23:2618.
- Months SR, Raney RB. Rhabdomyosarcoma of the head and neck in children: the experience at the Children's Hospital of Philadelphia. Med Pediatr Oncol 1986; 14:288.
- Hicks J, Flaitz C. Rhabdomyosarcoma of the head and neck in children. Oral Oncol 2002; 38:450.
- Shapiro E, Strother D. Pediatric genitourinary rhabdomyosarcoma. J Urol 1992; 148:1761.
- Lawrence W Jr, Hays DM, Moon TE. Lymphatic metastasis with childhood rhabdomyosarcoma. Cancer 1977; 39:556.
- Lawrence W Jr, Gehan EA, Hays DM, et al. Prognostic significance of staging factors of the UICC staging system in childhood rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS-II). J Clin Oncol 1987; 5:46.
- Wiener ES, Anderson JR, Ojimba JI, et al. Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma? Semin Pediatr Surg 2001; 10:146.
- Rodeberg DA, Garcia-Henriquez N, Lyden ER, et al. Prognostic significance and tumor biology of regional lymph node disease in patients with rhabdomyosarcoma: a report from the Children's Oncology Group. J Clin Oncol 2011; 29:1304.
- Raney RB Jr, Tefft M, Maurer HM, et al. Disease patterns and survival rate in children with metastatic soft-tissue sarcoma. A report from the Intergroup Rhabdomyosarcoma Study (IRS)-I. Cancer 1988; 62:1257.
- Koscielniak E, Rodary C, Flamant F, et al. Metastatic rhabdomyosarcoma and histologically similar tumors in childhood: a retrospective European multi-center analysis. Med Pediatr Oncol 1992; 20:209.
- Ruymann FB, Newton WA Jr, Ragab AH, et al. Bone marrow metastases at diagnosis in children and adolescents with rhabdomyosarcoma. A report from the intergroup rhabdomyosarcoma study. Cancer 1984; 53:368.
- Breneman JC, Lyden E, Pappo AS, et al. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV. J Clin Oncol 2003; 21:78.
- Weiss AR, Lyden ER, Anderson JR, et al. Histologic and clinical characteristics can guide staging evaluations for children and adolescents with rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee. J Clin Oncol 2013; 31:3226.
- McCarville MB, Christie R, Daw NC, et al. PET/CT in the evaluation of childhood sarcomas. AJR Am J Roentgenol 2005; 184:1293.
- Klem ML, Grewal RK, Wexler LH, et al. PET for staging in rhabdomyosarcoma: an evaluation of PET as an adjunct to current staging tools. J Pediatr Hematol Oncol 2007; 29:9.
- Völker T, Denecke T, Steffen I, et al. Positron emission tomography for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol 2007; 25:5435.
- Ben Arush MW, Bar Shalom R, Postovsky S, et al. Assessing the use of FDG-PET in the detection of regional and metastatic nodes in alveolar rhabdomyosarcoma of extremities. J Pediatr Hematol Oncol 2006; 28:440.
- Peng F, Rabkin G, Muzik O. Use of 2-deoxy-2-[F-18]-fluoro-D-glucose positron emission tomography to monitor therapeutic response by rhabdomyosarcoma in children: report of a retrospective case study. Clin Nucl Med 2006; 31:394.
- Dharmarajan KV, Wexler LH, Gavane S, et al. Positron emission tomography (PET) evaluation after initial chemotherapy and radiation therapy predicts local control in rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 2012; 84:996.
- Kawasaki H, Takayama J, Nagasaki K, et al. Hypercalcemia in children with rhabdomyosarcoma. J Pediatr Hematol Oncol 1998; 20:327.
- Fiegl M, Weltermann A, Stindl R, et al. Massive disseminated intravascular coagulation and hyperfibrinolysis in alveolar rhabdomyosarcoma: case report and review of the literature. Ann Hematol 1999; 78:335.
- Crist WM, Garnsey L, Beltangady MS, et al. Prognosis in children with rhabdomyosarcoma: a report of the intergroup rhabdomyosarcoma studies I and II. Intergroup Rhabdomyosarcoma Committee. J Clin Oncol 1990; 8:443.
- Rodary C, Gehan EA, Flamant F, et al. Prognostic factors in 951 nonmetastatic rhabdomyosarcoma in children: a report from the International Rhabdomyosarcoma Workshop. Med Pediatr Oncol 1991; 19:89.
- La Quaglia MP, Heller G, Ghavimi F, et al. The effect of age at diagnosis on outcome in rhabdomyosarcoma. Cancer 1994; 73:109.
- Crist WM, Anderson JR, Meza JL, et al. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol 2001; 19:3091.
- Raney RB, Anderson JR, Barr FG, et al. Rhabdomyosarcoma and undifferentiated sarcoma in the first two decades of life: a selective review of intergroup rhabdomyosarcoma study group experience and rationale for Intergroup Rhabdomyosarcoma Study V. J Pediatr Hematol Oncol 2001; 23:215.
- Williamson D, Missiaglia E, de Reyniès A, et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol 2010; 28:2151.
- CLINICAL PRESENTATION
- Presentation by anatomic site
- - Head and neck
- - Genitourinary tract
- - Extremities
- - Other
- Regional nodes
- Distant metastases
- INITIAL DIAGNOSTIC AND STAGING EVALUATION
- Diagnostic biopsy
- Staging evaluation
- - Radiographic imaging of the primary site
- - Metastatic workup
- - Laboratory studies
- - Lumbar puncture
- - Lymph node assessment
- STAGING AND PROGNOSTIC STRATIFICATION
- Clinical group
- TNM system
- Prognostic stratification scheme for risk-adapted therapy