You are in: eMedicine Specialties > Pediatrics: Surgery > General Surgery Rhabdomyosarcoma: Surgical PerspectiveArticle Last Updated: Feb 21, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Holly L Neville, MD, Assistant Professor of Clinical Surgery, Division of Pediatric Surgery, University of Miami Miller School of Medicine Holly L Neville is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Pediatric Surgical Association, and Association of Women Surgeons Coauthor(s): Richard Andrassy, MD, Denton A Cooley, MD Chair and Professor, Department of Surgery, University of Texas at Houston Health Science Center; Chief, Section of Pediatric Surgery, MD Anderson Cancer Center; Chief Surgeon, Department of Surgery, Memorial-Hermann Hospital Editors: Diana Farmer, MD, Associate Professor, Departments of Clinical Surgery, Pediatrics, Obstetrics, Gynecology and Reproductive Services, Division of Pediatric Surgery and the Fetal Treatment Center, University of California at San Francisco; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Nicholas A Shorter, MD, Professor of Clinical Surgery and Clinical Pediatrics, State University of New York-Downstate University; Division Chief, Department of Surgery, Division of Pediatric Surgery, State University of New York-Downstate Medical Center; H Biemann Othersen Jr, MD, Professor of Surgery and Pediatrics, Emeritus Head, Division of Pediatric Surgery, Medical University of South Carolina; Marleta Reynolds, MD, Professor of Surgery, Feinberg School of Medicine, Northwestern University; Interim Head, Division of Pediatric Surgery, Department of Surgery, Children's Memorial Hospital of Chicago Author and Editor Disclosure Synonyms and related keywords: rhabdomyosarcoma, pediatric rhabdomyosarcoma, rhabdomyosarcoma in children, soft tissue sarcomas, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, botryoid rhabdomyosarcoma, spindle cell rhabdomyosarcoma, undifferentiated rhabdomyosarcoma, p53 mutation, Li-Fraumeni syndrome, p53 gene, bony sarcomas, leukemia, brain neoplasms, adrenal neoplasms, maternal premenopausal breast cancer, neurofibromatosis type I, Beckwith-Wiedemann syndrome INTRODUCTIONSection 2 of 12
  Rhabdomyosarcoma is a malignancy that arises from embryonic mesenchymal cells that possess the potential to develop into skeletal muscle. History of the ProcedureThis clinical entity was first described in the English literature in 1937. Prior to the evolution of multimodal treatment of malignancies and the development and recognition of effective chemotherapeutic agents, the primary therapy for pediatric rhabdomyosarcoma was surgical excision. Unfortunately, this purely surgical approach was often unsuccessful and, even when curative, proved to be quite morbid. Formal investigations of the treatment of pediatric rhabdomyosarcoma have subsequently been carried out through the Intergroup Rhabdomyosarcoma Study (IRS) Group and have consisted of IRS-I from 1972-1978, IRS-II from 1978-1984, IRS-III from 1984-1991, IRS-IV from 1991-1997, and IRS V from 1997-2003. Current investigations are underway with IRS-VI. The formation of the IRS Group has allowed accrual of data in sufficient numbers for this uncommon tumor, which has led to improved therapy and survival. Treatment, once purely surgical, is now multimodal with conservative surgical resection, biopsy only, or surgical staging. ProblemApproximately 50% of soft tissue sarcomas in children are rhabdomyosarcomas. Although most frequently diagnosed in the head and neck or genitourinary system, rhabdomyosarcomas may occur anywhere in the body. Five subtypes of rhabdomyosarcoma have been described; however, most fall into one or two major subtypes, embryonal and alveolar. Other subtypes include botryoid, spindle cell, and undifferentiated. FrequencyRhabdomyosarcoma is the third most common solid malignancy outside the central nervous system in the pediatric population and accounts for 5-15% of such cases. Approximately 250 new cases of pediatric rhabdomyosarcoma are diagnosed in the United States each year. EtiologyThe etiology of pediatric rhabdomyosarcoma is unknown; however, rhabdomyosarcoma has been associated with a p53 mutation and Li-Fraumeni syndrome. Li-Fraumeni syndrome is a familial cancer syndrome, which exhibits autosomal dominant inheritance of a germline mutation of the p53 gene. This syndrome is characterized by a high incidence of soft tissue or bony sarcomas, leukemia, brain or adrenal neoplasms, and maternal premenopausal breast cancer. Rhabdomyosarcoma also is known to occur more commonly in patients with neurofibromatosis type I and in patients with Beckwith-Wiedemann syndrome. PathophysiologyFive variants of rhabdomyosarcoma are described in the international classification of rhabdomyosarcoma. Embryonal variant occurs most commonly and usually is found in the head and neck, genitourinary tract, or orbit. This subtype is characterized by a loss of heterozygosity at the 11p15.5 locus, the region of the IGFII gene. The alveolar variant has a translocation involving the PAX3 locus, between the long arm of chromosome 2 and the long arm of chromosome 13. This involves the PAX3 gene and the FKHR gene. Alveolar rhabdomyosarcoma usually is encountered in the extremities, trunk, or perineum. Although once thought to be a poor prognostic indicator, one review did not distinguish the alveolar subtype as a significant prognostic indicator in extremity rhabdomyosarcoma (Neville, 2000). PAX3-FKHR and PAX7-FKHR gene fusions have recently been shown to have a prognostic implication in patients with metastatic disease. It appears that, among gene fusion positive patients with the alveolar variant, the PAX3-FKHR gene fusion is an independent adverse prognosticator while the PAX7-FKHR gene fusion correlates with an improved prognosis. Gene fusion negative cases of alveolar histology appear to have an intermediate outcome in comparison to the gene fusion groups. The botryoid variant, named because of its gross resemblance to a cluster of grapes, arises in cavitary structures such as the vagina and bladder and is found more frequently in infants. Spindle cell rhabdomyosarcoma, found most commonly in the paratesticular area, is another variant of the embryonal histology. ClinicalClinical presentation varies by site of presentation. Most present as painless masses, often discovered after minor trauma. Importantly, tumors originating in the head and neck may present as a mass or as signs and symptoms of central nervous system involvement from intracranial extension of the tumor or infiltration of the cranial nerves, meninges, or brain stem. The differential diagnosis of a painless mass in a child should include benign masses such as lipoma, neurofibroma, or even hematoma. However, the differential diagnosis of any new or persistent mass must include soft tissue sarcoma. INDICATIONSSection 3 of 12
Any child with a suspected rhabdomyosarcoma requires tissue diagnosis confirmation and surgical staging. Thus, early surgical consultation is mandatory. The surgeon then helps determine, based on the location and stage of the tumor, how best to proceed. In general, a small resectable tumor of nongenitourinary origin may be treated initially with complete resection. A tumor that is unresectable, is resectable only through mutilating surgery, or originates in the head and neck or genitourinary system may be treated with incisional or needle biopsy, followed by excision of residual disease after chemotherapy and/or radiation. Wide local excision is avoided in head and neck tumors if excision will result in a significant cosmetic or functional defect. Orbital exenteration for orbital rhabdomyosarcoma should be performed only for local recurrence. Vaginal or uterine rhabdomyosarcoma in the pediatric patient is treated by performing a biopsy, followed by chemotherapy with or without radiation, and then second-look surgery. Residual disease may require partial vaginectomy. Bladder primary tumors are no longer treated with anterior pelvic exenteration. Instead, chemotherapy and, occasionally, radiation therapy for persistent disease are used. This therapy has allowed a functional bladder to be retained in 60% of patients 4 years after diagnosis, with a survival rate of 89%. While prior studies suggested that prognosis was not improved by a resection that did not remove all gross disease, recent studies suggest that pretreatment debulking of greater or equal to 50% of the tumor volume in patients with retroperitoneal and pelvic rhabdomyosarcoma does result in superior failure-free survival (Raney, 2004). The surgeon should perform an evaluation of the draining lymph node basin for selected sites such as extremity, trunk, or paratesticular location. The IRS Group recommends aggressive nodal sampling; however, the surgeon also may consider lymph node mapping and sentinel node biopsy with preoperative lymphoscintigraphy. RELEVANT ANATOMYSection 4 of 12
Although most frequently diagnosed in the head and neck or genitourinary system, rhabdomyosarcomas may occur anywhere in the body. Embryonal histology usually is found in the head and neck, genitourinary tract, or orbit. Alveolar rhabdomyosarcoma usually is encountered in the extremities, trunk, or perineum. The botryoid variant arises in cavitary structures such as the vagina and bladder, and spindle cell rhabdomyosarcoma is found most commonly in the paratesticular area. CONTRAINDICATIONSSection 5 of 12
Contraindications to initial surgical excision include unresectable disease outside of the pelvis or retroperitoneum or disease that requires disfiguring or disabling resection. WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Diagnostic Procedures
Histologic FindingsThe diagnosis should be confirmed through a tissue specimen, which may be attained via fine needle, core, incisional, or excisional biopsy. The characteristic histologic finding of rhabdomyosarcoma is that of a small, blue, round cell. Cross striations may be seen with light microscopy. The histologic subtypes are discussed in Pathophysiology. StagingOnce the diagnosis has been made, the tumor should be staged. The staging system currently used for rhabdomyosarcomas is the Lawrence/Gehan Staging System, which is initiated preoperatively and then completed after resection.
TREATMENTSection 7 of 12
Medical therapyCurrent recommendations stem from IRS-V, in which treatment is stratified according to risk: low, intermediate, and high, based on the risk of disease recurrence and overall survival. Patients are then staged based on the site of the primary tumor. Favorable sites include the orbit, nonparameningeal head/neck, and genitourinary nonbladder/prostate sites; all other sites are unfavorable. Staging continues based on the size of the primary tumor ( <5 cm or > 5 cm), regional lymph node involvement, distant metastases, and histologic subtype. Alveolar subtypes are now stratified based on gene fusion status. Low-risk patients receive vincristine weekly for 9 doses and actinomycin D with or without cyclophosphamide (VAC regimen) and granulocyte colony-stimulating factor (G-CSF) for 4 doses every 12 weeks (at weeks 0, 12, 24, and 36). Radiation therapy (XRT) is added for patients with residual localized disease. The protocol for intermediate-risk patients includes XRT and either VAC or VAC and topotecan (according to randomized assignment) for nearly 1 year. High-risk patients begin therapy with irinotecan followed by VAC and XRT. Recent investigations using the vinca alkaloid vinorelbine have been instituted for use in recurrent, advanced rhabdomyosarcoma (Casanova, 2002). Radiation therapy Radiation therapy is administered to patients who are at increased risk for local tumor recurrence. Intraoperative radiotherapy (IORT) or brachytherapy, implemented at the time of surgical intervention, has played a valuable role in patients whose tumors have positive or questionable margins. Surgical therapyFirst, the surgeon must obtain a tissue diagnosis. The initial surgical intervention may be wide local excision or incisional or excisional biopsy. Complete excision should be attempted only in cases where the tumor is clearly resectable with negative margins. Incisional biopsies should be planned to ensure that the scar does not impede later attempts at resection, particularly when dealing with extremity tumors. Thus, biopsy incisions on the extremity should always be longitudinal. Patients who have unknown or positive margins should be considered for reexcision. Anesthetic administration should be planned to incorporate any procedures that the child will need. For example, the surgeon should discuss the possible need for a central venous line, bone marrow aspiration, lymph node evaluation, and biopsy with the oncologist, the patient, and the family, so that, if needed, all procedures can be performed on the same day. Thorough preoperative planning is essential because of the variety of surgical options that may be necessary in children with rhabdomyosarcoma, and the surgeon should take into consideration the possibility of obtaining clear margins when determining the initial surgical approach. In the event of resection after chemotherapy and radiation, if the surgeon is unsure that complete excision can be obtained safely, the placement of brachytherapy catheters or the administration of intraoperative radiotherapy may be discussed prior to operative intervention. Unlike adult sarcomas, pediatric rhabdomyosarcoma may be present in the lymphatics approximately 40% of the time. Evaluating the lymphatics in all children with rhabdomyosarcoma is important. This is best performed at the time of the initial procedure, particularly if lymphatic mapping with sentinel node biopsy is planned because prior biopsy and/or excision may disrupt the lymphatics. Surgical options to evaluate the lymphatics include aggressive node sampling or sentinel node biopsy. Formal lymph node dissection is not recommended because it has not been shown to significantly improve survival, even in those patients with histologically positive nodes. Exceptions to wide local excision include head and neck tumors, vaginal/uterine tumors, and bladder tumors. Preoperative detailsPreoperatively, all radiographic studies should be reviewed for evidence of metastases or signs of local invasion that may complicate resection. The surgeon should be prepared to perform a complete resection, when indicated, in order to afford the child the best possible prognosis. Intraoperative detailsIndependent of the site of the tumor, the surgeon should strive for a complete resection, without causing mutilation or disability. When the margins are in doubt, send frozen sections for analysis. Frequently, major neurovascular structures will be in the field of resection. When these structures are essential, a careful resection should be undertaken to remove as much of the tumor as possible. In these cases, brachytherapy, intraoperative radiotherapy, or postoperative XRT may be beneficial. Postoperative detailsPatients should be followed up postoperatively to ensure adequate wound healing and to examine for signs of local or distant recurrence. Follow-upPostoperatively, the tumor is graded based on extent of resection. This should be determined once the pathology is completed to determine the need for additional medical or surgical therapy. When possible, tumors with positive margins should be reexcised. COMPLICATIONSSection 8 of 12
Complications vary based on tumor site. Because of the frequency of preoperative radiation therapy, the surgeon should be aware of the possibility of impaired wound healing. OUTCOME AND PROGNOSISSection 9 of 12
The use of multimodal therapy and the long-term investigations by the IRS Group have allowed for steady improvement in prognosis for pediatric patients with rhabdomyosarcoma. The IRS-IV revealed that the failure-free survival rate and overall 3-year survival rate are 77% and 86%, respectively, in patients without metastatic disease. Recent emphasis is on stratification of therapy to provide local control with less impairment in functionality or cosmetics. FUTURE AND CONTROVERSIESSection 10 of 12
Investigations are under way in IRS-VI. These studies seek to verify the stratification-based treatment algorithm. Future studies will aim to continue to improve survival while minimizing morbidity—both from surgery and chemotherapy. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Rhabdomyosarcoma: Surgical Perspective excerpt Article Last Updated: Feb 21, 2007 | ||||||||||||||||||||||||||
