Pediatric Rhabdomyosarcoma Surgery 

Rhabdomyosarcoma is a malignancy that arises from embryonic mesenchymal cells that possess the potential to develop into skeletal muscle.

Rhabdomyosarcoma is a clinical entity that was first described in the English literature in 1937. Prior to the evolution of multimodal treatment for 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 by the Soft Tissue Sarcoma Committee of the Children's Oncology Group to utilize risk assessment to refine treatment algorithms to improve outcome and morbidity related to treatment. The formation of the IRS Group and the Soft Tissue Sarcoma Committee of the Children's Oncology 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, combined with chemotherapy and radiation therapy, when necessary.

Approximately 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.

Frequency

Rhabdomyosarcoma 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.

The 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 that 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 is also known to occur more commonly in patients with neurofibromatosis type I and in patients with Beckwith-Wiedemann syndrome.

Five variants of rhabdomyosarcoma are described in the international classification of rhabdomyosarcoma.^[1]

The embryonal variant is most common and is usually 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. Anaplasia, which may be a feature of this subtype, adversely affects the likelihood of failure-free survival.

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 and FKHR genes. Alveolar rhabdomyosarcoma usually affects 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.^[2]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 compared with to the gene fusion groups.

The botryoid variant, named after 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.

For additional information, see the article Rhabdomyosarcoma in eMedicine’s Pathology volume.

The clinical presentation of rhabdomyosarcoma varies by the site of presentation. Most cases present as painless masses, often discovered after minor trauma. Importantly, tumors that originate in the head and neck may present as a mass or as signs and symptoms of central nervous system involvement due to intracranial extension of the tumor or infiltration of the cranial nerves, meninges, or brain stem.

The differential diagnoses of a painless mass in a child should include benign masses such as lipomas, neurofibroma, or even hematoma. However, the differential diagnoses of any new or persistent mass must include soft-tissue sarcoma.

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 with biopsy, followed by chemotherapy with or without radiation, and then second-look surgery. Residual disease may require partial vaginectomy. Primary bladder 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.^[3]

The surgeon should evaluate 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 may also consider lymph node mapping and sentinel node biopsy with preoperative lymphoscintigraphy.^{[4, 5]}

Although most frequently diagnosed in the head and neck or genitourinary system, rhabdomyosarcomas may occur anywhere in the body. Embryonal histology is usually found in the head and neck, genitourinary tract, or orbit. Alveolar rhabdomyosarcoma is usually 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.

Contraindications to initial surgical excision include unresectable disease outside of the pelvis or retroperitoneum or disease that requires disfiguring or disabling resection.