Pathology

Rhabdomyosarcoma is classified into three cell types: embryonal, alveolar (which has botryoid and spindle cell variants), and pleomorphic. The embryonal subtype accounts for 60% to 70% of childhood cases and is the most common subtype. It is also the most common subtype presenting in the head and neck (20-22).

Rhabdomyosarcomas are malignant tumors of skeletal muscle. They are part of the larger group of soft-tissue sarcomas. Sarcomas of bony origin are classified separately. Like most malignant tumors, the etiology is probably multifactorial. Studies have suggested that maternal exposure to ionizing radiation during pregnancy increases the risk of sarcoma development. There is also evidence that socioeconomic status and maternal use of recreational drugs during pregnancy play a role in soft-tissue sarcoma development. Chromosomal abnormalities probably play a role in sarcoma development (20), especially translocation of chromosomes 2,13 and 1,13. The associated chromosome abnormalities can be used for diagnostic confirmation and have a role in residual tumor diagnosis and monitoring. An example is the use of chromosomal confirmation to assess a residual mass for viable tumors cells. Several syndromes have been associated with the development of rhabdomyosarcoma. Among them are Li-Fraumeni, neurofibromatosis type I, and Beckwith-Wiedemann syndrome (22).

CLINICAL MANIFESTATIONS

Patient presentation depends on the tumor location and size. Head and neck presentations mimic other head and neck neoplasms and depend on the site and extent of the mass. These tumors occur along the anterior skull base, parameningeal surfaces, temporal bone, and within the orbit.

Temporal bone and middle ear tumors often present with unilateral otorrhea and conductive hearing loss. As the tumor progresses, facial nerve paralysis and other cranial nerve neuropathies occur. Other head and neck manifestations include nasal obstruction, facial swelling, oropharyngeal mass, and unilateral proptosis. Metastatic rhabdomyosar-coma is part of the differential diagnosis for pediatric neck masses (23).

Rhabdomyosarcomas may occur in multiple other locations. Common areas include the kidney, biliary tract, extremities, and spinal cord. The symptoms will depend on the site and severity of the disease.

DIAGNOSIS

Diagnosis is made by biopsy (fine needle or open biopsy). If rhabdomyosarcoma is strongly suspected, comprehensive imaging should be done prior to open biopsy to accurately delineate tumor extent. Once a diagnosis is established, a multidisciplinary approach is required for all patients. CT scan of the chest and bone marrow aspirate should always be performed. Further imaging is based upon tumor location, i.e., magnetic resonance imaging (MRI) scans of the skull base for parameningeal disease and a CT scan of the abdomen and pelvis for GU and lower extremity primaries (21,22,24).

TABLE 2 Grouping of Rhabdomyosarcoma

Group

Subgroup

Description

I: Localized disease or

Ia

Ia: Tumor limited to muscle of origin

completely resected (low risk)

Ib

Ib: Local spread beyond muscle of origin

II: Gross total resection

IIa

IIa: Residual microscopic tumor

IIb

IIb: Microscopic tumor cells in local lymph nodes

III: Incomplete resection

IIIa

IIIa: Biopsy only

(intermediate risk)

IIIb

IIIb: 50% resection

IV: (High risk)

-

Distant metastatic disease present at onset

TABLE 3 Tumor, Node, and Metastasis Staging

Tumor

T1

Tumor <5cm

T2

Tumor >5cm

Node

N0

Negative nodes

N1

Any positive nodes

Metastasis

M0

-

M1

Any metastasis

Stage I

-

Favorable sites, any size, any nodal status [orbit, GU (not bladder or prostate), head and neck]

Stage II

Unfavorable sites, but small and negative lymph nodes (extremities, bladder, prostate, and parameningeal)

Stage III

-

Unfavorable sites, small or large and positive lymph nodes

Stage IV

Distant metastatic disease

Abbreviations: GU, genitourinary.

Abbreviations: GU, genitourinary.

The Intergroup Rhabdomyosarcoma Study Group has established prognostic indicators for rhabdomyosarcoma. This group, along with the National Wilms Tumor Study Group and the Children's Oncology Group, produced a staging system based on tumor size, nodal involvement, and presence or absence of metastases (Tables 2 and 3). These staging systems help determine the level of risk of individual patients and can help tailor treatment options (Fig. 2A and B) (24).

TREATMENT

The management of previously untreated childhood rhabdomyosarcoma has been well studied. All patients are treated with multimodality therapy and are considered to have micrometastases. Therefore, all patients receive chemotherapy (22). The principles of

FIGURE 2 (A) Nasal rhabdomyosarcoma before treatment, staged as group III (biopsy only), T2N0M0 (Stage II—orbit involvement). (B) MRI of tumor after treatment with course of chemotherapy. Patient underwent medical maxillectomy and additional radiation therapy. Abbreviation: MRI, magnetic resonance imaging.

FIGURE 2 (A) Nasal rhabdomyosarcoma before treatment, staged as group III (biopsy only), T2N0M0 (Stage II—orbit involvement). (B) MRI of tumor after treatment with course of chemotherapy. Patient underwent medical maxillectomy and additional radiation therapy. Abbreviation: MRI, magnetic resonance imaging.

surgical treatment are to preserve all vital cosmetic and functional structures to accept close margins, and to reserve radical surgery for recurrence following radiotherapy and chemotherapy.

Orbital tumors require biopsy for diagnosis, followed by chemotherapy and radiation therapy. If a tumor persists after primary therapy, orbital exenteration should be considered (22).

Extraorbital head and neck tumors are treated with wide local excision and neck lymph node sampling of clinically involved lymph nodes. Close margins (< 1 mm) are reasonable if anatomic restrictions are present. Anterior skull base tumors can be resected in cases of children with recurrent locoregional disease and residual disease following chemotherapy and radiation therapy. Tumors that are considered unresectable should undergo radiation and chemotherapy, with surgery to remove any residual masses, if feasible.

As previously mentioned, chemotherapy is used in the treatment of all patients with rhabdomyosarcoma (22). The regimen depends on the risk status of the patient (Table 2). "Low-risk" patients receive vincristine and dactinomycin. "Intermediate-risk" patients receive additional doses of cyclophosphamide. "High-risk" patients have poor response rates to current chemotherapeutic options. High-dose chemotherapy with stem cell rescue is under investigation. In general, patients in this group receive the standard therapy plus additional drugs such as ifosfamide and doxorubicin.

Radiation therapy is tailored to the specific disease. Patients who do not have residual disease after primary treatment do well without radiation. Patients with gross residual disease receive a standard dose of 5000 cGy. Radiation is given after chemotherapy (20,22).

Patients with middle-ear rhabdomyosarcoma deserve special mention due to the potential role the otolaryngologist plays in early diagnosis and intervention. As mentioned, these patients can present with bloody otorrhea not responsive to conservative management. Middle-ear rhabdomyosarcoma tends to present in a parameningeal location and often is unresectable (Groups III and IV) (25). However, most tumors are small (<5 cm) and do not involve lymph nodes. These patients are usually treated with chemotherapy and radiation. Five-year survival rates are 67% for all patients and have improved over time (25).

PROGNOSIS

Recurrent rhabdomyosarcoma presents the most favorable prognosis if it is local or regional. Most children, however, present with advanced disease (distant metastasis or unresectable disease) and have a poor prognosis. These patients are generally treated with combinations of chemotherapeutics that have not been given to them previously.

The prognosis of low-risk patients is good, with greater than 95% five-year survival rates with standard therapies. Intermediate-risk patients have between 50% and 70% survival rates. High-risk patients have poor outcomes, with survival rates from 22% to 34% (22,26,27).

SUMMARY

In general, pediatric rhabdomyosarcoma is a soft-tissue malignancy commonly seen in the head and neck. Its presentation depends on the site and extent of the disease. Surgical management is an important part of treatment. Complete resection can place a patient in the low-risk group with a more favorable prognosis. A multidisciplinary approach is imperative in the management of this disease. As with most malignant tumors, early diagnosis and treatment can make a significant difference in outcomes.

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Part D ■ Other Systemic Disorders

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