Laboratory Studies
The following studies are indicated in rhabdomyosarcoma:
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CBC count: Anemia may be present because of inflammation, or pancytopenia may be present from bone marrow involvement.
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Liver function tests, including measurement of lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin levels: Metastatic disease of the liver may affect values of these proteins. Liver function must be assessed before chemotherapy.
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Renal function tests, including measurements of BUN and creatinine levels: Renal function must be assessed before chemotherapy.
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Urinalysis (UA): Hematuria may indicate involvement of the genitourinary (GU) tract.
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Blood electrolyte and chemistry, including evaluation of sodium, potassium, chlorine, carbon dioxide, calcium, phosphorous, and albumin values: Assess for abnormalities before chemotherapy.
Imaging Studies
Imaging studies that have been used in the workup include the following:
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Plain radiography: Radiography of the primary site and of the chest is helpful in determining the presence of calcifications and bone involvement of the primary tumor and to search for metastatic lung lesions.
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CT scanning
Obtain a chest CT scan to evaluate for metastases to the lungs. Chest CT scanning is best performed before surgery to avoid atelectasis, which can be confused with metastasis.
A CT scan of the primary site may also be helpful in evaluating for bone erosion, if present, and to follow up the patient's response to therapy.
Obtain a CT scan of the liver in patients with abdominal or pelvic primary tumors to assess for metastatic spread. Ultrasonography is an alternative.
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MRI: MRI improves definition of the mass and its invasion of adjacent organs, especially in orbital, paraspinal, or parameningeal regions. Obtain an MRI of the head if the patient is symptomatic at diagnosis.
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Bone scanning: Search for metastases to the bones.
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Ultrasonography: Obtain sonograms of the liver in patients with abdominal or pelvic tumors. CT scanning is an alternative.
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Echocardiography: Assess cardiac function before chemotherapy.
Procedures
Procedures include the following:
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Biopsy: Open biopsy best enables adequate tissue sampling for diagnosis and molecular studies. Core needle biopsy is an alternative. Depending on the location, definitive surgery can be postponed to allow for neoadjuvant chemotherapy to shrink the tumor.
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Cytogenetics, fluorescent in situ hybridization (FISH)
This study helps in determining if the translocations t(1;13) or t(2;13), which are associated with the alveolar subtype, are present.
FISH also helps in the diagnosis to assess for break-apart of the FKHR gene, though this test will miss the rare variants that don’t involve FKHR.
FISH is most sensitive for these translocations and can be helpful in evaluating residual disease.
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Reverse transcriptase–polymerase chain reaction (RT-PCR) testing
When cytogenetic testing is unavailable (eg, culture failure) or when its results are uninformative, order a RT-PCR reaction to assess for the characteristic translocations associated with alveolar rhabdomyosarcoma (ARMS) and other small, round blue-cell tumors of childhood.
In many centers, the use of RT-PCR to screen for a panel of translocations associated with soft tissue sarcomas is becoming a routine adjunct to morphologic analysis to help ascertain the diagnosis.
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Bone marrow aspiration and biopsy: Assess for metastatic spread to bone marrow.
Histologic Findings
Rhabdomyosarcoma is one of the small, round blue-cell tumors of childhood. Occasionally, these types of tumors can be difficult to differentiate. Rhabdomyosarcoma cells tend to have variable differentiation along the myogenesis pathway and may appear as strap cells or myotubes that sometimes contain muscle cross-striations. Rhabdomyosarcoma cells may demonstrate positive immunohistochemical results for muscle-specific markers, such as myoglobin, actin, and desmin. [19]
Cells from the rhabdomyosarcoma subtypes have the following distinctive features:
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Botryoid: The cambium layer is characteristic, containing a condensation of loose tumor cells below an epithelial surface.
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Alveolar: Cells line up along membranes that may be imperceptibly thin or that may be obvious collagen bands resembling the lung alveoli. A tumor should be classified as this type if any portion of it appears to be alveolar.
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Undifferentiated: No evidence of myogenesis differentiation is usually present.
Molecular Findings
Balanced translocations between chromosomes (2;13) or (1;13) have been identified in approximately 80% of alveolar RMS. [20] The clinical behavior and molecular characteristics of alveolar RMS without a fusion gene are indistinguishable from embryonal cases and have been shown to be significantly different from fusion-positive alveolar cases, implying the critical role of fusion gene status in risk stratification of RMS. [21]
Genetic Findings
Recent research has been focused on performing whole genome, whole exome and transcriptome sequencing to characterize the landscape of somatic alterations. In addition to well recognized gene mutations that include the FGFR4/RAS/AKT pathway, novel recurrently mutated genes such as PTEN, GAB1, ROBO, FBXW7 and BCOR have been identified. These new findings provide potential new avenues for therapeutic intervention. [22, 23]
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Axial CT scan of rhabdomyosarcoma in the left middle ear. Image provided by Suresh Muhkerji, MD, Department of Radiology, University of North Carolina Hospitals.
