Rhabdomyosarcoma

RMS is broadly classified as one of the small, round, blue cell malignancies of childhood.⁷ The histologic subtypes, in order by worsening prognosis, include embryonal rhabdomyosarcoma (ERMS), the most common form (with spindle cell and botryoid comprising two favorable variants), alveolar rhabdomyosarcoma (ARMS), and undifferentiated sarcoma. Patients with undifferentiated sarcoma were previously enrolled on the IRSG clinical trials in a fashion similar to ARMS. Currently, these patients receive systemic therapy similar to patients with Ewing’s sarcoma. Light microscopy often describes ERMS with spindle-shaped cells and ARMS with small, round, blue cells forming alveolar-like spaces, although tumor biopsy specimens may also look like collections of poorly differentiated cells complicating definitive diagnosis by hematoxylin and eosin staining alone. Immunohistochemical staining can include positivity for MyoD.⁸ Cytogenetic events occur in ERMS with a loss of heterozygosity on chromosome 11p and in ARMS with translocations between chromosomes 2 and 13 or 1 and 13. These represent loci of PAX3 and PAX7 (chromosomes 2 and 1) and their fusion with FKHR on chromosome 13. These fusion proteins act as transcription factors and are diagnostic of ARMS.⁷ Other genetic abnormalities and syndromes associated with RMS include neurofibromatosis type 1 (with a prevalence of 1 : 200 noted on IRSG-IV), Li-Fraumeni syndrome, and Beckwith-Wiedemann syndrome.^9–11

Nonrhabdomyosarcoma Soft Tissue Sarcoma

The pediatric NR-STS comprise a heterogeneous group of tumors managed homogeneously owing primarily to the limitations in both patient numbers and effective chemotherapy. The most common histologies noted in practice and clinical trials include synovial cell sarcoma and malignant peripheral nerve sheath tumor (MPNST), although several rarer variants including rhabdoid tumor and infantile fibrosarcoma are almost exclusive to the pediatric age group.^12,13 Although many NR-STSs have no genetic signature, several histologic variants do have specific translocations or deletions^12,14 (Table 66-1).

TABLE 66-1 Genetic Abnormalities: Nonrhabdomyosarcoma Soft Tissue Sarcomas

Rhabdomyosarcoma

The presentation of children with RMS is diverse and relates to the site of involvement and extent of disease. The median age for children presenting with RMS is younger than 5, although another peak occurs in the mid teens. The head and neck region is the most frequent site of involvement and is divided into favorable and unfavorable (parameningeal) sites.^15,16 This site comprised 42% of localized presentations in patients enrolled on IRSG III and IRSG IV and serves as an example of the important nature of primary tumor location.¹⁷ Metastatic disease occurs 20% of the time at presentation, and nodal involvement is rare (<5%) except for paratesticular (25%) and extremity (24%) sites of disease, which warrant either computed tomography (CT) (paratesticular, <10 years of age), nodal sampling (paratesticular, ≥10 years of age), or sentinel node biopsy (extremity site).^18–21

Nonrhabdomyosarcoma Soft Tissue Sarcoma

The presentation of NR-STS is often as a painless mass whereas other symptoms are site specific. Approximately half of the cases arise in the extremity, and the incidence increases throughout the adolescent years and into adulthood.^22,23 Although the vast majority of soft tissue “masses” are either not real or benign, consideration should be given to malignancy because an ill-chosen surgical approach may compromise future local therapy (Fig. 66-1).

Figure 66-1 Rhabdomyosarcoma of the pinna of the ear presenting as a painless soft tissue mass.

Fifteen to 22 percent of patients present with metastatic disease at diagnosis, with the lungs being the predominant site of metastatic involvement.^13,24 Clear cell sarcoma, epithelioid sarcoma, and angiosarcoma carry a risk of regional nodal involvement and warrant evaluation of the draining nodal bed(s) with sentinel node sampling.

Rhabdomyosarcoma

Staging workup is similar for most patients with RMS (Table 66-2). A site-specific history and physical examination should be performed by the treating radiation oncologist at the time of presentation to define the site of primary disease, its extent, and symptoms related to potential metastatic sites of involvement. Attention to cranial nerve involvement for head and neck primary sites as well as attending the examination under anesthesia for genitourinary sites (vaginal, cervix, uterus, bladder, and prostate) will assist in the multidisciplinary discussion regarding staging and local therapy approaches.

TABLE 66-2 Staging Workup and Follow-Up Evaluations for Patients with Rhabdomyosarcoma and Nonrhabdomyosarcoma Soft Tissue Sarcomas

Laboratory studies include a complete blood cell count and chemistry panel, which may be suggestive of bone marrow disease (anemia) or other organ-specific dysfunction related to metastatic involvement.

Review of the pretreatment imaging is critical to ensure both adequate imaging of the entire primary tumor as well as understanding the extent of disease. Often, standard diagnostic imaging protocols (particularly magnetic resonance imaging [MRI]) will not encompass the entire tumor, because the studies were designed for evaluation of joint or intracranial disease. Repeating these studies will facilitate better local therapy decisions and delivery. Standard diagnostic imaging should include MRI of the primary site of disease, CT of the chest (and abdomen for infradiaphragmatic primary tumors), bone scintigraphy, and site-specific imaging related to concern for metastatic disease. ¹⁸F-Fluorodeoxyglucose-labeled positron emission tomography (FDG-PET) may be helpful and could potentially replace bone scintigraphy, but current reimbursement may limit its routine application.

Bone marrow aspiration and biopsy should be performed for all patients, as well as cerebrospinal fluid cytology for patients with parameningeal, orbital, and paraspinal primary sites of disease. Lymph node sampling should be performed for patients 10 years of age or older with paratesticular primary tumors, and sentinel node mapping and sampling should be done for patients with disease of an extremity.

After staging evaluation, a clinical stage should be assigned (outlined in Table 66-3). If surgery has been performed (or after a planned surgical resection or biopsy), a grouping should be defined (Table 66-4). These two factors plus the patient’s histology are combined into a risk classification to assign patients to protocol therapy.