Pediatric Soft-Tissue Sarcomas

Rhabdomyosarcoma

Rhabdomyosarcoma is broadly classified as one of the small, round, blue cell malignancies of childhood. The 2013 World Health Organization (WHO) classification of RMS includes several histologic subtypes: ERMS, the most common form (with botryoid comprising a favorable variant); spindle cell/sclerosing RMS; ARMS; and pleomorphic RMS. Pleomorphic RMS is typically seen in adults and is considered to have poor prognosis. 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. Cytogenetic events occur in ERMS with a loss of heterozygosity on chromosome 11p15 and frequent mutations of the RAS/NF1 pathway. Anaplastic features in ERMS may indicate a possible germline TP53 mutation and diagnosis of Li-Fraumeni syndrome ; 80% of ARMS harbor translocations between FOXO1 on chromosome 13 and loci of either PAX3 ((t(2;13)(q35;q14)) or PAX7 (PAX7 (t(1;13)(p36;q14)). The resultant fusion proteins from these translocations act as transcription factors; fusion-positive tumors are considered biologically and clinically distinct from fusion-negative ARMS. Congenital/infantile spindle cell RMS have demonstrated fusions commonly involving VGLL2 , whereas sclerosing RMS often have MYOD1 mutations, occasionally concomitant with activating mutations of PIK3CA . Other genetic predisposition syndromes associated with RMS include neurofibromatosis type 1 (with a prevalence of 1 : 200 noted on IRSG-IV), pleuropulmonary blastoma/ DICER1 syndrome (typically genitourinary ERMS), Costello syndrome ( HRAS mutations), Noonan syndrome, and Beckwith-Wiedemann syndrome.

Nonrhabdomyosarcoma Soft-Tissue Sarcoma

The pediatric NR-STS comprise a heterogeneous group of tumors managed homogeneously largely because of the limitations in patient numbers and effective chemotherapy. The most common histologies include synovial cell sarcoma and malignant peripheral nerve sheath tumor, although several rarer variants, including infantile fibrosarcoma, are almost exclusive to the pediatric age group. Although many NR-STSs have no genetic signature, several histologic variants do have specific translocations or deletions ( Table 79.1 ). Others may harbor specific recurrent mutations, such as SMARCB1 aberrations seen in epithelioid sarcoma.

Rhabdomyosarcoma

The presentation of children with RMS is diverse, characterized by the site of involvement and extent of disease. The median age for children presenting with RMS is younger than 5, although a second incidence 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. Other common sites include the genitourinary tract (with bladder and prostate less favorable) and extremities. Trunk, chest wall, perineal, retroperitoneal, and biliary tree primary tumors are seen less frequently. 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 computed tomography (CT) including paratesticular sites at younger than 10 years of age), nodal sampling (paratesticular sites for10 years of age or older), or sentinel node biopsy (extremity sites).

Nonrhabdomyosarcoma Soft-Tissue Sarcoma

The presentation of NR-STS is often as a painless mass; additional symptoms may be site specific. Approximately 50% of cases arise in an extremity, and incidence increases throughout the adolescent years and into adulthood. Although many patients suspected to have soft-tissue “masses” are identified to have either normal tissues or a benign lesion, consideration should always be given to malignancy because an ill-chosen surgical approach may compromise future local therapy ( Fig. 79.1 ).

Of patients, 15% to 20% present with metastatic disease at diagnosis, with the lungs being the predominant site of metastatic involvement. Clear-cell sarcoma and epithelioid sarcoma carry a risk of regional nodal involvement and warrant evaluation of the draining nodal bed(s) with sentinel node sampling.