Rhabdomyosarcoma (RMS) is a high-grade malignant neoplasm, with a morphologic appearance mimicking that of developing skeletal muscle. Over the last 30 years, patient outcomes have improved with the incorporation of multimodal therapies, including chemotherapy, radiation therapy, and surgery. The overall cure rates exceed 70%, with patients who have low-, intermediate-, and high-risk disease experiencing long-term survival rates of >90%, 70%, and <30%, respectively. Historically, RMS was classified according to histology; however, recent advances have revealed new molecular subgroups that allow us to more accurately identify high-, intermediate-, and low-risk disease. In this review, we discuss recent advances made in understanding RMS tumor biology and propose how this understanding can drive a new classification system that can guide clinical approaches for treatment de-escalation in patients with expected favorable outcomes and escalation for those with expected poor outcomes.

Objective: To investigate the clinicopathological, therapeutic, and survival data on pediatric major salivary gland cancers. Materials and Methods: National Cancer Database (NCDB) query from 2004 to 2018. Results: In total, 967 cases of individuals under the age of 21 were identified. Most cancers affected the parotid gland (86%). Mucoepidermoid carcinoma (41.3%) and acinic cell adenocarcinoma (33.6%) were the most common. Tumors occurred more often from age 11 to 21, and females were more affected. Histology varied by age, gender, and race. In the 0–5 age group, mucoepidermoid carcinoma and myoepithelial carcinoma/sarcoma/rhabdomyosarcoma were the most common pathologies. In patients over 5 years old, mucoepidermoid carcinoma was the most frequent tumor in boys, while acinic cell adenocarcinoma was more common in girls. African American patients had a higher incidence of mucoepidermoid carcinoma, while White patients in the 0–5 age group had a higher incidence of myoepithelial carcinoma/sarcoma/rhabdomyosarcoma tumors. Low-grade tumors were commonly diagnosed at stage I, but the 0–5 age group had a high frequency of stage IV tumors. The overall 5-year survival rate was 94.9%, with 90% for the 0–5 years age group and 96% for the 11–15 years age group. Negative margins were associated with higher 5-year survival rates in high-stage tumors (93%) compared to positive margins (80%). Submandibular malignancies had worse 5-year survival rates across all age groups. Conclusions: Major salivary gland malignancies in pediatric patients exhibit variations in histopathologic characteristics by age, gender, and race. Negative margins impact 5-year survival rates, especially in high-stage tumors.

Infantile fibrosarcoma is the most common soft-tissue sarcoma in children under the age of 1 yr and is defined molecularly byNTRKfusion proteins. This tumor is known to be locally invasive; however, although rare, metastases can occur. TheNTRKfusion acts as a driver for tumor formation, which can be targeted by first- and second-generationTRKinhibitors. AlthoughNTRKgatekeeper mutations have been well-described as mechanisms of resistance to these agents, alternative pathway mutations are rare. Here, we report the case of a patient with infantile fibrosarcoma treated with chemotherapy andTRKinhibition that developed metastatic, progressive disease with multiple acquired mutations, includingTP53,SUFU, and anNTRKF617L gatekeeper mutation. Alterations in pathways ofSUFUandTP53have been widely described in the literature in other tumors; however, not yet in infantile fibrosarcoma. Although most patients have a sustained response toTRKinhibitors, a subset will go on to develop mechanisms of resistance that have implications for clinical management, such as in our patient. We hypothesize this constellation of mutations contributed to the patient's aggressive clinical course. Taken together, we report the first case of infantile fibrosarcoma withETV6::NTRK3and acquiredSUFU,TP53, andNTRKF617L gatekeeper mutation along with detailed clinical course and management. Our report highlights the importance of genomic profiling in recurrent infantile fibrosarcoma to reveal actionable mutations, such as gatekeeper mutations, that can improve patient outcomes.