Pitel, Beth

Context.— Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data. Objective.— To define the clinicopathologic spectrum of neoplastic and nonneoplastic diseases observed in resected mass lesions in the chest of pediatric patients, and to identify somatic alterations observed in primary neoplasms. Design.— Clinicopathologic features of thoracic mass lesions (n = 385) resected from 373 patients aged ≤21 years in a 25-year period (1993–2018) were included. Primary neoplasms having sufficient material were tested by a laboratory-developed comprehensive genomic profiling assay that assesses tumor mutational burden, microsatellite instability, somatic sequence variants, gene amplifications, fusions, and specific transcript variants. Results.— The most commonly resected space-occupying lesions were nonneoplastic mass lesions and cysts or malformations, resected in 117 (31.4%) and 58 of 373 patients (15.5%) respectively. Metastatic neoplasms were observed in 169 of 373 patients (45.3%; mean age 14.4 years, range 1–21 years); the most common was osteosarcoma (68 of 169; 40.2% of metastases). Primary lung neoplasms occurred in 24 of 373 patients (6.4%; mean age 14.5 years, range 6 months–21 years), and 16 patients had primary extrapulmonary thoracic tumors. Carcinoid tumor was the most common primary lung neoplasm (7 typical, 3 atypical). Molecular testing showed a prevalence of somatic pathogenic or likely pathogenic mutations and copy-number alterations. No fusions or splice variants were identified. Tumors were microsatellite-stable with low tumor mutational burden. Conclusions.— Resected pediatric thoracic mass lesions are more likely to be metastatic lesions, congenital cysts or malformations, or nonneoplastic lesions compared to primary thoracic neoplasms, which are encountered at a low frequency and tend to have relatively simple genetic profiles.

PURPOSE The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics to support case review and treatment planning. METHODS In this review, we evaluate and summarize the landscape of available tools, resources, and evidence used in the evaluation of somatic and germline tumor variants within the context of molecular tumor boards. RESULTS Molecular tumor boards (MTBs) are collaborative efforts of multidisciplinary cancer experts equipped with genomic interpretation resources to aid in the delivery of accurate and timely clinical interpretations of complex genomic results for each patient, within an institution or hospital network. Virtual MTBs (VMTBs) provide an online forum for collaborative governance, provenance, and information sharing between experts outside a given hospital network with the potential to enhance MTB discussions. Knowledge sharing in VMTBs and communication with guideline-developing organizations can lead to progress evidenced by data harmonization across resources, crowd-sourced and expert-curated genomic assertions, and a more informed and explainable usage of artificial intelligence. CONCLUSION Advances in cancer genomics interpretation aid in better patient and disease classification, more streamlined identification of relevant literature, and a more thorough review of available treatments and predicted patient outcomes.