Refractory alveolar rhabdomyosarcoma in an 11-year-old male

Abstract

Rhabdomyosarcoma (RMS) is a mesenchymal malignancy phenocopying muscle and is among the leading causes of death from childhood cancer. Metastatic alveolar rhabdomyosarcoma is the most aggressive subtype with an 8% 5-yr disease-free survival rate when a chromosomal fusion is present and a 29% 5-yr disease-free survival rate when negative for a fusion event. The underlying biology of PAX-fusion-negative alveolar rhabdomyosarcoma remains largely unexplored and is exceedingly rare in Li-Fraumeni syndrome patients. Here, we present the case of an 11-yr-old male with fusion-negative alveolar rhabdomyosarcoma studied at end of life with a comprehensive functional genomics characterization, resulting in identification of potential therapeutic targets for broader investigation.

Keywords: rhabdomyosarcoma.

Figure 1.

Orthopedic MRI of the humerus. An ovoid lesion (red asterisk) was found within the triceps region of the left upper arm utilizing a 1.5-Tesla magnet with the following sequences: axial T₂ turbo spin echo (TSE) with fat saturation, axial T₂ TSE pulse, axial T₁ combination, and axial T₁ TSE after 4.6 mL of gadolinium (+C) (from top to bottom, left). The following sequences were also obtained: coronal T₁ TSE + C with fat saturation, coronal T₁ TSE with fat saturation, coronal short-TI inversion recovery (STIR) combination, and sagittal T₁ TSE + C with fat saturation (from top to bottom, right). The lesion measured ∼2.6 × 2 cm in the axial plane and ∼3.5 cm in the craniocaudal dimension (top, left and top, right). The lesion demonstrated T₁ hypointensity and heterogeneous, but T₂ hyperintensity without significant fat saturation. Within the ovoid region, there are two punctate foci of STIR hypointensity (29/19) and T₁ hypointensity.

Figure 2.

Histology slides from alveolar rhabdomyosarcoma case. Hematoxylin and eosin (H&E) staining of the left forearm (A), right lower lobe of the lung (B), pleural fluid (C) showing a metastatic small round blue cell malignancy, 200× magnification of right lower lobe of the lung (D), 400× magnification of right lower lobe of the lung (E), and 200× magnification of myogenin staining (F). Scale bars, 300 µM.

Figure 3.

Circos plot. A Circos plot was generated using tumor DNA exome, normal DNA exome, and tumor RNA sequencing data. Exome data was analyzed for somatic point mutation, indel, and copy-number variation data, as denoted by the inner and middle rings, respectively. Gene expression from RNA sequencing data was plotted on the outer ring. Genes listed in blue bear germline mutations, whereas genes listed in red bear somatic mutations.