Background: An increasing number of soft tissue neoplasms with fusion of well-defined driver genes are being discovered. We report such a case in a 3-year-old girl with a 2-year follow-up. Design: The patient first presented at age of 3.5 years with a painless right axillary/chest wall mass without constitutional symptoms. MRI demonstrated a 4.5 x 3.5 x 3.5 cm T2 hyper- and T1 hypointense mass. The mass was excised and showed a well-demarcated solid lesion with a homogeneous pale-white fleshy cut surface. No necrosis, myxoid or cystic change, hemorrhage, or calcification was noted. Microscopically, it was a variably hypercellular lesion composed of two main distinct cell types: oval fibroblast-like cells arranged in sheets with focal transition to spindle cells in whirling or storiform, and ganglion-like cells with abundant pale granular cytoplasm singly or in small clusters scattered among the fibroblast-like cells (Figure-1). Fibroblast-like cells contained a single resinoid nucleus with an irregular nuclear membrane surrounded by variable amount of eosinophilic cytoplasm with indistinct cell borders. Focal nuclear clustering and molding were seen. Patchy mild lymphocytic infiltrate was noted. No nuclear pleomorphism, necrosis or mitotic figure was identified. Immunohistochemically, both types of tumor cells were diffusely positive for ALK, CD34 and TFE3 (Figure-2) but negative for most lineage markers (Table). Next-generation-sequencing revealed EML4-ALK gene fusion of 5 a/b variant. No NTRK gene rearrangement was detected. Results: The tumor recurred in 13 months with metastasis to regional lymph nodes and right lung. Biopsy showed similar morphology and immunohistochemical profile. Treatment with oral ALK inhibitor (crizotinib) was initiated at 200 mg BID. Seven weeks later, CT scan demonstrated partial radiological response with a measurable decrease in the main tumor size from 8.7 to 7.5 cm. The tumor regrew to 9.0 x 7.0 x 7.0 cm and became firm nine weeks thereafter crizotinib was inadvertently discontinued by her mother. Reinstituting the therapy led to second tumor reduction (to 8.7 x 5.4 x 6.4 cm) and tumor softening on palpation. The patient is currently alive, active, and stable without any constitutional symptoms. Conclusions: This tumor’s features of EML4-ALK gene fusion, distinct innocuous histology, but rapid growth and metastasis, and response to ALK inhibitor add to the pathological and clinical spectrum of the kinase fusion-positive soft tissue neoplasms.
Qu ZH, Hysell C, Zhang P, Micale M. A soft tissue tumor with EML4-ALK fusion, granular cell changes, metastasis, and response to kinase inhibitor therapy in a young girl. Mod Pathol. 2022 Mar;35(Suppl 2):1283-1285.