[Infantile rhabdomyofibrosarcoma with EGFR kinase domain duplication: a clinicopathological analysis of three cases]

Objective: To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD). Methods: The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed. Results: There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis. Conclusions: IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.