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.
目的： 探讨伴有EGFR激酶结构域重复（EGFR kinase domain duplication，EGFR-KDD）的婴儿横纹肌纤维肉瘤（infantile rhabdomyofibrosarcoma，IRFS）的临床病理及分子遗传学特征。 方法： 收集佛山市中医院病理科2022年1月至2024年1月明确诊断为伴有EGFR-KDD的IRFS会诊病例3例，对其临床、病理形态学和免疫组织化学特点进行回顾性分析，利用PCR及二代测序技术分析其分子遗传学特征，并复习相关文献。 结果： 3例患儿中男患儿1例（例1），女患儿2例（例2，3），年龄分别为1岁（例1）、4岁（例2）、1岁（例3），病变分别位于左大腿、右侧颌面部及右侧腘窝，临床表现多为无意间发现的无痛性肿物，肿瘤最大径3~5 cm。镜下观察，瘤组织境界不清，瘤细胞梭形，呈密集弥漫、束状排列，中等量嗜酸性淡染胞质，核分裂象易见，可见少许横纹肌母细胞样细胞，未见出血、坏死。免疫组织化学表达波形蛋白、局灶表达平滑肌肌动蛋白（SMA）、肌特异性肌动蛋白（MSA）、结蛋白、Myogenin及MyoD1，Ki-67阳性指数为10%~60%。3例行逆转录-聚合酶链反应（RT-PCR）检测均发现EGFR-KDD，3例均行二代测序检测但仅1例检测到EGFR-KDD。3例均获得随访资料，随访时间12~36个月，2例死亡，1例存活（无复发转移）。 结论： 伴有EGFR-KDD的IRFS是一种罕见的软组织肿瘤，形态上类似于先天性纤维肉瘤，但免疫组织化学具有横纹肌母细胞分化，婴幼儿常见，肿瘤好发躯干及四肢，预后不佳，患者需要积极的综合治疗。EGFR-KDD可能是其分子遗传学改变，未来可能成为治疗靶点。.