Pediatric primary lung carcinomas are extremely rare. Apart from known associations with congenital adenomatoid malformations, cases of primary lung adenocarcinomas after prolonged treatments of pediatric malignancy have been reported. We describe the morphological and molecular features of three cases of lung adenocarcinoma developed in adolescents aged 8 to 17 years during progression of their bone osteosarcoma or Ewing sarcomas. The morphological features overlapped those of adult lung adenocarcinoma including in situ, minimally invasive, and invasive forms. EGFR gene mutations were found in all three cases by targeted next-generation sequencing. The two patients with Ewing sarcoma had no progression of their lung cancer and no further progression of the metastatic bone tumor after additional chemo- and radio-therapy. Conversely, the osteosarcoma patient refused further treatments after thoracic surgery for metastatic osteosarcoma and locally advanced adenocarcinoma and died 2 years later of widespread distant metastases. Our results indicate that primary lung cancer might originate in pediatric patients during prolonged adjuvant therapies for primary bone neoplasm, and this possibility should be considered in the presence of suspected lung disease progression to correctly monitor the primary tumor evolution and define the appropriate therapeutic strategy at each time point. If appropriately treated, second primary lung cancer may not affect the patients’ prognosis. The pathogenetic mechanisms of these rare lung adenocarcinomas are not clear, but the presence of EGFR mutations in all three cases indicates an oncogene addiction of the lung tumor, rather than a direct cancerogenic effect of the sarcoma-related treatment.

小儿原发性肺癌极为罕见。除了已知与先天性腺瘤样畸形的关联外，还报道了长期治疗小儿恶性肿瘤后原发性肺腺癌的病例。我们描述了三例在其骨骨肉瘤或尤因肉瘤进展期间在8至17岁的青少年中发展的肺腺癌的形态和分子特征。形态学特征与成人肺腺癌的形态学特征重叠，包括原位，微创和浸润形式。表皮生长因子通过靶向下一代测序在这三例病例中均发现了基因突变。经过额外的化学和放射治疗后，两名尤因肉瘤患者无肺癌进展，转移性骨肿瘤无进一步进展。相反，骨肉瘤患者在胸外科手术后拒绝接受转移性骨肉瘤和局部晚期腺癌的进一步治疗，并于2年后因广泛的远处转移死亡。我们的结果表明，在长期对原发性骨肿瘤进行辅助治疗期间，原发性肺癌可能起源于儿科患者，因此，在存在可疑的肺部疾病进展的情况下，应考虑这种可能性，以正确地监测原发性肿瘤的进展，并在每种情况下确定适当的治疗策略时间点。如果得到适当治疗，第二原发性肺癌可能不会影响患者的预后。这些罕见的肺腺癌的致病机制尚不清楚，但存在在所有这三种情况下，EGFR突变都表明肺癌致癌基因成瘾，而不是肉瘤相关治疗的直接致癌作用。