Seven cases of primary lung tumors characterized histologically by clear cell morphology and a distinctive FGFR3::TACC3 gene rearrangement are described. The tumors arose in 4 women and 3 men, aged 47 to 81 years (mean=68). They occurred in peripheral locations, predominantly subpleural, and ranged in size from 1.4 to 6.5 cm (mean=4.1 cm). All tumors showed a solid growth pattern with abundant central areas of necrosis and marked nuclear pleomorphism. The tumors demonstrated clear cell histology, with large cohesive tumor cells displaying atypical nuclei and abundant clear cytoplasm. Immunohistochemical stains identified a squamous phenotype in 5 cases and an adenocarcinoma phenotype in 2 cases. One case was a squamous cell carcinoma with focal glandular component, and one of the squamous cell carcinomas showed focal sarcomatoid changes. Next generation sequencing identified FGFR3::TACC3 gene rearrangements in all 7 cases. One case demonstrated a concurrent activating FGFR3 mutation and a second case demonstrated concurrent FGFR3 amplification. Two cases harbored a concurrent KRAS G12D mutation. One case harbored both KRAS and EGFR mutations, and 1 case had a concurrent TP53 mutation. Non-small cell lung carcinoma harboring FGFR3::TACC3 gene rearrangements is extremely rare, and this rearrangement may potentially be enriched in tumors that demonstrate clear cell histology. Identification of FGFR3::TACC3 in patients with lung carcinomas with clear cell features may be of importance as they could potentially be candidates for therapy with tyrosine kinase inhibitors.

中文翻译：

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具有透明细胞特征和 FGFR3::TACC3 基因重排的非小细胞肺癌：7 例临床病理学和下一代测序研究。


描述了七例原发性肺肿瘤，其组织学特征为透明细胞形态和独特的 FGFR3::TACC3 基因重排。 4 名女性和 3 名男性出现肿瘤，年龄 47 至 81 岁（平均 68 岁）。它们发生在周围位置，主要是胸膜下，大小范围为 1.4 至 6.5 厘米（平均值 = 4.1 厘米）。所有肿瘤均显示出坚实的生长模式，具有丰富的中央坏死区和明显的核多形性。肿瘤表现出透明的细胞组织学，具有大的粘性肿瘤细胞，显示出非典型的细胞核和丰富的透明细胞质。免疫组织化学染色发现 5 例为鳞状细胞表型，2 例为腺癌表型。 1例为具有局灶性腺成分的鳞状细胞癌，其中1例呈局灶性肉瘤样改变。下一代测序在所有 7 例中均发现了 FGFR3::TACC3 基因重排。一个病例表现出同时激活的 FGFR3 突变，另一例表现出同时发生的 FGFR3 扩增。两个病例同时存在 KRAS G12D 突变。 1 例同时存在 KRAS 和 EGFR 突变，1 例同时存在 TP53 突变。携带 FGFR3::TACC3 基因重排的非小细胞肺癌极为罕见，这种重排可能在细胞组织学清晰的肿瘤中富集。在具有透明细胞特征的肺癌患者中鉴定 FGFR3::TACC3 可能很重要，因为他们可能是酪氨酸激酶抑制剂治疗的候选者。