Hussain Muhammad, Mackrides Nicholas, Su Stacey, Seth Anjali
Pathology and Laboratory Medicine, Temple University Hospital, Philadelphia, USA.
Hematopathology, Fox Chase Cancer Center, Philadelphia, USA.
Cureus. 2024 Oct 5;16(10):e70896. doi: 10.7759/cureus.70896. eCollection 2024 Oct.
Molecular profiling of lung tumors is crucial for guiding targeted therapeutic strategies and identifying potential resistance mechanisms to specific therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). During this profiling, mutations with uncertain treatment implications can be identified. This case study represents a 69-year-old female with a co-occurring EGFR mutation profile that presents a unique therapeutic challenge. Tumor DNA was used for next-generation sequencing (NGS) of a custom 275 cancer-related QIAseq Human Comprehensive Cancer Panel (Qiagen). Next-generation RNA sequencing was performed using the Illumina TruSight panel. FISH analysis and PD-L1 22C3 immunohistochemical testing were also performed. Microscopic analysis revealed an invasive adenocarcinoma with papillary, acinar, and focal micropapillary features with a 6 mm invasive component. The final pathology stage was determined to be pT1aN0M0. NGS for DNA variant detection identified two mutations in EGFR, an EGFR G719A and EGFR L833_V834delinsFL with a variant allele frequency (VAF) of 22.2% and 21.1%, respectively. Targeted NGS RNA fusion analysis was also performed, which came back negative. PD-L1 22C3 immunohistochemical testing showed only 1% of the tumor cells expression. FISH analysis revealed one copy of MET and D7Z1 in 27% of cells, indicating an aneuploid neoplastic clone with monosomy 7. EGFR TKIs are universally accepted as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with a sensitizing EGFR mutation. While mutations such as G719A are sensitive to all generations of EGFR-TKI, the effects are unknown for rare compound mutations in EGFR, such as EGFR L833_V834delinsFL. There are no reports in the literature with any mention of an algorithm of treatment for such a case. The patient had two metachronous lung primary cancers resected in 2022 and 2024. Due to the complete surgical resection, the sensitivity of this mutation of TKIs could not be established. This unique mutation profile still remains of paramount importance to understand if the patient relapses or presents with a new tumor with the same genetic profile.
肺肿瘤的分子特征分析对于指导靶向治疗策略以及识别对特定疗法（如表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs））的潜在耐药机制至关重要。在这种特征分析过程中，可能会发现对治疗意义不明确的突变。本病例研究呈现了一名69岁女性，其同时存在的EGFR突变谱带来了独特的治疗挑战。肿瘤DNA用于对定制的275个癌症相关基因的QIAseq人类综合癌症检测板（Qiagen）进行二代测序（NGS）。使用Illumina TruSight检测板进行二代RNA测序。还进行了FISH分析和PD-L1 22C3免疫组化检测。显微镜分析显示为浸润性腺癌，具有乳头状、腺泡状和局灶性微乳头特征，浸润成分6mm。最终病理分期确定为pT1aN0M0。用于DNA变异检测的NGS在EGFR中鉴定出两个突变，一个EGFR G719A和一个EGFR L833_V834delinsFL，变异等位基因频率（VAF）分别为22.2%和21.1%。还进行了靶向NGS RNA融合分析，结果为阴性。PD-L1 22C3免疫组化检测显示仅1%的肿瘤细胞表达。FISH分析显示27%的细胞中有一个MET和D7Z1拷贝，表明存在一个具有7号染色体单体的非整倍体肿瘤克隆。EGFR TKIs被普遍接受为具有敏感EGFR突变的晚期非小细胞肺癌（NSCLC）患者的一线治疗药物。虽然G719A等突变对所有代的EGFR-TKI均敏感，但对于EGFR中的罕见复合突变（如EGFR L833_V834delinsFL）的影响尚不清楚。文献中没有关于此类病例治疗方案的报道。该患者在2022年和2024年切除了两个异时性肺原发性癌。由于手术完全切除，无法确定该突变对TKIs的敏感性。如果患者复发或出现具有相同基因谱的新肿瘤，了解这种独特的突变谱仍然至关重要。
