# Non-small Cell Lung Cancer with Metachronous Mutations of EGFR and ALK Genes: A Case Report and Literature Review

## TL;DR

This paper reports a rare case of non-small cell lung cancer where a patient developed EGFR mutations four years after an initial ALK mutation, highlighting challenges in diagnosing and treating metachronous lung cancers.

## Contribution

The study presents a novel case of sequential EGFR and ALK mutations in lung cancer, offering insights into metachronous tumor development.

## Key findings

- A patient with ALK-positive lung cancer later developed EGFR mutations and multiple metastases.
- Molecular testing confirmed the distinct genetic origins of the two tumors, supporting a metachronous rather than metastatic origin.
- The case underscores the importance of genetic profiling in guiding personalized treatment for complex lung cancer cases.

## Abstract

多原发肺癌（multiple primary lung cancer, MPLC）指患者有两个或两个以上原发病灶的肺癌，根据发生时间的不同分为同时性多原发肺癌（synchronous MPLC, sMPLC）和异时性多原发肺癌（metachronous MPLC, mMPLC）。近年来，MPLC的检出率逐渐升高，但由于肿瘤的异质性，在鉴别MPLC和肺内转移（intrapulmonary metastasis, IM）上存在许多争议，特别是病理组织学类型相同时。考虑到目前二者在临床治疗策略及预后上的显著差异，对于MPLC和IM的精确诊断是个体化精准治疗的关键。分子遗传学及测序技术为检测肿瘤的克隆性起源提供了有效的策略，其中非小细胞肺癌表皮生长因子受体（epidermal growth factor receptor, EGFR）突变与间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合突变共存的病例陆续有报道，但ALK基因突变后再发EGFR突变的案例未见提及。本文通过分子遗传学技术准确诊断并回顾性分析了1例ALK突变型男性肺腺癌患者术后4年再发EGFR突变合并多发转移的临床资料，并复习相关文献，以期加深对mMPLC的认识，为该类病例的诊疗提供临床借鉴。

Genetic testing results of the patient