Liu Changjiang, Liu Chengang, Zou Xiao, Shao Lin, Sun Ying, Guo Yang
Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
Burning Rock Biotech, Guangzhou, 510300, China.
Diagn Pathol. 2021 Mar 11;16(1):21. doi: 10.1186/s13000-021-01083-6.
In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.
Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.
Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.
在肺癌治疗中，多原发性肺癌（MPLC）与肺内转移（IMP）的鉴别诊断是一个关键点，具有直接的治疗和临床意义。然而，这一过程往往缺乏金标准，导致出现模棱两可的病例。在此，我们展示了一系列三个病例，其中二代测序（NGS）揭示的基因组改变模式有助于MPLC与IMP的鉴别诊断。
病例1是一名57岁女性，左肺上叶和下叶有两个独立病灶，组织病理学均确诊为T2aN0M0腺癌。NGS在一个病灶中检测到EGFR L858R突变，在另一个病灶中检测到EGFR 20外显子插入突变，提示双原发性恶性肿瘤。患者接受了楔形切除术，并接受了埃克替尼辅助治疗及化疗。她的无病生存期（DFS）为19个月，且仍在持续。病例2是一名55岁女性，双肺有多个小病灶。对右上叶切除病灶的组织病理学检查显示有三种亚型：肺泡上皮非典型腺瘤样增生、原位腺癌和微浸润腺癌。NGS在原位腺癌的两个病灶中检测到两种不同的BRAF驱动基因突变G466E和V600_K601delinsE，在微浸润腺癌的一个病灶中检测到BRAF K601E突变。病例3是一名68岁男性，右上叶病灶经组织病理学分类为T3NxM0混合性腺神经内分泌癌，左上叶病灶为T1aN0M0腺癌。对手术组织不同位点进行的NGS检测显示，右上叶病灶和淋巴结共有一种罕见的敏感EGFR突变G719A，左上叶病灶有两种EGFR突变L861Q和G719S。患者术后接受了埃克替尼治疗，病情稳定，无进展生存期为5个月。
我们的病例为NGS在辅助诊断和治疗决策方面的实用性提供了证据。
