小细胞癌与腺癌双向转化晚期肺癌综合治疗1例报道并文献回顾

doi:10.3969/j.issn.1009-976X.2026.04.010

摘要/Abstract

摘要： 总结1例小细胞癌（SCLC）与腺癌（ADC）双向转化的晚期肺癌患者的诊疗过程,探讨其疾病转化及多线治疗策略。分析1例右侧SCLC Ⅳ期患者的临床资料、病理特征、基因检测结果及治疗经过。患者为51岁女性,历经阿替利珠单抗联合EP方案一线治疗、贝伐珠单抗联合奥希替尼二线治疗及后续治疗。治疗过程中出现SCLC→肺腺癌（ADC）→SCLC的双向病理转化,并检出EGFR基因第19外显子突变（p.L747_P753delinsS）。患者总生存期达37个月。本文展示了SCLC在治疗压力下出现病理转化和基因突变演变的复杂性,基于动态再活检的多线个体化治疗可为晚期患者带来生存获益,旨在为临床实践提供参考。

关键词: 小细胞肺癌, 肺腺癌, 病理转化, EGFR突变, 多线治疗, 病例报道

Abstract: This report aimed to summarize the diagnosis and treatment process of a patient with advanced lung cancer with bidirectional transformation between small cell lung carcinoma and lung adenocarcinoma and to explore the disease transformation and multi-line treatment strategies. The clinical data, pathological features, genetic testing results, and treatment course of a patient with stage Ⅳ right-sided SCLC were analyzed. The patient was a 51-year-old woman who received first-line therapy with atezolizumab plus EP regimen, second-line therapy with bevacizumab plus osimertinib, and multiple subsequent lines of treatment. During the treatment course, bidirectional pathological transformation （SCLC → lung adenocarcinoma → SCLC） occurred, and an EGFR exon 19 mutation （p.L747_P753delinsS） was detected. The patient's overall survival reached 37 months. This case demonstrates the complexity of pathological transformation and genetic mutation evolution in SCLC under therapeutic pressure. Multi-line individualized therapy based on dynamic re-biopsy can provide survival benefits for patients with advanced SCLC. This report aims to provide a reference for clinical practice.

Key words: small cell lung cancer, lung adenocarcinoma, pathological transformation, EGFR mutation, multi-line treatment, case report

中图分类号:

R734.2

乐灵丹, 谢德荣, 江志敏. 小细胞癌与腺癌双向转化晚期肺癌综合治疗1例报道并文献回顾[J]. 岭南现代临床外科, 2026, 25(04): 273-279.

YUE Lingdan, XIE Derong, JIANG Zhimin. Comprehensive treatment of advanced lung cancer with bidirectional transformation between small cell carcinoma and adenocarcinoma： a case report and literature review[J]. Lingnan Modern Clinics In Surgery, 2026, 25(04): 273-279.

参考文献

[1] Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors[J]. Sci Transl Med, 2011, 3(75): 75ra26.
[2] Oser MG, Niederst MJ, Sequist LV, et al.Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin[J]. Lancet Oncol, 2015, 16(4): e165-e172.
[3] Marcoux N, Gettinger SN, O'Kane G, et al. EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes[J]. J Clin Oncol, 2019, 37(4): 278-285.
[4] Reck M, Dziadziuszko R, Sugawara S, et al.Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study[J]. Lung Cancer, 2024, 196: 107924.
[5] Lee JK, Lee J, Kim S, et al.Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas[J]. J Clin Oncol, 2017, 35(26): 3065-3074.
[6] Kuang L, Wang P, Zhou L, et al.Transformation of lung adenocarcinoma to small cell lung cancer following osimertinib treatment: a case report and literature review[J]. Anticancer Drugs, 2025, 36(3): 253-259.
[7] Horn L, Mansfield AS, Szczęsna A, et al.First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer[J]. N Engl J Med, 2018, 379(23): 2220-2229.
[8] Han B, Li K, Zhao Y, et al.Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302)[J]. Br J Cancer, 2018, 118(5): 654-661.
[9] Ahn MJ, Cho BC, Felip E, et al.Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer[J]. N Engl J Med, 2023, 389(22): 2063-2075.
[10] Kawanaka Y, Yonesaka K, Tanizaki J, et al.Case Report: A small cell lung cancer transformed from an EGFR-mutated Adenocarcinoma demonstrated a long-term remission to anti PD-1 antibody[J]. Front Oncol, 2025, 15: 1651248.
[11] Paz-Ares L, Borghaei H, Liu SV, et al.Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial[J]. Lancet, 2025, 405(10495): 2129-2143.
[12] Zhang B, Zhong R, Shi C, et al.Durvalumab plus anlotinib versus durvalumab alone as maintenance treatment in extensive-stage small-cell lung cancer (DURABLE): a multicenter, randomized, phase II trial and biomarker analysis[J]. Nat Commun, 2026, 17(1): 6780.
[13] Paulson KG, Lau SCM, Ahn MJ, et al.Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study[J]. Lancet Oncol, 2025, 26(10): 1300-1311.
[14] Wang H, Gao N, Wang L, et al. Transformation from EGFR-mutant lung adenocarcinoma to small-cell lung cancer: from clonal evolution to lineage reprogramming[J]. Cancer Treat Rev, 2025, 141: 103044.
[15] Ju Q, Wu YT, Zhang Y, et al.Histology transformation-mediated pathological atypism in small-cell lung cancer within the presence of chemotherapy: A case report[J]. World J Clin Cases, 2021, 9(34): 10652-10658.
[16] Hao L, Chen H, Wang L, et al.Transformation or tumor heterogeneity: Mutations in EGFR, SOX2, TP53, and RB1 persist in the histological rapid conversion from lung adenocarcinoma to small-cell lung cancer[J]. Thorac Cancer, 2023, 14(11): 1036-1041.
[17] Chen X, He W, Yang N, et al.[Histological Transformation from Non-small Cell Lung Cancer to Small Cell Lung Cancer Induced by Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review][J]. Zhongguo Fei Ai Za Zhi, 2025, 28(7): 558-566.
[18] Wysota M, Asiry S, Goldstein Y, et al.Revolving Door of Histologic Transformation-Tumor Heterogeneity Complicating the Management of EGFR-Mutated Lung Adenocarcinoma: A Case of Jekyll and Hyde[J]. JTO Clin Res Rep, 2021, 2(2): 100128.
[19] Ninomaru T, Hata A, Hara S, et al.Heterogeneity or transformation? A whack-a-mole case of EGFR-mutant lung adenocarcinoma and small cell carcinoma: A case report[J]. Thorac Cancer, 2022, 13(16): 2394-2397.
[20] Tanaka S, Yokota K, Yoshimura N, et al.A case of EGFR-positive lung adenocarcinoma that once transformed into small cell carcinoma but worsened into adenocarcinoma again[J]. Respir Med Case Rep, 2025, 57: 102271.
[21] Takagi Y, Nakahara Y, Hosomi Y, et al.Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing “wax-and-wane” transformation[J]. BMC Cancer, 2013, 13: 529.
[22] Woo CG, Son SM, Lee HC, et al.Histologic Changes in Non-Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples[J]. Cancer Res Treat, 2022, 54(3): 737-743.
[23] Atashrazm F, Bradshaw G, Clark J, et al.Plasticity in EGFR-mutant NSCLC: SCLC transformation and subsequent re-emergence: case report[J]. Front Oncol, 2026, 16: 1902531.
[24] Li X, Ding K, Liu D, et al.Histologic transformation after targeted therapy resistance in driver gene-positive NSCLC: mechanisms and therapeutic challenges[J]. Ther Adv Med Oncol, 2025, 17: 17588359251369038.
[25] Iams WT, Beckermann KE, Almodovar K, et al.Small Cell Lung Cancer Transformation as a Mechanism of Resistance to PD-1 Therapy in KRAS-Mutant Lung Adenocarcinoma: A Report of Two Cases[J]. J Thorac Oncol, 2019, 14(3): e45-e48.
[26] Yin X, Li Y, Wang H, et al.Small cell lung cancer transformation: From pathogenesis to treatment[J]. Semin Cancer Biol, 2022, 86(Pt 2): 595-606.
[27] Mehta A, Stanger BZ.Lineage Plasticity: The New Cancer Hallmark on the Block[J]. Cancer Res, 2024, 84(2): 184-191.