A case report of idiopathic pulmonary fibrosis concurrent with EGFR 19 deletion lung adenocarcinoma
Case Report

A case report of idiopathic pulmonary fibrosis concurrent with EGFR 19 deletion lung adenocarcinoma

Zhiyi Li1#, Kai Xu2#, Ruxuan Chen1, Yujie Shi1, Mengqi Wang1, Qi Chen1, Ji Li3, Chi Shao1*, Hui Huang1*

1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; 2Radiological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; 3Pathological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

Contributions: (I) Conception and design: Z Li, K Xu, H Huang; (II) Administrative support: C Shao, H Huang; (III) Provision of study materials or patients: All authors; (IV) Collection and assembly of data: R Chen, Y Shi, M Wang, C Shao, J Li; (V) Data analysis and interpretation: Z Li, K Xu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

*These authors contributed equally to this work.

Correspondence to: Hui Huang, MD; Chi Shao, MD. Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan St, Dongcheng District, Beijing 100730, China. Email: pumchhh@126.com; shaochi@live.com.

Background: The likelihood of lung cancer in patients with pulmonary fibrosis is significantly increased, particularly the incidence of lung adenocarcinoma in areas affected by fibrosis, which is usually accompanied with epidermal growth factor receptor (EGFR) mutations. However, EGFR-tyrosine kinase inhibitor (TKI) can paradoxically induce or exacerbate pulmonary fibrosis as a serious adverse effect. Consequently, the use of EGFR-TKIs is approached with extreme caution in patients with lung cancer and co-existing interstitial lung disease, leading to a scarcity of clinical evidence regarding their application in individuals with both EGFR-mutated non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF).

Case Description: This article reports a rare and instructive case of a patient with a pre-existing diagnosis of IPF who subsequently developed lung adenocarcinoma harboring an EGFR mutation during clinical follow-up. The patient was managed with a combination therapy of icotinib (an EGFR-TKI) and Pirfenidone (an anti-fibrotic agent). This therapeutic strategy resulted in effective control of the lung adenocarcinoma while maintaining relative stability of the underlying pulmonary fibrosis. The patient’s eventual death was attributed to a severe coronavirus disease 2019 (COVID-19) infection, not to progression of cancer or pulmonary fibrosis.

Conclusions: This report aims to enhance clinicians’ understanding of pulmonary fibrosis complicated by lung cancer. Tumor molecular testing is also important in patients with NSCLC concurrent with IPF. Furthermore, it provides preliminary clinical evidence suggesting that, with careful monitoring and concomitant anti-fibrotic therapy, EGFR-TKIs like Icotinib may represent a viable treatment option for patients co-existing with IPF and EGFR-mutated NSCLC.

Keywords: Idiopathic pulmonary fibrosis (IPF); lung cancer (LC); epidermal growth factor receptor 19del (EGFR 19del); case report

Submitted Oct 01, 2025. Accepted for publication Dec 09, 2025. Published online Feb 10, 2026.

doi: 10.21037/tcr-2025-aw-2162

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Key findings

• We present a rare case of idiopathic pulmonary fibrosis (IPF) complicated by lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. Even if EGFR-tyrosine kinase inhibitor (TKI) is proved to induce pulmonary fibrosis, the application of TKI in our case achieved partial remission without severe exacerbation of pulmonary fibrosis.

What is known and what is new?

• IPF is a known risk factor for lung cancer, and EGFR mutations are commonly found in lung adenocarcinoma, particularly in non-smokers or light smokers. EGFR-TKIs are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC), but their safety in patients with pre-existing IPF remains poorly defined, with some evidence suggesting a possible association with pulmonary toxicity.

• Our case provides a concrete clinical example of EGFR-NSCLC arising in a patient with IPF, and discussed the therapeutic dilemma posed by the potential fibrogenic effect of EGFR-TKIs. It adds to the limited clinical literature on the management of this dual diagnosis and emphasizes the need for molecular profiling even in patients with concurrent interstitial lung disease.

What is the implication, and what should change now?

• Our case reinforces that tumor molecular testing should be routinely performed in NSCLC patients with coexisting IPF, as actionable mutations may influence treatment strategies. Clinicians should be vigilant about the potential pulmonary toxicity of EGFR-TKIs in this population and consider closer monitoring, multidisciplinary evaluation, and possibly alternative or modified treatment approaches.

Introduction

Lung cancer is a common complication of fibrotic interstitial lung disease (fILD), especially in patients with idiopathic pulmonary fibrosis (IPF). Lung cancer in these patients generally has a low positive rate of epidermal growth factor receptor (EGFR) mutations and a poor prognosis, and treatment with EGFR tyrosine kinase inhibitors (TKIs) carries the potential risk of drug-associated interstitial lung disease (ILD) and acute exacerbation of IPF. This article reports a case of a patient with a history of smoking, IPF, and EGFR exon 19 deletion mutation-positive non-small cell lung cancer (NSCLC), with combined treatment with pirfenidone and icotinib. We present this article in accordance with the CARE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2162/rc).

Case presentation

In April 2018, a 56-year-old male came to our hospital with the main complaint of recurrent cough and dyspnea on exertion, with no immunological features [including antinuclear antibody (ANA) profile, anti-neutrophil cytoplasmic antibody (ANCA) profile and etc.] but 40-year smoking history. Physical examination revealed bibasilar crackles. The patient’s immunological indicators, including ANA and ANCA, were all negative. Pulmonary function tests indicated reduced lung capacity [total lung capacity (TLC) at 69.6% of predicted value] and decreased diffusion function [diffusing capacity of the lung for carbon monoxide (DLCO) at 62.4% of predicted value]. As shown in Figure 1, high-resolution chest computed tomography (HRCT) (Figure 1, A1-A3) showed subpleural reticular opacities predominantly in the lower lobes, with some honeycombing changes, consistent with UIP. Pathological examination of a transbronchial lung biopsy from the right lower lobe revealed chronic inflammation and fibrous tissue proliferation. The patient was diagnosed as fILD, with a high possibility of IPF. Due to personal concerns, the patient refused antifibrotic medication. After 4 weeks of oral prednisone, there was no significant improvement in symptoms, and the patient discontinued the medication. However, pulmonary function tests indicated a further decline in DLCO (50.5% of predicted value), and the patient agreed to start pirfenidone, the only available anti-fibrotic choice at that time, but discontinued it after 1 month due to poor tolerance to gastrointestinal adverse events (especially nausea, abdominal distension and anorexia). In January 2021, a chest CT revealed a suspicious small nodule in the posterior basal segment of the right lower lobe and exacerbated fibrosis (Figure 1, B1-B3), with stable clinical symptoms. In January 2022, further laboratory tests revealed that the vital tumor markers [including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and Cyfra211] were all within normal range, and chest HRCT showed progression of pulmonary fibrosis predominantly near the pleura in both lower lungs, with a new small nodule in the right lower lung and some enlargement of the hilar and mediastinal regions (Figure 1, C1-C3). Further endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the 7th group of lymph nodes revealed clusters of atypical cells in the inflammatory exudate, consistent with malignancy, shown in Figure 2. Immunohistochemistry results showed CK7 (+), TTF-1 (+), ALK-D5F3 (−), P40 (−), ALK-D5F3 (NC) (−). Tumor molecular pathology testing indicated EGFR 19del (+) 5.2%, diagnosing NSCLC stage IIIB (EGFR exon 19 deletion). After a thorough discussion with clinicians of lung cancer and interstitial lung disease, the patient agreed to continue treatment with pirfenidone 600 mg tid and icotinib 125 mg tid on March 3, 2022. In this time, we adopted a dose titration strategy for pirfenidone, under which the patients achieved satisfactory tolerance. The chest CT in June showed that the right lung nodule size reduced from 1.0 to 0.6 cm, with no significant change in lymph node size or degree of pulmonary fibrosis (Figure 1, D1-D3), and the treatment was evaluated as partial remission (PR), defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. On December 4, 2022, the patient was tested positive for coronavirus disease 2019 (COVID-19) and passed away due to severe COVID-19 pneumonia and respiratory failure on Dec 22, 2022. The chest HRCT confirmed COVID-19 pneumonia was shown in Figure S1. The timeline of the patient’s history is shown in Table 1.

Figure 1 The serial chest CT of the patient. (A1-A3) Chest CT on June 15, 2018: subpleural reticular opacities predominantly in the lower lobes, with some honeycombing changes, and enlargement of the N7 lymph nodes; (B1-B3) chest CT on January 10, 2021: increased reticular and honeycombing opacities near the pleura in both lower lobes compared to previous scans, with a new small nodule in the posterior basal segment of the right lower lobe near the diaphragm, and no significant change in the enlargement of the N7 lymph nodes; (C1-C3) chest CT on January 6, 2022: further increased reticular and honeycombing opacities near the pleura in both lower lobes compared to previous scans, with a solid nodule (irregular shape, spiculated margins) in the posterior basal segment of the right lower lobe near the diaphragm, and significant enlargement of the N7 lymph nodes compared to previous scans; (D1-D3) CT on October 10, 2022: no significant change in pulmonary fibrosis compared to previous scans, disappearance of the solid nodule in the posterior basal segment of the right lower lobe, and significant reduction in the size of the N7 lymph nodes compared to previous scans. CT, computed tomography.
Figure 2 Pathological examination of the EBUS-TBNA specimen (hematoxylin and eosin stain). (A) Low-power view showing the tissue architecture (magnification ×150). (B) High-power view (magnification ×300) revealing cancer cells embedded in the crushed lymphoid tissue. EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration.

Table 1

The timeline in this case

Time Event
April 2018 Initial diagnosis of fILD based on chest HRCT
December 2018 Initial treatment of pirfenidone
January 2019 Discontinuation of pirfenidone due to gastrointestinal adverse events
January 2021 Chest CT revealed a suspicious small nodule and exacerbated fibrosis
January 2022 Chest HRCT showed progression of pulmonary fibrosis, with a new small nodule in the right lower lung and some enlargement of the hilar and mediastinal regions
February 2022 EBUS-TBNA of the 7th group of lymph nodes revealed clusters of atypical cells in the inflammatory exudate, consistent with malignancy
March 2022 Initiation of pirfenidone 600 mg tid and icotinib 125 mg tid
April 2022 Chest CT showed that the right lung nodule size reduced from 1.0 to 0.6 cm
October 2022 Treatment to NSCLC was evaluated as PR
December 2022 The patient was tested positive for COVID-19 and passed away due to severe COVID-19 pneumonia and respiratory failure

CT, computed tomography; COVID-19, coronavirus disease 2019; EBUS-TBNA, endobronchial ultrasound-guided transbronchial needle aspiration; fILD, fibrotic interstitial lung disease; HRCT, high-resolution chest computed tomography; NSCLC, non-small cell lung cancer; PR, partial remission.

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

FILD refers to a group of ILD with at least 10% fibrotic components confirmed by pathology or imaging (1), among which, IPF often presents as usual interstitial pneumonia (UIP) on imaging and pathology. In this case, the patient had no immunological features, no history of occupational dust exposure, and typical UIP HRCT patterns, suggesting a diagnosis of fILD, most likely IPF.

The incidence of lung cancer in ILD patients is significantly higher than that in the general population, with the probability of lung cancer in IPF patients ranging from 2.7% to 48% (2). The pathological types of lung cancer vary among different studies, while adenocarcinoma is more common in our center (3). Tumor molecular testing is valuable for the medical treatment of advanced lung cancer (4), but ILD is an independent negative indicator for EGFR mutation tumors, and the mutation rate of EGFR in IPF patients with lung cancer is even lower (5). The tumor molecular testing in this patient indicated an EGFR exon 19 deletion, which is relatively rare in clinical practice.

In the treatment of IPF with lung cancer, an individualized treatment plan should be developed based on the stage of lung cancer and tumor molecular typing: for patients with early-stage lung cancer, controllable IPF, and good overall health, surgical resection under antifibrotic drugs can be considered (6); for patients with advanced lung cancer but non-acute exacerbation of IPF, drug treatment is a generally choice. Given the low probability of gene mutations in IPF patients with NSCLC (5), the high risk of drug-associated ILD, poor prognosis, and the risk of inducing acute exacerbation of IPF (7,8), TKI drugs are not commonly used in IPF patients with NSCLC. As for immune checkpoint inhibitor (ICI)-based antitumor immunotherapy, its potential harm of ICI-related pneumonia to IPF patients relatively prevents its application in IPF patients with lung cancer (9). Therefore, chemotherapy is generally chosen for these patients.

EGFR is closely associated with ILD. Numerous studies have reported the upregulation of EGFR and its ligands in fibrotic lung tissue, confirming that EGFR pathway hyperactivation drives pulmonary fibrosis (10). Conversely, accumulating clinical evidence demonstrates that EGFR-TKIs also induce ILD, suggesting that pathway inhibition is equally detrimental to lung tissue. TKI-induced ILD is typically acute or subacute, with an onset of approximately one month. The incidence varies by generation; notably, osimertinib exhibits a significantly higher rate of drug-induced ILD compared to first-generation agents (11). Key risk factors include pre-existing lung disease, lung injury or inflammation, poor performance status, smoking history, and ethnicity (12). Nevertheless, given the therapeutic effect of EGFR-TKIs on lung cancer patients with EGFR mutations, studies have shown that re-administration of EGFR-TKIs in patients with EGFR-TKI-related ILD can benefit approximately 80% of patients, with only 16.7% experiencing grade 3 or higher EGFR-TKI-related ILD (13). In this case, the patient had a lung cancer with EGFR exon 19 deletion, and IPF was in a non-acute exacerbation, moderate stage. After fully explaining the benefits and risks of TKI drugs to the patient’s family, the patient and family agreed to receive antitumor TKI drug treatment. Multiple international IPF guidelines have advised advantages of antifibrotic drug treatment (14-17), it was recommended that the patient should continue regular antifibrotic drug treatment. There were no acute exacerbations occurred during subsequent TKI treatment. Unfortunately, the patient passed away due to severe COVID-19 pneumonia and rapid respiratory failure following a COVID-19 infection at the end of 2022, a course we attribute to their underlying IPF. Our previous studies have also demonstrated that patients with IPF are highly susceptible to developing severe pneumonia during the COVID-19 pandemic (18).

The quality of life and survival rate of IPF patients have improved thanks to the development of antifibrotic drugs (19). Complications such as lung cancer and acute exacerbations are important factors affecting prognosis. Although the mutation rate of EGFR is not high in IPF patients with NSCLC, standardized tumor molecular typing can help identify a small subset of IPF patients with lung cancer who have EGFR mutations.

Conclusions

Under the protection of a comprehensive treatment strategy based on antifibrotic drugs, targeted antitumor TKI drug treatment for EGFR mutations may provide survival benefits.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2162/rc

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2162/prf

Funding: This study was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0509500).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-2025-aw-2162/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient’s family for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Li Z, Xu K, Chen R, Shi Y, Wang M, Chen Q, Li J, Shao C, Huang H. A case report of idiopathic pulmonary fibrosis concurrent with EGFR 19 deletion lung adenocarcinoma. Transl Cancer Res 2026;15(2):134. doi: 10.21037/tcr-2025-aw-2162

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