Postoperative incision metastasis of lung cancer: A case report

Abstract

Incisional recurrence, also known as metastasis to the surgical scar, is a relatively rare but serious complication following the surgical resection of lung cancer. Herein, we report a case of postoperative incision metastasis of lung cancer. A 75-year-old Han Chinese male patient was admitted upon discovery of a chest wall mass during a routine physical examination 3 months ago. The patient underwent a radical resection of left lower lobe lung cancer 12 years ago. Notably, he experienced left chest pain and discomfort during a routine examination 12 years postoperatively, leading to the discovery of a chest wall mass measuring 3.5 cm × 2.1 cm × 4.2 cm at the original incision site. Ultrasound-guided core biopsy confirmed the pathological diagnosis of lung adenocarcinoma derived from the chest wall incision, and subsequent gene testing identified a SLC34A2–ROS1 (S4;R31) fusion gene mutation. After the patient underwent two cycles of chemotherapy, a re-examination of the chest computed tomography scan revealed that the mass on the chest wall had significantly shrunk. Subsequently, the patient underwent surgical resection of the chest wall mass. Postoperative pathology confirmed metastatic lung adenocarcinoma from the postoperative incision of lung cancer. The patient was discharged uneventfully and has not shown any obvious recurrence or metastasis during the 2-month follow-up. Improved prognosis of postoperative incisional metastasis of lung cancer is observed after timely comprehensive treatment.

Introduction

Lung cancer is the most prevalent malignant tumor worldwide. The rates of incidence and case fatality of lung cancer are found to be among the highest of all malignant tumors. Non–small cell lung cancer (NSCLC) accounts for 85%–90% of all lung cancers. ¹ Upon the diagnosis of lung cancer, 16% of patients are diagnosed as having early-stage (stages I–II) cancer, 22% as having locally advanced (stage III) cancer, and 57% as having advanced cancer. ¹ For patients with stage I, II, or stage IIIa NSCLC, radical surgical resection is the best treatment option, and the recognized standard procedure is “lobectomy +systemic mediastinal lymph node dissection.” However, approximately 30%–55% of patients still experience recurrence and metastasis after radical resection, leading to treatment failure. ² The 5-year recurrence-free survival rate of patients with NSCLC after radical resection varies substantially depending on the postoperative pathological stage. The 5-year disease-free survival (DFS) rate of patients with stages Ib–IIIb ranges from 17% to 73% and needs further improvement. ³ In addition, the site of recurrence varies with staging. For stage I cases, the local and distant recurrence rates are similar (approximately 10%). For stage IIb–IIIa cases, the local recurrence rate is 12%–15%, while the distant recurrence rate reaches 40%–60%.^4–6 Incisional recurrence, also known as metastasis to the surgical scar, is a relatively rare but serious complication following the surgical resection of lung cancer. Despite advancements in surgical techniques and adjuvant therapies, the incidence and mechanisms of incisional recurrence remain poorly understood. The possible mechanisms for the recurrence of cancer after resection include changes in the tumor microenvironment, residual microscopic lesions, the role of inflammation and immune responses in promoting tumor recurrence, and other factors. This phenomenon can significantly impact patient outcomes and quality of life, necessitating a deeper understanding of its pathophysiology and potential preventive strategies.

Case presentation

A 75-year-old Han Chinese male patient was admitted upon the discovery of a chest wall mass during a routine physical examination 3 months ago. The patient was admitted to the Thoracic Surgery Department of the Second Affiliated Hospital of the Army Medical University of Chongqing in January 2024.

Regarding medical history, the patient underwent radical resection of left lower lobe lung cancer 12 years ago (tumor size: 4 cm × 3.5 cm). Figure 1 shows the preoperative chest computed tomography (CT) scan from 12 years ago. The enhanced CT scan of the chest showed a solid tumor in the lower lobe of the left lung that had invaded the pleura, with visible pleural atrophy. Small air bubbles were noted inside the tumor. No significant enlargement of the mediastinal lymph nodes was observed. The postoperative stage of the patient’s lung cancer was T2N0M0IB. Postoperatively, the patient received four cycles of chemotherapy with pemetrexed disodium injection and cisplatin. Notably, 12 years postoperatively, the patient experienced left chest pain and discomfort during a routine examination, leading to the discovery of a chest wall mass measuring 3.5 × 2.1 cm × 4.2 cm at the original incision site. After admission, a contrast-enhanced chest CT and positron emission tomography–CT (PET–CT) were performed, which confirmed the location of the chest wall mass at the left pectoralis major and minor muscle interval between the 4th and 5th ribs, as shown by the arrow in Figure 2. Ultrasound-guided core biopsy confirmed the pathological diagnosis of lung adenocarcinoma derived from the chest wall incision, and subsequent gene testing identified a SLC34A2–ROS1 (S4;R31) fusion gene mutation. The patient received two cycles of chemotherapy with docetaxel injection and cisplatin, followed by 2 months of targeted therapy with crizotinib (250 mg oral, twice daily). A follow-up chest CT scan revealed a significant reduction in the size of the chest wall mass. Subsequently, the patient underwent surgical resection of the chest wall mass (Figure 3, intraoperative photo; Figure 4, complete resection of the chest wall tumor; Figure 5, postoperative chest wall incision, with the arrow indicating the original incision site). Postoperative pathology confirmed metastatic lung adenocarcinoma from the postoperative incision of lung cancer. The patient was discharged uneventfully and has not shown any obvious recurrence or metastasis during the 2-month follow-up.

Figure 1.

Preoperative chest CT scan conducted 12 years ago. CT: computed tomography.

Figure 2.

The chest wall mass is located between the 4th and 5th ribs of the left pectoralis major and minor intermuscular septum.

Figure 3.

Intraoperative photo.

Figure 4.

Complete resection of the chest wall tumor.

Figure 5.

Postoperative chest wall incision, with the arrow indicating the original incision site.

Discussion

The case of a 75-year-old Han Chinese male patient presented here is an illustrative example of the challenges faced in the management of recurrence in patients with lung cancer, particularly those with a history of surgical intervention. The patient’s initial diagnosis and treatment for lung adenocarcinoma of the left lower lobe, followed by chemotherapy, represented a successful management strategy conducted 12 years ago. However, subsequent development of a chest wall mass at the original incision site raises several important considerations for clinical management and highlights the potential for local recurrence even after an extended disease-free interval.

The discovery of a mass in the chest wall during a routine physical examination prompted further imaging and biopsy, which subsequently confirmed the mass as a metastatic lung adenocarcinoma. Localization of the mass between the 4th and 5th ribs, at the interval of the pectoralis major and minor muscles, suggests a direct extension or recurrence at the original surgical incision site. This finding is significant and indicates a potential weakness or vulnerability at the surgical site, which may serve as a conduit for metastasis.

The pathological diagnosis of lung adenocarcinoma derived from the chest wall incision, coupled with the identification of a SLC34A2–ROS1 fusion gene mutation, offers critical insights into the molecular biology of this recurrence. The presence of this mutation is particularly noteworthy as it is a known oncogenic driver that can be targeted with specific therapies, such as crizotinib, which the patient received following chemotherapy with docetaxel and cisplatin.

Late-stage tumor recurrence is often closely related to increased drug resistance and invasive behavior of tumor cells, which allows tumor cells to evade immune surveillance and various treatment methods and then regrow in residual or small metastases after surgery, resulting in recurrence. ⁷ The SLC34A2–ROS1 fusion gene, one of the important subtypes of ROS1 fusion mutations, exhibits a certain frequency of occurrence (approximately 10%) in several tumors such as NSCLC. It promotes tumor cell proliferation, survival, and migration by activating multiple downstream signaling pathways of ROS1 tyrosine kinase. The specific mechanism includes enhancement of the antiapoptotic ability and proliferation potential of tumor cells by activating signaling pathways such as PI3K/AKT, MAPK, and STAT3 while promoting the motility and invasive ability of tumor cells. ⁸ In addition, the presence of the SLC34A2–ROS1 fusion gene may regulate the tumor immune microenvironment, helping tumor cells evade immune surveillance by regulating the secretion of immunosuppressive factors or inhibiting the activity of effector T cells and natural killer cells, thereby promoting tumor cell survival in the local environment and forming late-stage recurrence foci. ⁹ Surgical incisions, a special area of the local microenvironment, often trigger inflammatory reactions, immune cell infiltration, and matrix remodeling due to tissue damage, providing favorable conditions for tumor cell metastasis and colonization. The activation of the signaling pathway driven by the SLC34A2–ROS1 fusion gene may enhance the adaptability and survival ability of tumor cells, leading to the formation of metastatic lesions in the incision area and resulting in late recurrence. ¹⁰

The significant reduction in the size of the chest wall mass following targeted therapy with crizotinib underscores the efficacy of this treatment in managing the recurrence of ROS1-positive lung cancer. The subsequent surgical resection of the chest wall mass, as evidenced by the intraoperative and postoperative photographs, demonstrates a comprehensive approach to the treatment of this aggressive recurrence. The postoperative pathology confirmed the metastatic nature of the tumor, validating the decision of surgical resection.

The World Health Organization classification of lung tumors defines adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) as cancers with no or limited histologic invasive components. It is reported that the surgical treatment of lung adenocarcinoma is mainly based on wedge resection (82%), with 97.7% of noninvasive lung cancer cases falling into this category. The 5-year recurrence-free survival rate after surgical treatment is 99.7%, with no events of local recurrence. ¹¹ Although the probability of patients with AIS or MIA being recurrence-free for 5 years postoperatively has been found to be 100%,^12,13 some studies extend the follow-up time to avoid the impact of time. A previous study reviewed the pathologic findings of 4768 patients who underwent resection for lung cancer between 1998 and 2010 and showed no recurrence of lung cancer for either AIS or MIA cases. The estimated 10-year postoperative disease-specific survival rates were 100% and 100% for AIS and MIA, respectively (p ¼: 0.72). ¹⁴ According to these investigations, the recognized 10-year recurrence-free survival rate for adenocarcinoma is 100%.

However, the patient in this case had undergone resection of the cancerous site of the lung 12 years ago and recently experienced a recurrence at the incision site. This demonstrates that patients with lung cancer are not cured without recurrence for 10 years postoperatively. Patients still need regular checkups and vigilance. In addition, the case is a relatively rare complication, which may be due to the shedding of tumor cells and implantation at the incision site during the surgical procedure. Therefore, for lung cancer surgery, the principle of tumor-free operation should be strictly followed to reduce the risk of such complications.

This case also highlights the importance of long-term surveillance in patients with lung cancer, even those who have remained disease-free for an extended period. The 2-month follow-up without evidence of recurrence or metastasis is encouraging; however, it serves as a reminder that such patients require ongoing monitoring, which can help detect and address potential recurrences promptly.

In addition, two cycles of docetaxel plus cisplatin chemotherapy, combined with 2 months of crizotinib targeted therapy, led to a marked reduction in the size of the chest wall mass on CT. Subsequently, the patient underwent surgical removal of the chest wall mass. In this treatment mode, chemotherapy drugs were initially used to inhibit the metastasis of cancer, after which surgical resection was performed. The patient was followed up for 2 months after discharge, and no recurrence was noted. Compared with the traditional treatment methods, the idea of chemotherapy drugs combined with surgical resection can provide reference for future clinical application.

In the study of postoperative incision metastasis of lung cancer, changes in gene expression levels, activation of cellular signaling pathways, and molecules in the tumor microenvironment have gradually received attention. An analysis of the literature showed that the mechanism of tumor cell metastasis through incisions after surgery is closely related to various molecular biological processes. Among them, changes in gene expression levels, activation of cellular signaling pathways, and remodeling of the tumor microenvironment play key roles in the process of metastasis. ¹⁵ The study of key regulatory networks revealed the importance of multiple signaling pathways in incision transfer. For example, the transforming growth factor-β (TGF-β) signaling pathway has been found to be closely related to the invasiveness and metastatic ability of lung cancer cells. TGF-β promotes the migration of tumor cells from the primary tumor site to the incision site by inducing epithelial–mesenchymal transition (EMT), leading to the occurrence of incision metastasis. ¹⁶ In addition, studies have found that certain interacting proteins, such as β-catenin and E-cadherin, play important roles in regulating intercellular adhesion and migration, affecting the metastatic ability of tumor cells. ¹⁷

In conclusion, this case report underscores the complexity of managing lung cancer recurrences, particularly when they involve the chest wall at the original surgical incision site. The integration of imaging, pathology, molecular testing, systemic therapy, and surgical resection can lead to effective management and improved outcomes for patients with this challenging condition. Postoperative incisional metastasis of lung cancer is rare, with improved prognosis after timely comprehensive treatment.