Aggressive Squamous Cell Lung Carcinoma in a Long-Term E-Cigarette User with Intracardiac Complications: A Case Report

Introduction

Lung carcinoma is the leading cause of cancer-related mortality globally, with tobacco smoking as the primary risk factor [1]. The U.S. Preventive Services Task Force (USPSTF) recommends annual low-dose computed tomography (CT) screening for lung cancer in individuals aged 50–80 with a smoking history of ≥20 pack-years, including current smokers or those who have quit within the past 15 years [2]. However, these guidelines do not account for electronic nicotine delivery systems (ENDS), also known as electronic cigarettes (e-cigarettes) [2]. E-cigarette use (vaping) has become increasingly prevalent, particularly among younger populations [3]. Although marketed as a safer alternative to traditional smoking, e-cigarettes expose vulnerable tissues to nicotine and other carcinogenic compounds [3,4]. Emerging evidence also suggests that e-cigarette use can increase the risk of lung cancer and accelerate tumor progression [3,5].

While literature exploring the relationship between ENDS use and lung cancer is still evolving, past reports have described cases of squamous cell carcinoma (SCC) of the lung with intracardiac tumor thrombus via invasion of the pulmonary veins [6–10]. These previously reported cases typically involved older individuals (≥60 years) and were characteristically associated with extensive tobacco smoking histories [6–10]. In contrast, the present case is notable for the patient’s relatively young age, limited history of combustible tobacco use, large tumor burden, rapid clinical decline, and prolonged history of e-cigarette use. While a causal link cannot be established, this case prompts further consideration of whether ENDS use is associated with the development or progression of malignancy in certain individuals.

Case Report

A 51-year-old man with a history of type 2 diabetes, hypertension, and obstructive sleep apnea, who was under regular follow-up with outpatient pulmonology and cardiology, first presented to the hospital with hemoptysis and a month-long history of weight loss, reduced appetite, nonspecific chest discomfort, and worsening dyspnea. He had a 10-pack-year smoking history (quit in 2009) and 11 years of e-cigarette use. A chest radiograph showed a large left upper-lobe mass near the aortic knob (Figure 1). CT angiography (CTA) revealed a 12×10×13 cm mediastinal mass extending into the left upper lobe, left mainstem bronchus, and left atrium (Figure 2). Notably, a chest radiograph taken 2 years earlier, when the patient was 49 years old, had been normal.

Bronchoscopy with biopsy confirmed poorly differentiated non-small cell lung carcinoma (NSCLC), favoring squamous cell histology. Transesophageal echocardiography (TEE) identified a 6.6×4.6×3.7 cm lobulated tumor thrombus occupying approximately 64% of the left atrial volume (Figure 3). The mass had prolapsed into the left ventricle during diastole, causing mild to moderate mitral regurgitation and dynamic stenosis. Pathological analysis revealed high-molecular-weight cytokeratin and focal positivity for CK5/6, p40, and p63. After a multidisciplinary discussion, surgical resection was deemed unfeasible due to extensive tumor infiltration into critical cardiac structures. Following stabilization, the patient was discharged from the hospital in stable condition with plans for close outpatient follow-up with oncology.

Approximately 2 weeks later, he returned to the hospital with worsening respiratory distress. Imaging revealed a 35% increase in intracardiac tumor volume and a moderate pericardial effusion without evidence of tamponade. Bronchoscopy found significantly worsening compression of the left and right mainstem bronchi secondary to mass effect. Placement of a Y-shaped stent led to clinical improvement, and the patient was discharged in stable condition with outpatient palliative radiation to maintain airway patency.

Outpatient oncology determined a tumor proportion score (TPS) of 95% and a tumor mutational burden (TMB) of 18 mut/Mb. PET imaging revealed a hypermetabolic anterior mediastinal and subcarinal mass, as well as hypermetabolism along the anterior pleural surface of the left upper lobe and mediastinal lymph nodes. Brain MRI excluded intracranial metastases. About 1 month after his initial diagnosis, the patient began a 21-day chemotherapy regimen consisting of paclitaxel (204 mg IV on chemotherapy cycle days 1, 8, and 15), carboplatin (810 mg IV on chemotherapy cycle day 1), and pembrolizumab (200 mg IV on chemotherapy cycle day 1), with the objective of completing 4–6 cycles.

Chemotherapy was generally well-tolerated; however, an episode of hypotension necessitated the omission of day 8 paclitaxel during the first chemotherapy cycle. Despite strict adherence to his treatment regimen, the patient’s clinical status deteriorated rapidly. He died 2 months after starting chemotherapy and 3 months following his initial diagnosis.

Discussion

This case demonstrates how squamous cell carcinoma of the lung can present with aggressive features, including intracardiac tumor thrombus, in a relatively young patient with a limited traditional smoking history and prolonged e-cigarette use. SCC is a subtype of NSCLC most commonly linked to smoking [1]. SCC of the lung is often characterized by large primary tumors and, in some cases, extends into nearby structures [1]. While heart involvement in lung cancer is uncommon, transmural intracardiac invasion with a left atrial tumor thrombus is even more rare [6].

Previously reported cases of SCC of the lung with intracardiac tumor thrombus have typically involved older individuals (>60 years of age) with extensive tobacco smoking histories [6–10]. Huang et al described a 67-year-old woman with a 55-pack-year smoking history and an asymptomatic left atrial tumor thrombus discovered incidentally, who responded well to chemotherapy [6]. Similarly, Cipriano et al reported a 62-year-old man with a 40-pack-year smoking history and left atrial invasion via the pulmonary vein, who underwent surgical resection, including tumor removal and right inferior lobectomy, but ultimately died of brain metastases 4 months postoperatively [7]. Notably, he had had a 10-month course of vague symptoms and progressive weight loss prior to diagnosis [7]. In contrast, our patient presented after only 1 month of symptomatic decline and weight loss. While definitive conclusions cannot be drawn, our patient’s younger age, limited combustible tobacco smoking history, rapid tumor growth, lack of response to chemotherapy, and accelerated clinical decline raise the possibility of a distinct or more aggressive disease pattern. These differences prompt consideration of potential contributing factors, including the prolonged use of ENDS.

ENDS are devices that vaporize a nicotine-containing liquid composed of propylene glycol, glycerin, flavorings, and other chemicals. Although often promoted as a safer alternative to traditional smoking, ENDS expose users to various harmful substances, including aldehydes, ultra-fine particles, volatile organic compounds, and heavy metals [3]. These substances are known carcinogens that can promote tumorigenesis by increasing free radical production, causing DNA damage, and activating carcinogenic enzymes [3,4]. In some individuals, ENDS use has been associated with electronic cigarette or vaping-associated lung injury (EVALI), a clinical syndrome marked by acute lung injury, diffuse infiltrates, systemic inflammation, and respiratory distress [11]. The mechanisms underlying EVALI are not fully understood but may involve direct alveolar epithelial damage, immune dysregulation, and exposure to lipid-containing additives such as vitamin E acetate [11,12,13]. In SCC, exposure to e-cigarette vapor may facilitate epithelial-to-mesenchymal transition, which can enhance malignant transformation, increase metastatic potential, and contribute to therapeutic resistance [5,14]. Although a definitive link to malignancy has not been established, emerging data on ENDS-related toxicity raise concerns about potential long-term effects, particularly in the context of respiratory epithelial injury, oxidative stress, and chronic inflammation [13].

Emerging reports and recent studies suggest that ENDS use can accelerate the progression of SCC and increase the risk of malignancy [15–18]. A notable case involved a 19-year-old with minimal smoking history who developed aggressive tongue SCC after prolonged e-cigarette use, dying within 6 months [15]. Although anecdotal, such cases underscore the need for further investigation, particularly in light of findings such as a recent case-control study from Ohio State University which found a 4-fold increased risk of lung cancer in individuals who both smoked and vaped compared to those who only smoked [17]. While causality cannot be established, our case adds to emerging observations that prolonged e-cigarette use may be associated with the development of lung cancer.

Even as the dangers of e-cigarette use become more evident, clinical guidelines to quantify vaping exposure and stratify cancer risk remain absent [2]. Tobacco use is traditionally quantified in “pack-years,” providing clinicians with a standardized measure to assess smoking risk. Patients can report the number of cigarettes smoked per day or per week, making their risk readily quantifiable. However, no equivalent measure exists for e-cigarette use. Attempts have been made to quantify vaping by asking patients about the number of puffs taken daily, the volume of liquid consumed in milliliters, or the number of pods used weekly [19]. These efforts are often undermined by patients’ inability to accurately report their vaping habits, as they may not consistently track puffs or pod usage [19].

The lack of standardization in quantifying e-cigarette use may lead to incomplete documentation by clinicians. In this case, although the patient self-reported 11 years of e-cigarette use, there was no record of the amount he vaped on a daily or weekly basis. Exploring standardized methods to quantify vaping exposure may be helpful in future studies of lung cancer risk. Such methods may include asking patients about the average number of days per week they vaped throughout their total period of use or inquire about the frequency of vaping-related purchases. These approaches may be potential avenues for future research aimed at understanding how to better assess cancer risk in individuals who do not meet current USPSTF criteria.

Despite following with outpatient cardiology and pulmonology, and having a 10-pack-year smoking history coupled with 11 years of e-cigarette use, this patient was not recommended for lung cancer screening, likely due to not meeting USPSTF criteria, which may reflect limitations in the current guidelines. Given the aggressive and rapid progression of his metastatic disease, low-dose CT screening initiated at the age of 50 or 51, consistent with age-based eligibility for traditional smokers, could have identified the malignancy at an earlier, more treatable stage. Early detection in this instance might have facilitated timely intervention and improved the clinical outcome, suggesting that future research should investigate whether e-cigarette use is an emerging risk factor worth considering in screening criteria.

Conclusions

This case illustrates an aggressive presentation of squamous cell lung carcinoma with intracardiac tumor thrombus in a relatively young former smoker with prolonged e-cigarette use. While this case suggests a possible association between e-cigarette use and aggressive lung cancer, it cannot justify changes to clinical practice or screening guidelines on its own. Further research is needed to better understand the long-term effects of e-cigarette use and inform future clinical decisions.