Sleeve Resection of the Right Upper Lobe for Tracheobronchial Metastasis of Hepatocellular Carcinoma With Superior Vena Cava Involvement: A Case Report and Literature Review

Introduction

The lungs are the most common site of metastasis in hepatocellular carcinoma (HCC); however, endobronchial metastasis is relatively rare in HCC compared with other malignancies [1]. Previous studies suggest that HCC with endobronchial metastasis is associated with a poor prognosis, and current treatment strategies are largely confined to systemic therapies, including chemotherapy, targeted agents, and immunotherapy [2,3]. To date [4,5], only 2 cases have been reported to undergo surgical resection – one treated with right upper lobectomy and the other with pneumonectomy. Here, we present a case in which 2 preoperative bronchoscopic examinations failed to conclusively determine the origin of the endobronchial tumor. Despite neoadjuvant chemotherapy combined with immunotherapy, the disease continued to progress. The patient subsequently underwent sleeve resection of the right upper lobe, which successfully achieved complete removal of the solitary metastatic lesion while preserving pulmonary function. To our knowledge, this is the first reported case of sleeve resection performed for histologically confirmed endobronchial metastasis from HCC.

Case Report

A 62-year-old man presented with a 5-month history of intermittent bloody sputum. He had a 40-pack-year smoking history and a medical background of hepatitis B virus infection. In September 2021, a hepatic tumor measuring 9.6×7.6 cm, located in segment VI of the right liver lobe, was identified during evaluation for abdominal pain. Preoperative serum tumor marker evaluation revealed elevated levels of alpha fetoprotein (AFP) at 320 ng/mL and prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) at 80 mAU/mL. The patient subsequently underwent radical right hepatectomy. Postoperative pathology confirmed HCC, classified as pT2N0M0 (China Liver Cancer Staging CNLC Ib). Given the postoperative pathology indicating pT2 stage large HCC with a high risk of recurrence, the patient underwent prophylactic/adjuvant transarterial chemoembolization (TACE) following multidisciplinary discussion, aiming to reduce the recurrence rate. In June 2022, a chest CT scan detected a 6-mm solid nodule in the right upper lobe. By October 2022, follow-up imaging showed enlargement to 11 mm, suggestive of metastatic disease, which led to radiofrequency ablation (RFA). Subsequent surveillance indicated gradual resolution of the treated lesion.

In January 2025, the patient developed cough and hemoptysis that persisted despite antibiotic treatment. In March 2025, positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic fluorodeoxyglucose (FDG)-avid mass (3.1×2.8 cm), with a standardized uptake value-maximum (SUVmax) of 10.3, in the right hilum, with imaging features highly consistent with malignancy (Figure 1A). Tumor markers, including AFP, CEA, NSE, CYFRA21-1, and PIVKA-II, were within normal ranges, while TSGF was elevated (74.96 U/mL). Bronchoscopy showed complete neoplastic obstruction of the right upper lobe bronchus (Figure 1B). The initial biopsy was non-diagnostic; however, a repeat bronchoscopy with immunohistochemical staining yielded the following profile: TTF-1(−), CK7(−), Napsin A(−), P40(−), Ki-67 (approximately 50%+), SMARCA4(+), GPC-3(−), Hep(−), and Arg-1(−). Expert pathology consultation suggested poorly differentiated non-small cell carcinoma.

The patient’s regimen was selected based on institutional experience and guidelines for advanced non-small cell lung cancer, as the tumor origin was still uncertain at that time. He received 3 cycles of neoadjuvant therapy consisting of tislelizumab (200 mg), polymeric micellar paclitaxel (360 mg), and carboplatin (0.5 g). A contrast-enhanced chest CT in June 2025 demonstrated disease progression, with the hilar mass enlarging to 6.1 cm (Figure 1C). Multidisciplinary team (MDT) assessment identified: (1) right upper hilar non-small cell carcinoma (primary vs metastatic); and (2) abdominal wall nodule (suspected metastasis).

Based on the MDT recommendation and after thorough discussion of the risks and benefits, the patient provided informed consent for surgery. Preoperative assessment revealed a Child-Pugh class A liver function with contrast-enhanced imaging confirming no evidence of HCC recurrence in the liver. Pulmonary function tests [Forced Expiratory Volume in 1 second (FEV1) of 2.8 L, 92% predicted; Forced Vital Capacity (FVC) of 3.5 L] and normal cardiac function were also documented, confirming his physiological tolerance for major thoracic surgery.

Port placement: A single 4-cm incision was made at the right fifth intercostal space along the midaxillary line. Intraoperative technical challenges included the fact that the tumor exhibited extensive adhesions to the hilar vessels, complicating dissection and increasing the risk of bleeding (Figure 1D). The estimated intraoperative blood loss was 400–800 mL, and 4 units of packed red blood cells had been prepared preoperatively. Frozen section analysis of the abdominal wall showed that the nodule was benign. The procedure performed included right upper lobectomy with bronchial sleeve resection, resection and direct repair of the lateral wall of the superior vena cava (SVC), and systematic lymphadenectomy (22 nodes retrieved). The tumor showed transmural invasion of the bronchial wall. No lymphovascular or perineural invasion was identified. The bronchial and vascular margins were free of tumor, with a distance of greater than 5 mm from the nearest invasive component, confirming an R0 resection.

Final histopathology confirmed metastatic HCC with involvement of stations 7 and 11, supported by its immunohistochemical profile: positive for creatine kinase (focal), SMARCA4, CD56 (rare), Arg-1 (rare), and GPC3 (rare); negative for NUT, P40, TTF-1, Napsin A, HEP-1, and AFP; Ki-67 was 40%. The patient’s postoperative recovery was uneventful. At the 3-month follow-up, a chest CT scan showed no evidence of recurrence, and the patient remained asymptomatic with complete resolution of hemoptysis.

Discussion

The lungs represent a common site of metastatic disease from various extrapulmonary malignancies. It is estimated that 20–50% of patients with solid tumors outside the thorax will develop pulmonary metastases during the course of their disease [6]. Among endobronchial biopsies performed for suspected malignancy, approximately 4% reveal endobronchial metastasis from an extrapulmonary primary tumor. The most frequent sources of such metastases include breast cancer (30%), colorectal cancer (24%), renal cell carcinoma (14%), gastric cancer (6%), melanoma (4.5%), and hepatocellular carcinoma (HCC) (2%) [6]. Thus, endobronchial metastasis from HCC remains a very rare clinical entity.

A systematic review of the English-language literature available on PubMed from 1988 to 2025 identified only 15 reported cases of endobronchial metastasis from HCC (Table 1), [2–5,7–17]. Notably, half of these cases were reported within the last decade, suggesting that improvements in diagnostic techniques may have contributed to increased detection over time. The most common clinical manifestations of endobronchial metastasis included hemoptysis (56.2%) and cough (43.7%). Anatomically, the right lung was more frequently involved (62.5%), with a predilection for the right main bronchus and the upper lobe. The clinical presentation in our case – hemoptysis and cough with a right upper lobe endobronchial lesion – aligns well with these previously reported characteristics.

Based on the table data, systemic medical therapy is the primary approach. Only 2 cases of surgical resection for endobronchial metastasis of HCC have been documented in the literature, one treated with right upper lobectomy (Lee et al, 2003) and the other with pneumonectomy (Purandare et al, 2009) [4,5]. In contrast, the present case, to our knowledge, is the first to utilize a right upper lobe sleeve resection, which was performed via a uniportal video-assisted thoracoscopic surgery (VATS) approach. This technique was selected to achieve complete tumor removal while maximizing the preservation of functional lung tissue.

HCC is the most common form of primary liver cancer. Although surgical resection offers the best opportunity for long-term survival, postoperative 5-year survival remains modest, at approximately 40–50% [18]. High mortality is largely attributable to disease recurrence, which occurs in nearly 70% of patients, with the lungs being a frequent site of metastasis [19]. Therefore, the management of metastatic HCC – particularly in unusual presentations such as endobronchial metastasis – requires individualized and multidisciplinary approaches.

Bronchoscopy represents a critical procedure for the diagnosis of endobronchial tumors, with immunohistochemistry and histopathological description serving as an essential ancillary diagnostic tool [20] (Figure 2). Key markers play a fundamental role in distinguishing primary bronchogenic lung cancer from endobronchial metastasis of HCC. Among these, TTF-1 and Napsin A are highly specific for primary lung adenocarcinoma when both show positive immunostaining. Cytokeratin profiles, such as CK7 positivity combined with CK20 negativity, may also provide valuable diagnostic information [21,22]. Conversely, markers indicative of hepatocellular origin include HepPar-1, Arg-1, GPC3, and AFP (Figure 3). Furthermore, emerging biomarkers – such as circulating tumor cells, proteins, nucleic acids, and exosomes – show potential for detecting HCC metastasis, monitoring immune evasion, and predicting prognosis [23,24].

In the present case, the immunohistochemical profile demonstrated TTF-1 (−), Napsin A (−), Arg-1 (focal +), and GPC3 (focal +). Integrated with morphological assessment and the patient’s history of HCC, these findings confirmed the diagnosis of endobronchial metastasis from HCC. This case underscores the importance of sufficient tissue sampling, a comprehensive immunohistochemistry marker panel, and the integration of histopathological and clinical data for achieving a definitive diagnosis.

Wang et al [25] conducted a multicenter retrospective study involving 2705 HCC patients who underwent radical hepatectomy. The prognosis of HCC with distant metastasis was notably poor, with a median overall survival (OS) ranging from only 4.9 to 10.3 months. Within the cohort, 1507 patients (55.7%) experienced recurrence, including 342 cases (22.7%) who developed distant metastases. The most common sites of metastasis included extrahepatic vasculature (36.2%), lungs (26.0%), and lymph nodes (20.8%). Patients with distant metastasis exhibited significantly inferior 5-year OS compared with those with intrahepatic recurrence only (9.1% vs 41.1%, P<0.001). Notably, pulmonary metastasis was associated with particularly dismal outcomes; Surveillance, Epidemiology, and End Results (SEER) data indicated a median OS of 3 months in these patients, compared with 19 months in those without lung involvement [26].

In the present case, the primary hepatic tumor measured 9.6 cm, suggesting high metastatic risk. A suspected – though unconfirmed – pulmonary metastasis was identified 9 months after surgery, with endobronchial metastasis confirmed at 43 months. RFA is an established local treatment modality for pulmonary oligometastases, offering a minimally invasive approach for tumor control [27]. In this patient, despite RFA treatment for the peripheral pulmonary lesion, subsequent endobronchial metastasis emerged, raising the possibility of iatrogenic airway seeding following RFA – a recognized, albeit rare, complication of transthoracic ablation procedures. Reported incidences of needle tract seeding after lung RFA range from approximately 0.3% to 0.7% [28,29]. This mechanism could plausibly explain the pathogenesis observed in the present case.

The failure of neoadjuvant chemoimmunotherapy in this case may be attributed to the intrinsic heterogeneity of metastatic HCC and its known resistance to conventional chemotherapy. Studies have shown that endobronchial metastasis from HCC often exhibits a poor response to systemic therapy, as evidenced by cases of disease progression even following immunotherapy [3], making local interventions like surgery crucial in selected patients [2].

In light of these limitations of systemic therapy, a growing body of evidence underscores the role of surgical resection as a viable and potentially curative option for well-selected patients. Hu et al investigated the therapeutic role and selection criteria for pulmonary metastasectomy (PMT) in HCC patients with pulmonary metastasis after liver resection. Their study identified several independent prognostic factors, including the stage of the primary intrahepatic tumor, status of pulmonary metastases, control of the primary tumor, and patient performance status or liver function [30]. In another study, Kim et al analyzed 63 patients who underwent PMT for pulmonary metastatic HCC between 2004 and 2022, reporting cumulative post-PMT survival rates of 79.1%, 63.9%, and 35.6% at 1, 2, and 5 years, respectively. These outcomes suggest that PMT can yield acceptable survival in patients with unilateral resectable metastases and adequate surgical margins [31].

Sleeve lobectomy has been established as a parenchyma-sparing alternative to pneumonectomy for centrally located lung tumors, providing comparable long-term survival while minimizing functional loss. By preserving functional lung tissue, it is associated with significantly better postoperative pulmonary function, exercise tolerance, and quality of life compared with pneumonectomy [32]. Use of a minimally invasive approach (VATS and/or robotic-assisted thoracoscopic surgery) to sleeve lobectomy further enhances recovery, demonstrating reduced blood loss, shorter drainage duration, and lower complication rates while maintaining equivalent oncological outcomes to open procedures [33]. This combination of lung preservation and minimal invasiveness establishes a superior physiological foundation for rapid recovery, making sleeve lobectomy the preferred approach when technically feasible [32,33].

Based on these findings and International Guidelines and Consensus, the management of pulmonary metastases necessitates a comprehensive evaluation by an MDT to formulate individualized treatment strategies. The primary goal is to achieve long-term survival or even cure through aggressive local therapy in carefully selected patients, provided that the primary tumor is controlled and systemic disease is effectively managed [34,35]. The MDT at our institution established the following selection criteria for surgical intervention in endobronchial metastasis:

The initial treatment was administered for suspected advanced non-small cell lung cancer based on inconclusive bronchoscopic biopsy immunohistochemistry results (TTF-1, Napsin A negative; GPC3, Arg-1 focally positive). Upon disease progression during that treatment, and given the solitary endobronchial lesion, absence of intrahepatic or other distant metastases, and good performance status (PS 0–1), the MDT considered radical local therapy (surgery) as the best option with potential for long-term benefit to control this systemic therapy-resistant isolated metastasis. This aligns with the principle of aggressive local treatment for oligometastatic disease, which is supported by expert consensus emphasizing the value of surgical resection when the primary tumor is controlled, metastases are resectable, and the patient is medically operable [35]. Following this comprehensive MDT evaluation and thorough informed consent, surgical resection was pursued as a feasible and potentially curative treatment option for this carefully selected patient. Building upon the inherent benefits of the parenchyma-sparing sleeve technique, the minimally invasive VATS approach was employed to further optimize perioperative outcomes and enhance clinical recovery.

This study has several limitations. First, it is a single-case report, which limits the generalizability of the findings. Second, the lack of long-term follow-up data precludes conclusions about overall long-term survival, which is particularly relevant given the high recurrence risk of HCC. Finally, the role of sleeve resection in patients with multiple endobronchial metastases or uncontrolled primary disease remains unclear and requires further investigation.

Conclusions

This case confirms the diagnostic and therapeutic viability of sleeve resection for endobronchial tumors within an MDT framework. In conclusion, sleeve resection should be considered a viable option in carefully selected patients with solitary endobronchial metastasis from HCC, controlled primary disease, good performance status, and progression after systemic therapy. More broadly, it highlights surgery as a crucial modality for such patients, underscoring the MDT’s indispensable role in balancing radical disease control with organ preservation. As a single-institution experience, however, these findings necessitate validation through larger, multicenter studies with extended follow-up to firmly establish the long-term efficacy and safety of this approach.