Needle tract seeding after endobronchial ultrasound-guided intranodal forceps biopsy and cryobiopsy: a case report

Introduction

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive standard procedure used for diagnosing intrathoracic lymphadenopathy (1). Although EBUS-TBNA offers a pooled sensitivity of approximately 90% for lung cancer, its diagnostic performance is suboptimal for conditions such as lymphoma and sarcoidosis, with sensitivities of 66% and 79%, respectively (1-4). This limitation is due to the cytological nature of the specimens. To address this, techniques such as EBUS-guided intranodal forceps biopsy (EBUS-IFB) and EBUS-guided cryobiopsy (EBUS-CRYO), which provide histologic samples, have been developed. These adjunctive methods not only improve diagnostic yield but also enhance the success rate of molecular testing when added to EBUS-TBNA, which may sometimes yield suboptimal samples (4-10). Zhang et al. demonstrated that mediastinal cryobiopsy alone had a genetic testing suitability of 93.3% compared with 73.5% with EBUS-TBNA alone (P<0.001) (6). Similarly, Fan et al. reported that combining EBUS-TBNA and EBUS-CRYO improved the suitability of genetic testing and programmed cell death-ligand 1 expression analysis to 97% compared with 79% for EBUS-TBNA alone (P=0.033) (7). Both techniques require the creation of a tract for insertion of forceps or cryoprobes into the lymph nodes, typically using high-frequency devices or needle manipulation (5-7,10,11). However, the potential adverse events associated with this tract remain unclear.

Needle tract seeding (NTS) is the implantation of tumor cells along a puncture site to form new tumor nodules. In endoscopic ultrasound-guided tissue acquisition (EUS-TA) for pancreatic cancer, NTS may manifest as gastric wall nodules or peritoneal seeding and is recognized as a rare but significant complication, with an incidence rate of 0.330% (12). In bronchoscopy, a survey on EBUS-TBNA complications in Japan found no occurrence of NTS (13). Only one case of NTS after EBUS-IFB for mediastinal lymph node metastasis of cutaneous adnexal carcinoma has been reported (14). Theoretically, NTS is a plausible complication of EBUS-CRYO, given the passage of larger tissue specimens through the tract. Herein, we report a case of NTS after EBUS-IFB and EBUS-CRYO in a patient with lung adenocarcinoma harboring MET exon 14 skipping mutation. We present this article in accordance with the CARE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-218/rc).

Case presentation

An 83-year-old woman with a 43.5-pack-year smoking history was referred to Japanese Red Cross Kyoto Daiichi Hospital for evaluation of right upper lobe nodules and multiple bilateral mediastinal lymphadenopathies (Figure 1A-1C). Laboratory findings revealed mildly elevated levels of carcinoembryonic antigen (7.4 ng/mL) and cytokeratin 19 fragment (3.2 ng/mL). Positron-emission tomography revealed no evidence of distant metastases. Previous diagnostic attempts at another hospital using EBUS with the guide-sheath method failed. Therefore, EBUS-TBNA was performed at Japanese Red Cross Kyoto Daiichi Hospital. Four passes were performed at #4R lymph node using a 22-gauge needle (NA-U401SX-4022; Olympus, Tokyo, Japan), yielding macroscopic fluid and necrotic specimens. Rapid on-site evaluation (ROSE) confirmed malignancy but indicated severe necrosis, rendering the sample insufficient for molecular testing. To obtain adequate specimens, EBUS-IFB was performed three times using 1.9-mm forceps (FB-231D; Olympus) following tract creation by needle manipulation (5) (Figure 2A). Subsequently, EBUS-CRYO was performed twice with a 1.1-mm cryoprobe (20402-401; Erbe Elektromedizin GmbH, Tübingen, Germany) with an 8-second freezing time (Figure 2B). These procedures yielded sufficient tissue for a definitive pathological diagnosis of lung adenocarcinoma with MET exon 14 skipping mutation (Amoy Dx Pan Lung Cancer PCR Panel; Amoy Diagnostics Co., Ltd., Xiamen, China). The pathological findings of EBUS-TBNA with ROSE, EBUS-IFB, and EBUS-CRYO are shown in Figure 3A-3C.

Figure 1 Computed tomography findings before bronchoscopy. (A,B) Right upper lobe nodules and (C) 4R lymph node before bronchoscopy.

Figure 2 EBUS images during EBUS-IFB and EBUS-CRYO. (A) EBUS-IFB was performed three times using 1.9-mm forceps following tract creation by needle manipulation (white arrow). (B) EBUS-CRYO was performed twice with a 1.1-mm cryoprobe (yellow arrow). EBUS, endobronchial ultrasound; EBUS-IFB, endobronchial ultrasound-guided intranodal forceps biopsy; EBUS-CRYO, endobronchial ultrasound-guided cryobiopsy.

Figure 3 Pathological findings of bronchoscopy specimens. (A) Diff-Quik staining of the endobronchial ultrasound-guided transbronchial needle aspiration cytology specimen (×100). Rapid on-site cytological evaluation confirmed malignancy but indicated severe necrosis. Hematoxylin and eosin staining of the (B) endobronchial ultrasound-guided intranodal forceps biopsy and (C) endobronchial ultrasound-guided cryobiopsy specimens. These specimens were sufficient for a definitive pathologic diagnosis of lung adenocarcinoma with MET exon 14 skipping mutation.

Twenty-nine days after bronchoscopy, a computed tomography (CT) scan performed at the referring hospital before the initiation of lung cancer treatment revealed rapid growth of the right upper lobe nodules (Figure 4A,4B). In addition, a soft tissue shadow protruding into the trachea was observed at the biopsy site, which was strongly suggestive of NTS (Figure 4C). Despite this finding, the patient remained asymptomatic, without dyspnea or hemoptysis. Therefore, the patient refused to undergo bronchoscopy. Additionally, no radiotherapy or airway intervention was performed. Tepotinib (500 mg/day) was immediately administered. After 19 days of treatment, the right upper lobe lesions and tracheal protrusion had regressed markedly (Figure 4D-4F). The patient continues the tepotinib therapy without complications and remains asymptomatic.

Figure 4 Computed tomography findings after bronchoscopy and tepotinib initiation. (A,B) The size of the right upper lobe nodules rapidly increased, and (C) a soft tissue shadow protruding into the trachea (yellow arrowhead) was observed at the biopsy site, suggestive of needle tract seeding, 29 days after bronchoscopy. (D-F) After 19 days of tepotinib treatment, the right upper lobe lesions and tracheal protrusion had markedly regressed.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committees and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient 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

In the present case, the NTS developed after bronchoscopic sampling, including EBUS-TBNA/IFB/CRYO. Previous meta-analyses have shown that both the procedures are relatively safe (4,15). The detailed mechanisms underlying this rare complication remain unclear. Although Romero et al. recommend avoiding biopsies from lymph nodes with abnormal mucosal findings due to the risk of fistula formation (16), our patient had no abnormal findings in the bronchial mucosa. We hypothesize that both tumor-related and procedural factors contribute to NTS.

From a tumor perspective, high malignancy, necrotic components, and sensitivity to chemotherapy are likely to play significant roles. Lung cancer with MET exon 14 skipping is associated with advanced pathological stage, larger tumor size, and poor prognosis (17). These high-grade genetic alterations may further increase the incidence of NTS. In EUS-TA, the incidence of NTS is significantly higher in patients with pancreatic ductal adenocarcinoma than in those with other tumors (0.409% vs. 0.071%, P=0.004), and NTS is more likely to occur in patients with high-grade malignancies (18). In addition, tumors with cystic or necrotic components were particularly prone to developing NTS (3.7% vs. 0%, P=0.01) (19). The mechanism likely involves the leakage of tumor cells with fluid components from the puncture site and the invasion of normal tissue. In cases of granuloma formation at the puncture site after EBUS-TBNA for tuberculous mediastinal lymphadenopathy, the specimens obtained were necrotic, supporting this hypothesis (19-21). However, sensitivity to chemotherapy is crucial. Advances in lung cancer chemotherapy have often resulted in favorable responses, as observed in this case. Without strict CT follow-ups, many cases of NTS may have been overlooked. In EUS-TA, neoadjuvant or adjuvant chemotherapy has been suggested to play a protective role against NTS complications (22). A previously reported case of NTS following EBUS-IFB in cutaneous adnexal carcinoma, without an established treatment, is, considered exceptional (14).

Technical factors should be considered on the procedural side. The use of larger tracts to accommodate EBUS-IFB and EBUS-CRYO may increase this risk. Compared with standard EBUS-TBNA, these advanced biopsy techniques inherently involve more invasive tissue collection, potentially facilitating tumor cell dissemination. The impact of needle diameter, needle tip shape, and the number of passes regarding the risk of NTS in EUS-TA remains unclear (22). The use of ROSE and fine-needle biopsy (FNB) needles, which require fewer passes, may reduce the risk of NTS. In EBUS-TBNA, the addition of EBUS-IFB or EBUS-CRYO in cases with nondiagnostic or inadequate ROSE or a Franseen FNB needle has also shown promise in improving diagnostic yield and tumor cellularity (23-25). However, the optimal procedural algorithm requires further investigation.

This case study provides several important insights. Given inadequate ROSE results, the decision to perform both EBUS-IFB and EBUS-CRYO was justified. However, considering the high risk due to necrotic findings, limiting the procedure to either EBUS-IFB or EBUS-CRYO may be preferable. Additionally, biopsies from more peripheral lymph nodes may mitigate the risk of airway stenosis associated with NTS. The diagnosis in this case was based solely on CT findings; no endoscopic observation or pathological confirmation was performed, leaving the possibility of inflammatory polyps. However, significant regression after tepotinib treatment strongly supported the diagnosis of NTS.

Conclusions

This case highlights a rare case of NTS following EBUS-IFB and EBUS-CRYO in a patient with lung adenocarcinoma harboring MET exon 14 skipping mutation. A combination of tumor-related factors, including high malignancy and necrosis, along with the procedural aspects of advanced biopsy techniques, likely contributed to its occurrence. Thus, the true incidence of NTS may be underestimated or underdiagnosed. Bronchoscopists should remain vigilant when using advanced biopsy methods and should consider procedural modifications and careful follow-up strategies, including CT and endoscopic surveillance, to mitigate this risk, especially in high-risk patients.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-218/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-218/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-218/coif). T.I. receives lecture fees from Amco, Fujifilm, Merck and Olympus. The other 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 and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient 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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