Impacting factors of diagnostic accuracy of ultrasound-guided percutaneous core needle biopsy in mediastinal lesions: an analysis with 622 cases

Introduction

Mediastinal masses are not uncommon, including a variety of different entities, and most of them are neoplastic lesions (1). The mediastinum is basically divided into three parts: anterior, middle and posterior regions according to the anatomic location. Different tumors tend to arise in different mediastinal areas, for example, thymic neoplasms frequently develop in anterior mediastinum, while neurogenic tumors dominate posterior mediastinal space. Although some early-stage typical tumors may receive upfront surgery directly, however, there are more clinical scenarios in which pre-treatment pathological diagnosis is mandatory and informative, such as lymphoma, seminoma, metastatic disease, infectious disease, etc.

Fine needle aspiration (FNA), percutaneous core needle biopsy (PCNB) and mini-thoracotomy are three major approaches to obtain specimens from mediastinal lesions (2-4). Compared with the other two, PCNB may guarantee more sufficient tissue than FNA, while avoiding general anesthesia and traumatic surgery in mini-thoracotomy. Currently, computed tomography (CT)-guided PCNB (CGNB) and ultrasound-guided PCNB (UGNB) are widely used in thoracic tumor biopsy. Since invasive mediastinal tumors are usually adjacent to chest wall, UGNB shows more advantages than CGNB: real-time monitoring, free from radiation exposure, lower cost, shorter operation time and lower risk of vascular injury. In the past decade, with the application of contrast-enhanced ultrasound (CEUS), the diagnostic accuracy of large necrotic lesions have been significantly improved (5). Yet, the diagnostic yield of UGNB still ranges from 80% to 96% (6-8). In this current study, we retrospectively reviewed 622 cases of mediastinal masses that underwent UGNB in our institution. By analyzing impacting factors of diagnostic accuracy, we aim to further improve this efficacious and minimally invasive intervention. We present this article in accordance with the STARD reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1727/rc).

Methods

We reviewed the patients’ name list who received UGNB from August 2013 to September 2022 in the registration system, then collected all their relevant information from the comprehensive medical history database of our hospital. Phone calls were made, if necessary, to confirm the final diagnosis by clinical outcome, if the patients did not undergo surgery. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Chest Hospital (No. IS22014) and individual consent for this retrospective analysis was waived.

The inclusion criteria of UGNB were summarized as follows: (I) tumor diameter longer than 20 mm; (II) normal coagulation function; (III) tumor detectable by sonography. Exclusion criteria: abnormal coagulation status or an incooperative patient.

The indications for UGNB: (I) suspected lymphoma; (II) suspected seminoma; (III) mediastinal tumor with hematogenous metastasis; (IV) suspected invasive epithelial tumor for induction therapy; (V) other tumors infeasible for surgery.

Preoperative evaluation

Chest CT and magnetic resonance imaging (MRI) were mandatory prior to biopsy, while positron emission tomography-CT (PET-CT) was optional. Serum tumor markers (α-fetoprotein, β-human chorionic gonadotropin and lactate dehydrogenase, etc.) were also routinely tested. The necessity of a biopsy for mediastinal tumor is usually raised by physician or surgeon. Then a panel discussion with ultrasonogist will be conducted to determine the feasibility of UGNB. After that, the patient’s position, puncture point, biopsy route are basically designed based on radiographic images. Additionally, anticoagulation or antiplatelet medication should be suspended at least 5 days before biopsy operation.

Operation procedure

Patients were accordingly placed in the supine, prone or lateral position based on the different locations of the tumor. For some special cases, sitting or semi-sitting position might also be adopted if the patient could not lie flat due to dyspnea. Parasternal, paravertebral and suprasternal routines are the main three biopsy paths. At first, local anesthesia with 2% lidocaine was used. Secondly, an introducer coaxial needle (Figure 1A) was punctured along the anesthesia path into the target, under the real-time monitoring of an ultrasound probe from a GE Logiq 9 ultrasound machine (GE Healthcare, Milwaukee, WI, USA). After withdrawal of the core, a side-cutting biopsy device (Figure 1B) was inserted into the hollow introducer needle. With re-conformation of the needle point position, the cutting device was triggered to cut tissue from lesions. The cutting procedure could be repeated until sufficient tissue was collected. Generally, a minimum of 3 specimens was requested for pathological diagnosis, as suggested by International Thymic Malignancy Interest Group (ITMIG) (9). There were varied gauges and lengths of the cutting needles (Figure 2) which were usually selected according to tumor size or individual preference of physician. The ultrasound graphs are illustrated in Figure 3.

Figure 1 Biopsy instruments: an introducer coaxial needle (A); a side-cutting biopsy device (B).

Figure 2 Different gauges and lengths of the cutting needles: 1 cm of 16 G (a); 2 cm of 16 G (b); 2 cm of 18 G (c).

Figure 3 The CT and ultrasound images of the UGNB process. (A) CT image of a large mediastinal lesion. (B) The lesion was detected by two-dimensional ultrasonography (heterogeneous pattern). (C) Internal mammary vessels (white arrow) under color Doppler ultrasonography. (D) Parasternal approach with biopsy needle toward the mediastinal lesion. CT, computed tomography; UGNB, ultrasound guided core-needle biopsy.

Definition of diagnostic accuracy

A successful diagnosis was defined as follows: (I) the biopsy results were consistent with the final post-surgery pathology; (II) when the disease was unsuitable for surgery, the clinical outcome matched the biopsy diagnosis after more than one year of follow-up. While unsuccessful diagnosis was described as: (I) the diagnostic conclusion could not be clearly made (insufficient tissue, necrotic tissue, small round tumor cells, atypical cells, fibrous tissues, etc.); (II) the biopsy diagnosis was different from post-surgery pathology. All biopsied slides were reviewed by our senior pathologist (L.Z.).

Complications

Puncture site pain, bleeding, pneumothorax and shock-like reaction are the main complications after UGNB. All complications were classified based on the definitions of the Clavien-Dindo system (10).

Statistical analysis

SPSS 22.0 software (IBM, Armonk, NY, USA) was used to perform statistical analysis. Categorical data were expressed as absolute numbers and percentages, and analyzed by the Chi-squared test or Fisher’s exact test. Binary logistic regression was applied to detect possible impacting factors among different variables, and P<0.05 was considered statistically significant.

Results

Participants’ characteristics

A total of 634 patients were listed from registration system, and 12 out of them were excluded from final analysis due to a lack of follow-up information. Figure 4 displays the inclusion procedure and overall diagnostic results. This patient cohort consists of 366 males and 256 females with an average age of 45 years old. Tumors originated from anterior, middle and posterior mediastinal areas were 590, 25 and 7, respectively. The median diameter of lesions was 65 mm, ranging from 21 to 175 mm. Other detailed information could be found in Table 1.

Figure 4 Flow diagram shows the diagnostic results of 622 patients in this study. UGNB, ultrasound guided core-needle biopsy.

Diagnostic accuracy

Finally, 585 (94.05%) patients obtained a successful diagnosis after biopsy. Among them, the results of 145 cases were consistent with post-resection pathological diagnosis, while for the other 440, the final diagnosis was confirmed by the clinical outcomes. There were 37 patients whose biopsy diagnosis was unsuccessful (unclear conclusions in 34 and wrong in 3), and detailed information about this group is presented in Table 2. The diagnostic results of the 34 indeterminate patients were eventually obtained by re-biopsy or mini-invasive surgery 2–4 weeks after the first UGNB.

As for histology subtypes, thymic epithelial tumor (n=295), lymphoma (n=190) and germ cell tumor (n=51) were the most common ones, others included epithelial carcinoma with unclear orientation (n=40), metastatic carcinoma (n=21), sarcoma (n=14), neurogenic tumor (n=4), fibroma (n=2), hemangiomas (n=2), tuberculous granuloma (n=1), Castleman’s disease (n=1) and thymic hyperplasia (n=1). Subtypes of lymphoma and germ cell tumors are listed in Table S1.

Among young-aged (<40 years) patients, 50% (135/270) of them were lymphoma and 19% (51/270) had germ cell tumors. While in the older patients, 76% (269/352) of them were epithelial malignant tumor. Cystic necrosis was detected in 17% (47/270) of younger patients, compared with 7% (26/352) in older patients (P<0.01).

Impacting factors of accuracy

Possible factors, including gender, age, tumor size, cystic necrosis, needle gauge and vascularity of the tumor were analyzed by binary logistic regression with a forward LR method. The result revealed that older age (≥40 years) and no cystic necrosis were two favorable factors for accurate diagnosis, with P=0.001 and P=0.02, respectively. The other factors, however, showed no significant effect on diagnostic accuracy (Table 3).

Safety

Most of the patients went through biopsy procedure safely. Adverse reactions of grade 2 or more were observed in 24 (3.86%) patients. Chest pain, hemothorax, and shock-like reaction were the most frequent complications. Coagulants were usually injected intravenously to combat hemothorax once new effusion in costodiaphragmatic recess was detected by ultrasound. No chest tube insertion or thoracotomy was needed to deal with the adverse events. As for shock-like reaction, most patients had their symptoms relieved after a lying-down position and oxygen inhalation. Main complications of different degrees were listed in Table 4.

Discussion

Pre-treatment pathological diagnosis is frequently essential in certain clinical scenarios for patients with mediastinal neoplasms, for example, when lymphoma or seminoma could not be excluded, or neo-adjuvant therapy is planned for other invasive malignancies. As a biopsy approach, UGNB is usually preferred due to its advantages (low radiation exposure, short operation time, low cost, vessel visibility, etc.) In our current study, UGNB yielded a 94.05% diagnostic accuracy with limited complications (3.86%) in 622 mediastinal tumors that abut the chest wall.

In 1976, Chandrasekhar et al. first reported UGNB in pulmonary masses (11). As for mediastinal tumors, Saito et al. published their results of UGNB in 45 cases in 1988, revealing a diagnostic rate of 79% and complication rate of 2% (12). After that, serial studies have proved the merits of UGNB in mediastinal lesions: clear visualization of needle point, tumor outline and heart/major vessel position in real-time, which ensures a safe path for needle insertion and avoids severe complications (13,14). These advantages allow UGNB to replace CGNB when tumors are located adjacent to heart or major vessels. Additionally, patients suffering from critical conditions (like superior vena cava syndrome) could also receive UGNB in a semi-sitting or sitting position, which, however, is infeasible in CGNB.

The technique of UGNB was applied from 2013 in our institution in eligible patients with mediastinal tumors. The results showed a 94.05% accuracy rate in 622 patients, which is comparable to previous large-sample studies (15). However, there were still 37 patients whose diagnosis was unclear or wrong after UGNB. Previous studies usually lacked analysis of factors impacting unsuccessful diagnosis, possibly due to limited case numbers. In the current study, factors including gender, age, tumor size, cystic necrosis, needle gauge and vascularity were analyzed via binary logistic regression in 622 patients. As a result, cystic necrosis and younger age were tested to be significant factors for false diagnosis, with each P value of 0.001 and 0.02, respectively. Cystic necrosis generally consists of insufficient tumor tissue, which may lower the diagnostic accuracy, which is explainable and has also been proven in other studies before (7). Age, however, maybe questionable to be an impacting factor. The reason we set 40-year-old as a cut-off value is mainly based on a guideline proposed by ITMIG (16). According to epidemiology, the differences in tumor incidence are quite distinct in the two groups (>40 and <40 years). To be detailed, lymphoma and germ cell tumors are more common in younger patients, while thymic epithelial tumors are more dominant in elders, which is also consistent with the results of our current study. In Nakazono et al. ’s study (17), the authors summarized that lymphoma and germ cell tumors are more prone to develop cystic necrosis judged by CT and MRI images, which could possibly explain the result in our study that cystic necrosis was more common in younger group than in elders (17% vs. 7%, P<0.01) and also explain the lower diagnostic accuracy in younger patients. As for tumor size, there were conflicting opinions about its influence on diagnostic outcome (18,19). Although larger lesions show clear images under ultrasound and make biopsy simple to perform, at the same time, necrosis is more frequently detected inside larger ones. In our current study, a larger size displayed no favorable influence on successful diagnosis at least.

In recent years, contrast-enhanced ultrasound (CEUS) has gained more attention in clinical practice due to its enhanced visualization of lesion vascularity and tissue perfusion superior to conventional ultrasound images (20). As a result, higher diagnostic yield has been obtained with CEUS guiding biopsy compared with ultrasound guiding in mediastinal tumors (21,22). However, whether CEUS should be applied to every single patient remains controversy, considering economic cost and potential allergic reaction. According to our study, the accuracy rate has already reached as high as 94.05% even with conventional ultrasound guidance. Thus, we advised that CEUS may be selectively useful in patients with cystic necrosis inside tumors or younger patients suspected of bearing lymphoma or germ cell tumors.

Complications were relatively rare (3.86% in our study) through the UGNB procedure. Hemothorax and shock-like reaction were the major side effects which needed prompt management. The symptoms of shock-like reaction include dizziness or fainting, low blood pressure, clammy skin, shortness of breath, etc. This reaction is possibly caused by patient’s nervousness, insufficient anesthesia, pleura stimulation by bleeding or long operation time. Bleeding along pleural surface could increase pain and probably trigger vagus nerve reflex, contributing to the fierce reaction. Recently, a novel instrument, CassiII rotational core needle, has been developed, boosting a “stick-freeze” technology (23). Theoretically, the needle point can freeze tumor tissue around it just before the cutting motion, which may simultaneously freeze microvessels nearby. As a result, the risk of hemothorax can be reduced, especially in tumors with rich vascular supply.

There are some limitations in this study. Firstly, data missing could not be avoided in a retrospective study. For example, we cannot analyze the influence of biopsy cores due to insufficient information. Additionally, CEUS has not been widely practiced in our institution until 2022. Efficacy of this technique should be investigated in our following prospective study.

Conclusions

UGNB is a highly effective approach for pre-treatment diagnosis in patients with mediastinal tumors with limited complications. Cystic necrosis and younger age are significant impacting factors for unsuccessful diagnosis. New techniques, such as CEUS and rotational core needle, may probably increase diagnostic accuracy and reduce complications.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1727/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1727/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1727/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1727/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. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Shanghai Chest Hospital (No. IS22014) and individual consent for this retrospective analysis was waived.

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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