Endobronchial ultrasound-guided mediastinal cryobiopsy: A retrospective study from two tertiary care centres in north-central India

Dear Editor,

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard modality for sampling mediastinal lymph nodes; however, its limitations are well recognized, particularly when larger tissue samples are required for histopathological subtyping.[1,2,3] Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a promising technique that may address these shortcomings by providing larger architecturally preserved tissue samples.[4,5,6]

We report our experience with EBUS-TMC performed through the transbronchial needle puncture site in patients with undiagnosed mediastinal lymphadenopathy at two tertiary care centres in north-central India.

This retrospective study included nine patients with mediastinal lymph nodes or masses having 1 cm or more short-axis diameter detected on computed tomography, showing increased fluorodeoxyglucose uptake on positron emission tomography, who underwent EBUS-TMC. All the patients had undergone EBUS-TBNA and EBUS-TMC during the same procedural setting after informed consent. Procedures were performed under deep sedation with airway secured using a laryngeal mask airway.

Patients underwent EBUS-TBNA using a linear EBUS bronchoscope (BF-UC 180F; outer diameter 6.9 mm, Olympus Medical Systems, Japan). A total of three passes were performed using a 19-G needle, with 10–15 jabbing movements during each pass. Smears were prepared from EBUS-TBNA samples.

Subsequently, a 1.1 mm cryoprobe (ERBE Flexible cryoprobe 202402-401, ERBE, Germany) was introduced through the same puncture site into the target lymph node under real-time ultrasound guidance for EBUS-TMC. Colour Doppler imaging was used to avoid vascular structures. The cryoprobe was activated for 5–6 seconds and then withdrawn along with the EBUS bronchoscope en bloc. The retrieved specimen was thawed in normal saline and fixed in formalin [Figure 1]. One to three cryobiopsy samples were obtained depending on tissue adequacy.

Figure 1.

(a) Bronchoscopic view shows a 1.1 mm cryoprobe being inserted into the mediastinal lymph node under real-time endobronchial ultrasound guidance. The endobronchial ultrasound view shows the tip of the cryoprobe in the mediastinal lymph node. (b) Bronchoscopic view of cryoprobe insertion site after retraction of cryoprobe. Minor bleeding was seen at the insertion site. (c) Sampled tissue obtained after EBUS-TMC. The sampled tissue is significantly larger in comparison to EBUS-TBNA. EBUS-TMC = Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy; EBUS-TBNA = Endobronchial ultrasound-guided transbronchial needle aspiration

Nine patients were included, with a mean age of 61 years; eight were male. In all but one case, sampling was performed from the subcarinal lymph node station. Adequate tissue was obtained with a single cryoprobe pass in three cases, while six cases required three passes. The mean diameter of cryobiopsy tissue obtained was 3.5 mm, with a range of 2–5 mm. Demographic data and results of EBUS-TBNA and EBUS-TMC are summarized in Table 1.

Table 1.

Demographic profile and endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy results in the study participants

Age	Sex	Radiological findings	Mediastinal lymph node station from which sampling was done	Number of cryoprobe passes made	Maximum diameter of cryobiopsy sample	EBUS-TBNA cytology diagnosis	EBUS cryobiopsy diagnosis
63	Male	10.0 cm × 8.0 cm × 11.5 cm middle mediastinal mass extending from the right paratracheal region up to carina	7	1	4 mm	Atypical cells seen	Non-Hodgkin’s lymphoma
35	Male	7.5 cm × 10.0 cm × 13 cm well-defined, lobulated, heterogeneously enhancing mass involving the left paratracheal region, subcarinal, and left hilar lymph node stations	7	1	3 mm	No granuloma/atypical cells seen	Hodgkin’s lymphoma
85	Female	3.2 cm × 3.8 cm × 3.7 cm lymph node mass at the right paratracheal region, precarinal, and right hilar region	R10	3	3 mm	Necrotizing granulomatous lymphadenitis	Necrotizing granulomatous lymphadenitis
65	Male	2.2 cm × 3.4 cm × 3.6 cm subcarinal lymph node, FDG avid left-sided pleural thickening	7	1	3 mm	Atypical cells seen	Metastatic mesothelioma
56	Male	1.5 cm × 2.0 cm subcarinal lymph node with lung nodules	7	3	2 mm	Haemorrhagic smear	Adenocarcinoma lung
54	Male	Conglomerate mediastinal lymphadenopathy (largest – Subcarinal 3.0 cm × 4.5 cm × 4.1 cm) with areas of necrosis	7	3	4 mm	Reactive node	Necrotising granuloma with caseation favouring tuberculosis
72	Male	2.9 cm × 5.2 cm × 5 cm lymph node mass at the subcarinal station	7	3	5 mm	Atypical cells present	Small cell carcinoma lung
46	Male	Mediastinal lymphadenopathy at the right paratracheal, subcarinal, and bilateral hilar adenopathy (largest subcarinal- 2.8 cm × 3 cm × 3.2 cm)	7	3	4 mm	Non-necrotising granulomatous inflammation	Non-necrotising granulomatous inflammation favouring sarcoidosis
70	Male	Conglomerate lymph node mass (largest subcarinal- 3.8 cm × 6.2 cm × 6.1 cm) encasing the right main bronchus	7	3	5 mm	Atypical cells present	Squamous cell carcinoma

EBUS-TBNA=Endobronchial ultrasound-guided transbronchial needle aspiration

EBUS-TMC demonstrated a diagnostic yield of 100% in this study. Six cases were diagnosed with neoplastic aetiology with EBUS-TMC. Carcinoma lung was diagnosed in three cases (cases 5,7, and 9), lymphoma in two cases (cases 1 and 2), and metastatic mesothelioma in one case (case 4). Tuberculosis was diagnosed in cases 3 and 6, while case 8 had sarcoidosis.

EBUS-TBNA demonstrated a diagnostic yield of 67% in this cohort. In multiple cases, TBNA either failed to establish a diagnosis or yielded non-specific findings, such as haemorrhagic smears, reactive lymphoid tissue, or atypical cells, without definitive classification (cases 2, 5, 6), which were subsequently diagnosed on cryobiopsy.

No major complications were observed during or after the procedure. Minor bleeding occurred in seven patients and was successfully managed with suctioning and bronchoscope wedging. There were no instances of pneumothorax, pneumomediastinum, or procedure-related mortality.

We used a 19-G EBUS-TBNA needle and 1.1 mm cryoprobe in all our cases. The mean tissue diameter obtained was 3.5 mm, compared with 4.6 mm reported by Zhang et al.[3]

Most studies have described the use of a 1.1 mm cryoprobe for EBUS-TMC.[2,3,5] Gershman et al. reported the use of both 1.1 mm and 1.7 mm cryoprobes.[6] EBUS-TBNA needles of sizes ranging from 22G to 19G have been used for initial puncture.[3,7,8,9,10] Utilizing the puncture site created by the EBUS-TBNA for cryoprobe passage is a safer approach in experienced hands.[2,4] Use of a high-frequency knife to create a hole in the airway for cryoprobe passage is an alternate approach.[3]

EBUS-TMC is a viable alternative for sampling of mediastinal lymph nodes, offering a similar safety profile with improved tissue yield. Although limited by a small sample size, our experience demonstrates that EBUS-TMC can substantially enhance diagnostic confidence and yield without compromising patient safety. Larger prospective studies are warranted to better define its role in the diagnostic algorithm of mediastinal lymphadenopathy, particularly in resource-limited settings where minimizing repeat procedures is desirable.

Informed consent

All appropriate patient consent forms were obtained.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.