Role of fiberoptic bronchoscopy-guided needle aspiration cytology (EBNA) in diagnosing lung cancer in endobronchial lesions: A single-center experience

Data source

Prospective and observational study conducted during January 2014−September 2022 in Respiratory Medicine and Critical Care Medicine Department in Venkatesh chest hospital and MIMSR Medical College, Latur. Objectives of the present study were to document the role of EBNA in EEL in confirming the diagnosis of lung cancer and to find out additive yield over other conventional techniques such as BW and FB. Total 1496 suspected lung malignancies on clinical and radiological basis were screened and finally 893 confirmed lung cancer cases were included in the study after the hospital’s ethical committee approval. We have taken written informed consent of all study patients [Figure 1].

Inclusion criteria

Suspected lung malignancies on clinical and radiological basis such as-

1. Cases with unexplained paralysis of vocal cord (hoarseness of voice) or stridor

2. Chest X-ray with radiological features of malignancy (coin lesions, mass lesions, mediastinal widening, unilateral high hemidiaphragm, segmental/complete lung collapse, and non-resolving pneumonia)

3. Normal chest X-ray with high clinical suspicion, localized monophonic wheeze, endobronchial disease, or growth symptoms such as hemoptysis, persistent cough, cases with suspected recurrent post-obstructive pneumonia, suspicious sputum cytology, unexplained, and recurrent pleural effusion.

Exclusion criteria

Cases unfit for bronchoscopy were excluded such as-

1. Cases with coagulopathy which cannot be corrected and platelets

2. Cases with mechanical ventilation with high PEEP

3. Cases with refractory hypoxemia

4. Cases with recent myocardial infarction or unstable angina

5. Cases with significant dysrhythmia and hemodynamic instability

6. Cases with poor ability to cooperate with procedure.

Ethical approval

This study is approved by the Ethics Committee of Venkatesh Chest Hospital and Critical Care Center and MIMSR Medical college, Latur, India (Approval # VCC/122014; Approval date September 2, 2014).

Bronchoscopic definition of exophytic endobronchial growth (EEL)

During the bronchoscopy procedure, operators notified different types of endobronchial growth patterns. These exophytic endobronchial lesions were described as cauliflower like, pedunculated, polypoidal, nodular exophytic, multinodular ulcerated’ endobronchial growth [Figure1].

Lesions with normal endobronchial mucosa with bulge (peribronchial growth) and abnormal endobronchial mucosa without oblivious growth were not included in the definition of endobronchial growth.

Bronchoscopy procedure in endoscopy suit

Bronchoscopy procedure was performed in endoscopy suit by Fujinon Epx 201H bronchoscope by two operators/teaching faculties of our institute trained in all bronchoscopy techniques including EBNA. Bronchoscopy procedure followed standard guidelines for topical analgesia during endoscopy used 10% lignocaine solution. Bronchoscope introduced transnasally in majority of cases and few cases required oral introduction whenever difficulty in nasal negotiation in the presence of nasal mucosa hypertrophy. Pre-procedure topical analgesia was given with xylocaine jelly for nasal mucosa and xylocaine spray for oropharyngeal mucosa. During bronchoscopy procedure, topical instillation of 10% xylocaine solution for analgesia of vocal cords and epiglottis.

Study design

After negotiation and entry of bronchoscope in trachea to carina, we have bronchoscopically installed small aliquots of diluted 1% lignocaine. During bronchoscopy procedure, conventional technique sequences were decided as EBNA first, BW, bronchial brush, and then FB to avoid contamination due to bleeding secondary to biopsy samplings. Following this sequence as EBNA first also helped us in avoiding false positivity and in some cases with fleshy vascular growth, we have avoided major bleeding by performing EBNA than FB. We have used 22-gauge MW 522 needle catheters (Mill-Rose Laboratories) during bronchoscopy to perform EBNA procedure. The bronchoscope was moved just proximal to endobronchial growth and the needle with catheter was moved out of scope, then needle was pushed out and introduced into endobronchial lesion. EBNA methodology as classically described in cytology technique “to and fro” used under applied suction from a 20-mL syringe. We have performed 4−5 passages of EBNA samplings during bronchoscopy and stop the EBNA only after confirmation by assistant and cytopathology technician for adequacy of specimen. We were having a ROSE facility and adequacy of samples was judged during the procedure in the majority of cases. Prepared EBNA cytology slides and fixed with 95% alcohol immediately for prevention of artefact and to increase the yield. All other bronchoscopic samples (forcep biopsy and bronchial wash) were sent for cytology and histopathology examination at the Pathology Department [Figure 1].

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Figure 1:

Image showing flow of study. EBNA: Endobronchial needle aspiration cytology, BW: Bronchial wash, FB: Forcep biopsy.

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EBNA cytology images documented during the present study with typical cytology findings of Non-small cell carcinoma [Figure 2], Small cell carcinoma [Figure 3], Squamous cell carcinoma [Figure 4] and Dysplasia [Figure 5] were categorized.

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Figure 2:

Non-small cell carcinoma in endobronchial needle aspiration cytology.

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Figure 3:

Small cell carcinoma in endobronchial needle aspiration cytology.

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Figure 4:

Squamous cell carcinoma in endobronchial needle aspiration cytology.

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Figure 5:

Dysplasia in endobronchial needle aspiration cytology.

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Statistical analysis

The statistical analysis was done using Chi-square test in R-3.4 software. Significant values of χ² were seen from probability table for different degree of freedom required. P value was considered significant if it was below 0.05 and highly significant in case if it was <0.001.

Covariates

In the present study, 893 diagnosed lung cancer patients between 29 and 85 age groups, male is 60.02% (536/893) and females are 39.97% (357/893). In addiction history, we have observed that 58.11% (519/893) cases are smoker and 39.16% cases with smoking index more than 20 pack years. Commoner symptoms are cough in 79.84% (713/893), shortness of breath in 46.13% (412/893), hemoptysis in 33.03% (295/893), and chest pain in 22.17% (198/893) cases. Clubbing on general physical examination is documented in 38.29% (342/893) cases. Commoner radiological presenting features are mass lesion in 48.60% (434/893) cases, Hilar opacity in 33.37% (298/893) cases, and collapse segmental/lobar in 12.54% (112/893) cases. During bronchoscopy, anatomical location is documented on the right side of tracheobronchial in 57.33% (512/893) cases as compared to left side of tracheobronchial wall 23.96% (214/893) and growth at carina documented in 18.70% cases (167/893) cases. Upper lobe bronchi are commoner site on both the sides as compared to other segmental bronchi [Table 1].

Core observations

In the present study, yield of FB and FB plus BW in EEL is 84.65% (756/893) and 88.35% (789/893), respectively. Yield of EBNA, EBNA plus BW, and EBNA plus FB in EEL is 70.99% (634/893), 73.48% (656/893), and 99.66% (890/893), respectively. Overall, yield of all bronchoscopy guided techniques (EBNA + FB + BW) in our study in EEL is 100%. Additional yield of EBNA in EEL over other CDTs (CDTs such as FB plus BW) is 11.65% [Table 2]. Sensitivity of FB and EBNA in diagnosing lung malignancy in EEL is 84.65% and 70.99%, respectively. FB is more sensitive technique than EBNA in EEL (P < 0.00001) [Table 2]. Sensitivity of forcep biopsy and EBNA in diagnosing lung malignancy in EEL is 84.65% and 70.99% respectively. Forcep biopsy is more sensitive technique than EBNA in EEL (P < 0.00001) [Table 3]. Histopathology type in the present study: We have documented adenocarcinoma in 40.76% (364/893) cases, squamous cell carcinoma in 35.72% (319/893) cases, non-small cell carcinoma in 12.43% (111//893) cases, small cell carcinoma in 7.61% (68/893) cases, and large cell carcinoma in 3.47% (31/893) cases. Adenocarcinoma trends are equally observed histological type as compared to squamous cell type irrespective of smoking trends in the study cases. We have documented that EBNA samples have given satisfactory results with histopathology specimens subjected to immunohistochemistry. In adenocarcinoma, 69% cases are EGFR positive, 6% ALK positive, and 8% ROS positive and 17% are all negative.

Diagnostic yield of EBNA and EBNA plus techniques in endobronchial lesions

Total yield of EBNA in EEL is 70.99% (634/893). In our previous published studies,^[11,12] we have documented 62.60% and 60.66%, respectively, in small sample sizes. Kacar et al.^[13] observed yield in 77.9% cases. Numerous studies^[5,14,15] have reported 70−96% diagnostic yield of EBNA in central airway tumors suspected of bronchogenic carcinoma.

In the present study, yield of EBNA, EBNA plus BW, and EBNA plus FB in EEL is 70.99% (634/893), 73.48% (656/893), and 99.66% (890/893), respectively. Thus, EBNA has documented complimentary role to other conventional diagnostic tests BW and FB in increasing significant yield. Similarly, studies by Salathe et al.^[16] Caglayan et al.^[17] reported increase in diagnostic yield after adding EBNA to CDTs were 65−79% and 79−91%, respectively (P < 0.001). Various authors, Hapomik et al.,^[10] Gullón et al.,^[18] and Gellert et al.,^[19] observed that addition of EBNA to conventional diagnostic yield increases diagnostic sensitivity of bronchoscopy in EEL. They also mentioned that yield is significantly reduced and chances of repeat procedure increased with CDTs without EBNA in the presence of endobronchial growth. Authors^{[5,14,15,17-19]} have observed that rationale for decreased yield with CDTs is chances of inadequate sampling during FB due to superficial necrosis resulting in to negative yield, the presence of blood clot over lesions giving negative biopsy results. Authors^{[5,14,15,17-19]} have mentioned chances of crush artifacts formation during FB technique resulted into inadequate sampling processed during histopathology especially during “serrated edges forcep type” in their studies.

We have used alligator forcep with needle and rat tooth type to prevent crush artifacts issue in our study. These hurdles of FB resulting into deceased bronchoscopy can be easily tackled with addition of EBNA to CDTs in diagnostic techniques during bronchoscopy procedure.^{[5,14,15,17-19]} American College of Chest Physicians (ACCPs)^[20] guidelines mentioned and recommended TBNA in endobronchial lesions to increase diagnostic yield due to chances of necrotic samplings in cauliflower type endobronchial growth and to prevent major bleeding with conventional FB use in fleshy hypervascular growth. TBNA will have more value in these two scenarios with EEL. In the literature search, we have found one study by Karahalli et al.^[21] which is not inline to our observations mentioning no added benefit of EBNA to CDTs in increasing diagnostic yield in EEL.

Yield of FB and FB plus techniques in EEL

In the present study, yield of FB and FB plus BW in EEL is 84.65% (756/893) and 88.35% (789/893), respectively. In our previous published studies,^[11,12] we have documented 79.67% and 88.18%, respectively, in small sample sizes. Kacar et al.^[13] observed yield in 86.4% cases. Popovich et al.^[22] mentioned that FB is the preferred test during bronchoscopy in EEL with 67−100% yield and EBNA will not replace FB in these types of lesions.

Sensitivity of FB and EBNA in EEL

Sensitivity of forcep biopsy & EBNA in diagnosing lung malignancy in EEL is 84.65% and 70.99% respectively. Thus, forcep biopsy is considered as gold standard diagnostic technique during bronchoscopy in Exophytic endobronchial lesions. We have compared our observations with our previously published data and authors with similar results in their respective studies [Table 5].

Various authors^[24] have reported diagnostic sensitivity of FB in endobronchial lesions in absence of EBNA. These authors have studies FB with other CDTs and observed sensitivity of FB by Verma et al., Funhasi et al., Kulpati et al., Zavala et al., and Martin et al. as 81.6%, 83%, 85.7%, 97%, and 98%, respectively, in endobronchial lesions.^[24]

Additional yield of EBNA over other methods

Additional yield of EBNA in Exophytic lesions over other CDTs (Conventional Diagnostic Techniques such as forcep biopsy plus bronchial wash) is 11.65%. We have compared our observations with our previously published data and authors with similar results in their respective studies [Table 6].

Shure and Fedullo^[27] studied additional increase in yield of EBNA to conventional FB. They have reported addition of EBNA to FB has increased diagnostic yield from 55% to 87%.^[27] Numerous authors, Dasgupta et al.^[5] and Bilaceroglu et al.,^[8] observed increased diagnostic sensitivity of addition of EBNA to conventional techniques. They have specifically mentioned that EBNA plus CDTs is superior to CDTs alone.^[5,8]

Sole yield of EBNA in EEL, safety of EBNA technique, and importance of rose in increasing yield

EBNA was the sole positive test in 71 of total 893, that is, 7.95% of confirmed lung cancer cases. Although FB has diagnosed 756/893 (84.65%) cases and EBNA 70.99% (634/893) cases, only EBNA was the positive test in 71 cases. In 71 cases diagnosed by cytopathologist in EBNA, samples are further processed to immunohistochemistry analysis. All EBNA samples are processed on site as we are having ROSE facility in our center and this may be the reason for superior diagnostic yield. First published non-randomized study documenting role of ROSE-EBNA performed by Govert et al.^[6] in central neoplasms and they especially mentioned benefits of ROSE facility in EBNA specimens in increasing yield in endobronchial lesions. Randomized controlled trail done by Mondoni et al.^[28] documented that addition of EBNA with ROSA facility will increase diagnostic sensitivity of bronchoscopy in EEL. Author observed.

Bronchoscopy procedure and techniques related complications including EBNA in the present study: Fiberoptic video bronchoscopy-related hypoxia documented in 36 cases and minor bleeding in 42 cases. Other complications such as significant bleeding, pneumothorax, and death were not seen. Minor bleeding was seen with FB mainly in 10.41% (93/893) cases. EBNA was very well tolerated in nearly all cases without any side effects except minor bleeding in few. Shure and Fedullo,^[27] Bollinger et al.,^[29] Jin et al.,^[30] and ACCP Guidelines on Interventional Pulmonology^[20] reported mortality rate of 0.01% and complication rate 0.7% during procedure and techniques which are comparable with our study. Other potentially life-threatening complications during procedure such as respiratory depression, airway obstruction, arrhythmias, and infections were also not observed in our study.