|Year : 2022 | Volume
| Issue : 1 | Page : 17-24
Role of endobronchial needle aspiration cytology in diagnosing lung cancer in bronchoscopically visible tumors: A single-center study
Shital Patil1, Abhijit Acharya1, Ganesh Narwade2
1 Pulmonary Medicine, MIMSR Medical College, Latur, India
2 Department of Pathology, MIMSR Medical College, Latur, Maharashtra, India
|Date of Submission||06-Jan-2023|
|Date of Decision||14-Jan-2023|
|Date of Acceptance||29-Jan-2023|
|Date of Web Publication||31-Mar-2023|
FCCP (USA) Pulmonary Medicine, MIMSR Medical College, Latur 413512, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Bronchoscopy is an important diagnostic tool for the diagnosis of lung cancer, and various techniques have documented increase in diagnostic sensitivity. In this study, we have analyzed the role of bronchoscopy in diagnosis of lung cancer with special emphasis on endobronchial needle aspiration cytology (EBNA) in comparison to other conventional diagnostic techniques (CDTs) such as bronchial wash (BW) and forcep biopsy (FB). Materials and Methods: Prospective, observational study screened 1564 cases with suspected lung malignancy on clinical and radiological basis. Bronchoscopy-guided techniques such as EBNA, BW, and FB are used in exophytic endobronchial lesions (EELs) in confirming the diagnosis of lung cancer and to find additive yield over other techniques such as BW and FB. Rapid onsite evaluation (ROSE) analysis of all EBNA samples done in pathology lab allied center. Finally, histopathology proven 917 lung malignancy cases are included in this study. Statistical analysis is done by using chi-test. Results: In this study, 917 diagnosed lung cancer patients between 29 and 85 age group predominant 61.83% (567/917) and smokers by addiction in 52.12% (478/917) cases. Presented with cough in 80.80% (741/917), clubbing in 55.83% (512/917) cases, and mass lesion in chest radiograph in 53.10% (487/917) cases. Anatomical location is documented on the right side of tracheobronchial in 58.66% (538/917) cases during bronchoscopy. Yield of FB and FB plus BW in EEL is 86.69% (795/917) and 90.94% (834/917), respectively. Yield of EBNA, EBNA plus BW, and EBNA plus FB in EEL is 70.22% (644/917), 75.13% (689/917), and 97.16% (891/917), 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 (FB plus BW) is 9.06%. Sensitivity of FB and EBNA in diagnosing lung malignancy in EEL is 86.69% and 70.22%, respectively. FB is more sensitive technique than EBNA in EEL (P < 0.00001). Sensitivity of FB plus BW in EEL is 90.94% (834/917). Sensitivity of EBNA plus BW in EEL is 75.13% (689/917). Sensitivity of EBNA plus FB in EEL is 97.16% (891/917) (P < 0.00001). Conclusion: EBNA is underutilized bronchoscopic technique in visible endobronchial lesions (exophytic endobronchial type) in spite of satisfactory diagnostic yield as compared with other CDTs. Although FB is most commonly preferred technique in bronchoscopically visible tumors, the addition of EBNA has improved overall diagnostic yield of bronchoscopy and decreased need for repeat bronchoscopy procedure.
Keywords: Adenocarcinoma, bronchial wash, bronchoscopy, cytology, EBNA, forcep biopsy, lung cancer
|How to cite this article:|
Patil S, Acharya A, Narwade G. Role of endobronchial needle aspiration cytology in diagnosing lung cancer in bronchoscopically visible tumors: A single-center study. Bengal J Cancer 2022;2:17-24
|How to cite this URL:|
Patil S, Acharya A, Narwade G. Role of endobronchial needle aspiration cytology in diagnosing lung cancer in bronchoscopically visible tumors: A single-center study. Bengal J Cancer [serial online] 2022 [cited 2023 Jun 6];2:17-24. Available from: http://www.bengaljcancer.org/text.asp?2022/2/1/17/373314
| Introduction|| |
Globally, lung cancer is the leading cause of new cancer diagnosis and deaths. In spite of advancement in diagnostic modalities, lung cancer diagnosis is often delayed due to lack of bronchoscopy facility and techniques. In India, lung cancer accounts for 5.9% of all cancers and 8.1% of all cancer-related deaths. History of bronchoscope use to examine tracheobronchial tree was traced to eighteenth century and used rigid illuminating pipes. In mid-nineteenth century, Ikeda invented fiberoptic bronchoscopy, which has revolutionized the practice of interventional pulmonary medicine. Modifications and advancements in bronchoscopy have undergone in the past five decades such as autofluorescence techniques for early diagnosis of lung cancer, real-time image-guided sampling for exact staging of lung cancer by mediastinal lymph. Additionally, bronchoscopy advancement such as cryotherapy, argon plasma coagulation, and laser and electrocautery can be utilized now for treatment of central airway lung cancers and maintaining patency of central airways.
Yield of various bronchoscopic techniques such as bronchial washing, bronchial brushing, and endobronchial and transbronchial biopsy depends on visibility of tumors endoscopically. In endobronchial pathology, the yield of these techniques is satisfactory and highest for forcep biopsy (FB) 74% in comparison to bronchial brushing 59% and bronchial washing 48%. Significant increase in yield of bronchoscopy observed with combination of all these modalities up to 88%. Bronchoscopic lesions or abnormalities have been classified as endobronchial, submucosal, and peribronchial types according to their visibility. Needle aspiration cytology has been validated over decades during bronchoscopy for the diagnosis of lung cancer in all these three types of lesions and categorized as endobronchial needle aspiration cytology (EBNA) or endobronchial needle aspiration cytology and transbronchial needle aspiration (TBNA) cytology. Addition of EBNA or TBNA in these lesions enhanced diagnostic yield and sensitivity of bronchoscopy procedure in addition to other conventional diagnostic modalities. TBNA is superior to all other conventional sampling modalities in peribronchial and submucosal lesions, and its results are comparable with bronchoscopic FB in endobronchial tumor with an average diagnostic yield of 80%. Dasgupta et al. and Govert et al. documented the use of EBNA along with other modalities during bronchoscopy in diagnosis of lung cancer in exophytic endobronchial lesions (EELs) and observed additive yield of EBNA and specifically mentioned EBNA is the only positive test in proportionate number of cases.
Bronchoscopy-guided EBNA/TBNA is complementary to other conventional diagnostic techniques (CDTs) such as bronchial wash (BW), bronchial brush cytology, and FB., Interestingly, conventional TBNA/EBNA is still underutilized in the majority of bronchoscopy centers across the world. Reasons for underutilization of this novel technique EBNA/TBNA would be inadequate trainings to technique, difficulty in needle handling during bronchoscopy and cytology technique, decreased yield with poor technique, and inadequate laboratory backup due to lack of Rapid onsite evaluation (ROSE) facility and lastly lack of cytopathology expertise over histopathology in lung malignancy. In spite of an increase in diagnostic yield by the addition of EBNA/TBNA to other conventional diagnostic modalities, it is not possible to perform all techniques in the same patient. In this study, we have utilized all conventional fiberoptic bronchoscopy-guided diagnostic modalities including EBNA in diagnosing lung malignancies.
| Materials and Methods|| |
Prospective, observational study conducted during January 2014 to October 2022 in Respiratory Medicine and Critical Care Medicine department in Venkatesh chest hospital and MIMSR Medical College Latur. Objectives of present study were to document the role of EBNA in EELs in confirming the diagnosis of lung cancer and to find out additive yield over other conventional techniques such as BW and FB. Total 1564 suspected lung malignancies on clinical and radiological basis were screened, and finally 917 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.
Inclusion criteria: suspected lung malignancies on clinical and radiological basis such as
- Cases with unexplained paralysis of vocal cord (hoarseness of voice) or stridor.
- Chest X-ray with radiological features of malignancy (coin lesions, mass lesions, mediastinal widening, unilateral high hemidiaphragm, segmental/complete lung collapse, and nonresolving pneumonia).
- 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, and unexplained and recurrent pleural effusion.
Exclusion criteria: cases unfit for bronchoscopy were excluded such as
- Cases with coagulopathy that cannot be corrected and platelets,
- Cases with mechanical ventilation with high PEEP,
- Cases with refractory hypoxemia,
- Cases with recent myocardial infarction or unstable angina,
- Cases with significant dysrhythmia and hemodynamic instability,
- Cases with poor ability to cooperate with procedure.
This study is approved by the Ethics Committee of Venkatesh chest Hospital and Critical Care Center and MIMSR Medical college, Latur, India (Approval # VCC/12-2014; Approval date 06/01/2014).
Bronchoscopic definition of exophytic endobronchial growth
During the bronchoscopy procedure, operators notified different types of endobronchial growth patterns. These EELs were described as “cauliflower like, pedunculated, polypoidal, nodular exophytic, multinodular ulcerated” endobronchial growth.
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 presence of nasal mucosa hypertrophy. Nasal analgesia with xylocaine jelly and oropharyngeal mucosa with xylocaine spray and vocal cords and epiglottis with bronchoscopic instillation topical 10% xylocaine.
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 [Figure 1]. 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 (FB and BW) were sent for cytology and histopathology examination at the Pathology Department.
The statistical analysis was done by using χ2 test in R-3.4 software, Vienna, Austria. 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.
EBNA cytology images
EBNA cytology images documented during the present study are non-small cell carcinoma, small cell carcinoma, squamous cell carcinoma and dysplasia respectively as shown in [Figure 2][Figure 3][Figure 4][Figure 5].
| Results|| |
In this study, 917 diagnosed lung cancer patients between 29 and 85 age group, male are 61.83% (567/917), and females are 38.16% (350/917). In addiction history, we have observed 52.12% (478/917) cases are smoker and 38.63% cases with smoking index more than 20 pack years. Commoner symptoms are cough in 80.80% (741/917), shortness of breath in 49.72% (456/917), hemoptysis in 32.49% (298/917), and chest pain in 24.86% (228/917) cases. Clubbing on general physical examination is documented in 55.83% (512/917) cases.
Commoner radiological presenting features are mass lesion in 53.10% (487/917) cases, Hilar opacity in 33.80% (310/917) cases, and collapse segmental/lobar in 12.21% (112/917) cases. During bronchoscopy, anatomical location is documented on the right side of tracheobronchial in 58.66% (538/917) cases as compared to left side of tracheobronchial wall 31.84% (292/917), and growth at carina documented in 9.48% cases (87/917) cases. Upper lobe bronchi are commoner site on both the sides as compared to other segmental bronchi [Table 1].
|Table 1: Clinical evaluation, radiological patterns, and anatomical sites during bronchoscopy (n = 917)|
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Core observations [Table 2] [Table 3]
In this study, yield of FB and FB plus BW in EEL is 86.69% (795/917) and 90.94% (834/917), respectively. Yield of EBNA, EBNA plus BW and EBNA plus FB in EEL is 70.22% (644/917), 75.13% (689/917) and 97.16% (891/917), 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 (FB plus BW) is 9.06% [Table 3].
|Table 2: Diagnostic yield of fiberoptic bronchoscopy-guided procedures in exophytic endobronchial lesions (n = 917)|
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|Table 3: Sensitivity of bronchoscopy-guided EBNA and forcep biopsy in exophytic endobronchial lesions (n = 917)|
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Sensitivity of FB and EBNA in diagnosing lung malignancy in EEL is 86.69% and 70.22%, respectively. FB is more sensitive technique than EBNA in EEL (P < 0.00001) [Table 2]. Sensitivity of FB plus BW in EEL is 90.94% (834/917). Sensitivity of EBNA plus BW in EEL is 75.13% (689/917). Sensitivity of EBNA plus FB in EEL is 97.16% (891/917) (P < 0.00001) [Table 4].
|Table 4: Sensitivity of bronchoscopy-guided conventional techniques EBNA, bronchial wash, and forcep biopsy in exophytic endobronchial lesions (n = 917)|
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| Discussion|| |
Diagnostic yield of EBNA and EBNA plus techniques in endobronchial lesions
Total yield of EBNA in EELs is 70.22 (644/917). In our previous published studies,, we have documented 62.60% and 60.66%, respectively, in small sample sizes. Kacar et al. observed yield in 77.9% cases. A numerous of studies,, have reported 70%–96% diagnostic yield of EBNA in central airway tumors suspected of bronchogenic carcinoma.
Yield of EBNA, EBNA plus BW, and EBNA plus FB in EEL is 70.22% (644/917), 75.13% (689/917), and 97.16% (891/917), 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., Caglayan et al. 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., Gullon et al., Gellert et al., observed that addition of EBNA to conventional diagnostic yield increases diagnostic sensitivity of bronchoscopy in EELs. They also mentioned that yield is significantly reduced and chances of repeat procedure increased with CDTs without EBNA in the presence of endobronchial growth. The authors,,,,, have observed rationale for decreased yield with CDTs is chances of inadequate sampling during FB due to superficial necrosis resulting in to negative yield, presence of blood clot over lesions giving negative biopsy results. Tha authors,,,,, have mentioned chances of crush artefacts formation during FB technique resulting in 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 the addition of EBNA to CDTs in diagnostic techniques during bronchoscopy procedure.,,,,, American College of Chest Physicians (ACCP) 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 EELs. In literature search, we have found one study by Karahalli et al., which is not inline to our observations mentioning no added benefit of EBNA to CDTs in increasing diagnostic yield in EELs.
Yield of forcep biopsy and forcep biopsy plus techniques in exophytic endobronchial lesions
Total yield of FB in EELs is 86.69% (795/917). In our previous published studies,, we have documented 79.67% and 88.18%, respectively, in small sample sizes. Kacar et al. observed yield in 86.4% cases. Popovich et al. mentioned that FB is the preferred test during bronchoscopy in EELs with 67%–100% yield and EBNA will not replace FB in these types of lesions.
Sensitivity of forcep biopsy and endobronchial needle aspiration cytology in exophytic endobronchial lesions
Sensitivity of FB and EBNA in diagnosing lung malignancy in EEL is 86.69% and 70.22%, respectively. Thus, FB is considered as gold standard diagnostic technique during bronchoscopy in EELs [Table 5].
|Table 5: Diagnostic sensitivity of forcep biopsy and EBNA in exophytic endobronchial lesions|
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The author has reported similar to our findings in their study and reported FB as sensitive tool to diagnose lung cancer in endobronchial lesions in absence of EBNA. The author has mentioned the sensitivity of FB up to 81.6% endobronchial lesions in diagnosing lung malignancy. They have documented superior yield of FB and diagnostic sensitivity in comparison to CDTs.
Additional yield of EBNA over other methods
Additional yield of EBNA in exophytic lesions over other CDTs (FB plus BW) is 9.06% [Table 6].
|Table 6: Additional yield of EBNA over CDTs in exophytic endobronchial lesions|
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Shure and Fedullo studied additional increase in the yield of EBNA to conventional FB. They have reported that the addition of EBNA to FB has increased diagnostic yield from 55% to 87%. Numerous authors, Dasgupta et al. and Bilaceroglu et al. observed increased diagnostic sensitivity of addition of EBNA to conventional techniques. They have specifically mentioned that EBNA plus CDTs is superior to CDTs alone.,
Sole yield of endobronchial needle aspiration cytology in exophytic endobronchial lesions and importance of rapid onsite evaluation in increasing yield
EBNA was the sole positive test in 89 of total 917 confirmed lung cancer cases. Although FB has diagnosed 795/917 (86.69%) cases and EBNA 644/917 (70.22%) cases, only EBNA is the positive test in 89 cases. The 89 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 nonrandomized study documenting role of ROSE–EBNA performed by Govert et al. 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. documented addition of EBNA with ROSA facility will increase diagnostic sensitivity of bronchoscopy in EELs. The author observed significant improvement in sensitivity in ROSE arm than without ROSE in confirming diagnosis and reported ROSE facility of high importance during bronchoscopy in these lesions in conforming final diagnosis and decreasing need for repeat bronchoscopy procedure.
Other important observations in this study
- A. Histopathology type in present study: We have documented adenocarcinoma in 36.96% (339/917) cases, squamous cell carcinoma in 27.91% (256/917) cases, nonsmall cell carcinoma in 24.20% (222//917) cases, small cell carcinoma in 7.52% (69/917) cases, and large cell carcinoma in 3.38% (31/917) cases. Adenocarcinoma trends are equally observed histological type as compared to squamous cell type irrespective of smoking trends in study cases. We have documented that EBNA samples have given satisfactory results with histopathology specimens subjected to immunohistochemistry. In adenocarcinoma, 59% cases are EGFR positive, 16% ALK positive, and 14% ROS positive and 11% are all negative.
- B. Bronchoscopy procedure and techniques related complications including EBNA in this study: Fiberoptic video bronchoscopy-related hypoxia documented in thirty-six 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 8.28% (76/917) cases. EBNA was very well tolerated in nearly all cases without any side effects except minor bleeding in few. Shure et al., Bollinger et al., Jin et al. and ACCP Guidelines on Interventional Pulmonology reported mortality rate of 0.01% and complication rate 0.7% during procedure and techniques, which is 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.
- C. In this study, predominant gender is male 61.83% (567/917), smoking addiction in 52.12% (478/917) of which 38.63% cases having smoking index more than 20 pack years. In spite of higher trends of tobacco exposure, adenocarcinoma histology has been documented in significant number with undifferentiated or nonsmall cell type. Rationale for same findings would be processed tobacco or tobacco with added mixtures of nitrous compounds resulting into predisposition to adenocarcinoma.
- D. Commoner radiological presenting features are mass lesion in 53.10% (487/917) cases, Hilar opacity in 33.80% (310/917) cases and collapse segmental/lobar in 12.21% (112/917) cases. During bronchoscopy, anatomical location is documented on right side of tracheobronchial in 58.66% (538/917) cases as compared to left side of tracheobronchial wall 31.84% (292/917) and growth at carina documented in 9.48% cases (87/917) cases. Upper lobe bronchi are commoner site on both the sides as compared to other segmental bronchi. Upper lobe bronchi are commoner site on both the sides as compared to other segmental bronchi.
| Conclusions|| |
EBNA has documented very crucial role and should be considered as complimentary to CDTs in diagnosing lung cancer in comparison to other CDTs during bronchoscopy in presence of EELs. Importantly, EBNA samples can give rapid results and decrease chance for repeat procedure by guiding adequacy of samples before end of bronchoscopy procedure.
EBNA considered safe, especially when fleshy vascular endobronchial growth is present and risk of bleeding is high with FB. EBNA cytology samples can give comparable results to histopathology. EBNA samples are equally processed for immunohistochemistry analysis as histopathology samples. Thus, EBNA is a beneficial, safe, and minimally invasive bronchoscopic technique with insignificant side effect in the diagnosis bronchogenic carcinoma.
Although FB is more sensitive test than EBNA in EEL in diagnosing disease, we have documented that EBNA has significant additive yield in proportionate number of cases. Rationale for decreased yield with CDTs in comparison with EBNA is chances of inadequate sampling during FB due to superficial necrosis, blood clot, or crush artefacts resulting in negative yield.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]