Submit Your Article CMED MEACR meeting
Home Print this page Email this page Users Online: 1344
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 5  |  Issue : 4  |  Page : 293-298

A study of usefulness of washes and brush cytology with respect to histopathology in diagnosis of lung malignancy by using fiberoptic bronchoscopy


1 Department of Pathology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
2 Department of Pulmonary Medicine, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
3 Department of Community Medicine, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India

Date of Web Publication12-Jul-2016

Correspondence Address:
Abhishek Bandyopadhyay
Andul Purbapara, P.O. Andul Mouri, P.S. Sankrail, Howrah - 711 302, West Bengal
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-0513.186107

Rights and Permissions
  Abstract 


Background: Examination of specimens obtained through flexible fiberoptic bronchoscope is important and often the initial diagnostic technique performed in patients with suspected malignant lung lesion. Aims: To evaluate the usefulness of cytological findings of bronchial washings (pre-and post-bronchoscopy) and bronchial brushing in the diagnosis of lung malignancy with histopathology of bronchial biopsy, taking the latter as the confirmatory diagnostic test. Settings and Design: It was a cross-sectional observational study conducted in a tertiary care center. Subjects and Methods: A total of fifty patients with suspected lung malignancy (clinically and radiologically) were included in this nonrandomized cross-sectional study. Bronchial brushings were obtained from all fifty cases. Prebiopsy bronchial washing (washing collected before the brushing and biopsy procedure) and postbiopsy washing (washing at the end of the procedure) were collected. Results: Prebiopsy (prebrushing) and postbiopsy washing showed high specificity of 92.31%, but a very low sensitivity of 32.43% and 35.14%, respectively. Sensitivity and specificity of brushing were found to be 74.36% and 81.82%, respectively. Positive predictive value of prebiopsy (prebrushing) washing, postbiopsy washing and brushing are 92.31%, 93.55%, and 92.86%, respectively. There was no significant difference in sensitivity between prebiopsy (prebrushing) and postbiopsy washing (Fisher exact probability test; PA= 0.99). However, there was statistically significant difference between sensitivity of brushing with prebiopsy (prebrushing) washing (Fisher exact probability test; PA = 0.0012793) and postbiopsy washing (Fisher exact probability test; PA = 0.00310282). Conclusions: Bronchial washing cytology in combination with brush cytology aids in the early diagnosis of lung malignancy in addition to histopathology.

Keywords: Bronchial washing, brushing, fiberoptic bronchoscopy, histopathology, nonsmall cell carcinoma, small cell carcinoma


How to cite this article:
Bandyopadhyay A, Pal M, Das I, Sarkar S, Sarkar R, Taraphdar P. A study of usefulness of washes and brush cytology with respect to histopathology in diagnosis of lung malignancy by using fiberoptic bronchoscopy. Clin Cancer Investig J 2016;5:293-8

How to cite this URL:
Bandyopadhyay A, Pal M, Das I, Sarkar S, Sarkar R, Taraphdar P. A study of usefulness of washes and brush cytology with respect to histopathology in diagnosis of lung malignancy by using fiberoptic bronchoscopy. Clin Cancer Investig J [serial online] 2016 [cited 2019 Aug 22];5:293-8. Available from: http://www.ccij-online.org/text.asp?2016/5/4/293/186107




  Introduction Top


Today lung cancer is one of the most common malignancies in the world. Moreover, with an estimated increase of about 5% a year, it now represents globally the first cause of cancer-related mortality in both sexes. In India, the exact incidence of lung cancer is not known due to lack of formal epidemiological data from across the country.[1] Overall the age distribution ranges from 20 to 90 years, with a peak incidence between 50 and 70 years of age.[2] The overall therapeutic results have changed very little in the past decade in the face of an increasing incidence of this disease throughout the world. Most patients are found to have advanced disease at the time of diagnosis, and thus, treatment of this population is disappointing, very often only palliative. Several studies, however, have demonstrated that early detection, localization, and aggressive treatment of lung cancer results in the 5-year survival rate of 70–80%.[3] Recent developments in molecular study of lung cancer along with subsequent targeted therapeutic approaches have given a new ray of hope.

Bronchoscopy is perhaps the most invaluable tool for diagnosis of lung cancer. Various diagnostic techniques have been developed using flexible fiberoptic bronchoscopy (FOB).[4] Among various bronchoscopic techniques, bronchial biopsy has the highest sensitivity and specificity for endobronchial malignant lesions. Thus, histopathological examination of bronchial biopsy specimen remains the confirmatory or the gold standard test in these situations. However, bronchial biopsies cannot be satisfactorily performed in more peripheral sites, in narrow bronchial lumen or patients at risk of hemorrhage. Hence, alternative methods for diagnosis are sometimes required. Both washing and brushing cytology are very effective in the diagnosis of lung cancers. Brushings often offer excellent specimens and accurate information about the site of the lesion.[5] Cytological assessment of specimens obtained through washing and brushing of the respiratory tract is important, and often the initial diagnostic technique carried out in a patient with suspected malignant lung lesion.[6] The utilities of cytology are extensive, and sometimes they help in planning the treatment without the requirement for an open biopsy. Imprint smears from bronchial biopsy have also been found to give a good diagnostic yield.[7]

This cross-sectional, observational study was conducted at a tertiary care center over the period of 18 months with the aim to correlate brushing and washing cytology with biopsy in the diagnosis of lung cancer.


  Subjects and Methods Top


It was a cross-sectional observational study conducted in the Department of Pathology in association with Department of Respiratory Medicine and Community Medicine, Nil Ratan Sircar Medical College and Hospital, Kolkata. The samples for cytological and histological examination were collected from the indoor/outdoor patients in whom clinical findings, radiological examination, and bronchoscopic examination suggested lung malignancy. Chronic cough, hemoptysis, significant weight loss, pallor, lymphadenopathy were among the most significant clinical findings that were considered. Among the radiological findings, mass with or without consolidation was the most characteristic indicator apart from pleural effusion. Among these suspicious patients, who were considered for bronchoscopy, endobronchial growth, and narrowing of bronchial lumen (due to compression from outside) were the predominant presentations. Patients with hemorrhagic diathesis, poor general condition, and sputum positive for acid fast bacilli were excluded from the study. A total of fifty cases were studied in the stipulated time frame of 18 months (January 2014–July 2015) which fulfilled our inclusion and exclusion criteria. The samples were obtained by Pentax flexible FOB done by the pulmonologists following standard protocol. Bronchial brushings were obtained by the use of a stiff-bristle disposable brush (outer diameter of brush is 2 mm, and outer diameter of sheath is 1.8 mm). Every case followed the following sequence of event: Pre-biopsy washing, brushing, biopsy, and postbiopsy washing. Brushing material smeared directly onto at least four clean glass slides. The two air-dried smears were stained with Leishman Giemsa stain and two slides are fixed with ethanol-ether mixture for Pap and hematoxylin and eosin (H and E) stain. Bronchial wash fluids taken both before brushing and after biopsy were first centrifuged (1500 rpm for 5 min) and then prepared into air dried and ethanol fixed smears (total 4 slides as before) and stained with Giemsa, H and E and Pap stain, respectively. Bronchial biopsy specimens were fixed in 10% formalin, sectioned cut at 3–4-micron thickness and stained with H and E.


  Results Top


Most patients were in their fifth and sixth decade of life with age, the range of 31–80 years. Of 50 study subjects, lung cancer was confirmed in 38 (76%) cases by histopathology of bronchial biopsy. Among patients with lung cancer, 79% were male and 21% were females [Table 1]. Squamous cell carcinoma was found to be the most common lung cancer (47.4%) [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], followed by adenocarcinoma (23.7%) [Figure 6], [Figure 7], [Figure 8], small cell carcinoma (15.8%) [Figure 9], [Figure 10], large cell neuroendocrine (5.2% ) and large cell anaplastic carcinoma [Figure 11] and [Figure 12] [Table 2]. All except two cases of bronchial biopsy could be differentiated into a specific type of nonsmall cell carcinoma (NSCC). Prebiopsy (prebrushing) and postbiopsy washing showed high specificity of 92.31%, but a very low sensitivity of 32.43% and 35.14%, respectively. Sensitivity and specificity of brushing were found to be 74.36% and 81.82%, respectively. Positive predictive value of prebiopsy (prebrushing) washing, postbiopsy washing and brushing are 92.31%, 93.55%, and 92.86%, respectively. Both sensitivity and accuracy of combined tests (postwash and brush together) increases significantly [Table 3] and [Table 4]. There was no significant difference in sensitivity between prebiopsy (prebrushing) and postbiopsy washing (Fisher exact probability test; PA = 0.99). However, there was statistically significant difference between sensitivity of brushing with prebiopsy (prebrushing) washing (Fisher exact probability test; PA = 0.0012793) and postbiopsy washing (Fisher exact probability test; PA = 0.00310282) [Table 5].
Table 1: Age-sex distribution of patients with lung malignancy

Click here to view
Table 2: Different types of lung cancers with relative distribution in percentage

Click here to view
Table 3: Results of different procedures used in the study

Click here to view
Table 4: Results of different cytological techniques compared to gold standard (bronchial biopsy) in percentage

Click here to view
Table 5: Statistical significance among different cytological procedures

Click here to view
Figure 1: Photomicrograph of squamous cell carcinoma: Wash cytology smear shows clusters of polygonal cells with eosinophilic cytoplasm and hyperchromatic nuclei (Pap, ×100)

Click here to view
Figure 2: Brush cytology smear of squamous cell carcinoma shows similar clusters of polymorphic cells with eosinophilic cytoplasm and hyperchromatic nuclei (Pap, ×400)

Click here to view
Figure 3: Histology of squamous cell carcinoma showing polygonal cells with hyperchromatic nuclei and eosinophilic cytoplasm (H and E, ×400)

Click here to view
Figure 4: Photomicrograph of squamous cell carcinoma: Post wash cytology smear shows clusters of polygonal cells with eosinophilic cytoplasm and hyperchromatic nuclei (H and E, ×100)

Click here to view
Figure 5: Corresponding histology section of squamous cell carcinoma shows tissue fragments of atypical squamous cells having polygonal shape with hyperchromatic nuclei and eosinophilic cytoplasm (H and E, ×400)

Click here to view
Figure 6: Photomicrograph of adenocarcinoma: Wash cytology smear showing cohesive clusters of round to oval cells with abundant vacuolated cytoplasm and hyperchromatic nuclei (Leishman and Giemsa, ×100)

Click here to view
Figure 7: Brush cytology smear of adenocarcinoma showing cohesive clusters of round to oval cells with abundant vacuolated bluish cytoplasm, intracytoplasmic inclusions and hyperchromatic nuclei (Leishman and Giemsa, ×400)

Click here to view
Figure 8: Corresponding histopathological section shows atypical cuboidal to low columnar cells showing an acinar architecture with pale eosinophilic intracytoplasmic mucin (H and E, ×400)

Click here to view
Figure 9: Photomicrograph of small cell carcinoma: Brush cytology smear showing cluster of small dark hyperchromatic cells with scanty cytoplasm (H and E, ×100)

Click here to view
Figure 10: Corresponding histopathological section shows small dark hyperchromatic cells having very scanty cytoplasm showing necrosis and molding (H and E, ×100)

Click here to view
Figure 11: Brush cytology smear shows large cell anaplastic carcinoma having large bizarre looking cells. High degree of cellular atypia and pleomorphism present (MGG, ×400)

Click here to view
Figure 12: Corresponding histopathological section of large cell anaplastic carcinoma having large bizarre looking cells with hyperchromatic nuclei and prominent nucleoli. Few tumor giant cells are also seen (H and E, ×400)

Click here to view



  Discussion Top


The age distribution in our study shows a wide range, i.e., from 30 years to 80 years. Mean age of presentation in our study is 56.67 years which corroborates with other Indian and international studies.[2],[8] In our study, most of the patient with lung malignancy are males (79%). We found male:female ratio in our study population 3.76:1, which is similar to sex ratios of other Indian studies.[2] Global sex ratio was found to be much lower (2.14:1) in few studies.[9] This may be due to changing smoking pattern and more accessibility and reporting of the females to healthcare facility in western countries. In our study, squamous cell carcinoma was most prevalent followed by adenocarcinoma and small cell carcinoma. This pattern is supported by other Indian studies [2] and the fact that we were dealing only with central lung malignancies. Although recently, there is an increase in adenocarcinoma cases worldwide. Bronchial washing is often used along with bronchial brushing and biopsy to diagnose lung cancer. However, the optimal timing of bronchial washing with respect to biopsy and brushing (i.e., whether before or after biopsy and brushing) has been subject to much debate. To assess the optimal sequence in which bronchial washing to be performed, the washing was obtained in two ways in this study: Prebiopsy (prebrushing) washing and postbiopsy washing.

This study was conducted with the objectives of assessing the sensitivity and specificity of bronchoscopic cytological procedures; bronchial brushing, and washing by comparing with the histopathology of bronchial biopsy obtained from lung tumors. In this study, we found that prebiopsy and postbiopsy washing showed high specificity of 92.31%, but a very low sensitivity of 32.43% and 35.14%, respectively. Sensitivity and specificity of brushing were found to be 74.36% and 81.82%, respectively. This finding of the present study is similar to the result that was observed by Mak et al.[10] and Chen et al.[11]

Previous studies by Park et al.[12] and Karahalli et al.[13] had found almost the comparable result of bronchial washing in lung cancer cases. However, in other previous studies by Solomon et al.[14] van der Drift et al.,[15] the diagnostic yield of bronchial washing was not similar with that of our study.

On comparing, no significant difference was found between sensitivity of prebiopsy washing and postbiopsy washing cytology in the current study (Fisher exact probability test; PA = 0.99). A similar trend was noticed in previous studies also.[15]

False positive results were noticed in these cytological techniques used in the present study. It may be possible that some of these classified as false positives in the present study might be true positives as methods other than bronchial biopsy to confirm the diagnosis of lung cancer were not used in the present study. Majority of the previous studies [13],[15] that have used other techniques such as re-bronchoscopy, surgery, transthoracic needle aspiration, CT-guided fine needle aspiration cytology, tumor markers, and autopsy, to prove the cases of lung cancer have shown that bronchial biopsy does not provide diagnostic yield in all cases of lung cancer. Chances of missing the diagnosis by bronchial biopsy are more in peripheral lung tumors. On bronchoscopic examination, the gross morphology of majority of these cases of adenocarcinoma was compression type lesion, i.e., extrinsic compression of the bronchus by the lesion [13] and thus there may be a possibility of getting less representative material by bronchial biopsy in such tumors. Furthermore, in mucinous type of adenocarcinoma, bronchial biopsy specimen may contain pools of mucin, very few neoplastic cells with a relative lack of atypia that make the diagnosis of adenocarcinoma more difficulties observed by Butnor.[16] In our study, two cases were diagnosed as NSCC not otherwise specified as Pap stain and periodic acid schiff and diastatse (PAS-D) stains were noncontributory.

There has been a controversy as to whether bronchial washing should be routinely used or not. Many studies like Trevisani et al.[17] Karahalli et al.[13] in the past reported that the diagnostic yield did not increase significantly further by the addition of bronchial washing to bronchial biopsy and recommended that washing should not be routinely used. However, authors like Mak et al.,[10] Jones et al.[18] and Bodh et al.[19] have suggested that bronchial biopsy, brushing, and washing should be performed to obtain optimal diagnostic yield. Liwsrisakun et al.[20] have observed that the addition of bronchial washing to either biopsy or brushing is beneficial but not cost-effective. Bronchial biopsies cannot be performed in more peripheral sites or patients with luminal obstruction or at risk of hemorrhage. Hence, alternative methods for diagnosis are sometimes required.


  Conclusion Top


The bronchial washing or brushing is a safer technique with much lesser risk of hemorrhage or mortality. Based on findings of the study, it may be concluded that obtaining of bronchial brushing and washing cytology specimens using bronchoscopy aids in the diagnosis of lung malignancy with a reasonable high accuracy rate and with morphological typing of neoplasms. Brush and wash cytology is particularly useful in patients with evidence of obstruction or risk of hemorrhage where bronchial biopsy is not possible. Furthermore, all these techniques may be used concurrently with bronchial biopsy to diagnose a very lethal disease like lung malignancy where early and effective diagnosis followed by appropriate treatment can reduce mortality.

Financial support and sponsorship

Department of Pathology, Department of Pulmonary Medicine and Department of Community Medicine.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Vigg A. Lung cancer. Lung India 1997;15:54-7.  Back to cited text no. 1
  Medknow Journal  
2.
Kirmani N, Jamil K, Naidu MU. Occupational and environmental carcinogens in epidemiology of lung cancer in South Indian population. Biol Med 2010;2:1-11.  Back to cited text no. 2
    
3.
Edell ES, Cortese DA. Bronchoscopic localization and treatment of occult lung cancer. Chest 1989;96:919-21.  Back to cited text no. 3
    
4.
Rosai J, editor. Respiratory tract – Lung and pleura. In: Rosai and Ackerman's Surgical Pathology. 9th ed. Missouri: Elsevier; 2004. p. 359-458.  Back to cited text no. 4
    
5.
Melamed MR. Tumours of the lung: Conventional cytology and aspiration biopsy. In: Koss LG, Melamed MR, editors. Koss's Diagnostic Cytology and its Histopathologic Basis. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. p. 643-712.  Back to cited text no. 5
    
6.
Guidelines of the Papanicolaou Society of Cytopathology for the examination of cytologic specimens obtained from the respiratory tract. Papanicolaou Society of Cytopathology task force on standards of practice. Diagn Cytopathol 1999;21:61-9.  Back to cited text no. 6
    
7.
Noronha V, Patil VM, Joshi A, Prabhash K. Efficacy and safety of metronomic administration of paclitaxel for advanced recurrent non-small-cell lung cancer. Indian J Cancer 2013;50:122-7.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
8.
International Agency for Research on Cancer. GLOBOCAN 2012 Cancer Incidence and Mortality Worldwide in 2012. Available from: http://www.globocan.iarc.fr/.  Back to cited text no. 8
    
9.
Popp W, Rauscher H, Ritschka L, Redtenbacher S, Zwick H, Dutz W. Diagnostic sensitivity of different techniques in the diagnosis of lung tumors with the flexible fiberoptic bronchoscope. Comparison of brush biopsy, imprint cytology of forceps biopsy, and histology of forceps biopsy. Cancer 1991;67:72-5.  Back to cited text no. 9
    
10.
Mak VH, Johnston ID, Hetzel MR, Grubb C. Value of washings and brushings at fibreoptic bronchoscopy in the diagnosis of lung cancer. Thorax 1990;45:373-6.  Back to cited text no. 10
    
11.
Chen WT, Chao TY, Wu CP, Perng WC, Shen CY, Chiang CH. Comparison of the diagnostic yield of bronchial brushing cytology before and after endobronchial biopsy of flexible fibroptic bronchoscopy – A prospective study. J Med Sci 1997;18:165-70.  Back to cited text no. 11
    
12.
Park KS, Park JY, Cha SI, Son JW, Kim KY, Kim JS, et al. Bronchial brushing and bronchial washing for diagnosis of central lung cancer. Tuberc Respir Dis 1999;46:817-25.  Back to cited text no. 12
    
13.
Karahalli E, Yilmaz A, Türker H, Ozvaran K. Usefulness of various diagnostic techniques during fiberoptic bronchoscopy for endoscopically visible lung cancer: Should cytologic examinations be performed routinely? Respiration 2001;68:611-4.  Back to cited text no. 13
    
14.
Solomon DA, Solliday NH, Gracey DR. Cytology in fiberoptic bronchoscopy. Comparison of bronchial brushing, washing and post-bronchoscopy sputum. Chest 1974;65:616-9.  Back to cited text no. 14
    
15.
van der Drift MA, van der Wilt GJ, Thunnissen FB, Janssen JP. A prospective study of the timing and cost-effectiveness of bronchial washing during bronchoscopy for pulmonary malignant tumors. Chest 2005;128:394-400.  Back to cited text no. 15
    
16.
Butnor KJ. Avoiding underdiagnosis, overdiagnosis, and misdiagnosis of lung carcinoma. Arch Pathol Lab Med 2008;132:1118-32.  Back to cited text no. 16
    
17.
Trevisani L, Pazzi P, Sartori S, Potena A. Value of washings and brushings at fibreoptic bronchoscopy in the diagnosis of lung cancer. Thorax 1991;46:74.  Back to cited text no. 17
    
18.
Jones AM, Hanson IM, Armstrong GR, O'Driscoll BR. Value and accuracy of cytology in addition to histology in the diagnosis of lung cancer at flexible bronchoscopy. Respir Med 2001;95:374-8.  Back to cited text no. 18
    
19.
Bodh A, Kaushal V, Kashyap S, Gulati A. Cytohistological correlation in diagnosis of lung tumors by using fiberoptic bronchoscopy: Study of 200 cases. Indian J Pathol Microbiol 2013;56:84-8.  Back to cited text no. 19
[PUBMED]  Medknow Journal  
20.
Liwsrisakun C, Pothirat C, Bumroongkit C, Deesomchok A. Role of bronchial washing in the diagnosis of endoscopically visible lung cancer. J Med Assoc Thai 2004;87:600-4.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Subjects and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed2511    
    Printed72    
    Emailed1    
    PDF Downloaded17    
    Comments [Add]    

Recommend this journal