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  • Essay / Cytology of bronchial brushing in the evaluation of lung cancer: effectiveness and pitfalls

    Lung cancer is the main cause of cancer mortality. Currently, various cytological diagnostic techniques are used to evaluate suspected lung tumors. Although the initial diagnosis of malignancy can be made on clinical-radiological grounds, the definitive diagnosis requires cytological or histopathological examinations of samples from the respiratory tract. Cytologic sampling is imperative because many lesions may not be biopsyable. Cytological diagnosis with auxiliary techniques has been included in the new World Health Organization (WHO) classification of lung tumors. In the present study, we aimed to evaluate the role of bronchial brushing cytology in the diagnosis of lung cancer and correlate with histopathological findings. Say no to plagiarism. Get a tailor-made essay on “Why Violent Video Games Should Not Be Banned”? Get the original essay The present study is a retrospective study carried out at the Department of Pathology over a period of 6 years (January 2012 - December 2017). A total of 302 reported cases of bronchial brushing cytology were included and correlated with histopathology; wherever it is available. The rest of the respiratory cytology samples like sputum, bronchoalveolar lavage, bronchial washings, fine needle aspiration cytology were excluded from the study. Bronchial brushing samples were obtained by the pulmonologist in cases of clinical and radiological suspicion of malignancy using a flexible fiberoptic bronchoscope. Impression smears were prepared from the bronchial brush and sent to the cytology laboratory for further examination. Smears were fixed in 95% ethyl alcohol and air dried, followed by staining with Papanicolaou and Giemsa stains; respectively. Ziehl-Neelsens staining for acid-fast bacilli was also performed wherever necessary. Cytological diagnoses on bronchial brushing smears were classified into: 1) Unsatisfactory, 2) Negative for malignant cells, 3) Suspicious for malignant cells, 4) Positive for malignant cells, 5) Others. Unsatisfactory cases were those with only hemorrhage and absence of bronchial epithelial cells. Suspicious cases reported by cytology were included in the malignant category for further statistical analysis. All cases with a specific diagnosis other than lung carcinoma were included in the “other” category. Positive malignant cases were divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Further typing of NSCLC on cytomorphology as adenocarcinoma (AC) and squamous cell carcinoma (SCC) was not possible in all cases and immunocytochemistry was not applied due to financial constraints. Bronchial biopsy was performed in feasible cases according to the clinicians' decision. The bronchial biopsy was fixed in 10% formalin for histopathological processing and then stained with hematoxylin and eosin stain. Immunohistochemistry was applied wherever necessary and the final histological diagnosis was considered the gold standard. Of the total 302 bronchial brushing cytology samples, 208 were from males and another 94 were from females; M:F=2. 22:1. Patient ages ranged from 17 to 84 years, with a mean age of 50.2 years. None of the cases was unsatisfactory on bronchial brushing cytology. Of the 302 cases, signshistological findings were present in 152 cases (152/302). A total of 68 cases (68/302) were reported as malignant on bronchial brushing. The different diagnoses made on bronchial brushings were: 1) NSCLC favoring either squamous cell carcinoma, adenocarcinoma or poorly differentiated, 2) SCLC, 3) large cell carcinoma (LGC), 4) Others. Of the 68 malignant cases, only 11 cases involved women and another 57 cases involved men. Three rare cases diagnosed during bronchial brushings were adenoid cystic carcinoma and primary B-cell non-Hodgkin lymphoma; both located at the carinal end of the trachea with one case of bronchial carcinoid tumor. These cases had similar corresponding histologic findings. 4 cases of pulmonary tuberculosis with positive staining for acid-fast bacilli on Ziehl-Neelsen staining were revealed on cytological examination. 2 cases showed signs of fungal elements; suggestive of aspergillus. Lung cancer is the most common cause of death among men. Recent studies have shown an increasing trend among women as well. Various diagnostic modalities available for early diagnosis of lung malignancy are radiology, bronchoscopy, bronchial biopsy, exfoliative cytology and fine needle aspiration cytology. The combined use of the above techniques gives the best result. A clear distinction between NSCLC and SCLC is important because it has therapeutic implications. Although histopathological findings remain the gold standard for diagnosing the type of lung malignancy; Bronchial biopsy cannot be performed in all clinically suspected cases of pulmonary malignancy, particularly if the tumor is more peripheral and in patients at risk of hemorrhage. In such cases, an alternative diagnostic modality is cytopathological examination of bronchial brushings, washings or fine needle aspiration cytology, which allows for early diagnosis. The recent WHO classification incorporates the importance of cytomorphology for the diagnosis of lung carcinoma using immunocytochemistry. Fiberoptic bronchoscopy was introduced in 1968 as a diagnostic procedure, after which methods to obtain satisfactory samples for exfoliative cytological examination were implemented. Our study evaluates the role of bronchial brushing cytology as a diagnostic modality for lung cancer. In our study, the male/female ratio was 2.22:1 in malignant cases diagnosed by cytology. Comparable results were noted in the study of Gaur et al & Arora et al. The male predominance is attributed to a higher prevalence of smoking, a risk factor for lung cancer. A study by Charles et al. reviewed 105 lung cytology samples acquired by bronchoscopy, of which 76 cases had a histological diagnosis. Few other studies have also noted similar results. In our study, a total of 302 cases of bronchial brushing were included, of which 152 cases had histological follow-up. It is important to distinguish NSCLC from SCLC from a clinical perspective because the subsequent management of the two differs. Decisions to treat with chemotherapy versus other definitive treatment strategies may be based on cytologic diagnosis with ancillary investigations in cases contraindicated for biopsy. In our study, biopsy was not available in 21 cases reported as malignant by cytology and cytological diagnosis provided the basis for guiding further treatment, thus emphasizing the importance of cytology. Some cytomorphological clues suggest broadly categorizinglung carcinoma in NSCLC or SCLC. In SCLC, there are cells with high nucleocytoplasmic ratios, delicate and scanty cytoplasm, nuclear casting, crush artifact, apoptotic bodies, diathesis, salt and pepper granular chromatin, inconspicuous nucleoli. NSCLC; favor CSC shows polygonal cells with orangeophilic cytoplasm and distinct cell borders, intercellular bridges, cell-in-cell arrangement, hyperkeratosis, spindle cells, and hyperchromatic nucleus. NSCLC, favoring AC, will show cells that are round to oval and arranged in three-dimensional groups, formation of glands and papillary fragments. Cells exhibit indistinct borders, intracytoplasmic mucin, foamy cytoplasm, and open vesicular chromatin with prominent nucleoli or coarse chromatin. In the current series, 33 cases of malignant lung tumors were diagnosed as NSCLC, the majority of which (31 cases) had a positive histological correlation. Two of these 33 cases reported as NSCLC were found to be small cell lung carcinoma based on histology. Bronchial brushing cytology smears in these two cases showed poorly differentiated cells in clusters, groups, and scattered individually with a focal gland-like pattern. A diagnosis of poorly differentiated adenocarcinoma was initially suggested with cells arranged in a focal glandular pattern. But upon examination, crushing was noted in focal areas, along with evidence of nuclear overlap and crowding as well as nuclear casting. Thus, it is possible that the lack of dotted chromatin in tumor cells on cytology led to a misdiagnosis of NSCLC. Histology was suggestive of SCLC and showed positive immunostaining for synaptophysin [Figure 3C]. Careful evaluation of the smear is essential to identify areas of crushing and cytologic features such as mold in the absence of characteristic nuclear features. Three cases of SCLC were reported in the present study; 1 case presented discordant histological findings with a final diagnosis of NSCLC. In these smears, a crush zone was noted with some degenerative cells showing signs of nuclear molding, which led to a misdiagnosis of SCLC. However, upon reevaluation of the slides, foci of glandular shaped cells were found. A final diagnosis of NSCLC was made on histology. Degenerative cellular changes may exclude specific subtyping, as was observed in this case. Categorization of poorly differentiated NSCLC into SCC and AC is difficult in cytology and requires immunocytochemistry. In our study, 1 case of AC and SCC was reported as SCC and AC on histology; respectively. One case diagnosed as adenocarcinoma on cytology showed primarily a cohesive cluster of atypical cells, along with a few individually scattered cells, revealing mild to moderate anisonucleosis and eccentric nuclei with granular chromatin. However, the morphology was noticeable at the periphery of the cluster. No marked pleomorphism or hyperchromasia was noted. However, upon re-examining the smears, the focal areas showed flattening of cells with a squamoid appearance at the periphery of the cohesive cell clusters. A final diagnosis of SCC was made based on histology and showed positive immunostaining for p63. Therefore, in cases where single cells are absent, a diagnosis of adenocarcinoma should be made with caution. Similarly, a case diagnosed as SCC ultimately turned out to be a,.