Topic > Bronchial brushing cytology in the evaluation of lung cancer: efficacy and pitfalls

Lung cancer is the leading cause of cancer mortality. Various cytological diagnostic techniques are currently used in the evaluation of suspected lung neoplasms. Although the initial diagnosis of malignancy can be made on clinical-radiological grounds, the definitive diagnosis requires cytological or histopathological examinations of respiratory tract specimens. Cytologic sampling is critical as many lesions may not be biopsiable. Cytological diagnosis with auxiliary techniques has been incorporated into the new World Health Organization (WHO) classification of lung tumors. In the present study, we aim to evaluate the role of bronchial brushing cytology in the diagnosis of lung cancer and correlate it with histopathological findings. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay. The present study is a retrospective study conducted 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 and correlation with histopathology were included; everywhere available. The rest of the respiratory cytology specimens such as sputum, bronchoalveolar lavage, bronchial lavage, fine needle aspiration cytology were excluded from the study. Bronchial brushing samples were obtained by the pulmonologist in clinically and radiologically suspicious cases of malignancy with the aid of a flexible fiberoptic bronchoscope. Impression smears were prepared by 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 stain; respectively. Where necessary, Ziehl-Neelsens staining for acid-fast bacilli was also performed. Cytological diagnosis on bronchial brushing smears was classified into; 1) Unsatisfactory, 2) Negative for malignant cells, 3) Suspicious for malignant cells, 4) Positive for malignant cells, 5) Other. Unsatisfactory cases were those presenting only hemorrhage and absence of bronchial epithelial cells. Suspected cases reported on cytology were included in the malignant category for further statistical analysis. All cases with a specific diagnosis other than lung cancer were included in the “other” category. Positive malignant cases were separated as non-small cell lung cancer (NSCLC) and small cell lung cancer (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 doctors' decision. The bronchial biopsy was fixed in 10% formalin for histopathological processing and subsequently stained with hematoxylin and eosin. Immunohistochemistry was applied where required and the final histological diagnosis was considered the gold standard. Of a total of 302 cytology specimens with bronchial brushing, 208 were male and the remaining 94 were female; M:F=2. 22:1. The patients' ages ranged from 17 to 84 years, with a mean age of 50.2 years. None of the cases were unsatisfactory on cytology with bronchial brushing. Of the 302 cases, histological findings were present in 152 cases (152/302). A total of 68 cases (68/302) were reported as malignant on bronchial brushing. The various diagnoses provided on brushingbronchial were; 1) NSCLC favoring squamous cell carcinoma, adenocarcinoma, or poorly differentiated, 2) SCLC, 3) Large cell carcinoma (LGC), 4) Others. Of all 68 malignant cases, only 11 cases were female and the remaining 57 cases were male. Three uncommon cases diagnosed by bronchial brushing were adenoid cystic carcinoma and primary B-cell non-Hodgkin's lymphoma; both located at the cicatricial end of the trachea together with a case of bronchial carcinoid tumor. These cases had correspondingly similar histological findings. Cytological examination revealed 4 cases of pulmonary tuberculosis with positive staining for acid-fast bacilli with Ziehl-Neelsen staining. 2 cases had evidence of fungal elements; indicative of aspergillus. Lung cancer is the most common cause of mortality in males. Recent studies have highlighted an increasing trend among women too. Various diagnostic modalities available for early diagnosis of lung cancers are radiology, bronchoscopy, bronchial biopsy, exfoliative cytology and fine needle aspiration cytology. The combined use of the above techniques produces the best result. A clear distinction between NSCLC and SCLC is important as it has therapeutic implications. Although histopathological findings remain the gold standard for diagnosing the type of lung neoplasm; Bronchial biopsy cannot be performed in all clinically suspected cases of lung cancer, especially if the tumor is in a more peripheral location and in patients at risk of hemorrhage. In these cases, an alternative diagnostic modality is cytopathological examination through brushing, washing or bronchial needle aspiration cytology, which helps to give an early diagnosis. The recent WHO classification incorporates the importance of cytomorphology for the diagnosis of lung cancer with the help of immunocytochemistry. Fiberoptic bronchoscopy was introduced in 1968 as a diagnostic procedure, after which methods were implemented to obtain satisfactory specimens for exfoliative cytology. Our study evaluates the role of bronchial brushing cytology as a diagnostic modality in lung cancer. In our study, the male-to-female ratio was 2.22:1 in malignant cases diagnosed by cytology. Comparable results were noted in the study by Gaur et al and Arora et al. The male predominance is attributed to the higher prevalence of smoking, being the risk factor in lung cancers. A study by Charles et al examined 105 bronchoscopically acquired lung cytology specimens of which 76 cases had histological diagnoses. A few other studies have also noted similar results. A total of 302 cases of bronchial brushing were included in our study, of which 152 cases had histological follow-up. It is important to distinguish NSCLC from SCLC clinically as the subsequent management of the two differs. The decision to treat with chemotherapy versus other definitive therapeutic strategies can be based on cytological diagnosis with ancillary investigations in cases contraindicated for biopsy. In our study, biopsy was not available in 21 cases reported as malignant on cytology, and cytological diagnosis was the basis for guiding further treatment, thus highlighting the importance of cytology. Some cytomorphological clues point towards a general classification of lung cancer into NSCLC or SCLC. In SCLC, there are cells with high nucleocytoplasmic ratios, sparse and delicate cytoplasm, nuclear modeling, crush artifact, apoptotic bodies, diathesis, granular salt-and-pepper chromatin, inconspicuous nucleoli. NSCLC; favoring SCC shows polygonal cells with cytoplasmorangeophilic 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 clusters, gland formation, and papillary fragments. Cells show indistinct borders, intracytoplasmic mucin, foamy cytoplasm, and open vesicular chromatin with prominent nucleoli or coarse chromatin. In the current series, 33 cases of lung neoplasms 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 on histology. Cytological smears with bronchial brushing in these two cases showed poorly differentiated cells in clusters, groups, and scattered singly along with a focal gland-like pattern. A diagnosis of poorly differentiated adenocarcinoma with cells arranged in a focal glandular pattern was initially considered. But during the exam, crushing in focal areas was noted along with some evidence of nuclear overlap and overcrowding along with nuclear molding. Thus, perhaps the lack of punctate chromatin in tumor cells on cytological examination led to the misdiagnosis of NSCLC. Histology was suggestive of SCLC and showed positive immunostaining for synaptophysin [Figure 3C]. Careful evaluation of the smear is required to identify areas of crushing and cytologic features such as patterning in the absence of characteristic nuclear features. Three cases of SCLC were reported in the present study; 1 case showed discordant histological findings with final diagnosis of NSCLC. In these smears, an area of ​​pinching 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 cells with a glandular pattern were detected. A final diagnosis of NSCLC was made on histology. Degenerative cellular changes may preclude specific subtyping as was seen 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 mostly cohesive clusters of atypical cells, along with a few scattered cells singly with a few cells revealing mild to moderate anisonucleosis and eccentric nuclei with granular chromatin. However, the morphology was distinguishable at the periphery of the cluster. No marked pleomorphism or hyperchromasia was noted. However, upon re-examining the smears, 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 missing, the diagnosis of adenocarcinoma should be made with caution. Similarly, a case diagnosed as SCC was finally proven by histology to be adenocarcinoma. Initially, the diagnosis of SCC was made on cytology, as few atypical epithelial cells with dense cytoplasm and hyperchromatic nuclei were observed in occasional and scattered clusters individually. However, reviewing the slide again, we could find single cells with eccentric nuclei with moderate to abundant cytoplasm with occasional gland-like pattern. Atypical epithelial cells with squamous metaplasia mimicked SCC in our case. In,.