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Table of Contents
Year : 2022  |  Volume : 10  |  Issue : 3  |  Page : 195-202

Changing Trends of adenocarcinoma among other nonperipheral lung tumors in smokers and nonsmokers: A Tertiary care center's experience

1 Department of Pulmonary Medicine, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
2 Department of Pathology, Government Medical College, Anantnag, Jammu and Kashmir, India

Date of Submission12-Aug-2021
Date of Decision30-Sep-2021
Date of Acceptance02-Jan-2022
Date of Web Publication12-Jul-2022

Correspondence Address:
Dr. Ajit Harsha
Department of Pulmonary Medicine, Vydehi Institute of Medical Sciences and Research Centre, 82, Near BMTC 18th Depot, Vijayanagar, Nallurhalli, Whitefield, Bengaluru - 560 066, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_88_21

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Background: Globally, modern lifestyles and the increasing incidence of lung cancer have changed the histopathological presentation of lung cancer to the point that it has reached epidemic proportions. It is well known that tobacco smokers are more prone to lung cancer. Nonsmokers are no exception. We conducted this study to determine if primary lung cancer is increasing in nonsmokers and examine the differences in clinicopathological patterns and disease staging between smokers and nonsmokers. Objective: (1) Comparing the occurrence of nonperipheral lung tumors in smokers and nonsmokers, (2) to determine whether bronchogenic carcinoma in smokers and nonsmokers exhibited the same histopathological shift, (3) a comparison of lung cancer in smokers and nonsmokers based on clinical and radiological findings. Materials and Methods: A prospective study in Pulmonary Medicine was conducted over 7 years from August 2012 to January 2020. All adult patients were screened with a detailed history and risk factors. Histopathological analysis was performed on patients with X-ray findings that appeared to be a mass or collapse caused by endobronchial growth, as well as on patients who were clinically, radiologically, and bronchoscopically suspicious for malignancy. Results: The study reports that out of the 386 cases of bronchogenic carcinoma, 295 (76.4%) were between 46 and 70 years of age, 282 (73.05%) were male, 250 (85%) smokers, and 104 (27%) females, 44 (14.9%) smokers. Smokers outnumbered nonsmokers by a ratio of 3.1:1. In 257 patients, fever was the most common symptom, followed by hemoptysis in 245 patients. Mass lesion was the most common radiological finding in 245 (63.4%) patients. Squamous cell carcinoma 123 patients (43.6%), Adenocarcinoma 107 patients (37.9%) and small cell carcinoma 35 patients (12.4%) were more common in males, while adenocarcinoma patients 48 (46.1%), squamous cell carcinoma 36 patients (34.6%) and small cell carcinoma 12 patients (11.5%) were more common in females. Conclusion: Majority of elderly patients have an increased risk of developing malignancy, as shown by this study. Smokers are still more likely to develop primary lung cancer than nonsmokers. Squamous cell carcinomas constituted a greater proportion of all histopathological types than adenocarcinomas. Adenocarcinomas are more likely to develop centrally during their later stages. The majority of adenocarcinoma patients presented at the terminal stage and were not smokers.

Keywords: Adenocarcinoma, bronchogenic carcinoma, endobronchial biopsy, never smokers, smoking, squamous cell carcinoma

How to cite this article:
Harsha A, Katare S, Kumar AR, Bhat S, Dhulipala S. Changing Trends of adenocarcinoma among other nonperipheral lung tumors in smokers and nonsmokers: A Tertiary care center's experience. APIK J Int Med 2022;10:195-202

How to cite this URL:
Harsha A, Katare S, Kumar AR, Bhat S, Dhulipala S. Changing Trends of adenocarcinoma among other nonperipheral lung tumors in smokers and nonsmokers: A Tertiary care center's experience. APIK J Int Med [serial online] 2022 [cited 2022 Aug 11];10:195-202. Available from: https://www.ajim.in/text.asp?2022/10/3/195/350753

  Introduction Top

Bronchogenic carcinoma is the name given to tumors that originate within the bronchi or the parenchyma of the lungs.[1] A century ago, lung cancer was uncommon, but now it is the most common malignancy and leads to the majority of deaths.[2],[3] Globally, lung cancer incidence has increased according to GLOBACON (2020), 2.3 million inhabitants (11.7% of all malignant neoplasms) and 1.8 million deaths (accounting for 18% of all malignant neoplasms) were reported.[3] 1,796,144 deaths were reported as a result of malignant lung tumors, accounting for 18% of all deaths from malignant neoplasms. The number of malignant lung neoplasms that were detected in India in 2020 was 72,500 (5.5% of all cases of malignant lung neoplasms).[3]

It has historically been more common among men than women to develop lung cancer based on age-adjusted rates. Although there is still a significant difference between the female and male incidence rates, the magnitude of the difference has decreased, reflecting the stabilization of the female incidence rate and the decline of the male incidence rate.[4],[5],[6] In addition, according to cancer registry data from 1995 to 2014, lung cancer incidence has declined significantly faster among young men than young women.[7] This reversal of trends has been linked to a variety of confounding factors, such as differences in exposure time or smoking status and other compounds.

Approximately 90% of lung cancers are associated with smoking. Apart from cigarette smoking, asbestos is the only substance identified as having a clear link to lung cancer. The compounding effect of smoking combined with asbestos exposure can lead to increased lung cancer risk. Currently, there is an estimated 16.5% prevalence of smoking among women in the West, which is far too high.[8] Due to the complex interaction between smoking and genetics and environmental factors, the number of packs smoked per year does not correlate with lung cancer risk. A significant amount of arsenic, chromium, and nickel, as well as polycyclic aromatic hydrocarbons, can also cause lung cancer. Therefore, establishing a causal relationship between risk factors and lung cancer is complex.

Studies conducted in Western and Asian countries have shown that nonsmokers develop lung cancer at a younger age, but only some cohort studies have validated that idea.[7],[11],[10],[12] Geographic differences in subtypes of the disease are evident, especially women from Asian countries, 60%–80% of them have never smoked.[9] Research has shown that, even if women do not smoke, their chances of developing lung cancer are higher than men.[9],[10],[11] Lung cancer in never smokers (LCINS) is distinct enough epidemiologically and biologically from a smoker's cancer and still has not been clearly understood. When nonsmokers are exposed to secondhand smoke, they are at a high risk of lung cancer.[13]

Lung cancer is commonly categorized into two categories based on histology and management i.e., small cell lung cancer and non-small cell lung cancer.[14],[15] Men and women's susceptibilities to a range of molecular aberrations that cause lung cancer may be altered by smoking and other probable carcinogens. As a result, gender-related differences in lung cancer histology and biology could play a role.[19] In Western countries, Adenocarcinoma has been the most common type of lung cancer for the past 30 years, while in India, squamous cell carcinoma is the dominant variant. An increase in adenocarcinomas has been linked to changes in smoking behavior.[3] Squamous cell carcinomas were once more common in men, but adenocarcinomas are now the most common kind and a primary cause of death in both men and women.[5],[16],[17],[18]

A radiographic image helps select the best modality for obtaining tissue samples for diagnosis and staging. Computed tomography (CT) is of particular importance to this process since it provides anatomic definitions of tumors within the thorax, and the biopsy is directed accordingly for histopathologic diagnosis and staging.

Objectives of the study

  1. A primary objective of this study is to investigate how smoking affects the histological patterns and changes in the geographic pattern of lung cancer
  2. Comparing the incidence of nonperipheral lung tumors in smokers and nonsmokers
  3. Comparison of lung cancer among smokers and nonsmokers based on clinical and radiological findings.

  Materials and Methods Top

After Institutional Ethics Committee approval was obtained, a prospective observational cohort study was conducted from August 2012 to January 2020. Patients presenting to the respiratory medicine department at the tertiary care center were recruited for the study. The data were collected once inclusion criteria had been met.

Adult patient (>18 years) with clinical features suggestive of primary lung cancer, patient willing to give consent and abnormal radiograph (X-ray and CT chest with central lung tumor [inner two-thirds in CT measurement was taken] and suspected lung cancer) were included in the study. WHO definition of smoking was used.

Patients with pulmonary metastasis from other organs, bleeding diathesis, poor respiratory function reserve were excluded from the study.

After calculating sample size for an infinite population using confidence interval at 95%, margin of error 5% and population proportion of 50%. Calculated sample size n = 385 cases was obtained.

Contrast-enhanced CT thorax was performed on 386 patients. BRONCHOVIDEOSCOPE OLYMPUS BF TYPE 1T150 was used to take Endobronchial biopsy using Boston Scientific M00515192 08714729818083 Single Use Biopsy Forceps Standard Capacity. BRONCHOVIDEOSCOPE biopsy samples were sent for histopathological examination.

Statistical analysis

The jamovi project (2021). jamovi (Version 2.0) [Computer Software]. Retrieved from https://www.jamovi.org, City: Sydney, Country: Australia program was used for this project. Descriptive statistics of cases were represented using percentages, and frequencies were used (the continuous demographic characteristics were represented using mean and standard deviation [SD]). Pearson's correlation test was used to determine the relationship between two variables. Accordingly, the correlation coefficient ranges from −1.0 to +1.0, and the negative value represents an inverse relationship between the parameters, whereas the positive value represents a direct relationship between them. The Chi-square test for independence was used, and the significance of this correlation coefficient was expressed as a P value. Data were presented as tables and graphs, with a significance level of P < 0.05 taken as statistically significant.

  Results Top

From August 2012 to January 2020, 386 cases underwent endobronchial biopsy followed by histopathological examination. Patients were divided into two groups: smokers and nonsmokers. A total of 294 (81.6%) patients were smokers, and 92 (25.6%) were nonsmokers.

Baseline demographical data of the patients are shown in [Table 1]a, [Table 1]b, [Table 1]c, [Table 1]d, [Table 1]e.
Table 1: Demographics of the present study

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The mean ± SD age of all patients studied was 54.35 ± 11.85 years, and 167 cases were below 55 years of age, 295 patients were between 46 and 70 years of age as shown in [Figure 1]. There were male predominance 282 (78.33%) cases with a male: female ratio of 2.7:1. Out of the total population, 294 (76.16%) were smokers as against 92 (23.8%) were nonsmokers as shown in [Figure 2]. Among female patients, 44 (11.3%) were exposed to passive smoking, chewing tobacco, and biomass fuel.
Figure 1: Age pyramid in males and females

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Figure 2: Smoker versus nonsmokers in males and females

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The most common clinical findings in smokers compared to nonsmokers were cough (64.9% vs. 29.3%), chest pain (62.2% vs. 28.2%), breathlessness (61.9% vs. 29.3%), wheezing (65.6% vs. 40.2%), fever (76.8 % vs. 33.6%), loss of appetite (68.3% vs. 32.6%) and weight loss (73.8% vs. 21.7%). In nonsmokers, hemoptysis (62.2% vs. 67.3%) and clubbing (18% vs. 76%) were more common than smokers as represented in [Table 1]a. In [Figure 3], squamous cell carcinoma predominates over other lung malignancies, and there is a narrow gap between squamous and adenocarcinoma. [Table 2] shows significant and non-significant correlations among smokers, especially hemoptysis, clubbing, and mass lesions.
Figure 3: Shows histopathological types of lung malignancies diagnosed

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Table 2: Statistical correlation of smokers with clinical and radiological features

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The most common occupation among smokers compared to nonsmokers was farming (63.6% vs. 30.4%), followed by homemaker (14.9% vs. 32.6%). Most of the teachers (4.4% vs. 32.6%) were nonsmokers. Most patients were smokers in squamous cell carcinoma (46.5% vs. 23.9%). Whereas in adenocarcinoma (36% vs. 53.2%) and small cell carcinoma (11.9% vs. 13%), nonsmokers were more. Most nonsmokers presented at stage 4 (52% vs. 57.6%).Smokers commonly presented at stage 3 (33.6% vs. 32.6%) of the disease as seen in [Table 3].
Table 3: Histopathological comparison

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Radiological findings more common in smokers than nonsmokers were mass lesion 245 (65.3 vs. 57.6) consolidations (57.1 vs. 26) 192 effusion 176 (53.4 vs. 20.6) cavity 160 (47.2 vs. 22.8) nodules 157 (48.2 vs. 16.3) ground-glass opacity 123 (37.4 vs. 14.1) atelectasis 103 (33.6 vs. 4.3). Military presentation in adenocarcinoma was noted in four cases.

  Discussion Top

A significant number of lung cancer patients do not smoke, despite lung cancer being labeled as a smoking-related disease. With the above background, the study was done to compare the clinicoradiological and histopathological changes of smokers versus nonsmokers with evidence of bronchogenic carcinoma in the rural residents attending a tertiary health center.

In the present study of 386 cases of endobronchial biopsy, the age ranged from 18 to 81 years.

As shown in [Table 1]a, 53.8% of the participants were 46–70-years-old, indicating that lung cancer is most common in younger people in rural settings, similarly to Indian studies, whereas in contrast to cancer statistics from other countries, lung cancer is most common in men and women over 70 years old.

According to the present study, the mean age of diagnosis of lung cancer was 54.35 years, which was closer to the 54 years of the GLOBOCAN 2018 Indian population. Study results from other countries ranged from 62 to 70 years old.[3],[20],[21]

The male to female ratio, in the present study, was 2.7:1, i.e., out of every four diagnosed lung cancers patients, 3 were male, and 1 was female whereas GLOBOCAN 2018 Indian statistics, the ratio is 4.5:1–8.2:1.[3] From the above comparison, it is evident that there is a narrowing gender gap regarding lung cancer development.

This present analysis showed a ratio of 3.1:1 between smokers and never smokers, i.e., out of 4 lung malignancies, 3 are smokers and 1 nonsmoker, similar to 4.4:1 as per Rawat et al.'s study.[22] According to the above comparison, smokers have a higher incidence of lung cancer compared to nonsmokers.

The present study consisted of 294 (76.1%) beedi smokers, 250 of whom were males, and 44 of were females. Rural Indians tend to smoke particular types of tobacco products, such as beedis. The Swadeshi movement called for a boycott of imported cigarettes, which explains the increase in the consumption of beedis as a consequence. Cheaper, easily available, cottage industry.

Bidi smoking typically delivers three to five times more nicotine tar and carbon monoxide than conventional cigarettes and carries a high risk of developing lung cancer compared to cigarette smoking. Globally, tobacco smoking is the largest modifiable risk factor for lung cancer.[23]

In the present study, most of the patients in the LCINSs group were females, 60 (65.2%), compared to males, 32 (34.7%), similar to the studies of Jindal et al.,[24] Singh et al.,[25] Gao et al.,[26] Shimizu et al.[27] and Jindal et al.,[28] where most of the lung cancer patients in the nonsmoker's group were female (52%).

According to the present study, adenocarcinoma was the predominant cell type in 49 cases (53.2%) of LCINS, followed by Squamous cell carcinoma 22 cases (40.9% females vs. 59% males) and small cell carcinoma 12 cases 50% male and 50%. The above result is similar to the proportion of nonsmokers who develop Adenocarcinoma from 1990 to 1995 to 2011–2013, showing an increase from 8.0% to 14.9%.[29]

Participants of the study were homemakers, shopkeepers, and pan shop workers, and exposed to various types of smoke such as passive smoking, chewing tobacco, and smoke from biomass fuel. According to the results, 44 of the women were exposed to biomass fuel and passive smoking. According to previous studies, women whose husbands smoke have a 1.4–1.9 times greater risk of lung cancer. India's rural areas burn wood biomass for cooking and heating. Around 3 billion households worldwide rely on solid fuels for energy. The relationship between exposure to cooking oil vapors and indoor coal burning and the development of lung cancer has been well documented.[30],[31]

A total of 215 (55.6%) of the participants in the study identified themselves as farmers. Farmers have been found to have a lower risk of developing lung cancer. When performing certain activities, they may be exposed to hazardous air pollutants such as pesticides, diesel exhaust, and mineral dust.[32],[33] Around 2.6 million metric tons of active pesticide ingredients are used by farmers to produce crops in developing countries each year.

In the present study, for every 15 cases of lung cancer, there are 6 cases of squamous cell carcinoma, 6 cases of Adenocarcinoma, 2 cases of small cell carcinoma, and 1 case of another. Results demonstrate that regardless of smoking status, squamous cell carcinoma was the most common histopathological pattern, with 41.1% followed by 40% adenocarcinoma and 12.1% small cell carcinoma.

Squamous cell carcinomas represented 46.5% of tumours in the current study. Smoking is strongly linked to squamous cell cancer. Recent observations from mayo clinical study have shown that squamous cell carcinomas are more commonly found on the periphery than in the center.[34]

According to the results, 106 (36%) of the cases were adenocarcinomas caused by smoking, and in 49 cases, 53.2% (71.4% in females vs. 28.5% males) were nonsmokers. These findings suggest that nonsmokers are at increased risk for adenocarcinoma. The evidence pointing to the association between smoking and adenocarcinoma is growing due to nitrates found in tobacco blends.[35] In 80% of cases, adenocarcinomas are found in the lung periphery. This study describes the location of adenocarcinoma in the center due to its late presentation. There were 35 cases of small cell carcinoma and 5 cases of large cell carcinoma. Small and large carcinoma rare aggressive or strong association with heavy smoking history. As compared with prior Indian and international research, our patients were younger, had a higher male preponderance, and had a higher prevalence of Squamous Cell Carcinoma as summarized in [Table 4].
Table 4: Summary of the Present study with various Indian and other countries.

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Radiological analysis of lung cancer patients showed right 216 (55.9%) versus left 170 (44%), similar to various published studies.[36],[37] Patients in the present study had mass 245 (63.4%), consolidation 192 (49.7%), effusion 176 (45.5%), cavity 160 (41.4%). Sharma et al.,[37] in their study of 373 lung cancer patients, had found that 66% of cavitating lung malignancies were of squamous cell type in contrast to the present study adenocarcinoma 69 (43.1%) presented with more cavitations compared to squamous cell carcinoma 67 (41.8%).

It was found that at the time of presentation majority of lung cancer patients had Stage 3 (129) or Stage 4 (206) of the disease regardless of their smoking status. Studies by Jindal et al.,[24] Singh et al.,[25] Youlden et al.,[38] and Parkin et al.[39] seem to support this conclusion. Asymptomatic earlier stages of lung cancer, the failure to recognize the symptoms at the onset, the delays in lung cancer screening, misdiagnosed as tuberculosis, and poor economic status may contribute to the presentation of the patient at an advanced stage of lung cancer. In the context above, it is necessary to make early attempts at diagnosis to extend the patient's life.

A total of 44 subjects (12.2%) in the current study were treated empirically with antitubercular drugs. In their study, Rawat et al.[22] reported a delay in referring patients to treating physicians. Almost 38 (29.3%) patients and 43 (12.1%) were misdiagnosed as having tuberculosis, as described in Bala et al.[40] and Mohan et al.[41] It is rare to see adenocarcinoma with miliary pattern 4 (1%), and there are many differential diagnoses[42] that can be a sign of advanced lung cancer.


  1. Limitations of the study is that not considering CT guided biopsy results, lymph node biopsy
  2. PET was not done to rule out metastasis.


Multicentric prospective studies are needed to determine whether there are differences in risk factors between men and women without smoking.

The results of these studies may shed light on future preventive measures for nonsmokers, the need for screening.

Further research into the behavioural shift of lung cancer can be conducted based on these findings.

  Conclusion Top

Smoking remained the most common preventable risk factor for the development of lung malignancy. Adenocarcinoma predominated in LCINSs who have exposure to biomass fuel and passive smoking. Among smokers and nonsmokers at tertiary care centres, the consistent histopathological trend indicates global and regional concordance. Adenocarcinomas appear to be an emerging histo-pathological type. The incidence of lung carcinoma in women is on the rise. Irrespective of smoking status and histopathological pattern, all patients presented with advanced Stage 3 and 4 lung cancer. Early screening and identification of lung malignancy can provide hope for treatment at the early stages.[50]


We, the authors, thank Dr. Alamelu Haran, HOD Department of Pulmonary Medicine, for her constant guidance.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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