The changing anatomic position of squamous cell carcinoma of the lung – a new conundrum


The changing anatomic position of squamous cell carcinoma of the lung – a new conundrum

William Krimsky, MD, Nargiz Muganlinskaya, MD, MMS, FACP*, Saiyad Sarkar, MD, FCCP, FACP, DAABIP, Manasa Vulchi, MD, Pujan Patel, MD, Suman Rao, MD, Joel Hammer, MD, Ruth Evans, BA, RN, CNOR, OCN, Muhammad Qureshi, MD and Daniel Harley, MD

MedStar Health, Baltimore, MD, USA


Background: Traditionally, squamous cell carcinoma (SCC) of the lung is a central rather than a peripheral form of lung cancer. Rates of SCC in the lung periphery are typically sited in the 15–30% range. Recently, we observed that a significant portion of newly diagnosed SCC was located on a periphery. A comprehensive review of the tumor data at our facility, a busy teaching hospital with a large cohort of cancer patients, was undertaken to assess whether there had been a substantive change in the traditional epidemiologic distributions of the lung cancer, specifically with respect to SCC. Given the differences in cell biology and carcinogenesis of central versus peripheral SCC, a potential epidemiologic shift might suggest a change in tumor biology.

Methods: From May 12, 2012 through May 13, 2013, all histopathologically confirmed diagnoses of SCC of the lung were retrospectively reviewed. Each patient’s lesion was then classified as peripheral or central based on CT evidence.

Results: A total of 56 patients were diagnosed with SCC. Of these, 55% (n=31) had peripheral and 45% (n=25) had central SCC. Twenty-nine patients did not have any prior history of malignancy. Of this subset of patients, 62% (n=18) had peripheral SCC, and 38% (n=11) had central SCC.

Conclusion: Our findings appear to correlate with our initial observation that, within our institution, there has been a substantive shift in the traditional distribution of SCC with the majority of these cancers now being diagnosed in the lung periphery as opposed to the more central locations.

Keywords: squamous cell carcinoma; lung cancer epidemiology; squamous cell carcinoma epidemiology; lung cancer; peripheral location cell carcinoma

Citation: Journal of Community Hospital Internal Medicine Perspectives 2016, 6: 33299 -

Copyright: © 2016 William Krimsky et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 29 August 2016; Revised: 23 October 2016; Accepted: 25 October 2016; Published: 15 December 2016

Competing interests and funding: The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

*Correspondence to: Nargiz Muganlinskaya, MedStar Franklin Square Medical Center, 9000 Franklin Square Drive, Baltimore, MD 21237, USA, Email:


Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for nearly 85% of the cases (13). Although adenocarcinoma has replaced squamous cell carcinoma (SCC) as the most common histological type of lung cancer, SCC accounts for 30% of the NSCLC cases. SCCs are classified into central (c-type) arising from the main stem, lobar, and segmental bronchi; and peripheral (p-type) based on the location of the primary lesion. Traditionally, in literature, the c-type has been reported to be the more common type accounting for nearly two-thirds of the cases, but we have noticed at our medical center, a busy outer city teaching hospital, a trend toward an increase in the occurrence of peripheral squamous cell cancers. Given the considerable differences in the clinicopathologic and presenting features of c-type SCC and p-type SCC, and the potential differences in carcinogenesis (47), we believe it is important to acknowledge to the fact that the p-type of SCC is on the rise and may account for more than 50% of the cases of SCC.

Materials and methods

Study population

All the patients aged 18 and above with a histopathologic diagnosis of pulmonary SCC between May 12, 2012 and May 13, 2013 at our medical center were identified retrospectively from the pathology database.


The medical records of the 56 patients were retrospectively reviewed. The diagnosis of squamous cell lung cancer was confirmed by a pathologist. The chest CT scans of all the patients were reviewed by a pulmonologist. The midline of each lung in the axial CT scan views was used as a definition point, the tumors medial to the midline were classified as being centrally located, and those lateral to the midline were classified as peripherally located tumors. Of the 56 patients, 27 patients were found to have a prior history of malignancy of various organs. The patients without prior history of malignancy were also analyzed as a separate subset. Demographic information of all the 56 patients, as well as other pertinent information including smoking history, inhaled steroid use, and proton pump inhibitor (PPI) use, was collected and described.

Statistical analysis

The data were collected and analyzed using Microsoft Excel 2010. Student’s t-test was used to compare the means for the ages of the two study groups, and a chi-square test was used to compare the rest of the demographic features and risk factors mentioned above. A p-value of <0.05 was used for all the analyzed data.


From May 12, 2012, through May 13, 2013, a total of 56 patients with new diagnosis of SCC were identified. Of them, 44.6% (n=25) were found to have tumors arising from the center, and the rest 55.4% (n=31) had tumors arising from the periphery of the lungs (Table 1).

Table 1.  Statistical analysis
    Central Peripheral Total
    Count Percent Count Percent Count Percent
No. of patients   25 44.6 31 55.4 56  
Age Range 52–88   52–82   52–88  
  Mean 67   70   69  
Sex Male 19 76.0 19 61.3 38 67.9
  Female 6 24.0 12 38.7 18 32.1
Race Caucasian 23 92.0 24 77.4 47 83.9
  African American 2 8.0 5 16.1 7 12.5
  Other 1   1 3.2 2 3.6
Smoking status Current 8 32.0 12 38.7 20 35.7
  Past (quit >6 months) 16 64.0 19 61.3 35 62.5
  Never 1 4.0 0 0.0 1 1.8
PPI use   7 28.0 6 19.4 13 23.2
Inhaler use   14 56.0 18 58.1 32 57.1
Right lung Total 13 52.0 16 51.6 29 51.8
    Upper 5 38.5 9 56.2    
    Middle 8 61.5 0 0.0    
    Lower 0 0.0 7 43.8    
Left lung Total 11 44.0 14 45.2 25 44.6
    Upper 4 36.4 11 78.6    
    Lower 7 63.6 3 21.4    
Data were managed with Microsoft Excel 2010. Student’s t-test was used to compare the means for the ages of the two study groups, and a chi-square test was used to compare the rest of the demographic features and risk factors mentioned above. A p-value of <0.05 was used for all the analyzed data.

Subgroup analysis

We also analyzed a subgroup with no prior history of any malignancy, and a total of 29 patients were included in this subset. Of the 29 patients, 37.9% (n=11) were found to have centrally located tumors, and the rest 62.1% (n=18) were found to have tumors arising from the periphery. The mean age was 68 (±6.73) for the patients with central tumors, whereas the mean age was 69 (±8.36) for the patients with peripheral tumors, and no statistically significant difference was found on the t-test. The rest of the variables including gender, race, smoking status, PPI use, and inhaled steroid use were analyzed in the subset of patients without previous history of malignancy, and no significant difference was found as well (Table 2).

Table 2.  De novo subgroup analysis
    Central Peripheral Total
    Count Percent Count Percent Count Percent
No. of patients   11 37.9 18 62.1 29 100
Age Range 54–76       52–81  
  Mean 68   69   68  
Sex Male 8 72.7 10 55.6 18 62.1
  Female 3 27.3 8 44.4 11 37.9
Race Caucasian 11 100.0 13 72.2 24 82.8
  African American 0 0.0 5 27.8 5 17.2
  Others 0 0.0 0 0.0    
Smoking status Current 4 36.4 5 27.8 9 31.0
  Past (quit >6 months) 7 63.6 13 72.2 20 69.0
  Never 0   0   0  
PPI use   3 27.3 2 11.1 5 17.2
Inhaler use   6 54.5 10 55.6 16 55.2
Right lung Total 5 45.5 8 44.4 13 44.8
    Upper 3 27.3 4 22.2    
    Middle 2 18.2 0 0.0    
    Lower 0 0.0 4 22.2    
Left lung Total 6 54.5 9 50.0 15 51.7
    Upper 2 18.2 1 5.6    
    Lower 1 9.1 8 44.4    


Lung cancer is the leading cause of cancer-related death among both men and women in the United States, of which SCCs account for a significant proportion. Traditionally, SCCs of the lung have been believed to arise from the central airways, with the prevalence of peripheral SCC among all SCC has been reported to range from 15 to 30% (8, 9). But recently, a few reports have documented a change in this distribution (4, 10, 11) with the peripheral form of SCC accounting for nearly 50% of SCC of the lung. We found in our study that the peripheral SCC accounted for 55% of the SCC in the entire study population and for 62% in the new lung cancer subgroup.

Our study has limitations. First, the study was a retrospective chart review. Second, only a small number of patients were studied. Finally, most of the study patients were Caucasians with a minor representation from African American and other races, and as a consequence, the results may not be generalizable.

Despite the limitations, our study correlates with the recent reports of increasing number of peripherally arising squamous cell cancers of the lung. Though we looked at some of the demographic variables and other factors that may be influencing this change in distribution, we were unable to identify a causative factor for this shift. As these two forms of SCC have considerable differences in clinicopathologic features and presentation, we believe larger prospective studies are needed to further delineate the causative factors for this change in distribution.


  1. American Cancer Society (2016). Cancer facts & figures 2016. Atlanta, GA: American Cancer Society, pp. 18.
  2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83(5): 584–94. Publisher Full Text
  3. Navada S, Lai P, Schwartz AG, Kalemkerian GP. Temporal trends in small cell lung cancer: Analysis of the national surveillance epidemiology and end-results (SEER) database [abstract 7082]. J Clin Oncol 2006; 24(18S) suppl: 384S.
  4. Funai K, Yokose T, Ishii G, Araki K, Yoshida J, Nishimura M, et al. Clinicopathologic characteristics of peripheral squamous cell carcinoma of the lung. Am J Surg Pathol 2003; 27: 978–84. Publisher Full Text
  5. Mizushima Y, Yamashita R, Kusajima Y, Sugiyama S. Prognostic comparison between peripheral and central types of squamous cell carcinoma of the lung in patients undergoing surgical resection. Oncol Rep 2000; 7: 319–22.
  6. Nagashima T, Sakao Y, Mun M, Ishikawa Y, Nakagawa K, Masuda M, et al. A clinicopathological study of resected small-sized squamous cell carcinomas of the peripheral lung: prognostic significance of serum carcinoembryonic antigen levels. Ann Thorac Cardiovasc Surg 2013; 19: 351–357. Publisher Full Text
  7. Yousem SA. Peripheral squamous cell carcinoma of lung: Patterns of growth with particular focus on airspace filling. Hum Pathol 2009; 40: 861–7. Publisher Full Text
  8. Huhti E, Saloheimo M, Sutinen S, Reinila A. Does the location of lung cancer affect its prognosis? Eur J Respir Dis 1983; 64: 460–5.
  9. Tomashefski JF, Jr, Connors AF, Jr, Rosenthal ES, Hsiue IL. Peripheral vs central squamous cell carcinoma of the lung. A comparison of clinical features, histopathology, and survival. Arch Pathol Lab Med 1990; 114(5): 468–74.
  10. Sakurai H, Asamura H, Watanabe S, Suzuki K, Tsuchiya R. Clinicopathologic features of peripheral squamous cell carcinoma of the lung. Ann Thorac Surg 2004; 78(1): 222–7. Publisher Full Text
  11. Hayashi T, Sano H, Egashira R, Tabata K, Tanaka T, Nakayama T, et al. Difference of morphology and immunophenotype between central and peripheral squamous cell carcinomas of the lung. Biomed Res Int 2013; 2013: 157838. doi:


Dr. Patel does not have any affiliations.

About The Authors

William Krimsky
MedStar Health, Baltimore
United States

Nargiz Muganlinskaya
MedStar Health Internal Medicine, Baltimore
United States

Saiyad Sarkar, MD
MedStar Health, Baltimore
United States

Manasa Vulchi
MedStar Health Internal Medicine, Baltimore
United States

Pujan Patel

United States

Suman Rao
MedStar Health, Baltimore
United States

Joel Hammer
MedStar Health, Baltimore
United States

Ruth Evans
MedStar Health, Baltimore
United States

Muhammad Qureshi
MedStar Health Internal Medicine, Baltimore
United States

Daniel Harley
MedStar Health, Baltimore
United States

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Related Content