J Pathol Transl Med.  2020 Jul;54(4):290-299. 10.4132/jptm.2020.05.04.

Peripheral type squamous cell carcinoma of the lung: clinicopathologic characteristics in comparison to the central type

• Sung YE
• Cho U
• Lee KY

• KMID: 2504559
• DOI: http://doi.org/10.4132/jptm.2020.05.04

Abstract

Background
Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type.
Methods
This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included.
Results
Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type.
Conclusions
In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.

Keyword

Squamous cell carcinoma; Lung neoplasms; Peripheral; Cytokeratin-7

Figure

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  Fig. 1. Clinicopathologic characteristics of peripheral lung squamous cell carcinoma. (A–C) Microscopic findings of the glandular component (adenocarcinoma component) in peripheral squamous cell carcinoma of the lung: H&E staining (A, B) and thyroid transcription factor-1 immunohistochemical staining (C). (D–F) Radiologic and pathologic images of cystic change of the mass: computed tomography (CT) image of the chest (D), gross examination (E), and H&E staining (F). (G–I) Interstitial fibrosis, especially usual interstitial pneumonia with squamous cell carcinoma in the peripheral lung; CT image showing coarse reticulation with honeycombing and mass in the lower lobe of the lung (G), H&E staining (H, I). (J) Overall anthracosis coexisting with squamous cell carcinoma in the left upper area of the image. (K, L) Peripheral squamous cell carcinoma in pneumoconiosis lung: CT image (K) and H&E staining (L) showing progressive massive fibrosis with irregular mass at the subpleural portion of the left lower lobe.

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  Fig. 2. Cytokeratin-7 (CK7) immunohistochemical staining of squamous cell carcinoma of the lung. (A) Less than 10% positivity of tumor cells. Entrapped normal bronchial cells (right lower area) are excluded from the evaluation. (B) Between 10%–50% CK7 positivity of tumor cells, with entrapped normal bronchial cells and pneumocytes in the left and upper area. (C) More than 50% CK7 positivity of tumor cells, with strong intensity.

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  Fig. 3. Survival analysis by Kaplan-Meier curves (A) Overall survival of each stage; stage I, including stage IA and IB; sage II, including stage IIA and IIB; stage III & IV, including IIIA, IIIB, and IV. (B) Overall survival according to the presence or absence of interstitial fibrosis; the presence of interstitial fibrosis was significantly associated with poor survival (p=.021). (C, D) Disease-free survival (DFS) (C) and overall survival (OS) (D) according to the peripheral or central type of lung squamous cell carcinoma (SqCC); peripheral SqCC had a tendency of better DFS, but the result was statistically not significant (p=.063); there was no significant difference in OS (p=.487).

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  Fig. 4. Hazard ratio by Cox proportional hazard model analyzed for disease-free survival (DFS) (A) and overall survival (OS) (B). Peripheral lung squamous cell carcinoma (SqCC) was significantly associated with a better prognosis (hazard ratio [HR], 0.43; 95% confidence interval [95% CI], 0.23 to 0.81; p=.009). It also had a tendency of better OS (HR, 0.55; 95% CI, 0.27 to 1.10) but was not statistically significant (p=.106).

Reference

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