Alveolar space filling ratio as a favorable prognostic factor in small peripheral squamous cell carcinoma of the lung

doi:10.1016/j.lungcan.2010.12.001

Lung Cancer

Volume 73, Issue 2, August 2011, Pages 217-221

https://doi.org/10.1016/j.lungcan.2010.12.001 Get rights and content

Abstract

Introduction

Squamous cell carcinomas (SqCCs) of the lung can be divided into two types according to the location of primary site; one is central type and another is peripheral type. Many reports on the central type revealed the clinicopathological characteristics relating carcinogenesis, therapeutics and prognosis. On the other hand, those on the peripheral type are very a few and prognostic indicators of peripheral type have not been enough elucidated. The aim of this study was to clarify clinicopathological prognostic factors of small peripheral SqCCs of the lung 30 mm or less.

Materials and methods

We evaluated various 15 clinicopathological parameters in 81 patients with peripheral type SqCCs, which are defined as tumors located in or more peripheral from the third branching bronchus, measuring 30 mm or less in diameter.

Results

Univariate analyses were performed using the log lank test and multivariate analyses using logistic regression model. As a result, two factors had a statistically significant influence on outcome of the patients in the univariate analysis; no relapse was observed in the patients with the ratio of alveolar space filling (ASF) area to tumor area of 70% or more and the maximum diameter of invasive area measuring 10 mm or less in size (P = 0.0214, P = 0.0373, respectively). Meanwhile, multivariate analysis showed that the ASF ratio of 70% or more significantly affected the outcome of the patients (P = 0.0337), however the maximum diameter of invasive area did not (P = 0.2136). We could not show the unfavorable prognostic factor contributory to tumor relapse.

Conclusions

We have shown that the ASF ratio is a significantly favorable prognostic factor for small peripheral type. Especially the focally invasive tumors with ASF ratio of 70% or more might be classified as “a microinvasive carcinoma” of the peripheral SqCCs of the lung and tumors with ASF ratio 100% as noninvasive carcinoma.

Introduction

Lung cancer is the leading cause of cancer death in the United States and other countries, including Japan. Squamous cell carcinoma (SqCC) occupies approximately 30% in all lung cancers [1]. About 70% of SqCC has been reported to arise from central portion of the lung, whereas the remaining 30% does from periphery [2]. According to a statistical report by Kodama in Japan, the peripheral type of SqCC goes on increasing around 50% of all SqCCs of the lung [3]. Many reports of the central type SqCC have revealed the pathological and clinical characteristics relating therapeutics and prognosis, but those of the peripheral type have been very a few because the biological behavior has not been well evaluated [4], [5], [6].

Central type SqCC of the lung is generally believed to arise from bronchial dysplastic epithelium through the multiple steps of dysplasia–carcinoma sequence, which is the same well-known carcinogenic pathway as observed in uterine cervical neoplasia [7]. During this pathway, carcinoma in situ (CIS) is the earliest stage of the progression of central type SqCC and showed favorable prognosis. If the CIS lesion is localized, a non-surgical procedure like photodynamic therapy may be selected instead of operation. On the other hand, the carcinogenic pathway observed as dysplasia–CIS sequence in the central type has not been fully established in the peripheral SqCC of the lung, so that the standard treatment of peripheral SqCC in the early stage is confined to lobectomy at the present time.

Recently, several studies of peripheral SqCC have been presented. Funai et al. studied 109 cases of peripheral SqCC and indicated that those can be divided into three subtypes based on two distinctive structural patterns based on the tumor growth pattern and the condition of the elastic fiber framework (EFF): the alveolar space filling (ASF) type, the expanding type and the mixed type consisting of the mixture of the former two types [5]. Pure ASF type tumors, which showed no destruction of elastic fiber framework, had a favorable prognosis, showed 100% 5-year survival and thought to be classified as CIS of peripheral SqCCs. Meanwhile, Maeshima et al. studied 101 cases of peripheral SqCCs and proposed three types based on the minimal tumor nest (MTN) pattern: large nest consisting of more than 6 tumor cells, small nest consisting of 2–5 tumor cells, or single cell [6]. They considered tumors with single cell invasive component appeared to be highly malignant, whereas those composed only of large tumor nest or small tumor nest components seemed to have a relatively low potential for malignancy and recurrence, despite these two types also being invasive.

We consider that the clarification of clinicopathological prognostic factors in the peripheral SqCCs leads to the prediction of recurrence or survival and contribution to increase of therapeutic selections. The aim of this study was to identify favorable and unfavorable clinicopathological factors for small peripheral SqCCs of the lung.

Section snippets

Patients

Between January 1993 and September 2008, surgical resection was performed in 364 cases of lung SqCCs at Kanagawa Cancer Center Hospital. The subjects of the study were consecutive 81 patients with small peripheral SqCC of the lung measuring 30 mm or less in diameter. “Peripheral type” in this study was defined as tumors located in or more peripheral to the third branching bronchus.

The patients included 72 men and 9 women with a median age of 70.5 years (range, 47–84 years). We obtained the

Results

We reviewed 81 patients with SqCC of the peripheral lung measuring 30 mm or less in diameter. Clinicopathological characteristics are shown in Table 1. Peripheral SqCC patients showed male preponderance (89%) and high smoking habit (99%). In the present population, 70% took lobectomy, 80% diagnosed as T1a or T1b, 75% showed the tumor size over 20 mm, vessel invasion was more frequent than lymphatic permeation and lymph node metastasis was only 9%. UIP was observed in 9% of the patients. The

Discussion

In the present study, we evaluated several clinicopathological factors to reveal prognostic indications for peripheral lung SqCCs and found ASF ratio to be significant. The multivariate analysis showed that the patients having focally invasive tumors with ASF ratio 70% or more had no recurrence as same as those pure ASF type SqCCs (ASF ratio 100%).

The definition of ASF depends on the observation of alveolar EFF whose complete preservation is considered to represent noninvasive area. It has been

Conflict of interest statement

The authors report no conflicts of interest.

Acknowledgements

We thank Ms. Seki and Ms. Ueda for their technical assistance. This work was supported in part by the Kanagawa Cancer Research Fund and Kanagawa Prefectural Hospitals Cancer Research Fund.

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Lung Cancer

Abstract

Introduction

Materials and methods

Results

Conclusions

Introduction

Section snippets

Patients

Results

Discussion

Conflict of interest statement

Acknowledgements

References (20)

Clinicopathologic features of peripheral squamous cell carcinoma of the lung

Ann Thorac Surg

Histologic prognostic factors for small-sized squamous cell carcinomas of the peripheral lung

Lung Cancer

A logistic regression predictive model and the outcome of patients with resected lung adenocarcinoma of 2 cm or less in size

Lung Cancer

Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma of the lung 3 cm or less in diameter

Lung Cancer

Differences in clinicopathological and biological features between central-type and peripheral-type squamous cell carcinoma of the lung

Lung Cancer

Cancer statistics in Japan 1999

Aberrant methylation of p14ARF, p15INK4b and p16INK4a genes and location of the primary site in pulmonary squamous cell carcinoma

Pathol Int

Clinicopathological characteristics of peripheral squamous cell carcinoma of the lung

Am J Surg Pathol

Squamous cell carcinoma of the lung: an update

Semin Diagn Pathol

Cited by (22)

Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones

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Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer–Specific Death in Squamous Cell Carcinoma

The prognostic value of morphologic findings for lung squamous cell carcinoma patients

Pathology: Malignant and Interstitial Lung Diseases

Prognostic factors in resected lung carcinomas