Lung adenocarcinoma with GGO nodules:HRCT radiological and pathological correlation

·論 著·

Lung adenocarcinoma with GGO nodules:HRCT radiological and pathological correlation

Background: Lung cancer is the most common cancer related death in the world for the both male and female as well. Adenocarcinoma is the most common pathological type which is in increasing trend. With recent advancement of screening of lung cancer with HRCT， GGO lesion has been noted frequently. GGO is a nonspecific finding that may be caused by various disorders， including inflammatory diseases， focal fibrosis， atypical adenomatous hyperplasia， bronchoalveolar carcinoma (BAC)， and adenocarcinoma.This study intends to analyze the correlation between high resolutions computed tomography (HRCT) findings and the pathological findings of lung adenocarcinoma. Material and methods: Retrospective review of 16 cases of lung adenocarcinoma lesions after surgical resection. Tumors were defined as air containing type based on ratio of maximum dimension of the tumor on mediastinal window to the maximum diameter of the tumor on lung window was≤50% and as solid density if the ratio was>50%. The correlation between CT findings (homogenous/heterogeneous， airbronchogram， pleural tag， speculation， vascular involvement， pleural thickening， margin， shape) and pathological findings were investigated. Results: Of 3 air containing 2 were pre-invasive type and 1 was invasive. Among 13 solid density type all 13 were invasive type. Presence of speculation， heterogeneous appearance was found significantly associated with pathological invasion. Conclusion: Air containing type of small cells lung adenocarcinomas are preinvasive whereas solid densities are invasive. Speculation and heterogeneous are significant factor in invasive adenocarcinoma.

ground glass opacity；adenocarcinoma；heterogenous；homogenous

1 Introduction

Lung cancer is the most common cancer related death in world for both sexes. Adenocarcinoma (ADC) is the most common histopathological type of small sized lung cancer in worldwide， attributing 50% of lung cancers[1]With recent advances in CT screening for lung cancer， an increase in the detection of ground-glass opacity (GGO) lesions has been noted[2]. GGO is a nonspecific finding that may be caused by various disorders， including inflammatory diseases， focal fibrosis， atypical adenomatous hyperplasia， bronchoalveolar carcinoma(BAC)， and adenocarcinoma[3]. Heterogeneous and solid GGO pattern in lung periphery has mostly been associated with neoplastic lesions. The main aim of this article is to correlate pathologic and radiographic feature of GGO in order to early diagnosis.

The tumor were first classified as air containing lesions or solid density lesions based on percentage of reduction of maximum tumor size on the mediastinal window compared with the area on lung window image on HRCT.More than≥50 air containing type and <50 were classified as solid density type.The following formula was applied to calculate the disappearance rate:

Tumordisappearancerate=(tumorsizeinlungwindow-tumorsizeinmediastinalwindow)/(tumorsizeonlungwindow)×100.

The example of measurement is shown in the Fig 1. Some researchers have indicated that there is a relation between the percentages of GGO and the prognosis of tumor[4-5]. Kodama and Aoki et al. indicated that the adenocarcinomas with GGO more than 50%， show a better prognosis than for GGO with less than 50%[5-6].

the maximum tumor diameter shown in lung window. A is 39 mm and that on B is 5 mm in mediastinal window

Fig 1 Measurement of the disappearance rate on CT images

In the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) Classification of Lung Adenocarcinoma[7](termed the new IASLC classification)， Travis et al.[7]defined new classification for lung adenocarcinoma， as follows:adenocarcinoma in situ [AIS, ≤30 mm; formerly termed bronchioloalveolar carcinoma (BAC)]; minimally invasive adenocarcinoma (MIA, ≤30 mm lipid growth predominant adenocarcinoma with ≤5 mm invasion); and invasive adenocarcinoma (including lepidic predominant with >5 mm invasion， acinar， papillary， micro papillary， or solid predominant)[8]. Lung adenocarcinoma is divided into pre invasive lesions (PL) including atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) and invasive adenocarcinoma (IA).

2 Materials and methods

2.1 Patients

All the patients form Zhongda Hospital， who had done HRCT and had GGO nodules findings on result from 2013 January to 2014 November， were collected first. After that only those cases that were in regular follow-up and had gone to surgical resection， with surgical pathological report proven to be lung adenocarcinoma were included in this study after getting permission from hospital ethical board.

2.2 HRCT screening

CT scans were obtained with 64 detectors row scanner( Siemen′s ) using unenhanced helical technique at the end of inspiration during one breath hold. The scanning parameters of CT were as follows: detector collimation 1.0 mm， pitch 1.0-1.2 mm，section thickness and interval 3 mm/5 mm， matrix 512×512， scan time 5-7 s， FOV 500 mm， kVp 120 and mA 220. The reconstruction algorithms of HRCT were standard and sharp.

2.3 Evaluation of CT features

CT features were evaluated by top radiologist of Zhongda Hospital， Nanjing who had many years of experience in Chest CT with clinical and histological knowledge findings assessed HRCT retrospectively. Nodules were classified according to following characteristics such as shape， location， margins， presence of air bronchogram， pleural tag， speculation， vascular-involvement， location(central/peripheral)， lobes(RUL/RML/RLL/LUL/LLL)， pleural thickening and CT appearance (homogenous/heterogeneous)

2.4 Pathological evaluation

The surgically resected specimens were send to the pathology lab after resection. Specimens were fixed in 10% formalin， embedded in paraffin， sectioned with a microtone， and stained with hematoxylin and eosin (H and E). Histopathological analysis of nodule was performed and was classified according to the 2011 international multidisciplinary classification of lung adenocarcinoma by the senior pathologist of Zhongda Hospital.

2.5 Statistical analysis

Data is first categorically divided and kept in Microsoft excel. After that the correlation between radiological and pathological finding and statistical analysis were done with SPSS v.11.0 software. Correlations were calculated by Chi-square test and mean is compared by independent T-test.

3 Results

Patients and tumor characteristics are shown in Tab 1. Radiological and Pathological findings were analyzed among 16 patients diagnosed with adenocarcinoma of lungs and undergone surgical resection of lungs. Out of 16 patients， majority (81%) were female. Mean age of the patients was 61 years (range 49-76 years). Most of the patients (31%) were office workers.

On basis of CT findings on lung window and mediastinal window， by using disappearance rate formula， majority of the tumor were solid density type (81%). Other major CT finding includes heterogeneous appearance (81%)， presence of pleural tag (56%)， presence of speculation (69%)， airbronchogram (75%) and vascular involvement (94%). Mean radiological tumor size was 21 mm (12-43).

According to the new IASLC classification， Pathological tumor was classified as AIS， MIA and IA. For our convenience， AIS and MIA were grouped as Pre-invasive (AIS+MIA) and Invasive two group. Majority (87.5%) were invasive adenocarcinoma followed by preinvasive (AIS+MIA). Regarding TNM classification， 12 (75%) of them were Stage IA and 4 (25%) were in or more than stage IB. Mean Pathological tumor size was 19 (12-32) mm.

Tab 2 demonstrates the correlation between pre-invasive and invasive adenocarcinoma with the CT findings. CT finding of speculation was found to be significantly associated with pathological invasion as the calculatedPvalue from Fisher′s Exact Test was less than 0.05 i.e. 0.024 at 95% confidence level.

Tab 1 Patients and tumor characteristics (n=16)case

Similarly， Heterogeneous GGO appearance in CT was also found to be significantly associated with pathological invasion as the calculatedPvalue was less than 0.05 i.e. 0.002 at 95% confidence level (See Table 3). Invasive lesion there were 14 cases (87.5%) of total cases and pre-invasive lesion there were 2 cases (12.5%) of total cases. Pre-invasive lesion there were 2 cases (100%) which were homogenous in CT appearances and 0 cases with heterogeneous CT appearances.

Tab 2 Correlation of pathological invasion with speculation case

Tab 3 Correlation of Pathological Invasion with CT appearance case

Radiological tumor types and invasion was also found to be significantly correlated as the calculatedPvalue was less than 0.05 i.e. 0.025 at 95% confidence level as shown in Tab 4.

Tab 4 Correlation of pathological invasion with radiological tumor type

Likewise， correlation between pathological tumor size and radiological tumor size was significant as the calculatedPvalue was less than 0.05 i.e. 0.022 at 95% confidence level. Given the positive value of pearson’s r i.e. 0.566， we can conclude that radiological tumor size increases as the pathological tumor size increases as shown in Tab 5.

Tab 5 Correlations between Pathological tumor size with radiological tumor size

a Correlation is significant at the 0.05 level (2-tailed)

However， no any significant association was found between CT findings of Pleural tag， airbronchogram， vascular involvement with pathological invasion. Likewise， association of pathological staging of tumor (IA and more than IB) with the CT findings were also found to be insignificant.

4 Discussion

The correlation between CT finding and new IASLC classification were investigated. The present result signified that air containing type on CT findings were Pre-invasive (AIS+MIA) lesions but not invasive adenocarcinoma. Honda et al in his study had also found that all the air containing type of lesion were AIS and MIA[8]. Pre-invasive were classified as air containing type because they all were pure lepidic growth. Despite of this invasive adenocarcinoma were mostly (92.8%) solid density type. Lee et al described invasive adenocarcinoma is usually a solid nodule， but may also present as GGO[9]. Solid density were noted as poor prognosis where as air containing lesions were excellent prognosis with 100% prognosis of 5 years survival[10-11].The radiologic characteristic of carcinoma is heterogeneity of GGO. GGO with heterogeneous attenuation were invasive adenocarcinoma out of 13 of 13 lesions， which is extremely high rate. Some studies[12-13]have already suggested the importance of these findings. Many investigators[8，11，13]have reported a correlation between CT findings and pathological findings. Pre-invasive were classified as mostly homogenous type there were large area of lepidic growth pattern， whereas invasive were classified as heterogeneoustype because there were large area of predominantly acinar， papillary or solid type of growth. Preinvasive lesions appeared to be 100 % homogenous. Zhang et al had proved only 66% preinvasive lesions appear to be homogeneous[14].

Speculation was completely absent in pre-invasive type of adenocarcinoma. Despite of that 78.57% invasive lesions were present with speculations. There is significant correlation between pathological invasion of tumor and radiological speculation. These changes suggest malignant transformation to invasive adenocarcinoma may reflects histopathological lesion of Noguchi type C or D (advanced form of adenocarcinoma)[15]. However， Yoshino et al. had proved that significance between air bronchogram and stage Ⅰ tumor but our study found no statistically significance[16].

5 Conclusion

GGO at HRCT has been strongly suggestive of a neoplastic condition such as adenocarcinoma in situ， atypical adenomatous hyperplasia， or invasive adenocarcinoma. The probability of invasive adenocarcinoma is much higher when the lesion contains a solid component， heterogeneous and speculation. Whereas preinvasivelesion were air containing type， homogenous and no speculation. Most of the invasive lung adenocarcinoma were proved be heterogeneous with speculation on CT feature.GGO has been shown histologically to correlate with pathological areas of tumor cells replacing alveolar cells. A meticulous evaluation of those CT features， and their correlation with specific histopathologic characteristics can enable a more accurate and early prognosis in cases of neoplastic disease.

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ACHARYA Prashanta1，PAUDEL Rasmita1，XU Qiu-zhen2

(1.SchoolofMedicine，SouthEastUniversity，Nanjing210009，China; 2.DepartmentofRadiology，ZhongdaHospital，SouthEastUniversity，Nanjing210009，China)

Xu Qiu Zhen E-mail:xuqiuzhen831@sina.com

format] ACHARYA Prashanta，PAUDEL Rasmita，XU Qiu-zhen.Lung adenocarcinoma with GGO nodules:HRCT radiological and pathological correlation[J].Journal of Southeast University:Medical Sciences，2015，34(3):415-419.

R445.3 [Document code] A [Article ID] 1671-6264(2015)03-0415-05

10.3969/j.issn.1671-6264.2015.03.021

[Received date] 2014-12-15 [Revised date] 2015-01-30

[Author] Acharya Prashanta(1987-)，Male，Nepalese，Post Graduate Student.E-mail:acharyaprashanta1987@gmail.com