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Ann Thorac Surg 2003;76:1016-1022
© 2003 The Society of Thoracic Surgeons
a Division of Thoracic Surgery, National Cancer Center Hospital, and Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
* Address reprint requests to Dr Asamura, Division of Thoracic Surgery, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
e-mail: hasamura{at}ncc.go.jp
Presented at the Poster Session of the Thirty-ninth Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 31Feb 2, 2003.
| Abstract |
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METHODS: During a 10-year period from 1991 through 2000 a total of 1,769 lung tumors were resected at the National Cancer Center Hospital, Tokyo. According to the pathology files of these patients, 51 patients had a primary tumor with the diameter of 1 cm or less. Three tumors arising in the bronchial lumina of hilum with a squamous cell carcinoma histology were excluded and the remaining 48 tumors of peripheral origin were studied. The clinicopathological features were analyzed according to three types of appearance on high-resolution CT: non-solid ground glass opacity (GGO) type (n = 19); part-solid GGO type (n = 9); and solid type (n = 20). Non-solid GGO is made up of homogeneous moderate increased density on CT, which cannot obscure the bronchovascular structure, whereas partly solid GGO contains a mere solid part but did not exceed 50% of the whole area (n = 9). All other lesions were considered solid type.
RESULTS: For the three types of lesions, the distribution of age and sex was similar with the average age of 61 years and an almost even distribution of male/female patients. Although 6 patients had symptoms, the symptoms were not associated with the nodule itself. Twenty-six patients (54%) were screen-detected (16 chest roentgenogram films and 10 CT scans) and the others were detected by incidentally taken chest roentgenogram film or CT for other reasons than nodules detected. Two squamous carcinomas were positive for sputum cytology. Preoperative cytologic/histologic diagnosis was given in 14 patients (29%). The histologic type of GGO lesion was bronchioloalveolar carcinoma in all 28 cases. In solid lesions, besides 16 adenocarcinomas 2 cases of squamous cell carcinoma, 1 case each of small cell carcinoma and carcinoid tumor was seen. Lymph node involvement was seen only in 3 patients with solid lesions (N1 in 2 patients, N2 in 1 patient). As for operative mode, the limited resection was performed for 15 GGO lesions (54%) and 4 solid lesions (20%). Tumor recurrence was seen in 2 patients with solid lesions1 in bone and the other in locoregional lymph node, and the former died of disease.
CONCLUSIONS: Among subcentimeter lung cancers, GGO lesions (both non-solid and part-solid) constitute true early lung cancers. Since they have minimal or no invasive growth, limited resection for cure is justified. Conversely the solid lesion had significant invasive features such as lymph node metastasis. Lobectomy should remain as the standard mode of surgery despite such small size.
| Introduction |
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The CT appearance of small-sized peripheral adenocarcinomas has been described [48] and adenocarcinoma that appears as localized GGO without spiculation is likely to be BAC [9]. The correlation between CT appearance and pathology has been also studied [10, 11]. The prognosis of very small lung cancers in relation to the CT appearance and histology has not been fully clarified however. Therefore in this retrospective study we focused on the resected lung cancers with tumor diameter of 1 cm or less and studied their pathologic features and prognoses. The clinicopathological characteristics of these lung cancers were also described in detail. The surgical management of such small-sized lung cancer seems to have more clinical importance because of the increasing discovery in our practice.
| Material and methods |
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Forty-eight patients with peripheral subcentimeter lung cancer comprised 2.5% of the total. Their histologic type and TNM stage were determined according to the World Health Organization (WHO) classification [3] and UICC staging system [12], respectively. As for adenocarcinoma histology, WHO classification describes BAC as a form of adenocarcinoma with a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. If there is histologic evidence of invasive growth it is termed as "adenocarcinoma with mixed subtypes." The patients' medical, operative, and pathologic records were reviewed to characterize the pathobiological features of such subcentimeter lung tumors.
The patients ranged in age from 43 to 77 years (median, 63). Twenty-five patients were female and 23 were male. Most of the patients underwent a physical examination, chest roentgenography, chest CT scan, bone scintigraphy, and abdominal ultrasonography for staging and the evaluation of resectability before the operation. Especially for chest CT scan, the thin-sliced, high-resolution images (2-mm thickness) of the primary lesion were taken to characterize the CT appearance besides the routine 1-cm thickness images of the entire lung and mediastinum. The clinical characteristics, diagnostic workup, surgical intervention, postsurgical pathologic evaluation, and prognosis were analyzed in detail. As for the cause of discovery, "incidental chest roentgenogram" and "incidental CT" were used to describe those taken for any other reasons than the nodule itself for the evaluation.
Type of lesions
According to the CT appearance, type of lesion was categorized as GGO lesion (Figs 1 and 2) or solid lesion (Fig 3).
The GGO refers to the CT appearance, in which the internal density of nodule is low and the bronchovascular structures in the GGO area still can be visualized. Conversely in the solid lesions the internal
density of solid nodule is so high as to obscure the bronchovascular structures. The GGO lesion may or may not be accompanied by solid part mainly in the center of the nodule: GGO without a solid part is defined as "nonsolid" GGO (Fig 1) and GGO with a solid part that occupies less than 50% of the whole area, as "part-solid" GGO (Fig 2). In these series, if the solid component exceeds 50% of the whole area the nodule was defined as a solid lesion.
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| Results |
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Clinical profiles of subcentimeter lung cancers
In terms of age and sex distributions there was no difference between non-solid GGO, part-solid GGO, and solid lesions (Table 1). One characteristic feature was that almost half of patients were female for every type of lesion. Although there were some symptoms such as cough and chest pain in 6 patients, all of these symptoms were nonspecific in nature and in no case the lung nodules were speculated to be the cause of symptoms even though the symptoms became a trigger for chest examinations.
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| Comment |
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The correlation between CT appearance as GGO and pathologic findings has been studied. The replacing growth of adenocarcinoma cells along the alveolar wall is reflected as "GGO" appearance with patent alveolar spaces and small airways on CT. The solid part on CT represents the collapse of the alveoli, subsequent formation of fibrotic focus, and proliferation of tumor cells. Therefore the absence or small, if any, amount of solid part within the nodule on CT generally indicates the absence of invasive growth. The prognostic significance of solid part in the small-sized GGO-type of adenocarcinoma has been already realized in the previous literature [13, 14]. In the present series the GGO appearance with or without minimal solid part on CT also correlated well with the degree of invasive growth of the tumor, where only 2 cases had a tiny amount of vascular/lymphatic permeation. Since the WHO classification of lung tumors denotes BAC only for tumors without invasive growth, they were not classified as BAC because of a tiny amount of lymphatic permeation. However they can be "BAC with minimal invasion" or "minimally invasive BAC." Actually there has been neither tumor recurrence nor tumor-related death seen for 28 patients with GGO type of lung cancer in the previous series. The prognostic significance of the GGO appearance of subcentimeter lung cancer as a completely curable disease should be stressed.
Several characteristic features in GGO type of lung cancer were noted in the present study. One of the distinct features of GGO type of lung cancer is the female dominancy: 16 of 28 patients (57.1%) with the GGO type of subcentimeter lung cancer were female. The second feature was that the half of the patients were nonsmokers and only 2 patients were present smokers. The GGO type of lung cancer seemed to be less related to the tobacco smoking. The third feature was the multicentric nature. Nine of 28 GGO type lesions (32%) presented similar GGO lesions elsewhere in the lung. On the contrary, in solid lesions, multiple lesions were seen in only 1 patient. This contrast suggests that the process of tumor growth as well as tumorigenesis might be different between the two types of subcentimeter lung cancers.
As for the mode of operation for T1 peripheral lung cancers, lobectomy has been the standard operation of choice since the randomized trial by the Lung Cancer Study Group in 1995 [15]. This study demonstrated that the lesser resection such as wedge/segmentectomy had three times more local recurrence than the lobectomy. However it is unfair to simply apply these results to the treatment of small-sized lung cancer as the LCSG study exclusively focused on the solid T1 tumors, in which the invasive growth within the nodule are most likely to happen. Especially for GGO type of lesions, another rationale is necessary as for the extent of surgical resection. Basically the radical resection by lobectomy and hilar/mediastinal lymph node dissection should be indicated only for tumors with present or possible risk of invasion. For tumors with no or very minimal if any invasion, the local excision might be curative enough. Considering the extremely low chance of invasive features in GGO type of small lung cancers, in which the solid part occupies less than 50% of the entire area of the nodule, the limited resection might well justified. Another rationale for choosing the limited resection for GGO type of lung cancer is the multicentric nature of the lesion. In 5 of 28 GGO types of subcentimeter lung cancers (18%), the lesions were multiple. We should expect that the surgical candidate with GGO type of lung cancer may develop another one after some years. In resecting the GGO type of lesions, the preservation of lung parenchyma has greater significance.
The one important issue in the management of GGO type of lesions, especially the non-solid type of GGO, is the indolent nature of the tumor. The adenoma-adenocarcinoma sequence is proposed also in the tumorigenesis in adenocarcinoma of the lung. However there has been no persuasive data as to what percentage of non-solid type of GGO lesions are indolent over a long clinical course and what percentage of GGO lesions progress to be solid lesions. Furthermore how long does it take for GGO lesions to progress to solid tumors? Indeed we anecdotally experience cases of nonsolid GGO lesions that remain the same size and appearance over some years. To date the nonsolid type of GGO with tumor diameter less than 1 cm might be managed without surgical intervention by periodic CT follow-up at proper intervals such as 4 months. Further study on CT-detected GGO type of lesions should include careful and watchful follow-up to establish the management of such minute lung cancers.
| Acknowledgments |
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| References |
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