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Ann Thorac Surg 2002;73:1071-1075
© 2002 The Society of Thoracic Surgeons


Original article: general thoracic

Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography

Shun-ichi Watanabe, MD*a, Toshio Watanabe, MDa, Kazunori Arai, MDb, Takahiko Kasai, MDc, Joji Haratake, MDc, Hiroshi Urayama, MDa

a Departments of Thoracic and Vascular Surgery, Kurobe, Japan
b Department of Radiology, Kurobe, Japan
c Department of Pathology, Kurobe City Hospital, Kurobe, Japan

Accepted for publication December 11, 2001.

* Address reprint requests to Dr Shun-ichi Watanabe, Department of Thoracic and Vascular Surgery, Kurobe City Hospital, Kurobe 938-8502, Japan
e-mail: shunuk{at}aol.com


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. Focal bronchioloalveolar carcinoma (BAC) showing pure ground-glass attenuation (GGA) on thin-section computed tomography (CT), which is considered to be an early-stage adenocarcinoma, has been diagnosed with increasing frequency due to the development and spread of the helical CT scanner. We discussed the appropriateness of limited resection for this type of lesion.

Methods. Between July 1996 and June 2001, 17 patients with localized BAC showing "pure GGA" (GGA without central scar formation) on thin-section CT underwent limited pulmonary resections. The mean patient age was 57.2 ± 10.5 years old. Among these patients, four tumors were detected in a CT mass-screening program and the others were incidentally detected on CT during follow-up for other diseases. Fourteen patients underwent thoracoscopic wedge resection, and 3 underwent segmentectomy because of tumor location.

Results. The mean tumor diameter was 7.9 ± 1.9 mm. On pathological examination, all tumors showed a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. The median follow-up time was 32.0 months, with no cancer death or relapse to date.

Conclusions. Focal BAC showing pure GGA on thin-section CT is peripheral in situ adenocarcinoma. Wedge resection by VATS is considered to be an appropriate treatment for this type of lung cancer. It can be a minimally invasive complete resection for this type of early cancer, and offer the best chance for long-term survival and good quality of life.


    Introduction
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 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Bronchioloalveolar carcinoma (BAC) is one of subtypes of adenocarcinoma, and has a broad spectrum of radiographic and pathological appearances [13]. Among the various types of BAC, the diagnosis of focal BAC, which is chest film negative and showing ground-glass attenuation (GGA) on thin-section computed tomography (CT), has been increasing with the development and spread of the helical CT scanner. Shimosato and colleagues [4] demonstrated that the characteristics of the central fibrosis (scar) were probably more important than the size of tumor for estimating the prognosis of patients with peripheral adenocarcinoma of the lung. Suzuki and colleagues [5] reported that the size of central fibrosis was a significant prognostic factor in adenocarcinoma. Therefore a focal area of "pure GGA" (GGA without central scar formation) on thin-section CT seems to be an early sign of BAC [6, 7]. We considered that this type of focal lesion could be peripheral in situ adenocarcinoma and a candidate for pulmonary wedge resection. This report describes the results and discusses the appropriateness of wedge resection by videoassisted thoracoscopic surgery (VATS) as a minimally invasive and curative surgery for this type of peripheral adenocarcinoma.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Patients
Between July 1996 and June 2001, 17 patients with focal peripheral BAC showing pure GGA on thin-section CT underwent pulmonary resection. GGA was defined as a hazy increased attenuation of the lung without obscuration of the underlying vascular marking [8].

Preoperative investigations
When a round-shaped GGA without central scar formation was detected on thin-section CT (Fig 1), repeat CT was performed 3 months later on suspicion of focal BAC. If the tumor size had increased or was unchanged, surgery was planned because of the high probability of BAC (Fig 2). According to this management schedule, 20 patients agreed to surgery and underwent pulmonary resection. Among them, 17 patients were histopathologically revealed to have noninvasive BAC and 3 to have atypical adenomatous hyperplasia (AAH). Percutaneous biopsy was not attempted in our series. Preoperative staging included CT of the chest and abdomen in all patients, and there was no cervical mediastinoscopy employed. All tumors were indeterminate before surgery. The diagnosis was confirmed by frozen-section examination intraoperatively.



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Fig 1. Typical thin-section CT finding of focal BAC showing "pure GGA" appearance, in which vessels can be seen. GGA was defined as a hazy increased attenuation of the lung without obscuration of the underlying vascular marking. (BAC = bronchioloalveolar carcinoma; CT = computed tomography; GGA = ground-glass attenuation.)

 


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Fig 2. Management schedule after detection of pure GGA lesion. When a round-shaped GGA without central scar formation was detected on thin-section CT as shown in Figure 1, repeat CT was performed 3 mo later on suspicion of focal BAC. If the tumor size had increased or was unchanged, surgery was planned because of the high probability of BAC. (BAC = bronchioloalveolar carcinoma; CT = computed tomography; GGA = ground-glass attenuation.)

 
Surgical procedure
When the tumors were separate from the pleura, CT-guided marking of the tumor was performed immediately before surgery using a marking kit. Under general anesthesia, 14 patients underwent "wide-wedge resection" by VATS with a surgical margin of at least 15 mm in the collapsed lung, and 3 underwent segmentectomy through open thoracotomy because of tumor location. When the tumor is located in the peripheral lung, we confirm the lesion by touching with a finger through the port-site wound to secure the surgical margin of wedge resection. No systematic nodal dissection or nodal sampling was performed intraoperatively. Surgical specimens were submitted for further examination, and the surgical procedure was finished regardless of the results of frozen-section examination. The maximal diameter of the tumor was measured by surgeons intraoperatively on the fresh resected specimen (Fig 3A).



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Fig 3. (A) Surgical specimen and focal bronchioloalveolar carcinoma lesion (arrow). (B,C) Microscopic examination showing pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, lymphatic, or pleural invasion (hematoxylin and eosin stain; B: x20, C: x400 original magnifications).

 
Follow-up
All patients in this study were followed at the outpatient clinic by chest roentgenogram every 2 months, serum tumor markers (carcinoembryonic antigens [CEA] and sialyl-SSE1 [SLX]) examination every 3 months, and helical CT scan of the chest and upper abdomen every 6 months.

All values were expressed as means ± standard deviation (SD) throughout the article.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Patient characteristics
The patient characteristics are shown in Table 1. The patient population consisted of 4 men and 13 women with a mean age of 57.2 ± 10.5 years (range 39 to 72) at the time of surgery. All patients were asymptomatic and detected by chest CT scan. Among these patients, four lesions were detected in a CT mass-screening program, which we started on May 1997, and the remaining 13 patients were incidentally detected on CT during follow-up for other diseases. Fourteen (82.4%) patients had no smoking history. The lobe of origin was the right upper lobe in 4 patients, right middle lobe in 1, right lower lobe in 6, left upper lobe in 4, and left lower lobe in 2. Tumor diameter ranged from 5 to 12 mm with a mean value of 7.9 ± 1.9 mm. Sixteen out of 17 (94.1%) lesions measured 10 mm or less, and only one lesion was more than 10 mm.


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Table 1. Patients Characteristics

 
Pathological examination
On pathological examination, all tumors showed a pure bronchioloalveolar growth pattern with no evidence of stromal, vascular, lymphatic, or pleural invasion (Fig 3B and 3C).

Prognosis
All patients were discharged from hospital within 3 days after surgery without any complications. The follow-up periods have ranged from 4 to 62 months, the median follow-up period was 32.0 months. No postoperative death (including other causes of death) and cancer relapse has been detected to date.


    Comment
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
Bronchioloalveolar carcinoma is considered to be one of the adenocarcinoma subtypes. The increasing incidence of BAC seems to be contributing to the dramatic rise in the number of cases of adenocarcinoma [9]. Although the original report of BAC described patients with advanced bilateral pulmonary tumors, more recent studies on BAC have focused on patients with early stage disease [10, 11].

The pathologic features of BAC are the presence of aerogenous spread and advance along the alveolar wall [12]. Eto and colleagues [13] classified BAC into two subtypes. In the early development of peripheral adenocarcinoma, there is preservation of the elastic network of the stroma due to contraction and thickening of the alveolar walls (type 1). As the tumor grows, the elastic framework is disrupted, indicating stromal invasion (type 2). Based on the clinicopathologic findings and outcome, type 1 tumor is considered in situ peripheral lung adenocarcinoma. In this article, we focused on the appropriateness of minimally invasive pulmonary resection for this type of lesion.

As for the detection of this lesion, all patients participating in this study were asymptomatic and detected by CT. Early detection and treatment are essential for improving the survival of lung cancer patients. In our series, four lesions were detected by a CT mass-screening program which we started in 1997. Sone and colleagues [14] reported that CT screening was an important investigation for the detection of early peripheral lung cancer. Patients with BAC in our series tended to be younger at diagnosis, were more likely to be female, and less likely to be cigarette smokers when compared with other patients with non-small cell lung cancer as previously described [10, 12, 15]. A CT screening program widely performed regardless of smoking history, age, or gender may be effective to detect early BAC and consequently reduce the death rate of lung cancer.

Lobectomy and regional lymph node dissection, termed "radical lobectomy," has been a standard surgery for lung cancer since Cahan [16] reported the first 48 cases successfully undergoing this procedure in 1960. However, this procedure can be an excessive resection for early lesions. Although sleeve bronchial resection has been accepted as a standard procedure for hilar early cancer, there is no standard limited resection for peripheral early cancer established to date. As the number of early-stage peripheral lung cancers is increasing, we consider that the surgical procedure for lung cancer should be tailored to each case. Trials of limited resection for lung cancer have already been undertaken [11, 17]. In lung parenchyma-preserving surgery, however, increased rates of recurrence and cancer death in the clinical stage I patients undergoing segmentectomy or wedge resection compared with those in patients undergoing lobectomy have been reported [18]. Therefore, sufficient criteria for limited resection have been explored in clinical stage I disease [19]. In this study, every BAC showing focal GGA on thin-section CT was revealed to be in situ adenocarcinoma by histopathological examination. We consider that wide-wedge resection by VATS would be a minimally invasive and curative surgery for this type of lung cancer as well as lung biopsy for indeterminate lesion.

Noguchi and colleagues [20] classified small adenocarcinoma into six subgroups (type A to F) according to the clinicopathological characteristics. Two of these six types, named type A (localized bronchioloalveolar carcinoma [LBAC]) and type B (LBAC with foci of alveolar structural collapse) showed a 100% 5-year survival after lobectomy with systematic nodal dissection and no lymph node metastasis. These types correspond to BAC without central scar formation as shown here and can be candidates for limited resection. This classification, however, was made postoperatively by microscopic pathological examination of tumors fixed in 10% formalin and embedded in paraffin after lobectomy. Therefore this technique is not very helpful in the surgical setting. This is the reason why we employed thin-section CT findings to preoperatively select candidates for limited resection in this study.

Among 20 patients operated upon for pure GGA lesion in our series, three patients were histopathologically revealed to be AAH as described. It appears to be difficult to discriminate AAH from noninvasive BAC preoperatively, because both lesions show the similar thin-section CT finding, focal round-shaped GGA without solid component. AAH was classified as a preinvasive lesion of adenocarcinoma by the World Health Organization in 1998 [21], for many investigators had provided evidence of a sequence from AAH to adenocarcinoma [22, 23]. Although AAH is not classified as a malignant lesion, wedge resection of this potential precursor lesion from which adenocarcinoma arises also seems to be an acceptable option.

The prognosis for BAC was originally thought to be poor. The lungs are the predominant sites of BAC recurrences, especially when BAC is of the pneumonic type [24]. However, more recent reports demonstrate a good prognosis for localized tumors [4, 25]. Breathnach and colleagues [10] described that stage I BAC are fourfold less prone to the development of extrathoracic disease. Our good results of wedge resection for BAC as described here support their opinion.

In conclusion, this study illustrates that focal BACs showing pure GGA on thin-section CT were histopathologically proven to be in situ adenocarcinomas. Wedge resection by VATS will achieve complete surgical resection of this type of early cancer, and offer the best chance for long-term survival and good quality of life. Detection and treatment of pure GGA lesions may improve a dismal prognosis of lung cancer.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

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