ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Hiroyuki Sakurai
Masahiko Matsumoto
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sakurai, H.
Right arrow Articles by Matsumoto, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sakurai, H.
Right arrow Articles by Matsumoto, M.
Related Collections
Right arrow Lung - cancer

Ann Thorac Surg 2004;78:1728-1733
© 2004 The Society of Thoracic Surgeons

Original article: general thoracic

Bronchioloalveolar Carcinoma of the Lung 3 Centimeters or Less in Diameter: A Prognostic Assessment

Hiroyuki Sakurai, MDa,b,*, Yoh Dobashi, MDb, Eiki Mizutani, MDa, Hirochika Matsubara, MDa, Shoji Suzuki, MDa, Kunio Takano, MDa, Shunya Shindo, MDa, Masahiko Matsumoto, MD, PhDa

a Second Department of Surgery, University of Yamanashi, Yamanashi, Japan
b First Department of Pathology, University of Yamanashi, Yamanashi, Japan

Accepted for publication May 4, 2004.

* Address reprint requests to Dr Sakurai, Second Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Tamaho-cho, Nakakoma-gun, Yamanashi 409–3898, Japan
sakuraihm{at}ybb.ne.jp


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
BACKGROUND: Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma for which the incidence is actually rising, but the histologic definition of BAC has been recently changed by the revised World Health Organization (WHO) classification in 1999. The clinical features of patients with BAC diagnosed according to the recently revised WHO classification have not yet been clarified. In this retrospective study, we investigated the pattern of recurrence and survival outcome for patients with resected BAC by pathology review, compared with those in patients who had adenocarcinoma other than BAC.

METHODS: From 1985 through 2002, 108 patients underwent surgical resection for pulmonary adenocarcinoma 3 cm or less in diameter at the University of Yamanashi, Japan. All of the resected specimens of these 108 patients were pathologically reviewed again to confirm the diagnosis as BAC or adenocarcinoma other than BAC. The tumor was defined as BAC when the adenocarcinoma lesion had a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion according to the WHO classification (third edition).

RESULTS: Twenty-five patients (23%) had a diagnosis of BAC, and 83 (77%) had a diagnosis of other adenocarcinoma. There was a female predominance among both patients with BAC and those with other adenocarcinoma. Lymph node involvement was seen for 30 lesions (36%) of adenocarcinoma other than BAC, but not for any BAC lesions. The median duration of follow-up after surgery was 5.1 years. There was no recurrence in the postoperative course in patients with BAC for a 5-year disease-free survival rate of 100%, whereas the 5-year disease-free survival rate for other adenocarcinoma was 63.5%.

CONCLUSIONS: The patients with resected BAC, which is defined as a noninvasive adenocarcinoma by the revised WHO classification, had an excellent prognosis. However, these results may depend on a strictly accurate pathology diagnosis as BAC. Limited resection might be curative in patients with focal BAC based on evidence of pathologic noninvasive features.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of adenocarcinoma that is characterized by its unique growth pattern along the alveolar wall. So far many of the clinical and radiologic features of BAC have been distinct from those of other adenocarcinomas [1–3]. Bronchioloalveolar carcinoma has shown aerogenous, rather than lymphatic, spread [4–9], and radiologic diversity from focal to diffuse disease [10–12]. It was reported that there was an increase in the incidence of BAC year after year [13, 14]. In a recent series, BAC accounted for approximately 20% of adenocarcinomas of the lung [15, 16]. However, the definition of BAC has been revised according to the most recent World Health Organization (WHO) classification in 1999 [17].

On the other hand, the most recent revision of the histologic classification of lung and pleural tumors by WHO [17] has clearly limited the designation of BAC to an adenocarcinoma with no evidence of stromal, vascular, or pleural invasion. An excellent prognosis would justifiably be expected for BACs, which are noninvasive adenocarcinomas. However, it is difficult to compare the results across many previous studies because of the changes in the WHO definition of BAC. Consequently, there is little information available on the clinicopathologic significance of BAC defined as a pathologic noninvasive lesion.

Therefore, we retrospectively examined the pattern of recurrence and survival outcome in patients with resected BAC, which was defined as a noninvasive adenocarcinoma based on the revised WHO classification, compared with the pattern in patients with adenocarcinoma other than BAC, as evaluated by a repeat pathology review.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Patients
For the 18-year period from January 1985 to December 2002, there were 210 pulmonary resections for primary lung adenocarcinoma at the Department of Thoracic Surgery, University of Yamanashi, Japan. These accounted for 61% of all resections for primary lung carcinomas resected during the same period (344 resections). Among the 210 patients with adenocarcinoma, 108 (51%) had adenocarcinoma that measured 3.0 cm or less in diameter and was located in the periphery of the lung parenchyma, excluding patients with a history of resection of other malignancy or preoperative treatment. These 108 patients with peripheral adenocarcinoma 3 cm or less in diameter were the focus of this retrospective study. Clinicopathologic records were reviewed to characterize patients with BAC compared with patients who had adenocarcinoma other than BAC, and included age, sex, history, serum tumor marker level, mode of resection, recurrence, and survival. The surgical and postsurgical stages were determined according to the TNM system of the UICC (Union Internationale Conte le Cancer) [18]. The serum tumor marker carcinoembryonic antigen (CEA) was measured preoperatively in all patients. The normal range for the CEA level at our institute was 5.0 ng/mL or less. Operative death was defined as any death within 30 days of the operation or during hospitalization.

Pathology Examinations
Formaldehyde-fixed, paraffin-embedded blocks were stained using hematoxylin-eosin, elastica, and periodic acid-Schiff, and the entire nodule, including the largest cut surface of the tumor, was retrospectively examined by light microscopy. The histologic subtype was determined based on the WHO classification revised in 1999 (third edition) as BAC, acinar, papillary, solid with mucin, or adenocarcinoma with mixed subtypes. The tumor was defined as BAC when the adenocarcinoma lesion had a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. If invasive foci were present within the tumor, the tumor was classified as adenocarcinoma mixed bronchioloalveolar subtype (adenocarcinoma with mixed subtypes). These findings were independently investigated by two experienced pulmonary pathologists (Y.D., H.S.), and discrepancies were resolved by joint examination of the slides under a two-headed microscope. The two pathologists were masked with respect to outcomes when they carried out the classification of adenocarcinoma into the histologic subtype based on the revised WHO classification. For the purpose of comparison, patients were divided into two groups: those with BAC and those with adenocarcinoma other than BAC, such as acinar, papillary, solid, or mixed subtypes. In addition, BAC was subdivided into three groups: nonmucinous, mucinous, and mixed mucinous and nonmucinous or indeterminate. The following histopathologic findings were also evaluated in the same slides: tumor size (maximum tumor dimension), pleural involvement, vascular/lymphatic permeation, and lymph node involvement. Pleural involvement was classified as positive when the tumor was exposed on the pleural surface or when the tumor invaded the parietal pleura or chest wall. Vascular/lymphatic permeation was evaluated according to the presence of identifiable tumor cells in the blood vessel lumen or lymphatic lumen, respectively.

A clinicopathologic summary of all 108 patients is shown in Table 1. The patients ranged in age from 34 to 79 years with a mean age of 65.3 years. Thirty-six patients (33%) were male and 72 (67%) were female. The mode of operation was lobectomy in 101 patients (94%). The other 7 patients underwent limited resection such as segmentectomy or wedge resection because of being at poor risk such as impaired pulmonary or cardiovascular disease. Surgical curability was complete in all patients.


View this table:
[in this window]
[in a new window]
  		Table 1. Characteristics of Patients With Adenocarcinoma 3 cm or Less in Diameter

 
Statistics
A {chi}2 test or Fisher's exact test was used to compare the frequencies between subgroups. A survival curve was estimated by the Kaplan-Meier method using the date of initial resection as the starting point and the date of recurrence or last follow-up as the endpoint. Differences between survival curves were assessed by the log-rank test. Deaths by causes other than lung cancer were considered censored.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Clinicopathologic Features
Twenty-five patients (23%) had a diagnosis of BAC, and 83 (77%) had a diagnosis of other adenocarcinoma (acinar, n = 9; papillary, n = 10; solid with mucin, n = 7; mixed subtypes, n = 57), according to the 1999 WHO classification. The clinicopathologic characteristics of BAC compared with those of other adenocarcinomas are shown in Table 2. There were no significant differences between BAC and other adenocarcinoma with regard to age (p = 0.423) or sex (p = 0.519). There was a predominance of female patients in both groups. An elevated CEA level was not observed in any of the patients with BAC, although this was observed in 18% of patients with other adenocarcinoma. There were no significant differences in tumor size between BACs and other adenocarcinomas (p = 0.086). None of the BAC lesions showed pleural involvement or vascular/lymphatic permeation, whereas other adenocarcinomas showed pleural involvement in 33%, and vascular/lymphatic permeation in 42%. Lymph node involvement was seen for 30 lesions (36%) in the other adenocarcinoma group, but not in the BAC group. The pathologic stage was IA in all of the lesions in the BAC group, whereas 50 lesions (60%) in the other adenocarcinoma group were stage IA. The distribution of the cytologic subtype for BAC lesions is shown in Table 3. Nonmucinous subtype accounted for 82% of all BACs.


View this table:
[in this window]
[in a new window]
  		Table 2. Relationship Between Histologic Subtype and Clinicopathologic Factors in Pulmonary Adenocarcinoma

 

View this table:
[in this window]
[in a new window]
  		Table 3. Cytologic Subtype of 25 BACs According to the WHO Classification

 
Prognosis
The postoperative median duration of follow-up was 5.1 year. There were no operative deaths. The 5-year disease-free survival rate in all 108 patients with adenocarcinoma 3 cm or less in diameter was 70.0% (Fig 1). The 5-year disease-free survival rates for patients with BAC and those with adenocarcinoma other than BAC were 100% and 63.5%, respectively (Fig 2). No patients with BAC had recurrence in their postoperative clinical course. One of the patients with BAC had a contralateral adenocarcinoma 16 years after the initial resection and underwent a second resection. This lesion was an adenocarcinoma with a mainly bronchioloalveolar growth pattern. Although we could not morphologically differentiate second primary from pulmonary metastasis because of the histologic growth pattern similar to BAC, this lesion was diagnosed as second primary adenocarcinoma based on the previous report by Martini and Melamed [19].



View larger version (11K):
[in this window]
[in a new window]
  		Fig 1. Survival among all 108 patients with pulmonary adenocarcinoma 3.0 cm or less in diameter. The 5-year disease-free survival rate was 70.0% (95% confidence interval, 57.6% to 82.3%).

 


View larger version (14K):
[in this window]
[in a new window]
  		Fig 2. Survival according to the histologic subtype of adenocarcinoma (Ad). The 5-year survival rates were 100% for bronchioloalveolar carcinoma (BAC) and 63.5% for adenocarcinoma other than BAC.

 

   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Before the 1999 revised WHO classification, adenocarcinomas of the lung were classified into four subtypes (acinar, papillary, BAC, or solid) based on their predominant histologic growth pattern. Then, BAC was regarded as an adenocarcinoma with a striking alveolar replacing growth pattern, and so far its clinicopathologic characteristics had been discussed in many researches. However, the definition of BAC was changed by the 1999 WHO classification [1–8, 10–13, 15].

According to the revised WHO histologic classification of lung and pleural tumors in 1999, adenocarcinoma can be grouped into five subtypes according to the histologic growth pattern, ie, acinar, papillary, BAC, solid with mucin formation, and adenocarcinoma with mixed subtypes. Among these, BAC is an adenocarcinoma with a unique replacing growth pattern along the alveolar wall and no evidence of stromal, vascular, or pleural invasion. If an invasive component is identified, the tumor is classified as adenocarcinoma mixed bronchioloalveolar (and acinar or papillary, if present) subtype rather than BAC. Patients with BAC should be expected to have an excellent prognosis because BACs are noninvasive tumors. Nevertheless, in recent reports based on the revised WHO classification, resected stage I BACs were not necessarily associated with excellent 5-year survival. The reported 5-year disease-free survival rates were 73% to 83% (Table 4) [14, 16, 20–22]. These reports included patients with distant metastasis as well as locoregional recurrence. Perhaps these tumors should have been classified as invasive adenocarcinoma rather than as BAC. These reports did not provide pathologic details on how closely they followed the WHO criteria. The issue for a rigorous pathologic evaluation of tumors regarded as BAC must be addressed. A standardized morphologic criteria defining what constitutes invasive features are needed now. Unless the pathologic diagnosis as BAC is precise, the true clinicopathologic characteristics would be equivocal.


View this table:
[in this window]
[in a new window]
  		Table 4. Postoperative 5-Year Survival Rates for Patients With Stage I BAC

 
In the present study, the diagnosis of histologic invasion was based on the 1999 WHO classification. Histologic invasion was suggested by tumor cells arranged in acinic, papillotubular structures or solid nests in a fibroblastic stroma, often accompanied by collagenization. Tumors were classified as BAC only if the entire lesion met the WHO description. In the present study, these findings were independently investigated by two pathologists (Y.D., H.S.), and discrepancies were resolved by joint examination of the slides under a two-headed microscope. Thus, with respect to the tumor histology, all the tumors without any invasive features within the lesion, ie, the tumors showing a pure bronchioloalveolar growth pattern, had no pleural, vascular, or lymphatic involvement. In other words, an adenocarcinoma with tumor histology showing a pure bronchioloalveolar carcinoma could be regarded as having no pleural, vascular, or lymphatic invasion, although BAC according to the WHO classification was defined as an adenocarcinoma with not only a pure bronchioloalveolar growth pattern but also no evidence of vascular or pleural invasion. On the other hand, several reports have supposed that the interobserver concordance was poor for pathologic findings in lung adenocarcinoma [23, 24]. The prevalent definition of histologic "invasion" would be essential. Several investigators have reported that disruption of the stromal elastic framework, which is the supporting architectural structure of the lung, indicated tumor invasion [25, 26]. We pathologically examined not only the tumor morphology by hematoxylin-eosin staining but also preservation of the elastic framework by elastic staining (Fig 3, A and B). Elastic staining highlights the elastic framework quite well. The tumors were regarded as adenocarcinomas other than BAC based on evidence of disruption of the elastic framework. Consequently, it seemed that we could accurately diagnose BAC as a noninvasive lesion from a prognostic perspective, since none of the patients with BAC in our study had postoperative locoregional recurrence or distant metastasis.



View larger version (131K):
[in this window]
[in a new window]
  		Fig 3. Histology of bronchioloalveolar carcinoma by (A) hematoxylin & eosin staining (original magnification x200) and (B) elastic staining (original magnification x200). The tumor shows a pure bronchioloalveolar growth pattern and preserved elastic framework.

 
Conversely, mucinous BACs have been suggested to be more likely than nonmucinous BACs to develop an aerogenous spread, which leads to an unfavorable prognosis [3, 5, 6, 27–29]. Immunohistochemical studies have demonstrated that mucinous BAC was more likely to detach from the underlying basement membrane than other subtypes [30, 31]. In the present study, the prognosis of resected BAC, whether mucinous or nonmucinous, was excellent although the number of mucinous BAC lesions was quite small. Many reports have supposed that a nodular BAC later becomes multifocal and finally diffuse, and this was found more frequently in mucinous BAC [5, 10]. Bronchioloalveolar carcinoma, particularly mucinous type, should be resected before the potential occurrence of aerogenous spread.

For patients with stage I BAC, surgical resection is the treatment of choice [9]. Bronchioloalveolar carcinoma cannot be diagnosed based on small biopsy specimens in a preoperative procedure because the definition of BAC requires that there be no evidence of invasive features within the entire lesion [17]. Therefore, complete surgical resection plays an important role in the final diagnosis and treatment. The extent of resection is somewhat controversial. With regard to the mode of operation for T1 peripheral nonsmall cell lung cancers, lobectomy has been the standard operation of choice based on the results of a prospective, randomized phase III trial by the Lung Cancer Study Group [32]. This trial demonstrated that limited resection, such as wedge or segmentectomy, was inferior to lobectomy with regard to locoregional recurrence and survival. However, recent reports have suggested that patients with no or very minimally invasive lesions could be possible candidates for limited resection [33, 34]. For T1 focal BACs with no invasive features, limited resection with a reasonable margin might be curative [35] only if BAC is correctly diagnosed in a frozen section of the tumor. However, it is unknown that how precisely BAC can be diagnosed in a frozen section. As stated in the present study, the histologic invasive features based on tumor cells accompanied by fibroblastic stroma (collagenization) should be carefully evaluated in a frozen section as well as a permanent section. Then, we believe that BAC with no invasive features can be almost precisely diagnosed in a frozen section. Recently, we prospectively diagnose BAC in a frozen section and get almost consist with the diagnosis as BAC in a permanent section. However, if any invasive features are suspected in a frozen section, major lung resection would be recommended. Furthermore, this issue, however, must be examined in a prospective study.

The selection of only a subset of patients with BAC is not necessarily crucial to defining a subset with a good prognosis. Indeed BAC is an adenocarcinoma defined as a lesion with no invasive features by the revised WHO classification, but it does not include minimal invasive adenocarcinoma, which would compare with BAC as to prognosis. However, the histopathologic concept of "minimally invasive" adenocarcinoma is still unknown, although several studies have been reported about minimal invasion of adenocarcinoma [36]. Thus, it would be expected that patients with at least BAC could have a good prognosis.

Recently, several radiologic-pathologic studies have suggested that lung adenocarcinomas that appear as ground-glass opacity, which is defined as hazy, increased attenuation with preservation of bronchial and vascular margins [37], on high-resolution computed tomography (CT) can seem to be BACs [34, 38–40]. Among the 25 patients with BAC, the CT appearances of 15 patients could be checked in our study. Seven patients had pure GGO lesions without solid part on high-resolution CT and 7 had lesions of GGO with solid part; the other patient had a solid lesion without GGO, which was histologically a mucinous BAC. By contrast, there were no pure GGO lesions in the CT appearances of patients with adenocarcinoma other than BAC.

In conclusion, the prognosis in patients with resected BAC 3 cm or less in diameter was excellent. A strict pathologic diagnosis of tumors considered to be BAC, which is defined as a noninvasive adenocarcinoma according to the revised WHO classification, is needed. Limited resection might be suitable for patients with a stringently diagnosed focal BAC. Further studies based on immunohistochemical or molecular markers would be required to define biologic behavior in BAC.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Clayton F. The spectrum and significance of bronchioloalveolar carcinomas. Pathol Annu. 1988;23:361–394[Medline]
  2. Grover FL, Piantadosi SLung Cancer Study Group. Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung—the Lung Cancer Study Group experience. Ann Surg. 1989;209:779–790[Medline]
  3. Barkley JE, Green MR. Bronchioloalveolar carcinoma. J Clin Oncol. 1996;14:2377–2386[Abstract]
  4. Storey CF, Knudtson KP, Lawrence BJ. Bronchiolar ("alveolar cell") carcinoma of the lung. J Thorac Surg. 1953;26:331–406[Medline]
  5. Manning JT, Spjut HJ, Tschen JA. Bronchioloalveolar carcinoma: the significance of two histopathologic types. Cancer. 1984;54:525–534[Medline]
  6. Clayton F. Bronchioloalveolar carcinomas. Cell types, patterns of growth, and prognostic correlates. Cancer. 1986;57:1555–1564[Medline]
  7. Donovan WD, Yankelevitz DF, Henschke CI, Altorki N, Nash TA. Endobronchial spread of bronchioloalveolar carcinoma. Chest. 1993;104:951–953[Free Full Text]
  8. Okubo K, Mark EJ, Flieder D, et al. Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival. J Thorac Cardiovasc Surg. 1999;118:702–709[Abstract/Free Full Text]
  9. Barlesi F, Doddoli C, Gimenez C, et al. Bronchioloalveolar carcinoma: myths and realities in the surgical management. Eur J Cardiothorac Surg. 2003;24:159–164[Abstract/Free Full Text]
  10. Liebow AA. Bronchiolo-alveolar carcinoma. Adv Intern Med. 1960;10:329–358[Medline]
  11. Hill CA. Bronchioloalveolar carcinoma: a review. Radiology. 1984;150:15–20[Abstract/Free Full Text]
  12. Mihara N, Ichikado K, Johkoh T, et al. The subtypes of localized bronchioloalveolar carcinoma: CT-pathologic correlation in 18 cases. AJR Am J Roentgenol. 1999;173:75–79[Abstract/Free Full Text]
  13. Barsky SH, Cameron R, Osann KE, Tomita D, Holmes EC. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer. 1994;73:1163–1170[Medline]
  14. Furak J, Trojan I, Szoke T, et al. Bronchioloalveolar lung cancer: occurrence, surgical treatment and survival. Eur J Cardiothorac Surg. 2003;23:818–823[Abstract/Free Full Text]
  15. Higashiyama M, Kodama K, Yokouchi H, et al. Prognostic value of bronchiolo-alveolar carcinoma component of small lung adenocarcinoma. Ann Thorac Surg. 1999;68:2069–2073[Abstract/Free Full Text]
  16. Rena O, Papalia E, Ruffini E, et al. Stage I pure bronchioloalveolar carcinoma: recurrences, survival and comparison with adenocarcinoma of the lung. Eur J Cardiothorac Surg. 2003;23:409–414[Abstract/Free Full Text]
  17. Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E. Histological typing of lung and pleural tumors. World Health Organization international histological classification of tumors. 3rd ed. Berlin: Springer; 1999.
  18. Sobin LH, Wittekind CH. International Union Against Cancer: TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss; 2002.
  19. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70:606–612[Abstract]
  20. Breathnach OS, Kwiatkowski DJ, Finkelstein DM, et al. Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease. J Thorac Cardiovasc Surg. 2001;121:42–47[Medline]
  21. Volpino P, Andrea ND, Cangemi R, Mingazzini P, Cangemi B, Cangemi V. Bronchioloalveolar carcinoma: clinical, radiographic, and pathological findings. Surgical results. J Cardiovasc Surg. 2001;42:261–267[Medline]
  22. Ebright MI, Zakowski MF, Martin J, et al. Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma. Ann Thorac Surg. 2002;74:1640–1647[Abstract/Free Full Text]
  23. Schraufnagel D, Peloquin A, Pare JA, Wang NS. Differentiating bronchioloalveolar carcinoma from adenocarcinoma. Am Rev Respir Dis. 1982;125:74–79[Medline]
  24. Roggli VL, Vollmer RT, Greenberg SD, McGavran MH, Spjut HJ, Yesner R. Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases. Hum Pathol. 1985;16:569–579[Medline]
  25. Eto T, Suzuki H, Honda A, Nagashima Y. The changes of the stromal elastotic framework in the growth of peripheral lung adenocarcinomas. Cancer. 1996;77:646–656[Medline]
  26. Yokose T, Suzuki K, Nagai K, Nishiwaki Y, Sasaki S, Ochiai A. Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma on the lung 3 cm or less in diameter. Lung Cancer. 2000;29:179–188[Medline]
  27. Daly RC, Trastek VF, Pairolero PC, et al. Bronchoalveolar carcinoma: factors affecting survival. Ann Thorac Surg. 1991;51:368–376[Abstract]
  28. Dumont P, Gasser B, Rouge C, Massard G, Wihlm JM. Bronchoalveolar carcinoma. Histopathologic study of evolution in a series of 105 surgically treated patients. Chest. 1998;113:391–395[Abstract/Free Full Text]
  29. Carretta A, Canneto B, Calori G, et al. Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma. Eur J Cardiothorac Surg. 2001;20:367–371[Abstract/Free Full Text]
  30. Ohori NP, Yousem SA, Griffin J, et al. Comparison of extracellular matrix antigens in subtypes of bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma. An immunohistochemical study. Am J Surg Pathol. 1992;16:675–686[Medline]
  31. Gaeta M, Blandino A, Pergolizzi S, et al. Patterns of recurrence of bronchioloalveolar cell carcinoma after surgical resection: a radiological, histological, and immunohistochemical study. Lung Cancer. 2003;42:319–326[Medline]
  32. Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 1995;60:615–622[Abstract/Free Full Text]
  33. Yamato Y, Tsuchida M, Watanabe T, et al. Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung. Ann Thorac Surg. 2001;71:971–974[Abstract/Free Full Text]
  34. Asamura H, Suzuki K, Watanabe S, Matsuno Y, Maeshima A, Tsuchiya R. A clinicopathological study of resected subcentimeter lung cancers: a favorable prognosis for ground glass opacity lesions. Ann Thorac Surg. 2003;76:1016–1022[Abstract/Free Full Text]
  35. Sawabata N, Ohta M, Matsumura A, et al. Optimal distance of malignant negative margin in excision of nonsmall cell lung cancer: a multicenter prospective study. Ann Thorac Surg. 2004;77:415–420[Abstract/Free Full Text]
  36. Sakurai H, Maeshima A, Watanabe S, et al. Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis. Am J Surg Pathol. 2004;28:198–206[Medline]
  37. Austin JHM, Muller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology. 1996;200:327–331[Free Full Text]
  38. Collins J, Stern EJ. Ground-glass opacity at CT: the ABCs. AJR Am J Roentgenol. 1997;169:355–367[Free Full Text]
  39. Watanabe S, Watanabe T, Arai K, Kasai T, Haratake J, Urayama H. Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground-glass attenuation on computed tomography. Ann Thorac Surg. 2002;73:1071–1075[Abstract/Free Full Text]
  40. Suzuki K, Asamura H, Kusumoto M, Kondo H, Tsuchiya R. "Early" peripheral lung cancer: prognostic significance of ground glass opacity on thin-section computed tomographic scan. Ann Thorac Surg. 2002;74:1635–1639[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
T. Koike, K.-i. Togashi, T. Shirato, S. Sato, H. Hirahara, M. Sugawara, F. Oguma, H. Usuda, and I. Emura
Limited resection for noninvasive bronchioloalveolar carcinoma diagnosed by intraoperative pathologic examination.
Ann. Thorac. Surg., October 1, 2009; 88(4): 1106 - 1111.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
R. Rami-Porta and M. Tsuboi
Sublobar resection for lung cancer
Eur. Respir. J., February 1, 2009; 33(2): 426 - 435.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
B. Goudarzi, H. A. Jacene, and R. L. Wahl
Diagnosis and Differentiation of Bronchioloalveolar Carcinoma from Adenocarcinoma with Bronchioloalveolar Components with Metabolic and Anatomic Characteristics Using PET/CT
J. Nucl. Med., October 1, 2008; 49(10): 1585 - 1592.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Radiol.Home page
D Patsios, H C Roberts, N S Paul, T Chung, S J Herman, A Pereira, and G Weisbrod
Pictorial review of the many faces of bronchioloalveolar cell carcinoma
Br. J. Radiol., December 1, 2007; 80(960): 1015 - 1023.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
D. Arenberg
Bronchioloalveolar Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)
Chest, September 1, 2007; 132(3_suppl): 306S - 313S.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. Riquet, C. Foucault, P. Berna, J. Assouad, A. Dujon, and C. Danel
Prognostic Value of Histology in Resected Lung Cancer With Emphasis on the Relevance of the Adenocarcinoma Subtyping
Ann. Thorac. Surg., June 1, 2006; 81(6): 1988 - 1995.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
C.S. Pramesh, R. C. Mistry, and J. Agarwal
How Should Bronchioloalveolar Carcinoma of the Lung 3 Centimeters or Less Be Treated?
Ann. Thorac. Surg., November 1, 2005; 80(5): 1978 - 1978.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
H. Sakurai, Y. Dobashi, and M. Matsumoto
Reply
Ann. Thorac. Surg., November 1, 2005; 80(5): 1979 - 1979.
[Full Text] [PDF]

Home page
 JCOHome page
W. D. Travis, K. Garg, W. A. Franklin, I. I. Wistuba, B. Sabloff, M. Noguchi, R. Kakinuma, M. Zakowski, M. Ginsberg, R. Padera, et al.
Evolving Concepts in the Pathology and Computed Tomography Imaging of Lung Adenocarcinoma and Bronchioloalveolar Carcinoma
J. Clin. Oncol., May 10, 2005; 23(14): 3279 - 3287.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Hiroyuki Sakurai
Masahiko Matsumoto
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sakurai, H.
Right arrow Articles by Matsumoto, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sakurai, H.
Right arrow Articles by Matsumoto, M.
Related Collections
Right arrow Lung - cancer

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS