Bronchioloalveolar Cell Carcinoma Research Articles

MS 03.03 Limited vs. Standard Surgical Resection: European Experience

MS 03.03 Limited vs. Standard Surgical Resection: European Experience

喀痰中の CA19-9 が著明高値を示した細気管支肺胞上皮癌の 1 例

喀痰中の CA19-9 が著明高値を示した細気管支肺胞上皮癌の 1 例

Invasive adenocarcinoma of the lung is associated with the upper lung regions

ObjectivesWe postulated that ventilation–perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior–inferior regional distribution, and associated variables such as emphysema. Materials and MethodsOne hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema. ResultsThe majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P=0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P=0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P=0.008, compared to lower region), whereas lobar location of tumor was not (P=0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P=0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P=0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P=0.217). ConclusionInvasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is not related to smoking, history of COPD, or total emphysema. The regional distribution of invasive adenocarcinoma may be due to V/Q relationships or other local factors.

The Use of Octreotide to Manage Symptoms of Bronchorrhea: A Case Report

Octreotide, a synthetic analogue of the hormone somatostatin, is primarily used in palliative medicine because of its antisecretory effect and has been shown to be effective in the management of bowel obstruction, nausea, and diarrhea. Octreotide also has been successfully used for the management of bronchorrhea in both inpatient and outpatient settings. We report the case of a 47-year-old female with a history of bronchioloalveolar cell carcinoma whose copious bronchial secretions were controlled with octreotide. Octreotide should be further evaluated as a first-line treatment for bronchorrhea.

Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model

BackgroundSonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours.MethodsFourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed.ResultsThe ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely examined in vivo. There is no residual gas, which interferes with ultrasound. Pulmonary vessels and bronchi are clearly differentiated. Simulated lung lesions can easily be detected inside the lung lobe.ConclusionsLung flooding enables complete lung sonography and tumour detection. We have developed a novel method that efficiently uses ultrasound for guiding intraoperative interventions in open and endoscopic lung surgery.

Incidental, subsolid pulmonary nodules at CT: etiology and management

Pulmonary nodules, both solid and subsolid, are common incidental findings on computed tomography (CT) studies. Subsolid nodules (SSNs) may be further classified as either pure ground-glass nodules or part-solid nodules. The differential diagnosis for an SSN is broad, including infection, organizing pneumonia, inflammation, hemorrhage, focal fibrosis, and neoplasm. Adenocarcinomas of the lung are currently the most common type of lung cancer, representing 30–35% of all primary lung tumors, and the subtype of bronchioloalveolar cell carcinoma (BAC) commonly presents as an SSN. In 2011, a new classification system for lung adenocarcinomas was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. An important feature of the new system is the relinquishment of the term BAC in favor of more specific histologic subtypes. It has been reported that these subtypes are associated with characteristic CT findings. This article reviews the new classification system of lung adenocarcinomas, discusses and illustrates the associated CT findings, and outlines the current recommendations for further diagnosis, treatment, and follow-up of SSNs based on computed tomography findings.

Nodal involvement pattern in resectable lung cancer according to tumor location

The aim in this study was to define the pattern of lymph node metastasis according to the primary tumor location. In this retrospective cohort study, each of the operable patients diagnosed with lung cancer was grouped by tumor mass location. The International Association for the Study of Lung Cancer nodal chart with stations and zones, established in 2009, was used to define lymph node levels. From 2006 to 2010, 197 patients underwent a lobectomy with systematic nodal resection for primary lung cancer at Chiang Mai University Hospital. There were 123 male and 74 female patients, with ages ranging from 16– 85 years old and an average age of 61.31. Analyses of tumor location, histology type, and nodal metastasis were performed. The locations were the right upper lobe in 63 patients (31.98%), the right middle lobe in 18 patients (9.14%), the right lower lobe in 30 patients (15.23%), the left upper lobe in 55 patients (27.92%), the left lower lobe in 16 patients (8.12%), and mixed lobes (more than one lobe) in 15 patients (7.61%). The mean tumor size was 4.45 cm in diameter (range 1.2–16.5 cm). Adenocarcinoma was the most common histological type, which occurred in 132 cases (67.01%), followed by squamous cell carcinoma in 41 cases (20.81%), bronchiolo alveolar cell carcinoma in nine cases (4.57%), and large cell carcinoma in seven cases (3.55%). Eighteen cases (9.6%) had skip metastasis (mediastinal lymph node metastasis without hilar node metastasis). Adenocarcinoma and intratumoral lymphatic invasion were the predictors of mediastinal lymph node metastases. There were statistically significant differences between a tumor in the right upper lobe and the right lower lobe. However, there were no statistically significant differences between tumors in the other lobes. In conclusion, tumor location is not a precise predictor of the pattern of nodal metastasis. Systematic lymph node dissection is the only way to accurately determine lymph node status. Further studies are required for evaluation and conclusions.

Correlations between thin-section CT findings, histopathological and clinical findings of small pulmonary adenocarcinomas

Study objectives Previously, we reported that small pulmonary adenocarcinomas (tumor diameter 20 mm or less) could be classified according to attenuation on thin-section CT (TS-CT) images as either ‘air-containing type’ or ‘solid-density type’ (Lung Cancer 2002;36:49–57). Air-containing type was defined as having areas where TOM (tumor opacity on mediastinal window images) was half or less than half the size of those noted on lung window images. Solid-density type was defined as having areas where TOM was greater than half the size of those noted on lung window images. Our findings indicated that there was no microscopic evidence of metastasis with air-type nor any relapses nor deaths, after resection. By contrast, patients with solid-density types demonstrated a poor prognosis. At this time, the histopathological characteristics of areas of TOM have not been fully investigated. The purpose of this study is to define the correlations between TOM and histopathological findings of small lung adenocarcinomas. Method We retrospectively reviewed the records and CT scans of 134 patients, who had undergone surgical resection of peripheral adenocarcninomas. All tumor diameters were 20 mm or less in size. All 134 patients had undergone TS-CT prior to surgery. TS-CT Images were acquired by a model X-Vigor/Real or an Aquillion CT scanner (Toshiba Medical Systems). Thin-section images of tumors were obtained at 135 kVp at 250 mAs with 1–2 mm section thicknesses. All images were photographed using mediastinal (level, 40 HU; width, 400 HU) and lung (level, −600 HU; width, 1600 HU) window settings. We researched the histopathological components corresponding to the areas of TOM. Results Areas of TOM demonstrated five possible histopathological findings; (1) collapse (C), (2) collapse with bronchioloalveolarcell carcinoma (CwB), (3) adenocarcinoma cells (Cells), (4) fibroblasts (F), and (5) mucus (M). Areas of TOM in air-containing type adenocarcinomas (52 cases) demonstrated predominantly C and/or CwB (C/CwB type, 44 cases). Areas of TOM in solid-density type adenocarcinomas (82 cases), in comparison, demonstrated predominantly Cells and/or Cells/F (Cell/F type, 67 cases). We noted a statistically significant difference between the histopathological findings of the areas of TOM of air-containing type and solid-density type tumors. The 39 cases of Cell/F type adenocarcinomas revealed microscopic evidence of metastasis (pleural involvement, vascular invasion, lymphatic permeation, or lymphnode metastasis). Whereas, no C/CwB type adenocarcinomas cases revealed any microscopic metastasis. The prognosis of C/CwB type after resection is better than for Cell/F type. Conclusion We found that air-containing type adenocarcinomas demonstrated C/CwB type, and that solid-density type adenocarcinomas demonstrated Cell/F type. The histopathological findings of small pulmonary adenocarcinomas could be classified into three groups: C/CwB type, Cell/F type and M type. The prognosis of C/CwB type is better than for Cell/F type. Our results indicate that there are clear correlations between the areas of TOM and the histopathological components of small pulmonary adenocarcinomas. Therefore TS-CT findings are a useful aid in determining the best surgical methods.

Gefitinib as First-line Therapy for Advanced or Metastatic Non-small Cell Lung Cancer Patients in Southern Taiwan

Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is effective in treating patients with non-small cell lung cancer (NSCLC) after unsuccessful chemotherapy. However, survival outcomes and predictors for its effectiveness in chemotherapy-naive NSCLC patients are still not clear. The goal of this study was to investigate the response and survival rates and identify the predictive factors for patients with advanced or metastatic disease receiving gefitinib as first-line therapy. We retrospectively analyzed the response and survival rates of patients with advanced or metastatic NSCLC who had received gefitinib as first-line therapy across six medical institutes in Southern Taiwan between May 2004 and April 2006. The relationship between the response and survival rates to the known predictive factors for gefitinib response and survival was also investigated. A total of 97 patients (65 females and 32 males) were enrolled in this study. Seventy-four patients (76%) had never smoked. Eighty-eight patients (91%) had adenocarcinoma or bronchioloalveolar cell carcinoma. The objective response rate was 56% and the disease control rate (partial response plus stable disease) was 76%. Only poor performance status (Eastern Cooperative Oncology Group score, 3-4) was statistically significantly associated with overall response in this study. The 1-year survival rate was 77%. We suggest that first-line gefitinib monotherapy is promising in some subgroups of Asian patients with NSCLC. Further randomized controlled studies are needed to validate the effectiveness of first-line gefitinib therapy.

Bronchioloalveolar Carcinoma (Lepidic Growth) Component Is a More Useful Prognostic Factor than Lymph Node Metastasis

Although many factors predictive of patient survival have been reported for lung cancer, no comparative studies have attempted to determine those that are most significant for practical medicine. We conducted a retrospective review of 139 patients who underwent complete resection of adenocarcinomas less than 2 cm in diameter between 1993 and 2000 at the National Cancer Center Hospital (Tokyo, Japan). The MIB-1 labeling index (LI), immunohistochemical staining for carcinoembryonic antigen (CEA), p53, p27, epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), Cox-2, neuronatin, gammaH2AX, and thyroid transcription factor-1 (TTF-1), the prevalence of a micropapillary pattern, and the ratio of the bronchioloalveolar cell carcinoma (BAC) or lepidic growth (LG) component were determined, and their significance as prognostic factors for lung adenocarcinoma was compared. Univariate analysis showed that lymph node metastasis (p-N status), BAC/LG component, vascular invasion (p-V status), MIB-1 LI, pEGFR, and CEA were prognostically significant (p-N status: p < 0.0001, BAC/LG: p = 0.0005, p-V status: 0.002, MIB-1 LI: p = 0.005, pEGFR: p = 0.024, and CEA: p = 0.049). Multivariate analysis showed that only p-N status (p = 0.013) was of prognostic significance. However, BAC/LG component (p = 0.051) was a more reliable prognostic factor than p-N status in mixed adenocarcinoma with a BAC/LG component. In comparison with other immunohistochemical and histopathologic factors, BAC/LG component is independently and reliably prognostic for small adenocarcinoma of the lung, and, in particular, for the major histologic subtype (adenocarcinoma mixed subtype with BAC/LG), BAC/LG component is more reliably prognostic than lymph node metastasis.

Incidence of EGFR and K-ras mutations in Japanese patients with mucinous bronchiolo-alveolar cell carcinoma of the lung

14553 Background: In lung adenocarcinomas, especially Bronchiolo Alveolar Carcinomas (BACs), it has been reported that Epidermal Growth Factor Receptor- Tyrosine Kinase Inhibitors (EGFR-TKIs) have a high potency. But in fact, its efficacy differs among subtypes: in mucinous BACs (mBACs), it exhibits a poor effect compared to its performance in non-mucinous BACs (non-mBACs). One reason why is EGFR mutations are rare, and K-ras mutations are frequent, in mBACs relative to non-mBACs. Methods: From January 2004 to October 2007, 180 lung adenocarcinomas were diagnosed in pathological specimens after resections. 51 cases (28%) of BACs were classified. In these specimens, 17 mBACs (9%) and 34 non-mBACs (19%) were found. We extracted 41 cases of BACs (all mBACs and 24 cases of non-mBACs as control), and examined their EGFR mutations and K-ras mutations. We used the PNA-LNA PCR clump method to detect EGFR mutations, and K-ras mutations were explored by sequences after the enriched PCR method. Results: Only three EGFR mutations were found in 17 mBACs (18%), and 12 K-ras mutations were present (71%). By comparison, 14 EGFR mutations were detected in 24 non-mBACs (58%), and 11 K-ras mutations were identified (46%). Conclusions: In mBAC cases, the efficacy of EGFR-TKIs is poor, because EGFR mutation is rare and K-ras mutation is frequent. No significant financial relationships to disclose.

Increased [11C]Choline Uptake in Bronchioloalveolar Cell Carcinoma with Negative [18F]FDG Uptake. A PET/CT and Pathology Study

A case of a patient with bronchioloalveolar cell predominate lung adenocarcinoma (BAC) studied using integrated Positron Emission Tomography and Computed Tomography (PET/CT) with both 18F-fluorodeoxyglucose ([18F]FDG-PET) and [11C]Choline ([11C]Choline-PET) is described, with the aim of evaluating a new non invasive imaging method to detect and stage BAC, and providing information on tumour biology in vivo. The information derived from combining the two tracers could help in distinguishing lung adenocarcinoma with large BAC components ([18F]FDG negative and [11C]Choline positive) from inflammatory lesion ([18F]FDG and [11C]Choline positive). In addition, the simultaneous use of two PET tracers, evaluating two different metabolic pathways, together with histopathologic, immunohistochemical and gene expression analysis, could help to improve understanding of tumour in vivo behaviour. Keywords: Positron Emission Tomography, [11C]Choline, [18F]FDG, BAC, gene expression, lung cancer

EGFR Inhibitors as First-Line Therapy in Advanced Non-small Cell Lung Cancer

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the treatment of advanced non-small cell lung cancer (NSCLC). Although platinum-based doublet chemotherapy remains the cornerstone for the first-line treatment of metastatic NSCLC, several phase II and III trials have been conducted utilizing EGFR TKIs in this setting. Patients with advanced NSCLC who are life long never-smokers, those with EGFR TK mutations, and those with bronchioloalveolar cell carcinoma histology seem to have promising efficacy with first-line therapy with EGFR TKIs compared with unselected groups of patients receiving the same agents. Phase III trials have clearly demonstrated no improvement in survival when EGFR TKIs were combined with conventional platinum-based doublets, with the exception of subset analysis in nonsmokers. This review will summarize the results of clinical trials on erlotinib or gefitinib in the first-line treatment of select and unselected patients with NSCLC and describe ongoing studies with these agents in NSCLC.

What's your treatment option in a patient with impending respiratory failure due to disseminated lung cancer?

Diffuse bronchiolo-alveolar cell carcinoma (BAC) with endolymphatic tumor emboli involving whole lung fields was found in a 25-year-old male. He had a history of 6 pack years of smoking. After a thoracoscopic lung biopsy, his condition was aggravated leading to imminent respiratory failure. Although gefitinib is not usually recommended as a first-line chemotherapeutic drug, we decided to use it considering that the added toxicity of conventional drugs would be fatal to him. Surprisingly, the patient showed the dramatic improvement and was able to exercise 1 week after the treatment. The immunostainings for p-Akt and E-cadherin were strongly positive. A deletion mutation (delE746–750) was detected in exon 19 by sequencing. The fluorescent in situ hybridization (FISH) was negative as low trisomy suggesting that the epidermal growth factor receptor (EGFR) mutation is a more reliable finding for prediction of the response to this novel drug, even in a patient with unfavorable clinical characteristics such as male gender and smoker. An EGFR–tyrosine kinase inhibitor (EGFR–TKI), either alone or combined with other chemotherapeutic drugs, should be considered an initial therapeutic option in patients with disseminated lung cancer requiring urgent treatment.

Pictorial review of the many faces of bronchioloalveolar cell carcinoma

Bronchioloalveolar cell carcinoma (BAC) has a varied appearance on CT that often leads to an incorrect or delayed diagnosis. The purpose of this pictorial review is to define common CT characteristics that are specific to BAC. A retrospective review was undertaken of 20 CT scans of pathologically proven cases of BAC; tumours were categorized as focal or diffuse, single or multiple, and infiltrative or well defined. Additional radiological features noted include the density (solid, part solid, non-solid), the presence of unaffected vessels within the tumour(s), and the presence of internal air bronchograms. We illustrate cases of localized and diffuse BAC presenting as (i) solitary or multiple pulmonary nodules, with and without air bronchograms, (ii) bubble-like lucencies of pseudocavitation associated with nodules of varying density, (iii) unifocal or multifocal ground-glass opacities, (iv) crazy paving, (v) nodules and airspace opacities with unaffected vessels coursing through them and (vi) lobar or multilobar consolidation and cavitating nodules. In conclusion, BAC may present with a variety of CT appearances. However, there are typical features such as the CT-angiogram sign or air-brochochograms in solitary nodules and in the periphery of larger consolidations, persisting pure ground-glass opacities, unresolving consolidation and the combination of diffuse nodules and consolidation. These features should alert the radiologist to the diagnosis of BAC.

SEVERE INTRAPULMONARY SHUNTING IN BRONCHIOLOALVEOLAR CELL CARCINOMA CORRECTED BY SELECTIVE PULMONARY ARTERY OCCLUSION AND PALLIATIVE TUMOR RESECTION

INTRODUCTION: Severe lobar venoarterial shunting in bronchioloalveolar cell carcinoma (BAC) has been infrequently reported [1,2]. A patient with BAC is presented with a severe right lower lobe venoarterial shunt corrected by pulmonary artery occlusion and effectively palliated with a right lower lobectomy.

EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): Results of a prospective phase II trial

7003 Background: Erlotinib produces dramatic responses in a subset of patients with NSCLC. Mutations in the EGFR tyrosine kinase domain, EGFR amplification or polysomy and EGFR overexpression on immunohistochemistry have all been associated with sensitivity and benefit; pts with KRAS mutation are commonly resistant to this agent. These correlative studies were prospectively undertaken to characterize the ability of these markers to predict response rate, time to progression and survival in pts with BAC treated with the EGFR-TKI, erlotinib. Methods: One hundred and two patients received erlotinib as part of a phase II trial in BAC (Kris, Proc ASCO 2005); 84 had one or more correlative studies completed. Analysis of EGFR exons 19 and 21 (n=82) (Pao, et al PNAS 2004), EGFR IHC (n=62) (DAKO) was performed and EGFR copy number was determined by chromogenic in situ hybridization (CISH) (n=74) (Zymed); detection of ≥ 4 signals per cell was considered evidence of amplified copy number. KRAS exon 2 (n=79) testing was performed by direct sequencing. Fisher’s exact test was used to study the association of each feature in pts with partial response or no partial response. Time to progression and survival were analyzed with log-rank test. Results: See table below. Conclusions: 1) EGFR exon 19 or 21 mutation is a powerful predictor of response and TTP but not OS in pts with BAC treated with erlotinib. 2) CISH ≥4 is associated with response and improved TTP but not OS. 3) Patients with both EGFR mutation and amplification fare well supporting the concept of “oncogene addiction”; erlotinib should be considered as initial therapy in this population. 4) EGFR amplification without mutation is uncommon. 5) There is no clear utility of EGFR IHC in clinical decision making. 6) The presence of KRAS mutation predicts resistance to erlotinib. Supported, in part, by Genentech. [Table: see text] [Table: see text]

Synchronous multiple primary lung cancers with different response to gefitinib

Synchronous bronchiolo-alveolar cell carcinoma (BAC) in both lungs and squamous cell carcinoma in left lung were found in a 66-year-old male smoker. After two courses of chemotherapy with gemcitabine and carboplatin, the left lung mass had partially resolved, however, the extent of BAC had been increased. When gefitinib was used as a second-line chemotherapy, the consolidation lesions of BAC was improved while the mass of squamous cell carcinoma was aggravated. The analysis of epidermal growth factor receptor-tyrosine kinase (EGFR-TK) mutations showed that BAC had the deletion, delE746-A750 in exon 19, however, squamous cell carcinoma had no mutations. These synchronous tumors with different location, histology, status of EGFR-TK mutations and response to chemotherapy might be caused by different molecular pathogenesis.

Pulmonary blastoma within bronchioloalveolar cell carcinoma

Pulmonary blastoma is a rare tumour of the lung composed of epithelial and mesenchymal elements that morphologically resemble the embryonal structure of the lung. The authors report a 79-year-old man who was diagnosed with a pulmonary blastoma within bronchioloalveolar cell carcinoma. Macroscopic, histopathological and immunohistochemical findings suggested that the pulmonary blastoma was closely associated with the bronchioloalveolar cell carcinoma.

Pathologic and Biological Assessment of Lung Tumors Showing Ground-Glass Opacity

We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO). Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically. The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter. If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.