Cases Of Bronchioloalveolar Carcinoma Research Articles

Pathological Examination and Differential Diagnosis of Pulmonary Ground-Glass Opacities by CT-Guided Percutaneous Needle Biopsy

In order to explore the pathological examination and differential diagnosis of pulmonary ground-glass opacities (GGO) with CT-guided percutaneous needle biopsy (CTPNB), this study retrospectively analyzed the medical records of 120 cases of patients who were diagnosed with pulmonary GGO and underwent CTPNB in a hospital designated by this study from December 2014 to December 2018. The results showed that all the 120 cases of patients were successfully punctured at one time and obtained sufficient tissue specimens with the puncture success rate and diagnostic accuracy both of 100%, being able to make a clear qualitative diagnosis. Among them, 30 cases were malignant lesions including 14 cases of bronchioloalveolar carcinoma and 16 cases of metastatic carcinoma; 90 cases were benign lesions including 52 cases of hematogenous pulmonary tuberculosis, 14 cases of sarcoidosis, 12 cases of silicosis and coal workers’ pneumoconiosis, 6 cases of interstitial pneumonia, 4 cases of alveolar proteinosis, and 2 case of allergic pneumonia. The complications of the 120 patients during the treatment included 8 cases of pneumothorax with an incidence of 6.67% (8/120), in which 2 case had the pulmonary tissue compression rate of about 25% and the other cases had no obvious perceived symptoms and required no special treatment, and 10 cases of hemoptysis with an incidence of 8.33% (10/120), whose symptoms disappeared after the treatment with batroxobin, and had no serious symptoms such as air embolism complication. The sensitivity, specificity, and accuracy of CTPNB in the diagnosis of malignant pulmonary GGO were 83.67% (82/98), 100% (22/22), and 86.67% (104/120), respectively, without statistically significant differences in diagnostic efficacy (P > 0.05). In summary, the CTPNB for the diagnosis of malignant pulmonary GGO has high sensitivity, specificity, and accuracy, and the CTPNB is also the simplest and most important approach to obtain effective pathological examinations and differential diagnoses of pulmonary GGO, which has simple operation, high accuracy and few complications, and has high application value for the qualitative diagnosis of pulmonary GGO.

Complete video-assisted thoracoscopic anatomic segmentectomy for pulmonary diseases: the early experiences

To evaluate the safety and feasibility of video-assisted thoracic surgery (VATS) anatomic segmentectomy for pulmonary diseases. Between November 2009 and July 2011, 20 patients received consecutive VATS anatomic segmentectomy by single surgical group. There were 3 male and 17 female, aging from 32 to 81 years with a mean of 53 years. The patients included 12 cases of non-small cell lung cancer (NSCLC) (5 cases of bronchioloalveolar carcinoma, 6 cases of adenocarcinoma, and 1 case of squamous cell carcinoma), 7 cases of benign diseases (3 cases of bronchiectasis, 2 cases of inflammatory pseudotumor, 1 case of tuberculosis, and 1 case of sclerosing hemangioma) and 1 case of metastasis tumor. The locations of resected segments included 1 anterior segment, 3 posterior segments, 4 apical segments, and 2 superior segments in the right side; and 5 lingular segments, 3 trisegments, and 2 superior segments in the left side. Simultaneously, 3 patients with bronchiectasis underwent segmentectomy and lobectomy, 1 of 6 patients with adenocarcinoma underwent lingulectomy and thymectomy. The pathological TNM stages of 12 NSCLC patients were 9 cases of T1aN0M0, 1 case of T1bN0M0 and 2 cases of T2aN0M0. Of these 20 patients, the median operative time was 155 minutes (range, 120 to 235 minutes), the median blood loss was 50 ml (range, 10 to 600 ml), the median drainage duration was 3 d (range, 1 to 6 d), and the median hospital stay was 6 d (range, 3 to 9 d). One patient who had undergone lingulectomy had a 600 ml intraoperative bleeding from lingular artery, and the bleeding was controlled by suturing the rupture under VATS. Bloody sputum occurred in 2 patients, prolonged air leak occurred in one patient for 5 days, and one patient developed subcutaneous emphysema that spontaneously resolved. No mortality was observed for 30 days after the surgery. VATS anatomic segmentectomy is a feasible and safe technique with acceptable operative time, less blood loss, fewer complications, and shorter hospital stay.

Differentially expressed genes between pure bronchioloalveolar carcinoma and pure bronchioloalveolar carcinoma features by genechip

Objective To investigate the genetic differences between pure bronchioloalveolar carcinoma (BAC) and invasive mixed type adenocarcinoma with BAC features (AWBF) and to explore the molecular mechanism of pure BAC progression.Methods Total RNA was extract froml6 lung tissue specimens,includig 8 cases of BAC and 8 cases of AWBF.The BAC and AWBF were analyzed for gene expression profiles using the Agiilent 4 * 44K arrays.Differentially expressed candidate genes were validated using quantitative real-time polymerase chain reaction (PCR).The SPSS software was used for the analysis.Two-sided values of P were given,and statistical signifcance was set at P ＜ 0.01.Results We selected 43 genes correlated with tumor progression and metastasis.A total of 23 genes were significantly higher in the AWBF and 20 genes were lower.Of the 43 validated genes,CLDN18 and ATF-2 were found to have ＞ 10 fold higher expression in AWBF (P ＜0.01 ) than in BAC.Conclusion CLDN18 and ATF-2 may be related with the progression of BAC to AWBF.Furthermore,targeting these genes may be a promising way for AWBF treatment. Key words: Bronchioloalveolar carcinoma; Differentially expresse ; Genes expression

肺炎治療後の浸潤影で発見された細気管支肺胞上皮癌の1例

肺炎治療後の浸潤影で発見された細気管支肺胞上皮癌の1例

Different efficacy of CT screening for lung cancer according to histological type: Analysis of Japanese-smoker cases detected using a low-dose CT screen

The efficacy of CT screening for lung cancers is still a controversial issue, although one of the recently publicized large randomized controlled trials of this methodology, the National Lung Screening Trial (NLST), reported a decrease in the lung cancer-specific mortality for heavy smokers. We here performed case-matched comparative analyses, as a retrospective study, of three lung cancer arms detected by CT screen, X-ray screen, and by individual analysis of the clinicopathological features and outcomes in smokers from a symptomatic-prompted group of patients. We also considered the impacts of various potential biases in this cohort. The total study cohort comprised 136 patients in the CT screen group, 263 in the X-ray screen group and 254 in the symptomatic-prompted group. The ratio of stage IA cancers in the CT screen group was 67.7% and the ratio of advanced cases (i.e. stages IIIB+IV) was 12.5%. The percentage of bronchioloalveolar carcinoma (BAC) was 28.7% in the CT screen group. The 5-year survival rates were 82.4% in the CT screen group, 38.0% in the X-ray screen group and 17.8% in the symptomatic-prompted group. CT screening was found to be an independent prognostic factor for lung cancer even when BAC cases were eliminated (HR 0.35, P<0.01). Based on our sub-analysis by individual histological sub-type, CT screen lung cancer cases had a better survival rate than non-screened patients, which included adenocarcinoma, squamous cell carcinoma and large/small cell carcinoma. However, by multi-variant analysis a CT scan would not be expected to reduce the risk of lung cancer mortality in patients with large/small cell carcinoma, although would be expected to reduce the risk of lung cancer death by 80% in cases of both adenocarcinoma and squamous cell carcinoma. In conclusion, our current findings indicate that CT screening for lung cancer is an effective strategy for smokers and that patients with adenocarcinoma and squamous cell carcinoma of all variant histological types may benefit from this test. In this regard, early stage large/small cell carcinomas are insufficiently detected by the existing annual screening system.

The diagnosis and differential diagnosis of the pneumonia-lung cancer

Objective To investigate the diagnosis and differential diagnosis of the pneumonia-lung cancer. Methods The clinical, radiological and pathological findings of 32 case of pneumonia-lung cancer were retrospective analysis. Results There were of cough and sputum in 30 cases, fever in 20 cases, Chest tightness and shortness of breath in 14 cases,and 2 cases of no obvious symptoms. The tumor size was 2.1～11.7cm. There were 24 cases of peripheral lung, 8 cases in hilar. There were 16 cases of bronchioloalveolar carcinoma, adenocarcinoma 12 cases, 2 cases of adenosquamous carcinoma, small cell carcinoma in 2 cases. Conclusion pneumonia-lung cancers often lie in the peripheral lung, and often misdiagnosed as pneumonia. Bronchioloalveolar carcinoma and adenocarcinoma were more common. The treatment is mainly surgery and anti-inflammatory treatment is no benefit. Key words: Pneumonia-lung cance; Diagnosis; Differential diagnosis; Clinical

Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO).

BackgroundThe International Lung Cancer Consortium (ILCCO) was established in 2004, based on the collaboration of research groups leading large molecular epidemiology studies of lung cancer that are ongoing or have been recently completed. This framework offered the opportunity to investigate the role of tobacco smoking in the development of bronchioloalveolar carcinoma (BAC), a rare form of lung cancer.MethodsOur pooled data comprised seven case–control studies from the United States, with detailed information on tobacco smoking and histology, which contributed 799 cases of BAC and 15,859 controls. We estimated the odds ratio of BAC for tobacco smoking, using never smokers as a referent category, after adjustment for age, sex, race, and study center.ResultsThe odds ratio of BAC for ever smoking was 2.47 (95% confidence interval [CI] 2.08, 2.93); the risk increased linearly with duration, amount, and cumulative cigarette smoking and persisted long after smoking cessation. The proportion of BAC cases attributable to smoking was 0.47 (95% CI 0.39, 0.54).ConclusionsThis analysis provides a precise estimate of the risk of BAC for tobacco smoking.

Clinical Features of Bronchioloalveolar Carcinoma with New Histologic and Staging Definitions

To assess clinical features of bronchioloalveolar carcinoma (BAC) based on the 1999 World Health Organization Classification ("pure BAC"), compare patients with pure BAC with patients previously diagnosed as BAC not meeting the 1999 definition, and compare survival changes of pure BAC based on the old and new (2009) staging systems. A pulmonary pathologist reviewed each BAC tumor diagnosed between January 1, 1997, and December 31, 2007, identifying cases meeting the new criteria. Cases were restaged according to the seventh edition of the tumor, node, metastasis classification introduced in 2009. Patients with pure BAC were analyzed under both staging systems for changes in overall survival estimation. Of 338 total patients who were diagnosed with BAC, 117 were classified as pure and 221 were non-pure BAC. Seventy-eight of the 117 and 178 of the 221 had no other primary lung cancer. One-year and 5-year survival for the 78 patients with pure BAC were 94.8 and 83.5%, and for the 178 patients were 92.6 and 46.4%, respectively. Restaging for pure BAC cases resulted in nine of the 78 cases (12%) changing stage. Compared with the old staging, patients with advanced stage under the new stage had a worse 5-year survival (53% versus 45%), but no change was observed for stage IA. For patients with pure BAC, the new pathologic system favorably affects survival and the new staging system may more accurately reflect prognosis in advanced stage cancer. Our results have important implications for researchers, clinicians, and patients.

Reply to Promoter methylation of glutathione S‒transferase π1 and multidrug resistance gene 1 in bronchioloalveolar carcinoma and its correlation with DNA methyltransferase 1 expression

It is our great pleasure to reply to the comments from Garfield et al regarding our recent article.1 In our study, bronchioloalveolar carcinoma (BAC) samples were reviewed by 2 pathologists. Determination of BAC was performed according to the 2004 World Health Organization (WHO) Classification of Lung Tumors. The cases demonstrated growth of tumor cells along alveolar structures with no evidence of stromal, vascular, or pleural invasion. The presence of lymph node metastasis was not considered as a criterion to exclude a diagnosis of BAC, because both the 1999 and 2004 WHO classifications did not address lymph node metastases specifically in the description of BAC. In fact, other investigators also reported lymph node involvement in patients with BAC. Varlotto et al reported that, of a total of 4303 patients with BAC, 408 and 216, respectively, were classified as having N1 disease and N2 disease, with 16.6% and 50%, respectively, of examined lymph nodes determined to be positive metastatic ones.2 The Surveillance, Epidemiology, and End Results (SEER) database demonstrated that 9.5% and 6.4% of patients with BAC, respectively, had N1 disease and N2 disease.3 Furthermore, a positive rate of lymph node metastasis might differ between races, and be significantly more common in patients of nonblack/nonwhite race.2 The study focused on the prognostic values of glutathione S‒transferase π1 (GSTP1), multidrug resistance gene 1 (MDR1) promoter methylation, and methyltransferase 1 (DNMT1) protein expression for patients with BAC. The histological subtype of BAC, nonmucinous (NM) versus mucinous (M), was reported by some investigators to be associated with patient prognosis. However, to the best of our knowledge, its prognostic value is controversial. The M type of BAC tends to present with multifocal or higher stage of disease. Therefore, other investigators believe that its clinical pattern (solitary or multifocal) and disease stage, rather than histological subtype, are predictive of patient prognosis.4 The BAC cases in our study were comprised of 23 cases of the NM subtype and 13 cases of the M subtype. When the histological subtype of BAC was analyzed in combination with patient survival, no significant association was found (P >.05). Therefore, the prognostic significance of GSTP1 promoter methylation and DNMT1 protein expression appear to be independent of histological subtype.

The Importance of Distinguishing Mucinous and Nonmucinous Bronchioloalveolar Carcinomas

It was with some surprise and dismay that we noted the recent paper in your journal, ‘‘Expression of FAK and PTEN in bronchioloalveolar carcinoma and lung adenocarcinoma,’’ [1] did not distinguish between the two subtypes of bronchioloalveolar carcinoma (BAC) nodules— mucinous (M) and nonmucinous (NM)—which are welldescribed in the most recent 2004 lung cancer classification [2]. The more frequent BAC is NM, reported in up to 50% of cases. M is reported in 25–50% [2–4], although these percentages may not be the same in patients from East Asia. Rarely there is a combination of both. Now there is increasing evidence that M and NM represent two separate disease entities [3–8], so it is important to distinguish them, especially in resected cases. Although it is difficult, if not impossible, to distinguish the two preoperatively, CT findings may be suggestive. Of the 77 BAC cases described in your study, 27 (35%) demonstrated an air bronchogram, seen more often in M in the most recent study [9]. Also, what is described in the study as ‘‘cavitation,’’ rare in BAC, perhaps is the same as ‘‘pseudocavitation,’’ although only noted in 6 of 77 (8%), is seen more often in M nodules (\3.0 cm; P 0.01) [9]. Therefore, as many as 33 of 77 (43%) BAC nodules could have been M-BAC in this study. Because NM-BAC seems driven more by the epidermal growth factor receptor (EGFR) pathway, whereas M-BAC is driven by mutations of K-ras, a potent oncogene [7], it might be informative to determine where PTEN (phosphate and tensin homolog), a tumor-suppressor gene regulating apoptosis, and FAK (focal adhesion molecule), a cell migration and differentiation molecule, are involved in M and NM in these 77 resected BAC cases. In fact, such results may be more robust. Clearly, much more needs to be known about these two apparently separate entities.

Targeted therapies in bronchioloalveolar carcinoma

Bronchioloalveolar carcinoma (BAC) is a subtype of adenocarcinoma with unique epidemiology, pathology, clinical features, radiographic presentation, and natural history compared with other non-small cell lung cancer (NSCLC) subtypes. According to criteria of the revised 2004 World Health Organization classification it accounts for only 5% of all cases of NSCLC. BAC cases are mostly represented by females and non-smokers and are diagnosed at a younger age. Patients with resected BAC have prolonged survival and a lower recurrence rate after surgical resection than other NSCLC subtypes. In advanced BAC cytotoxic chemotherapy seems as effective as in other NSCLC, although studies on pure BAC are based on small numbers of patients and mainly tested paclitaxel based regimens on preclinical activity on cell lines. A higher than expected response rate to the epidermal growth factor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib was recorded in BAC or in adenocarcinomas with BAC features compared with other NSCLC subtypes, mainly due to a higher rate of never-smoking patients. In fact, these agents demonstrated activity in the first-line setting especially in patients harboring EGFR mutations. The role of molecular predictors of response and survival such as EGFR gene amplification or EGFR mutations is an open field of research in fine-tuning BAC management. New drugs are being tested in advanced BAC, while more prospective data must be collected on predictive and prognostic factors.

Lung Transplantation: Bronchogenic Carcinoma in the Native Lung

In lung transplantation, the presence of bronchogenic carcinoma in the native organ is uncommon, but doubtless affects patient survival, independently of the transplantation process itself. We describe 2 cases in which a primary tumor was found in the explanted lung--1 case of adenocarcinoma in a patient with pulmonary emphysema and 1 case of bronchioloalveolar carcinoma in a patient with idiopathic pulmonary fibrosis. Both patients died due to the recurrence of the neoplastic disease. Distant metastasis was the initial manifestation of the recurrence.

Prognostic significance of clinical factors and Akt activation in patients with bronchioloalveolar carcinoma

Lung cancer is the leading cause of cancer related mortality in the world. Bronchioloalveolar carcinoma (BAC) is a subset of NSCLC that has recently gained attention because of distinct biological and clinical features, increased incidence, and enhanced responsiveness to new therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, prognostic features for BAC have not been well defined. Because activation of Akt is highly prevalent and a poor prognostic factor for other types of NSCLC, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Forty-six cases of BAC in Iceland were classified according to WHO 1999 criteria. Akt activation was assessed using two phospho-specific antibodies against Akt (S473 and T308) in immunohistochemical (IHC) analysis. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method and log-rank test, with hazard ratios (HR) determined by Cox proportional hazard models. The Cox model was also used to assess the joint effect of multiple factors on survival when they are considered simultaneously. Age and histology (mucinous versus non-mucinous) were not associated with survival. Activation of Akt was highly prevalent in BAC, with only 2 out of 46 patients exhibiting negative staining with either antibody. Moderate to high Akt activation was observed in 63% of cases and was associated with non-mucinous histology. Akt activation was not associated with differences in survival or smoking status. In contrast, Cox model analysis revealed that male gender (HR 2.24, 95% CI, 1.07-4.71, p=0.032), advanced stage (III or IV) (HR 2.17, 95% CI, 1.004-4.71, p=0.049) and smoking status (HR 6.89, 95% CI, 1.49-31.88, p=0.013) were associated with a worse prognosis. Male gender, advanced stage, and especially smoking status (but not Akt activation) are potentially important prognostic features for BAC. These features should be considered in the design and interpretation of clinical trials that enroll BAC patients.

Multiple Lung Adenocarcinomas Showing Ground-Glass Opacities on Thoracic Computed Tomography

It is difficult to distinguish multiple primary lung cancers from pulmonary metastasis. We experienced a case of surgically resected lung tumors that showed multiple ground-glass opacities on thoracic computed tomographic scan. There were eight nonsolid and two part-solid ground-glass opacities in the bilateral lungs. Surgical resection was performed because all tumors had a ground-glass opacity appearance on computed tomographic scan, which is compatible with a finding of primary lung adenocarcinoma. The postoperative pathologic diagnoses were two cases of invasive adenocarcinoma, six cases of bronchioloalveolar carcinoma, and eight cases of atypical adenomatous hyperplasia. The patient remains alive without any evidence of recurrence 40 months after surgery. A ground-glass opacity appearance on computed tomographic scan could be interpreted as supportive evidence for multiple primary lung adenocarcinoma rather than pulmonary metastases.

Long-term survival differences for bronchiolo-alveolar carcinoma patients with ipsilateral intrapulmonary metastasis at diagnosis

Background: It has been suggested that the current staging system does not accurately reflect survival outcomes for advanced bronchiolo-alveolar carcinoma (BAC) patients.Methods: We conducted a case-only analysis of US Surveillance, Epidemiology, and End Results (SEER) data (1998–2002). Overall survival (OS) and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios.Results: 2345 incident cases of BAC were analyzed, including 707 patients with stage IIIB or IV BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n = 93) had significantly improved median OS (46m) and LCSS (>58m) compared to other stage IIIB BAC patients (n = 111; OS = 9m, P < 0.0001; LCSS = 10m, P < 0.0001). Among stage IV BAC patients, those with intrapulmonary metastasis (n = 278) had significantly improved median OS (13m) and LCSS (15m) compared to those with distant metastasis (n = 225; OS = 7m, P < 0.0001; LCSS = 7m, P = 0.0001). These survival differences persisted after adjustment for age, gender, ethnicity, and surgical treatment status.Conclusions: Among stage IIIB and IV BAC patients, those presenting with ipsilateral intrapulmonary metastasis have improved survival outcomes. Our results add further support for modification to the current staging system for BAC.

A clinicopathological study of resected pulmonary nodules with focal pure ground-glass opacity

Pulmonary lesions with focal ground-glass opacity (GGO) have been detected increasingly by low-dose helical computed tomography (CT). However, the strategy of treatment for focal pure GGO lesions is still undecided. This study evaluates clinicopathological characteristics of resected pulmonary nodules with focal pure ground-glass opacity. Between January 1997 and December 2005, 26 patients (35 lesions) with pure GGO lesions underwent pulmonary resection. The data on patient age, lesion size, pathology, carcinoembryonic antigen (CEA) level and palpability of the tumor in the resected specimen were evaluated. The histological diagnosis was bronchioloalveolar carcinoma (BAC) in 10 patients (12 lesions), atypical adenomatous hyperplasia (AAH) in 15 patients (22 lesions), and focal scar in 1 patient (1 lesion). There were no significant differences in age, sex, tumor size, and CEA level between the patients with BAC, AAH, and focal scar. However, the lesions >10mm in size were all BAC. Palpability of the tumor in the resected specimen was significantly more frequent in BAC cases than in AAH cases (p<0.01). For BAC, lobectomy was performed for four lesions, and limited resection for eight. None of the BACs showed lymphatic or vascular invasion upon pathological examination. At the median follow-up point of 44 months (range: 4-84 months), no recurrences were observed. BAC and AAH cannot be discriminated by their size. In the resected specimen, BAC lesions are more frequently palpable than AAH lesions. Thoracoscopic surgery is recommended for focal pure GGO after repeated CT even if the GGO lesion is small. Partial resection is a sufficient treatment for pure GGO.

Multiple Pulmonary Nodules in an Elderly Woman

72-year-old woman presented to the outpatient department with a 2-month history of a nonproductive cough and a 5-lb weight loss. She was a lifelong nonsmoker. Her physical examination was unremarkable. Chest radiography revealed multiple bilateral ill-defined nodules with multifocal right lung alveolar infiltrates (Fig. 1). A chest computed tomography scan after the administration of intravenous contrast showed multiple noncalcified nodules of varying size throughout both lungs, as well as alveolar infiltrates scattered throughout the right lung (Fig. 2A–C). Bronchoscopic lung biopsy samples of the right lower and right upper lobes showed adenocarcinoma with bronchioloalveolar features. Bronchioloalveolar carcinoma (BAC) is a subset of pulmonary adenocarcinoma with several unique features. It accounts for 4% of all non-small cell lung cancer, although its incidence is rising. 1 In sharp contrast to other forms of non-small cell lung cancer, women make up slightly more than half of BAC cases 1 and lifelong nonsmokers represent as many as one third of patients. 2,3 Not uncommonly, asymptomatic patients are discovered on routine chest radiography. The radiographic presentation of BAC fits one of three patterns: consolidation of one or more segments or lobes (37%–55% of the time); a solitary pulmonary nodule or mass (38% of the time), or multiple pulmonary nodules (7%–25% of the time). 2,4 Our patient’s radiographic evaluation demon

Prognostic significance of clinical features and Akt activation in the survival of patients with bronchioloalveolar carcinoma (BAC)

7217 Background: Lung cancer is the leading cause of cancer related mortality in the world. BAC is a subset of NSCLC that has recently gained attention because of enhanced efficacy of epidermal growth factor receptor (EGFR) inhibitors in this population. Prognostic features for BAC have not been well defined. Because activation of Akt is a poor prognostic factor for other types of NSCLC, and because changes in Akt may predict outcome for EGFR inhibitors, we assessed the prognostic significance of clinical features and Akt activation in patients with BAC. Methods: 46 cases of BAC were classified according to WHO 2001 criteria. Akt activation was assessed using immunohistochemistry. Associations between ordered Akt levels and other dichotomous parameters were evaluated using an exact Cochran-Armitage test for trend. Survival was analyzed by the Kaplan-Meier method, and hazard ratios (HR) were determined based on Cox proportional hazard models. Results: Tissues from 45 patients were analyzed. Age and histology (mucinous vs. non-mucinous) were not associated with survival. Akt activation was observed in 63% of cases, but was not associated with differences in survival. Complete clinical data (except smoking) were available for 43 patients, and smoking history was available for 31 patients (8 never-smokers, 23 smokers). Cox model analysis revealed that male gender (HR 2.24, 95% CI 1.07–4.71, p = 0.032) and advanced stage (III or IV) (HR 2.17, 95% CI 1.004–4.71, p = 0.049) were associated with a worse prognosis. A model limited only to the 31 patients with smoking data demonstrated that smoking alone (HR 6.89, 95% CI 1.49–31.88, p = 0.013) was associated with a worse prognosis. Conclusions: These studies identify gender, stage, and especially smoking status as potentially important prognostic features for BAC. Akt was not prognostic. Given that the recent NSCLC clinical trials with erlotinib and gefitinib that showed varying survival benefit did not stratify by smoking status and BAC, it is possible that these characteristics could have affected the clinical outcomes. Investigators studying EGFR inhibitors should consider stratifying by smoking status and BAC to determine if there are subsets of patients who could benefit most from these therapies. No significant financial relationships to disclose.

Long-term survival differences for bronchioloalveolar carcinoma (BAC) patients with ipsilateral intrapulmonary metastasis at diagnosis

7207 Background: It has been suggested that survival for BAC patients with stage IIIB disease due to multiple lesions in the same lobe is improved over other stage IIIB patients, and that patients with multicentric BAC have improved survival over BAC patients with distant metastasis. To determine the prognostic implications of these various subsets of advanced stage BAC patients, we compared survival rates using a large population-based cohort. Methods: A case-only analysis of data from the U.S. SEER database during 1998–2002 was conducted. The primary outcome measured was overall survival (OS). OS and lung cancer-specific survival (LCSS) univariate analyses were conducted using the Kaplan-Meier method; multivariate survival analyses were performed using Cox proportional hazards ratios. Results: 2653 incident cases of BAC were analyzed with a 5-year follow-up duration, including 831 patients with advanced (i.e. stage IIIB or IV) BAC. Patients with stage IIIB BAC due to multiple lesions in the same lobe (n = 96) had significantly improved median OS (46 months) and LCSS (not reached at &gt;58 months) compared to other stage IIIB BAC patients on univariate analysis (n = 133; OS = 8 months, LCSS = 9 months) (P &lt; 0.0001). Stage IV BAC patients with intrapulmonary metastasis (n = 320) had significantly improved median OS (13 months) and LCSS (15 months) compared to those with stage IV BAC due to distant spread on univariate analysis (n = 282; OS = 7 months, LCSS = 7 months) (P &lt; 0.0001). These observed survival differences remained after adjustment for age, gender, ethnicity, and surgical treatment status (Table). Conclusions: Patients with stage IIIB BAC due to tumors in the same lobe have significantly better outcomes than other stage IIIB BAC patients. Stage IV BAC patients due to intrapulmonary spread have significantly improved outcomes over stage IV BAC patients with distant metastasis. These results add further support for modification to the current NSCLC staging system. [Table: see text] No significant financial relationships to disclose.

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung

Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM). The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung. The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity. In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.