Primary tumors of the lung are uncommon in pediatric patients, particularly bronchioloalveolar carcinoma (BAC). An 11-year-old female suffering from back pain for 1 month was referred to Seoul St. Mary's Hospital for treatment of a pathologic fracture of the lumbar spine. Comprehensive evaluation disclosed numerous pulmonary metastases of rhabdomyosarcoma (stage IV). During chemotherapy, most of the lung lesions regressed, with the exception of two nodules. Wedge resections, intended for diagnosis and cure, yielded a histologic diagnosis of BAC.
Adenocarcinoma, Bronchiolo-Alveolar* ; Back Pain ; Child ; Diagnosis ; Drug Therapy ; Female ; Fractures, Spontaneous ; Humans ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Rhabdomyosarcoma ; Seoul ; Spine

OBJECTIVETo study the relationship between Chinese medical syndrome types of bronchioloalveolar carcinoma (BAC) and Th1/Th2.

METHODSTotally 60 BAC patients were syndrome typed as qi and yin deficiency syndrome (QYDS) and qi stagnation and phlegm-blood stasis syndrome (QSPSS), 30 cases in each group. Meanwhile, 30 subjects with benign pulmonary nodules were recruited as the control group. The contents of interferon-gamma (INF-gamma), interleukin 4 (IL-4), IL-2, and IL-5 were detected using thoracoscopic technique.

RESULTSAs for Th1 (INF-gamma and IL-2), it was ranked from high to low as the control group > the QSPSS group > the QYDS group (P < 0.05). As for Th2 (IL-4 and IL-5), it was ranked from high to low as the QYDS group > the QSPSS group >the control group (P < 0.05). As for Th1/Th2 (INF-gamma/lL-4, IL-2/IL-5), it was ranked from high to low as the control group > the QSPSS group >the QYDS group (P < 0.05).

CONCLUSIONSCompared with the tissue of benign nodules, Th1 function in tumor tissue of BAC patients was weaker and Th2 function stronger. Chinese medical syndrome types of BAC had correlation with Th1/Th2. Patients of excess syndrome had stronger immunity with Th1/Th2 shifting left,while those of deficiency syndrome were predispose to humoral immunity with Thl/Th2 shifting right.

Adenocarcinoma, Bronchiolo-Alveolar ; diagnosis ; immunology ; pathology ; Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; diagnosis ; immunology ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology

PURPOSE: This study was conducted in order to investigate the significance of transforming growth factor beta1 (TGFbeta1) and E-cadherin proteins in tumor progression of lung adenocarcinoma and to evaluate their differential expression in association with morphologic characteristics. MATERIALS AND METHODS: A total of 65 pulmonary adenocarcinomas were reclassified according to the new classification system proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar carcinoma [BAC]), 9 minimally invasive adenocarcinomas (MIA, formerly BAC with < or = 5 mm invasion), 17 lepidic predominant adenocarcinomas (LPA, formerly mixed adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19 invasive adenocarcinomas with no BAC features were analyzed by immunohistochemistry for expression of TGFbeta1 and E-cadherin proteins. RESULTS: TGFbeta1 expression was detected in 46% (21/46) of noninvasive elements and 87% (39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent in invasive components than in noninvasive components (38% vs. 65%, p=0.009). Negative correlation was identified between TGFbeta1 expression and E-cadherin expression in noninvasive elements (p=0.022). More importantly, significantly higher frequency of TGFbeta1 expression was observed in noninvasive components of LPA (14/17, 82%), compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%) (p=0.008). CONCLUSION: Our data indicate involvement of both TGFbeta1 and E-cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is noteworthy that TGFbeta1 up-regulation precedes alveolar destruction by invasion of tumor cells. TGFbeta1 may thus have the potential to improve lung adenocarcinoma diagnostics and therapeutics.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Cadherins ; Immunohistochemistry ; Lung ; Lung Neoplasms ; Proteins ; Transforming Growth Factor beta1 ; Transforming Growth Factors ; Up-Regulation

Atypical adenomatous hyperplasia (AAH) has been considered to be a precursor lesion of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma. It usually coexists with BAC and/or an adenocarcinoma. Chest computed tomography reveals multiple well-defined nodules with ground-glass opacity. Usually, AAH does not exceed 10 mm in size. AAH with extensive involvement on one side of the lung field or one that is larger than 2 cm has not been previously reported. We herein report a case of a 71-year-old nonsmoking female with lung AAH of larger than 2 cm.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Female ; Humans ; Hyperplasia ; Lung ; Precancerous Conditions ; Thorax

OBJECTIVETo assess the relationship between preoperative maximum standardized uptake value (SUVmax) measured on (18)F-FDG PET-CT and clinicopathologic parameters in patients with surgically resected non-small cell lung cancer (NSCLC).

METHODSA total of 540 patients (348 men and 192 women, mean age 60 ± 10 years) with histologically proven non-small cell lung cancer, who had undergone both preoperative (18)F-FDG PET-CT imaging and curative surgery in our institution from October 2006 to January 2013, were analyzed retrospectively in this study. Primary tumor (18)F-FDG uptake, measured as SUVmax corrected for lean body mass, was compared among different variables and correlated with tumor size, histologic grade and postoperative pathologic TNM stage. Histologic grade was categorized into three degrees, where grade I represents highly, grade II moderately and grade III poorly differentiated. Large cell carcinomas were all assessed as poorly differentiated (grade III). Pathologic stage was assigned according to the seventh AJCC TNM staging system.

RESULTSThere were 344 adenocarcinomas (AC, non- BAC type), 146 squamous cell carcinomas (SCC), 28 bronchioloalveolar carcinomas (BAC), 10 adenosquamous carcinomas (ASC) and 12 other type carcinomas (OTC, including 6 large cell carcinomas, 5 sarcomatoid carcinomas and 1 lymphoepitheloid carcinoma); the SUVmax in ascending order was BAC (1.3 ± 1.1), AC (5.1 ± 3.4), ASC (8.5 ± 2.8), SCC (9.9 ± 4.6) and OTC (10.9 ± 5.1), respectively. There were 76 grade I, 251 grade II and 213 grade III; the SUVmax in ascending order was grade I (2.4 ± 2.2), grade II(5.9 ± 3.9), grade III (8.4 ± 4.4), respectively, and significant difference was identified among grade I, grade II and grade III (all P < 0.01). The SUV max was positively correlated with tumor size (r = 0.564, P < 0.01), histologic grade (r = 0.492, P < 0.01), T stage (r = 0.306, P < 0.01), N stage (r = 0.368, P < 0.01), and TNM stage (r = 0.437, P < 0.01).

CONCLUSIONSThe preoperative SUV max of the primary tumor differed significantly among histologic types in NSCLC. There were positive correlations between SUV max and tumor size, histologic grade and pathologic stage. Our findings may suggest that a high SUVmax could be used to identify a high-risk population who would benefit most from adjuvant therapies.

Adenocarcinoma ; diagnosis ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; diagnosis ; pathology ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed ; Tumor Burden

OBJECTIVETo assess the value of (18)F-FDG PET/CT in the diagnosis of solitary nodular-type bronchoalveolar carcinoma (BAC).

METHODSThe clinical and radiographic data were analyzed retrospectively in 30 patients with pathologically confirmed solitary nodular-type BAC who underwent (18)F-FDG PET/CT examinations between August, 2005 and December, 2006. The morphological and radioactive findings of the lesions were reviewed, and the maximum standard uptake values (SUVmax) were measured. The diagnostic accuracy of PET, PET/CT, and HRCT were analyzed.

RESULTSThe (18)F-FDG SUV was markedly lower in BAC than in other well differentiated adenocarcinoma. In 19 of the BAC cases, PET showed a SUVmax of no less than 2.5, demonstrating positive changes. Of the total of 30 cases, 5 had ground glass opacity (GGO) changes, 3 exhibited mixed nodules with GGO changes around the lesions, and 22 cases presented with solid nodules. HRCT showed that BAC located often in the superior lobes of the bilateral lungs, mostly below the pleura in the surrounding lung field; the lesions were patchy or nodular with irregular shapes, showing lobulation in 22 cases, spiculation in 15 cases, pleural indentation in 21 cases, and vacuolar changes in 4 cases. The diagnostic accuracy of PET, PET/CT and HRCT for solitary nodular-type BAC was 36.67%, 93.33%, and 93.33%, respectively.

CONCLUSIONThe SUVmax of BAC provides only limited value for defining the nature of the lesions, but can serve as a general reference for assessing the disease activity. PET/CT, which allows both functional and imaging assessment, can be a valuable modality to reduce the misdiagnosis rate of BAC.

Adenocarcinoma, Bronchiolo-Alveolar ; diagnostic imaging ; Adult ; Aged ; Female ; Fluorodeoxyglucose F18 ; Humans ; Lung Neoplasms ; diagnostic imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed

PURPOSE: There is evidence supporting the concept of tumor progression from pulmonary adenocarcinoma in situ (formerly bronchioloalveolar carcinoma, BAC) to adenocarcinoma with varying degrees of invasion. The aim of this study was to investigate the role of transforming growth factor beta1 (TGFbeta1) in tumor invasiveness in lung adenocarcinoma, and to determine the potential relationships between its expression and immunophenotypes of cell adhesion molecules. MATERIALS AND METHODS: Tumor samples from adenocarcinoma in situ (n=13), minimally invasive adenocarcinoma (formerly BAC with < or =5 mm invasion, n=2), and lepidic predominant invasive adenocarcinoma (formerly mixed adenocarcinoma showing non-mucinous BAC features with >5 mm invasion, n=25) were examined for the expression of TGFbeta1, E-cadherin, N-cadherin, and H-cadherin proteins using immunohistochemistry. RESULTS: Of a total of 40 cases, 25 (63%) were positive for TGFbeta1. The frequency of immunoreactivity in patients with adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma was 23% (3/13), 50% (1/2), and 84% (21/25), respectively (p=0.001). TGFbeta1 correlated with T classification (p=0.006) and stage (p=0.001). Loss of E-cadherin expression was more frequently observed in invasive adenocarcinomas than in adenocarcinomas in situ (p=0.034). E-cadherin expression inversely correlated with T classification (p=0.009). TGFbeta1 expression showed a statistically significant correlation with H-cadherin expression (p=0.040), but not with E-cadherin expression (p=0.752). CONCLUSION: These results suggest that TGFbeta1 and E-cadherin may play an important role in invasive progression of lung adenocarcinoma through regulating epithelial-to-mesenchymal transition.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Cadherins ; Cell Adhesion ; Humans ; Lung ; Lung Neoplasms ; Proteins ; Transforming Growth Factor beta1 ; Transforming Growth Factors

BACKGROUND: The aims of the study were to determine the accuracy of fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting pulmonary metastasis through video-assisted thoracoscopic surgery (VATS), a technique that allows the excisional biopsy of small pulmonary nodules in patients with known malignancies. MATERIALS AND METHODS: Between October 2007 and April 2010, 28 patients with known malignancies and small pulmonary nodules underwent VATS excisional biopsies. All patients were in follow-up for a previously treated malignancy. The malignancies included the following: colorectum (9), breast (6), head and neck (5), stomach (3), lymph (1), ovary (1), uterus (1), bladder (1), and liver (1). RESULTS: There were 16 men and 12 women whose mean age was 56.7 years old (range, 38 to 77 years). The sizes of the mean nodules removed were 11.3 mm (range, 7 to 21 mm). Diagnoses included metastatic (11), bronchioloalveolar carcinoma (1), primary adenocarcinoma (1), pulmonary tuberculosis (6), fibrosis (5), organizing pneumonia (3), lymphoid hyperplasia (1). Among these lesions, 46.4% were malignant. CONCLUSION: True positive FDG-PET was 39.2%. FDG-PET is not a sensitive test in the evaluation of patients with a history of an extrathoracic malignancy and newly diagnosed small pulmonary nodules. VATS excision allows the early diagnosis of small pulmonary nodules, with low morbidity, in patients with known malignancies.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Biopsy ; Breast ; Early Diagnosis ; Electrons ; Female ; Fibrosis ; Follow-Up Studies ; Head ; Humans ; Hyperplasia ; Liver ; Male ; Neck ; Neoplasm Metastasis ; Ovary ; Pneumonia ; Positron-Emission Tomography ; Stomach ; Thoracic Surgery, Video-Assisted ; Tuberculosis, Pulmonary ; Urinary Bladder ; Uterus

OBJECTIVETo investigate the gene mutation of EGFR and KRAS in Chinese patients with non-small cell lung cancer (NSCLC), and to analyze the relationship between the gene mutations and the clinicopathological features and EGFR-TKI efficiency.

METHODSEGFR mutation was detected in 120 patients and KRAS mutation in 104 patients with NSCLC in Peking Union Medical College Hospital from March 2009 to December 2010, and the correlation of the gene mutations with the clinicopathological features and EGFR-TKI efficiency was analyzed in the study.

RESULTSEGFR mutation was detected in 44 of 120 (36.7%) patients with NSCLC, in which three types of EGFR gene mutations were found: deletion in exon 19, exon 21 L858R (2573T > G) and Exon 21 L861Q (2582T > A) mutations. There were 29(24.2%) patients with EGFR exon 19 deletion, 14 (11.7%) patients with EGFR exon 21 L858R mutation and one (0.8%) with EGFR exon 21 L861Q mutation in the patients. All the mutations were single point mutations, and no multiple points mutations detected. EGFR mutation rate of bronchioloalveolar carcinoma and adenocarcinoma were higher than that of non-adenocarcinoma (P = 0.009). EGFR mutation rate was higher in female patients or patients without smoking history than male patients or patients with smoking history (P = 0.014, P = 0.001, respectively) in NSCLC patients. EGFR mutation rate was higher in patients without smoking history or patients with well-differentiated carcinoma than patients with smoking history or patients with moderately-and poorly-differentiated carcinoma (P = 0.008, P = 0.018, respectively). There was no difference in prognosis and EGFR-TKI treatment response rate between EGFR mutation patients and EGFR wild-type patients. Nine (8.7%) patients with KRAS mutation were detected in 104 NSCLC patients. There were four types of KRAS gene mutations detected: KRAS Gly12Ala (GGT > GCT), KRAS Gly12Arg (GGT > CGT), KRAS Gly12Val (GGT > GTT) and KRAS Gly12Cys (GGT > TGT). There were 4 patients with Cys mutation, 2 with Arg mutation, 2 with Val mutation and 1 with multiple points mutation of both Cys and Arg in exon 12. No relationship was found between KRAS mutation and clinicopathological feature either in NSCLC or in adenocarcinoma. Prognosis was worse in patients with KRAS mutation than in wild-type patients (P = 0.008). No patient with both EGFR and KRAS mutation was detected.

CONCLUSIONSEGFR mutation rate is related with gender, smoking history and pathological type in NSCLC patients, and is also related with differentiation and smoking history in adenocarcinoma patients. And prognosis is worse in patients with KRAS mutation than that with wild type.

Adenocarcinoma ; genetics ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; pathology ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Carcinoma, Squamous Cell ; genetics ; pathology ; Exons ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Staging ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; genetics ; Sex Factors ; Smoking ; Survival Rate ; ras Proteins ; genetics

Adenocarcinoma ; classification ; genetics ; pathology ; Adenocarcinoma, Bronchiolo-Alveolar ; genetics ; pathology ; Exons ; Humans ; Lung Neoplasms ; classification ; genetics ; pathology ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; genetics ; ras Proteins ; genetics