Yoshimasa Nakazato

Bronchioloalveolar carcinoma (lepidic growth) component is a more useful prognostic factor than lymph node metastasis.

Introduction: 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. Methods: 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, &ggr;H2AX, 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. Results: 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. Conclusion: 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.

Nuclear Grading of Primary Pulmonary Adenocarcinomas: Correlation Between Nuclear Size and Prognosis

According to the World Health Organization Classification of Tumors, the prognostic value of morphometric cytologic atypia has not been assessed in pulmonary adenocarcinoma.

Magnetic resonance imaging in peripheral lung adenocarcinoma: correlation with histopathologic features.

Objective Magnetic resonance imaging (MRI) with various technologic advancements has generally been used to elevate the accuracy of diagnosis for several malignant tumors. This study retrospectively evaluated the efficacy of newer MRI techniques for differentiating among the different types of invasiveness in lung adenocarcinoma by comparing the MRI findings with the pathologic findings. Materials and Methods From May 2005 to April 2007, 46 patients with lung adenocarcinoma measuring 3 cm or less across the greatest dimension underwent a surgical operation including preoperative MRI study in this hospital. The MR imaging protocol included 3 pulse sequences: (1) respiratory-triggered T2-weighted short TI inversion recovery; (2) respiratory-triggered high b-value diffusion-weighted imaging (DWI); (3) gadolinium-enhanced dynamic MRI studies. Results Of all the tumors, 13 were bronchioloalveolar carcinoma (BAC), 24 were adenocarcinomas with mixed subtypes (advanced BAC), and 9 were other histologic subtypes (non-BAC). Both the moderate and strong signal intensity on DWI was significantly greater in the advanced BAC (79.2%) and the non-BAC (88.9%) than in the BAC (38.5%). In the dynamic study, a strong enhancement on the time-intensity curve was significantly greater in the advanced BAC (95.2%) and the non-BAC (87.5%) than in the BAC (25%). When the lesions demonstrated a strong enhancement in dynamic study or showed strong signal intensity on DWI, they were judged to be positive. Sensitivity, specificity, and accuracy were 97%, 76.9%, and 91.3%, respectively. Conclusions DWI could therefore be a useful diagnostic modality for differentiating the subtypes of lung adenocarcinomas, and the MRI finding may thus provide useful supplementary information before surgery comprising limited resections.

Interobserver Agreement in the Nuclear Grading of Primary Pulmonary Adenocarcinoma

Introduction: Nuclear grading involves an evaluation of the size and shape of nuclei and the percentage of tumor cells that are in the mitotic phase. To estimate the degree of aggressiveness, this approach has been applied to various types of carcinomas, such as breast carcinoma and pulmonary adenocarcinoma (Nakazato et al.). In the present study, we estimated and evaluated the interobserver variability of nuclear grading in primary pulmonary adenocarcinomas. Methods: We selected 122 primary pulmonary adenocarcinomas measuring 2 cm or less in diameter. Eight pathologists independently evaluated the nuclear factors, using the nuclear grading system reported previously by Nakazato et al. The same pathologists also used both the international multidisciplinary classification of pulmonary adenocarcinoma (2011 International Association for the Study of Lung Cancer classification) and Noguchi’s classification, and assessed the extent of the lepidic pattern in the largest cut surface of the tumor. Interobserver agreement was evaluated using the &kgr; statistic. The disease-free survival curves of the patients were obtained using the Kaplan–Meier method and analyzed with the log-rank test. Results: The mean (±SD) &kgr; values for the two histological classifications, the extent of the lepidic pattern, and nuclear grading were 0.46 ± 0.09, 0.48 ± 0.09, 0.45 ± 0.16, and 0.58 ± 0.09, respectively. The cases judged as negative on the basis of nuclear grading showed a significantly better prognosis (5-year disease-free survival rate; 91.8% ± 2.7) than the positive cases did (68.6% ± 3.1). Conclusion: Nuclear grading is practical for prognostic evaluation of pulmonary adenocarcinoma. The interobserver agreement for nuclear grading is significantly higher than for histological classifications and the extent of the lepidic pattern. Nuclear grading is a reliable prognostic indicator for small adenocarcinomas.

Abnormality of the hepatocyte growth factor/MET pathway in pulmonary adenocarcinogenesis

BACKGROUND Signaling mediated by hepatocyte growth factor (HGF)/MET promotes multiple biological activities, including cell proliferation, motility, invasion, angiogenesis, and morphogenesis. Overexpression of HGF and MET and an increase of the MET gene copy number have recently been found in various cancers that had a poor outcome. Here we investigated the copy number of the MET gene and expression of MET and HGF in small pulmonary adenocarcinomas. METHODS Tumor tissues were obtained from 106 pulmonary small adenocarcinomas 2 cm or less in diameter. MET gene copy number, and the expression of MET and HGF, were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry, respectively. RESULTS MET FISH-positive signals were observed in 11 (10.4%) of 106 cases. One case (0.9%) showed gene amplification and 10 (9.4%) exhibited high polysomy. High immunoreactivity for MET and HGF in tumor cells was found in 30 (28.3%) and 19 cases (17.9%), respectively. HGF was also expressed in stromal cells in 32 cases (30.2%). No cases of non-invasive adenocarcinoma (adenocarcinoma in situ, localized bronchioloalveolar carcinoma) showed MET FISH-positive signals or high expression of HGF in the tumor cells. Expression of both MET and stromal HGF was stronger in invasive than in non-invasive adenocarcinoma. MET FISH-positive signals and high immunoreactivity for MET and HGF in tumor cells were associated with factors indicative of poor prognosis such as pleural invasion, vascular invasion, lymphatic permeation, lymph node metastasis, and nuclear grading. Univariate and multivariate analyses that included these factors showed that all statuses except for MET and HGF immunoreactivity were significantly associated with an increased risk of death. However, multivariate analysis revealed no independent factors related to poor prognosis. CONCLUSION Our results suggest that abnormality of the HGF/MET pathway occurs during the course of progression from non-invasive to invasive pulmonary adenocarcinoma. An increased MET gene copy number is indicative of a poor outcome in patients with small pulmonary adenocarcinomas.

Lung Cancer Complicated with IgG4-related Disease of the Lung

Few have reported a concomitant malignant neoplasm with immunoglobulin G4 (IgG4)-related diseases. We describe a case of lung cancer and gastric cancer accompanied with IgG4-related disease. A 78-year-old man had an area of ground-glass opacity with central collapse in right upper lobe and a gastric cancer. The patient underwent a right upper lobectomy following a gastrectomy for the gastric cancer. Histological examination of the resected lung specimen revealed a lepidic pattern of an adenocarcinoma and a large amount of plasmacyte infiltration around the tumor. In immunohistochemical findings, the plasmacytes were stained for IgG4. Therefore, the lung tumor was considered to have associated with IgG4-related interstitial lesions.

Diffusion-weighted imaging and positron emission tomography in various cytological subtypes of primary lung adenocarcinoma

The purpose of the study was to retrospectively characterize diffusion-weighted magnetic resonance imaging (DWI) and positron emission tomography for differentiating among the various cytological subtypes of primary lung adenocarcinomas. The maximum diffusion signal intensities and the maximum standardized uptake value (SUV max) of 31 lesions were analyzed after delineation of regions of interest on the images. Diffusion intensities were 0.934 for Clara type, 0.938 for type II type, 1.473 for nongoblet type, and 1.617 for poorly differentiated adenocarcinoma type based on Shimosatos cytological classification (P=.020). The SUV max values were 4.926, 5.491, 5.709, and 12.132, respectively (P=.044). DWI might reflect some of the cytological characteristics of the tumor cells for differentiating the subtypes of lung adenocarcinomas.

Diffusion-weighted magnetic resonance imaging in differentiating the invasiveness of small lung adenocarcinoma.

Backgound Magnetic resonance imaging (MRI) with several sequences may provide a valuable additional modality for evaluating the grade of invasiveness lesions. Diffusion-weighted magnetic resonance imaging (DWI) represents the biological characteristics of tissues. Purpose To retrospectively evaluate the usefulness of DWI for evaluating the invasiveness of small lung adenocarcinomas. Material and Methods From May 2005 to June 2008, 46 patients with lung adenocarcinomas measuring 2 cm or less across the greatest dimension underwent a preoperative MRI study followed by surgery at the Gunma Prefectural Cancer Center. Fourteen of the tumors were bronchioloalveolar carcinomas (so-called Noguchis type A+B group), 26 were adenocarcinomas with mixed subtypes (type C group) and six were other histological subtypes of adenocarcinomas (type D+E+F group). The mean signal intensities of a lesion (DWI) and the spinal cord (SC) were analyzed in the region of interests (ROIs), and the mean DWI/SC ratio was then calculated with the value of DWI divided by the value of SC. Results The calculated mean DWI/SC ratio for the lesions were as follows: 0.448±0.261 (mean±standard deviation [SD]) for type A+B group, 0.963±0.465 for type C group, and 0.816±0.291 for type D+E+F group. The mean DWI/SC ratio of type A+B group was significantly lower than that for the type C (P = 0.0005) or type D+E+F groups (P = 0.0117). Conclusion DWI may thus provide useful supplementary information before determining the surgical strategy, including a limited resection.

Partial anomalous pulmonary venous connection in right lung cancer: Report of a case

A partial anomalous pulmonary venous connection (PAPVC) is an uncommon congenital anomaly which is frequently associated with congenital heart disease such as an atrial-level shunt. This report documents the case of an 81-year-old man with PAPVC which was incidentally discovered during a right upper lobectomy for lung cancer. Surgery was performed through a minithoracotomy of an auscultatory triangle using a video-assisted procedure (video-assisted thoracic surgery: VATS). Although the ramus lobi medii was connected normally, the right superior lobe vein was found to drain into the superior vena cava. The surgery was successful, and the patient had an uneventful postoperative course. Asymptomatic PAPVC without an atrial septal defect (ASD) is extremely rare. If the PAPVC is located in a different lobe, a pulmonary resection for lung cancer would precipitate an adverse outcome without a correction of the PAPVC. Surgeons should therefore be cautious regarding the potential existence of a PAPVC when a patient undergoes surgical procedures, especially VATS, for lung cancer.

Immediate cytology improves accuracy and decreases complication rate in real-time computed tomography-guided needle lung biopsy

Computed tomography‐guided percutaneous transthoracic needle biopsy (CTNB) of the lung is a well‐established diagnostic technique for the evaluation of thoracic lesions. At our institution, we have performed real‐time CTNB using automated biopsy needles since 1998 and we introduced immediate cytology in 2004. We evaluate immediate cytology in CTNB to increase the diagnostic accuracy and to reduce the number of inadequate specimens.