A single-arm, phase 2 study of adjuvant chemotherapy with oral tegafur-uracil for pathologically lymphovascular invasion positive stage IA non-small cell lung cancer: LOGIK0602 study.

BACKGROUND: Lymphovascular invasion (LVI), which includes vascular or lymphatic invasions, is a representative prognostic factor even in patients with resected stage IA non-small cell lung cancer (NSCLC). Because tegafur-uracil is effective on cancers with LVI, we conducted a multi-center single-arm phase II study to estimate the efficacy of adjuvant tegafur-uracil in patients with LVI-positive stage IA NSCLC. METHODS: Patients with completely resected LVI-positive stage IA NSCLC were registered. LVI was diagnosed by consensus of two of three pathologists. Adjuvant chemotherapy consisted of 2 years of oral tegafur-uracil at 250 mg/m2/day. Fifty-five patients from 7 institutions were enrolled from June 2007 to September 2012. RESULTS: Among the 52 eligible patients, 36 (69.2%) completed the treatment course. There were 39 male and 13 female patients. The observation period was calculated as 562 to 3107 days using the reverse Kaplan-Meier method. The 5-year overall and relapse free survival rates were 94.2 and 88.5% respectively, which were significantly better than that of any other studies conducted on patients with LVI-positive stage IA NSCLC. Notably, the overall survival rate was 15% better than that of our prior retrospective study. The retrospective analysis of stage IA NSCLC patients who had received an operation in the same period revealed that the 5-year overall survival rate of the LVI positive group was 73.6% when adjuvant chemotherapy was not applied. Among 55 safety analysis sets, 4 cases of grade 3 hepatic function disorder (9.1%) and 5 cases of grade 2 anorexia (10.9%) were most frequently observed. No grade 4 adverse effects were encountered. CONCLUSION: A 2-year course of oral tegafur-uracil administration is feasible and might have a significant benefit in the adjuvant treatment of LVI-positive stage IA NSCLC. TRIAL REGISTRATION: UMIN identifier: UMIN000005921 ; Date of enrolment of the first participant to the trial: 19 June 2007; Date of registration: 5 July 2011 (retrospectively registered).

[A Case of Organizing Chronic Subdural Hematoma Treated with Endoscopic Burr-Hole Surgery Using a Curettage and Suction Technique].

A 70-year-old man presented to our hospital because of difficulty with discrete movement of the right upper limb and dysarthria. Computed tomography(CT)of the head revealed a chronic subdural hematoma(CSDH)on the left side. The patient underwent single burr-hole irrigation and drainage on the same day. In addition to the burr hole, a cross-shaped dural incision was made which revealed a thick outer membrane and solidified hematoma. We removed as much of the clotted hematoma as possible using a curved suction tube under neuroendoscopy. The postoperative CT revealed that the hematoma was partially removed and the mass effect was reduced. As a result, the patient's neurological deficits improved. We reached a diagnosis of organizing CSDH following histologic examination of the removed hematoma that showed inflammatory cell infiltration and multiplication of fibroblasts. Neuroendoscopic hematoma evacuation via a burr hole is minimally invasive and may be a useful procedure in the treatment of some cases of organizing CSDH.

Histological evolution of pleuroparenchymal fibroelastosis.

AIMS: To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). METHODS AND RESULTS: We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3-12 years. CONCLUSIONS: Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE.

Diffusivity of intraorbital lymphoma vs. IgG4-related DISEASE: 3D turbo field echo with diffusion-sensitised driven-equilibrium preparation technique.

OBJECTIVES: 3D turbo field echo with diffusion-sensitised driven-equilibrium preparation (DSDE-TFE) is a novel non-echo planar technique for diffusion-weighted (DW) imaging. The purpose of this study was to differentiate intraorbital lymphoma from immunoglobulin G4-related disease (IgG4-RD) using the apparent diffusion coefficient (ADC) derived from DSDE-TFE. METHODS: Fifteen patients with lymphomas and 8 with IgG4-RDs underwent imaging. ADC and signal intensities compared with normal grey matter on T1-weighted images, fat-suppressed T2-weighted images and fat-suppressed postcontrast T1-weighted images were measured. Statistical analyses were performed using the Mann-Whitney U test and receiver operating characteristic (ROC) analysis. RESULTS: Intraorbital lesions were clearly visualised on DSDE-TFE without obvious geometrical distortion. The ADC of lymphoma (1.25 ± 0.50 × 10(-3) mm(2)/s; mean ± standard deviation) was significantly lower than that of IgG4-RD (1.67 ± 0.84 × 10(-3) mm(2)/s; P < 0.05). Conventional sequences could not separate lymphoma from IgG4-RD (0.93 ± 0.18 vs. 0.94 ± 0.21 on T1-weighted images, 0.92 ± 0.17 vs. 0.95 ± 0.14 on T2-weighted images and 2.03 ± 0.35 vs. 2.30 ± 0.58 on postcontrast T1-weighted images, for lymphoma and IgG4-RD, respectively; P > 0.05). ROC analysis showed the best diagnostic performance with ADC. CONCLUSION: The apparent diffusion coefficient derived from diffusion-sensitised driven-equilibrium preparation techniques may help to differentiate lymphoma from immunoglobulin G4-related disease. KEY POINTS: • Distinguishing between orbital lymphoma and immunoglobulin G4-related disease can be difficult • Intraorbital lesions were clearly visualised on diffusion-sensitised driven-equilibrium preparation magnetic resonance techniques. • Variations in field homogeneity do not affect DSDE-TFE techniques all that much. • ADCs derived from DSDE-TFE may help differentiate lymphoma from IgG4-RD.

[Case of pulmonary inflammatory pseudotumor with cysts].

We herein report a case involving a 58-year-old female patient with multiple cystic lesions in the right lobe of the lung. The lesions were revealed on chest computed tomography in 2002 and followed up. Transbronchial lung biopsy showed no malignancy in June 2013. The lesions gradually increased in size and thickness and were associated with fluid-filled cysts. We performed a right lower lobectomy in November 2013. Pathological examination revealed inflammatory pseudotumor. Such a case of inflammatory pseudotumor presenting as a pulmonary cyst has not been previously described. Intractable infection and inflammation are regarded as common causes of inflammatory pseudotumor. This condition should be considered in patients with a medical history consistent with infectious disease and a pulmonary cyst found on chest computed tomography.

Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma.

BACKGROUND: The clinical significance of Brachyury expression and its relationship to epithelial-mesenchymal transition in primary lung carcinoma is unclear. METHODS: Expression of Brachyury mRNA was investigated in 104 surgically resected primary lung carcinoma tissues. Immunohistochemical analysis of Brachyury transcription factor, Slug, E-cadherin, IL-8, N-cadherin, and Ki67 was performed in 67 of 104 cases, and their expression was correlated to prognoses and clinicopathological factors. RESULTS: Brachyury mRNA expression in primary lung carcinoma tissues was a significant predictor of poor prognosis for 5-year disease-free survival and overall survival rates and was significantly correlated to vascular invasion, lymphatic permeation, histological grade, pathologic T stage, and pathologic N stage (P < 0.05). Brachyury mRNA expression was significantly inversely correlated to E-cadherin expression (P = 0.0252) and positively correlated to IL-8 protein (P = 0.0241) and to Slug protein (P = 0.0243) in adenocarcinoma tissues. CONCLUSIONS: A positive association between Brachyury and Slug and IL-8, and a negative association with E-cadherin may lead to invasiveness and metastasis in primary lung carcinoma. Brachyury mRNA expression is a significant predictor of poor prognosis in primary lung carcinoma.

Effects of dietary genistein on hormone-dependent rat mammary carcinogenesis induced by ethyl methanesulphonate.

Genistein, a major soy isoflavone having weak estrogenic activities, has been suggested to reduce the risk of breast cancer incidence. However, many studies have yielded inconsistent results. We investigated the effects of dietary genistein on the development of breast cancer using ethyl methanesulphonate (EMS) chemically induced rat model of hormone-dependent mammary carcinoma. Female Wistar King A rats were orally given EMS for 12 wk and fed isoflavone-free NIH-07PLD diets with or without genistein, beginning immediately after weaning period. All EMS-treated rats fed either diet developed estrogen and/or progesterone receptor-positive mammary carcinoma by 24 wk. The addition of either low or high genistein, which produced the plasma concentrations comparable with those observed in humans consuming high soy diets, did not show any preventive activity. Soy-containing pellet food, exhibiting substantial plasma concentrations of isoflavones such as genistein, daidzein, equol, and glycitein, significantly increased the latency periods, compared to either NIH-07PLD diet with low (P = 0.027) or high (P = 0.034) genistein. Body weights, total EMS uptakes, and urinary estradiol concentrations were not significantly different among groups. These data indicate that genistein does not exert clear preventive effects and that isoflavone components other than genistein might be preventive against hormone-dependent mammary carcinogenesis.

Localized pleural amyloidosis: report of a case.

We herein describe an asymptomatic 31-year-old male who was admitted for an investigation of an abnormal pleural tumor detected by chest radiography. We performed various preoperative investigations including fluorodeoxyglucose-positron emission tomography. The maximum standardized uptake value (SUVmax) was 2.2, and malignancy could not be ruled out. We therefore carried out a thoracoscopy-assisted partial resection of the right upper lobe combined with a parietal pleurectomy. The pathological examination showed that there was a tumor localized with pleural amyloidosis.

CHFR hypermethylation and EGFR mutation are mutually exclusive and exhibit contrastive clinical backgrounds and outcomes in non-small cell lung cancer.

Aberrant promoter methylation of the checkpoint gene with forkhead-associated domain and ring finger (CHFR) gene is frequently detected in human cancer. We previously demonstrated that diminished CHFR expression was significantly correlated with both poor prognosis and heavy smoking in nonsmall cell lung cancer (NSCLC). Conversely, epidermal growth receptor (EGFR) mutation is detected in NSCLC among those who have never smoked or smoked lightly. To address the frequency of CHFR hypermethylation as well as differences in the distributions and clinicopathologic backgrounds against EGFR mutation in NSCLC, we investigated a large group of 208 NSCLC patients, including 165 with adenocarcinoma (ADC), 40 with squamous cell carcinoma and three others. We found that CHFR hypermethylation and EGFR mutation are mutually exclusive and have contrastive clinicopathologic backgrounds in NSCLC. Methylation-specific polymerase chain reaction (MSP) and direct DNA sequencing were performed to detect CHFR hypermethylation and EGFR mutation, respectively. CHFR hypermethylation was found in 29 cases (14%) (16 ADC (8%), 12 SCC (6%) and one adenosquamous carcinoma), while EGFR mutation was detected in 48 (23%) cases, all of which were ADC. CHFR hypermethylation and EGFR mutation were mutually exclusive (p = 0.004). NSCLC with altered CHFR was significantly correlated with smoking history, poor differentiation, lymphatic invasion, and poor prognosis; this contrasted sharply with EGFR mutation, which had statistically better clinical outcomes. Our results demonstrate that CHFR loss might be critical for the tumorigenesis of NSCLC in patients with a history of smoking and induces tumors of a more malignant phenotype than the EGFR mutation. Thus, CHFR alteration should be considered a therapeutic target against NSCLC in patients with poor prognoses.

[A case of pulmonary actinomycosis mimicking chronic necrotizing pulmonary aspergillosis].

A 60-year-old man was admitted to our hospital with fever, appetite loss, and fatigue. Chest X-ray films and computed tomography scans showed fungus-ball-like lesions in the thoracic cavity, and pleural thickening with surrounding infiltration in the left upper lobe, developing over several months. The white blood cell count (WBC) and serum C-reactive protein (CRP) levels of the patient at the time of admission were 8800/microl and 2.7 mg/dl, respectively. He showed a negative reaction for the serum Aspergillus precipitating antibody, and a positive reaction for the serum Aspergillus antigen (Pletelia Aspergillus) according to the new cut-off index (the result was 0.8). From these clinical findings, we diagnosed this lesion as chronic necrotizing pulmonary aspergillosis (CNPA) and administered anti-fungal drugs (itraconazole plus micafungin, voriconazole) for several months. Despite medication, his condition appeared to deteriorate, and Aspergillus was never confirmed from frequent sputum cultures and bronchial lavage specimens. Finally, a pneumectomy was performed. Histopathological findings revealed a Gram-positive, filament-form Actinomyces cluster inside the cavity, which we diagnosed pulmonary actinomycosis. In this case, there was a possibility that the serum aspergillus antigen showed a false-positive reaction. Case must be taken in the evaluation of serum Aspergillus antigen testing.

Prenatal findings in a case of massive fetomaternal hemorrhage associated with intraplacental choriocarcinoma.

We describe biochemical assessment of maternal circulation in a case of massive fetomaternal hemorrhage at term associated with intraplacental choriocarcinoma. Markedly elevated maternal serum hCG level at 37 weeks of gestation suggested choriocarcinoma as a cause of fetomaternal hemorrhage in this case. Measurement of maternal hCG may be a useful parameter when intraplacental choriocarcinoma is in the differential diagnosis. In addition, the placenta should be examined in all cases of fetomaternal hemorrhage.

[Autopsy case of rapidly progressive pulmonary spindle cell carcinoma with multiple metastases to the brain and pancreas].

A 53-year-old man was admitted to our hospital because of an abnormal lung shadow on his chest X-ray film. His symptoms were cough and shortness of breath. Chest X-ray and computed tomography showed a large mass lesion in the right lower lobe of the lung. We diagnosed primary non-small cell lung cancer; cT3N1M1 stage IV. Systemic chemotherapy using carboplatin and paclitaxcel was performed. However, the treatment had no effect and he died two months after admission. An autopsy showed pulmonary spindle cell carcinoma, with multiple metastases to the brain, pancreas, etc. Pulmonary spindle cell carcinoma had been recognized as a variant of the squamous cell carcinoma for years, however, in the recent WHO and Japanese classification of lung tumors, it was redefined as an independent histological type. It is a rare form of lung cancer, representing 0.2 to 0.3% of all primary pulmonary malignancies and seems to have poor prognosis. We need to pay more attention to this type of lung cancer.

CHFR expression is preferentially impaired in smoking-related squamous cell carcinoma of the lung, and the diminished expression significantly harms outcomes.

Loss of tumor suppressors and activation of oncogenes lead to carcinogenesis. Abnormal expression of CHFR, a novel checkpoint gene, or of Aurora kinases, key regulators of mitosis, has been detected in a variety of solid tumors. Recently, CHFR has been revealed to ensure chromosomal stability by controlling the expression level of Aurora-A in vitro. However, the frequency of aberrant expression of these proteins and the association with clinicopathologic parameters remain poorly defined in nonsmall-cell lung cancer (NSCLC). In this study, we investigated the immunohistochemical protein expression of CHFR and Aurora-A in 157 NSCLC cases and evaluated the association between clinicopathologic parameters statistically. The relationship between CHFR protein and mRNA levels and the association between this relationship and promoter methylation of the CHFR gene were also examined in 20 frozen sections of NSCLC. Overexpression of Aurora-A and reduced expression of CHFR were found in 94 cases (59.8%) and 62 cases (39%) of NSCLC, respectively, and those were significantly correlated with tumor differentiation and size. Moreover, diminished CHFR expression was significantly associated with smoking-related squamous cell carcinoma cases and poor prognosis. Multivariate analysis revealed that CHFR expression was an independent prognostic factor. A statistical correlation was evident between CHFR protein and mRNA expression. In conclusion, our results suggest the aberrant expression of Aurora-A and/or of CHFR contributed to the increase in the malignant potential of NSCLC. We also revealed that CHFR expression was predominantly impaired in smoking-related squamous cell carcinoma and might be a useful prognostic marker in NSCLC.

[An autopsy case of amyotrophic lateral sclerosis with ampulla cardiomyopathy].

We herein report an autopsy case of a 63-year-old man with amyotrophic lateral sclerosis (ALS) who developed "ampulla cardiomyopathy." At the age of 56, he noticed a progressive weakness in his right upper extremity. One year later, a progressive weakness of the left upper extremity began. Dropped head and progressive weakness of the lower extremities emerged at the ages of 61 and 62, respectively. Intravenous immunoglobulin and plasma-exchange therapies did not improve his weakness. At the age of 63, one month before his death, he was hospitalized due to aspiration pneumonia. A tracheostomy was performed to secure his airway. Four days after the operation, an ST elevation of his electrocardiogram was incidentally found on the ECG monitor. An echocardiogram revealed diffuse hypokinesia of the wall of the left ventricle except in the basal portion, which is the typical finding of "ampulla cardiomyopathy." Wall motion of the left ventricle improved and his circulatory condition was stabilized after treatment, but his condition thereafter worsened again and he died 3 weeks later. An autopsy examination revealed diffuse fibrosis and degeneration of the cardiomyofibers. Neuropathological examination revealed neuronal cell loss, Bunina bodies and skein-like inclusions in the hippoglossal nuclei. In the thoracic spinal cord, degenarated anterior horn cells were seen and macrophage permeation in the corticospinal tract were shown by CD68 immunostaining. Therefore, the final neuropathological diagnosis was ALS. This report is the first autopsy case of ALS complicated with "ampulla cardiomyopathy."

An autopsy case report of annuloaortic ectasia with cardiac tamponade ruptured from an aneurysm of the right Valsalva sinus.

Annuloaortic ectasia (AAE) is a clinicopathologic condition with primary or secondary dilatation of the aortic annulus and aneurysm of the proximal thoracic aorta, leading to aortic regurgitation. We herein report an autopsy case of a Japanese 57-year-old male with AAE who died of a cardiac tamponade rupture from the sinus of the right coronary. The wall of the aortic root, particularly that of the sinus of the right coronary Valsalva, underwent extensive fibrosis with loss or fragmentation of the elastic lamina in the medial layer and perforation directly into the pericardial space. The adventitia of the proximal aorta to the aortic arch was diffusely fibrotic with both acute and chronic hemorrhage and chronic inflammatory infiltrate. However, the ascending aortic media was largely intact, except for focal laminar necrosis at the center of the medial layer; no medial cystic necrosis, laminar necrosis, or mesoaortitis/panaortitis was present in the thoracic or abdominal aorta, nor in the main aortic branches, which was suggestive of Takayasu disease and giant cell arteritis. Thus, this patient was diagnosed to have idiopathic AAE with sustained peri-aortic hemorrhage, and he finally died of a cardiac tamponade resulting from an aneurysmal rupture.

Platelet-derived growth factor-AA is an essential and autocrine regulator of vascular endothelial growth factor expression in non-small cell lung carcinomas.

It is widely accepted that angiogenesis is required for tumor progression. Vascular endothelial growth factor (VEGF) is a key molecule for tumor angiogenesis; however, its expressional regulation is not well understood during all stages of tumorigenesis. Using cell lines and surgical specimens of human non-small cell lung cancers (NSCLCs), we here show that platelet-derived growth factor-AA (PDGF-AA) is an essential autocrine regulator for VEGF expression. To directly assess the expression of PDGF-AA-dependent VEGF and its roles in tumorigenesis, we stably transfected established cell lines with their antisense genes. In addition, the levels of PDGF-AA and VEGF expression in surgical sections were measured and compared with clinicopathologic findings such as tumor size and patient prognosis. PDGF-AA tightly regulated VEGF expression and had a greater effect on tumor size and patient prognosis than did VEGF in both cell lines and surgical sections. PDGF-AA expression was not seen in the atypical adenomatous hyperplasia at all, whereas VEGF was occasionally seen. Furthermore, the frequency of VEGF expression was higher in advanced NSCLCs than in precancerous lesions, which was tightly correspondent to the results for PDGF-AA. These results indicate that PDGF-AA is an important regulator of the frequency and level of VEGF expression during the transition from a precancerous lesion to advanced cancer. The PDGF-AA/VEGF axis, therefore, may be a ubiquitous autocrine system for enhancing angiogenic signals, and PDGF-AA, and its related pathways could be a more efficient target of antiangiogenic therapy for cancers than VEGF and its pathways.

A case of IgG4-related lung disease complicated by asymptomatic chronic Epstein-Barr virus infection.

INTRODUCTION: IgG4-related disease is characterized by IgG4-positive plasmacyte infiltration into various organs, but its etiology is not unknown. OBJECTIVES: To elucidate the etiology of IgG4-related disease. METHODS: We experienced an interesting case of IgG4-related lung disease complicated by chronic EB virus infection. RESULTS: A 70-year-old male visited our hospital due to failure of pneumonia treatment. Chest computed tomography (CT) showed consolidation in the right middle field and slight mediastinal lymphadenopathy in the subcarinal region. Lung consolidation improved with antibiotics; subcarinal lymphadenopathy progressed after 4 months. Malignant lymphoma was suspected given elevated sIL2-R levels (1862 U/mL). Patchy ground glass opacities appeared in the bilateral lung field just before surgical biopsy. He was diagnosed with IgG4-related lung disease after inspection of a pathological specimen obtained from the right upper lung and right hilar lymph node. EB virus-infected cells were also detected in the lymph node. Blood examination revealed EB virus viremia, but the patient did not present with symptoms or organ involvement. This led to a diagnosis of asymptomatic chronic EB virus infection. CONCLUSION: Recent studies have suggested an association between EB virus infection and IgG4-related diseases in the pathological exploration of surgically resected lymph nodes. Our case is the first case of IgG4-related lung disease in which EB virus infection was both pathologically and clinically proved. The present case is of particular interest in view of this newly reported association, and may serve as a fundamental report for future studies connecting EB virus infection with IgG4-related diseases.

Immunohistochemical alpha- and beta-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma.

The E-cadherin/catenin complex (alpha-catenin, beta-catenin, and E-cadherin) plays a crucial role in cell-cell adhesion and tissue remodeling, and abnormalities in these molecules have been suggested to participate in the proliferation and invasive and metastatic potentials of several human carcinomas. However, in human lung adenocarcinomas, its importance has not yet been sufficiently investigated. We immunohistochemically examined the expressions of E-cadherin/catenin complex in 35 primary lung adenocarinomas, and evaluated their expressions in a semiquantitative manner. Correlations between these expression levels, MIB-1 and nuclear p53 indices, and clinicopathological factors were analyzed by subdividing the cases into high- and low-expression groups for each protein. The reduction in membranous E-cadherin/catenin complex expression correlated significantly with low-grade histological differentiation and with high MIB-1 index. Survival analyses were also performed to clarify which factors potentially affected the prognosis of lung adenocarcinoma patients. The low expression of beta-catenin and the high MIB-1 index had a significantly unfavorable influence on the patients' survival. Moreover, the immunohistochemical expression of beta-catenin by cancer cells and MIB-1 index are considered useful prognostic factors for lung adenocarcinoma.

Identification of MGB1 as a marker in the differential diagnosis of lung tumors in patients with a history of breast cancer by analysis of publicly available SAGE data.

The risk of developing second primary cancers is increased in patients with breast cancer. The lung is one of the major target organs, and therefore a differential diagnosis between primary and metastatic cancers is required for the treatment of lung tumors in patients with a history of breast cancer. However, biopsy specimens frequently result in small, fragmented tissues containing only a few, degenerated cancer cells. We attempted to find a useful marker for differential diagnosis, using the online SAGE database. We selected three molecules, small breast epithelial mucin (SBEM), prostate epithelium-specific Ets transcription factor (PDEF), and mammaglobin (MGB1), as potential markers for breast cancer. SBEM and PDEF proved of no use for practical differential diagnosis because they are expressed in the normal bronchus. In contrast, expression of MGB1 was detected in all 22 primary breast cancers, but not in 22 normal lung tissues. Furthermore, all 12 metastatic breast cancers examined demonstrated positive MGB1 transcripts, whereas one of 48 primary lung adenocarcinomas expressed MGB1. This suggests that MGB1 can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis.

Lung adenocarcinoma with bronchioloalveolar carcinoma component is frequently associated with foci of high-grade atypical adenomatous hyperplasia.

We assessed the occurrence of atypical adenomatous hyperplasia (AAH) in whole lung lobes with primary cancer lesions. Following surgical resection, tissue specimens were sliced to a thickness of 4 mm (3,641 specimens from 61 cases; mean = 59.7 specimens per case). A total of 119 AAH foci were found and an association was evident in 25 (57%) of 44 adenocarcinomas, 3 (30%) of 10 squamous cell carcinomas, and 2 (29%) of 7 other lung cancers. Histologic evaluation showed that 108 AAH foci were categorized as low-grade and the other 11 as high-grade AAH. These 11 foci of high-grade AAH were present in 7 patients with adenocarcinoma, and in 1 patient there was a synchronous double primary lung adenocarcinoma. High-grade AAH was closely associated with bronchioloalveolar carcinoma (BAC) type adenocarcinoma, and low-grade AAH with non-BAC adenocarcinoma. The mean +/- SD Ki-67 labeling index in high-grade AAH (3.5%+/-2.9%) was significantly higher than for the low-grade index (1.4%+/-1.6%). We propose that foci of high- but not low-grade AAH may be potential precursor lesions of lung adenocarcinoma, especially with the BAC component.