Shugo Uematsu

The Usefulness of Positron-Emission Tomography Findings in the Management of Anterior Mediastinal Tumors

PURPOSE We performed a retrospective analysis to evaluate the usefulness of positron-emission tomography/computed tomography (PET/CT) findings in the classification and management of anterior mediastinal tumors. METHODS Between 2006 and 2015, 105 patients with anterior mediastinal tumor received PET/CT. 18F-fluorodeoxyglucose (18F-FDG)-PET images were obtained 60 minutes after the injection of 18F-FDG. RESULTS The histological classifications were as follows: thymoma (n = 49), thymic carcinoma (TC) (n = 19), malignant lymphoma (ML) (n = 8), teratoma (n = 7), thymic cyst (n = 14), and others (n = 8). Upon visual inspection (SUV max: >2.0), all of the malignant tumors showed 18F-FDG accumulation (with the exception of one type A thymoma). Two of the 14 thymic cysts and three of the seven teratomas showed slight 18F-FDG accumulation. The SUV max values of the low-grade thymomas, high-grade thymomas, TCs and MLs were 3.14 ± 0.73, 4.34 ± 1.49, 8.59 ± 3.05, and 10.08 ± 2.53, respectively, with significant differences between the low- and high-grade thymomas, and between TCs and MLs. The sensitivity, specificity and accuracy of 18F-FDG in the detection of low-grade thymomas and thymomas with a maximum diameter of ≤50 mm and an SUV max of ≤3.4 were 85%, 48%, and 60%, respectively. CONCLUSION FDG-PET/CT is an objective and useful modality in the differential diagnosis and management of anterior mediastinal tumors.

Pulmonary Neoplasms in Patients with Birt-Hogg-Dubé Syndrome: Histopathological Features and Genetic and Somatic Events

Birt-Hogg-Dubé syndrome (BHD) is an inherited disorder caused by genetic mutations in the folliculin (FLCN) gene. Individuals with BHD have multiple pulmonary cysts and are at a high risk for developing renal cell carcinomas (RCCs). Currently, little information is available about whether pulmonary cysts are absolutely benign or if the lungs are at an increased risk for developing neoplasms. Herein, we describe 14 pulmonary neoplastic lesions in 7 patients with BHD. All patients were confirmed to have germline FLCN mutations. Neoplasm histologies included adenocarcinoma in situ (n = 2), minimally invasive adenocarcinoma (n = 1), papillary adenocarcinoma (n = 1), micropapillary adenocarcinoma (n = 1), atypical adenomatous hyperplasia (n = 8), and micronodular pneumocyte hyperplasia (MPH)-like lesion (n = 1). Five of the six adenocarcinoma/MPH-like lesions (83.3%) demonstrated a loss of heterozygosity (LOH) of FLCN. All of these lesions lacked mutant alleles and preserved wild-type alleles. Three invasive adenocarcinomas possessed additional somatic events: 2 had a somatic mutation in the epidermal growth factor receptor gene (EGFR) and another had a somatic mutation in KRAS. Immunohistochemical analysis revealed that most of the lesions were immunostained for phospho-mammalian target of rapamycin (p-mTOR) and phospho-S6. Collective data indicated that pulmonary neoplasms of peripheral adenocarcinomatous lineage in BHD patients frequently exhibit LOH of FLCN with mTOR pathway signaling. Additional driver gene mutations were detected only in invasive cases, suggesting that FLCN LOH may be an underlying abnormality that cooperates with major driver gene mutations in the progression of pulmonary adenocarcinomas in BHD patients.

Expression of PTEN and its pseudogene PTENP1, and promoter methylation of PTEN in non-tumourous thymus and thymic tumours

Aims Mutation or promoter methylation of the phosphatase tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN) promotes some cancers. Moreover, PTENP1 (PTEN pseudogene) transcript regulates PTEN expression and is thought to be associated with tumourigenesis in some cancers. Here, we investigated PTEN expression in thymic epithelium and thymic epithelial tumours. Methods Immunohistochemical analysis of PTEN was performed on two non-tumourous thymus (NT) samples, 33 thymomas (three type A, eight type AB, 11 type B1, six type B2, and five type B3), and four thymic carcinomas (TCs). In 16 cases (two NT, three A, five B1, two B2, one B3 and three TC), analyses of mutations, promoter methylation and comparisons of PTEN mRNA and PTENP1 transcripts were undertaken using PCR-direct sequencing, methylation-specific PCR, and reverse-transcription real-time PCR after target cell collection with laser microdissection. Results PTEN protein was not immunohistochemically detected in NT epithelium or types B1 or B2 thymoma cells, but was expressed in type A thymoma and carcinoma cells. Neither PTEN mutations nor promoter methylation were detected in any samples. Statistical analysis revealed that PTEN mRNA expression was highest in NT epithelium and lowest in type A thymoma cells. PTENP1 transcript expression did not significantly differ among NT, thymoma and TC samples. Conclusions We speculated that NT epithelium and types B1/B2 thymoma cells have a mechanism of PTEN translation repression and/or acceleration of protein degradation, whereas type A thymoma cells exhibit transcriptional repression of PTEN mRNA and accelerated translation and/or protein accumulation.

A Surgical Case of Bronchial Artery Aneurysm Directory Connecting with Pulmonary Artery.

We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful.

Radical resection of a pleomorphic carcinoma after relieving airway obstruction by the endobronchial snare method

A 69-year-old man was hospitalized for fever and cough. He was diagnosed with and treated for an abscess in the left lower jaw and pneumonia by an otolaryngologist, but the pneumonia persisted with no improvement. Chest computed tomography revealed the presence of a heterogeneous torose lesion in the inlet of the left upper bronchus, and bronchoscopy revealed an endobronchial tumor with a smooth surface. An episode of sudden dyspnea occurred and was resolved after the patient changed his sitting position. We concluded that this symptom occurred because the tumor was incarcerated in the left lower lobe bronchus. The tumor was excised by bronchofi berscopic snare resection under tracheal intubation. It was found to be a pleomorphic carcinoma, and left upper lobectomy was performed. There has been no recurrence during the 3 years since the operation.