A case of synchronous multiple primary lung adenocarcinomas harboring epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement successfully treated with combination of osimertinib and alectinib.

Synchronous multiple primary lung cancers (SMPLC) should be distinguished from intrapulmonary metastasis to define the optimal treatment approach. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are typically mutually exclusive and the co-existence of both mutations is relatively rare. Herein, we report a case of SMPLC harboring each EGFR mutation and ALK rearrangement successfully treated with combination of osimertinib and alectinib. A combination of EGFR- and ALK-tyrosine kinase inhibitors could be an effective and tolerable therapeutic option for SMPLC with EGFR mutations and ALK rearrangement.

A case of diffuse large B-cell lymphoma originating from chest wall complicated by benign asbestos pleural effusion.

A 78-year-old man with exposure to asbestos was admitted to our hospital for back pain. A chest computed tomography showed right pleural effusion and a significant increase in the size of masses in the right chest wall over an interval of six months. He did not undergo further examinations and expired one month later. Autopsy revealed the presence of diffuse large B-cell lymphoma (DLBCL) and complicated by benign asbestos pleural effusion. We considered that this tumour had originated from the soft tissue in the chest wall based on the radiological and autopsy findings. The present report highlights that primary DLBCL of chest wall might be associated with chronic inflammation due to asbestos-related pleural diseases.

[A case of Churg-Strauss syndrome with subarachnoid hemorrhage and left phrenic nerve paralysis].

A 60-year-old woman was given a diagnosis of Churg-Strauss syndrome (CSS) in 2000 because of peripheral blood eosinophilia, eosinophilic pneumonia, asthma, polyarticular pain, and limb numbness. She was treated with prednisolone (PSL), and the above symptoms improved but then relapsed on tapering of PSL. In September 2009, after 7 days of tapering of PSL to 5mg/day, the patient developed a subarachnoid hemorrhage and was admitted. MRA and cerebral angiography revealed no aneurysm; the source of bleeding could not be determined, but her symptoms indicated a benign course. A chest X-ray 27 days after admission showed left diaphragmatic elevation, and left phrenic nerve paralysis was diagnosed by a phrenic nerve stimulation test. Peripheral blood eosinophilia had progressed gradually during the admission period, and although it is rare for subarachnoid hemorrhage and phrenic nerve paralysis to be associated with CSS, we regarded these as vasculitis symptoms related to CSS.

Connexin 43, E-cadherin, beta-catenin and ZO-1 expression, and aberrant methylation of the connexin 43 gene in NSCLC.

BACKGROUND: The relationships between connexin 43 (Cx43) expression and clinicopathological factors, epithelial markers, and CpG island methylation in non-small cell lung cancer (NSCLC) are controversial. The aim of this study was to investigate whether the Cx43 expression related with clinicopathological factors, epithelial markers and methylation status of the Cx43 gene. PATIENTS AND METHODS: Correlations between the degree of immunohistochemical staining for Cx43 and epithelial markers (E-cadherin, beta-catenin, ZO-1), clinicopathological factors, and CpG island methylation status of the Cx43 gene, as assessed by pyrosequencing, were studied in 33 specimens of surgically treated NSCLC. RESULTS: Weak Cx43 staining was correlated significantly with heavy smoking and weak E-cadherin or ZO-1 expression. The CpG island hypermethylation level was significantly associated with heavy smoking, poorly-differentiated tumour, and low expression of Cx43. CONCLUSIONS: Both aberrant localization and epigenetic changes are associated with aberrant expression of connexin 43 in human NSCLC.

[An autopsy case of invasive thymoma extending to the right atrium with superior vena cava syndrome as the initial manifestation].

We report a case of invasive thymoma presenting with superior vena caval obstruction and intracardiac extension. A 74-year-old man was admitted in July 2002 with swelling of the face and right upper extremity. Computed tomography of the chest revealed a small anterior mediastinal mass, which infiltrated the lumen of the superior vena cava extending into the right atrium. Invasive thymoma was strongly suspected, but he refused any medical treatment. His health declined steadily, with repeated right-sided heart failure. He died due to cardiac tamponade 50 months after his first visit. On autopsy, the tumor was diagnosed as a thymoma classified as type B3 according to the WHO histological classification. Formation of a tumor thrombus in the superior vena cava and the right atrium is a rare mode of extension of thymoma. In this respect, our case may be valuable for improving the understanding of the natural course of invasive thymoma.

The characterization of gefitinib sensitivity and adverse events in patients with non-small cell lung cancer.

BACKGROUND: Factors predicting gefitinib sensitivity and adverse events in non-small cell lung cancer (NSCLC) remain controversial. PATIENTS AND METHODS: Correlations among clinicopathological characteristics, gefitinib sensitivity and adverse events were studied in 154 patients with NSCLC, whereas epidermal growth factor receptor (EGFR) mutations were analyzed in 44 patients. RESULTS: Female, non-smoker, adenocarcinoma of stage I-II, and gefitinib effectiveness correlated with longer time to progression (TTP) and overall survival (OS), while the rate of interstitial lung disease in patients undergoing thoracic radiotherapy and stomatitis in females or those who never smoked were significantly higher. EGFR mutations were identified in 18 cases, and among 34 gefitinib-treated patients, 16 patients harboring mutations tended to do better, both in terms of TTP and OS. The results of the mutation analysis from surgical and non-surgical specimens were identical. CONCLUSION: Certain clinicopathological characteristics and EGFR mutations can be either predictive of gefitinib sensitivity or adverse events.