Mizue Hasegawa

Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma : a case report and review of the literature

A 50-year-old woman who had undergone lung lobectomy because of lung adenocarcinoma presented with thyrotoxicosis, neck swelling, and cervical lymphadenopathy one month after the operation. The total serum triiodothyronine (T3) and thyroxine (T4) levels were markedly elevated to 514 ng/dL and 26.4 microg/dL, respectively, and serum thyrotropin (TSH) was suppressed to less than 0.005 microU/mL. Although the thyroid gland had been normal before surgery, chest computed tomography (CT) scan revealed a markedly enlarged thyroid gland only 1 month after surgery. 123I uptake for 24 hours was suppressed to 4% in the thyroid gland with no uptake elsewhere including the lung. Fine-needle aspiration cytology (FNAC) of the thyroid showed invasion of poorly differentiated adenocarcinoma cells, cytologically identical to the cells obtained from sputum and those infiltrating the resected sections of the lung adenocarcinoma. Immunohistochemical studies of resected lung tissues did not show positive staining for thyroglobulin, carcinoembryonic antigen (CEA), or surfactant protein A. Clinically, the thyrotoxicosis had spontaneously improved, followed by a hypothyroid state with shrinkage of the thyroid gland after chemotherapy. Despite repeated chemotherapy and the administration of thyroxine for hypothyroidism, the patient died of respiratory failure 9 months after the onset of thyrotoxicosis. From these findings and the clinical course, thyroid metastasis, developing subacutely from lung adenocarcinoma, was diagnosed. We speculate that aggressive invasion of tumor cells into the thyroid gland resulted in highly destructive thyrotoxicosis.

CT Features of Epidermal Growth Factor Receptor–Mutated Adenocarcinoma of the Lung: Comparison with Nonmutated Adenocarcinoma

Introduction: The purpose of this study was to analyze the high‐resolution computed tomography (HRCT) features of lung carcinoma on the basis of epidermal growth factor receptor gene (EGFR) mutation status. Methods: A total of 263 consecutive patients in whom lung adenocarcinoma was diagnosed at our institution between January 2010 and December 2011 were enrolled in the study. All patients underwent HRCT and analysis of EGFR mutation status. The HRCT findings were retrospectively analyzed for tumor size, multiple bilateral lung metastases, convergence of surrounding structures, surrounding ground‐glass opacity, prominent peribronchovascular extension, air bronchogram, notch, pleural indentation, spiculation, cavity, and pleural effusions. Results: EGFR mutations were demonstrated in 103 patients (39.2%); the remaining 160 patients (60.8%) had the nonmutated type of adenocarcinoma. Compared with the nonmutated group, the mutated group had significantly higher frequencies of multiple bilateral lung metastases (p = 0.0152), convergence of surrounding structures (p < 0.0001), ground‐glass opacity (p = 0.0011), and notch (p = 0.0428), but significantly lower frequencies of cavitation (p = 0.0004) and pleural effusions (p = 0.0064). The frequencies of the other CT findings were similar between the two groups. The devised prediction HRCT score for EGFR mutation was 78.4% sensitive and 70.4% specific. Conclusions: EGFR‐mutated adenocarcinoma showed significantly higher frequencies of multiple bilateral lung metastases, convergence of surrounding structures, surrounding ground glass opacity, and notch at HRCT compared with the non–EGFR‐mutated type. Conversely, EGFR‐mutated adenocarcinoma showed cavity and pleural effusions less frequently than the nonmutated type did.

EGFR Mutation of Adenocarcinoma in Congenital Cystic Adenomatoid Malformation/Congenital Pulmonary Airway Malformation: A Case Report

An 80-year-old man underwent right upper lobectomy for the resection of multiple cysts accompanied by a nodule. The pathological diagnosis was adenocarcinoma with surrounding atypical epithelial cell proliferation in a Type 1 congenital cystic adenomatoid malformation/congenital pulmonary airway malformation. There was epidermal growth factor receptor mutation in the adenocarcinoma and surrounding atypical epithelial cells that had proliferated. Malignant transformation of congenital cystic adenomatoid malformation/congenital pulmonary airway malformation may be related to the epidermal growth factor receptor pathway in this case, with atypical epithelial cell proliferation as a precursor. We emphasize the importance of complete resection of congenital cystic adenomatoid malformation/congenital pulmonary airway malformation and the possibility of treatment with epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor-mutated cases.

Cytologic Differential Diagnosis of Malignant Mesothelioma and Reactive Mesothelial Cells With FISH Analysis of p16

Mesothelioma patients often present with serosal effusions, which are ideal for cytopathological diagnoses. However, the morphological overlap between malignant and benign mesothelial proliferation can make a conclusive cytological diagnosis of mesothelioma elusive because immunohistochemical staining does not discriminate definitively between the two in this setting. p16 is deleted in up to 80% of pleural mesotheliomas. The aim of this study was to establish the correlation between the p16 deletion status of the cell block with that of its corresponding tumor using fluorescence in situ hybridization (FISH) analysis for individual patient tumors.

Comparative risk of hospitalized infection between biological agents in rheumatoid arthritis patients: A multicenter retrospective cohort study in Japan

Objective Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. Methods We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders. Results A total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6–8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78–3.04) for infliximab, 1.72 (0.88–3.34) for adalimumab, 1.11 (0.55–2.21) for abatacept, and 1.02 (0.55–1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1–5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72–11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection. Conclusions The magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use.

Size of noncancerous hilomediastinal lymph nodes measured on coronal and sagittal reconstruction CT images

PurposeTo determine the sizes of hilomediastinal lymph nodes on coronal and sagittal reconstruction computed tomographic images of subjects without known malignancies.Materials and methodsWe evaluated 560 lymph nodes of 246 consecutive patients who underwent multidetector-row computed tomography (MDCT) of the chest, then reconstructed coronal and sagittal images on a viewer and measured short-axis diameters of lymph nodes in each station according to the American Thoracic Society (ATS) map for axial, coronal, and sagittal images.ResultsOn coronal images, short-axis diameters were signifi cantly larger than on axial images in station #4R (P < 0.01). On sagittal images, short-axis diameters were signifi cantly smaller than on axial images in stations #4L (P < 0.01), #10R (P < 0.001), and #10L (P < 0.05). On coronal and sagittal images, short-axis diameters were signifi cantly smaller than on axial images in stations #11R (P < 0.001). In #7, diameters were signifi cantly larger on coronal images than on axial and sagittal images (P < 0.001), and diameters were signifi cantly smaller on sagittal images than on axial images (P < 0.01).ConclusionIn stations #4R, #4L, #7, #10R, #10L, and #11R, measurements of short-axis diameters of hilomediastinal lymph nodes differed on coronal and sagittal images. On coronal and sagittal images, evaluation of hilomediastinal lymph nodes requires unique size criteria for every station.

A surgical case of lung cancer with poor general status associated with parathyroid hormone-related protein

Parathyroid hormone-related protein (PTHrP), which is released in the presence of malignant disease, is associated with hypercalcemia. Complete resection of the tumor in such patients is rarely performed because of their poor general condition. We herein report a case of lung cancer associated with PTHrP in a patient whose condition dramatically improved after surgery. We also review the literature on the benefits of various surgical options. Although only a few cases of complete resection in such patients have been reported, the mental and physical condition of the patients improved postoperatively and the median survival time was longer than 12 months. A poor general status is frequently considered a contraindication for surgery, even in a palliative setting; however, we conclude that resection of lung cancer may lead to improved symptom control and survival when the patients condition is induced by hypercalcemia secondary to PTHrP secretion from the tumor.

Pulmonary ground-glass opacity: Computed tomography features, histopathology and molecular pathology

The incidence of pulmonary ground-glass opacity (GGO) lesions is increasing as a result of the widespread use of multislice spiral computed tomography (CT) and the low-dose CT screening for lung cancer detection. Besides benign lesions, GGOs can be a specific type of lung adenocarcinomas or their preinvasive lesions. Evaluation of pulmonary GGO and investigation of the correlation between CT imaging features and lung adenocarcinoma subtypes or driver genes can be helpful in confirming the diagnosis and in guiding the clinical management. Our review focuses on the pathologic characteristics of GGO detected at CT, involving histopathology and molecular pathology.

A case of respiratory infection possibly caused by Mycobacterium triviale: Current problems on diagnostic and therapeutic strategies

Mycobacterium triviale is a subspecies of the Mycobacterium terrae complex, which rarely causes disease in humans. We encountered a case of respiratory infection, possibly caused by M. triviale, which was successfully treated by levofloxacin and clarithromycin. Although DNA-DNA hybridization identified M. triviale in one of three samples, clinical validations convinced us that it was the pathogen. 16s ribosomal RNA sequencing would have been reliable and ideal to perform in this case, although it is not covered by the insurance system in Japan. Nevertheless, this experience remains to be instructive because the clinical course, guidelines on the diagnosis, and therapeutic strategies for respiratory infections caused by M. triviale are not well-known or have not been established. Awareness of the possibility of respiratory infections caused by M. triviale and further collection and analysis of its predisposing conditions are essential.

The efficacy of transbronchial needle aspiration with endobronchial ultrasonography using a guide sheath for peripheral pulmonary lesions suspected to be lung cancer

BACKGROUND The efficacy of transbronchial needle aspiration (TBNA) with endobronchial ultrasonography using a guide sheath (EBUS-GS) for cases of peripheral pulmonary lesions (PPLs) has not been well established. The purpose of this study was to evaluate the efficacy of TBNA with EBUS-GS for PPLs. METHODS We evaluated 130 patients suspected to have lung cancer who underwent transbronchial brushing (brushing), transbronchial biopsy (TBB), and TBNA with EBUS-GS. The pathological diagnostic yields of TBNA were compared to that of TBB and brushing. The histological diagnosis of TBNA was compared to that of surgical specimens. The results of epidermal growth factor receptor (EGFR) gene mutation in TBNA samples were compared to that in TBB or surgical specimens. RESULTS The diagnostic yields of this study were 62.9% for brushing, 80.0% for TBB, and 77.1% for TBNA. Histological diagnosis was 84.8% for TBB and/or TBNA and pathological diagnosis was 86.7% for all the procedures. TBB and TBNA had significance higher than brushing (p < 0.05). TBB and TBNA had a tendency of higher diagnostic yields than brushing if EBUS probe was adjacent to PPLs (p = 0.058). Histological evaluations were obtained from TBNA specimens from 50 of 105 patients (47.6%) and these were identical to those of surgical specimens from 29 of 32 patients (90.6%). The results of EGFR gene mutation in TBNA specimens were identical to the same tissue obtained by surgery or TBB. CONCLUSIONS TBNA with EBUS-GS for PPLs was a useful tool for accurate diagnosis and EGFR gene mutation analysis. This method may improve diagnostic accuracy and be useful for molecular testing. This study was approved by the institutional review board (Date of approval: May 27, 2013, approval number: 2816) of Tokyo Womens Medical University Hospital.