Yuko Iida

Adenomyoepithelioma with carcinoma of the breast: A report of two cases and a review of the literature.

We herein described two cases of adenomyoepithelioma (AME) with carcinoma of the breast. Both of them were Japanese women, and they presented with a mass in their breast. Post-operative specimens revealed encapsulated and well-circumscribed tumors with local invasion, necrosis, cytological atypia, and a high mitotic rate. In immunohistochemistry, coincidentally with the loose adhesion pattern of myoepithelial cells in both cases, the intensities of E-cadherin and beta-catenin were much weaker in myoepithelial than luminal epithelial cells, with almost negative finding of beta-catenin in one case. We first found deletion of CDH1 and polysomy of CEP16 in myoepithelial cells by double color-fluorescence in situ hybridization. The two cases have been followed up for 5-8 years, and both remained free from local recurrence and distant metastases. We also presented an overview of 47 cases of AME with carcinoma in English-language literatures.

Clinicopathological characteristics of thyroid transcription factor 1–negative small cell lung cancers

Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer; however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (ASCL1, BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (NF1B). Formalin-fixed and paraffin-embedded sections of SCLC tumors were subjected to immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analyses. In a case-control cohort matched for basic clinical factors, expression of ProGRP, synaptophysin, chromogranin A, and ASCL1 was significantly decreased in TTF-1-negative SCLC samples. In contrast, there was no significant correlation between Ki-67 labeling index and TTF-1. In a larger serial case cohort, TTF-1-negative SCLC cases were older at diagnosis, but there was no significant difference in the overall survival of patients with TTF-1-negative and TTF-1-positive SCLC. In conclusion, TTF-1-negative SCLC showed decreased neuroendocrine differentiation, and significantly worse clinical outcomes were not observed.

Serum free IgE guided dose reduction of omalizumab: a case report

BackgroundOmalizumab is a human IgG1 antibody against IgE used as a therapy for sever asthmatic patients with asthma. According to the guidelines of the Global Initiative for Asthma, omalizumab is an add-on drug at treatment step 5 that is used for severe asthma patients who are allergic to perennial allergens. The effects of omalizumab for severe asthma therapy have been validated in multiple clinical studies. However, the long-term effects of omalizumab on IgE production and possibility of resetting of administration dose of omalizumab remain unknown.Case PresentationThe serum total and free IgE levels were measured over time in a 63-year-old female patient with allergic asthma who was administered 375 mg omalizumab biweekly for 36 months. Her symptoms did not worsen and clinical course remained favorable after reducing the dose to 375 mg per month. The serum free IgE levels temporarily increased following a dose reduction of omalizumab. The serum free IgE trough level temporarily increased at 4 weeks after capable to reduce the dosage; however, thereafter, the serum free IgE level decreased to desired levels (below 30 ng/mL).ConclusionsThe present case shows the possibility of reducing the dose following the long-term use of omalizumab. Considering the high medical cost of omalizumab, the dose reduction may be a viable option. It may be useful to measure the serum free IgE level to appropriately identify patients in whom the dose can be reduced, and to carefully monitor the clinical course.

Long-term course of serum total and free IgE levels in severe asthma patients treated with omalizumab

Omalizumab, a human immunoglobulin G1 antibody to immunoglobulin E (IgE), is an antibody drug indicated for the treatment of asthma. It can improve symptoms in patients with intractable atopic asthma and reduce the risk of exacerbation and is one of the few drugs that improve the quality of life of patients. As omalizumab improves airway inflammation and causes IgE level depression, there is a possibility that IgE production levels will be reduced after long-term omalizumab administration. The reduction in IgE production in such patients would be advantageous for the management of atopic asthma. However, not enough research has been conducted on the long-term effects of omalizumab administration on IgE production. In general, serum total IgE revels are believed to reflect IgE production levels in the body. However, the traditional methods of measuring IgE levels, such as the ImmunoCAPmethod for measurement of total serum IgE (Thermo Fisher Scientific, Waltham, MA, USA), cannot distinguish between omalizumab-binding IgE and free IgE. Hence, these methods cannot evaluate IgE production levels in omalizumab-administered patients. On the other hand, it is conceivable that serum free IgE levels are associated with IgE production levels in omalizumab-administered patients. Using a mathematical model, Lowe et al. simulated changes in total blood IgE after several years of continued treatment with omalizumab, based on data on total blood IgE from 10 clinical trials, and predicted that total blood IgE levels would gradually decline with the long-term use of omalizumab. They further predicted that this long-term decline in IgE level would be more marked as the duration of omalizumab treatment extended.1 However, this was merely a prediction based on a mathematical model. At present, several methods are available for measuring free IgE after omalizumab administration.2,3 No reports have actually directly measured changes in serum free IgE levels as an indicator of IgE production during long-term omalizumab treatment. As we previously reported, the method that we established involves measuring IgE by Enzyme-Linked ImmunoSorbent Assay (ELISA) using antibodies refined from human FcεRI recombinant proteins.4 In our previous report, we showed the term course of serum free IgE levels at baseline and at 4 weeks in four cases.4 In the short term, two cases of them did not reach the target concentration of free IgE (below 25 ng/ml). Here we presented data from 8 patients in whomwe measured fluctuations in total serum IgE and

Evaluation of airway resistance in primary small cell carcinoma of the trachea by MostGraph: a case study

The case subject was a 58-year-old woman who presented to our hospital with a chief complaint of respiratory discomfort. Wheezing could be heard in both lungs; treatment was initiated with inhaled steroids for suspected bronchial asthma. However, 1 week later, the respiratory discomfort had not improved and the wheezing sound had progressed to the neck area. Upper airway obstruction was suspected; therefore, chest computed tomography (CT) was performed, revealing tracheal stenosis caused by a tumor in the upper airway. Because of the high risk of airway obstruction, tracheotomy and tracheal tumor resection were performed. Histopathological examination of the resected tumor revealed small cell lung cancer (SCLC); the stage was determined to be clinical stage IIIB (cT4N2M0), for which chemotherapy with two cycles of cisplatin plus etoposide followed by radiation therapy were administered. Pulmonary function testing revealed no change in the forced expiratory volume in 1 sec and flow volume (FV) curve before and after tumor resection, whereas airway resistance measured by MostGraph-01 showed a marked decrease following treatment. We believe that MostGraph-01 may be useful for measuring airway resistance and evaluating a tracheal tumor, and report a case using MostGraph-01.