Acute airway obstruction due to benign asymptomatic nodular goiter in the cervical region: A case report.

Benign nodular goiter is a common disease. Although large goiters with obstructive symptoms including shortness of breath and dyspnea are a clear indication for surgery, acute upper airway obstruction, particularly in benign cervical goiter cases, is rare. We herein report the case of 46-year-old female with acute upper airway obstruction due to benign nodular goiter. The patient had a large and elastic goiter which was more pronounced on the left side of her neck, and surgery was scheduled for within a few months. Three months after the initial presentation, while still waiting for surgery, the patient was brought to the emergency room due to loss of consciousness and breathing difficulty and was immediately intubated. A computed tomography (CT) scan revealed that the trachea was markedly compressed by a nodular lesion in the left lobe, and bilateral pneumonia was also evident. Total thyroidectomy was immediately performed via the supraclavicular approach. The patient had an uneventful postoperative course and recovered well. The resected specimen included a well-encapsulated solid and cystic mass. Histopathological examination mainly revealed adenomatous goiter. The present case suggests that benign asymptomatic nodular goiter mostly located in the neck may cause acute airway obstruction, even if the nodules are not large. Early surgery should be performed when tracheal deviation and stenosis due to a large goiter is prominent by CT scan.

Primary acinic cell carcinoma of the breast: a clinicopathological and immunohistochemical study.

Acinic cell carcinoma of the breast is an extremely rare, malignant neoplasm characterized by widespread acinar cell-like differentiation and clinically low-grade malignancy. Herein, we report a case of acinic cell carcinoma of the breast in a 41-year-old woman. The tumor was poorly demarcated but had a firm consistency. It was removed with lumpectomy, and sentinel lymph node biopsy was performed to check for metastasis. Microscopically, the tumor showed an infiltrative growth pattern with a combination of solid, trabecular, and microglandular areas. Many of the tumor cells had abundant clear vacuolated cytoplasm containing zymogen-typed granules which resemble acinar cells of the salivary glands. The immunohistochemical profile of the tumor was also similar to that of salivary gland acinic cell carcinoma: the tumor cells were positive for amylase, lysozyme, α -1-antichymotrypsin, S-100 protein, and epithelial membrane antigen and negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. She received postoperative chemoradiation therapy and has been well for 3 years since surgery. As studies on large series are lacking, further studies are needed to elucidate the biological characteristics of acinic cell carcinoma of the breast.

Increased nuclear localization of transcription factor Y-box binding protein 1 accompanied by up-regulation of P-glycoprotein in breast cancer pretreated with paclitaxel.

PURPOSE: The Y-box binding protein 1 (YB-1) regulates expression of P-glycoprotein encoded by the MDR1 gene. There have been no previous studies regarding the involvement of YB-1 in the development of resistance to paclitaxel. The present study was done to examine how paclitaxel affects the localization and expression of YB-1 in breast cancer. EXPERIMENTAL DESIGN: We evaluated the expression and localization of YB-1 and P-glycoprotein in breast cancer tissues obtained from 27 patients before and after treatment with paclitaxel. The effect of paclitaxel on localization of cellular YB-1 was examined by using GFP-YB-1. Interaction of YB-1 with the Y-box motif of the MDR1 promoters was studied by electrophoretic mobility shift assay. The effects of paclitaxel on MDR1 promoter activity were examined by luciferase assay. RESULTS: Of 27 breast cancer tissues treated with paclitaxel, nine (33%) showed translocation of YB-1 from the cytoplasm to the nucleus together with increased expression of P-glycoprotein during the course of treatment. Twelve breast cancer tissues (44%) showed neither translocation of YB-1 nor increased expression of P-glycoprotein. Nuclear translocation of YB-1 was correlated significantly with increased expression of P-glycoprotein (P=0.0037). Confocal analysis indicated that paclitaxel induced nuclear translocation of green fluorescent fused YB-1 in MCF7 cells. Furthermore, binding of YB-1 to the Y-box of MDR1 promoter was increased in response to treatment with paclitaxel. In addition, MDR1 promoter activity was significantly up-regulated by paclitaxel in MCF7 cells (P<0.001). CONCLUSIONS: The results of the present study suggested that YB-1 may be involved in the development of resistance to paclitaxel in breast cancer.

A case of unilateral gravid macromastia in 23-year-old Japanese woman associated with elevated serum CA19-9.

We report a rare case of gravid macromastia (GM) treated after delivery. A 23-year-old woman with left breast enlargement was referred to our hospital. Laboratory investigations revealed an elevated serum CA19-9 level of 200.3 U/ml. Gravid macromastia was diagnosed by clinical examination (US, MRI) and 11G mammotome biopsy. Tumorectomy of the left breast and mammoplasty were performed. The mass had proliferated to the exclusion of normal gland. Histological examination revealed abundant proliferation of stromal loose connective tissue and interposed fat cells surrounding normal and lactating lobules. The epithelial cells were positive for CA19-9 on immunohistochemical staining. Serum CA19-9 decreased to normal levels 3 months after operation. GM is exceedingly rare and occurs in less than 0.001-0.003% of all pregnant women. Once established, the condition is likely to continue to successive pregnancies. This benign tumor is sometimes difficult to distinguish from malignant tumors since it shows few histological characteristics and grows rapidly. Attention is necessary to diagnose tumors of the breast during pregnancy.

CD26 expression determines lung metastasis in mutant F344 rats: involvement of NK cell function and soluble CD26.

The association between CD26 expression, tumor cell adhesion, metastasis, and natural killer (NK) cell function was investigated in a CD26 mutant Fischer 344 (F344/DuCrj) substrain from Japanese breeders (F344JAP) in comparison with wild-type F344 substrains from US (F344/Crl) and Hannover (HAN; F344/Ztm) breeders. F344JAP rats lack the dipeptidyl peptidase IV activity of CD26 and show a reduced cell surface expression of the mutated CD26 glycoprotein. In vivo adhesion of vital dye-labeled MADB106 tumor cells, tumor colonization, CD26 enzymatic activity, and CD26 immunoreactivity in lungs and soluble CD26-like protein expression in serum were markedly reduced in F344JAP rats. These findings demonstrate that CD26 protein expression exerts a key role in lung metastasis. In addition, NK cell cytotoxicity against MADB106 cells was diminished in the mutant F344 substrain, suggesting that CD26 enzymatic activity sustains NK cytotoxicity. Interestingly, tumor cells lacked CD26 immunoreactivity in vitro, but displayed CD26 immunoreactivity in situ after in vivo inoculation as well as after incubation with rat serum, indicating that soluble CD26-like protein assembles in tumor cells during in vivo passage, which may interact with the process of tumor adhesion and metastasis. Overall, these findings indicate that altered expression and function of a single enzyme-the CD26 protein--can drastically change the outcome of metastatic disease.

Mutation of the class I beta-tubulin gene does not predict response to paclitaxel for breast cancer.

Mutation of the class I beta-tubulin gene has been reported to be one of the mechanisms that cause resistance to paclitaxel. To assess the relationship between paclitaxel-resistance and class I beta-tubulin gene mutation in breast cancer, Japanese patients with breast cancer were screened for the class I beta-tubulin gene mutation. Total RNA was isolated from 82 breast cancer specimens and the corresponding normal tissues. Twenty-four of the 82 patients were treated with paclitaxel preoperatively and 12 of them did not respond to the treatment. Of the 82 breast cancer patients, 15 (18.3%) had silent polymorphism in exon 4, Leu217Leu (CTG/CTA). However, no mutations showing amino acid substitution of the beta-tubulin gene were detected in any of the patients, including 12 patients who did not respond to paclitaxel. Class I beta-tubulin gene mutation with amino acid substitution was not detected in 82 breast cancer specimens. Our results suggest that mutation of the class I beta-tubulin gene is unlikely to play an important role in the mechanism of resistance to paclitaxel in breast cancer.

Intratracheal macrophage-activating lipopeptide-2 reduces metastasis in the rat lung.

Primary surgery of tumors bears the risk of metastasis to organs such as the lungs. In order to prevent such metastatic processes, in the present study, local intratracheal instillation of macrophage-activating lipopeptide-2 (MALP-2) as a bacterial-derived immunomodulator of cellular host defense responses was performed, and the effects on tumor cell clearance as well as tumor colonization were investigated in the lungs of Fischer 344 (F344) rats. Compared with vehicle controls, local administration of MALP-2 parallel to intravenous inoculation of MADB106 mammary adenocarcinoma tumor cells resulted in a significant reduction of lung colony numbers, whereas MALP-2 application 1 or 3 d afterwards was not effective. Quantification of leukocyte subsets in the lung tissue by immunohistochemistry revealed a significant increase of the number of monocytes in situ, as well as an increased co-localization of Natural Killer (NK) cells with tumor cells. Synthetic MALP-2 is easily available, with virtually no limitation to the amount of compound, and easily applicable by inhalation. Therefore, as local immunostimulative effects of the bacterial antigen MALP-2 have successfully been demonstrated, its use as an immunotherapeutic agent is worth further investigation.

Stromal sarcoma of the breast with leiomyosarcomatous pattern.

We report an unusual case of stromal sarcoma of the breast with leiomyosarcomatous pattern, which recurred locally and was finally treated by radical mastectomy. The tumor was composed of pleomorphic and hyperchromatic spindle-shaped cells arranged in an interdigitating fascicle. The nuclei were of moderate to severe atypia. An average of 10 mitoses per 10 high-power fields was seen. Immunohistochemically, the stromal cells were positive for vimentin and alpha-smooth muscle actin, but negative for S-100 protein, cytokeratin and desmin. The average Ki-67 (MIB1) labeling index in the stromal cells was 34%. Electron microscopic evaluation revealed further evidence of smooth muscle differentiation; stromal cells had frequently indented nuclei, well-developed rough endoplasmic reticulum, thin basal lamina and dense patch-like structures within the cytoplasm. Analysis of previous literature on 17 cases reveals mitotic activity of the tumor seemingly of little prognostic value. This case indicated difficulty in diagnosing leiomyosarcoma. The risk of local recurrence remains even if the surgical margin is free of tumor cells.

Kinetics of the early recruitment of leukocyte subsets at the sites of tumor cells in the lungs: natural killer (NK) cells rapidly attract monocytes but not lymphocytes in the surveillance of micrometastasis.

Early host defense mechanisms play a critical role for the outcome of metastatic disease but most of the initial steps of such responses against tumor cells are still unknown. Here, the specificity and kinetics of leukocyte subsets in response to intravenous inoculation of vital dye labeled Fischer 344 rat syngeneic MADB106 tumor cells were monitored in lungs in situ by immunohistochemistry and image analysis over a time-period of 6 hr. In comparison with sham injections, tumor cell inoculation induces a dynamic sequence of rapidly increasing granulocyte (+40% at 5 min), NK and T cell (+60% at 15 min) as well as monocyte (+100% at 30 min) numbers in lung tissue. Already within the first minutes frequent colocalizations of granulocytes and NK cells with tumor targets were found in situ. Within the first hour NK cells selectively kill tumor targets, because depletion of NK cells in vivo drastically increases both the number of MADB106 cells retained in lungs and the emerging numbers of lung tumor colonies. In addition, the tumor-cell-induced increase of monocytes strictly depends on the presence of NK cells because NK-depletion completely abrogates the time specific response of monocytes. Under NK depleted conditions the tumor-induced recruitment of CD4(+) T cells is more pronounced suggesting a compensatory mechanism. In contrast, B cell numbers progressively decrease within hours after cell inoculation. These findings demonstrate that NK and T cells mediate the initial steps in the surveillance of lung metastasis. NK cells rapidly kill tumor cells and subsequently recruit monocytes in vivo.