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A mammary nodular lesion was recognized one month before the surgery in the right upper breast of a 55-year-old female. The fine needle aspiration cytology specimens contained many individual bizarre, multi-nucleated, and/or giant cells having hyperchromatic pleomorphic nuclei, prominent nucleoli, and relatively abundant cytoplasm, admixed with numerous mitotic figures in a hemorrhagic or inflammatory background. A small amount of sheet-like or three-dimensional clusters of malignant cells coexisted. We first interpreted it as high-grade malignancy, such as invasive carcinoma, not otherwise specified. A right breast-conserving surgery was performed, and gross examination revealed a cystic cavity-formed and solid tumor lesion, measuring 35 × 35 × 25 mm and looking gray-yellowish to -whitish. On microscopic examination, the tumor was composed of a diffuse proliferation of highly atypical cells devoid of adhesive characteristics, including many multi-nucleated giant bizarre cells, in a haphazard fashion with stromal invasion, alternating with sarcomatoid features of spindle tumor cells. The cystic cavity was surrounded by hemorrhagic and inflammatory granulation tissue and lined by mostly denuded but atypical tumor cells or bland-looking flattened epithelial cells. Immunohistochemically, these tumor cells are specifically positive for all epithelial markers. Therefore, we made a conclusive diagnosis of pleomorphic carcinoma of the breast with cyst formation. We should be aware that, owing to its characteristic findings, cytopathologists can diagnose correctly, based on careful cytological examination of adequate samplings. [ABSTRACT FROM AUTHOR]

Abstract: A history of a recent rapid increase in long-standing swelling mass was presented in the right parotid gland of an 85-year-old male. The inadequate cytologic specimens contained few small clusters of three-dimensional malignant epithelial cells having hyperchromatic pleomorphic nuclei and prominent nucleoli, adjacent to a cluster of benign monomorphic myoepithelial cells. We first interpreted it merely as an adenocarcinoma, not otherwise specified. A radical parotidectomy was performed, and gross examination revealed an encapsulated and firm tumor lesion, looking grayish-blue to yellowish-white, focally associated with extracapsular invasion. On microscopic examination, the tumor was predominantly composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, often arranged in a Roman-bridge appearance with foci of comedo necrosis, alternating with extensive infiltration to adjacent stroma in a trabecular or alveolar fashion with severe vessel permeation. Within the background of pleomorphic adenoma, the carcinoma cells sometimes replaced ductal luminal cells while retaining an intact-like myoepithelial layer. Therefore, we finally made a diagnosis of invasive salivary duct carcinoma ex pleomorphic adenoma. We should be aware that owing to its characteristic features, cytopathologists might be able to determine correct diagnosis, based on multiple and adequate samplings. [ABSTRACT FROM AUTHOR]

A 78-year-old Japanese male noticed a difficulty in the beginning of standing up, followed by 7a progressive numbness of extremities with pain, Bell's palsy, dysarthria, and difficulty in swallowing. A clinician had suspected cancer of unknown primary origin, accompanied by the diverse and elusive neurological symptoms, likely presenting as painful mononeuropathy simplex and cranial neuropathy. He developed dysbasia over weeks and died 1 month after the symptom onset. At autopsy, an ill-defined large and soft tumor mass in the right lobe of the liver with direct invasion into the right adrenal gland was observed. The left adrenal gland or right iliopsoas muscle was also involved. Microscopic findings showed a monotonous proliferation of medium-sized to large atypical lymphoid cells, which were diffusely positive for CD20 in immunohistochemistry, consistent with diffuse large B-cell lymphoma (DLBL). Furthermore, the lymphoma cells aggressively infiltrated endoneurial and subperineurial spaces not only in the peripheral nerves and plexuses, but partly in the spinal nerve roots, and intravascular spaces in various tissues. Therefore, systemic lymphoma (DLBL) complicated with neurolymphomatosis (NL) and intravascular lymphoma (IVL) was diagnosed. Very early diagnosis and treatment are necessary for the NL patients with poor prognosis. [ABSTRACT FROM AUTHOR]

A contact algorithm, based on the hybrid-Trefftz (HT) finite element method (FEM), is developed for the solution of contact problems with Coulomb friction. Contact conditions are directly imposed with the aid of a direct constraint approach. On the other hand, static condensation technique is used to reduce the contact system to a smaller one which involves nodes within the potential contact surfaces only so that it may save computing time significantly. The final contact interface equation is constructed by considering contact conditions as additional equations. An incremental-iterative algorithm is introduced to determine proper load increments and find correct contact conditions. The applicability and accuracy of the proposed approach are demonstrated through three numerical problems. [ABSTRACT FROM AUTHOR]

A letter to the editor, discussion a case of stromal luteoma and nodular hyperthecosis of the bilateral ovaries associated with atypical endometrial hyperplasia of the uterus is presented.

As some evidences demonstrated that atypical antipsychotics (AA) may be efficacious in treating post-traumatic stress disorder (PTSD), we preformed a meta-analysis of randomized, double-blind, placebo-controlled clinical trials (RCTs) of AAs for the treatment of PTSD. Two hundred and fifty one papers were searched and screened. Eight RCTs met the inclusion criteria. AAs may be superior to placebo in the treatment of PTSD, as indicated by the changes in Clinician Administered PTSD Scale (CAPS) total scores (weighted mean differences (WMD)=-5.89, 95% confidence interval (CI) [-9.21, -2.56], P=0.0005) and also in CAPS subscale intrusion (WMD=-2.58, 95% CI[-3.83, -1.33], P<0.0001 ) and subscale hyperarousal (WMD=-2.94, 95% CI[-5.45, -0.43], P=0.02). The acceptability measured by dropout rates between AAs and placebo showed no statistical difference (OR=1.24, 95%CI [0.78, 1.97], P=0.36). PTSD symptom cluster, especially in intrusion and hyperarousal. However, we should be careful to generalize the conclusion because of the small number of included trails. We expect more RCTs will be done in the future so as to clarify the specific value of AAs for PTSD. [ABSTRACT FROM AUTHOR]

The proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is expressed in inflammatory and atherosclerotic lesions. GM-CSF is known to enhance monocytic expression of monocyte chemoattractant protein-1 (MCP-1). However, the molecular mechanism(s) by which GM-CSF up-regulates the MCP-1 expression remains to be clarified. Thus, in this study, we examined our hypothesis that GM-CSF up-regulates the MCP-1 expression via Jak2-Stat5 signaling pathway. In human monocytic cell line U937, GM-CSF increased MCP-1 expression in protein and mRNA levels. Furthermore, analysis of the GM-CSF promoter element revealed that the STAT5 (signal transducer and activator of transcription-5) transcription factor binding site, located between -152 and -144 upstream of the transcription start site, as well as Janus kinase-2-mediated Stat5 activation were necessary for the GM-CSF-induced transcriptional up-regulation of the MCP-1 gene. This GM-CSF-induced MCP-1 expression, measured as both protein and mRNA levels, was down-regulated by atorvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor. However, this decrease in MCP-1 expression was not at the transcriptional level of MCP-1 gene but rather at the level of the stability of MCP-1 mRNA. These results indicate that GM-CSF regulates MCP-1 expression via Janus kinase-2-Stat5 pathway and by a novel regulatory mechanism of statins to reduce inflammatory reactions by down-regulating the expression of monocytic MCP-1, which promotes atherogenesis. [ABSTRACT FROM AUTHOR]

A 4-mo history of both epigastralgia and back pain was presented in a 39-year-old male. Computed tomography showed right lung nodule and abdominal mass attached to the gastric wall, measuring approximately 30 mm and 70 mm in diameter. Since biopsy samples from the lung and abdomen revealed poorly differentiated adenocarcinoma and malignant tumor, clinicians first interpreted the abdominal mass as metastatic carcinoma, and a right lower lobectomy with following resection of the mass was performed. Gross examination of both lesions displayed gray-whitish to yellow-whitish cut surfaces with hemorrhagic and necrotic foci, and the mass attached to the serosa of the lesser curvature on the gastric body. On microscopic examination, the lung tumor was composed of a proliferation of highly atypical epithelial cells having abundant eosinophilic cytoplasm, predominantly arranged in an acinar or solid growth pattern with vessel permeation, while the abdominal tumor consisted of sheets or nests with markedly atypical epithelioid cells having pleomorphic nuclei and abundant eosinophilic to clear cytoplasm focally in a radial perivascular or infiltrative growth pattern. Immunohistochemically, the latter cells were positive for HMB45 or α-smooth muscle actin, but the former ones not. Therefore, we finally made a diagnosis of malignant perivascular epithelioid cell tumor (PEComa) arising in the gastric serosa, combined with primary lung adenocarcinoma. Furthermore, small papillary carcinoma of the thyroid gland was identified. The current case describes the coincidence of malignant PEComa with other carcinomas, posing a challenge in distinction from metastatic tumor disease.

Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H2O2) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-π (GSTπ). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSTπ. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.