Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are modulated by dietary polyunsaturated fatty acids

The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22–25 and at 36–40 weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36–40 weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.     

软骨肿瘤异柠檬酸脱氢酶基因突变的研究进展

软骨肿瘤是常见的原发性骨肿瘤,根据频发或特异的驱动基因变异可以对软骨肿瘤进行分子分型,从而更精准地指导临床诊疗.异柠檬酸脱氢酶(IDH)是一类代谢酶家族,广泛参与糖代谢、氨基酸代谢和脂类代谢过程.IDH1/IDH2突变后的代谢产物能够导致基因过甲基化和组蛋白修饰改变,进而诱发肿瘤.既往研究显示,良性和恶性软骨肿瘤中均存...     

胃肠道及胃肠道外间质瘤的临床病理及免疫组化分析

目的:研究胃肠道及胃肠道外间质瘤的临床病理及免疫组化特点。方法:应用光学显微镜观察20例胃肠道及胃肠道外间质瘤的形态特征,用免疫组化SP法检测CD117、CD34、Vimentin、SMA、desmin及S-100等6种抗体的表达情况。结果:20例间质瘤中,女性11例,男性9例,平均年龄59·82岁(27~80岁)。发生部位:胃8例(40%),小肠4例(20%),大肠2例(10%),食管1例(5%),肠系膜4例(20%),大网膜1例(5%)。肿瘤镜下主要由梭形和上皮样细胞组成,有栅栏状、交叉束状、漩涡状及巢状等多种排列。CD117、CD34、Vimentin、SMA、desmin及S-100表达阳性率分别为95%(19/20),75%(15/20),100%(20/20),40%(8/20),5%(1/20)及25%(5/20)。临床症状以腹部包块、腹部不适及消化道出血为主。良性3例(3/20),潜在恶性4例(4/20),恶性13例(13/20)。恶性间质瘤中的核分裂>5/50HPF、肿瘤细胞坏死及细胞密集比良性和低度恶性者常见(P<0·05)。结论:间质瘤多发生于老年人,无性别差异,胃肠道是其好发部位,细胞排列多样,具有多向分化能力,免疫组化证实部分GIST具有不完全的平滑肌、神经单向或双向分化特征。核分裂>5/50HPF、肿瘤细胞坏死及细胞密集是重要的恶性指征。CD117及CD34是其较特异及敏感的抗体,免疫组化在间质瘤的诊断及鉴别诊断中起重要作用。     

MR化学位移成像在腹腔含脂病变中的应用价值

目的评价梯度回波化学位移成像诊断腹腔含脂病变诊断的价值。资料与方法对55例上腹部脏器患有含脂局灶病变的病例(其中局灶性脂肪肝15例、肝细胞腺瘤2例、脂肪变性的高分化肝细胞癌9例、肾上腺腺瘤l8例、肾脏血管平滑肌脂肪瘤8例)进行扰相梯度回波(SPGR)T1WI同/反相位成像,分析病灶在各序列上的信号变化。结果所有的含脂病变在SPGR T1WI反相位图像出现类似的信号衰减。结论利用扰相GRET1WI序列,选用双回波技术在同一次扫描中同时获得反相位和同相位图像成像在检测病灶内脂肪方面具有重要诊断价值。     

Ethanol induces hyperprolactinemia by increasing prolactin release and lactotrope growth in female rats

BACKGROUND: Alcohol drinking is known to cause hyperprolactinemia in both humans and laboratory animals. The mechanism by which alcoholism causes hyperprolactinemia is not known. This study investigated whether increased pituitary production of prolactin, which leads to alcohol-induced hyperprolactinemia, results from an increase in cell number and/or cell production of prolactin in the pituitary. METHODS: The effects of ethanol on lactotropes were determined in vivo using female rats as an animal model and in vitro using primary cultures of mixed rat anterior pituitary cells and enriched lactotropes. In vivo experiments involved administration of ethanol for 2 and 4 weeks using a liquid diet containing 8.7% ethanol (v/v), which provides 37% of the calories in cyclic, ovariectomized, and estradiol-17beta-treated ovariectomized Fischer-344 rats. The control group was pair-fed an isocaloric diet minus the ethanol or fed a normal diet ad libitum. These animals were used to determine ethanol's effects on plasma prolactin levels, pituitary wet weights, pituitary total protein levels, and the number of mitotic lactotropes. In vitro studies determined ethanol's effects in the presence and absence of estradiol on prolactin release and lactotropic cell proliferation. Prolactin levels in plasma and media samples were measured using radioimmunoassay. Mitotic lactotropes were determined using bromodeoxyuridine incorporation assay. RESULTS: Ethanol treatment increased in a time-dependent manner the plasma levels of prolactin in cyclic, ovariectomized, and estradiol-treated ovariectomized rats. Ethanol treatment also increased pituitary wet weight and/or pituitary total protein levels and DNA synthesis in lactotropes. Determination of ethanol's action on lactotropic cell proliferation and hormone secretion in vitro using primary cultures of mixed pituitary cells revealed that ethanol stimulated both basal and estradiol-induced prolactin secretion and lactotropic cell proliferation. When ethanol's actions were studied in isolated lactotropes, ethanol alone or in combination with estradiol stimulated prolactin secretion but failed to increase lactotropic cell proliferation. CONCLUSIONS: These results suggest that ethanol causes hyperprolactinemia by elevating prolactin release from lactotropes and by increasing the number of lactotropes in the anterior pituitary gland. The mitotic action of ethanol requires cell-cell communication between lactotropes and other pituitary cells. Furthermore, ethanol's mode of action on prolactin release and lactotrope growth is similar to that observed for estradiol.     

Mixed Tumors,Myoepitheliomas, and Oncocytomas of the Soft Tissues Are Likely Members of the Same Family: A Clinicopathologic and Ultrastructural Study

Four diagnostically unusual soft tissue tumors are presented. All lesions were of consistent size and long duration. Histologically, one lesion was analogous to mixed tumors of the usual sites (i.e., salivary glands), one lesion was totally spindled, and the two other lesions both had oncocytic appearances ( epithelioid and spindle biphasic pattern in a case, purely epithelioid in the other). Immunohistochemically, the mixed tumor was positive for vimentin, cytokeratins, S-100 protein, and focally for EMA. The purely spindled tumor exhibited immunoreactivity for vimentin, actins, S-100 protein, EMA (focally), and GFAP. The oncocytic biphasic tumor was positive for mitochondrial antigen, vimentin, and actins. The purely epithelioid oncocytic neoplasm was immunoreactive only for mitochondrial antigen and vimentin. Ultrastructurally, in the epithelial-like portion of the first (mixed) tumor, peripheral arrays of contractile filaments were detected along with well-developed desmosomes. In the second (spindled) case, peripheral contractile filaments and attenuated desmosomes were also seen. In the third case, a huge number of mitochondria, some desmosomes, and actin-type microfilaments were found. In the fourth case, desmosomes and punctate subplasmalemmal densities, in addition to numerous mitochondria, were documented. In all cases an external basal lamina were present, which was discontinuous in the first three cases and almost continuous in the fourth. These tumors were respectively designated as mixed tumor, myoepithelioma of the classic type, myoepithelioma of oncocytic type with biphasic cell architecture, and true oncocytoma. So far, all tumors have followed benign clinical courses (median follow up: 12 months). Comparisons with similar tumors of other sites are drawn, and suggestions for considering all of them as members of the same myoepithelial-derived tumor family are given.     

Primary Composite Angiogenic Leiomyosarcoma?Epithelioid Angiosarcoma of the Brain

The authors describe a primary sarcoma of the brain with immunohistochemical and ultrastructural features of leiomyosarcoma as well as epithelioid hemangiosarcoma. The leiomyosarcomatous component consisted of spindle cells with well-developed external lamina, subsarcolemmal densities composed of microfilaments, pinocytic vesicles, and abundant intermediate filaments, and showed immunohistochemical reactions for smooth muscle actin. The epithelioid part of the tumor contained scattered cells reactive for alkaline phosphatase as well as CD31 and factor VIII. Many epithelioid cells were lipidized and remarkably similar to "stromal cells" of a hemangioblastoma. Occasional Weibel-Palade bodies, indicating endothelial differentiation, were present in scattered neoplastic cells. There were also cells with features intermediate between endothelium, pericytes and smooth muscle cells, and undifferentiated mesenchymal cells. The brain at the periphery of sarcoma showed conglomerates of well-differentiated capillaries, telangiectasias and small dysplastic arteries, features that raise the possibility of origin of this tumor from a preexisting vascular developmental abnormality.     

Ultrastructure of Adrenal Cortical Carcinoma

The ultrastructural features of 30 adrenal cortical carcinomas have been reviewed and compared with those seen in adrenal cortical adenomas, adrenal cortical hyperplasia, and the normal cortex. A broad range of ultrastructural appearances was found among the carcinomas, but the differences were mainly in the amount of cytoplasmic lipid, number of lysosomes, and quantity and architecture of the mitochondria and endoplasmic reticulum. Structural variants among the carcinomas included lipid-rich, oncocytic, and glycogen-rich cells. Electron microscopy can be extremely useful in differential diagnoses that include adrenal cortical carcinoma.     

Imaging of the spine and spinal cord: An overview of magnetic resonance imaging (MRI) techniques

This review will discuss conventional and advanced magnetic resonance (MRI) imaging techniques used to study the spine and spinal cord according to the anatomical structures and clinical indications. Clinical challenges that neuroradiologists may face are also discussed, such as the “when” and “where” concerning the use of each technique, and in which pathology or clinical scenario each technique is useful. Finally, some “tips and tricks” to overcome the challenges are provided with clinical examples.     

Diagnostic Utility of Diffusion-weighted Magnetic Resonance Imaging in Differentiating Small Solid Renal Tumors (≤4 cm) at 3.0T Magnetic Resonance Imaging

Background:

The aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤4 cm).

Methods:

In this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm² and values compared via the Kruskal–Wallis and Mann–Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression.

Results:

The tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10⁻³ mm²/s), ccRCCs ([1.53 ± 0.31] × 10⁻³ mm²/s) and the normal renal parenchyma ([2.22 ± 0.12] × 10⁻³ mm²/s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10⁻³ mm²/s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs.

Conclusions:

DW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.