With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.
Angiotensin Receptor Antagonists ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Aortic Valve ; pathology ; Aortic Valve Stenosis ; complications ; drug therapy ; etiology ; Calcinosis ; complications ; drug therapy ; etiology ; Calcium Metabolism Disorders ; complications ; Disease Progression ; Dyslipidemias ; complications ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; therapeutic use ; Inflammation ; complications ; Phosphorus Metabolism Disorders ; complications ; Quality of Life

Aortic valve calcification is a common disease in the elderly, but its cellular and molecular mechanisms are not clear. In order to verify the hypothesis that Wnt/β-catenin signaling pathway is involved in the process of calcification of aortic valve, porcine aortic valve interstitial cells (VICs) were isolated, cultured and stimulated with oxidized low density lipoprotein (ox-LDL) for 48 h to induce the differentiation of VICs into osteoblast-like cells. The key proteins and genes of Wnt/β-catenin signaling pathway, such as glycogen synthase kinase 3β (GSK-3β) and β-catenin, were detected by using Western blotting and real-time polymerase chain reaction (PCR). The results showed that the VICs managed to differentiate into osteoblast-like cells after the stimulation with ox-LDL and the levels of proteins and genes of GSK-3β and β-catenin were increased significantly in VICs after stimulation for 48 h (P<0.05). It is suggested that Wnt/β-catenin signaling pathway may play a key role in the differentiation of VICs into osteoblast-like cells and make great contribution to aortic valve calcification.
Alkaline Phosphatase ; genetics ; metabolism ; Animals ; Aortic Valve ; metabolism ; pathology ; Aortic Valve Stenosis ; Blotting, Western ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Calcinosis ; Cell Differentiation ; drug effects ; genetics ; Cells, Cultured ; Gene Expression ; drug effects ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Lipoproteins, LDL ; pharmacology ; Osteoblasts ; drug effects ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Swine ; Wnt Signaling Pathway ; genetics ; physiology ; beta Catenin ; genetics ; metabolism

OBJECTIVETo investigate the morphological features, immunohistochemical phenotype, diagnosis and differential diagnosis of collagenous spherulosis of the breast.

METHODSClinicopathologic observation, immunohistochemistry using EnVision method and histochemical staining were applied in 33 cases of collagenous spherulosis of the breast.

RESULTSCollagenous spherulosis of the breast was a benign lesion, consisting of proliferative myoepithelial and ductal epithelial cells. These cells were arranged in a cribriform pattern with esinophilic, round, oval or star-shaped fibrillary spherules in the lumen.SMA, calponin and p63 by immunohistochemistry identified the proliferative myoepithelium, while E-cadherin identified the proliferative ductal epithelial cells. The esinophilic spherules were stained with collagen type IV, AB-PAS and reticulin. Collagenous spherulosis was often found in sclerosing adenosis.

CONCLUSIONSCollagenous spherulosis of the breast is often associated with other diseases. It has special morphological presentation and is easily confused with malignant tumors such as adenoid cystic carcinoma or cribriform carcinoma in situ, and needs to be differentiated from these disease entities.

Actins ; metabolism ; Adult ; Aged ; Breast ; pathology ; Breast Diseases ; metabolism ; pathology ; Cadherins ; metabolism ; Calcinosis ; Calcium-Binding Proteins ; metabolism ; Collagen ; metabolism ; Collagen Type IV ; metabolism ; Female ; Humans ; Hyperplasia ; Membrane Proteins ; metabolism ; Microfilament Proteins ; metabolism ; Middle Aged

This study aimed to determine and quantitate the mammographic and sonographic characteristics in 13 cases of solid neuroendocrine breast carcinoma (NEBC) and to analyze the association of radiological findings with the clinical and histopathologic findings. The clinical data and imaging findings of 13 female patients with histologically confirmed solid NEBC were reviewed. Imaging data were evaluated by two radiologists for a consensual diagnosis. All patients presented with one palpable mass; only 1 experienced occasional breast pain, and 5 complained of fluid discharge. In 7 patients, the masses were firm and mobile. Regional lymph node metastasis was noted in only 1 patient. For the 10 patients who underwent mammography, 6 had a mass, 1 had clustered small nodules with clustered punctuate microcalcifications, 2 had asymmetric focal density, and 1 had solitary punctuate calcification. Most of the masses had irregular shape with indistinct or microlobulated margins. For the 9 patients who underwent ultrasonography (US), 9 masses were depicted, all of which were hypoechoic, mostly with irregular shape and without acoustic phenomena. Different types of acoustic phenomena were also identified. One patient had developed distant metastases during follow-up. NEBC has a variety of presentations, but it is mostly observed on mammograms as a dense, irregular mass with indistinct or microlobulated margins. Sonographically, it typically presents as an irregular, heterogeneously hypoechoic mass with normal sound transmission. Histories of nipple discharge and calcification observed using imaging are not rare.
Adult ; Aged ; Biopsy, Fine-Needle ; Breast Neoplasms ; diagnostic imaging ; metabolism ; pathology ; Calcinosis ; diagnostic imaging ; Carcinoma, Neuroendocrine ; diagnostic imaging ; metabolism ; pathology ; Chromogranin A ; metabolism ; Female ; Follow-Up Studies ; Humans ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Phosphopyruvate Hydratase ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Synaptophysin ; metabolism ; Ultrasonography, Mammary

The purpose of this review is to investigate the value of the calcification in differentiating malignant thyroid neoplasm and the molecular mechanisms for the formation of the calcification. Many published reports have proved the presence of calcifications in thyroid neoplasm and calcified nodules in these studies are more frequently malignant than noncalcified nodules. Through viewing the related references, we found that psammoma bodies (PBs), Runx2, osteocalcin, osteopontin, CD44v6 play an important role in the molecular mechanisms in the formation of the calcification in PTC. But further study is required for elucidating the mode of action.
Calcinosis ; diagnosis ; pathology ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Humans ; Hyaluronan Receptors ; metabolism ; Osteocalcin ; metabolism ; Osteopontin ; metabolism ; Thyroid Neoplasms ; diagnosis ; pathology ; Thyroid Nodule ; pathology

OBJECTIVETo study the clinicopathologic features and histogenesis of calcifying fibrous tumor (CFT).

METHODSThe clinical manifestations, histopathologic characteristics and immunophenotype were analyzed in 11 cases of CFT.

RESULTSThe male-to-female ratio was 5:6, with a mean age of 38 years and age range of 25 to 52 years. The sites of involvement included abdominopelvic cavity (n=6), soft tissue (n=4) and scrotum (n=1). Most patients presented with a gradually enlarging and painless mass. Nearly half of the cases were associated with other diseases or history of inflammation, trauma or surgical intervention. One third of the tumors represented incidental findings and showed no recurrence after resection. Imaging revealed a solitary solid soft tissue mass or multiple nodules with clear borders and associated high-density calcifications. Macroscopically, the tumors were well-circumscribed but non-encapsulated. They ranged from 0.5 to 20.0 cm in diameter and were tan-greyish, round to oval, lobulated or irregular and solid with rubbery consistency. The cut surface was whitish to tan-yellowish, gritty and showed scattered spotty yellowish discoloration corresponding to the foci of dystrophic calcifications. Histologically, CFT was composed of hyalinized fibrous tissue and thickened vessel walls with interspersed bland spindly fibroblastic cells, scattered psammomatous calcifications, dystrophic calcification and lymphoplasmacytic infiltration. In addition, focal cloak-like polymorph infiltration at the tumor periphery and entrapment of adipocytes and nerves were demonstrated in some cases. Foci resembling solitary fibrous tumor, fibromatosis, keloid or inflammatory myofibroblastic tumor were observed. Immunohistochemical study showed that the tumor cells were diffusely positive for vimentin and focally positive for CD34, factor VIII-related antigen and beta-catenin. The admixed plasma cells were notably IgG positive, with more than 50% being IgG4 positive.

CONCLUSIONSCFT has characteristic histopathologic manifestations and shows morphologic and immunohistochemical overlaps with known IgG4-related sclerosing diseases. It is possible that CFT may represent another example of IgG4-related diseases. It often runs a benign clinical course, with rare recurrence after surgical resection. Previous inflammation and trauma may be the precipitating factors of CFT.

Abdominal Neoplasms ; metabolism ; pathology ; surgery ; Adult ; Antigens, CD34 ; metabolism ; Calcinosis ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Genital Neoplasms, Male ; metabolism ; pathology ; surgery ; Humans ; Immunoglobulin G ; metabolism ; Incidental Findings ; Male ; Middle Aged ; Neoplasms, Fibrous Tissue ; metabolism ; pathology ; surgery ; Pelvic Neoplasms ; metabolism ; pathology ; surgery ; Retrospective Studies ; Scrotum ; pathology ; Soft Tissue Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; beta Catenin ; metabolism ; von Willebrand Factor ; metabolism

OBJECTIVETo examine the relationship between reduction of serum fetuin A and coronary artery calcification (CAC) in patients starting hemodialysis.

METHODSTwenty-nine patients on chronic hemodialysis (duration of hemodialysis less than 6 months) were enrolled in this study. Serum fetuin A and such potential CAC-related risk factors as C-reactive protein (CRP), Ca, P, iPTH, body mass index (BMI) were examined. CAC was detected by multislice spiral CT scan (MSCT) and quantified by the modified Agaston's scoring system. All the 29 patients were followed up for 18 months to appraise the cardiovascular events defined as cardiac failure, angina pectoris or myocardial infarction.

RESULTSEleven patients (78.57%) were found to have CAC as detected by MSCT in low serum fetuin A (below the average serum concentration of 0.71 g/L) group, a rate significantly higher than that in high serum fetuin A group (7 patients, 46.67%, P<0.05). Serum fetuin A in these 29 patients was related with CAC score (Pearson correlation coefficient of -0.734, P=0.001) and stepwise regression analysis indicated that serum fetuin A (standardized beta=-0.568, P=0.003) and age (standardized beta=0.416, P=0.019) were independently correlated to CAC. Such factors as CRP, Ca, P, iPTH, Chol, TG, HDL-C, LDL-C, BMI and blood pressure were excluded from the regression equation. Reduction of serum fetuin A was associated with cardiovascular events (Spearman's rho -0.758, P<0.01). No significant difference was found between low and high serum fetuin A groups by Kaplan-Meier survival analysis (P=0.065).

CONCLUSIONReduced serum fetuin A may be a potential risk factor of coronary artery calcification, and can contribute to cardiovascular events in patients starting hemodialysis.

Adult ; Aged ; Blood Proteins ; metabolism ; Calcinosis ; blood ; etiology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Renal Dialysis ; adverse effects ; Risk Factors ; alpha-2-HS-Glycoprotein

Adult ; Calcinosis ; metabolism ; pathology ; surgery ; Fibrosis ; metabolism ; pathology ; surgery ; Humans ; Male ; Neoplasms, Muscle Tissue ; metabolism ; pathology ; surgery ; Thoracic Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Adult ; Calcinosis ; metabolism ; pathology ; Diagnosis, Differential ; Fibroma ; metabolism ; pathology ; Gastrointestinal Stromal Tumors ; pathology ; Humans ; Male ; Stomach Neoplasms ; metabolism ; pathology ; Vimentin ; metabolism

PURPOSE: To evaluate radiological findings of non-calcified ductal carcinoma in situ (DCIS) and to correlate those with histological features. MATERIALS AND METHODS: From July 2002 to March 2006, 22 patients with histologically-proven non-calcified DCIS were included. Mammography was obtained in 19 patients, ultrasound in 18 patients, and both examinations in 15 patients. Radiological findings were evaluated according to the Breast Imaging Reporting and Data System by American College of Radiology. Histological tumor subtype and Van Nuys classification of DCIS were assessed. RESULTS: Histological subtypes consisted of mixed type in 11 patients (50%), comedo in 4 (18%), cribriform in 4 (18%), papillary type in 2 (9%), and solid in one (5%). According to Van Nuys classification, group 3 DCIS was observed in 13 (59%) patients. In the 19 patients who underwent mammography, 13 patients presented with abnormal findings: focal asymmetry in 7 patients (37%), masses in 4 (21%), skin thickening in one (5%), and architectural distortion in one (5%). In the 18 patients who had received breast ultrasound, a mass was present in 15 (83%) patients and ductal changes in 3 patients (17%). Sixty percent of patients with masses on ultrasound had group 3 DCIS and 100% of patients with ductal change had group 1 DCIS (p=0.017). CONCLUSION: Diagnosis of non-calcified DCIS by mammography is not an easy task due to the lack of typical malignant calcifications or masses. High resolution ultrasound can be useful for detecting non-calcified DCIS, and ultrasound findings are correlated with histological features.
Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/metabolism/pathology/*radiography/*ultrasonography ; Calcinosis/metabolism/pathology ; Carcinoma, Intraductal, ; Female ; Humans ; Mammography ; Middle Aged