Extensive left ventricular, pulmonary artery, and pericardial metastasis from myxoid liposarcoma 16 years after the initial detection of the primary tumour: a case report and review of the literature.

Liposarcoma is regarded as the second most common soft tissue malignant tumour. Metastasis of liposarcoma to the heart is very rare, and to date, less than 40 cases have been reported in the literature. We report a 46 year-old male with myxoid liposarcoma of the lower extremity who developed extensive metastasis to the left ventricle, pulmonary artery, and pericardium. The patient presented with acute symptoms of dyspnea 16 years after surgical resection of the primary tumour, and his dyspnea progressed to cardio-respiratory arrest within the first few days of hospital admission.

Inhibition of breast tumor growth and abnormal angiogenesis in mice treated with endothelial cells and their progenitor mesenchymal stem cells derived from bone marrow.

Incorporation of endothelial cells or their progenitor cells into newly sprouting blood vessels can contribute to tissue vascularization after ischemic injury. However, the interaction of the stem cells-derived endothelial cells with angiogenesis within tumors is not well understood. The aim of this study was to examine the efficiency of endothelial-like cells derived from MSCs in controlling breast tumor growth associated with abnormal angiogenesis. For this purpose, Balb/c mouse model of breast carcinoma was developed and subjected to intra tumor (I.T)/intra venous (I.V) therapy with undifferentiated MSCs or endothelial cells derived from them. The homing of the stem cells was approved by measuring different markers as well as tracing green fluorescence protein (GFP)-labeled MSCs in the tumors. Tumor growth was measured following cell therapy using a digital caliper. At the end of treatment period (30 days) the angiogenesis markers; VEGFR2 expression as well as micro-vessel density (MVD) using CD31 were estimated in tumor tissues. Stem cell transplantation to mice bearing breast tumors resulted in tumor growth suppression in all experimental groups. The endothelial markers; CD31 and VEGFR2 were down regulated following I.T delivery of the endothelial cells. Accordingly, angiogenesis was suppressed following I.T administration of endothelial cells which was associated with increased focal necrosis in the tumors. In conclusion, data show that endothelial cells directly injected into tumors is more efficient compared to undifferentiated MSCs in controlling tumor-associated angiogenesis and tumor growth.

Lung tissue engineering and preservation of alveolar microstructure using a novel casting method.

We used a rat model to decellularize and seed alveolar cells on a three-dimensional lung scaffold to preserve alveolar microarchitecture. We verified the preservation of terminal respiratory structure by casting and by scanning electron microscopy (SEM) of the casts after decellularization. Whole lungs were obtained from 12 healthy Sprague-Dawley rats, cannulated through the trachea under sterile conditions, and decellularized using a detergent-based method. Casting of both natural and decellularized lungs was performed to verify preservation of the inner microstructure of scaffolds for further cell seeding. Alveolar cell seeding was performed using green fluorescent protein (GFP) lung cells and non-GFP lung cells, and a peristaltic pump. We assessed cell seeding using histological and immunohistochemical staining, and enzymatic evaluation. All cellular components were removed completely from the scaffolds, and histological staining and SEM of casts were used to verify the preservation of tissue structure. Tensile tests verified conservation of biomechanical properties. The hydroxyproline content of decellularized lungs was similar to native lung. Histological and immunohistochemical evaluations showed effective cell seeding on decellularized matrices. Enzymatic measurement of trypsin and alpha 1 antitrypsin suggested the potential functional properties of the regenerated lungs. Casts produced by our method have satisfactory geometrical properties for further cell seeding of lung scaffolds. Preservation of micro-architecture and terminal alveoli that was confirmed by SEM of lung casts increases the probability of an effective cell seeding process.

Histopathological Study of Chronic Hepatitis B: A Comparative Study of Ishak and METAVIR Scoring Systems.

BACKGROUND: Ishak and METAVIR scoring systems are among the most commonly used histopathological systems to evaluate chronic hepatitis. OBJECTIVE: To assess the level of agreement between these two scoring systems in patients with chronic hepatitis B. METHODS: Liver biopsy samples taken from 92 patients with chronic hepatitis B were considered as the training set; 57 more biopsy specimens were used as the validation set. In the training set, grade of necroinflammation and stage of fibrosis for each liver biopsy specimen were determined by two expert liver pathologists using both Ishak and METAVIR systems. Inter-observer variability between the two pathologists was evaluated. Biopsy specimens of the validation set were seen and scored by a third expert pathologist. In the training set, criteria were developed to categorize Ishak grading and staging systems separately to best fit with the METAVIR scoring system. The criteria found in the training set, was then tested in the validation set. The level of agreement between the two scoring systems was assessed by weighted kappa statistics. RESULTS: For the training set, agreement between the two pathologists was excellent. Using our proposed criteria in the training set, there was excellent level of agreement in grading (κ = 0.89) and staging (κ = 0.99) between Ishak and METAVIR systems. In the validation set, the criteria led to substantial correlation (κ = 0.61) in grading, and excellent correlation (κ = 0.94) in staging between the two systems. CONCLUSION: Using our proposed criteria, excellent or at least substantial concordance between Ishak and METAVIR scoring systems can be achieved for the degree of both necro-inflammatory changes and fibrosis.

Immunohistochemical analysis of nm23 protein expression in thyroid papillary carcinoma and follicular neoplasm.

INTRODUCTION: We aimed at assessing the significance of nm23 gene expression in papillary and follicular carcinomas, the two most common differentiated thyroid carcinomas. MATERIALS AND METHODS: During a cross-sectional study, 173 paraffin blocks, including 131 papillary thyroid carcinomas, 12 follicular carcinomas and 30 follicular adenomas were stained with nm23 marker by immunohistochemistry method. Cytoplasmic staining in more than 10% of the tumor cells was considered as positive, and alpha<0.05 was established as the level of statistical significance for the evaluation of the correlation between nm23 expression and age, sex, tumor size, vascular /capsular invasion and lymph node involvement. RESULTS: nm23 was positive in 40% of the follicular adenoma, 67.2% of the papillary carcinoma and 66.7% of the follicular carcinoma. p value was more than 0.05 in the assessment of the relationship between nm23 and all of the above-mentioned parameters in differentiated thyroid carcinomas. nm23 expression did not significantly differentiate between follicular adenoma and carcinoma. CONCLUSION: According to our results, there is no relationship between nm23 immunoreactivity and age or sex of the patients. Also, nm23 cannot be considered as a useful marker for the evaluation of invasion in differentiated thyroid carcinomas or in distinctions between follicular adenoma and carcinoma.

Relationship between genetic polymorphism of glutathione S-transferase-p1 and p53 protein accumulation in Iranian esophageal squamous cell carcinoma patients.

BACKGROUND: It has been reported that the activity of glutathione S-transferase (GST) is over-expressed in plasma and esophagus biopsies in Iranian patients suffering from esophageal squamous cell carcinoma (SCC). The aim of this study was to find out the frequency of GST-P genotypes in these patients. Moreover, the association of GST-P genotypes with p53 protein accumulation in esophageal epithelium was investigated. MATERIALS AND METHODS: DNA isolated from paraffin-embedded tissue biopsies from patients suffering from esophageal SCC (n = 56) were collected. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using Alw261 enzyme was applied to determine GST-P genotypes (Ile 105 Val). All the samples were also subjected to immunohistochemistry (IHC) for p53. RESULTS: The frequency of GST-P genotypes in Iranian esophagus SCC patients for Ile/Ile, Ile/Val and Val/Val was 73.2, 21.5 and 5.3%. There was no association between GST-P polymorphism and p53 accumulation in esophageal epithelial cells. CONCLUSIONS: The frequency of GST-P polymorphism was not associated with p53 protein accumulation in esophagus epithelium. The frequency of polymorphic variants of GST-P, Ile/Ile, Ile/Val and Val/Val in SCC patients may suggest that Ile to Val substitution in GST-P gene dose not represent susceptibility to SCC in high-risk Iranian population.

Assessment of the factors involving in the development of hypothyroidism in HIV-infected patients: a case-control study.

OBJECTIVES: Increased prevalence of thyroid dysfunction has been reported in HIV-infected patients, and recent studies have shown hypothyroidism as the most common thyroid function abnormality in this population, especially after treatment with antiretroviral drugs (HAART). The aim of this study is to assess risk factors of hypothyroidism in HIV-infected patients in Iran. DESIGN: This case-control study was conducted among 15 hypothyroid (cases) and 70 euthyroid (control group) HIV-infected outpatients. Serum Free T4, Free T3, and TSH levels were measured, and data on age, sex, body mass index, opium addiction or injection of illicit drugs, duration of HIV infection and HAART, disease stage, CD4-cell count, opportunistic infection (OI) or malignancy, HCV co-infection, and drug use were collected. RESULTS: We found no association between hypothyroidism in HIV-infected patients and any parameters measured, and P value was not significant for receipt of HAART (0.141), CD4-cell count (0.094), duration of HIV infection (0.474), duration of HAART (0.418), HCV co-infection (0.146), OI (0.566), or receipt of rifampin (0.816). CONCLUSION: In this study, age, sex, HAART, mean CD4- cell count, duration of HIV infection, HCV co-infection, and OI were not significant risk factors of hypothyroidism in HIV-infected patients. The occurrence of hypothyroidism may be related to other factors or HIV infection itself. Therefore, hypothyroidism should be considered in all HIV-infected patients.

Immunohistochemical study of oestrogen receptors in 351 human thyroid glands.

INTRODUCTION: It is well recognised that the pathogenesis of thyroid diseases is complex and different factors such as genetic factors, iodine deficiency, sex, age, radiation therapy in childhood, growth stimulating antibodies, and other epithelial growth factors can influence them. Epidemiological features of thyroid tumours and experimental evidence suggest that female sex hormones may exert effects on the thyroid gland and its neoplasms. This possibility was addressed by investigating the expression of oestrogen receptor protein in 351 thyroid lesions. METHODS: The tissues from 351 human thyroid glands comprising 130 nodular goitres and 221 neoplastic lesions were used for the present immunohistochemical assessment of oestrogen receptor expression. RESULTS: Incidence of oestrogen receptor positive cases were 24 percent (31/130) for nodular goitres, 22 percent (8/37) for follicular adenomas, 11 percent (2/18) for follicular carcinomas, 31 percent (37/119) for papillary carcinomas, zero percent (0/35) for medullary carcinomas and zero percent (0/12) for undifferentiated carcinomas. The incidence of oestrogen receptor positivity, which is compatible with other studies, is higher in well-differentiated thyroid lesions. The incidence of oestrogen receptor reactivity does not significantly differ between females and males of different age groups and it does not correlate with lymph node status, and vascular and capsular invasions. CONCLUSION: The relatively high proportion of oestrogen receptor positivity in goitres, follicular adenomas and papillary carcinomas, compared with its reactivity in other thyroid neoplasms, and contrasted against normal thyroid tissue, suggests that the incidence of oestrogen receptor reactivity tends to increase with better differentiation of thyroid lesions. This finding may have clinical relevance.

Endocrine cancer in Iran: based on cancer registry system.

BACKGROUND: A population-based registry of endocrine cancer cases in four Iranian provinces, was performed for the years 1996-2000. MATERIALS AND METHODS: Patients in each province were grouped according to age, gender and tumor specifics (site, morphology, behavior) and the data was coded according to the international classification of diseases for oncology. STATISTICAL ANALYSIS USED: Person-years of population at risk were calculated and the results were presented as incidence rates by sex, age, age specific rates and age standard rate (ASR) per 100,000 person-years, using direct method of standardization to the world population. RESULTS: A total of 319 cases of primary endocrine cancer were found and registered, including 313 cases of thyroid carcinoma and 6 cases of adrenal cancer. The thyroid carcinoma group cases consisted of papillary (82.7%), follicular (8.6%), medullary (7.0%) and anaplastic (1.6%) carcinomas. The ASR for thyroid carcinoma was 1.289 (0.627 for men, 1.59 for women), with the highest incidence rate in Kerman (ASR 1.643) and the lowest incidence rate in Golestan (ASR 0.735). For the 6 cases of adrenal cancer, 4 were neuroblastoma and 2 were pheochromocytoma. CONCLUSIONS: Iran was considered as an endemic, iodine-deficient area, until fairly recently. Iodinization of salt has been started about 12 years ago, in the nation. Considering the effect of improvement in the iodine intake in previously deficient communities, which is associated with an increase in the incidence of papillary carcinoma compared to other histologic types, the frequency and distribution of histologic types of thyroid carcinoma was closer to what can be seen in iodine-rich areas.

Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats.

AIM: The aim of this study was to investigate the hypothesis that the opioid system is involved in the development of hepatic fibrosis. METHODS: The effect of naltrexone (an opioid receptor antagonist) on hepatic fibrosis in bile duct ligated (BDL) or sham rats was assessed by histology and hepatic hydroxyproline levels. Liver matrix metalloproteinase 2 (MMP-2) was measured by zymography, and alpha smooth muscle actin (alpha-SMA) and CD45 (leucocyte common antigen) by immunohistochemistry. The redox state of the liver was assessed by hepatic glutathione (GSH)/oxidised glutathione (GSSG) and S-nitrosothiol levels. Subtypes of opioid receptors in cultured hepatic stellate cells (HSCs) were characterised by reverse transcriptase-polymerase chain reaction, and the effects of selective delta opioid receptor agonists on cellular proliferation, tissue inhibitor of metalloproteinase 1 (TIMP-1), and procollagen I expression in HSCs determined. RESULTS: Naltrexone markedly attenuated the development of hepatic fibrosis as well as MMP-2 activity (p<0.01), and decreased the number of activated HSCs in BDL rats (p<0.05). The development of biliary cirrhosis altered the redox state with a decreased hepatic GSH/GSSG ratio and increased concentrations of hepatic S-nitrosothiols, which were partially or completely normalised by treatment with naltrexone, respectively. Activated rat HSCs exhibited expression of delta1 receptors, with increased procollagen I expression, and increased TIMP-1 expression in response to delta(1) and delta(2) agonists, respectively. CONCLUSIONS: This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.

Multifocal pigmented villonodular synovitis in a child.

Pigmented villonodular synovitis is a rare benign disorder and usually affects young and middle-aged adults. It occurs either as a localised pedunculated form or more common diffuse form, and is almost always unifocal. Only few cases of multifocal involvement have been reported, all of them in children. Multifocal pigmented villonodular synovitis occurring in a 5-year-old girl is presented. Both her knees and left elbow were involved. All three lesions were of localised pedunculated type and were completely excised. She is believed to be one of the youngest patients reported.

Histopathological findings in cardiac transplant recipients: an assessment after 10 years' experience in Iran.

BACKGROUND: For many patients with end-stage heart failure, cardiac transplantation remains the definitive therapeutic option. The first Iranian heart transplantation was successfully performed on July 8, 1993, at Dr Shariati Hospital, Tehran. This article reports the pathology of heart transplants performed in one decade at Dr. Shariati Hospital. METHODS: All individuals who underwent heart transplantation between July 1993 and July 2003 were studied for the pathology reports of endomyocardial biopsies of heart transplant recipients. One-month, 1-year, and 5-year survival rates are also presented. RESULTS: Forty-five patients (14 females and 31 males) aged 29.6 +/- 12 years underwent heart transplantation. One-month, 1-year, and 5-year survival rates were 80%, 59.5%, and 50%, respectively. The grades of rejection were: 0 in 31 biopsies (24.2%); 1A in 27 (21.1%); 1B in one (0.8%); 2 in 21 (16.4%); 3A in 34 (26.6%); 3B in 9 (7%); 4 in four specimens (3.1%), and one biopsy was inadequate (0.8%). A Quilty B effect was observed in one specimen (0.8%), but a Quilty A effect, cytomegalovirus or toxoplasmic myocarditis, or previous biopsy sites were not observed. CONCLUSION: Survival rates of heart transplant recipients were lower compared with the international statistics. The incidence and severity of rejection episodes were higher among our patients. These findings may be due in part to the noncompliance of heart transplant recipients with the follow-up biopsy schedules, leading to late detection of rejection episodes.

Epidemiologic analysis of the Tehran Cancer Institute Data System Registry (TCIDSR).

OBJECTIVE: To review epidemiological data on thyroid cancer in Iran. METHODS: The Tehran Cancer Institute Data System Registry (TCIDSR) was used to identify patients with different histological types of thyroid cancer (TC) in Iran. Data were analysed from 438 thyroid cancer cases identified by the TCIDSR in 1998-99. Disease prevalence was calculated with reference to age, time and place. RESULTS: The TCIDSR recorded 438 primary malignancies of the thyroid gland: papillary, follicular, medullary, and anaplastic carcinomas accounted for 67.1%, 10.7%, 5.3% and 4.3% of cases, respectively. The remaining 12.6% were classified as OD (other diagnoses). The prevalence of TC was highest in ethnic Farsis. The age range of patients was 8-85 years. Mean patient age was 44.52+17.03 years (mean + SD) overall, 47.74+18.10 years in female patients and 43.04+16.34 years in male patients. Anaplastic (6.5% vs. 3.3%) and medullary (10.0% vs. 3.0%) cancers were more common in men than women. CONCLUSION: This study was undertaken to define the epidemiological aspects of thyroid carcinoma in Iran, an area of endemic iodine deficiency until fairly recently. Against expectation for an iodine-deficient area, the frequency distribution of tumours in our study was closer to that seen in iodine-rich areas. Additional research on the risk factors for thyroid cancer--genetic, ethnic, geographic and environmental--is needed to explain the high incidence of PTC overall, and among ethnic Farsis in particular, in Iran.

Correlation between prostate needle biopsy and radical prostatectomy Gleason gradings of 111 cases with prostatic adenocarcinoma.

PURPOSE: There are conflicting reports in the literature about correlation of biopsy and prostatectomy Gleason scores in prostate carcinoma. The goal of this study was to determine the correlation of grading in these two types of pathologic materials. MATERIALS AND METHODS: The coupled Hematoxylin and Eosin slides of 111 patients with prostate carcinoma were collected. Gleason scores were determined. Patients who had undergone any therapy except surgery were excluded from the study. Correlation between grades was calculated by determination of correlation coefficient. Accuracy of biopsy grading in prediction of final grade was also determined by measuring the sensitivity, specificity, and positive and negative predictive values. RESULTS: In 50 cases (45%), grade was underestimated in the biopsy. After dividing the cases into Gleason scores of 2 to 4, 5 to 6, 7, and 8 to 10, the most of undergraded cases (84.2%) were in the first group (Gleason score 2 to 4) and this rate reached 5% in the fourth group (Gleason score 8 to 10). The correlation coefficient measured was 0.535 in grade to grade comparing and 0.514 in group to group comparison of the specimens. In low-grade tumors, grading in biopsy, in spite of high sensitivity (90.9%), had low positive predictive value (26.3%). CONCLUSION: There is a moderate direct linear relationship between scores in biopsy and prostatectomy specimens. But there is a high probability of underestimation of real Gleason score of the radical prostatectomy specimen in low-grade tumors. Pathologists and urologists must consider the phenomenon of undergrading in reporting prostate specimens and managing patients.

Spot urine 5-hydroxy indole acetic acid and acute appendicitis.

BACKGROUND/AIMS: Appendectomy for suspected appendicitis cases is a common procedure. Its clinical diagnosis needs to be supported by accurate confirmatory tests. No single paraclinical test with a high degree of sensitivity and specificity is available for its diagnosis. The appendix contains numerous serotonin-producing cells (enterochromaffin cells). In the inflammatory process and subsequent cell injury, serotonin is released and converted to 5-HIAA (5-hydroxy indole acetic acid). We studied the elevation of 5-HIAA in the spot urine of acute appendicitis patients. METHODOLOGY: 5-HIAA was measured by high-performance liquid chromatography in the spot urine samples of 40 healthy individuals and 166 patients who presented to emergency units of the university hospitals with acute abdominal pain. The results of the urine concentrations were compared to the histopathology reports of the removed appendices and the final diagnosis of other diseases. RESULTS: From 80 cases with a presumptive diagnosis of appendicitis, 73 were operated on and seven cases discharged after a few hours observation. Sixty-five out of 66 documented appendicitis patients showed a striking increase of urinary spot 5-HIAA with significant differences vs. all cases of healthy control individuals (P < 0.001). The 5-HIAA values of all of the negative appendectomy cases (n = 7) and all of the discharged cases after the observation period (n = 7) were within healthy control ranges. The mean value of the appendicitis group (42.76 +/- 2.26 mumol/L) was also significantly higher vs. all other acute abdomens which could mimic acute appendicitis (P < 0.05) excepting gastroenteritis patients. Considering 20 mumol/L as the cutoff value sensitivity, specificity, positive and negative predictive values of this test for discriminating appendicitis in clinically suspected patients were 98%, 100%, 100% and 93%, respectively and in all acute abdomens were 98%, 71%, 69% and 98.6%, respectively. The patients with gastroenteritis also showed elevation of 5-HIAA (43.05 +/- 2.7 mumol/L) vs. other nonappendicitis groups (P < 0.05). CONCLUSIONS: We have concluded that measurement of 5-HIAA in spot urine is a highly reliable test supporting the clinical diagnosis of appendicitis and if it does not show an increase, appendicitis can be ruled out with a very high degree of confidence which helps to reduce unnecessary appendectomies. In clinically suspected appendicitis patients with diarrhea, an increase of 5-HIAA may not confirm the diagnosis.

Lymphoepithelial-like intrathyroidal thymic carcinoma with foci of squamous differentiation. Case report.

Thymoma is only rarely reported within the thyroid gland. In this communication a case of thymic carcinoma with lymphoepithelial-like appearance and foci of squamous differentiation is described. The tumor showed no evidence of recurrence or metastasis at clinical follow-up. The histogenesis of such a lesion is discussed.