Immunohistochemical and Molecular Characteristics of Follicular Patterned Thyroid Nodules with Incomplete Nuclear Features of Papillary Thyroid Carcinoma

Background : Follicular patterned thyroid nodules with incomplete nuclear features of papillary thyroid carcinoma (FTN-INPTCs) are difficult to diagnose, and their biological behavior and association with follicular variants of PTC (FVPTCs) have not yet been established. The aim of this study is to determine immunohistochemical and molecular characteristics of FTN-INPTCs. Methods : We investigated immunohistochemical features (galectin-3, HBME-1, CK19, fibronectin-1, CITED1), BRAF V600E mutation and RASSF1A promoter methylation status in 30 FTN-INPTC cases, along with 26 FVPTCs, 21 follicular adenomas (FAs) and 14 nodular hyperplasias (NHs). Results : Expression of galectin-3, HBME-1, CK19 and CITED1 was significantly higher in FTN-INPTCs than in FAs or NHs, but expression of galectin-3, CK19 and fibronectin-1 was lower in FTN-INPTCs than in FVPTCs. The BRAF V600E mutation was not detected in the benign nodules or FTN-INPTCs, whereas 57% of FVPTCs had the mutation. RASSF1A promoter methylation was higher in FTN-INPTCs than in benign nodules but there was no difference between FTN-INPTCs and FVPTCs. Conclusions : Our results represent the borderline immunohistochemical and molecular characteristics of FTN-INPTC. We conclude that FTN-INPTC is an intermediate lesion between a benign nodule and a FVPTC, and that it is pathogenetically related to FVPTC.This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006- 331-E00050).Arora N, 2008, WORLD J SURG, V32, P1237, DOI 10.1007/s00268-008-9484-1Park YJ, 2007, J KOREAN MED SCI, V22, P621CHAN JKC, 2007, DIAGNOSTIC HISTOPATH, P997Rhoden KJ, 2006, J CLIN ENDOCR METAB, V91, P2414, DOI 10.1210/jc.2006-0240de Matos PS, 2005, HISTOPATHOLOGY, V47, P391, DOI 10.1111/j.1365-2559.2005.02221.xNakamura N, 2005, LAB INVEST, V85, P1065, DOI 10.1038/labinvest.3700306Xing M, 2005, ENDOCR-RELAT CANCER, V12, P245, DOI 10.1677/erc.1.0978Papotti M, 2005, MODERN PATHOL, V18, P541, DOI 10.1038/modpathol.3800321Prasad ML, 2005, MODERN PATHOL, V18, P48, DOI 10.1038/modpathol.3800235Weisenberger DJ, 2005, NUCLEIC ACIDS RES, V33, P6823, DOI 10.1093/nar/gki987Vasko VV, 2004, EUR J ENDOCRINOL, V151, P779Kim KH, 2004, YONSEI MED J, V45, P818Gasbarri A, 2004, BRIT J CANCER, V91, P1096, DOI 10.1038/sj.bjc.6602097Xing MZ, 2004, CANCER RES, V64, P1664Kimura ET, 2003, CANCER RES, V63, P1454Hirokawa M, 2002, AM J SURG PATHOL, V26, P1508Schagdarsurengin U, 2002, CANCER RES, V62, P3698Fusco A, 2002, AM J PATHOL, V160, P2157Shivakumar L, 2002, MOL CELL BIOL, V22, P4309, DOI 10.1128/MCB.22.12.4309-4318.2002Coli A, 2002, HISTOPATHOLOGY, V40, P80Bartolazzi A, 2001, LANCET, V357, P1644Eads CA, 2001, CANCER RES, V61, P3410Williams ED, 2000, INT J SURG PATHOL, V8, P181Orlandi F, 1998, CANCER RES, V58, P3015Sack MT, 1997, MODERN PATHOL, V10, P668Herman JG, 1996, P NATL ACAD SCI USA, V93, P9821OKAYASU I, 1995, CANCER, V76, P2312BERHO M, 1995, ANN CLIN LAB SCI, V25, P513RAPHAEL SJ, 1994, MODERN PATHOL, V7, P295ROSAI J, 1992, ATLAS TUMOR PATHOL, P65

Intrapancreatic Accessory Spleen: Findings on MR Imaging, CT, US and Scintigraphy, and the Pathologic Analysis

Although the tail of the pancreas is the second most common site of an accessory spleen, intrapancreatic accessory spleen (IPAS) has rarely been noted radiologically. However, as the imaging techniques have recently advanced, IPAS will be more frequently detected as an incidental pancreatic nodule on CT or MRI. Because accessory spleens usually pose no clinical problems, it is important to characterize accessory spleens as noninvasively as possible. An IPAS has similar characteristics to those of the spleen on the precontrast and contrast-enhanced images of all the imaging modalities. In particular, inhomogeneous enhancement of an IPAS in its early phases may be a diagnostic clue. Superparamagnetic iron oxide (SPIO)-enhanced MRI and Levovist-enhanced US, and the mechanisms of which are theoretically similar to that of Tc-99m scintigraphy, can be used as alternative tools to confirm the diagnosis of IPAS. An IPAS shows a significant signal drop similar to the spleen on the SPIO-enhanced T2 or T2*-weighted imaging and prolonged enhancement on the delayed hepatosplenic phase of contrast-enhanced US. We review and illustrate the differential points between IPAS and hypervascular pancreatic tumors in this manuscript

Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct

Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy

High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients with High-risk Stage 3 Neuroblastoma: 10-Year Experience at a Single Center

High-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was applied to improve the prognosis of patients with high-risk stage 3 neuroblastoma. From January 1997 to December 2006, 28 patients were newly diagnosed as stage 3 neuroblastoma. Nine of 11 patients with N-myc amplification and 5 of 17 patients without N-myc amplification (poor response in 2 patients, persistent residual tumor in 2 and relapse in 1) underwent single or tandem HDCT/ASCR. Patients without high-risk features received conventional treatment modalities only. While 8 of 9 patients underwent single HDCT/ASCR and the remaining one patient underwent tandem HDCT/ASCR during the early study period, all 5 patients underwent tandem HDCT/ASCR during the late period. Toxicities associated with HDCT/ASCR were tolerable and there was no treatment-related mortality. While the tumor relapsed in two of eight patients in single HDCT/ASCR group, all six patients in tandem HDCT/ASCR group remained relapse free. The 5-yr event-free survival (EFS) from diagnosis, in patients with N-myc amplification, was 71.6±14.0%. In addition, 12 of 14 patients who underwent HDCT/ASCR remained event free resulting in an 85.1±9.7% 5-yr EFS after the first HDCT/ASCR. The present study demonstrates that HDCT/ASCR may improve the survival of patients with high-risk stage 3 neuroblastoma

Stroke awareness decreases prehospital delay after acute ischemic stroke in korea

BACKGROUND: Delayed arrival at hospital is one of the major obstacles in enhancing the rate of thrombolysis therapy in patients with acute ischemic stroke. Our study aimed to investigate factors associated with prehospital delay after acute ischemic stroke in Korea. METHODS: A prospective, multicenter study was conducted at 14 tertiary hospitals in Korea from March 2009 to July 2009. We interviewed 500 consecutive patients with acute ischemic stroke who arrived within 48 hours. Univariate and multivariate analyses were performed to evaluate factors influencing prehospital delay. RESULTS: Among the 500 patients (median 67 years, 62% men), the median time interval from symptom onset to arrival was 474 minutes (interquartile range, 170-1313). Early arrival within 3 hours of symptom onset was significantly associated with the following factors: high National Institutes of Health Stroke Scale (NIHSS) score, previous stroke, atrial fibrillation, use of ambulance, knowledge about thrombolysis and awareness of the patient/bystander that the initial symptom was a stroke. Multivariable logistic regression analysis indicated that awareness of the patient/bystander that the initial symptom was a stroke (OR 4.438, 95% CI 2.669-7.381), knowledge about thrombolysis (OR 2.002, 95% CI 1.104-3.633) and use of ambulance (OR 1.961, 95% CI 1.176-3.270) were significantly associated with early arrival. CONCLUSIONS: In Korea, stroke awareness not only on the part of patients, but also of bystanders, had a great impact on early arrival at hospital. To increase the rate of thrombolysis therapy and the incidence of favorable outcomes, extensive general public education including how to recognize stroke symptoms would be important.ope

Prognostic factor for Korean patients with renal cell carcinoma and venous tumor thrombus extension: application of the new 2009 TNM staging system

Purpose To study the surgical outcomes of radical nephrectomy with thrombectomy and to determine prognostic factors for survival of Korean patients with renal cell carcinoma (RCC) and venous tumor thrombus. Materials and Methods A total of 124 patients with RCC and venous tumor thrombus who underwent radical nephrectomy and thrombectomy were included in this retrospective study. Cancer-specific survival (CSS) and recurrence-free survival (RFS) rates were analyzed retrospectively according to various prognostic factors. Results The median overall follow-up period for all patients was 29.0 months; the median survival period was 50.0 months. The 2-, 5- and 10-year CSS rates for all patients were 64.2%, 47.1% and 31.7%, respectively. Those for 76 patients (pN0/xM0) without metastasis at presentation were 80.9%, 64.5% and 44.9%, respectively. For all patients, lower body mass index (BMI), higher Fuhrman grade, presence of symptoms, perinephric fat invasion, invasion of inferior vena cava (IVC) wall, lymph node (LN) involvement and distant metastasis at presentation were independent predictors for decreased CSS on multivariate analysis, while thrombus level was not. For non-metastatic patients, lower BMI, presence of symptoms and tumor size were independently associated with decreased CSS. In terms of RFS, lower BMI, presence of perinephric fat invasion were prognostic factors for recurrence. Conclusions Our data suggest that obesity is independently associated with better survival or lower risk of tumor recurrence in Korean patients undergoing radical nephrectomy with tumor thrombectomy. Also, our results indicate that Fuhrman grade, presence of symptoms, perinephric fat invasion and invasion of IVC wall, LN involvement and distant metastasis at presentation are independent predictors for survival

The Impact of Pathologic Upgrading of Gleason Score 7 Prostate Cancer on the Risk of the Biochemical Recurrence after Radical Prostatectomy

Objective. To investigate the impact of pathologic upgrading of Gleason score (GS) 7 prostate cancer on the risk of the biochemical recurrence. Materials and Methods. A total of 1678 patients with postoperative GS 7 prostate cancer without lymph node metastasis were reviewed retrospectively. The patients were categorized into four groups depending on pathologic upgrading: upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3. Kaplan-Meier multivariate model was created. Results. The mean age was significantly higher in the nonupgraded GS 4+3 group than in other groups, whereas the mean prostate-specific antigen (PSA) level was lower in the upgraded GS 3+4 group. Pathologic findings, such as extracapsular extension, seminal vesical invasion, and the surgical margin rate, were different from each other. Five-year biochemical recurrence-free survival rate was 85%, 73%, 69%, and 60% in upgraded GS 3+4, nonupgraded GS 3+4, upgraded GS 4+3, and nonupgraded GS 4+3 group, respectively. There was significant difference between the nonupgraded 4+3 and upgraded 4+3 group, as well as between upgraded 3+4 and nonupgraded 3+4 group. However, the two middle patient groups, that is, the nonupgraded GS 3+4 group and the upgraded GS 4+3 group, did not show the statistical difference (Log-rank test, p value = 0.259). Conclusion. The information on pathologic upgrading in the biopsy reports of patients could help to provide more detailed analysis for the biochemical recurrence of GS 7 prostate cancer

EphA2 Is a Potential Player of Malignant Cellular Behavior in Non-Metastatic Renal Cell Carcinoma Cells but Not in Metastatic Renal Cell Carcinoma Cells.

To investigate the role of EphA2 in malignant cellular behavior in renal cell carcinoma (RCC) cells and whether FAK/RhoA signaling can act as downstream effectors of EphA2 on RCC cells.Expression of EphA2 protein in non-metastatic RCC (Caki-2 and A498), metastatic RCC cells (Caki-1 and ACHN), HEK-293 cells and prostate cancer cells (PC-3 and DU-145; positive controls of EphA2 expression) was evaluated by Western blot. Changes in mRNA or protein expression of EphA2, FAK or membrane-bound RhoA following EphA2, FAK or RhoA small interfering RNA (siRNA) transfection were determined by reverse transcription polymerase chain reaction or Western blot. The effect of siRNA treatment on cellular viability, apoptosis and invasion was analyzed by cell counting kit-8, Annexin-V and modified Matrigel-Boyden assays, respectively.In all RCC cell lines, the expression of EphA2 protein was detectable at variable levels; however, in HEK-293 cells, EphA2 expression was very low. Treatment with EphA2 siRNA significantly reduced the expression of EphA2 mRNA and protein in all RCC cell lines. For non-metastatic RCC cells (Caki-2 and A498) but not metastatic RCC cells (Caki-1 and ACHN), cellular viability, invasiveness, resistance to apoptosis, expression of membrane-bound RhoA protein and FAK phosphorylation were significantly decreased in EphA2 siRNA-treated cells compared to the control. In non-metastatic RCC cells, FAK siRNA significantly attenuated the invasiveness, resistance to apoptosis, as well as expression of membrane-bound RhoA protein without changing protein expression of EphA2. RhoA siRNA significantly decreased the malignant cellular behavior and expression of membrane-bound RhoA protein without changing EphA2 protein expression or FAK phosphorylation.Our data provide the first functional evidence that the EphA2/FAK/RhoA signaling pathway plays a critical role in the malignant cellular behavior of RCC and appears to be functional particularly in the early stage of malignant progression of non-metastatic RCC

Graves 및 Hashimoto병에서의 면역형광소견

Direet immunofluorescent study with antisera against Ig G, A, M, C3 & fibrinogen was performed on thyroid specimens from 21 cases of Graves' disease and 11 cases of Hashimoto's thyroiditis to define immunofluorescent findings in each disorder and their functional significance, with the following results; 1. Ninety five % of Graves' disease cases showed significant granular immunofluorescent deposit along follicular basement menbrane and remainder showed scanty granular deposit on interfollicular space. 2. Forty five % of Hashimoto's thyroiditis cases showed immunofluorescent deposit along follicular basement membrane, whereas 63% showed deposition on interfollicular space. 3. Three cases histologically appreciated as Hashimoto's thyroiditis had significant deposit along follicular basement membrane, and all of them showed physical findings and past history compatible with Graves' disease. 4. 'there was no significant correlation between immunofluorescent deposit, and thyroid function or the presence of thyroid autoantibodies. 5. Comparing immunofluorescent studies with light microscopic findings, degree of immunofluorescent deposit along follicular basement membrane was correlated well with the degree of lymphocytic infiltration in Graves' disease. In this study, it was shown that the pattern of immunofluorescent deposition in Graves' disease was different from that of Hashimoto's disease, and the degree of immunofluorescent deposit along follicular basement membrane was correlated well with the degree of lymphocytic infiltration in Graves' disease