Prognostic factors of recurrence in encapsulated Hurthle cell carcinoma of the thyroid gland: a clinicopathologic study of 50 cases. (57/183)

BACKGROUND: Follicular carcinomas of the thyroid gland, including its oncocytic variant (so-called Hurthle cell carcinoma), are subdivided into the indolent encapsulated ("minimally invasive") and the clinically aggressive widely invasive tumors. There are, however, cases of encapsulated follicular carcinoma that recur and metastasize. Identifying these cases at the time of diagnosis is crucial for prognostic and therapeutic considerations. Because to the authors' knowledge most studies do not focus exclusively on the encapsulated Hurthle cell carcinoma (EHC), the current study attempted to identify predictors of recurrence in EHC. METHODS: A tumor was defined as EHC if it was encapsulated, macroscopically well defined with microscopic but no macroscopic evidence of vascular or capsular invasion, and composed of > 75% follicular oncocytic cells. Retrospective chart review and microscopic examination identified 50 primary tumors meeting the above criteria at the Memorial Sloan-Kettering Cancer Center between 1967 and 2005. The cases were analyzed for various histologic and clinical parameters. Each parameter was correlated with recurrence-free survival (RFS). RESULTS: Seven of 50 (14%) patients developed disease recurrence. All patients who developed recurrence were found to have a high number of foci of vascular invasion (> or = 4). In univariate analysis, > or = 4 foci of vascular invasion (P <.0001), tumor size > 4 cm (P = .049), the presence of mitosis (P = .018), and a solid/trabecular growth pattern (P = .009) were found to be correlated with a decreased RFS. Extensive capsular invasion, gender, and age did not confer a statistically higher recurrence rate. The finding of a solid/trabecular growth and mitosis correlated with the presence of numerous foci (> or = 4) of vascular invasion (P = .01 and P = .005, respectively). CONCLUSIONS: A diligent search for vascular invasion is recommended in EHC that display mitosis or a solid/trabecular growth pattern. The presence of > or = 4 foci of vascular invasion should alert the pathologist and the clinician to a significantly higher risk of recurrence in EHC.  (+info)

Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management. (58/183)

The aim of this study was to investigate the diagnostic accuracy and impact on patient management of the new integrated PET/CT modality in patients with suspected iodine-negative, differentiated thyroid carcinoma (DTC). METHODS: Forty patients with DTC and a suggestion of iodine-negative tumor tissue underwent PET/CT examination (370 MBq (18)F-FDG, coregistered PET/CT whole-body images). As the first step of analysis, PET and CT images were scored blindly and independently by 2 nuclear medicine physicians and 2 radiologists. A 5-point scale was used. The second step consisted of a consensus reading, during which a virtual side-by-side fusion of PET and CT images was initially evaluated and afterward the "real" fusion (i.e., coregistered) PET/CT images were also scored with the same 5-point scale. The imaging results were compared with histopathologic findings and the course of disease during further follow-up examinations. RESULTS: One hundred twenty-seven lesions in 40 patients were evaluated. Diagnostic accuracy was 93% and 78% for PET/CT and PET, respectively (P = 0.049, per-patient analysis). In 17 (74%) of 23 patients with suspicious (18)F-FDG foci, integrated PET/CT added relevant information to the side-by-side interpretation of PET and CT images by precisely localizing the lesion(s). In tumor-positive PET patients, PET/CT fusion by coregistration led to a change of therapy in 10 (48%) patients. Futile surgery was prevented in an additional 3 patients. CONCLUSION: Integrated PET/CT is able to improve diagnostic accuracy in a therapeutically relevant way in patients with iodine-negative DTC. By precisely localizing tumor tissue, image fusion by integrated PET/CT is clearly superior to side-by-side interpretation of PET and CT images.  (+info)

Caveolin-1 immunohistochemical analysis in differentiating chromophobe renal cell carcinoma from renal oncocytoma. (59/183)

Chromophobe renal cell carcinoma (ChRCC) and oncocytoma might mimic each other histologically. We studied the immunohistochemical staining pattern of caveolin-1 in 21 ChRCCs and 26 oncocytomas and compared it with cytokeratin (CK) 7 to evaluate its usefulness in differentiating these 2 neoplasms. All 21 ChRCCs (100%) were positive for caveolin-1, 20 of which were stained in 20% or more of the tumor cells. In contrast, only 3 (12%) of 26 oncocytomas showed positivity in fewer than 20% tumor cells and 23 (88%) of 26 were negative. In the nonneoplastic kidney, positive caveolin-1 staining was detected in the interstitial blood vessels and the parietal cells of the Bowman capsules but not in the tubular epithelium and glomerular and peritubular capillaries. All 21 ChRCCs (100%) were positive for CK7, with 18 (86%) stained in 20% or more of the tumor cells and 3 (14%) in fewer than 20%. Of 26 oncocytomas, 25 (96%) were positive for CK7, with 7 (27%) stained in 20% or more of the tumor cells and 18 (69%) in fewer than 20%. These results strongly suggest that caveolin-1 immunohistochemical analysis is useful for differentiating ChRCC from oncocytoma and is superior to CK7.  (+info)

Differential expression of a new isoform of DLG2 in renal oncocytoma. (60/183)

BACKGROUND: Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type. METHODS: In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis. RESULTS: We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour. CONCLUSION: The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma.  (+info)

Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data. (61/183)

OBJECTIVE: The aim of this study was to examine pituitary adenomas in a series of postmortem pituitaries by use of modern technologies of immunostaining, to classify the adenomas according to the current WHO classification and to analyse the possible associations to the available clinical data. METHODS: In this study, pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991-2004 were examined. RESULTS: A total of 334 pituitary adenomas were found in 316 pituitaries. One hundred and thirty-two sparsely granulated prolactin cell adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19 sparsely granulated) and one adenoma composed of Crooke's cells were detected. Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four sparsely granulated, three densely granulated), one mixed GH cell-PRL cell adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four plurihormonal adenoma type II and two alpha-subunit-only adenomas were seen. Six adenomas remained unclassified because the tissue was not contained in all sections for immunohistochemistry. Seventeen pituitaries included multiple tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76 adenomas (22.7%), which had a tumour size of > or = 3 mm, only three tumours were macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation of the available clinical data showed 99 cases of hypertension, 65 cases of diabetes mellitus, six patients with hyperthyroidism and four with hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were reported. The statistical correlations to clinical data were discussed. CONCLUSIONS: Adenomas in postmortem pituitaries differ from those in surgical series in proportion of adenoma types and biological behaviour.  (+info)

Expression of kidney-specific cadherin in chromophobe renal cell carcinoma and renal oncocytoma. (62/183)

Kidney-specific cadherin (Ksp-cad) recently was proposed to differentiate chromophobe renal cell carcinoma (RCC) from oncocytoma based on a finding of Ksp-cad expression in 97% of chromophobe RCCs but only 3% of oncocytomas. However, another study showed no difference in Ksp-cad immunoreactivity between these 2 tumors. We attempted to evaluate Ksp-cad expression in renal tumors using expression microarrays and immunohistochemical analysis. Ksp-cad messenger RNA (mRNA) levels were examined in 158 renal tumors, including 15 chromophobe RCCs and 15 oncocytomas. Immunohistochemical analysis was performed on tissue microarrays containing 125 renal tumors, including 36 chromophobe RCCs and 41 oncocytomas. Ksp-cad mRNA compared with normal kidney tissue was 89% in chromophobe RCC and 64% in oncocytoma. Furthermore, 31 of 36 chromophobe RCCs and 31 of 41 oncocytomas showed Ksp-cad immunoreactivity. Ksp-cad was present in chromophobe RCCs and oncocytomas at mRNA and protein levels, providing strong evidence that Ksp-cad immunohistochemical analysis cannot be used in differentiating these tumors.  (+info)

Defective oxidative phosphorylation in thyroid oncocytic carcinoma is associated with pathogenic mitochondrial DNA mutations affecting complexes I and III. (63/183)

Oncocytic tumors are characterized by cells with an aberrant accumulation of mitochondria. To assess mitochondrial function in neoplastic oncocytic cells, we studied the thyroid oncocytic cell line XTC.UC1 and compared it with other thyroid non-oncocytic cell lines. Only XTC.UC1 cells were unable to survive in galactose, a condition forcing cells to rely solely on mitochondria for energy production. The rate of respiration and mitochondrial ATP synthesis driven by complex I substrates was severely reduced in XTC.UC1 cells. Furthermore, the enzymatic activity of complexes I and III was dramatically decreased in these cells compared with controls, in conjunction with a strongly enhanced production of reactive oxygen species. Osteosarcoma-derived transmitochondrial cell hybrids (cybrids) carrying XTC.UC1 mitochondrial DNA (mtDNA) were generated to discriminate whether the energetic failure depended on mitochondrial or nuclear DNA mutations. In galactose medium, XTC.UC1 cybrid clones showed reduced viability and ATP content, similarly to the parental XTC.UC1, clearly pointing to the existence of mtDNA alterations. Sequencing of XTC.UC1 mtDNA identified a frameshift mutation in ND1 and a nonconservative substitution in cytochrome b, two mutations with a clear pathogenic potential. In conclusion, this is the first demonstration that mitochondrial dysfunction of XTC.UC1 is due to a combined complex I/III defect associated with mtDNA mutations, as proven by the transfer of the defective energetic phenotype with the mitochondrial genome into the cybrids.  (+info)

Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma. (64/183)

BACKGROUND: The down regulation of protein p27(kip1) (p27) in most cases of thyroid cancer has relevant diagnostic and prognostic implications. However, the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma expresses more p27 than benign oxyphilic lesions do. AIM: To evaluate the mechanism underlying this difference in expression of p27. METHODS: Because high levels of cyclin D3 lead to p27 accumulation in cell lines and clinical samples of thyroid cancer, the immunocytochemical pattern of cyclin D3 in oxyphilic (n = 47) and non-oxyphilic (n = 70) thyroid neoplasms was investigated. RESULTS: In the whole study sample, there was a significant correlation between p27 and cyclin D3 expression (Spearman's r: 0.64; p<0.001). The expression of cyclin D3 and p27 was significantly higher in the oxyphilic variant of follicular carcinomas than in non-oxyphilic carcinomas (p<0.001). In the former, cyclin D3 overexpression and p27 accumulation were observed in a median of 75% and 55% of cells, respectively. In co-immunoprecipitation experiments, the level of p27-bound cyclin D3 was much higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours. CONCLUSION: These results show that increased p27 expression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3 overexpression.  (+info)