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Cancer Cytopathology Aug 2011Although a wide variety of papillary carcinomas of the thyroid can have abundant granular cytoplasm and may be difficult to distinguish from Hürthle cell lesions in...
BACKGROUND
Although a wide variety of papillary carcinomas of the thyroid can have abundant granular cytoplasm and may be difficult to distinguish from Hürthle cell lesions in fine-needle aspirations (FNAs), the literature on these tumors is limited. The author described 18 cases with a spectrum of cytologic appearances.
METHODS
A series of 7089 FNAs was correlated with 1331 subsequent resection specimens. Cases in which the original cytologic and histologic diagnoses included the differential diagnosis of papillary carcinoma or Hürthle cell lesions were identified.
RESULTS
A total of 18 (1.3% of cases with resection) cases were identified. On review, 3 cases had classic features of papillary carcinoma, including nuclear crowding, along with a moderate amount of granular cytoplasm. Four cases had a population of cells that mimicked repair and/or cyst-lining cells with almost no other epithelial cells. In 2 of those 4 cases, the cells were extremely large, and in 2 other cases, they could not be distinguished from typical cyst-lining cells. The remaining 11 cases had cells with overlapping features including pale to granular chromatin, small to medium nucleoli either centrally or eccentrically, occasional grooves, and rare intranuclear inclusions. Typical Hürthle cells also were commonly present. Nuclear crowding was not present, and the cells were in sheets, follicles, or appeared alone. No papillae were identified. On resection, 7 cases were follicular variants of papillary carcinoma, 2 cases occurred in the setting of Hashimoto thyroiditis, and 2 cases had features of the tall-cell variant.
CONCLUSIONS
The author concluded that a subset of papillary carcinomas of the thyroid were difficult to distinguish from Hürthle cell lesions or repair and/or cyst-lining cells because of the presence of abundant granular cytoplasm and a lack of nuclear crowding. These tumors were often follicular or cystic variants of papillary carcinoma.
Topics: Adenoma, Oxyphilic; Biopsy, Fine-Needle; Carcinoma, Papillary; Cell Nucleus; Cytodiagnosis; Diagnosis, Differential; Humans; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms
PubMed: 21400667
DOI: 10.1002/cncy.20148 -
Endocrine Journal 2010Reactive C-cell hyperplasia (CCH) has been observed in cases of autoimmune Hashimoto's thyroiditis; however, its occurrence in Graves' disease, the other major...
Reactive C-cell hyperplasia (CCH) has been observed in cases of autoimmune Hashimoto's thyroiditis; however, its occurrence in Graves' disease, the other major autoimmune disorder, has not yet been investigated. On the other hand, although Carcinoembryonic Antigen (CEA) serum levels have been reported elevated in patients with autoimmune thyroid disease (ATD), the source of CEA production at the cellular level is not elucidated. The aim of this study was to evaluate CCH and CEA immunohistochemical expression and comparatively analyze them in 136 ATD cases (107 Hashimoto's and 29 Graves' disease cases) and 20 cases of nodular hyperplasia (NH). Immunohistochemistry using monoclonal antibodies to chromogranin and CEA was performed. A scoring system for CCH and semiquantitative evaluation for CEA expression were applied. C-cell hyperplasia was absent in NH cases. In contrast, it was detected in 11% of ATD cases being more frequently observed in Hashimoto's (12.1%) than Graves' disease (6.8%) CCH associated to male sex and older age of Hashimoto's patients. CEA was detected only in ATD cases (33.8%), in C-cells and in follicular cells as well, being more frequently detected in Graves' (44.8%) than Hashimoto's (30.8%) disease. An interesting finding was an emerging possible association of CEA expression with oxyphilic change but not with C-cell hyperplasia in Hashimoto's thyroiditis. No significant correlation was established between CCH and CEA follicular cell expression in neither disease. In conclusion, C-cell hyperplasia and CEA expression may be encountered in the setting of Hashimoto's thyroiditis and Graves' disease.
Topics: Adult; Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Chromogranins; Female; Graves Disease; Hashimoto Disease; Humans; Hyperplasia; Immunohistochemistry; Male; Middle Aged; Oxyphil Cells; Thyroid Neoplasms; Thyroid Nodule
PubMed: 20616436
DOI: 10.1507/endocrj.k10e-071 -
PloS One Nov 2009Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular...
BACKGROUND
Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown.
METHODOLOGY/PRINCIPAL FINDINGS
Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors.
CONCLUSIONS/SIGNIFICANCE
In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism.
Topics: Adenoma, Oxyphilic; Animals; Cell Nucleus; Female; Gene Expression Regulation; Hashimoto Disease; Humans; Hypothyroidism; Immune System; Interferon-gamma; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oxyphil Cells; Phenotype; Proteasome Endopeptidase Complex; Thyroid Gland
PubMed: 19924240
DOI: 10.1371/journal.pone.0007857 -
Archives of Pathology & Laboratory... Aug 2008Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis... (Review)
Review
CONTEXT
Hürthle cells are eosinophilic, follicular-derived cells that are associated with a variety of nonneoplastic and neoplastic thyroid lesions. The differential diagnosis of Hürthle cell lesions is quite broad.
OBJECTIVE
To review the pathologic conditions associated with Hürthle cells in the thyroid and to discuss pathology of thyroid lesions associated with oncocytic cytology.
DATA SOURCES
A variety of thyroid nonneoplastic (autoimmune thyroiditis, multinodular goiter) and neoplastic conditions (Hürthle cell adenoma, Hürthle cell carcinoma) are associated with Hürthle cell cytology. In addition, there are several thyroid neoplasms that should be considered when one observes a Hürthle cell neoplasm in the thyroid (oncocytic variant of medullary carcinoma, several variants of papillary thyroid carcinoma).
CONCLUSIONS
Oncocytic cytology is seen in a variety of thyroid conditions that are associated with a broad differential diagnosis and care must be used for accurate diagnosis. Newer molecular-based techniques may be useful for further classification of thyroid neoplasms with oncocytic pathology.
Topics: Adenocarcinoma; Biopsy, Needle; Diagnosis, Differential; History, 19th Century; Humans; Metaplasia; Oxyphil Cells; Pathology, Surgical; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms
PubMed: 18684023
DOI: 10.5858/2008-132-1241-TTHOCA -
Clinical Journal of the American... May 2008Vitamin D receptor activation by vitamin D sterols and calcium-sensing receptor stimulation by cinacalcet are the most powerful treatments of secondary... (Comparative Study)
Comparative Study
Does vitamin D receptor and calcium receptor activation therapy play a role in the histopathologic alterations of parathyroid glands in refractory uremic hyperparathyroidism?
BACKGROUND AND OBJECTIVES
Vitamin D receptor activation by vitamin D sterols and calcium-sensing receptor stimulation by cinacalcet are the most powerful treatments of secondary hyperparathyroidism. This study was aimed to assess a possible association between histopathologic changes of parathyroid tissue and treatment modality.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Studies were performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing first parathyroidectomy. The type of hyperplasia and the distribution of chief and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three groups could be studied according to treatment modality: group A consisted of 6 patients who were treated with cinacalcet, intravenous calcitriol, and phosphate binders; group B consisted of 6 patients who were treated with intravenous calcitriol and phosphate binders, and group C consisted of 10 patients who were treated with phosphate binders alone.
RESULTS
Sixty-eight (82.9%) out of 82 glands removed showed nodular hyperplasia. It was more frequent in groups A and B than in group C. A stepwise forward logistic regression model showed that the probability of nodular hyperplasia was higher in patients who were on calcitriol and/or cinacalcet therapy, in female gender and in patients with a higher body mass index. Oxyphil/chief cell ratio also was significantly different among the three groups. Cinacalcet treatment was the only predictor of this ratio.
CONCLUSIONS
An association was found between calcitriol and/or cinacalcet therapy and a high prevalence of nodular hyperplasia, and between cinacalcet therapy and high oxyphil/chief cell ratio. The meaning of the observed associations remains uncertain.
Topics: Adult; Aged; Body Mass Index; Calcitriol; Cinacalcet; Drug Therapy, Combination; Female; Humans; Hyperparathyroidism, Secondary; Hyperplasia; Logistic Models; Male; Middle Aged; Naphthalenes; Oxyphil Cells; Parathyroid Glands; Parathyroidectomy; Phosphates; Receptors, Calcitriol; Receptors, Calcium-Sensing; Renal Dialysis; Risk Assessment; Risk Factors; Sex Factors; Treatment Failure; Uremia; Vitamins
PubMed: 18322048
DOI: 10.2215/CJN.04150907 -
Molecular Vision Jan 2008To explore the possibility of the c-erbB2 oncogene antisense probe labeled with superparamagnetic iron oxide (SPIO) nanoparticles as a target contrast agent for magnetic...
PURPOSE
To explore the possibility of the c-erbB2 oncogene antisense probe labeled with superparamagnetic iron oxide (SPIO) nanoparticles as a target contrast agent for magnetic resonance (MR) imaging whose morphology was observed with atomic force microscopy (AFM), and its efficiency was examined by MR imaging.
METHODS
The c-erbB2 oncogene antisense probe labeled with SPIO was synthesized by a chemical cross-linking approach. Its morphology was observed with AFM.
RESULTS
The chemical constitution of c-erbB2 oncogene antisense probes can be observed with AFM. The molecular structure of probes is easily visualized under AFM. Probes with diameters of 25-40 nm are in order, follow uniformity and the arrangement rule, can be separated from each other, and appear as cubes with a rugged surface morphology. Strong, low signals of the probes in transfected cells were observed by MR cellular imaging.
CONCLUSIONS
AFM is ideal for morphological observation and for analyzing the molecular structure of synthesized c-erbB2 oncogene antisense probes.
Topics: Antisense Elements (Genetics); Cell Line, Tumor; Contrast Media; Genes, erbB-2; Humans; Iron Compounds; Magnetic Resonance Imaging; Magnetics; Microscopy, Atomic Force; Nanoparticles; Oxides; Oxyphil Cells; Transfection
PubMed: 18253092
DOI: No ID Found -
BMC Endocrine Disorders Oct 2007The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly...
BACKGROUND
The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors.
METHODS
We sought acquired mitochondrial DNA mutations by sequencing the entire 16.6 kb mitochondrial genome of each of thirty sporadic parathyroid adenomas (18 chief cell and 12 oxyphil cell), eight independent, polyclonal, parathyroid primary chief cell hyperplasias plus corresponding normal control samples, five normal parathyroid glands, and one normal thyroid gland.
RESULTS
Twenty-seven somatic mutations were identified in 15 of 30 (9 of 12 oxyphil adenomas, 6 of 18 chief cell) parathyroid adenomas studied. No somatic mutations were observed in the hyperplastic parathyroid glands.
CONCLUSION
Features of the somatic mutations suggest that they may confer a selective advantage and contribute to the molecular pathogenesis of parathyroid adenomas. Importantly, the statistically significant differences in mutation prevalence in oxyphil vs. chief cell adenomas also suggest that mtDNA mutations may contribute to the oxyphil phenotype.
PubMed: 17916247
DOI: 10.1186/1472-6823-7-8 -
Proceedings of the National Academy of... May 2007Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in...
Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in the thyroid gland. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the accumulation of mitochondria, we sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by using recently developed technology that allows specific and reliable amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only two samples (3.8%) presented such mutations in the nononcocytic control group. In one case with multiple thyroid nodules analyzed separately, a disruptive mutation was found in the only nodule with oncocytic features. In one of the five mitochondrion-rich breast tumors, a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes, and the association between these mutations and the oncocytic phenotype was statistically significant (P=0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors.
Topics: Base Sequence; Biomarkers, Tumor; DNA, Mitochondrial; Electron Transport Complex I; Humans; Mutation; Oxyphil Cells; Phenotype; Protein Subunits; Thyroid Neoplasms; Tumor Cells, Cultured
PubMed: 17517629
DOI: 10.1073/pnas.0703056104 -
Endocrine Journal Jun 2007We report the case of a 64-year-old woman who had a severe hypercalcemia. Serum calcium, intact parathyroid hormone (PTH), 1alpha, 25 (OH)(2 )vitamin D(3) levels were...
We report the case of a 64-year-old woman who had a severe hypercalcemia. Serum calcium, intact parathyroid hormone (PTH), 1alpha, 25 (OH)(2 )vitamin D(3) levels were all elevated, and serum phosphorus level was decreased, which were all consistent with primary hyperparathyroidism (PHPT). (201)Tl/(99m)Tc subtraction scintigraphy failed to detect any abnormal accumulation in the neck and chest, while (99m)Tc-MIBI scintigraphy demonstrated the focal accumulation of increased radiotracer uptake in the mediastinum only on the early image, but not on the delayed image. Neck and chest computerized tomography scanning showed a small nodule at the retrosternal region, and a selective venous sampling study of the intact PTH suggested PTH production from the nodule. Together with the observation of the early image of (99m)Tc-MIBI scintigraphy, it was diagnosed that the patient had an ectopic parathyroid adenoma. Video-assisted thoracic surgery was performed. A 15-mm diameter mass, visualized by an intravenous infusion of methylene blue, was excited. The histopathology was consistent with the parathyroid adenoma. The adenoma was composed of mainly chief cells and rarely oxyphil cells. The absence of oxyphil cells would explain the lack of (99m)Tc-MIBI retention on late-phase imaging in our case. Even without uptake on the delayed image of (99m)Tc-MIBI scintigram, the early image was available for the localization of an ectopic parathyroid adenoma.
Topics: Adenoma; Choristoma; Female; Humans; Hyperparathyroidism, Primary; Middle Aged; Models, Biological; Parathyroid Glands; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Thoracic Neoplasms
PubMed: 17457014
DOI: 10.1507/endocrj.k06-164 -
Hormones (Athens, Greece) 2006
Review
Topics: Adenoma, Oxyphilic; Algorithms; Biopsy, Fine-Needle; Calcitonin; Humans; Oxyphil Cells; Palpation; Thyroid Nodule
PubMed: 16950751
DOI: 10.14310/horm.2002.11188