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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 -
Romanian Journal of Morphology and... 2017Chronic thyroiditis may present a focal lesion, often-palpable abnormality, simulating nodular disease. The number and morphology of the Hürthle cells (HC) vary in the...
Chronic thyroiditis may present a focal lesion, often-palpable abnormality, simulating nodular disease. The number and morphology of the Hürthle cells (HC) vary in the thyroid aspirate. Distinguishing between neoplastic and non-neoplastic HC lesions is difficult when using the fine-needle aspiration cytology (FNAC). We present the case of a 46-year-old female with a large right nodular goiter and hypothyroidism and high titer of anti-thyroid peroxidase antibody (TPO). The thyroid ultrasound showed a large well-defined nodule (more than 6.8 cm) with hypoechogenicity and microcalcification. FNAC (Mayo Clinic technique) smears revealed HC arranged in flat sheets in 75% in the sample with moderate nuclear pleomorphism, abundant granular cytoplasm showing eosinophilia and well-defined cytoplasmic borders, a lightly eccentric enlarged nuclei; the colloid was reduced and lymphocytes were also described. The final histological examination revealed that oncocyte cell proliferation is limited to the thyroid parenchyma and does not exceed the capsule and has no vascular invasion. The presence of lymphocytic infiltration and a performing FNAC (like Mayo Clinic technique) is absolutely necessary in a focal autoimmune thyroiditis in order to exclude HC carcinoma.
Topics: Biopsy, Fine-Needle; Female; Hashimoto Disease; Humans; Inflammation; Middle Aged; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms
PubMed: 28523326
DOI: No ID Found -
Modern Pathology : An Official Journal... Apr 2020Recently discovered DNAJB1-PRKACA oncogenic fusions have been considered diagnostic for fibrolamellar hepatocellular carcinoma. In this study, we describe six... (Comparative Study)
Comparative Study
Recently discovered DNAJB1-PRKACA oncogenic fusions have been considered diagnostic for fibrolamellar hepatocellular carcinoma. In this study, we describe six pancreatobiliary neoplasms with PRKACA fusions, five of which harbor the DNAJB1-PRKACA fusion. All neoplasms were subjected to a hybridization capture-based next-generation sequencing assay (MSK-IMPACT), which enables the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving ≥410 genes (n = 6) and/or to a custom targeted, RNA-based panel (MSK-Fusion) that utilizes Archer Anchored Multiplex PCR technology and next-generation sequencing to detect gene fusions in 62 genes (n = 2). Selected neoplasms also underwent FISH analysis, albumin mRNA in-situ hybridization, and arginase-1 immunohistochemical labeling (n = 3). Five neoplasms were pancreatic, and one arose in the intrahepatic bile ducts. All revealed at least focal oncocytic morphology: three cases were diagnosed as intraductal oncocytic papillary neoplasms, and three as intraductal papillary mucinous neoplasms with mixed oncocytic and pancreatobiliary or gastric features. Four cases had an invasive carcinoma component composed of oncocytic cells. Five cases revealed DNAJB1-PRKACA fusions and one revealed an ATP1B1-PRKACA fusion. None of the cases tested were positive for albumin or arginase-1. Our data prove that DNAJB1-PRKACA fusion is neither exclusive nor diagnostic for fibrolamellar hepatocellular carcinoma, and caution should be exercised in diagnosing liver tumors with DNAJB1-PRKACA fusions as fibrolamellar hepatocellular carcinoma, particularly if a pancreatic lesion is present. Moreover, considering DNAJB1-PRKACA fusions lead to upregulated protein kinase activity and that this upregulated protein kinase activity has a significant role in tumorigenesis of fibrolamellar hepatocellular carcinoma, protein kinase inhibition could have therapeutic potential in the treatment of these pancreatobiliary neoplasms as well, once a suitable drug is developed.
Topics: Adult; Aged; Biliary Tract Neoplasms; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; Female; Gene Fusion; Genetic Predisposition to Disease; HSP40 Heat-Shock Proteins; Humans; Liver Neoplasms; Male; Middle Aged; Oxyphil Cells; Pancreatic Neoplasms; Phenotype; Prognosis; Sodium-Potassium-Exchanging ATPase
PubMed: 31676785
DOI: 10.1038/s41379-019-0398-2 -
Journal of Nuclear Medicine : Official... May 1997Preoperative localization of hyperactive parathyroid glands is useful to minimize operative time and reduce patient morbidity. This investigation compared the... (Comparative Study)
Comparative Study
UNLABELLED
Preoperative localization of hyperactive parathyroid glands is useful to minimize operative time and reduce patient morbidity. This investigation compared the sensitivity of radionuclide imaging with 99mTc tetrofosmin with that of ultrasonography and magnetic resonance (MR) imaging in patients with hyperparathyroidism.
METHODS
Twenty-six patients with primary (n = 7) or secondary (n = 19) hyperparathyroidism were imaged with 99mTc tetrofosmin, ultrasound and MR imaging of the neck and thorax to localize the lesions. The presence of hyperparathyroidism was identified by an intact parathyroid hormone in vitro assay. The parathyroid/normal thyroid tissue activity ratio was calculated for all patients with evidence of an abnormality on tetrofosmin images. Pathological findings were compared with the results of imaging in 18 of the 26 patients who underwent parathyroidectomy.
RESULTS
Technetium-99m tetrofosmin scans demonstrated focal uptake in 46 glands of 26 patients. The uptake was categorized as slight in 78.3% (36/46) and intense (parathyroid/normal thyroid tissue activity ratio, > 1.4) in 21.7% (10/46). Ultrasonography and MR imaging identified 44 and 47 glands, respectively, in these patients. Eleven of the 18 patients who underwent parathyroidectomy within 1 mo after tetrofosmin imaging had hyperplastic glands, while 7 had parathyroid adenomas. Tetrofosmin imaging successfully localized 7 of 7 (100%) adenomas and 27 of 37 (73.0%) hyperplastic glands. The sensitivities of each technique for localizing abnormal parathyroid glands were 77.3% (34/44) for tetrofosmin imaging: 68.2% (20/44) for ultrasonography: and 68.2% (30/44) for MR imaging. Technetium-99m tetrofosmin uptake ratio in the 18 patients with surgical exploration was not proportional to several oxyphil cells.
CONCLUSION
Technetium-99m tetrofosmin parathyroid imaging may be useful for localizing abnormal glands in patients with primary and secondary hyperparathyroidism. The sensitivity of 99mTc tetrofosmin parathyroid imaging was high as compared to ultrasonography or MR imaging. The prolonged retention of tetrofosmin may not depend on the number of mitochondria-rich oxyphil cells.
Topics: Adenoma; Female; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hyperplasia; Magnetic Resonance Imaging; Male; Middle Aged; Organophosphorus Compounds; Organotechnetium Compounds; Parathyroid Glands; Parathyroid Neoplasms; Preoperative Care; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Ultrasonography
PubMed: 9170432
DOI: No ID Found -
Clinical and Experimental Immunology May 1973Fresh surgical material from forty-eight patients undergoing partial thyroidectomy for thyroid tumour was examined by immunofluorescence staining with antisera for the...
Fresh surgical material from forty-eight patients undergoing partial thyroidectomy for thyroid tumour was examined by immunofluorescence staining with antisera for the presence of thyroid-microsomal, mitochondrial and thyroglobulin antigens. Light microscopy on cryostat and paraffin-wax embedded sections was carried out in all cases. Electron microscopy was done on samples from thirteen tumours. Microsomal antigen was present in all normal thyroid tissue, in all eight colloid nodules, in twenty-three out of twenty-four follicular adenomas, in four out of six microangeioinvasive follicular carcinomas, in none of the six papillary, one anaplastic and three medullary carcinomas. Mitochondrial antigen was present in all tumours. Electron microscopy showed marked reduction or absence of microvesicles and other organelles in the papillary and anaplastic carcinomas, thus confirming the suggestion put forward by Goudie & McCallum (1963) that a negative microsomal reaction is associated with dedifferentiation. A negative reaction was also associated with tumours showing advanced oxyphil (Hürthle) cell metaplasia, i.e. total replacement of cytoplasmic organelles by proliferated mitochondria.
Topics: Adenocarcinoma; Adenoma; Adult; Antibodies, Anti-Idiotypic; Antigens; Carcinoma; Carcinoma, Papillary; Female; Fluorescent Antibody Technique; Humans; Male; Microscopy, Electron; Microsomes; Middle Aged; Mitochondria; Thyroid Neoplasms
PubMed: 4577288
DOI: No ID Found -
Ear, Nose, & Throat Journal Jun 2020
Topics: Aged; Cysts; Female; Humans; Laryngeal Diseases; Larynx; Medical Illustration; Oxyphil Cells; Recurrence
PubMed: 30987461
DOI: 10.1177/0145561319840208 -
Cancer Cytopathology Oct 2021Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously...
Impact of molecular testing on detecting mimics of oncocytic neoplasms in thyroid fine-needle aspirates diagnosed as follicular neoplasm of Hürthle cell (oncocytic) type.
BACKGROUND
Some thyroid nodules cytologically presenting as follicular neoplasm, Hürthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation-type DNA copy number alterations (GH-CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics.
METHODS
Consecutive fine-needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow-up was available for 79 of 180 nodules (44%).
RESULTS
No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8-GLIS3 (n = 1). GH-CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS-like alterations without GH-CNA (n = 25) and 2) TERT and/or TP53 mutations co-occurring with GH-CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH-CNA (n = 2).
CONCLUSIONS
A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH-CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms.
Topics: Biopsy, Fine-Needle; Humans; Metaplasia; Molecular Diagnostic Techniques; Oxyphil Cells; Thyroid Neoplasms; Thyroid Nodule
PubMed: 33901345
DOI: 10.1002/cncy.22439 -
British Journal of Experimental... Feb 1959
Topics: Endocrine Cells; Humans; Oxyphil Cells; Parathyroid Glands
PubMed: 13638486
DOI: No ID Found -
Cancer Cytopathology Jul 2014
Topics: Adenocarcinoma, Follicular; Cell Transformation, Neoplastic; Female; Humans; Male; Oxyphil Cells; Thyroid Gland; Thyroid Neoplasms
PubMed: 24706512
DOI: 10.1002/cncy.21420 -
Physiological Research Nov 2018(18)F-fluorocholine positron emission tomography/computed tomography (FCH) was performed after inconclusive neck ultrasound and (99)Tc-sestaMIBI SPECT (MIBI)...
(18)F-fluorocholine positron emission tomography/computed tomography (FCH) was performed after inconclusive neck ultrasound and (99)Tc-sestaMIBI SPECT (MIBI) scintigraphy in patients with primary hyperparathyroidism (PHPT) to localize abnormal parathyroid glands before surgery. The results were retrospectively evaluated and compared to postoperative histopathological findings. 13 patients with PHPT were enrolled (mean age 64.3 years, preoperative calcium 2.74 mmol/l and parathyroid hormone 114.6 ng/l). FCH localized hyperfunctioning parathyroid glands in 12 patients of 13 (per patient sensitivity 92 % and positive predictive value (PPV) 100 %). Fourteen parathyroid lesions (11 adenomas, 3 hyperplastic glands) were resected with a mean size of 11.9 mm (per lesion sensitivity 93 % and PPV 81 %). Four adenomas and one hyperplastic gland were composed of only chief cells, whereas five lesions contained both chief and oxyphil cells. In three patients an exclusively oxyphil adenoma was found, surprisingly with negative MIBI scintigraphy in spite of a high mitochondria content in the oxyphil parathyroid cells. 12 of 13 patients had thyroid disease. In our limited study sample, FCH correctly identified parathyroid adenomas and/or hyperplastic glands in 92 % of patients with previously inconclusive conventional imaging. Unlike MIBI, FCH successfully localized small, hyperplastic and multiple hyperfunctioning parathyroid glands, irrespective of their histopathological composition.
Topics: Adult; Aged; Choline; Female; Fluorine Radioisotopes; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Glands; Positron Emission Tomography Computed Tomography; Retrospective Studies
PubMed: 30484682
DOI: 10.33549/physiolres.934029