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Frontiers in Endocrinology 2021Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the... (Review)
Review
Hürthle cell lesions have been a diagnostic conundrum in pathology since they were first recognized over a century ago. Controversy as to the name of the cell, the origin of the cell, and even which cells in particular may be designated as such still challenge pathologists and confound those treating patients with a diagnosis of "Hürthle cell" anything within the diagnosis, especially if that anything is a sizable mass lesion. The diagnosis of Hürthle cell adenoma (HCA) or Hürthle cell carcinoma (HCC) has typically relied on a judgement call by pathologists as to the presence or absence of capsular and/or vascular invasion of the adjacent thyroid parenchyma, easy to note in widely invasive disease and a somewhat subjective diagnosis for minimally invasive or borderline invasive disease. Diagnostic specificity, which has incorporated a sharp increase in molecular genetic studies of thyroid tumor subtypes and the integration of molecular testing into preoperative management protocols, continues to be challenged by Hürthle cell neoplasia. Here, we provide the improving yet still murky state of what is known about Hürthle cell tumor genetics, clinical management, and based upon what we are learning about the genetics of other thyroid tumors, how to manage expectations, by pathologists, clinicians, and patients, for more actionable, precise classifications of Hürthle cell tumors of the thyroid.
Topics: Adenoma, Oxyphilic; Biopsy; Genome, Mitochondrial; Humans; Mutation; Oxyphil Cells; Thyroid Neoplasms; Thyroidectomy
PubMed: 34177816
DOI: 10.3389/fendo.2021.696386 -
Southern Medical Journal Aug 1993Despite several extensive reviews of the literature within the past decade, the treatment of oxyphil cell tumors of the thyroid gland remains controversial. The foremost... (Review)
Review
Despite several extensive reviews of the literature within the past decade, the treatment of oxyphil cell tumors of the thyroid gland remains controversial. The foremost questions today concern the acceptable criteria for diagnosis of oxyphil malignancies and the appropriate surgical treatment of these neoplasms. This review provides a forum for debate on the treatment of oxyphil neoplasms, with emphasis on their unique histopathologic features and unpredictable clinical behavior.
Topics: Adenoma; Humans; Thyroid Neoplasms
PubMed: 8351555
DOI: 10.1097/00007611-199308000-00015 -
International Urology and Nephrology Jan 2020Parathyroid glands consist of chief cells and oxyphil cells. The parathyroid oxyphil cell proportion increased dramatically in patients with chronic kidney disease...
BACKGROUND
Parathyroid glands consist of chief cells and oxyphil cells. The parathyroid oxyphil cell proportion increased dramatically in patients with chronic kidney disease (CKD). The importance of the oxyphil cell in the treatment of secondary hyperparathyroidism (SHPT) has been enhanced in recent years. The aim of this study was to explore the possible relationship between parathyroid oxyphil cell proportion and clinical features of patients with CKD.
METHODS
From December 2010 to December 2018, 78 consecutive patients with CKD 5 who underwent parathyroidectomy (PTX) were reviewed. None of the patients had used Cinacalcet. Patients were divided into two groups according to their parathyroid oxyphil cell proportion. The mean parathyroid oxyphil cell proportion of all the patients was obtained. Group 1 consisted of 37 patients, the parathyroid oxyphil cell proportion of whom was more than or equal to mean proportion. Group 2 consisted of 41 patients, the parathyroid oxyphil cell proportion of whom was less than mean proportion. The demographic and biochemical data of the two groups were compared.
RESULTS
Preoperative parathyroid hormone (PTH) and total weight of removed parathyroid glands in the patients of group 1were less than those in group 2. There was no difference between the two groups in terms of preoperative calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), age and dialysis years.
CONCLUSION
The parathyroid oxyphil cell proportion was associated with preoperative PTH and total weight of removed parathyroid glands in the patients with CKD. Patients with more parathyroid oxyphil proportion had lower preoperative PTH level and smaller total weight of the removed parathyroid glands.
Topics: Adult; Female; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Oxyphil Cells; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 31686279
DOI: 10.1007/s11255-019-02330-y -
Kidney International Mar 2024The parathyroid gland is one of the main organs that regulate calcium and phosphorus metabolism. It is mainly composed of chief cells and oxyphil cells. Oxyphil cell...
The parathyroid gland is one of the main organs that regulate calcium and phosphorus metabolism. It is mainly composed of chief cells and oxyphil cells. Oxyphil cell counts are low in the parathyroid glands of healthy adults but are dramatically increased in patients with uremia and secondary hyperparathyroidism (SHPT). Increased oxyphil cell counts are related to drug treatment resistance, but the origin of oxyphil cells and the mechanism of proliferation remain unknown. Herein, three types of parathyroid nodules (chief cell nodules, oxyphil cell nodules and mixed nodules, respectively) excised from parathyroid glands of uremic SHPT patients were used for single-cell RNA sequencing (scRNA-seq), other molecular biology studies, and transplantation into nude mice. Through scRNA-seq of parathyroid mixed nodules from three patients with uremic SHPT, we established the first transcriptomic map of the human parathyroid and found a chief-to-oxyphil cell transdifferentiation characterized by gradual mitochondrial enrichment associated with the uremic milieu. Notably, the mitochondrial enrichment and cellular proliferation of chief cell and oxyphil cell nodules decreased significantly after leaving the uremic milieu via transplantation into nude mice. Remarkably, the phenotype of oxyphil cell nodules improved significantly in the nude mice as characterized by decreased mitochondrial content and the proportion of oxyphil cells to chief cells. Thus, our study provides a comprehensive single-cell transcriptome atlas of the human parathyroid and elucidates the origin of parathyroid oxyphil cells and their underlying transdifferentiating mechanism. These findings enhance our understanding of parathyroid disease and may open new treatment perspectives for patients with chronic kidney disease.
Topics: Adult; Animals; Mice; Humans; Parathyroid Glands; Oxyphil Cells; Mice, Nude; Cell Transdifferentiation; Hyperparathyroidism, Secondary; Sequence Analysis, RNA
PubMed: 38142040
DOI: 10.1016/j.kint.2023.11.027 -
Nephron 1996Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal failure was evaluated using in situ hybridization and heterotransplantation of...
Oxyphil cell function in secondary parathyroid hyperplasia due to chronic renal failure was evaluated using in situ hybridization and heterotransplantation of parathyroid tissue. In situ hybridization and histologic analysis were performed on continuous frozen sections using 22 parathyroid tissues. A restricted area composed exclusively of oxyphil cells was observed in 10 specimens, and an area of only chief cells was found in 12 specimens. Silver grains demonstrating the existence of parathyroid hormone (PTH) mRNA were 18.8 +/- 7.8 (mean +/- SD) in oxyphil cells while those in chief cells were 17.2 +/- 7.5. PTH mRNA was abundant in both the oxyphil and chief cells. Further analysis of oxyphil cell function was assessed by the heterotransplantation of parathyroid nodules, consisting exclusively of oxyphil or chief cells, into nude mice. The function of these implants was assessed by measuring the concentration of human intact PTH which did not cross-react with mouse PTH. Serum PTH concentrations were correlated with the volume of implanted tissue. Elevations of PTH concentrations were similar in the mice transplanted with oxyphil or chief cells, indicating that both cell types had similar PTH secretory activity. The basic histologic characteristics of both cell types were not altered following transplantation. These results demonstrate that oxyphil cells in secondary parathyroid hyperplasia synthesize and secrete PTH, and that this secretion contributes to the pathophysiology of hyperparathyroidism.
Topics: Alkaline Phosphatase; Animals; Calcium; Cell Transplantation; Eosinophils; Female; Humans; Hyperparathyroidism; Hyperplasia; In Situ Hybridization; Mice; Mice, Nude; Parathyroid Glands; Parathyroid Hormone; Phosphorus; RNA, Messenger; Transplantation, Heterologous
PubMed: 8856255
DOI: 10.1159/000189144 -
Journal of Proteomics May 2018SHPT is one of the most common complications of CKD-MBD. Recent studies indicate that oxyphil cell proliferation is related to SHPT progression, while not inhibited by... (Clinical Trial)
Clinical Trial Comparative Study
UNLABELLED
SHPT is one of the most common complications of CKD-MBD. Recent studies indicate that oxyphil cell proliferation is related to SHPT progression, while not inhibited by current treatments. The aim of this study was to analyze the correlation between oxyphil cell and clinical indicators in SHPT, further explore the protein expression differences of oxyphil cell. Among 33 MHD patients, 84.8% patients have one or more oxyphil dominant glands and the overall oxyphil cells proportion was 39.5 ± 16.3%. Univariate correlation and multivariable linear regression model showed that oral calcitriol dosage and treatment duration were independently correlated to oxyphil cell ratio. Proteomic study showed that mitochondrial protein, protein synthesis, and cell cycle regulation were significantly altered in oxyphil cell nodules. DBP was downregulated in oxyphil nodules on protein level, which may contribute to calcitriol resistance by reducing vitamin D transport. Through KEGG and PPI network analysis, Wnt signaling, TGF-β, ubiquitin mediated proteolysis and cell cycle pathways were significantly enriched in oxyphil cell nodules. Among which, MIF-CUL1 axis was significantly increased. These results suggest that the limitations of vitamin D in SHPT treatment is closely related to oxyphil cell and may be attributed to the dysregulation of vitamin D transport and ubiquitin regulation of oxyphil cell.
SIGNIFICANCE
Secondary hyperparathyroidism in end stage renal patients is one of the major challenges nephrology field faces. Emerging data indicate that oxyphil cell may participate in the pathophysiology of secondary hyperparathyroidism, while both calcimimetics and vitamin D receptor activators treatments are underperformed in controlling oxyphil cell proliferation. In the present study, we validated that the proliferation of oxyphil cells is associated with calcitriol treatment, and discovered that oxyphil cell nodules were significantly different from chief cells nodules in protein expression of mitochondria, protein synthesis and cell cycle regulation. It is noteworthy that DBP was downregulated in oxyphil nodules on protein level and may therefore participate in the resistance of calcitriol therapy by reducing the vitamin D transport capacity. Wnt signaling, TGF-β, ubiquitin mediated proteolysis and cell cycle pathways were significantly enriched in oxyphil cell nodules, among which, MIF-CUL1 axis may play an important role in the regulation of oxyphil proliferation and calcitriol resistance through ubiquitin mediated proteolysis. These results suggest that calcitriol treatment has limitations in oxyphil cell predominant SHPT, which may be attributed to the dysregulation of vitamin D transport and ubiquitin regulation of oxyphil cell, and the influence of microenvironment in uremia status may be the underlying reason.
Topics: Adult; Calcitriol; Chromatography, Liquid; Female; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Oxyphil Cells; Proteomics; Tandem Mass Spectrometry; Uremia
PubMed: 29526777
DOI: 10.1016/j.jprot.2018.02.029 -
The American Journal of Pathology Nov 2014Oxyphil cell transformation of epithelial cells due to the accumulation of mitochondria occurs often during cellular aging. To understand the pathogenic mechanisms, we...
Oxyphil cell metaplasia in the parathyroids is characterized by somatic mitochondrial DNA mutations in NADH dehydrogenase genes and cytochrome c oxidase activity-impairing genes.
Oxyphil cell transformation of epithelial cells due to the accumulation of mitochondria occurs often during cellular aging. To understand the pathogenic mechanisms, we studied mitochondrial DNA (mtDNA) alterations in the three cell types of the parathyroids using multiplex real-time PCR and next-generation sequencing. mtDNA was analyzed from cytochrome c oxidase (COX)-positive and COX-negative areas of 19 parathyroids. Mitochondria-rich pre-oxyphil/oxyphil cells were more prone to develop COX defects than the mitochondria-poor clear chief cells (P < 0.001). mtDNA increased approximately 2.5-fold from clear chief to oxyphil cells. In COX deficiency, the increase was even more pronounced, and COX-negative oxyphil cells had approximately two times more mtDNA than COX-positive oxyphil cells (P < 0.001), illustrating the influence of COX deficiency on mtDNA biosynthesis, probably as a consequence of insufficient ATP synthesis. Next-generation sequencing revealed a broad spectrum of putative pathogenic mtDNA point mutations affecting NADH dehydrogenase and COX genes as well as regulatory elements of mtDNA. NADH dehydrogenase gene mutations preferentially accumulated in COX-positive pre-oxyphil/oxyphil cells and, therefore, could be essential for inducing oxyphil cell transformation by increasing mtDNA/mitochondrial biogenesis. In contrast, COX-negative cells predominantly harbored mutations in the MT-CO1 and MT-CO3 genes and in regulatory mtDNA elements, but only rarely NADH dehydrogenase mutations. Thus, multiple hits in NADH dehydrogenase and COX activity-impairing genes represent the molecular basis of oxyphil cell transformation in the parathyroids.
Topics: Adult; Aged; Aged, 80 and over; Cellular Senescence; DNA, Mitochondrial; Electron Transport Complex IV; Humans; Metaplasia; Middle Aged; Mutation; NADH Dehydrogenase; Oxyphil Cells; Parathyroid Diseases; Parathyroid Glands
PubMed: 25418474
DOI: 10.1016/j.ajpath.2014.07.015 -
Acta Ophthalmologica Jun 1994A case of oncocytoma of the lacrimal sac is presented. An 84-year-old woman with a mass in the lacrimal sac area and epiphora was operated with excision. Histological... (Review)
Review
A case of oncocytoma of the lacrimal sac is presented. An 84-year-old woman with a mass in the lacrimal sac area and epiphora was operated with excision. Histological and electron microscopic examination revealed it to be an oncocytic adenoma. Oncocytic tumours of the lacrimal sac are very rare and to our knowledge this is the 14th case to be reported. Oncocytomas are composed of polyhedric cells with abundant oxyphil cytoplasm which is granular and contains large numbers of abnormal mitochondria. Non-neoplastic oncocytes may arise from the secretory epithelium of the sac in various chronic inflammatory states. They may also occur at an old age, as a result of the normal aging process.
Topics: Adenoma, Oxyphilic; Aged; Aged, 80 and over; Dacryocystorhinostomy; Female; Humans; Lacrimal Apparatus Diseases
PubMed: 7976277
DOI: 10.1111/j.1755-3768.1994.tb02782.x -
Endocrine Pathology Sep 2015Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically... (Observational Study)
Observational Study
Oxyphil cell parathyroid adenomas (OPA) are considered to be an uncommon cause of primary hyperparathyroidism (PHPT), and were historically thought to be clinically silent. It has been our clinical impression that these adenomas present more often than previously thought and may manifest a more severe form of primary hyperparathyroidism than classical adenoma. The aim of this study was to describe the incidence and clinical presentation of OPA. An observational case-control study was undertaken. The study group comprised patients undergoing parathyroidectomy for PHPT where the final pathology confirmed OPA. The controls were made up of an age- and sex-matched group of patients having parathyroidectomy in the same time period where the final pathology confirmed a classical or non-oxyphil adenoma. OPA were defined as parathyroid tumours containing >75% oxyphilic cells. The OPA cases were obtained by reviewing all histopathology slides over an 11-year period (2002-12) where the reports contained the words 'oxyphil' or 'oxyphilic' parathyroid adenomas. These were then reviewed by two independent pathologists to confirm a diagnosis of OPA. The primary outcome measures were preoperative serum calcium and parathyroid hormone (PTH) levels. Secondary outcome measures were symptoms at presentation, accuracy of preoperative localization studies, parathyroid gland weight following surgery, and type of surgery undertaken. In the period 2002-2012, 2739 patients underwent surgery for PHPT. Following pathological review, 91 cases were confirmed as being OPA and formed the study group. A control group (n = 91) from the same period was selected following matching on the basis of age at presentation and sex. OPA were associated with higher preoperative serum calcium (10.84 versus 10.48 mg/dL, p < 0.001) and parathyroid hormone (139 versus 64 ng/L, p < 0.001). At presentation, a lower proportion of OPA cases had asymptomatic disease (15 versus 29%, p = 0.03). There was a trend toward a higher rate of renal calculi at presentation in the OPA group (9 versus 3%, p = 0.07). Preoperative ultrasound was less accurate in localization of OPA when compared with classical adenoma. The rate of minimally invasive surgery was 67% for OPA and 78% for the control group (p = 0.06). All patients were cured of hypercalcaemia at 6-month follow up. There was no significant difference in the weight of removed parathyroid tissue between the groups (868 mg for OPA versus 789 mg for the control group, p = 0.6). OPA are frequently symptomatic and are associated with higher preoperative serum calcium and parathyroid hormone levels than classical types of parathyroid adenomas. OPA are less likely to be localised on preoperative ultrasound examination.
Topics: Adenoma; Aged; Case-Control Studies; Female; Humans; Hyperparathyroidism, Primary; Male; Middle Aged; Oxyphil Cells; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy
PubMed: 26091632
DOI: 10.1007/s12022-015-9378-3