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Histopathology Sep 2021Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three...
AIMS
Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4-RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27-RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC.
METHODS AND RESULTS
Six IDCs with oncocytic changes were retrieved from the authors' archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1-23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33-RET in two of six cases, NCOA4-RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations.
CONCLUSIONS
Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Diagnosis, Differential; Female; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Mutation; Oncogene Fusion; Oxyphil Cells; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-ret; Salivary Gland Neoplasms; Salivary Glands; Sequence Analysis, RNA; Transcription Factors
PubMed: 33135196
DOI: 10.1111/his.14296 -
Cancer Cytopathology Jun 2021Identifying crystalloids, which includes amylase and tyrosine crystalloids, is relatively uncommon in salivary gland fine-needle aspiration (FNA) cytology. Although it...
BACKGROUND
Identifying crystalloids, which includes amylase and tyrosine crystalloids, is relatively uncommon in salivary gland fine-needle aspiration (FNA) cytology. Although it has been suggested that the presence of crystalloids favors a benign process, the full significance has not been well established.
METHODS
The authors performed a review of slides from all salivary gland FNA cases received in their laboratory from January 2017 to September 2019 to identify cases with crystalloids (screened cohort). In addition, the departmental archives were searched retrospectively for all salivary gland FNA cases that had specifically reported crystalloids. Cytologic findings as well as correlation with surgical pathology and clinical follow-up were examined.
RESULTS
There were 664 cases in the screened cohort. Crystalloids were present in 37 cases (incidence, 5.6%). Amylase crystalloids were the most commonly identified (n = 28; 75%), followed by tyrosine crystalloids (n = 4; 11%), and collagenous crystalloids (n = 1; 3%). Four cases with crystalloids could not be further classified because of low quantity (n = 4; 11%). An additional 54 cases were identified in the 10-year retrospective review. Diagnostic categorization for the total cohort (N = 91) was as follows: nondiagnostic, 30 cases (33%); nonneoplastic/benign, 42 cases (46%); neoplasm: benign, 10 cases (11%); and atypia of undetermined significance, 9 cases (10%). Twenty-six cases had subsequent resection findings, including oncocytic cyst/cystadenoma in 8 cases (31%), chronic sialadenitis/ductal obstructive change in 7 cases (27%), pleomorphic adenoma in 5 cases (27%), developmental cyst in 3 cases (12%), lymphoepithelial cyst in 2 cases (8%), and Warthin tumor in 1 case (4%).
CONCLUSIONS
This cohort represents the largest FNA series of salivary gland crystalloids. All cases were associated with nonneoplastic or benign neoplastic lesions.
Topics: Adenoma, Pleomorphic; Adolescent; Adult; Aged; Aged, 80 and over; Amylases; Biopsy, Fine-Needle; Child; Cytodiagnosis; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxyphil Cells; Prognosis; Retrospective Studies; Salivary Gland Neoplasms; Tyrosine; Young Adult
PubMed: 33296146
DOI: 10.1002/cncy.22395 -
The Journal of Cell Biology Feb 1963The normal parathyroids of six humans and a Virginia deer were studied by light and electron microscopy. The parenchyma of the deer parathyroid is composed of uniform...
The normal parathyroids of six humans and a Virginia deer were studied by light and electron microscopy. The parenchyma of the deer parathyroid is composed of uniform chief cells, which contained 100 to 400 mmicro electron-opaque, membrane-limited granules, presumed to be secretory granules, in addition to the usual cytoplasmic organelles. Desmosomes are present between adjacent cells, and rare cilia are observed protruding from the chief cells into the intercellular space. The human parathyroids contain chief cells in two phases-active and inactive-as well as oxyphil cells. Active chief cells have a large Golgi apparatus, sparse glycogen, numerous secretory granules, and rare cilia. Inactive chief cells contain a small Golgi apparatus, abundant glycogen, and few secretory granules. Both forms have the usual cytoplasmic organelles and, between adjacent cells, desmosomes. Oxyphil cell cytoplasm is composed of tightly packed mitochondria and glycogen granules, with rare secretory granules. Cells with cytoplasmic characteristics intermediate between chief and oxyphil cells, possibly representing transitional cells, have been observed. Secretory granules of both man and deer are composed of 100 to 200 A particles and short rods, and the granules develop from prosecretory granules in the Golgi region of the cell. The human secretory granules are smaller and more variable in shape than those of the deer. The granules are iron and chrome alum hematoxylin-positive, argyrophilic, and aldehyde fuchsin-positive, permitting light microscopic identification. They are also found in the capillary endothelial cells of the parathyroid and in its surrounding connective tissue. The secretory granules of the parathyroid cells can thus be followed from their formation in the Golgi apparatus almost to their extrusion into the blood stream.
Topics: Animals; Artiodactyla; Cytoplasm; Cytoplasmic Granules; Deer; Electrons; Golgi Apparatus; Humans; Male; Microscopy, Electron; Mitochondria; Organelles; Parathyroid Glands; Secretory Vesicles; Virginia
PubMed: 13936618
DOI: 10.1083/jcb.16.2.379 -
The Journal of Clinical Endocrinology... Jan 2013The most difficult thyroid tumors to be diagnosed by cytology and histology are conventional follicular carcinomas (cFTCs) and oncocytic follicular carcinomas (oFTCs).... (Comparative Study)
Comparative Study
OBJECTIVE
The most difficult thyroid tumors to be diagnosed by cytology and histology are conventional follicular carcinomas (cFTCs) and oncocytic follicular carcinomas (oFTCs). Several microRNAs (miRNAs) have been previously found to be consistently deregulated in papillary thyroid carcinomas; however, very limited information is available for cFTC and oFTC. The aim of this study was to explore miRNA deregulation and find candidate miRNA markers for follicular carcinomas that can be used diagnostically.
DESIGN
Thirty-eight follicular thyroid carcinomas (21 cFTCs, 17 oFTCs) and 10 normal thyroid tissue samples were studied for expression of 381 miRNAs using human microarray assays. Expression of deregulated miRNAs was confirmed by individual RT-PCR assays in all samples. In addition, 11 follicular adenomas, two hyperplastic nodules (HNs), and 19 fine-needle aspiration samples were studied for expression of novel miRNA markers detected in this study.
RESULTS
The unsupervised hierarchical clustering analysis demonstrated individual clusters for cFTC and oFTC, indicating the difference in miRNA expression between these tumor types. Both cFTCs and oFTCs showed an up-regulation of miR-182/-183/-221/-222/-125a-3p and a down-regulation of miR-542-5p/-574-3p/-455/-199a. Novel miRNA (miR-885-5p) was found to be strongly up-regulated (>40-fold) in oFTCs but not in cFTCs, follicular adenomas, and HNs. The classification and regression tree algorithm applied to fine-needle aspiration samples demonstrated that three dysregulated miRNAs (miR-885-5p/-221/-574-3p) allowed distinguishing follicular thyroid carcinomas from benign HNs with high accuracy.
CONCLUSIONS
In this study we demonstrate that different histopathological types of follicular thyroid carcinomas have distinct miRNA expression profiles. MiR-885-5p is highly up-regulated in oncocytic follicular carcinomas and may serve as a diagnostic marker for these tumors. A small set of deregulated miRNAs allows for an accurate discrimination between follicular carcinomas and hyperplastic nodules and can be used diagnostically in fine-needle aspiration biopsies.
Topics: Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Algorithms; Biomarkers, Tumor; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Papillary; Cluster Analysis; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Microarray Analysis; Oxyphil Cells; Prognosis; Thyroid Cancer, Papillary; Thyroid Neoplasms; Validation Studies as Topic
PubMed: 23150679
DOI: 10.1210/jc.2012-2694 -
PloS One 2012Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic...
BACKGROUND
Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20).
METHODS
Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways.
RESULTS
All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent).
CONCLUSIONS
We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828).
Topics: Adenocarcinoma, Follicular; Aged; Aged, 80 and over; Alleles; Carcinoma, Neuroendocrine; Chromosomes, Human, Pair 7; Cohort Studies; DNA Mutational Analysis; DNA, Neoplasm; Disease Progression; Female; Flow Cytometry; Gene Dosage; Genes, Neoplasm; Genome, Human; Haploidy; Homozygote; Humans; Male; Middle Aged; Models, Biological; Oxyphil Cells; Phenotype; Polymorphism, Single Nucleotide; Recurrence; Reproducibility of Results; Thyroid Neoplasms
PubMed: 22675538
DOI: 10.1371/journal.pone.0038287 -
Journal of Endocrinological... Nov 2019The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular...
PURPOSE
The aim was to find whether the presence of Hürthle cells (HC) in a smear influences the categorization of FNA results or the risk of malignancy (RoM) of particular categories of cytological diagnosis.
METHODS
25,220 FNA performed in a single center in years 2005-2017 were analyzed. Almost all the examined patients were exposed to moderate iodine deficiency for most of their lives. The distribution of FNA outcome categories was compared between two groups: with or without HC (HC and non-HC). The RoM was evaluated on the basis of postoperative histopathological examination (3082 patients).
RESULTS
HC were found in 7.5% of diagnostic FNA. HC nodules were classified into categories II (78.2% vs. 91.9%, p < 0.0000) and VI (0.4% vs. 1.2%, p = 0.0017) less often than non-HC nodules, but more frequently to categories III (14.4% vs. 5.8%, p < 0.0000), IV (11.2% vs. 0.9%, p < 0.0000) and V (1.5% vs. 0.8%, p = 0.0013). There were no significant differences in RoM between HC and non-HC nodules. The RoM in HC and non-HC nodules of particular categories of the Bethesda system was as follows: II: 1.8% vs. 0.8%, III: 9.7% vs. 3.8% when only the last FNA was considered and 10.8% vs. 6.4% when the category III in any performed FNA was considered; IV: 12.7% vs. 10.9%; V: 41.7% vs. 58.2%; and VI: 100% vs. 96.9%.
CONCLUSIONS
HC nodules are classified into categories of equivocal cytological outcomes more often than nodules without HC. Nevertheless, the presence of HC in a smear does not significantly affect the RoM of FNA categories.
Topics: Adenocarcinoma, Follicular; Biopsy, Fine-Needle; Cytodiagnosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxyphil Cells; Prognosis; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule; Thyroidectomy
PubMed: 31077094
DOI: 10.1007/s40618-019-01055-0 -
Cancer Cytopathology Aug 2017Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is a benign process that does not inherently require surgical excision. However, cytologic findings in...
BACKGROUND
Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is a benign process that does not inherently require surgical excision. However, cytologic findings in fine-needle aspiration (FNA) of oncocytosis cases have not been well characterized previously, limiting preoperative identification.
METHODS
All available cases of oncocytosis with corresponding FNA specimens were identified from the pathology archives of 3 academic institutions. Clinical, cytologic, and histologic findings were tabulated for all cases.
RESULTS
Twelve cases of oncocytosis were identified from 11 patients, including 11 parotid FNA specimens and 1 submandibular FNA specimen. On the original diagnoses, 6 specimens were classified as benign, 4 as atypical, and 2 as nondiagnostic. Oncocytosis was listed in the differential diagnosis in only 1 case. Among diagnostic aspirates, 8 demonstrated low cellularity and 2 demonstrated moderate cellularity. All 10 cases demonstrated oncocytic cells in small to medium groups, with single cells in just 1 case. Spindled and squamous morphology were each noted in 3 cases. Four cases demonstrated cystic change and 1 showed background mucin without goblet cells. No necrosis or mitoses were observed.
CONCLUSIONS
Although oncocytosis demonstrates some overlap with Warthin tumor and oncocytoma, it lacks the diagnostic findings specific to oncocytic salivary gland malignancies such as salivary duct carcinoma, acinic cell carcinoma, mammary analog secretory carcinoma, and mucoepidermoid carcinoma. Despite current limitations in the understanding of oncocytic salivary gland lesions, the presence of a paucicellular specimen comprised of small groups of oncocytic cells should raise the possibility of oncocytosis in the differential diagnosis and can favor it in elderly patients with multiple salivary nodules. Cancer Cytopathol 2017;125:627-34. © 2017 American Cancer Society.
Topics: Adenolymphoma; Adenoma, Oxyphilic; Aged; Aged, 80 and over; Biopsy, Fine-Needle; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Mucoepidermoid; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Oxyphil Cells; Parotid Diseases; Salivary Gland Diseases; Salivary Gland Neoplasms; Submandibular Gland Diseases
PubMed: 28411376
DOI: 10.1002/cncy.21865 -
PloS One 2011Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the...
Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.
Topics: Animals; Animals, Newborn; Biomarkers; Cell Adhesion Molecules; Cell Differentiation; Embryo, Mammalian; Enzyme Activation; Fluorescent Antibody Technique; Humans; Hypothyroidism; Mice; Mice, Knockout; MicroRNAs; Morphogenesis; Oxyphil Cells; RNA Processing, Post-Transcriptional; Ribonuclease III; Thyroid Gland
PubMed: 22132122
DOI: 10.1371/journal.pone.0027648 -
World Journal of Surgery Jun 2019The inability to identify the pathological gland at surgery results in failure to cure hyperparathyroidism in 2-5%. The poorly understood characteristic of parathyroid...
BACKGROUND
The inability to identify the pathological gland at surgery results in failure to cure hyperparathyroidism in 2-5%. The poorly understood characteristic of parathyroid tissue to manifest autofluorescence (AF) under near-infrared (NIR) light has been promoted as an intraoperative adjunct in parathyroid surgery. This study sought to explore potential clinical correlates for AF and assess the clinical utility of AF in parathyroid surgery.
METHODS
Consecutive patients undergoing parathyroid surgery for primary and renal disease were included. NIR imaging was used intraoperatively and the degree of AF of parathyroid glands graded by the operating surgeon. Variables assessed for correlation with AF were: pre-operative serum calcium and PTH, SestaMIBI positivity, gland weight and histological composition.
RESULTS
Ninety-six patients underwent parathyroidectomy over an 8-month period: 49 bilateral explorations, 41 unilateral and 6 focussed lateral approaches: 284 potentially 'visualisable' glands in total. Two hundred and fifty-seven glands (90.5%) were visualised with NIR. Correlation was found between the degree of fluorescence and pre-operative serum calcium and PTH, but not between gland weight and SestaMIBI positivity. In those with renal hyperparathyroidism, a predominance of oxyphil cells correlated with increased AF.
CONCLUSION
Autofluorescence intensity correlates with serum calcium, PTH and gland composition. Further refinements would be required for this information to be of value in a clinical setting. Improvements allowing NIR to visualise the additional 9.5% of parathyroids and overcome the variation in signal intensity due to depth of access are required for the routine adoption of this technology. At present, its routine use in a clinical setting cannot be justified.
Topics: Adult; Aged; Aged, 80 and over; Calcium; Female; Fluorescence; Humans; Intraoperative Care; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Prospective Studies; Reproducibility of Results; Spectroscopy, Near-Infrared; Young Adult
PubMed: 30737552
DOI: 10.1007/s00268-019-04929-9 -
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