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European Journal of Medical Research Jan 2024N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our...
BACKGROUND
N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats.
METHODS
Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised.
RESULTS
There was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal.
CONCLUSIONS
We showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.
Topics: Rats; Male; Animals; Oxyphil Cells; Nitrosamines; Thyroid Gland; Adrenal Glands
PubMed: 38245764
DOI: 10.1186/s40001-024-01654-5 -
The American Journal of Case Reports Oct 2023BACKGROUND Brain metastasis of papillary thyroid cancer (PTC) is rare. Treatment of these patients is challenging due to the lack of specific guidelines. Early diagnosis...
Thyroglobulin as a Rapid and Cost-Effective Biomarker for Diagnosis of Thyroid Carcinoma Brain Metastasis: A Case Report of a Patient with Metastatic Hurthle Cell Thyroid Carcinoma.
BACKGROUND Brain metastasis of papillary thyroid cancer (PTC) is rare. Treatment of these patients is challenging due to the lack of specific guidelines. Early diagnosis is accompanied by immediate treatment and less morbidity. Total resection of brain lesions may be unattainable when they include infiltration of eloquent areas. This report is of an 81-year-old man who had undergone total thyroidectomy for goiter in the past and presented with metastatic papillary thyroid carcinoma (PTC) to the neck after a gap of 16 years. After two years, the patient developed a solitary cystic brain PTC metastasis associated with raised thyroglobulin (Tg) inside the cystic lesion aspirated during brain surgery. CASE REPORT An 81-year-old male patient was admitted for a space-occupying brain lesion in the right frontal lobe. The patient's history included metastatic disease of PTC to the neck with cervical lymph node metastasis and local recurrence after surgery and radioactive iodine-131 treatment. The patient underwent craniotomy and removal of the lesion. The aspirated fluid was sent for cytological examination and measurement of Tg levels, which were interestingly high. Pathology of the brain lesion revealed infiltration of brain parenchyma from a metastatic lesion characterized by eosinophilic cells with irregular contours forming grooves, resulting in cytoplasmic pseudo-inclusions, an oncotic variant of PTC. CONCLUSIONS This report has shown that residual tissue may be present following total thyroidectomy and may be the origin of PTC with metastasis to the brain. The patient in this study suffered from a brain lesion that could be excised. However, aspiration of cystic compartments could provide a rapid diagnosis in patients with non-removable brain lesions.
Topics: Male; Humans; Aged, 80 and over; Thyroid Neoplasms; Thyroglobulin; Iodine Radioisotopes; Cost-Benefit Analysis; Oxyphil Cells; Carcinoma, Papillary; Thyroid Cancer, Papillary; Thyroidectomy; Brain Neoplasms; Biomarkers
PubMed: 37853680
DOI: 10.12659/AJCR.939025 -
Indian Journal of Pathology &... 2023Neoplastic lipomatous lesions of the salivary glands constitute ≤0.5% of all the salivary gland tumors. Oncocytic sialolipoma of the parotid glands is extremely... (Review)
Review
Neoplastic lipomatous lesions of the salivary glands constitute ≤0.5% of all the salivary gland tumors. Oncocytic sialolipoma of the parotid glands is extremely uncommon. We report a case of oncocytic sialolipoma of the parotid gland in a 59-year-old male who presented with a gradually increasing swelling of the right parotid. Excisional parotid biopsy performed in view of possible pleomorphic adenoma as suggested on ultrasonography showed histological features consistent with oncocytic sialolipoma. We also described the characteristics of 24 previously reported cases of oncocytic sialolipoma of the parotid gland. The median age of the patients including the present case was 56 years (range 7-89), and 14 were male. The largest and the least reported sizes of the tumor were 7.0 and 1.4 cm, respectively. The left-sided parotid gland was more commonly involved (14/23). Despite its rarity, oncocytic sialolipoma should be considered in lipomatous parotid lesions showing epithelial components with oncocytic changes.
Topics: Humans; Male; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Female; Parotid Gland; Adenoma; Salivary Gland Neoplasms; Oxyphil Cells; Lipoma; Parotid Neoplasms
PubMed: 37530346
DOI: 10.4103/ijpm.ijpm_323_21 -
Cancer Research Communications Jul 2023Hürthle cell carcinoma (HCC) is a rare type of thyroid cancer with high rates of distant metastasis and recurrence. Along with the scarcity of effective systemic...
UNLABELLED
Hürthle cell carcinoma (HCC) is a rare type of thyroid cancer with high rates of distant metastasis and recurrence. Along with the scarcity of effective systemic therapies for HCC, these factors contribute to poor clinical outcomes. The immunologic features of HCC are poorly defined and response rates with immune checkpoint blockade have not been reported. A more comprehensive understanding of the immune landscape and factors that predict response to checkpoint inhibitors is needed. We performed RNA sequencing on 40 tumors to characterize the neoantigen landscape and immune microenvironment of HCC. We analyzed transcriptomic profiles, tumor-infiltrating immune cell populations, and measures of T-cell activation/dysfunction and correlated these to genetic features such as tumor mutation burden, neoantigen burden, mitochondrial mutations, and LOH from chromosomal uniparental disomy. Finally, immune profiles of patients with recurrence were compared with those of patients without recurrence. HCC tumors exhibited low levels of immune infiltration, with the more aggressive widely invasive phenotype associated with more immune depletion. There was a negative correlation between tumor mutation burden, neoantigen burden, programmed cell death ligand 1 (PD-L1) expression, and the immune infiltration score. HCC tumors that exhibited a global LOH from chromosomal uniparental disomy or haploidization had the lowest level of immune infiltration. HCC tumors that recurred displayed an immune-depleted microenvironment associated with global LOH and aerobic glycolysis. These findings offer new insights into the functional immune landscapes and immune microenvironment of HCC. Our data identify potential immunologic vulnerabilities for these understudied and often fatal cancers.
SIGNIFICANCE
The immune landscape of HCC is poorly defined and response rates to immunotherapy have not been reported. The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Uniparental Disomy; Oxyphil Cells; B7-H1 Antigen; Tumor Microenvironment
PubMed: 37529400
DOI: 10.1158/2767-9764.CRC-23-0120 -
Frontiers in Endocrinology 2023Bethesda category III - atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous class of the Bethesda system for...
Clinico-cytopathological subcategorization in thyroid nodules of atypia of undetermined significance/follicular lesion of undetermined significance using the TIRADS and Bethesda classifications.
INTRODUCTION
Bethesda category III - atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is a heterogeneous class of the Bethesda system for thyroid nodules. In order to clarify the therapeutic road for clinicians, this category was subclassified based on the cytopathological features. In this study, we evaluated the risk of malignancy, surgical outcome, demographic characteristics, and correlation of ultrasound features with the final outcome in patients with thyroid nodules based on AUS/FLUS subclassification.
METHOD
After evaluating 867 thyroid nodules from three different centers, 70 (8.07%) were initially diagnosed as AUS/FLUS. The cytopathologists re-interpreted the FNA samples and subclassified them into five subcategories: architectural atypia, cytologic atypia, cytologic and architectural atypia, and Hürthle cell AUS/FLUS, and atypia, which was not specified. Based on the suspicious ultrasound features, an appropriate ACR TI-RADS score was allocated to each nodule. Finally, the malignancy rate, surgical outcomes, and ACR TI-RADS scores were evaluated among Bethesda category III nodules.
RESULTS
Among the 70 evaluated nodules, 28 (40%) were subclassified as Hürthle cell AUS/FLUS, 22 (31.42%) as cytologic and architectural atypia, 8 (11.42%) as architectural atypia, 7 (10%) as cytologic atypia, and 5 (7.14%) as atypia which was not specified. The overall malignancy rate was 34.28%, and the architectural atypia and Hürthle cell nodules displayed lower malignancy compared to other groups (P-Value<0.05). Utilizing ACR TI-RADS scores showed no statistical significance between Bethesda III subcategorization and ACR TI-RADS scores. However, ACR TI-RADS can be a reliable predictor for Hürthle cell AUS/FLU nodules.
CONCLUSION
ACR TI-RADS helps evaluate malignancy only in the Hürthle cell AUS/FLUS subcategory of AUS/FLUS. Besides, cytopathological reporting based on the suggested AUS/FLUS subclassification could help clinicians take appropriate measures to manage thyroid nodules.
Topics: Humans; Thyroid Nodule; Cytology; Cerebellar Vermis; Oxyphil Cells
PubMed: 37313444
DOI: 10.3389/fendo.2023.1135196 -
Cancer Discovery Aug 2023Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here,...
UNLABELLED
Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.
SIGNIFICANCE
HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.
Topics: Humans; Thyroid Gland; Carcinoma, Hepatocellular; Lipid Peroxides; Fermentation; Oxyphil Cells; Liver Neoplasms; DNA, Mitochondrial
PubMed: 37262067
DOI: 10.1158/2159-8290.CD-22-0976 -
PNAS Nexus Mar 2023Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated...
Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1-3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.
PubMed: 36992820
DOI: 10.1093/pnasnexus/pgad073 -
Frontiers in Endocrinology 2023To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients.
OBJECTIVE
To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients.
METHODS
Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells.
RESULTS
No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes.
CONCLUSION
These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.
Topics: Humans; Female; Male; Hyperparathyroidism, Primary; Sex Characteristics; Endothelial Cells; Parathyroid Hormone; Sequence Analysis, RNA
PubMed: 36960393
DOI: 10.3389/fendo.2023.1165890 -
Head and Neck Pathology Mar 2023Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the... (Review)
Review
BACKGROUND
Oncocytes are a component of many metaplastic and neoplastic lesions throughout the head and neck area, primarily originating in salivary/seromucinous glands and the thyroid gland. In addition, other lesions can contain cells that mimic oncocytes (pseudo-oncocytes); these can be of epithelial or non-epithelial origin.
METHODS
Review article.
RESULTS
Oncocytic metaplasia is common in seromucinous glands throughout the upper aerodigestive tract, most notable in the oral cavity, nasopharynx and larynx. The main oncocytic salivary gland neoplasms are Warthin tumor and oncocytoma. Infarction of Warthin tumor may lead to recognition difficulties. Oncocytic subtypes of mucoepidermoid carcinoma and intraductal carcinoma have morphologic and immunohistochemical features that allow distinction from major oncocytic entities. Oncocytic thyroid tumors include adenoma, carcinoma (follicular, papillary and medullary), along with poorly differentiated tumors. Oncocytic papillary sinonasal and middle ear tumors must be distinguished from low grade adenocarcinomas. Pseudo-oncocytic entities include paraganglioma, Langerhans cell histiocytosis, giant cell tumor, rhabdomyoma, and metastatic tumors.
CONCLUSIONS
Correct diagnosis of oncocytic head and neck lesions requires a knowledge of the spectrum of possible entities, their characteristic sites of occurrence, architecture, histomorphology, and immunohistochemistry. Oncocytic subtypes of several newly described entities are now recognized. Both epithelial and non-epithelial mimics of oncocytes exist. The molecular features of oncocytic tumors can be helpful in their diagnosis and understanding their pathogenesis.
Topics: Humans; Oxyphil Cells; Adenolymphoma; Salivary Gland Neoplasms; Salivary Glands; Adenoma, Oxyphilic
PubMed: 36928735
DOI: 10.1007/s12105-022-01520-y