Oncocytic lesions represent a group of benign and potentially precancerous tumors characterized by the accumulation of oncocytes, which are large, granular, and eosinophilic cells. Diagnosing oncocytic lesions in the parotid gland typically involves a combination of imaging techniques, such as ultrasound, Computed Tomography (CT) scans, and Magnetic Resonance Imaging (MRI). Fine-needle aspiration (FNA) biopsy with histopathological examination remains the primary diagnostic tool for these lesions. Accurate diagnosis is crucial for appropriate management decisions. Treatment options for oncocytic lesions in the parotid gland include surgery, conservative management, and radiation therapy (RT). However, in the head and neck region, radiation doses can be a double-edged sword. While RT is a treatment modality, low radiation doses can promote the development of oncocytic lesions in the parotid gland. The prognosis for patients with oncocytic lesions is generally favorable, especially when the lesions are benign and appropriately managed. Current research focuses on the molecular mechanisms underlying oncocytic lesions in response to low-dose radiation exposure. The development of these lesions following low radiation doses represents a significant clinical concern. This manuscript provides a comprehensive overview of the current knowledge regarding oncocytic lesions in the parotid gland, including risk factors, diagnosis, treatment options, and ongoing research, offering valuable insights for clinicians and researchers.

Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally been classified as separate entities in thyroid pathology. To illustrate the diversity of these thyroid lesions, we describe three cases of fine needle aspiration biopsies (FNAB) diagnosed as Bethesda Category IV: Follicular neoplasm, oncocytic type, under the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), with ThyroSeq v3 molecular testing and subsequent surgical excision.

This commentary explores the recent application of single-cell RNA sequencing in the study of uremic secondary hyperparathyroidism, shedding light on the cellular dynamics within parathyroid glands. The use of single-cell RNA sequencing reveals new insights into the differentiation processes of chief and oxyphil cells, challenging traditional views and highlighting the potential of this technology in advancing our understanding of parathyroid anatomy.

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.

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.

Indeterminate thyroid nodules with Hürthle cell cytology remain a diagnostic challenge. The low benign call rate and positive predictive value of first-generation molecular tests precluded their use to rule out malignancy. We examined the diagnostic performance of current tests.
This subset analysis of our prospective randomized trial compared the benign call rate and positive predictive value of Afirma Gene Sequencing Classifier and Thyroseq v3 in Bethesda III and IV nodules with Hürthle cell cytology. Molecular test samples were obtained at initial fine-needle aspiration (8/2017-7/2022) and reflexively sent for processing.
Molecular testing was performed on 140 Hürthle cell nodules. Of 79 nodules tested with the Afirma Gene Sequencing Classifier, the benign call rate was 84% (66/79). Nine of 66 nodules with benign results were resected, with no malignancies. Twelve of 13 nodules with suspicious results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and one Hürthle cell carcinoma (positive predictive value 25%). Of 61 nodules tested with Thyroseq v3, the benign call rate was 56% (34/61; (P < .01 versus Afirma Gene Sequencing Classifier). Five of 34 nodules with negative results were resected, with no malignancies. Nineteen of 27 nodules with positive results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and 1 Hürthle cell carcinoma (positive predictive value 16%).
The high benign call rate of current molecular tests in Hürthle cell nodules strengthens their value in enabling patients to avoid surgery.

Papillary cystadenoma (PC) of the salivary gland is an uncommon benign epithelial neoplasm that shows predominantly multicystic growth pattern with intraluminal papillary proliferation and areas of oncocytic differentiation. We report a case of papillary cystadenoma of the parotid gland in a 44-years-old female. The patient presented with painful nodular swelling in the right parotid region for two months. Ultrasonography revealed a well marginated oval lesion with altered signal intensity involving the superficial lobe. The excision specimen showed a neoplasm with multicystic spaces having papillary projections lined by benign low-grade epithelium and supported by fibrovascular cores. No significant cytological atypia or mitosis was observed. The cells were immunoreactive for Keratin, Keratin 7, and were negative for Keratin 20, AR, HeR2/neu, TTF1, CDX2, and GATA3. p63 and Keratin 5/6 highlighted the myoepithelial cell layer lining the cystic spaces as well as the papillary projections. The Ki-67 proliferation index was 6%. The patient is on close clinical and imaging follow-up for the last 1year and 8 months without any evidence of disease recurrence or metastasis. Rarity of the lesion and distinct histomorphology warrants appropriate knowledge and discussion of the subject.

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.

BACKGROUND: Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow-up studies. However, traditional cytologic-histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular-derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics.
METHODS: This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2-year period with at least 3 years of follow-up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic-type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic-histologic correlation outcomes.
RESULTS: The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%-20.8%), 28.1% (range, 22.1%-36.7%), and 27.0% (range, 19.5%-41.5%), respectively, and most individual cytopathologists\' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists\' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p = .06), the AUS PCRs were quite different (p = .002). By cytologic-histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false-positive cases.
CONCLUSIONS: MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement.

BACKGROUND: To better understand the molecular alterations associated with Hurthle cell lesions of the thyroid, we retrospectively reviewed the association of clonal DNA copy number alterations (CNAs) with fine needle aspiration (FNA) cytomorphology and surgical follow-up.
METHODS: Hurthle cell type (HCT) and non-Hurthle cell type (NHCT) thyroid FNAs that were classified according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as atypia of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN) with corresponding molecular testing performed by ThyroSeq v3 genomic classifier were compared to surgical follow-up.
RESULTS: A total of 54 thyroid FNA cases were identified, distributed among the following categories: AUS-HCT (n = 15, 27.8%), SFN-HCT (n = 11, 20.4%), AUS-NHCT (n = 19, 35.2%), and SFN-NHCT (n = 9, 16.6%). The lesions classified as AUS-HCT and SFN-HCT showed a higher prevalence of CNAs (n = 10/26; 38.5%) compared to their NHCT counterparts (n = 3/28; 10.7%) (p < .03). Of the 42 patients (77.8%) with surgical follow-up, CNAs were more often seen in benign (n = 10/26, 38.5%) than malignant conditions (n = 1/16, 6.3%) (p < .03). CNAs were encountered in more lesions with Hurthle cell features on histologic examination (n = 8/14, 57.1%) than those without (n = 3/28, 10.7%) (p < .002). The presence of CNAs alone was seen only in benign adenomas and more commonly with Hurthle cell features (n = 5/7, 71.4%).
CONCLUSIONS: In this study, CNAs were associated with Hurthle cell morphology on thyroid FNA and benign adenomas upon surgical follow-up. Therefore, if the only finding of a positive ThyroSeq v3 GC result is a CNA, conservative management can be considered if clinically indicated.