PurposeThe differential diagnosis of parathyroid carcinoma (PC) or parathyroid adenoma (PA) in parathyroid tumors is crucial for their treatment and prognostic outcomes. We have reported previously that exosomal miR-27a-5p is different in PC or PA, although there are no published studies on a large number of samples, with the role of miR-27a-5p in regulating the effects of PC progression remaining unknown. The current study was designed to investigate the differential expression pattern of exosomal miR-27a-5p in both PC and PA and its relationship with clinicopathologic features, with the aim of further investigating the effect of PC at the cellular level.MethodsThe miRNA profiles of serum exosomes from 9 PC and 9 PA patients were evaluated using high-throughput sequencing. The differential expression of exosomal miR-27a-5p was detected in 29 PC and 36 PA patients. We also evaluated the diagnostic efficacy of exosomal miR-27a-5p to identify PC or PA and examined its correlation with the clinicopathologic features of PC. Primary PC cells were obtained by primary cell culture, while the effect of exosomes on PC cell apoptosis was investigated using miR-27a-5p mimic transfection and exosome mixed culture. Finally, the possible target gene of miR-27a-5p, PIK3CA, was identified using a dual-luciferase assay.ResultsExosomal miR-27a-5p differed significantly in PC and PA and was upregulated in PC with good diagnostic efficacy. Exosomal miR-27a-5p was also associated with T-staging of PC. miR-27a-5p inhibited PC cell apoptosis, an action that may be related to its target gene PIK3CA. However, the specific mechanism of this inhibition requires further exploration.ConclusionsThe exosomal miR-27a-5p assay is a noninvasive liquid biopsy method that provides an important reference for the timely and accurate identification and treatment of PC. Studies to reveal the mechanism of miR-27a-5p regulation in PC progression are of great significance to improve the current prognostic status of the tumor.

Summary:The simultaneous occurrence of parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma is exceptionally rare. Herein, we present an uncommon case in which the right malignant parathyroid lesion was 99mTc-MIBI-negative and the contralateral benign parathyroid lesion was 99mTc-MIBI-positive, which was confirmed by pathological examination postoperatively. In addition, we performed bilateral internal jugular venous sampling of PTH (IJ PTH), and the results showed that the IJ PTH was higher on the side of 99mTc-MIBI-negative lesion than on the other side. These findings suggest that 99mTc-MIBI-negative lesions with ipsilateral high IJ PTH should be highly suspected of parathyroid carcinoma in the setting of patients with two suspicious parathyroid lesions detected by cervical ultrasonography or computed tomography. No germline mutations associated with hereditary endocrine tumors were identified by whole-exome sequencing. Learning points:Parathyroid carcinoma can appear negative on 99mTc-sestamibi scintigraphy; therefore, comprehensive evaluation with both ultrasound and computed tomography is essential. In cases with discordant imaging and multiple lesions, bilateral internal jugular venous parathyroid hormone sampling serves as a decisive adjunct to guide en bloc resection when carcinoma is suspected. Preoperative evaluation for concurrent thyroid nodules is recommended during parathyroid surgery planning to avoid the need for secondary neck procedures.

Objective:To explore the influencing factors of negative preoperative technetium-99m methoxyisobutyl isonitrile（99mTc-MIBI） imaging in patients with single parathyroid adenoma. Methods:A total of 378 patients with single parathyroid tumors who underwent primary open cervical surgery were retrospectively enrolled. According to the results of preoperative 99mTc-MIBI imaging results, the patients were divided into the 99mTc-MIBI negative group and positive group. The baseline data, laboratory indicators, imaging findings and pathological characteristics were compared between the two groups to analyze the correlative and independent influencing factors of preoperative negative 99mTc-MIBI results. ROC curve analysis was performed to evaluate the predictive value of preoperative serum calcium and tumor volume for 99mTc-MIBI negativity. Results:Of the 378 enrolled patients, postoperative pathology confirmed 372 cases（98.4%） of parathyroid adenoma and 6 cases（1.6%） of atypical parathyroid tumor. Among them, 70 patients（18.5%） presented with negative preoperative 99mTc-MIBI scintigraphy results. Compared with the 99mTc-MIBI positive group, the negative group had a milder elevation of preoperative serum calcium, lower alkaline phosphatase（ALP） levels, a lower proportion of tumor cystic degeneration and smaller tumor volume, with all differences being statistically significant（P<0.05）. Multivariate Logistic regression analysis demonstrated that mild preoperative hypercalcemia and small tumor volume were independent risk factors for 99mTc-MIBI negativity. ROC curve analysis showed that the area under the curve（AUC） of preoperative serum calcium for predicting99mTc-MIBI negativity was 0.612（95%CI 0.538-0.687, P<0.01）, with an optimal cut-off value of 2.59 mmol/L. The AUC of tumor volume was 0.750（95%CI 0.692-0.808, P<0.01）, and the optimal cut-off value was 563 mm³. The median follow-up duration was 39.5 months, and the biochemical cure rate was 99.7%. Conclusion:In patients with single parathyroid tumors, the correlated factors for negative preoperative 99mTc-MIBI imaging included mild elevation of preoperative serum calcium, low ALP level, absence of tumor cystic degeneration and small tumor volume. Among these factors, mild preoperative hypercalcemia and small tumor volume were independent risk factors for negative 99mTc-MIBI imaging.

Parathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare malignant lesions characterized by high recurrence and metastasis rates, and accurate preoperative diagnosis remains a clinical challenge. The purpose of this study was to explore the diagnostic value of preoperative grayscale ultrasound combined with shear wave elastography (SWE) for such lesions. In this retrospective case-control study, patients with primary hyperparathyroidism and suspicious parathyroid abnormality on ultrasonography were recruited. All the lesions were assessed by SWE before surgery. Sonographic features and SWE performance along with demographic and related clinical parameters between PC/APT and PA groups were analyzed. This study included 21 patients with PC or APT matched to 84 patients with PA who underwent parathyroid surgery. The best subset selection method and multiple logistic regression analysis identified the sonographic features of intra-nodal fibrous bands and the ratio of mean shear wave velocity in tumor (SWVmean)/shear wave velocity in thyroid parenchyma (SWVth) as independent factors for PC/APT prediction (odds ratio [OR] = 38.536, 95

Objective:To investigate the preoperative coagulation characteristics and postoperative changes in patients with primary hyperparathyroidism（PHPT）. Methods:A retrospective analysis was conducted on the clinical data of 55 PHPT patients treated at Beijing Chaoyang Hospital, including preoperative and postoperatively（1 week） serum calcium, serum phosphorus, parathyroid hormone（PTH）, 25-hydroxyvitamin D, prothrombin time（PT）, activated partial thromboplastin time（APTT）, fibrinogen（FIB）, thrombin time（TT）, D-dimer（D-Dimer）, and thromboelastography（TEG） parameters such as coagulation index（CI）, reaction time（R）, kinetic time（K）, maximum amplitude（MA）, and lysis at 30 minutes（LY30）. The preoperative coagulation status and the impact of postoperative biochemical changes on coagulation function were analyzed. Results:All 55 patients successfully underwent parathyroid tumor resection, pathological findings were 41 cases of adenoma（74.5%）, 12 cases of atypical tumor（21.8%）, and 2 cases of carcinoma（3.6%）. The median preoperative serum calcium and PTH levels were 2.67 mmol/L and 171.60 pg/mL, respectively. All patients had PT, APTT, FIB, TT, CI, MA, K, and LY30 values within normal ranges, but 11 patients（20.0%） exhibited reduced preoperative R values. Compared to the normal R-value group, the reduced R-value group had shorter APTT, higher D-Dimer, and higher CI values, with statistically significant differences（P<0.05）, suggesting a hypercoagulable state preoperatively. One week postoperatively, the median serum calcium and PTH levels significantly decreased to 2.14 mmol/L and 35.10 pg/mL, respectively（P<0.05）. Except for a slight increase in D-Dimer, PT, APTT, FIB, TT, CI, MA, K, and LY30 values remained stable within normal ranges. The differences in APTT, D-Dimer, and CI values between the reduced R-value group and the normal R-value group were no longer statistically significant（P>0.05）. Conclusion:Some PHPT patients exhibit a hypercoagulable state with reduced R values preoperatively, and surgical resection of parathyroid tumor helps improve coagulation function in these patients.

Objectives Role of Vitamin D Receptor (VDR), Calcium Sensing Receptor (CaSR) and their associated long non-coding RNAs (lncRNAs) in Parathyroid Cancer (PC) development and PC diagnosis need to be explored. LncRNA SLC2A1-DT and SLC22A5-AS1 were dysregulated in previous microarray study. LncRNA SLC2A1-DT may target on VDR in prediction. Meanwhile, lncRNA SLC22A5-AS1was associated with CaSR. Methods 12 patients with PC and 43 patients with Parathyroid Adenoma (PA) were enrolled in this study. Fresh tissue samples were collected. Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) were used to assess the mRNA expression level of VDR and CaSR. In addition, protein level of VDR and CaSR were evaluated by Immunofluorescence (IF) detecting. Furthermore, expression level of lncRNA SLC2A1-DT, which may target on VDR in prediction, was validated by RT-qPCR in this study. Meanwhile, expression level of lncRNA SLC22A5-AS1, which was associated with CaSR in previous microarray study, was also detected by RT-qPCR. Results Down-regulated mRNA expression levels of VDR (p = 0.003) and CaSR (p = 0.000) were detected in patients with PC. Consistent with the mRNA profile, protein expression levels for these two genes were also decreased in PC group in IF detection. In addition, association between VDR and CaSR were also confirmed in patients with hyperparathyroidism (p = 0.000). However, there was no significant difference in Area Under Curve (AUC) among VDR, CaSR and PTH in parathyroid cancer diagnosis. Meanwhile, there was no difference in lncRNA SLC2A1-DT and SLC22A5-AS1 expression levels in RT-qPCR validation. However, expression levels of lncRNA SLC2A1-DT (p = 0.004) and SLC22A5-AS1 (p = 0.002) were increased in PC patients with normal serum phosphorus. In patients with normal serum phosphorus, the AUC of SLC2A1-DT was 0.896 (p < 0.001). Similarly, the AUC of SLC22A5-AS1 was 0.920 (p < 0.001). Conclusion Decreased VDR and CaSR may play a role in parathyroid cancer. VDR and CaSR may have interaction in hyperparathyroidism. LncRNA SLC2A1-DT and SLC22A5-AS1 were dysregulated in PC patients with normal phosphorate. These lncRNAs could serve as potential biomarkers for PC patients with normal phosphorus. Level of evidence This diagnostic or monitoring test accurate? (Diagnosis). Level 4 Case-control studies.

INTRODUCTION:Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with rising incidence in recent years. Long non-coding RNAs (lncRNAs) have been implicated in various cancers, including PTC. This study aims to identify novel lncRNA biomarkers involved in thyroid cancer progression and their potential role in carcinogenic pathways. MATERIAL AND METHODS:Using whole transcriptome sequencing, lnc-MPEG1-1 was identified as a potential target. Expression levels of lnc-MPEG1-1 were analyzed in 43 PTC tissue samples and data from the Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) cohort. Correlations between lnc-MPEG1-1 expression and clinical-pathological features were assessed. Functional assays, including cell proliferation, migration, and invasion, were conducted in vitro to investigate the biological role of lnc-MPEG1-1. Additionally, correlation analyses were performed to explore the relationship between lnc-MPEG1-1 expression and the B-Raf proto-oncogene, serine/threonine kinase V600E (BRAFV600E) mutation, a common genetic alteration in PTC. RESULTS:lnc-MPEG1-1 was significantly upregulated in PTC tissues, with higher expression in BRAF-mutated samples. Knockdown of lnc-MPEG1-1 in PTC cell lines significantly reduced cell proliferation, migration, and invasion, indicating its role in promoting tumor aggressiveness. Correlation analyses revealed a strong association between lnc-MPEG1-1 expression and BRAF mutation-related genes. Pathway analysis suggested that lnc-MPEG1-1 is involved in oncogenic processes such as cell growth, epithelial-mesenchymal transition (EMT), and cell cycle regulation. CONCLUSION:lnc-MPEG1-1 is a novel lncRNA linked to BRAF mutations, promoting PTC progression. It holds potential as a prognostic biomarker and therapeutic target, particularly in BRAF-mutant PTC cases.

PurposeThis study aimed to analyze the three-dimensional enhanced computed tomography (3D-EnCT) and ultrasound imaging features of recurrent parathyroid carcinoma lesions and develop a prediction model based on these features.MethodsThe clinical data of 34 patients (48 cases) with recurrent parathyroid carcinoma who underwent surgical treatment at Beijing Chaoyang Hospital's Thyroid and Neck Surgery Department between January 2017 and April 2024 were retrospectively analyzed. A total of 103 suspicious lesions were identified through a combination of preoperative 3D-EnCT and ultrasound examinations. Patients admitted prior to 1 January 2023 were included in the training set, and those admitted after 1 January 2023 were included in the validation set. In the training set, lesions were categorized as positive or negative based on pathological analysis. Statistically significant imaging features were identified via intergroup comparisons. An imaging prediction model was developed based on the 3D-EnCT and ultrasound features, and the predictive performance of the model was evaluated via receiver operating characteristic curves in the validation set.ResultsArterial- and venous-phase CT values, lesion boundaries, and blood flow signals were associated with pathological positivity. The 3D-EnCT prediction model based on these features achieved areas under the curve (AUCs) of 0.9 and 0.714 in the training and validation sets, respectively, whereas the ultrasound prediction model achieved AUCs of 0.601 and 0.621, respectively. The 3D-EnCT model demonstrated superior predictive performance.ConclusionThe 3D-EnCT prediction model demonstrated superior predictive performance for recurrent parathyroid carcinoma lesions.

Parathyroid carcinoma(PC) is an extremely rare malignant tumor of the parathyroid glands. The lung is the most common target organ for PC distant metastases. In this study, twelve patients diagnosed with PC with lung metastases were enrolled in the study. Hematoxylin and Eosin(H&E) stained, immunohistochemical stained and next-generation sequencing (NGS) of a 425-gene panel were performed on tumor tissue samples. At the same time, we also evaluated its histopathologic characteristics. The results indicate that the microscopic examination of metastatic lesions reveals the same structure and characteristics as PC; the tumor was composed of relatively uniform cells organized in nests and separated by thin fibrous bands and abundant blood vessels. Immunohistochemical evaluation of Ki67, CyclinD1, PTH, SYN, CgA, and CD56 was useful in diagnosing PC with lung metastases. The most frequently genetic alterations were mutations of CDC73 and copy number variation (CNV) of MCL1, with a mutation rate of 25 %. In addition, the mutations of CDC73, ATM, TP53, ALK, ERBB2, MAP3K4, TSC1, CCND1 and CNV of CDK4, MCL1, SMARCB1 overlap between metastatic lesions and primary lesions. In conclusions, PC is a rare endocrine malignant tumor that is very difficult to diagnose preoperatively and prone to clinical recurrence or distant metastasis. Genetic mutations, presentation and histological characteristic were the basis for diagnosing PC with lung metastases.

The differential diagnosis of parathyroid carcinoma (PC)/parathyroid adenoma (PA) in parathyroid tumors is critical for their management and prognosis. Circulating tumor cells (CTCs) identification in the peripheral blood of parathyroid tumors remains unknown. In this study, we proposed to investigate the differences of CTCs in PC/PA and the relationship with clinicopathologic features to assess its relevance to PC and value in identifying PC/PA. Peripheral blood was collected from 27 patients with PC and 37 patients with PA treated in our hospital, and the number of chromosome 8 aberrant CTCs was detected by negative magnetic bead sorting fluorescence in situ hybridization (NE-FISH). The differences of CTCs in PC/PA peripheral blood were compared and their diagnostic efficacy was evaluated, and the correlation between CTCs and clinicopathological features of PC was further explored. CTCs differed significantly in PC/PA (p = 0.0008) and were up-regulated in PC, with good diagnostic efficacy. CTCs combined with alkaline phosphatase (ALP) assay improved the diagnostic efficacy in identifying PC/PA (AUC = 0.7838, p = 0.0001). The number of CTCs was correlated with tumor dimensions, but not significantly correlated with clinical markers such as calcium and PTH and pathological features such as vascular invasion, lymph node metastasis and distant metastasis. As a non-invasive liquid biopsy method, CTCs test combined with ALP test can be used as an important reference basis for timely and accurate identification and treatment of PC. It is of great significance to improve the current situation of PC diagnosis, treatment and prognosis.

Ectopic parathyroid carcinoma (EPC) is a rare clinical entity with multiple diagnostic pitfalls, making surgical cures challenging. We assessed the clinicopathological spectrum and outcome of EPCs. In this retrospective cohort study, 24 EPCs were identified from 133 PC patients treated at a tertiary referral center. The relationship between clinicopathological findings and locations was analyzed. The locations of EPCs were predominantly intrathyroidal (62.5

BACKGROUND:Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS:In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS:The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS:Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

Abstract Purpose To analyze the accuracy of three imaging methods for locating parathyroid tumors preoperatively in patients with primary hyperthyroidism (PHPT). Methods We retrospectively analyzed the accuracy of dual-energy computed tomography (DECT), cervical ultrasound (US), and 99m-technetium-labeled methoxyisobutylisonitrile single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) for the preoperative localization of abnormal parathyroid glands in 277 patients, who underwent parathyroidectomy from February 2017 to March 2023 in our department. We compared the diagnostic efficiency of the three imaging methods for localization of abnormal parathyroid glands, including those with single parathyroid adenomas or carcinomas, double adenomas (DAs), multiple gland hyperplasia disease (MGHD), and ectopic parathyroid tumors. Results A total of 283 pathological parathyroid glands were found in the 277 PHPT patients. The DECT sensitivity of 93.3% was superior to that of US at 92.2% and 99mTc-MIBI SPECT/CT at 75.6%. Ectopic locations were diagnosed by DECT in 12/13 (92.3%) patients by 99mTc-MIBI SPECT/CT in 11/13 (84.6%) patients and by US in 8/13 (61.5%) patients. The diagnostic efficiency was 98.59% for the combination of US and DECT, 97.17% for MIBI and DECT, and 95.76% for US and 99mTc-MIBI SPECT/CT. The diagnostic efficiency of the combination of all three methods for identifying pathological parathyroid glands was 99.29%. Conclusion DECT has a higher diagnostic accuracy rate than US and 99mTc-MIBI SPECT/CT for the preoperative localization of abnormal parathyroid glands, and it has advantages for the localization of ectopic parathyroid glands. DECT shows promise as a first-line preoperative localization imaging method for PHPT patients and may lead to significantly improved preoperative localization of pathological parathyroid glands when combined with US and 99mTc-MIBI SPECT/CT.

Patients with parathyroid carcinoma (PC) are often diagnosed postoperatively, due to incomplete resection during the initial surgery, resulting in poor outcomes. The aim of our study was to investigate the pre-surgery indicators of PC and try to develop a predictive model for PC utilizing machine learning. Evaluation of pre-surgery neuropsychological function and confirmation of pathology were carried out in 133 patients with primary hyperparathyroidism in Beijing Chaoyang Hospital from December 2019 to January 2023. Patients were randomly divided into a training cohort (n = 93) and a validating cohort (n = 40). Analysis of the clinical dataset, two machine learning including the extreme gradient boosting (XGBoost) and the least absolute shrinkage and selection operator (LASSO) regression were utilized to develop the prediction model for PC. Logistic regression analysis was also conducted for comparison. Significant differences in elevated parathyroid hormone and decreased serum phosphorus in PC compared to (BP). The lower score of MMSE and MOCA was observed in PC and a cutoff of MMSE < 24 was the optimal threshold to stratify PC from BP (area under the curve AUC 0.699 vs 0.625). The predicted probability of PC by machine learning was similar to the observed probability in the test set, whereas the logistic model tended to overpredict the possibility of PC. The XGBoost model attained a higher AUC than the logistic algorithms and LASSO models. (0.835 vs 0.683 vs 0.607). Preoperative cognitive function may be a probable predictor for PC. The cognitive function-based prediction model based on the XGBoost algorithm outperformed LASSO and logistic regression, providing valuable preoperative assistance to surgeons in clinical decision-making for patients suspected PC.

Background Cognitive function in patients with primary hyperparathyroidism (PHPT) may be affected and be identified to have been linked to the level of parathyroid hormone (PTH). Previous studies have suggested that patients with PHPT present poor sleep quality, which might interact with cognitive decline. The purpose of this study was to determine whether sleep quality mediates the association between PTH level and cognitive function and investigate whether surgery improves sleep quality and cognition in PHPT patients. Methods Between June 2019 and August 2022, we recruited 146 patients diagnosed with PHPT (n = 146). We collected clinical data from medical records and evaluated sleep quality and cognition preoperatively and 2 months postoperatively by using the Pittsburgh Sleep Quality Index and Min-Mental State Examination. We examined the mediation effects of sleep disturbance and latency on correlations between PTH level and cognitive impairment by using the Bootstrap method. Results The sleep quality and cognitive function were correlated with PTH level before surgery. Sleep latency or sleep disturbance exhibited a partial mediating effect on the association between PTH level and MMSE scores in PHPT patients. (p < 0.05) In PHPT patients, there was a significant decline in PTH levels and an improvement in cognitive function post-surgery compared to pre-surgery, but no significant differences in sleep quality. Conclusion Sleep disturbance and sleep latency may mediate the association between PTH level and cognitive impairment in PHPT before surgery. The surgery could reduce PTH levels and improve cognition, but might not improve sleep quality in PHPT patients.

Abstract Background To investigate the characteristics of reticular fibre structure (RFS) in parathyroid adenoma (PTA), atypical parathyroid tumour (APT), and parathyroid carcinoma (PTC), and to assess its value as a diagnostic indicator. Methods Clinical data and pathological specimens of patients with PTA, APT or PTC were collected. Reticular fibre staining was performed to observe the characteristics of RFS. This study evaluated the incidence of RFS destruction in parathyroid tumours, compared RFS destruction between primary PTC and recurrent and metastatic PTC, and explored the association between RFS destruction and clinicopathological features of APT and primary PTC. Results Reticular fibre staining was performed in 50 patients with PTA, 25 patients with APT, and 36 patients with PTC. In PTA cases, a delicate RFS was observed. In both the APT and PTC groups, incomplete RFS areas were observed. The incidence of RFS destruction was different among the PTA, APT, and PTC groups (P < 0.001, χ2-test), at 0% (0/50), 44% (11/25), and 86% (31/36), respectively. When differentiating PTC from APT, the sensitivity and specificity of RFS destruction were 81% and 56%, respectively. The incidence of RFS destruction was 73% (8/11) in the primary PTC group and 92% (23/25) in the recurrent and metastatic PTC groups. In both the APT group and primary PTC group, no correlation was found between RFS destruction and clinicopathological features. Conclusion RFS destruction may indicate that parathyroid tumours have unfavourable biological behaviours.Reticular fibre staining may be a valuable tool for improving the diagnostic accuracy in parathyroid tumours.

Abstract Parathyroid cancer (PC) is a highly aggressive cancer with high relapse and metastasis rate. However, there still lack effective preoperative and intraoperative ways to discriminate between PC and parathyroid adenoma (PA). The intrinsic biological alternations that lead to PC still unclear. Here, we performed integrated analysis on the transcriptomic data of parathyroid tumors. To identify pivotal genes associated with PC diagnosis, we integrated the immune infiltration analysis, gene differential analysis and ROC analysis, and discovered that fibroblast expressed gene FN1 and CFD (FC score) was of great importance. The cancer diagnostic value of FC score was also validated in pan-cancer data covering the TCGA bulk tumor and single cell data. Cell communication and cancer hallmark correlation analysis showed that FC score was strongly associated with EMT process, which was the key step for tumor invasion and metastasis. Our results suggest the tumor fibroblast phenotype defined by FC score contributed to PC identification.