Esophageal schwannoma mimicking non-functional parathyroid adenoma on 99mTc-sestamibi imaging: a case report.

Technetium-99m sestamibi single-photon emission computed tomography/computed tomography (99mTc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was 99mTc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal 99mTc-sestamibi uptake in the neck region.

KMT2A and chronic inflammation as potential drivers of sporadic parathyroid adenoma.

BACKGROUND: Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood. METHODS: Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations. RESULTS: There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues. CONCLUSIONS: We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications. HIGHLIGHTS: Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.

Parathyroid tumors in the 5th edition of the WHO Classification of Tumors of the Endocrine Organs.

The diagnosis of pathological conditions of the parathyroid glands is the answer to clinically more frequently detected hypercalcemic conditions, including MEN syndromes. In routine biopsy practice, enlarged bodies are also a differential diagnosis for the diagnosis of thyroid nodules. In the chapter of parathyroid tumors, the 5th edition of the WHO classification brings changes influenced similarly to other endocrine organs by the increase in genetic information. At the terminological level, the concept of hyperplasia has been narrowed down to secondary hyperplasia, most of the previously primary hyperplasias are referred to as multiglandular parathyroid disease due to evidence of multiglandular clonal proliferations. The term atypical parathyroid tumor replacing atypical adenoma is newly introduced - the uncertain biological behaviour is emphasized. The basic examination includes parafibromin immunohis- tochemistry, the deficiency of parafibromin being an indicator of an inactivating CDC73 mutation and an increased risk of familial forms, or MEN. Methodologically, refinements are introduced in the quantification of mitotic activity per 10 mm2. Oncocytic subtypes have an arbitrarily declared threshold of more than 75% oncocytes. The definition of lipoadenoma (multiplication of both components, more than 50% of adipose tissue in the tumor) is similarly specified. The diagnosis of cancer remains histopathological with unequivocal evidence of invasion, or microscopically verified metastasis.

Parathyroidectomy for solitary parathyroid adenoma via trans-areola single site endoscopic approach: Results of a case-match study.

BACKGROUND: This study aimed to establish the standardized procedure of trans-areola single site endoscopic parathyroidectomy (TASSEP), and to compare the performance of TASSEP with that of conventional open parathyroidectomy (COP). METHODS: This study enrolled 40 patients with primary hyperparathyroidism (PHPT) who underwent TASSEP, and included 40 of 176 PHPT patients who underwent COP based on propensity score matching. The retrospective analysis was conducted based on prospectively collected data. Perioperative outcomes, including surgical profile, surgical burden and cosmetic results and follow-up were reported. The learning curve was described using a cumulative sum (CUSUM) analysis. RESULTS: 40 TASSEPs were completed successfully without conversions or severe complications. There was no statistically significant difference in operation time between TASSEP and COP groups (80.83 ± 11.95 vs. 76.95 ± 7.30 min, p = 0.084). Experience of 17 cases was necessitated to reach the learning curve of TASSEP. Postoperative pain score and traumatic index (C-reactive protein and erythrocyte sedimentation rate) in TASSEP were apparently lower than those in COP group (p < 0.05). During the proliferation and stabilization phases, TASSEP was associated with significantly better incision recovery and cosmetic scores. Postoperative serum calcium and PTH levels throughout the follow-up period indicated satisfactory surgical qualities in both groups. CONCLUSION: Based on precise preoperative localization and intraoperative planning facilitated by three-dimensional (3D) virtual modeling, TASSEP can be feasibly performed on selected patients with satisfactory success rates and low complication rates, providing preferable cosmetic results and alleviating the surgical burden to a certain extent.

Thoracoscopic treatment of mediastinal ectopic parathyroid adenomas: a Latinamerica experience case series and literature review.

BACKGROUND: Hyperparathyroidism (HPT) is a disease caused by hypersecretion of one or more parathyroid glands, it can be associated with ectopic mediastinal parathyroid glands (MEPA) in 2% of cases. The use of video-assisted thoracoscopic surgery (VATS) for the surgical resection of these glands is a safe, cost-effective, and low morbidity option for patients with MEPA. We report a case series of patients with this disease managed with VATS, the first in Mexico and Latinamerica. METHODS: From 2008 to 2022, a retrospective study involving patients with MEPA and treated by VATS approach was performed in a tertiary hospital in Mexico city. Relevant biochemical and clinical variables such as imaging studies, pre and postoperative laboratory results, surgical strategy, outcomes and pathological analysis were analyzed. RESULTS: Four cases of mediastinal parathyroid adenomas causing HPT were included. All patients were female with a median age of 52.5 years-old (range 46-59 years), half of the patients had primary HPT and the others tertiary HPT after kidney transplant. 75% of cases had a MEPA in the medium mediastinum, all had a preoperative positive SPECT-CT 99mTc Sestamibi scan. Mean preoperative PTH was 621.3pg/mL (182-1382pg/mL). All patients successfully underwent parathyroidectomy with a VATS approach, no deaths were reported. CONCLUSIONS: VATS is a minimally invasive surgery that provides adequate access to mediastinal located glands, optimal visualization of mediastinal structures and has a high resection success rate with less complications and morbidity than open approaches.

Use of [18F]fluorocholine PET/CT in the detection of primary hyperparathyroidism in paediatrics: a case report.

OBJECTIVES: The most common cause of primary hyperparathyroidism (PPH) in children is a parathyroid adenoma. Among this population, PPH exhibits higher levels of morbidity, severity and target organ involvement compared to adults. When there is suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/CT are the imaging test traditionally indicated. Among adults, the use of [18F]fluorocholine PET/CT has shown a higher sensitivity than ultrasound and [99mTc]sestamibi SPECT/CT, leading to an expanding adoption in recent years. However, its role in paediatrics has not been clearly defined yet. CASE PRESENTATION: The patient is an adolescent female aged 13 years presented with lithiasis. The analytical study revealed elevated PTH, hipovitaminosis D, hypercalcaemia and hypophosphataemia. Due to the suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/C were performed, failing to identify hyperfunctioning parathyroid glands. We proceeded to carry out a [18F]fluorocholine PET/CT where a hypermetabolic nodular image was identified, compatible with a hyperfunctioning parathyroid adenoma. The patient underwent surgery, resulting in the normalisation of PTH levels. Pathological anatomy confirmed the presence of a parathyroid adenoma. CONCLUSIONS: In cases where conventional imaging tests yield negative results or discrepancies, we suggest the possibility of the use of [18F]fluorocholine PET/CT for the detection of hyperfunctioning parathyroid adenomas.

Characteristics, management and outcomes of primary hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.

BACKGROUND: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH. METHODS: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded. RESULTS: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008). CONCLUSIONS: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.

Persistent hypercalcaemia associated with two pathogenic variants in the CYP24A1 gene and a parathyroid adenoma-a case report and review.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild. Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases. Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively). Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis.

BACKGROUND: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. METHODS: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. FINDINGS: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. INTERPRETATION: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. FUNDING: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.

BACKGRUOUND: Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses. METHODS: We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis. RESULTS: The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations. CONCLUSION: Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

Transplantation and Noninvasive Longitudinal In Vivo Imaging of Parathyroid Cells: A Proof-of-Concept Study.

The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells ex vivo for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive in vivo imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With in vivo confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive in vivo investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease.

The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC. METHODS: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively. RESULTS: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC. CONCLUSION: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss.

Bilateral exploration in primary hyperparathyroidism: Double adenoma distribution and biochemical patterns over two decades.

BACKGROUND: We investigated if anatomic patterns of abnormal parathyroid glands have ch anged for primary hyperparathyroidism (pHPT) as atypical biochemical presentation (normohormonal and normocalcemic) has increased. METHODS: Retrospective review of patients with pHPT who underwent routine bilateral neck exploration. RESULTS: 2762 patients were included. The "late" cohort (2014-2020) exhibited lower preoperative calcium (10.8 vs 11.1 â€‹mg/dL; P â€‹= â€‹0.001) and PTH levels (101 vs. 146 â€‹pg/mL; P â€‹= â€‹0.001) compared to the "early" cohort (2000-2006). Patients with atypical biochemical profiles increased from 25.5% to 31.3% (P â€‹< â€‹0.001). The prevalence of single adenoma (SA) decreased (66.1% vs 58.9%, P â€‹= â€‹0.02) while the proportion of double adenoma (DA) increased (17.3% vs. 22.6%, P â€‹< â€‹0.01). Upper parathyroid adenoma(s) remained the most common finding for SA and DA in both time points. CONCLUSIONS: Despite changes in patient characteristics, single upper adenoma and bilateral double upper adenomas remain the most common findings for patients with pHPT.

Generation of induced pluripotent stem cell line (MIPTi002-A) derived from a patient with a heterozygous type mutation in the CDC73 gene.

CDC73-related disorders are inherited in an autosomal dominant manner. An individual with a CDC73-related disorder may have inherited the disorder from an affected parent or developed it as the result of a de novo pathogenic variant of CDC73. The iPSC line was obtained by reprogramming the PBMCs of a patient with a heterozygous type mutation of the CDC73 gene. This cell line could be useful to scrutinize and study the development of CDC73-associated parathyroid carcinoma.

Fine needle aspiration biopsy of parathyroid; is it meaningful? A cytologic study of 81 cases with histological and clinical correlations.

BACKGROUND: Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify cytomorphologic features suggestive of parathyroid origin and to assess the utility of cytopathology in conjunction with ancillary tests in the identification of parathyroid glands. MATERIALS AND METHODS: Ultrasound (US) guided FNA of parathyroid gland and lesions in 81 patients were reviewed concerning clinical history and correlated to histopathologic findings in available cases. FNA smears were evaluated for cellularity, architectural patterns, cellular and nuclear features, and background of the smears. In 78 cases, FNA was supplemented by a measurement of parathormone (PTH) levels in the needle washout fluid (FNA-PTH assay) and/or GATA3/PTH/chromogranin-A immunostainings. RESULTS: Sixty-four cases were diagnosed cytologically as parathyroid lesions in conjunction with FNA-PTH assay and/or immunocytochemical examinations. In an additional nine cases, a diagnosis of parathyroid lesions was rendered after repeated FNA with FNA-PTH assay. The histolopathologic diagnosis of surgically excised cases (n = 75) included parathyroid adenoma (60 cases), atypical parathyroid adenoma (4 cases), parathyroid hyperplasia (10 cases), and parathyroid carcinoma (1 case). Major cytological findings of parathyroid tissue included high cellularity, scattered naked nuclei, cribriform and three-dimensional clusters, stippled chromatin, and oxyphilic cytoplasm while papillary pattern or colloid-like material was identified in three cases respectively. No nuclear grooves or inclusions were seen in any case. CONCLUSIONS: High cellularity scattered naked nuclei, cribriform and three-dimensional patterns, stippled chromatin and oxyphilic cytoplasm are cytomorphologic features that favour parathyroid origin. A combination of these features with FNA-PTH assay and/or GATA3, PTH, and chromogranin-A immunostainings on cytologic specimens aid in the identification of parathyroid glands and the distinguishing of parathyroid from thyroid lesions.

Syndromic MEN1 parathyroid adenomas consist of both subclonal nodules and clonally independent tumors.

Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.

Is there a role for liquid biopsy in the surveillance of parathyroid carcinoma?

BACKGROUND: Parathyroid carcinoma is a rare malignancy with high recurrence rates. Liquid biopsy is a stratifying tool in disease recurrence/progression in other malignant processes. This study sought to assess the feasibility and application of liquid biopsy in parathyroid carcinoma and its impact on surveillance. METHODS: Retrospective review of a prospectively maintained database of adults treated for parathyroid carcinoma at a tertiary care center (2017-2023). Demographics, clinical characteristics, and laboratory variables were collected. Circulating cell-free deoxyribonucleic acid enrichment and circulating tumor cell enumeration were obtained from serial blood samples. RESULTS: A total of 25 patients were identified-64% were male patients, with a median age of 56 years (interquartile range 45-63). Fifty blood samples were collected postoperatively. At first, circulating tumor cell enumeration, 56% (14/25) of patients had no evidence of disease, and 32% (8/25) had distant metastasis. Median follow-up was 53 months (interquartile range 23-107). At the last follow-up, 40% (10/25) of patients were found to have distant metastasis. Serial circulating tumor cell enumeration was performed in 52% of patients, median highest circulating tumor cell was (interquartile range 1-22). Circulating cell-free deoxyribonucleic acid was assessed in 64% of patients (16/25). There was no difference in circulating tumor cells or circulating cell-free deoxyribonucleic acid between those with distant metastasis and those without distant metastasis. The most common mutation identified was TP53, present in 88% of circulating cell-free deoxyribonucleic acid samples with a mutation. Circulating cell-free deoxyribonucleic acid and parathyroid hormone levels were not found to have any association (r = -0.27, P = .39), but parathyroid hormone and circulating tumor cell had a linear relationship (r = 0.76, P < .001). CONCLUSION: Liquid biopsy appears to be a feasible tool in parathyroid carcinoma surveillance. The relationship between circulating cell-free deoxyribonucleic acid and parathyroid hormone levels remains unclear, and the association between circulating tumor cell enumeration and parathyroid hormone levels may be impactful. The finding that TP53 mutation is more prevalent in patients with distant metastasis may impact further management.

Incidental Detection of Parathyroid Adenoma on 18F-PSMA PET/CT.

ABSTRACT: A 70-year-old man, diagnosed with prostate cancer, was referred to the Department of Nuclear Medicine for tumor staging with prostate-specific membrane antigen (PSMA) PET/CT. High PSMA uptake was observed in the prostate without PSMA-avid lymph nodes or distant metastases. Coincidentally, a PSMA-avid nodule was observed dorsal to the right thyroid lobe. A complementary 4-dimensional CT showed a round nodule of 18 mm with quick contrast enhancement well demarcated from its surroundings. Blood tests revealed elevated serum calcium and parathyroid hormone consistent with primary hyperparathyroidism. Subsequently, parathyroidectomy was performed, and histopathological examination of the nodule confirmed a parathyroid adenoma.