Parathyroid Adenoma Research Articles

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

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. 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. 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. 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.

Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0–3.5 g are called “large” or “giant” adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm<sup>3</sup> (control group). In both groups, the majority were women (81.5% – study group, 90.5% – control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3–0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>

Preoperative Lateralization and Diagnostic Value of Selective Bilateral Internal Jugular Venous Sampling in Primary Hyperparathyroidism: Single-Center Experience.

Background and Objectives: Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by excessive production of parathyroid hormone (PTH) leading to elevated calcium levels. Diagnosis is primarily based on biochemical evaluation, and surgery is the curative treatment. Imaging techniques like ultrasound and Tc-99m Sestamibi scintigraphy are used for localization, but selective Internal Jugular Venous (SVS) becomes valuable in cases of inconclusive or conflicting results. This study evaluated the diagnostic efficacy of SVS for localizing parathyroid adenomas in cases where non-invasive radiological diagnostic methods yielded inconclusive results or negative findings despite clinical symptoms suggestive of pHPT. Materials and Methods: In this retrospective study, a total of 28 patients diagnosed with pHPT underwent SVS at a tertiary center known for receiving referrals from 2017 to 2022. The diagnoses were confirmed through biochemical analysis. The SVS results in 22 patients were compared with non-invasive imaging methods, including ultrasound, scintigraphy, and computed tomography with/without contrast material. SVS was indicated when at least two non-invasive diagnostic procedures failed to clearly localize the parathyroid glands or provided ambiguous results. Results: SVS demonstrated higher sensitivity for localizing parathyroid adenomas compared to non-invasive imaging methods, accurately lateralizing the adenoma in 68.18% of cases. Among the SVS findings, 31.8% of patients had negative results, with 9.1% not having clinically proven parathyroid adenoma, while 22.7% had false negative SVS findings but were later confirmed to have adenoma during surgery. Ultrasound correctly identified the location in 45.45% of cases, CT in 27.27%, and scintigraphy in 40.9%. Conclusions: SVS is a valuable diagnostic tool for accurately localizing parathyroid adenomas in patients with inconclusive non-invasive imaging results. It aids in targeted surgical interventions, contributing to improved management and treatment outcomes in primary hyperparathyroidism.

Biochemical characteristics and clinical manifestation of normocalcemic primary hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (nPHPT) is a condition characterized by persistently high levels of parathyroid hormone (PTH) and normal serum calcium levels in the absence of other causes for secondary hyperparathyroidism. The aim of the present study was to assess the clinical presentation and the biochemical characteristics in patients with nPHPT and to compare them with those in patients with hypercalcemic PHPT (hPHPT). The study included 316 patients (277 women and 39 men, average age 58.7 ± 12.1) diagnosed with PHPT. Total serum calcium, inorganic phosphates (PO4), PTH, urinary Ca (uCa), albumin, creatinine, 25(OH)D and bone markers (b-CTX and ALP) were examined in all of them. BMD of the lumbar spine (LS), distal third of the radius (DR), femoral neck (FN) and total proximal femur (TF) were measured by a dual-energy X-ray absorptiometry (DXA). The patients were divided into two groups according to albumin-corrected calcium (Ca) level - with hPHPT (Ca>2.62 mmol/L) and with nPHPT (Ca 2.12-2.62 mmol/l), without other causes for secondary hyperparathyroidism. The frequency of nPHPT was 15.2%. Normocalcemic patients had lower levels of PTH, higher PO4 and 25(OH)D, and smaller parathyroid adenomas. No significant difference in the frequency of osteoporosis, low-energy fractures, nephrolithiasis and gastrointestinal disorders was found between nPHPT and hPHPT. There was no difference in BMD between the two groups. The patients with nPHPT show a more favorable biochemical profile compared to those with hPHPT. Nevertheless, clinical manifestations and complications are similar, without a significant difference in the frequency of osteoporosis, nephrolithiasis, gastrointestinal disorders and low-energy fractures.

A case of mediastinal ectopic parathyroid adenoma completely resected after identification using a radioisotope technique combined with intraoperative intact-PTH monitoring

A case of mediastinal ectopic parathyroid adenoma completely resected after identification using a radioisotope technique combined with intraoperative intact-PTH monitoring

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

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. In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10×Genomics platform. 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. 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. 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).

Explainable Classification of Patients with Primary Hyperparathyroidism Using Highly Imbalanced Clinical Data Derived from Imaging and Biochemical Procedures

Primary hyperthyroidism (PHPT) is a common endocrine disorder characterized by hypercalcemia and elevated parathyroid hormone (PTH) levels. The most common cause is a single parathyroid adenoma, though the rest of the cases are due to multiglandular disease [double adenoma/hyperplasia]. The main focus driving this work is to develop a computer-aided classification model relying on clinical data to classify PHPT instances and, at the same time, offer explainability for the classification process. A highly imbalanced dataset was created using biometric and clinical data from 134 patients (six total features, 20.2% multiglandular instances). The features used by the current study are age, sex, max diameter index, number of deficiencies, Wisconsin index, and the reference variable indicating the type of PHPT. State-of-the-art machine learning (ML) classification algorithms were used in order to create trained prediction models and give predicted classifications based on all features/indexes. Of the ML models considered (Support Vector Machines, CatBoost, LightGBM, and AdaBoost), LightGBM was able to procure the best performing prediction model. Given the highly imbalanced nature of the particular dataset, oversampling was opted for, so as to increase prediction robustness for both classes. The ML model’s performance was then evaluated using common metrics and stratified ten-fold validation. The significance of this work is rooted in two axes: firstly, in the incorporation of oversampling to smooth out the highly imbalanced dataset and offer good prediction accuracy for both classes, and secondly, in offering an explainability aspect to an otherwise black-box ML prediction model. The maximum achievable accuracy for adenoma is 86.9% and for multigland disease 81.5%. Summarizing the above, this study demonstrates the potential for an ML approach to improve the diagnosis of PHPT and also highlights the importance of explainable artificial intelligence (AI).

Diagnostic Performance of 18F-fluorocholine PET/CT Compared to 99mTc-Sestamibi Scintigraphy in Diagnosis of Parathyroid Adenoma

Background: In most hyperparathyroidism cases, the disease is related to parathyroid adenoma (PTA). Owing to the inconsistencies of currently approved imaging methods, novel methods for detecting PTA are being evaluated. This study aimed to compare 18F-fluorocholine PET/CT with 99mTc-sestamibi SPECT/CT in identifying PTA in Saudi patients.Methods and Results: The study included 40 adult patients with PTA diagnosed by histopathological findings. 99mTc-sestamibi SPECT/CT and 18F-fluorocholine PET/CT examinations were performed for each patient, and parathyroid hormone (PTH) levels and histologic findings were recorded. The diagnostic ability of 18F-fluorocholine PET/CT (AUC=0.720; P=0.029) was superior to 99mTc-sestamibi SPECT/CT (AUC=0.623; P=0.214) in identifying PTA. The sensitivity and accuracy of 18F-fluorocholine PET/CT (81.5% and 75%, respectively) were significantly (P<0.05) higher than that of 99mTc-sestamibi SPECT/CT (63% and 62.5%, respectively). 18F-fluorocholine PET/CT findings were correlated significantly (P=0.023) with PTH results. Conclusion: 18F-fluorocholine PET/CT is a diagnostic imaging method superior to conventional modality 99mTc-sestamibi SPECT/CT in the detection of PTA and, thus, allows for accurate preoperative localization.

Primary Hyperparathyroidism due to Parathyroid Adenoma in Children and Adolescents

ObjectiveIn contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder. MethodsA retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications. ResultsTen children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results. ConclusionsPHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up.

Parathyroid Adenoma with Multiple Bone Fractures: A Case Report

Background: Parathyroid adenoma is a benign neoplasm of the parathyroid glands and can result in hypercalcemia due to excessive secretion of parathyroid hormone (PTH). This elevated PTH can have various manifestations, including bone fractures.
 Case presentation: We report the case of Tn. AB is a 41-year-old man with a series of recurrent bone fractures following minor traumas. Within a span of three years, he suffered from fractures in the right femur, left femur, and left humerus, which led to multiple surgeries, including total hip replacements. Further assessments showed an increased level of PTH and a suspicious lesion in the neck region. A CT scan revealed a potential parathyroid adenoma in the peritracheal region of the right side. Moreover, a Sestamibi scan confirmed an adenoma in the postero-inferior lobe of the right thyroid, consistent with Perrier type C, alongside osteoblastic processes and brown tumours. A subsequent parathyroidectomy confirmed a 2 cm diameter adenoma in the right lower parathyroid lobe. Histopathology from the excised tissue confirmed the diagnosis of parathyroid adenoma.
 Conclusion: Parathyroid adenomas can have significant clinical manifestations, including recurrent bone fractures, due to their metabolic effects on bone integrity. Early detection and surgical intervention can prevent complications and improve the quality of life for these patients.

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours.

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

Our experience with robotic-assisted thymic surgery.

Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior mediastinum. The previously standard approach to the thymus via partial sternotomy was gradually replaced by the videothoracoscopic approach in most cases. In recent years, robotically assisted surgery has been gaining ground worldwide in this area, as well. The aim of our paper is to provide a comprehensive overview of procedures in the field of the thymus, including their indications, and to share our first experience with robot-assisted thymus surgery. At the 3rd Department of Surgery, since the start of the robot-assisted thymus surgery program, 23 thymectomies have been performed using this approach, of which 17 were performed for thymoma, 3 for myasthenia gravis, and 3 for parathyroid adenoma localized in thymus tissue. From our experience and the available data, it follows that the length of hospitalization, the rate of complications and the resulting effect of robot-assisted procedures is comparable to VTS procedures; however, the robot-assisted surgery also allows for mini-invasive treatment even in significantly obese patients and in patients with advanced thymic tumors who would otherwise be indicated for open thymectomy.

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

PurposeParathyroid 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.MethodsIn 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.ResultsA 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.ConclusionAn 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.

Four-Dimensional Computed Tomography for Parathyroid Adenoma Localization: A Pre-Operative Imaging Protocol.

Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging. Retrospective Study. University Hospital. All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings. There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%. A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery.

192 - A case of parathyroid adenoma in a pediatric patient

192 - A case of parathyroid adenoma in a pediatric patient

Simultaneous Papillary Thyroid Carcinoma and Primary Hyperparathyroidism: Unusual Presentation

The coexistence of Primary Hyperparathyroidism (PHPT) with Papillary Thyroid Carcinoma (PTC) is a rare clinical occurrence. Thyroid pathology is reported in 20% to 84% of Primary Hyperparathyroidism (PHPT) cases, with malignancies identified in 2% to 20% of instances. We report a case of a 49-year-old woman referred for evaluation of left iliac wing and hip pain with elevated parathyroid hormone levels. Imaging revealed a toxic multinodular goiter with a parathyroid adenoma. The patient underwent total thyroidectomy with parathyroid adenoma excision. Subsequent histological examination unexpectedly identified a papillary thyroid microcarcinoma associated with the parathyroid adenoma. The association between PHPT and PTC is complex, influenced by shared embryological origins and genetic factors. Elevated PTH levels in PHPT may contribute to thyroid cell proliferation, and hypercalcemia is suggested to promote thyroid carcinogenesis. Molecular analyses suggest the involvement of pathways like MAPK and Wnt/β-catenin. The coexistence of PHPT and PTC highlights the necessity for thorough preoperative assessment and the ongoing need for research. While minimally invasive parathyroid surgery is favored, the risks associated with coexisting thyroid pathology should be carefully considered. Routine thyroid ultrasonography in PHPT patients is crucial to exclude nodular thyroid disease, emphasizing the role of research in guiding clinical practices. A balanced approach integrating technical advancements and thoughtful risk assessment is essential in navigating this complex clinical scenario.

Use of preoperative ultrasonography adenoma size measurements for accurate localization estimation in parathyroid adenomas

Background: It is known that Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia. It is characterized by high serum calcium and parathyroid hormone (PTH) levels. Also, hyperactivity is seen in one or more of the parathyroid glands and preoperative ultrasonography (USG) usually localizes the location of parathyroid adenomas. In this study, the factors that affect the success of parathyroid surgery have been investigated. Methods: In total, the medical records of 245 patients with pHPT who underwent parathyroidectomy have been reviewed, retrospectively. In order to confirm the location of hyperactive parathyroid gland and the factors that affect the success of laboratory methods have been examined by using imaging techniques. Results: As a result, false localization is found in 7.8% (19) of the patients. The weight calculated by using the preoperative USG measurements has been approximately similar to the macroscopic weight (p = 0.651). When the preoperative USG results in patients with false localization have been analyzed, it is seen that the lesion diameter was significantly less than 12 mm and the calculated weight was significantly less than 39 g (p = 0.005 and p < 0.001). Conclusion: It has been concluded that a second-line imaging should be used to obtain an accurate localization in patients with a small lesion suspected of being a parathyroid adenoma on preoperative USG. In addition, an intraoperative PTH (IOPTH) should be used to increase the success rate of the surgery in patients who cannot undergo a second-line imaging.

A case report: acute necrotizing pancreatitis secondary to hypercalcemia in case of parathyroid adenoma

The incidence of primary hyperparathyroidism (PHPT) in India is 2.5/1000 individuals. The major cause for PHPT is parathyroid adenoma. To arrive at the correct diagnosis, clinical setting, biochemical and radiological investigations, the status of other glands assessed lntraoperatively and finally histopathological confirmation is essential. The association between acute pancreatitis and PHPT has widely been reported in literature, but a causal relationship remains controversial. This case report is about a patient admitted with acute pancreatitis as a first manifestation of a parathyroid adenoma. The purpose of this paper is to keep in mind the metabolic etiology, by evaluating calcium and parathyroid hormone (PTH) in the differential diagnosis of non-Biliary, non-alcoholic acute pancreatitis.

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.

Giant parathyroid adenoma masquerading as a goiter.

Giant parathyroid adenoma masquerading as a goiter.