Search Results (68)

Thyroid cancer survivors often experience worse quality of life than other cancer survivors, with fatigue and sleep disturbance being common contributors. In this prospective cohort from the ICaRe2 cancer registry, survivors completed the Brief Fatigue Inventory (BFI) and Pittsburgh Sleep Quality Index (PSQI) at enrollment and follow-up, with univariate and multivariable analyses identifying factors associated with fatigue and sleep quality. Among 249 survivors (83% female, median age 42), 205 completed the BFI and 224 the PSQI. Most were low (57%) or intermediate (34%) risk or recurrence at diagnosis, and 74% had no structural recurrence. Poor sleep and greater fatigue were significantly associated with female sex (p = 0.0003 and 0.001), younger age at diagnosis (p = 0.02 and 0.0006), and vocal cord paralysis (p = 0.01 and 0.046). Fatigue was also higher in those with hypoparathyroidism (p = 0.04). No associations were found with recurrence risk, therapy response, thyroid hormone type, or TSH levels. Younger female survivors, particularly those with vocal cord paralysis or hypoparathyroidism, are more prone to fatigue and poor sleep, highlighting potential targets for interventions to improve quality of life. Full article

Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy, accounting for less than 1% of all primary hyperparathyroidism (pHPT) cases. It typically presents with pronounced hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. Accurate imaging plays a pivotal role in diagnosis, staging, surgical planning, and long-term surveillance, although differentiating PC from benign disease on imaging remains a significant challenge. A multimodal imaging strategy combining cervical ultrasonography (US) and nuclear medicine techniques provides high sensitivity for lesion detection. Ultrasonography with advanced detective flow imaging allows detailed anatomical assessment and evaluation of vascular patterns of the primary tumor. [^99mTc]Tc-methoxyisobutylisonitrile ([^99mTc]Tc-MIBI) scintigraphy frequently demonstrates prolonged tracer retention in PC, while [¹⁸F]fluorocholine positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging have shown superior performance for detecting both primary tumors and metastatic disease due to its higher spatial resolution and higher molecular sensitivity. [¹⁸F]FDG PET serves as an adjunct modality for identifying aggressive, metabolically active lesions. Emerging radiotracers such as [¹⁸F]-fibroblast activation protein inhibitor ([¹⁸F]FAPI) and [⁶⁸Ga]Ga-trivehexin have shown potential in cases where initial imaging is inconclusive. Theranostic strategies that integrate molecular imaging with targeted radioligand therapy may transform PC management by enabling personalized treatment approaches tailored to each tumor’s biological and imaging characteristics. This review aims to evaluate available imaging modalities for PC diagnosis and provide guidance for their clinical application. Full article

Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article

Synchronous multiple parathyroid carcinoma is a rare condition within the already uncommon landscape of parathyroid malignancies, which comprise less than 1% of sporadic primary hyperparathyroidism cases. To date, only seven cases of synchronous multiple parathyroid carcinoma in sporadic primary hyperparathyroidism have been documented. This exceptional rarity complicates both the diagnostic process and therapeutic decision-making. Clinically, parathyroid carcinoma typically presents as a single mass determining severe symptoms. However, no single clinical, biochemical, or imaging feature allows for definitive preoperative diagnosis. Imaging modalities such as ultrasound and sestamibi scans exhibit variable sensitivity and may overlook multi-gland involvement. Histopathological examination remains the only reliable diagnostic method. Management strategies are also controversial: while some advocate for conservative surgery, en bloc resection is generally recommended for its association with improved local control and disease-free survival. Given the exceptional occurrence of synchronous multiple parathyroid carcinoma, there is a lack of standardized protocols for managing parathyroid carcinoma in cases of synchronous and multiple gland involvement. Early multidisciplinary evaluation and individualized treatment planning are therefore crucial. This review aims to synthesize the presently available knowledge about synchronous multiple parathyroid carcinoma, assist clinicians with the limited data available, and discuss the main challenges in the management of this rare entity. Full article

Primary hyperparathyroidism is commonly caused by parathyroid adenomas, hyperplasia, or, rarely, carcinoma. In up to 20% of cases, parathyroid tissue may be ectopic, often located in the mediastinum due to aberrant embryologic migration. Ectopic parathyroid glands pose a diagnostic and therapeutic challenge, and an accurate preoperative localization is essential for an effective and safe resection. Imaging modalities such as CT scan, TC-sestamibi scintigraphy, PET/CT, ultrasonography and MRI are routinely employed, whereas combined techniques offer improved diagnostic accuracy. Emerging approaches, however, including PET/CT with choline tracers, have shown promise in enhancing sensitivity in complex or recurrent cases. When ectopic glands are in the mediastinum, thoracic surgical intervention is required. Traditional open approaches, such as sternotomy or thoracotomy, are associated with significant morbidity. The development and evolution of minimally invasive surgery (MIS) has become the preferred approach in selected cases. When MIS is performed, intraoperative assessment and parathyroid identification are crucial to ensure complete gland removal. Intraoperative parathyroid hormone (ioPTH) monitoring provides real-time confirmation of surgical success. The integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques significantly improves surgical outcomes while minimizing complications and accelerating patient recovery. Ultimately, the effective treatment of ectopic parathyroid glands relies on a personalized approach, adapting both diagnostic and surgical strategies to the unique anatomical and clinical context of each patient. Integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques, combined with a multidisciplinary team involving endocrinologists, radiologists, and thoracic surgeons, is key to optimizing outcomes and reducing patient morbidity. Full article

Background: Parathyroid neoplasia is a heterogeneous group of tumors, including parathyroid adenoma (PA), atypical parathyroid tumors (aPTs), and parathyroid carcinoma (PC). Differential diagnosis, especially preoperatively, between parathyroid carcinoma and the other two entities is challenging. The purposes of this study were to highlight the main differences between different parathyroid tumors and to evaluate how combined PC suspicion and intraoperative adjuncts can influence surgical decision-making and outcome-related issues. Methods: We performed a retrospective study of a database of patients diagnosed with parathyroid tumors who underwent surgical treatment at our endocrine surgery referral center between June 2019 and July 2024. Demographic, clinical, biochemical, imaging, intraoperative, immunohistochemical, and follow-up data were analyzed. Results: A total of 83 cases were included in our study, divided for analysis into PA (n = 67), aPT (n = 9) and PC (n = 7) subgroups. The clinical profile of the cohort showed a significant difference (p < 0.05) between the PA, aPT, and PC subgroups regarding the presence of palpable tumors (0% vs. 11.11% vs. 14.29%), both bone and kidney involvement (14.93% vs. 44.44% vs. 85.71%), and extensive disease beyond bone and kidney involvement (4.48% vs. 44.44% vs. 71.43%). PTH levels over five times the normal value were present at significantly different rates (p < 0.001), with higher rates in the aPT and PC subgroups (55.56% and 85.71%, respectively) compared with the PA subgroup (7.46%). Also, a significant difference (p < 0.001) was observed when analyzing extreme albumin-corrected serum calcium elevations over 14 mg/dL, with much higher rates in the PC subgroup (71.43%) compared to PA (1.49%) and aPT (33.33%). On preoperative ultrasonography, a significantly higher number of PCs presented diameters ≥ 3 cm (p < 0.001), depth-to-width ratios (D/W) ≥ 1 (p = 0.003), suspicious delineation (p < 0.001), and suspicious echotexture features (p < 0.001), compared to PAs. On preoperative US performed by the surgeon, suspicious features for thyroid cancer were identified in five more patients compared to the four identified by the initial US evaluation, and all (10.84% of all patients) were confirmed on final histopathology as papillary thyroid cancers. Intraoperatively, a significant difference (p < 0.001) regarding parathyroid macroscopic suspicious features, including adhesions to the thyroid gland, was seen between subgroups. When analyzing only cases with en bloc resection, we found that, in all PC cases, a combined preoperative suspicion was present, and in five cases an intraoperative suspicion was raised. Immunohistochemical data showed significantly different median Ki-67 indices between subgroups (1, 2, and 5; p = 0.008) and a different parafibromin staining profile between PC and aPT. Regarding intraoperative neuromonitoring use, a significantly lower incidence of voice changes related to the external branch of the superior laryngeal nerve was observed in the monitoring vs. non-monitoring group (57.14% vs. 12.5%, p = 0.019). Conclusions: Our findings confirm that, in a multimodal and combined diagnostic approach, early pre- and intraoperative PC suspicion can be raised in order to optimize surgical treatment and, thus, favorably influence the outcome. Utilizing all resources available, including intraoperative parathormone determination, laryngeal nerve neuromonitoring, and immunohistochemistry staining, can bring extra benefit to the management of these challenging cases. Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article

Background: Oral squamous cell carcinoma (OSCC) frequently invades the jawbone, leading to diagnostic and therapeutic challenges. While tumor–bone interactions have been studied, the specific roles of dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) in OSCC-associated bone resorption remain unclear. This study aimed to compare the effects of DFCs and PDLCs on OSCC-induced bone invasion and elucidate the underlying mechanisms. Methods: Primary human DFCs and PDLCs were isolated from extracted third molars and characterized by Giemsa and immunofluorescence staining. An in vitro co-culture system and an in vivo xenograft mouse model were established using the HSC-2 OSCC cell line. Tumor invasion and osteoclast activation were assessed by hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining. Immunohistochemical analysis was performed to evaluate the expression of receptor activator of NF-κB ligand (RANKL) and parathyroid hormone-related peptide (PTHrP). Results: DFCs significantly enhanced OSCC-induced bone resorption by promoting osteoclastogenesis and upregulating RANKL and PTHrP expression. In contrast, PDLCs suppressed RANKL expression and partially modulated PTHrP levels, thereby reducing osteoclast activity. Conclusions: DFCs and PDLCs exert opposite regulatory effects on OSCC-associated bone destruction. These findings underscore the importance of stromal heterogeneity and highlight the therapeutic potential of targeting specific stromal–tumor interactions to mitigate bone-invasive OSCC. Full article

Background and Objectives: Thyroid cancer (TC) is a common malignancy that accounts for approximately 1% of all human cancers. Given their anatomical proximity to the thyroid, the parathyroid glands (PTGs) are theoretically at risk of tumor involvement. However, PTG metastases are rare and may be underdiagnosed because of routine PTG preservation during thyroidectomy. This study aimed to identify cases of PTG invasion by TC through a 10-year retrospective review at Chosun University Hospital, along with an analysis of the existing literature. Materials and Methods: A total of 1032 thyroidectomy cases were reviewed, and PTG involvement was detected in 10 cases (0.97%). Clinicopathological characteristics were evaluated, and literature data were analyzed. Results: The affected patients included nine females and one male, with a mean age of 46 years (range: 25–77 years). Histological examination confirmed papillary thyroid carcinoma (PTC) in all cases. Tumor invasion into the perithyroid soft tissues was observed in nine patients, and central cervical lymph node metastases were present in four. All patients exhibited PTG Pattern A (direct invasion). Conclusions: Based on our findings and literature data, PTG involvement by TC has an incidence rate of 0.05–3.9%, predominantly affects women in their sixth to seventh decade of life, and appears to have no impact on prognosis unless accompanied by extensive extrathyroidal invasion. Further studies are necessary to determine whether PTG invasion should be integrated into the TNM staging system and to assess its prognostic and therapeutic implications. Full article

Background: Multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism (MPHPT) belongs to genetic PHPT that accounts for 10% of all PHPT cases, being considered the most frequent hereditary PHPT (less than 5% of all PHPT). Objective: We aimed to provide an updated clinical perspective with a double purpose: to highlight the clinical features in MPHPT, particularly, the bone health assessment, as well as the parathyroidectomy (PTx) impact. Methods: A comprehensive review of the latest 5-year, English-published, PubMed-accessed original studies. Results: The sample-based analysis (n = 17 studies) enrolled 2426 subjects (1720 with MPHPT). The study design was retrospective, except for one prospective and one case–control study. The maximum number of patients per study was of 517. Female predominance (an overall female-to-male ratio of 1.139) was confirmed (except for three studies). Age at MPHPT diagnosis (mean/median per study): 28.7 to 43.1 years; age at PTx: 32 to 43.5 years. Asymptomatic PHPT was reported in 38.3% to 67% of MPHPT. Mean total calcium varied between 1.31 and 2.88 mmol/L and highest PTH was of 317.2 pg/mL. Two studies reported similar PTH and calcaemic levels in MPHPT vs. sporadic PHPT, while another found higher values in MPHPT. Symptomatic vs. asymptomatic patients with MPHPT had similar PTH and serum calcium levels (n = 1). Osteoporosis (n = 8, N = 723 with MPHPT) was reported in 10% to 55.5% of cases, osteopenia in 5.88% to 43.9% (per study); overall fracture rate was 10% (of note, one study showed 0%). Lower bone mineral density (BMD) at DXA (n = 4) in MPHPT vs. sporadic PHPT/controls was found by some studies (n = 3, and only a single study provided third distal radius DXA-BMD assessment), but not all (n = 1). Post-PTx DXA (n = 3, N = 190 with MPHPT) showed a BMD increase (e.g., +8.5% for lumbar spine, +2.1% for total hip, +4.3% for femoral neck BMD); however, post-operatory, BMD remains lower than controls. Trabecular bone score (TBS) analysis (n = 2, N = 142 with MPHPT vs. 397 with sporadic PHPT) showed a higher prevalence of reduced TBS (n = 1) or similar (n = 1). PTx analysis in MPHPT (n = 14): rate of subtotal PTx of 39% to 66.7% (per study) or less than subtotal PTx of 46.9% (n = 1). Post-PTx complications: persistent PHPT (5.6% to 25%), recurrent PHPT (16.87% to 30%, with the highest re-operation rate of 71% in one cohort); hypoparathyroidism (12.4% to 41.7%). Genetic analysis pointed out a higher risk of post-PTx recurrence in exon 10 MEN1 pathogenic variant. Post-PTx histological exam showed a multi-glandular disease in 40% to 52.1% of MPHPT, and a parathyroid carcinoma prevalence of 1%. Conclusions: MPHPT remains a challenging ailment amid a multi-layered genetic syndrome. Current data showed a lower age at MPHPT diagnosis and surgery than found in general population, and a rate of female predominance that is lower than seen in sporadic PHPT cases, but higher than known, for instance, in MEN2. The bone involvement showed heterogeneous results, more consistent for a lower BMD, but not necessarily for a lower TBS vs. controls. PTx involves a rather high rate of recurrence, persistence and redo surgery. About one out of ten patients with MPHPT might have a prevalent fracture and PTx improves the overall bone health, but seems not to restore it to the general population level, despite the young age of the subjects. This suggests that non-parathyroid components and potentially menin protein displays negative bone effects in MEN1. Full article

Background: Primary hyperparathyroidism (PHPT) represents a multi-faced disease with a wide spectrum of manifestations. Familial forms of PHPT (affecting up to 10% of the cases) involve a particular category that encompasses a large range of hereditary syndromes, including parathyroid hyper-function, frequently in the setting of a multi-glandular disease. Objective: The aim was to analyze the most recent findings regarding PHPT in multiple endocrine neoplasia type 2 (MEN2) to a better understanding of the timing with respect to the associated ailments, MEN2-related PHPT (MEN2-PHPT) clinical and genetic particularities, optimum diagnostic, and overall management, particularly, surgical outcomes. Methods: This was a PubMed-based compressive review with regard to the latest data published in English from January 2020 until January 2025, using the following keywords: “primary hyperparathyroidism” and “multiple endocrine neoplasia”, “multiple endocrine neoplasia type 2”, “MEN2”, or “MEN2A”. We included original full-length studies of any study design that provided clinically relevant data in MEN2-PHPT and excluded reviews, meta-analysis, and case reports/series. Results: A total of 3783 individuals confirmed with MEN2 or RET pathogenic variants carriers were analyzed across 14 studies that provided data on PHPT. The prevalence of MEN2-PHPT subjects varied between 7.84% and 31.3%, with particularly low rates in non-index patients (3.8%). PHPT was the first syndrome manifestation in 0.9% of MEN2 patients. In terms of gender distribution, females represented 42.85% or 54.9% (similar rates between women and men, and only a single cohort showed a female rate up to 80%). Most subjects were diagnosed with PHPT and underwent surgery in the third or fourth decade of life. The highest median age at MEN2 diagnosis was 42 years. The youngest patients were RET pathogenic variants carriers who underwent (genetic) screening with median ages of 12 or 14 years. RET pathogenic variants analysis (n = 10/14 studies) showed that 16.67% of patients with p.Cys634Arg and 37.5% of those with p.Cys611Tyr had symptomatic PHPT, while those with p.Cys618Phe and p.Leu790Phe were asymptomatic. Timing analysis with respect to the medullary thyroid carcinoma diagnosis showed synchronous PHPT diagnosis in 80% and metachronous in 10% of MEN2 patients; with respect to MEN2-pheochromocytoma, synchronous diagnosis of PHPT was found in 56%, while pheochromocytoma was identified before PHPT in 22% of the cases and after PHPT in 22%. Studies (n = 10/14, N = 156 subjects with MEN2-PHPT) on parathyroidectomy identified that 72.7% to 100% of the individuals underwent surgery, typically performed in adulthood, at ages spanning from a mean of 34.7 to 48.5 years. The post-surgery outcomes varied (e.g., the rate for persistent PHPT was of 0%, 8% to 16.7%; recurrent PHPT of 12.5% to 23%; permanent hypoparathyroidism of 33% to 46%; permanent unilateral vocal cord palsy of 0% up to16.7%). Data regarding the number of involved glands (n = 7, N = 77): the prevalence of multi-glandular disease was pinpointed between 12.5% and 50%. Conclusions: MEN2-PHPT involved unexpected high rates of single-gland involvement (from 33.3% to 87.5%), probably due to an early detection across genetic screening. Traditional female higher prevalence in PHPT was not confirmed in most MEN2 cohorts. As expected, a younger age at PHPT diagnosis and surgery than seen in non-MEN2 patients was identified, being tidily connected with the syndromic constellation of tumors/malignancies. Overall, approximately, one out of ten patients were further confirmed with MEN2 starting with PHPT as the first clinically manifested element. Full article

Background: Parathyroid cancers are rare endocrine malignancies that pose diagnostic and therapeutic challenges, particularly when discovered incidentally or in the presence of multiple endocrine disorders. This study aims to provide clinical, biochemical and pathological insights into these malignancies through a retrospective case series. Methods: We analyzed retrospectively, from a tertiary and an endocrine surgery referral center, 13 cases of parathyroid cancers, where 4 cases were associated with thyroid cancers, including demographic data, clinical presentation, biochemical markers, imaging, surgical interventions, histopathological findings and follow-up outcomes. Descriptive statistics were used to summarize patient characteristics. Results: The median age of the cohort was 64 (range: 40–81 years), with a female-to-male ratio of 8:5. More than half of the cases (61.53%) were diagnosed incidentally, with common biochemical findings including elevated parathyroid hormone (PTH) levels (median: 430 pg/mL) and hypercalcemia in 80% of the patients. All patients underwent surgery, with parathyroid resections with concomitant total thyroidectomy (62%) or lobectomy (23%) as the most common interventions. Histopathological analysis confirmed parathyroid carcinoma in all cases, with coexisting thyroid malignancies observed in 31%. An immunohistochemical profile performed in about half of the patients was in accordance with previously published data. Postoperative normalization of PTH levels was achieved in 77% of patients, and no recurrence or metastasis was observed in 85% of cases during follow-up. Conclusions: Despite the exceptional rarity of the disease, this case series highlights the importance of preoperative biochemical and imaging evaluation and the efficacy of surgical management. Long-term outcomes remain favorable with early diagnosis and diligent postoperative monitoring. Further research into molecular biomarkers and targeted therapies is warranted to improve the management of advanced or recurrent disease. Full article

Parathyroid cancer (PC) presents clinically as a case of hyperparathyroidism associated with local compression symptoms. The definitive diagnosis of PC is complex as it requires unequivocal criteria of invasion in postoperative biopsy. Given the difficulty in confirming the diagnosis of PC, attempts have been made to address this problem through the search for biomarkers, mainly using immunohistochemistry. Within this theme, the phenomenon of epithelial–mesenchymal transition and cancer stem cell markers have been scarcely studied; this could eventually help discriminate between a diagnosis of parathyroid adenoma or carcinoma. On the other hand, identification of oncogenes and tumor suppressing genes, as well as epigenetic markers such as miRNAs, lncRNAs, and circRNAs all play a crucial role in tumorigenesis and have enormous potential as diagnostic tools. Furthermore, proteomic-based and inflammatory markers have also been described as diagnostic aids for this uncommon neoplasm. This review presents a clinical approach to the disease, as well as providing a state-of-the-art analysis of basic biomarkers in diagnosis and future projections in this field. Full article

Parathyroid carcinoma (PC) is a rare endocrine malignancy that poses significant diagnostic challenges due to its resemblance to benign conditions. This case series describes the clinical presentation, diagnosis, management, and short-term outcomes of four male patients (aged 54, 65, 73, and 74 years) with primary hyperparathyroidism and hypercalcemia. The preoperative diagnosis of PC remains challenging; suspicion should arise in cases of severe hypercalcemia, elevated parathyroid hormone levels, and the presence of a mass on imaging or during surgery. All patients underwent an initial localized parathyroidectomy, with PC confirmed postoperatively. Subsequently, they received ipsilateral hemithyroidectomy and prophylactic central lymph node dissection. Over a two-year follow-up period, all patients maintained normocalcemia without evidence of disease recurrence or metastasis. In conclusion, whether to perform a complete en bloc resection or a two-step surgical strategy remains a difficult decision in PC patients with intricate preoperative evaluations. Full article

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes. Full article