Molecular Analysis of Renal/Adrenal Angiosarcomas Reveals High Frequency of Recurrent Genetic Alterations.

Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the KDR gene, while one-third demonstrated mutations in the PIK3CA gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated BRIP1 gene amplification, CTNNB1 and ETV6 mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot KDR and PIK3CA mutations represent potential therapeutic targets for these highly aggressive cancers.

Metastatic disease and major adverse cardiovascular events preceding diagnosis are the main determinants of disease-specific survival of pheochromocytoma/paraganglioma: long-term follow-up of 303 patients.

Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival. Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234). Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1). Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease.

Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/ß-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.

Effectiveness of Robot-assisted Adrenalectomy for a Giant Adrenal Hemangioma: A Case Report.

BACKGROUND: Adrenal hemangiomas are extremely rare benign tumors that often need to be distinguished from malignancies. Adrenal tumors >4 cm in size are treated surgically because the possibility of malignancy cannot be ruled out. Traditionally, open surgery has been the mainstay of treatment; however, in recent years, robot-assisted surgery has been increasingly used for tumors of larger size and suspected malignancy. Here, we report a case of robot-assisted adrenalectomy for an 11 cm adrenal hemangioma. CASE REPORT: A 62-year-old male with lateral abdominal pain was referred to our hospital for further examination and treatment. His medical history was significant for hypertension, diabetes, and dyslipidemia. Computed tomography revealed an 11 cm left adrenal tumor, and all endocrinological screening tests were negative. Because the possibility of malignancy could not be ruled out, a robot-assisted adrenalectomy was performed. The operation time was 129 min, and the estimated blood loss was 7 ml. Pathological findings revealed an adrenal hemangioma. The postoperative course was uneventful, and patient's condition subsequently improved postoperatively. CONCLUSION: Robot-assisted adrenalectomy was performed for a giant adrenal hemangioma without any complications. Robotic surgery is useful for resecting adrenal hemangiomas even exceeding 11 cm in diameter.

Acute onset of hypertensive encephalopathy in a dog with right adrenal pheochromocytoma and neoplastic invasion of the caudal vena cava: Case report and review of the literature.

Background: Canine pheochromocytomas (PCCs) are rare tumors of the adrenal medulla. Clinical signs are often vague, resulting in intermittent catecholamine over secretion or neoplastic invasion of adjacent structures. Case Description: A 12-year-old Epagneul Breton dog with a 1-year history of chronic kidney disease, was examined for acute onset of severe neurological signs. Based on clinical and instrumental data, hypertensive encephalopathy was suspected. Cardiac and abdominal ultrasound were performed. Severe hypertensive cardiopathy and a right adrenal gland mass with invasion of the caudal vena cava were diagnosed. Computed tomography imaging confirmed the suspect of invasive malignant neoplasia. Emergency pharmacological therapy was started to reduce systemic pressure, improve clinical signs, and stabilize the dog in view of surgical resolution. After initial improvement, patient conditions abruptly worsened, and euthanasia was elected. Histology examination confirmed a right adrenal PCC, with caval invasion. Conclusion: To the authors' conclusions, acute hypertensive encephalopathy is a peculiar manifestation of PCCs. Ultrasound is a useful, and rapid test to suspect PCC as it can detect adrenal alterations, caval invasion, metastasis, and cardiac sequelae consistent with the condition. PCC can mimic multiple affections, and be misinterpreted, especially when a concurrent disease has already been diagnosed. Veterinarians need to be aware that comorbidities could mask clinical signs and delay diagnosis. Furthermore, this clinical case reminds us to include PCC also in the differential diagnosis of dogs with an acute onset of severe neurological signs.

Role of Different Variants of Leptin Receptor in Human Adrenal Tumor Types.

The aim of the study was to evaluate the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. In a single-center study, 96 patients (19 with adrenal cortical carcinoma and 77 with benign tumors) underwent an adrenalectomy. A total of 14 unaffected adrenal gland tissues from kidney donors were used as controls. Fasting blood samples were collected for laboratory tests, and mRNA expressions of leptin receptor isoforms were assessed by RT-qPCR. The study analyzed correlations between mRNA expressions and clinical data and measured NCI-H295R cell proliferation via a real-time cell analyzer. All adrenal lesions expressed leptin receptor isoforms. Significantly lower LepR1 expression was observed in carcinoma tissues than in adenomas and controls (p = 0.016). Expressions of LepR3&LepR6 were correlated with overall survival (p = 0.036), while LepR2&LepR4 and LepR5 expressions were inversely related to morning serum cortisol levels (p = 0.041). Leptin reduced NCI-H295R cell proliferation (p < 0.0001). The study highlights the diagnostic and prognostic significance of leptin receptor isoforms in adrenal tumors. Specifically, LepR1 may serve as a diagnostic marker for carcinomas, while LepR3&LepR6 have potential use as prognostic markers.

Expression Patterns of MOTS-c in Adrenal Tumors: Results from a Preliminary Study.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.

Metastatic pheochromocytoma and paraganglioma: Integrating tumor biology in clinical practice.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells in the autonomic nervous system. Depending on their location, these tumors are capable of excessive catecholamine production, which may lead to uncontrolled hypertension and other life-threatening complications. They are associated with a significant risk of metastatic disease and are often caused by an inherited germline mutation. Although surgery can cure localized disease and lead to remission, treatments for metastatic PPGL (mPPGL)-including chemotherapy, radiopharmaceutical agents, multikinase inhibitors, and immunotherapy used alone or in combination- aim to control tumor growth and limit organ damage. Substantial advances have been made in understanding hereditary and somatic molecular signaling pathways that play a role in tumor growth and metastasis. Treatment options for metastatic disease are rapidly evolving, and this paper aims to provide a brief overview of the management of mPPGL with a focus on therapy options.

Uncommon adrenal rest tumors and massive adrenal enlargement in adult with congenital adrenal hyperplasia mimicking metastasis from pleomorphic sarcoma.

BACKGROUND: Congenital adrenal hyperplasia (CAH) encompassed a bunch of autosomal recessive disorders characterized by impaired cortisol levels due to an enzymatic deficiency in steroid synthesis. In adult male patients with CAH, a frequent complication related to poor disease control is the development of ectopic adrenocortical tissue in the testes, named testicular adrenal rest tumors (TART). Conversely, ovarian adrenal rest tumors (OART) in females are extremely rare and adrenal rests in sites other than gonads are so uncommon to have been described only few times in literature. CASE PRESENTATION: We report a case of a male patient with untreated CAH and oncologic history of pleomorphic sarcoma who presented with massive bilateral adrenal enlargement and adrenal rest tumors in peri-lumbar and peri-cecal sites, which mimicked metastasis from sarcoma. CONCLUSIONS: The development of massive adrenal enlargement and ectopic adrenal rest tumors in sites other than gonads, even if very uncommon, should be suspected in patients with CAH and prolonged periods of undertreatment.

Case report: A challenging case of severe Cushing's syndrome in the course of metastatic thymic neuroendocrine carcinoma with a synchronous adrenal tumor.

Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.

Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene succinate dehydrogenase subunit B (SDHB) are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of SDHB-associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous SDHB pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous sdhb mutant zebrafish as a potential model to study SDHB-related PPGLs. Adult sdhb mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, sdhb mutants showed significantly increased succinate levels, a major hallmark of SDHB-related PPGLs. While basal activity was increased during day periods in mutants, mitochondrial complex activity and catecholamine metabolite levels were not significantly different. In conclusion, we characterised an adult in vivo zebrafish model, genetically resembling human carriers. Adult heterozygous sdhb mutants mimicked their human counterparts, showing systemic elevation of succinate levels despite the absence of a tumour phenotype. This model forms a promising basis for developing a full tumour phenotype and gaining knowledge of the pathomechanism behind SDHB-related PPGLs.

Genetic and Molecular Biomarkers in Aggressive Pheochromocytomas and Paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neoplasms producing catecholamines that occur as hereditary syndromes in 25-40% of cases. To date, PPGLs are no longer classified as benign and malignant tumors since any lesion could theoretically metastasize, even if it occurs only in a minority of cases (approximately 10-30%). Over the last decades, several attempts were made to develop a scoring system able to predict the risk of aggressive behavior at diagnosis, including the risk of metastases and disease recurrence; unfortunately, none of the available scores is able to accurately predict the risk of aggressive behavior, even including clinical, biochemical, and histopathological features. Thus, life-long follow-up is required in PPGL patients. Some recent studies focusing on genetic and molecular markers (involved in hypoxia regulation, gene transcription, cellular growth, differentiation, signaling pathways, and apoptosis) seem to indicate they are promising prognostic factors, even though their clinical significance needs to be further evaluated. The most involved pathways in PPGLs with aggressive behavior are represented by Krebs cycle alterations caused by succinate dehydrogenase subunits (SDHx), especially when caused by SDHB mutations, and by fumarate hydratase mutations that lead to the activation of hypoxia pathways and DNA hypermethylation, suggesting a common pathway in tumorigenesis. Conversely, PPGLs showing mutations in the kinase cascade (cluster 2) tend to display less aggressive behavior. Finally, establishing pathways of tumorigenesis is also fundamental to developing new drugs targeted to specific pathways and improving the survival of patients with metastatic disease. Unfortunately, the rarity of these tumors and the scarce number of cases enrolled in the available studies represents an obstacle to validating the role of molecular markers as reliable predictors of aggressiveness.

Metastatic diseases to the adrenal gland: A comprehensive study from an academic institution with emphasis on clinical occult cases.

The adrenal gland is one of the common sites of metastasis and distinguishing metastatic diseases from adrenal primary neoplasms is essential for accurate clinical management of patients. Our study aimed to elucidate the spectrum and clinicopathologic features of metastatic solid tumors to the adrenal gland at an academic institution, with special focus patients presented with solitary adrenal masses without previously known malignancies. Our departmental database (2013-2022) was retrospectively searched and 129 patients with metastatic solid tumors involving the adrenal gland were identified. The median age at the initial diagnosis of metastatic diseases was 64 years old (range, 54-70 years). The majority of the diseases were presented as unilateral (n=118) or unifocal (n=119) involvement. Most patients had known prior or concurrent malignancies (n=125), whereas adrenal gland involvement was the initial clinical presentation in 4 patients. The most common primary carcinomas included renal cell carcinoma (n=84), lung adenocarcinoma (n=21), urothelial carcinoma (n=3) and hepatocellular carcinoma (n=3). In 104 (80 %) patients with available follow up (median of 39 months, ranging 0-81 months), 43 patients died of disease. Metastatic diseases are usually exercised in the differential diagnosis when there is clinically known malignant primary. In patients without clinical known malignancies, close clinical and radiologic correlation and thorough relevant clinical work up are critical, because clinical occult malignancy may metastasize to the adrenal gland as a solitary mass at the initial presentation, although it is rare.

Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review.

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

Robotic Left Pancreatectomy with Perirenal Tissue Excision and Left Adrenalectomy (Posterior Ramps) for Pancreatic Ductal Adenocarcinoma Abutting the Adrenal Gland.

BACKGROUND: Radical antegrade modular pancreato-splenectomy (RAMPS) has been largely described in left-sided pancreatic cancers.1.J Hepato-Biliary-Pancreat Sci 29:1156-1165 Its prognostic advantage is not clear, although a theoretical improvement in R0 resection rate has been shown.2.J Am Coll Surg 204:244-249 Furthermore, RAMPS is usually carried out without adrenal gland removal, the so-called anterior RAMPS, while extending the resection to the adrenal plane could impair perioperative outcomes.3.HPB 25:311-319 METHODS: A 40 mm pancreatic ductal adenocarcinoma (PDAC) was found in a 70-year-old patient. Tumor infiltrates the adrenal gland and a robotic posterior RAMPS was indicated. RESULTS: After sectioning the splenic vessels and the pancreatic neck, the dissection was directed vertically in a sagittal plane along the left border of the superior mesenteric artery to identify the left renal vein. Our dissection plane was then directed on a caudo-cranial axis, after identification of the left renal artery and below the adrenal gland. The resection was also delimitated medially by the left borders of the superior mesenteric artery and the aorta, and posteriorly by the renal parenchyma. Postoperative course was marked by a biochemical leak. The patient was discharged on postoperative day (POD) 5 and the drain removed at POD 18. Pathological examination confirmed a pT2N2 PDAC with negative margins, with 4/18 positive nodes. CONCLUSIONS: The robotic platform is routinely employed in pancreatic surgery. Thanks to its increased degree of movement, its dexterity, and the magnification, this approach can help surgeons with vascular identification and control, in performing extended lymphadenectomies, and finding the correct planes of dissection. All these elements are crucial in a well-performed posterior RAMPS.

Safety and efficacy of thermal ablation of adrenal metastases secondary to lung cancer.

OBJECTIVES: Assess safety and efficacy of thermal ablation for adrenal metastases (AM) secondary to non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective study included patients with NSCLC AM treated with thermal ablation between 2/2010-11/2021. Local tumor progression free survival (LTPFS) and overall survival (OS) were calculated using Kaplan-Meier method. Adverse events were graded using Common Terminology Criteria for Adverse Events v5. RESULTS: Seven patients (mean age ± SD, 63.9 ± 12.5 years; 6 males) with seven AM were treated in eight sessions. Retreatment was performed in one patient with residual disease. Five sessions were with microwave ablation and 3 with radiofrequency ablation. Mean tumor size was 20.1 ± 7.0 mm. Median number of ablation probes used was 1 (range, 1-5), with a median of 3 activations (range, 1-3), and average ablation time of 14.4 ± 15.0 minutes. Response based on RECIST v 1.1 or PERCIST criteria revealed stable disease in 1 tumor, progression of disease in 3 tumors (one was re-ablated), and partial response in 3 tumors. Median LTPFS was not reached (NR) [95 % CI: 1- NR]. Median OS was 47.97 months (95 % CI: 18.63- NR). Intraprocedural hypertension (blood pressure ≥180 mmHg) occurred during 5/8 (62.5 %) sessions and intraoperative tachycardia occurred during 2/8 (25 %) sessions. Complications within one month of ablation occurred in 3/8 (37.5 %) sessions: grade 2 pneumothorax, grade 1 hematuria, and grade 2 adrenal insufficiency. CONCLUSIONS: In this small series, thermal ablation for NSCLC AM resulted in prolonged local control and OS with no major complications.

Management of a giant adrenal schwannoma.

In this case report, we present a man in his 60s who presented with an incidentally discovered right adrenal mass, which turned out to be an adrenal schwannoma. This is a very rare tumour that originates from Schwann cells and involves the peripheral nerves. The tumour was removed by open adrenalectomy, and this 15-cm adrenal schwannoma is one of the largest reported in the literature, with none >16 cm having ever been reported. This case highlights the importance of keeping an open mind about the cause of an incidentally discovered adrenal mass, which is an increasingly common way for adrenal tumours to present given the increased access to cross-sectional imaging. As well as presenting the case and the pathological basis behind adrenal schwannomas, we include a review of the literature and a general discussion about incidentally discovered adrenal masses.

[The relationship between clinical characteristics and pathological features in patients with pheochromocytomas/paragangliomas].

Objective: To explore the correlation between clinical characteristics and pathological features in patients with pheochromocytoma/paraganglioma (PPGLs). Methods: A case series study. A retrospective analysis was conducted on patients with single and primary PPGLs after postoperative pathological diagnosis who were admitted to Peking Union Medical College Hospital between January 2019 and December 2022. The patients were divided into the Ki-67<3% group and the Ki-67≥3% group with Ki-67 proliferation index of 3% as the threshold. The relationship between clinical and pathological characteristics of PPGLs was analyzed. Results: A total of 399 PPGLs patients were included, with 177 males and 222 females, aged [M(Q1, Q3)] 45.0(35.5, 53.0) years. Among them, 226 (56.6%) cases originated from the adrenal gland, while 104 cases (26.1%) from the retroperitoneum. 20.9% (27/129) of the patients were found to harbor germline mutations of susceptibility genes, with SDHB mutations being the most common (10.1%, 13/129). The Ki-67 staining was performed on 302 cases, with a Ki-67 proliferation index [M(Q1, Q3)] of 2.0% (1.0%, 3.0%). There were 194 cases in Ki-67<3% group and 108 cases in Ki-67≥3% group. Compared with the patients in Ki-67<3% group, the age of onset in Ki-67≥3% group was younger (P=0.029). Compared with the patients with paragangliomas without SDHB or Cluster 1A-related gene mutations, positive 131I-meta-iodobenzylguanidine (131I-MIBG) imaging or negative O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry staining, those with SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging or positive MGMT immunohistochemistry staining had a higher Ki-67 index (all P<0.05). Compared with adrenal pheochromocytoma, retroperitoneal paragangliomas had a higher proportion of SDHB mutations and a higher proportion of normetanephrine (NMN) secretory types (all P<0.05). Compared with adrenal pheochromocytoma, the maximum diameter of head and neck paraganglioma tumors was smaller [3.0 (1.9, 3.8) cm vs 4.7 (3.4, 6.4) cm, P<0.001] and the proportion of Ki-67≥3% was higher (61.3% vs 33.8%, P=0.007). Conclusions: PPGLs patients with earlier onset age, SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging, or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index. Head and neck tumors, though smaller, exhibit a higher proliferation potential.

Clinical, radiological, and surgical outcomes of 431 patients with adrenal incidentalomas: retrospective study of a 10-year single-center experience.

Background/aim: The incidence of adrenal tumors is increasing due to the widespread utilization of radiographic imaging techniques. Factors such as tumor size, radiological characteristics, and functionality of adrenal adenomas play crucial roles in diagnosis and subsequent management. In this retrospective study, we investigated the clinical, radiological, and surgical features of patients with adrenal incidentalomas (AIs) and evaluated their follow-up results. Materials and methods: We analyzed data from 431 patients diagnosed with AIs (130 males, 301 females) who underwent adrenal hormone evaluation at our center. We compared nonfunctioning and functioning AIs in terms of radiological features. We also compared baseline and follow-up characteristics in nonfunctioning AIs. Results: The mean age of the patients was 55.4 ± 11.5 years, with a mean tumor size of 25.9 ± 14.3 mm. Mean follow-up duration was 3.17 ± 2.07 years. Adenoma localization revealed 165 (38.3%) right-sided, 185 (42.9%) left-sided, and 81 (18.8%) bilateral cases. Most patients (76.6%) had nonfunctioning AIs. During follow-up, nonfunctioning AIs exhibited increased fasting blood glucose, fasting insulin and HOMA-IR values (p = 0.002, <0.001 and 0.004, respectively). Among the functioning AIs cases (23.4%), autonomous cortisol secretion, Cushing's syndrome, pheochromocytoma, and primary aldosteronism were observed in 10.4%, 5.1%, 3.9%, and 3.9% of cases, respectively. Receiver operating characteristic curve analysis determined an adrenal adenoma size of 26.5 mm as the optimal cut-off for distinguishing between functioning and nonfunctioning AIs, with a sensitivity and specificity of 61.4% and 70.0%, respectively. Conclusion: Although the majority of AIs are nonfunctioning, the prevalence of functioning adrenal adenomas is not rare. Our findings suggest that adenoma size emerges as a valuable predictor for early detection of functioning adenomas. In addition, smaller masses appear to carry a lower risk of malignancy.