Endocrine Tumors Research Articles

6637 A Rare Case of a Possible Non-functional (Clinically Silent Biochemically Negative) Adrenal Pheochromocytoma

Abstract Disclosure: V.K. Babu: None. M.T. Corwin: None. S.T. Olatunbosun: None. Introduction: Adrenal pheochromocytomas (pheo) are rare neuroendocrine tumors arising from the chromaffin cells of the adrenal medulla. Their incidence is around 0.8 per 100,000 patient years. They are usually sporadic, with about 40% having a pre-existing familial genetic disease. About 3% of adrenal incidentalomas prove to be pheo. They have a heterogenous presentation and are diagnosed by measuring urinary and plasma fractionated metanephrines (met) and catecholamines (catecho). The diagnosis becomes challenging in patients presenting with small tumors and normal levels of biochemical metabolites, as in our patient. Clinical Case: A 32-year-old male with no significant past medical history was referred to us with a left adrenal incidentaloma of 1.2 cm x 1 cm with 23 Hounsfield units during a non-contrast CT scan performed for abdominal pain. He denied spells of headaches, excessive perspiration, palpitations, history of hypertension, hypokalemia, history of kidney stones, fractures, muscle weakness, easy bruisability, new abdominal striae, change in weight, steroid use, or family history of endocrine tumors. MRI with adrenal protocol 3 months later showed a 1.2 cm x 1.4 cm left adrenal nodule that was markedly hyperintense on T2-weighted and hypointense on T1-weighted images without microscopic fat, suspicious for a pheo. It also demonstrated peripheral enhancement with progressive central filling on the delayed images without washout. Plasma met and catecho were normal: normetanephrines (normet) (45.2 pg/mL), met (36.4 pg/mL), epinephrine (epi) (34 pg/mL), norepinephrine (norepi) (295 pg/mL) and dopamine (<30 pg/mL). Subsequent 24-hour urine testing revealed normal met (155 mcg/day, 154 mcg/day), and normal normet (248 mcg/day, 236 mcg/day) on two separate occasions, and normal epi (9 mcg/L), norepi (36 mcg/day), and dopamine (228 mcg/day). The patient was subsequently referred to Endocrine Surgery for evaluation. Conclusion: Our patient likely has a non-functional pheo. Another possibility is an adrenal hemangioma, which would show discontinuous peripheral nodular enhancement in addition to progressive central filling. Patients with pheo less than 2 cm may present with normal biochemical testing. The size of a pheo is usually proportional to the levels of its biochemical metabolites. This case is unique because patients with a similar sized pheo are expected to have 3 times higher levels of plasma met and catecho, even if still within normal limits. It is important to take tumor size into consideration when interpreting labs to determine its functional status. This may help in determining the need for a pre-operative alpha blockade prior to adrenal surgery. A definitive diagnosis of a pheo’s non-functional status can only be confirmed after histopathological examination of the tumor tissue. Presentation: 6/3/2024

Understanding the Dosage-Dependent Role of Dicer1 in Thyroid Tumorigenesis.

Tumors originating from thyroid follicular cells are the most common endocrine tumors, with rising incidence. Despite a generally good prognosis, up to 20% of patients experience recurrence and persistence, highlighting the need to identify the underlying molecular mechanisms. Dicer1 has been found to be altered in papillary thyroid cancer (PTC). Studies suggest that Dicer1 functions as a haploinsufficient tumor suppressor gene: partial loss promotes tumorigenesis, while complete loss prevents it. To investigate the effects of partial or total Dicer1 loss in PTC in vitro, we generated stable Dicer1 (+/-) cell lines from TPC1 using CRISPR-Cas9, though no Dicer1 (-/-) lines could be produced. Therefore, siRNA against Dicer1 was transfected into Dicer1 (+/-) cell lines to further decrease its expression. Transcriptomic analysis revealed changes in proliferation and cell locomotion. BrdU staining indicated a slow-down of the cell cycle, with fewer cells in S phase and more in G0-G1-phase. Additionally, transwell assays showed decreased invasion and migration after Dicer1 knockdown by siRNA. Moreover, Dicer1 overexpression led to decreased proliferation, invasion, and increased apoptosis. Our findings deepen the understanding of Dicer1's role in thyroid cancer, demonstrating that both complete elimination and overexpression of Dicer1 inhibit thyroid oncogenesis, highlighting Dicer1 as a promising target for novel therapeutic strategies.

Treatment outcome of anaplastic thyroid cancer patients in Vietnam (period 2014-2022).

Anaplastic thyroid carcinoma (ATC) is an endocrine tumor with low incidence and one of the most aggressive human malignancies. The median survival is only 3-10 months, and the optimal therapeutic approach as well as prognostic factors have not been established. The aim of this study was to evaluate the long-term survival and good prognostic factors of patients with ATC. The retrospective study used our institution's single-center database system. 31 patients with histopathological confirmation of anaplastic thyroid cancer from January 2014 to June 2022 were included. 31 patients with ATC [11 males (35.5%), 20 females (64.5%); average age, 58.7 years] were identified, 32.3% were stage IVA, 32.3% stage IVB, and 35.4% IVC. The median overall survival (OS) of the entire cohort was 6.9 ± 1.45 months. The OS at two years was 12.1%. The female with no cervical lymph node metastasis, undergoing surgery, and tumor size < 6 cm were associated with improved OS. Patients undergoing surgery followed by chemoradiation therapy had the highest median OS (11 ± 1.83 months) and 21.8% of 2-year survival. Anaplastic thyroid carcinoma is a highly malignant tumor. Patients receiving surgical resection had better OS than patients without these treatments. The combination of surgery and chemoradiation could improve OS.

Robotic Surgery in Paediatric Oncology: Expanding Boundaries and Defining Relevant Indications

This article reviews the establishment and progress of the Multidisciplinary Paediatric Robotic Program in a high-volume paediatric surgery department at Hôpital Necker-Enfants Malades, Paris, France. A major foundational principle of the program was to establish a safe and secure environment for patients and staff, both pre-operatively, intra-operatively and post-operatively. This founding principle when applied systematically has allowed increasing confidence across the program and service. The robotic platform allows for precision surgery when approaching tumours, with freedom of movement adapted to meticulous vascular and organ dissection. Surgical feasibility is based on tumour characteristics, pre-operative imaging, with a focus on vascular and organ involvement, considering goals of surgery and surgical experience. Case complexity has been gradually increased (where appropriate) through an iterative process. The future of surgery is robotic, and even more so image-guided surgery, and this synergy has been instrumental when approaching tumour surgery in children. The current principles that guide application of robot-assisted surgery in paediatric tumours are presented. With this blueprint, excellent oncological outcomes can be achieved while utilising a minimally invasive approach in children with selected endocrine, neuroblastic and renal tumours.

Thyroglobulin and calcitonin measurements: pitfalls and future perspectives.

Thyroid cancer is the most prevalent endocrine cancer. Prognosis depends on type and stage of cancer when discovered. Treatment involves (hemi-)thyroidectomy, possibly followed by additional therapeutic options. After treatment, patients are monitored using serum concentrations of endocrine tumour marker thyroglobulin in case of differentiated cancer and calcitonin in case of medullary thyroid cancer. Measuring thyroglobulin and calcitonin concentrations in serum may be challenging. In this review we give a complete overview of the evolvement in laboratory measurements regarding thyroglobulin and calcitonin with an emphasis on (pre-)analytical challenges and potential approaches to overcome current pitfalls.

Nouveautés en pathologie thyroïdienne : classification OMS 2022, système Bethesda 2023, biologie moléculaire et testing moléculaire

WHO CLASSIFICATION 2022, BETHESDA SYSTEM 2023, MOLECULAR BIOLOGY AND MOLECULAR TESTING: Thyroid pathology has experienced significant advances with the publication of the 5th edition of the World Health Organization classification of endocrine tumors in 2022 and the third edition of the Bethesda system for thyroid cytopathology in 2023. At the same time, the availability of next-generation sequencing data coupled with numerous translational research projects have considerably increased our knowledge of the genomics and mechanics of thyroid cancers, enabling us to refine prognosis and propose new targeted therapies. In this review, we will take up the main new features of the WHO 2022 and Bethesda 2023 classifications, as well as molecular biology findings, with an emphasis on the practical implications for clinicians.

Chromosomal Alteration Patterns in PitNETs: Massive Losses in Aggressive Tumors.

The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO classification of endocrine tumors. A genome wide NGS panel targeting 1500 single-nucleotide polymorphisms (SNP) was used to classify chromosomal imbalances, loss of heterozygosity and copy number variations in DNA from formalin fixed paraffin embedded tissues. We identified four distinct chromosomal patterns, with varying distribution among different tumor lineages. Forty-two of 61 (69%) PitNETs showed chromosomal alterations. Gonadotroph PitNETs showed mostly quiet genomes. The majority of lactotroph PitNETs (19/20, 95%) were altered, exhibiting a gained genome and a remarkably low recurrence rate. Nine of ten (90%) corticotroph PitNETs harbored chromosomal alterations, of which two aggressive corticotroph tumors and one metastatic corticotroph PitNET showed massive chromosomal losses leading to near haploid/near homozygous genomes. The comparison of the molecular profile of primary and recurrent PitNETs of five patients showed no significant accumulation of alterations over time. A simple genome wide 1500 SNP test can be used in the identification of outspoken aggressive subsets of PitNET by the occurrence of a near haploid/near homozygous genome. Furthermore, the presence of neoplastic tissue in resected material can be potentially confirmed for non-gonadotroph PitNETs in suboptimal histological assessment conditions.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Prevalence, cyto-histo correlation, and molecular and ultrasonographic profile

Non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP) was introduced in 2017 WHO Classification of Endocrine Tumors. In this study, we aim to characterize the molecular and ultrasonographic profiles of NIFTP and evaluate the performance of fine needle aspiration (FNA) cytology. Consecutive thyroid resections at our institution between 2018 and 2022 were collected; 1282 thyroid resections were identified. NIFTP was diagnosed in 109 cases (prevalence: 8.5 %); 65 (60 %) were the targeted nodules with an average size of 2.5 cm. Among these 65 targeted, 27 had Afirma testing results, 44 had Thyroid Imaging Reporting and Data System (TIRADS) scores, and 53 had FNA results. Of the 27 cases with Afirma reports, 23 were labeled “suspicious”, including 5 with RAS-related mutations (risk of malignancy (ROM) 75 %) and 17 without a reportable genetic alternation (ROM 50 %). 60 % cases with TIRADS scores were classified as TIRADS 4, while 16 % were classified as TIRADS 5. The majority of the 53 FNA cases had a diagnosis of AUS/FLUS (53.7 %) or FN (31.5 %). One additional targeted nodule with a diagnosis of NIFTP had BRAFV600E mutation and was reclassified as papillary thyroid carcinoma. In summary, the majority of the targeted NIFTPs had “suspicious” Afirma testing results (85 %), TIRADS 4 scores (60 %) and either AUS/FLUS (53.7 %) or FN (31.5 %) FNA results. The sensitivity and specificity of cytology for diagnosing NIFTP were 90 % and 57 %, respectively, with a positive predictive value (PPV) of 16 % and negative predictive value of 98 %.

The Application of microRNAs in Papillary Thyroid Cancer: A Bibliometric and Visualized Analysis.

Thyroid cancer is the most common malignant endocrine tumor, with papillary thyroid carcinoma (PTC) being the most prevalent type, accounting for 85% of thyroid cancer cases. Here, we conducted a bibliometric analysis of the literature in the field of microRNAs in PTC research to demonstrate current trends and research hotspots, and present a visual map of past and emerging trends. We searched the Web of Scientific Core Collection (WoSCC) database for publications from 1999 to 2023 centered on this field. Next, we employed visualization tools such as VOSviewer, CiteSpace, and Microsoft Excel 2019 to present co-occurrence and co-citation analyses, trends, hotspots, and visual representations of contributions from authors, institutions, journals, and countries/regions. The bibliometric analysis encompassed the period from 1999 to 2023, with 994 papers from 54 countries/regions. The country with the most publications and highest total citations was the People's Republic of China, but the United States held the highest average citation rate. Among the top ten productive institutions, the Ohio State University (Ohio State Univ) was the most prominent contributor to this field. The JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (J Clin Endocrinol Metab) ranked first in terms of citation counts and average citations among the top ten productive journals. In terms of keywords, "circular RNAs", "promotes", and "progression" have become prominent research areas. This study elucidates current trends, hotspots, and emerging frontiers in miRNA research within PTC, and provides new insights and guidance for future identification of new PTC biomarkers and clinical trials.

Genotype/phenotype correlations in multiple endocrine neoplasia type 2.

Multiple endocrine neoplasia type 2 (MEN 2) is a rare hereditary endocrine tumour syndrome caused by mutations in the rearranged during transfection (RET) gene. MEN 2 is divided into two main entities, MEN 2A and MEN2B, both of which present with medullary thyroid cancer (MTC) in approximately 100% of cases and pheochromocytoma in 50% of cases. Specific RET mutations are associated with a risk of early onset of MTC, from 1 year of age (highest risk) to 5 years of age (high risk). This risk defines the optimal timing for thyroidectomy, ideally at an age when the disease has not spread. This is the most important genotype-phenotype correlation observed in MEN 2. Specific RET mutations also define the penetrance of pheochromocytoma. However, despite the presence of these highest/high risk variants, some patients unexpectedly present with non-aggressive MTC or never present with pheochromocytoma, suggesting that factors other than the major RET variant may modify the natural history and genotype-phenotype correlations. Improving our understanding of the genotype-phenotype correlations would allow individualizing the management and follow-up of patients with MEN 2. The aim of this brief review is to discuss the main genotype-phenotype correlations in MEN 2 and the potential factors that might influence these correlations.

Near-Infrared Autofluorescence Signatures of Single- vs Multigland Disease in Primary Hyperparathyroidism

The success of parathyroidectomy depends on accurate intraoperative localization and identification of all diseased glands in parathyroid exploration based on surgeon expertise to prevent persistent hyperparathyroidism. Near-infrared autofluorescence (NIRAF) imaging has recently emerged as a promising adjunctive intraoperative tool for localizing parathyroid glands; however, its potential utility in the assessment of parathyroid glands has yet to be established. To analyze the differences in NIRAF signatures of parathyroid glands in single vs multiple glands in primary hyperparathyroidism (pHPT). This prospective diagnostic study analyzed in vivo NIRAF images of parathyroid glands obtained during parathyroidectomies between November 18, 2019, and December 31, 2023, at a single tertiary referral center. Pixel intensities of the images were measured using third-party software. Patients who underwent parathyroidectomy for sporadic pHPT using a second-generation NIRAF imaging device were included. Patients with multiple endocrine neoplasm disorders were excluded. In vivo NIRAF images obtained during the procedures were analyzed. Near-infrared autofluorescence imaging during parathyroidectomy. The primary outcomes were the autofluorescence intensity and heterogeneity of single adenomas and multigland disease (ie, double adenomas and 3- or 4-gland hyperplasia) in sporadic pHPT. Normalized autofluorescence intensity was calculated by dividing the mean pixel intensity of the parathyroid gland by the background tissue. A heterogeneity index was calculated by dividing the standard deviation by the mean pixel intensity of the gland. The secondary outcome was the visibility of each parathyroid gland on NIRAF imaging before it became apparent to the naked eye during exploration. A total of 1287 in vivo NIRAF images obtained from 377 patients (median [IQR] age, 66 [56-73] years; 299 female [79.3%]) were analyzed. Of all patients, 230 (61.0%) had a single adenoma, 91 (24.1%) had double adenomas, and 56 (14.9%) had 3- or 4-gland hyperplasia. A mean (SD) of 3.4 (1.1) parathyroid glands were identified in the procedures. A comparison of 581 diseased glands (45.1%) and 706 normal glands (54.9%) showed a lower median normalized autofluorescence intensity of 2.09 (95% CI, 1.07-4.01) vs 2.66 (95% CI, 1.43-4.20; effect size = 0.36) and higher heterogeneity index of 0.18 (95% CI, 0.07-0.41) vs 0.11 (95% CI, 0.01-0.27; effect size = 0.45), respectively. Of diseased glands, single adenomas (233 [40.1%]) vs double adenomas (187 [32.2%]) and 3- or 4-gland hyperplasia (161 [27.7%]) had a lower median autofluorescence intensity of 1.92 (95% CI, 1.02-4.44) vs 2.22 (95% CI, 1.10-3.97; effect size = 0.21), respectively. On receiver operating characteristic analysis, the optimal autofluorescence intensity threshold to differentiate between single adenomas vs multigland disease was 2.14, with a sensitivity of 64.4%, specificity of 58.1%, and area under the curve of 0.626. These findings suggest that parathyroid glands in single- vs multigland disease may exhibit different autofluorescence characteristics. Although the effect size was modest, the differences identified should be kept in mind when assessing the parathyroid glands during surgical exploration.

MAOA uVNTR Polymorphism in a Sample of Patients Diagnosed with Papillary Thyroid Cancer

Thyroid gland carcinoma (TGC), though only 1% of all carcinomas, is the most common endocrine neoplasm with an increasing incidence since the 1990s. Of the TGC types, papillary thyroid carcinoma (PTC) is the most common and has the best overall prognosis. Although primarily studied in various neural spectrum disorders, monoamine oxidase A (MAOA) may also contribute to cancer occurrence. This case control study assessed the prevalence of MAOA uVNTR polymorphism in PTC patients, compared its frequency with a healthy control, and assessed the variant’s impact on clinical features. The research participants consisted of 30 PTC patients (20 female, 10 male) over 18 years old who underwent thyroidectomy and radioiodine therapy at a Federal District private clinic and 30 paired and unrelated healthy volunteers (18 female, 12 male). The most frequent MAOA uVNTR alleles were 3R and 4R. Although no significant difference was detected in the genotypic distribution nor the PTC patients’ thyroglobulin, thyroid-stimulating hormone, and antithyroglobulin levels; body mass indexes; administered radiopharmaceutical (131I) doses; or biological sex, the presence of at least one 3R allele was associated with a larger tumor size (T3 + T4 staging). Thus, the 3R allele seems to be associated with PTC pathogenesis severity.

Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review.

Most cases of high blood pressure have no identifiable cause, termed essential hypertension; however, in approximately 15% of cases, hypertension occurs due to secondary causes. Primary aldosteronism (PA) and pheochromocytoma and paraganglioma (PPGL) are representative endocrine hypertensive diseases. The differentiation of endocrine hypertension provides an opportunity to cure and prevent target organ damage. PA is the most common cause of secondary hypertension, which significantly increases the risk of cardiovascular disease compared to essential hypertension; thus, patients with clinical manifestations suggestive of secondary hypertension should be screened for PA. PPGL are rare but can be fatal when misdiagnosed. PPGL are the most common hereditary endocrine tumors; therefore, genetic testing using next-generation sequencing panels is recommended. Herein, we aimed to summarize the characteristic clinical symptoms of PA and PPGL and when and how diagnostic tests and treatment strategies should be performed.

From cortisol-producing adrenal adenoma to atrial myxoma, through nivolumab-induced hypophysitis: a complicated case report of Carney Complex.

Carney complex (CNC) is a rare, autosomal dominant syndrome, most commonly caused by PRKAR1A gene mutations and characterized by pigmented skin and mucosal changes with multiple endocrine and non-endocrine tumours. This case report highlights the diagnostic challenges associated with CNC in a patient with multiple neoplasms and a complex medical history, including cortisol-producing adrenal adenoma, breast cancer, melanoma, and atrial myxoma. We report the case of a 41-year-old woman with a medical history of left adrenalectomy for cortisol producing adenoma (2005) with no sign of adrenal insufficiency at follow-up, right mastectomy for BRCA1/2 negative carcinoma (2013) and left parotid BRAF-V600E wild-type melanoma (2019), treated with nivolumab adjuvant therapy. In August 2019, following the fifth nivolumab administration, the patient developed central hypocortisolism due to iatrogenic hypophysitis, confirmed by brain MRI and properly treated with oral hydrocortisone. Nivolumab was discontinued due to the patient's decision. In October 2020 and April 2021, the patient had ischaemic strokes, requiring systemic thrombolysis. Echocardiographic examination then revealed a left atrial mass, with histological finding of myxoma. Given the rarity of this neoplasm and the suspicion of a syndromic disorder, a genetic evaluation was conducted, which confirmed a PRKAR1A gene mutation and the diagnosis of Carney complex. This case illustrates the diagnostic challenges in CNC, especially in patients with multiple tumourous manifestations and a wide spectrum of life-threatening clinical presentations. It underscores the importance of a multidisciplinary approach to diagnose and manage rare diseases, improving patient outcomes through timely genetic testing and coordinated care.

An Uncommon Culprit: Pancreatic Neuroendocrine Tumor in a Patient with Uncontrolled Diabetes

Pancreatic Neuro Endocrine Tumors (NETs) are rare neoplasms that originate from the endocrine tissues of the pancreas, accounting for only 1-2% of pancreatic tumors. Despite their low incidence, these tumors present with a wide range of symptoms and have the ability to secrete hormones, posing significant challenges for their diagnosis and treatment. There are two distinct types of pancreatic NETs: functioning and nonfunctioning. Functioning tumors are characterized by hormone-related clinical syndromes, while nonfunctioning tumors are often found incidentally. The pathogenesis of pancreatic NETs involves both sporadic and hereditary factors, including syndromes such as MEN1, VHL, and NF1. Typically, these tumors are diagnosed in individuals between the ages of 40 and 60, and their effective management requires a multidisciplinary approach. Diagnostic imaging techniques, such as CT and EUS, play a crucial role in accurate diagnosis, while PET scans aid in staging and treatment planning. Histological analysis is essential for determining the tumor grade and predicting prognosis. Treatment strategies are tailored to the tumor's characteristics and the patient's overall health. These may include the use of somatostatin analogs, such as Lanreotide and Octreotide, to control hormone secretion and inhibit tumor growth, as well as systemic therapies like everolimus, sunitinib, and PRRT for metastatic disease. This case report describes the clinical course of a 66-year-old male with a well-differentiated pancreatic NET who initially presented with persistent hyperglycemia. Further investigations revealed a sizable pancreatic mass and liver metastases. Diagnostic evaluation confirmed a grade 1 Neuro Endocrine Tumor, and the patient was started on treatment with Lanreotide. However, his management was complicated by the development of hepatic encephalopathy, which necessitated treatment with lactulose and rifaximin. This case highlights the importance of considering pancreatic NETs in cases of atypical diabetes presentations and emphasizes the need for a multidisciplinary team to provide optimal care. Given the complex nature of pancreatic NETs, a comprehensive diagnostic workup and personalized treatment approach are essential for improving patient outcomes.

Factors Affecting Cell Viability during the Enzymatic Dissociation of Human Endocrine Tumor Tissues.

The enzymatic dissociation of human solid tissues is a critical process for disaggregating extracellular matrix and the isolation of individual cells for various applications, including the immortalizing primary cells, creating novel cell lines, and performing flow cytometry and its specialized type, FACS, as well as conducting scRNA-seq studies. Tissue dissociation procedures should yield intact, highly viable single cells that preserve morphology and cell surface markers. However, endocrine tissues, such as adrenal gland tumors, thyroid carcinomas, and pituitary neuroendocrine tumors, present unique challenges due to their complex tissue organization and morphological features. Our study conducted a morphological examination of these tissues, highlighting the intricate structures and secondary degenerative changes that complicate the dissociation process. We investigated the effects of various dissociation parameters, including the types of enzymes, incubation duration, and post-dissociation purification procedures, such as debris removal and nontarget blood cell lysis, on the viability of cells derived from different tumor types. The findings emphasize the importance of optimizing tissue digestion protocols to preserve cell viability and integrity, ensuring reliable outcomes for downstream analyses.

Grading and staging for pituitary neuroendocrine tumors.

Pituitary adenoma/pituitary neuroendocrine tumors (PitNETs) are the second most common primary intracranial tumor and the most frequent neuroendocrine tumors/neoplasms of the human body. Thus, they are one of the most frequent diagnoses in neuropathologist's practise. 2022 5th edition WHO Classification of Endocrine and Neuroendocrine Tumors does not support a grading and/or staging system for PitNETs and argues that histological typing and subtyping are more robust than proliferation rate and invasiveness to stratify tumors. Numerous studies suggest the existence of clinically relevant molecular subgroups encouraging an integrated histo-molecular approach to the diagnosis of PitNETs to deepen the understanding of their biology and overcome the unresolved problem of grading system. The present review illustrates the main issues involved in establishing a grading and a staging system, as well as alternative systems validated by independent series to date. The state of art of the current histological and molecular markers is detailed, demonstrating that a standardized and reproducible clinico-pathological approach, combined with the integration of molecular data may help build a workflow to refine the definition of PitNETs with 'malignant potential' and most importantly, avoid delay in patient treatment. Next molecular studied are needed to validate an integrated histo-molecular grading for PitNETs.

Expression characteristics of TBC1D4 activating protein molecule and identification of key module genes for preventing thyroid cancer progression

Endocrine tumors like thyroid carcinoma are becoming more frequent. No clinically informative predictors were found. Thus, effective gene networks and representative biomarkers can illuminate thyroid cancer prevention molecular mechanisms. TBC1D4 is an activating protein molecule that plays an important role in regulating cell metabolism and signal transduction. The aim of this study was to investigate the expression characteristics of TBC1D4 activating protein molecules and identify key module genes that prevent thyroid cancer progression. GSE65144 data were downloaded from GEO. “limma” in R found DEGs with a false discovery rate < 0.05 and a log2 fold change <1. WGCNA builds gene co-expression networks, screens key modules, and filters hub genes. Overlapping genes become hub genes. Hub genes underwent GO and KEGG pathway enrichment analysis. We used Lasso to extract hub gene expression results' distinctive genes. Key genes. GEPIA database determined expression and survival impact. A total of 3220 DEGs. Thyroid cancer was mostly associated with darkred, darkturquoise, and green modules. Venn screened 639 hub genes. Cytokine-cytokine receptor interaction was the primary KEGG enrichment. Hub genes were 14. Finally, ARHGAP6, TBC1D4, and TC2N were important genes. Through gene screening and functional enrichment analysis, we identified a group of genes related to TBC1D4 activating protein and constructed the corresponding protein interaction network.

Advancing Pancreatic Cancer Surgical Treatments and Proposal of New Approaches.

Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems-the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition-assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center's neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy's Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes.

The Role of Inositols in Endocrine and Neuroendocrine Tumors.

Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy.