Neuroendocrine Tumors Research Articles

Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor: A case report

BACKGROUND Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare malignancies affecting the pancreas. The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting 30% or more of the tumor volume. Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination. A well-differentiated neuroendocrine tumor (NET) component is rarely reported in MiNENs. CASE SUMMARY Here we report a rare case with intermingled components of ductal adenocarcinoma and grade 1 well-differentiated NET in the pancreas. The two tumors show distinct histology and significant differentiation discrepancy (poorly differentiated high grade adenocarcinoma and well-differentiated low grade NET), and also present as metastases in separate lymph nodes. Next generation sequencing of the two components demonstrates KRAS and TP53 mutations in the ductal adenocarcinoma, but no genetic alterations in the NET, suggesting divergent origins for these two components. Although tumors like this meet the diagnostic criteria for MiNEN, clinicians often find the diagnosis and staging confusing and impractical for clinical management. CONCLUSION Mixed NET/non-NET tumors with distinct histology and molecular profiles might be better classified as collision tumors rather than MiNENs.

Critical considerations for the management of gastrointestinal mixed neuroendocrine non-neuroendocrine neoplasms and pure neuroendocrine carcinomas

Mixed neuroendocrine non-neuroendocrine neoplasms constitute rare tumors that are located mainly in the gastrointestinal (GI) tract and have high degrees of malignancy, and the frequency of these tumors has been increasing. They consist of a neuroendocrine neoplastic component with another component of adenocarcinoma usually and have a dismal prognosis. The rare GI pure neuroendocrine carcinoma is highly aggressive and requires complex and extensive management since a genetic distinction exists between it and GI non-neuroendocrine neoplasms, which are generally slow-growing lesions. The most common GI-mixed neuroendocrine non-neuroendocrine neoplasms are colorectal, followed by gastric, mainly in the gastroesophageal junction. Current imaging modalities of nuclear medicine and radiology play important roles in the accuracy of diagnosis. Liquid biopsy may contribute to early detection and timely diagnosis. Ultrasonography, either endoscopic or abdominal, is a technique that contributes to a diagnosis; additionally, contrast-enhanced ultrasonography is very helpful in follow-up appointments. Histopathology establishes a definite diagnosis and stage by evaluating the cell differentiation grade and the cell proliferation index Ki67. The genetic profile can be valuable in diagnosis and gene therapy. Surgical resection with wide lymphadenectomy, whenever possible, and adjuvant chemotherapy constitute the main therapeutic management strategies. Targeted therapy and immunotherapy achieve encouraging results.

Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center

BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen (TEMCAP) exhibits a certain level of efficacy in treating advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET). However, published data from Peru are limited. We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population. AIM To evaluate overall survival (OS) in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima-Perú. METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN. A total of thirty-eight patients were included in the final analysis: Thirty-five received TEMCAP as a first-line treatment, and three as a second-line treatment. The primary objective was to evaluate OS. The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS The median age of the patients was 52 years (range 24-77 years), and 53.3% were female. The most common symptoms at diagnosis were abdominal pain in 31 patients (81.6%). Primary tumors included 12 in the rectum (31.6%), 11 in the pancreas (28.9%), 3 in the ileum (7.9%), 2 in the mesentery (5.3%), 2 in the small intestine (5.3%), 1 in the appendix (2.6%), 1 in the stomach (2.6%) and 6 cases of liver metastasis of unknown primary (15.8%). Five were neuroendocrine tumors (NET) G1 (13.2%), 33 were NET G2 (86.8%), five had Ki67 < 3% (13.2%), and 33 had Ki67 between 3% and 20% (86.8%). TEMCAP was administered to 35 (92.1%) patients as first-line treatment. OS at 12, 36, and 60 months was estimated in 80%, 66%, and 42%, respectively, with a median OS of 49 months. CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.

Mixed neuroendocrine non-neuroendocrine tumors: The quest for evidence

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine and non-neuroendocrine components that occupy at least 30% of the whole tumor. Biologically, both components appear to derive from an identical cellular precursor undergoing early dual differentiation or late transdifferentiation. While our understanding of MiNENs has improved in recent years, many areas of uncertainty remain. In this context, setting diagnostic criteria capable of capturing the continuum of disease biology while providing clinically meaningful information in terms of prognosis and response to treatments appears vital to advance the field and improve patients’ outcomes. Evidence is needed to generate robust classification schemes, and multi-institutional cooperation will likely play a crucial role in building adequately powered cohorts to address some of the most pressing questions discussed in this Editorial. What is the minimum representation for each component needed to define MiNENs? How can the epidemiology of MiNENs change according to different diagnostic definitions? How can we generate the clinical evidence needed to optimize the management of MiNENs?

Estimating prognosis of gastric neuroendocrine neoplasms using machine learning: A step towards precision medicine

Survival rates following radical surgery for gastric neuroendocrine neoplasms (g-NENs) are low, with high recurrence rates. This fact impacts patient prognosis and complicates postoperative management. Traditional prognostic models, including the Cox proportional hazards (CoxPH) model, have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients. Machine learning methods offer a unique opportunity to analyze complex relationships within datasets, providing tools and methodologies to assess large volumes of high-dimensional, multimodal data generated by biological sciences. These methods show promise in predicting outcomes across various medical disciplines. In the context of g-NENs, utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies. This editorial reviews a study exploring the advantages and effectiveness of the random survival forest (RSF) model, using the lymph node ratio (LNR), in predicting disease-specific survival (DSS) in postoperative g-NEN patients stratified into low-risk and high-risk groups. The findings demonstrate that the RSF model, incorporating LNR, outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.

Limitations and suggestions for type 2 diabetes mellitus and pancreatic neuroendocrine tumors based on meta-analysis

We read with great interest the systematic review and meta-analysis by Cigrovski Berkovic et al published recently, which evaluated the association between type 2 diabetes mellitus (T2DM) and pancreatic neuroendocrine tumors (pNETs). The study identified T2DM as a risk factor for the development of pNETs and linked it to poor tumor-free survival. However, due to the limited number of studies and high heterogeneity, the role of metformin in the diagnosis and prognosis of pNETs remained inconclusive. We believe the study has some limitations regarding literature search, risk of bias assessment, and analysis of heterogeneity and publication bias. Expanding the search to more databases, applying more appropriate bias assessment tools, and using better statistical methods to evaluate heterogeneity and publication bias would strengthen the study’s conclusions. Addressing these concerns could provide more robust evidence for understanding the diagnostic and prognostic impact of T2DM in pNETs.

User-friendly prognostic model for rectal neuroendocrine tumours: In the era of precision management

In this letter, we explore into the potential role of the recent study by Zeng et al . Rectal neuroendocrine tumours (rNETs) are rare, originate from peptidergic neurons and neuroendocrine cells, and express corresponding markers. Although most rNETs patients have a favourable prognosis, the median survival period significantly decreases when high-risk factors, such as larger tumours, poorer differentiation, and lymph node metastasis exist, are present. Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care, but their complex calculation formulae limit clinical use. Moreover, the prognostic models that have been developed for rNETs to date still have several limitations, such as insufficient sample sizes and the lack of external validation. A high-quality prognostic model for rNETs would guide treatment and follow-up, enabling the precise formulation of individual patient treatment and follow-up plans. The future development of models for rNETs should involve closer collaboration with statistical experts, which would allow the construction of clinical prediction models to be standardized and robust, accurate, and highly generalizable prediction models to be created, ultimately achieving the goal of precision medicine.

Consensus on immunotherapy for small cell lung cancer(2024 edition)

Lung cancer is one of the malignant tumors with high morbidity and mortality worldwide. Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is closely associated with tobacco exposure, accounting for 13% to 15% of all lung cancer cases. It is characterized by a high proliferation rate and exceptional metastatic capacity. At the time of diagnosis, approximately 70% of the patients have metastasized and are classified as extensive-stage small cell lung cancer (ES-SCLC). From 1980 to 2018, chemotherapy and radiotherapy were the main treatment strategies for SCLC. Etoposide combined with platinum has remained the standard first-line treatment for ES-SCLC. Although SCLC is very sensitive to initial treatment, the majority of patients have disease progression within 6 months, and treatment options after recurrence are very limited, and the median survival time is only about 8-10 months. The advent of immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) and programmed death -1 (PD-1) inhibitors, has brought new hope to patients with SCLC. PD-1/PD-L1 plus chemotherapy have significantly prolonged overall survival of patients with ES-SCLC, which has become the new standard of first-line treatment for ES-SCLC. Currently, a raised number of immune checkpoint inhibitors (ICIs) have been approved in China for the treatment of SCLC, providing more treatment options for SCLC patients. To further standardize the clinical practice of SCLC immunotherapy, the "Expert Consensus on Immunotherapy for SCLC" has been developed based on domestic and international guidelines, consensus, and relevant medical evidence, aiming to provide reference and guidance for domestic clinicians.

Therapeutic Exploitation of Neuroendocrine Transdifferentiation Drivers in Prostate Cancer

Neuroendocrine prostate cancer (NEPC), an aggressive and lethal subtype of prostate cancer (PCa), often arises as a resistance mechanism in patients undergoing hormone therapy for prostate adenocarcinoma. NEPC is associated with a significantly poor prognosis and shorter overall survival compared to conventional prostate adenocarcinoma due to its aggressive nature and limited response to standard of care therapies. This transdifferentiation, or lineage reprogramming, to NEPC is characterised by the loss of androgen receptor (AR) and prostate-specific antigen (PSA) expression, and the upregulation of neuroendocrine (NE) biomarkers such as neuron-specific enolase (NSE), chromogranin-A (CHGA), synaptophysin (SYP), and neural cell adhesion molecule 1 (NCAM1/CD56), which are critical for NEPC diagnosis. The loss of AR expression culminates in resistance to standard of care PCa therapies, such as androgen-deprivation therapy (ADT) which target the AR signalling axis. This review explores the drivers of NE transdifferentiation. Key genetic alterations, including those in the tumour suppressor genes RB1, TP53, and PTEN, and changes in epigenetic regulators, particularly involving EZH2 and cell-fate-determining transcription factors (TFs) such as SOX2, play significant roles in promoting NE transdifferentiation and facilitate the lineage switch from prostate adenocarcinoma to NEPC. The recent identification of several other key novel drivers of NE transdifferentiation, including MYCN, ASCL1, BRN2, ONECUT2, and FOXA2, further elucidates the complex regulatory networks and pathways involved in this process. We suggest that, given the multifactorial nature of NEPC, novel therapeutic strategies that combine multiple modalities are essential to overcome therapeutic resistance and improve patient outcomes.

Surgical and Oncologic Outcomes of Primary Tumor Resection in Patients with Small Intestinal Neuroendocrine Tumors: Results from a Single-Center Series Over a 15-Year Period.

The role of prophylactic primary tumor resection (PTR) in patients with small intestinal neuroendocrine tumors (SI-NETs) and unresectable liver metastases is a matter of debate. We aimed to evaluate outcomes in patients with SI-NETs who underwent PTR, according to the presence of metastasis and symptoms from primary. Data from patients who underwent PTR for SI-NETs from a single referral center (2007-2023) were prospectively collected. Patients were divided into three groups: non-metastatic (M0) and metastatic with primary tumor-related symptoms (MS) or metastatic asymptomatic (MA). Kaplan-Meier curves for overall survival (OS) and event-free survival (EFS) were generated and compared by group. Univariate and multivariable Cox regression analyses were performed to assess the significance of risk factors. Of 147 patients, 53 were M0, 23 were MS, and 71 were MA. Median follow-up was 26 months. The 5- and 10-year OS estimates were 100% and 100% in M0 patients, 82 and 21% in MS patients, and 89 and 80% in MA patients, respectively (p<0.001). Median EFS was 91 months overall and 43,126 months and not reached for the MS, MA, and M0 groups, respectively (p<0.001). In multivariable analysis, MS (hazard ratio [HR] 3.92, 95% confidence interval [CI] 1.71-9.52), functioning tumors (HR 1.98, 95% CI 1.03-3.81), and G2 grade (HR 3.20, 95% CI 1.64-6.85) were associated with a shorter EFS. In this large retrospective series, the MS group had a significantly worse OS and EFS compared with M0 and MA. This finding suggests that prophylactic PTR might benefit SI-NET patients with unresectable liver metastases, as symptom development could impair long-term prognosis after surgery.

Systemic Cancer Hallmarks as Novel Markers Associated with Progression-free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing PRRT.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors often detected at the metastatic stage. The aim of this study was to profile the peripheral blood transcriptome through RNA-Seq and investigate the association of the systemic cancer hallmarks with progression-free survival in PRRT-treated GEP-NET patients. The cohorts were: discovery cohort [PRRT-naïve well-differentiated GEP-NETs, n=59; age- and sex-matched healthy individuals, n=38], and independent evaluation cohort [GEP-NETs, n=66]. Peripheral blood transcriptomes were profiled through RNA sequencing and cancer hallmarks were identified via Gene Set Enrichment Analysis (GSEA). Activities of cancer hallmarks in each sample were calculated using Gene Set Variation Analysis (GSVA). Differentially expressed genes were identified with DESeq2. Progression-free survival was used as a primary endpoint and prognostic association was evaluated using univariate and multivariate COXPH analyses. RNA-Seq captured global changes in the peripheral blood transcriptome of GEP-NET patients. Peripheral blood transcriptome of NET patients showed differential enrichment of 30 systemic cancer hallmarks viz., TNF-α signaling via NF-κB, IL2/STAT5 signaling, TNF-α response, TNF-γ response, IL6/JAK/STAT signaling, TGF-β signaling, heme metabolism. etc. In the univariate analyses, two cancer hallmarks were prognostically significant (p<0.05) in GEP-NETs. Heme metabolism and IL2/STAT5 signaling were statistically significant in the Discovery cohort (n=58) and independent evaluation cohort (n=66). In multivariate COXPH analyses, heme metabolism and IL2/STAT5 signaling were independently associated with PFS in GEP-NET patients undergoing PRRT. This study provides comprehensive coverage of the peripheral blood transcriptome of GEP-NET patients via RNA-Seq and identifies systemic cancer hallmarks as independent prognostic factors in NETs.

Quantification of PD-L1 expression and tumor mutational burden in biologically distinct advanced pancreatic cancers responding to pembrolizumab: case reports

BackgroundThe advent of checkpoint therapy is one of the most important recent advancements in cancer therapy. Though checkpoint therapy is a mainstay in some cancers, it has been largely ineffective in treating cancers of the pancreas. Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are seldom responsive to checkpoint inhibition.Case presentationsHere we present two cases of advanced pancreatic cancers that either failed to respond or recurred following conventional treatments. Tissue from each tumor was sequenced and analyzed for PD-L1 expression. Each patient was started on checkpoint blockade after assessing for a predictive biomarker, either the combined positive score or the tumor mutational burden. In each case, checkpoint blockade led to durable radiographic responses.ConclusionsWe therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

High Diagnostic Yield of Fine Needle Biopsy for Pancreatic Serous Cystadenomas - a Multi-Center Study.

Distinguishing serous cystadenoma, a benign pancreatic cyst, from potentially malignant mucinous pancreatic cystic lesions carries significant clinical and prognostic implications; and while endoscopic ultrasound-guided fine needle aspiration is the standard diagnostic tool, its low diagnostic yield often results in additional workup. This study evaluates diagnostic yield of fine needle biopsy (FNB) on lesions suggestive of serous cystadenoma on endoscopic ultrasound. Patients with microcystic EUS appearance were identified through retrospective chart review in two institutions. Prior cross sectional imaging diagnosis was also obtained. All microcystic lesions with classic "honeycomb" appearance for serous cystadenoma on EUS were targeted for FNB and their pathology evaluated. Patients were identified through database search from 2015 to 2022 and procedure information was obtained through a retrospective chart review from two large academic centers. Thirty-one patients with suspected serous cystadenoma who underwent EUS-FNB were included. EUS FNB was successful in obtaining diagnosis in 96.8% of patients. Serous cystadenoma was diagnosed via EUS FNB in 27 of 31 patients (87.1%). Of the remaining four patients, there was one invasive pancreatic ductal adenocarcinoma, one pancreatic neuroendocrine tumor, one intraductal papillary mucinous neoplasm, and one nondiagnostic sample. EUS-FNB sampling for histopathology is a safe and accurate diagnostic tool for pancreatic serous cystadenoma. When microcytic lesions are found on endoscopic ultrasound, our study results suggest that fine needle biopsy for histopathology should be considered as the initial diagnostic evaluation tool given the demonstrated improved diagnostic yield for serous cystadenoma.

Gastrointestinal Neuroendocrine Tumors-Case Series from a Tertiary Care Center with Review of Literature.

Neuroendocrine tumors account for 0.5% of all malignancies, and their incidence is around 2/100,000 with a female predilection within the age range of 50years at the time of presentation. NETs in India have a different clinicopathological profile compared to those in Western countries. Very few limited studies are available in Indian literature with regard to the epidemiology, presentations, histopathological characteristics, and treatment outcomes in patients with gastrointestinal neuroendocrine tumors. This warrants the need for documentation of these tumors, and we hereby present a case series of four patients diagnosed with NETs who presented within a period of 9months at our rural tertiary care center.

MMP-2, MMP-9 and TIMP-2 expression in pituitary neuroendocrine tumors and their relationship with cavernous sinus invasion

Objective: To evaluate the expression of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pituitary tumors, and investigate their correlation with circulating plasma proteins and cavernous sinus invasion. Additionally, the Ki-67 index was also assessed. Methods: Seventy-four patients (37 females) with pituitary adenomas were included, with preoperative peripheral blood collected in 29 cases. Tumor samples were evaluated for MMP-2, MMP-9, TIMP-2, and Ki-67 expression by immunohistochemistry. Protein plasma was semi-quantitatively detected using a commercial membrane antibody array. Results: Sixteen patients presented tumors invading the cavernous sinus. MMP-2 and TIMP-2 were slightly increased in these tumors compared to the non-invasive group, but the difference was not statistically significant. MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor protein expression and also did not differ between the two groups. MMP-2 was not detected in plasma in any case. No statistically significant difference was observed when different tumors subtypes were considered. A significant difference was observed in tumor size [3.4 cm (2.8-4.9) vs. 1.9 cm (1.3-2.6); p &lt; 0.001] and in the Ki-67 index [1.8% (0.3-2.5) vs. 0.5% (0.2-1.0); p = 0.01] between the invasive and non-invasive groups, respectively. Conclusions: In this cohort, we found no significant correlation between tissue and plasma levels of MMP-2, MMP-9, and TIMP-2 and cavernous sinus invasion in pituitary tumors. Further investigation is needed to elucidate the potential role of these markers in invasiveness of pituitary tumors.

Embolize, supercharge, resect: Embolization to enhance hepatic vascularization prior to en-bloc pancreas and arterial resection

IntroductionEmbolization could increase the resectability of pancreatic tumors by supercharging visceral arterial perfusion prior to pancreatic surgery with arterial en-bloc resection. Its indications, however, are controversial. MethodsWe retrospectively analyzed the results of a single-center database of patients undergoing pancreatic surgery with arterial resection (AR) after preoperative arterial embolization (PAE) to increase hepatic vascular flow and spare arterial reconstruction. ResultsPAE was planned in 15 patients with arterial involvement due to pancreatic tumors. Three patients were excluded due to the finding of irresectable disease during surgery. Twelve cases were resected because of pancreatic cancer (10), distal cholangiocarcinoma (1), and pancreatic neuroendocrine tumor (1). Arterial involvement in these cases required embolization of the substitute right hepatic artery (RHA) (5), left hepatic artery (1), and common hepatic artery (CHA) (6) to enhance liver vascularization. Two patients presented migration of the vascular plug after PAE. Six pancreatoduodenectomies and 6 distal pancreatectomies were performed, the latter associated with en-bloc celiac trunk and CHA resection. R0 was achieved in 7 out of 12 patients, and pathological vascular involvement was confirmed in 8. Postoperative complications included one patient who developed gastric ischemia and underwent gastrectomy, and one patient who underwent reoperation for acute cholecystitis with liver abscesses. ConclusionPreoperative arterial embolization before pancreatic surgery with hepatic arterial resection enables surgeons to precondition hepatic vascularization and prevent hepatic ischemia. In addition, this avoids having to perform arterial anastomosis in the presence of pancreatic suture.

Incidence and factors associated with heart disease in patients diagnosed with small bowel and broncho-pulmonary neuroendocrine tumors: a population-based analysis

Incidence and factors associated with heart disease in patients diagnosed with small bowel and broncho-pulmonary neuroendocrine tumors: a population-based analysis

Clinicopathological Features of Epstein-Barr Virus-Positive Neuroendocrine Carcinoma: Analysis of Twenty-Two Cases.

Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) is a rare neoplasm with limited histopathological and therapeutic data. This report presents 22 cases of EBV-positive NEC, analyzing age distribution, morphology, and immunophenotype. The median patient age was 47years (range: 27-67years), with a male-to-female ratio of 17:5. Most cases (86%, 19/22) were localized to the nasal cavity or nasopharynx, while the remaining three (14%, 3/22) involved the lung, eyelid, and chest wall. Tumors were identified as small cell neuroendocrine carcinoma (SCNEC) or large cell neuroendocrine carcinoma (LCNEC) based on cellular morphology. Immunohistochemical analysis showed positivity for at least one, but generally, two neuroendocrine markers and INI1, while negativity for NUT and squamous cell carcinoma markers, such as p63, p40, and CK5/6. In situ hybridization consistently revealed EBV early RNAs (EBERs) in all cases. Notably, eight patients benefited from chemoradiotherapy. Recognizing this rare tumor is essential for optimizing treatment strategies.

Neuroendocrine carcinoma of the nasal cavity and paranasal sinuses: A case report and literature review

Neuroendocrine carcinoma of the nasal cavity and paranasal sinuses: A case report and literature review

Pterygopalatine Catecholamine-Secreting Paraganglioma: A Diagnostic and Therapeutic Challenge.

Paragangliomas are rare neuroendocrine tumors originating from the paraganglia. They are mostly benign, slow-growing, and non-secretory. This report describes a rare case of a catecholamine-secreting paraganglioma located in the pterygopalatine fossa. A 45-year-old man presented with severe hypertension, occipital headache, and facial pain. Imaging revealed a large pterygopalatine mass, initially misdiagnosed as chondrosarcoma. Gamma knife stereotactic radiosurgery was performed, followed by surgical resection via a maxillary swing approach. Histological examination confirmed the zellballen pattern typical of paraganglioma. Post-surgery, the patient's blood pressure normalized immediately and subsequently. This case highlights the diagnostic challenges of head and neck paragangliomas in atypical locations and underscores the importance of surgical intervention for catecholamine-secreting tumors. Future studies should focus on refining diagnostic protocols and comparing the efficacy of radiosurgery versus surgical resection for these tumors.