Jugular Paragangliomas Research Articles

7553 Thyroid Paraganglioma: A Complex Tale of the Familiar Thyroid Nodule

Abstract Disclosure: V. Moorthy: None. A. Kondapally: None. L.E. Kimball-Ravari: None. Background: Thyroid paragangliomas are rare and often misdiagnosed on fine-needle aspiration (FNA). Clinical Case & Discussion: A 58-year-old female presented with an asymptomatic “cold” thyroid nodule. Ultrasound demonstrated a 2 cm hypoechoic nodule in the isthmus. FNA yielded a follicular lesion of undetermined significance, and genomic sequencing estimated a 50% risk of malignancy prompting the patient to opt for total thyroidectomy. Histopathology and immunohistochemistry (IHC) confirmed the diagnosis of benign paraganglioma (PGL). SDH-B (succinate dehydrogenase subunit B) was notably absent on IHC. Past medical history is significant for hysterectomy for uterine fibroids and obesity, along with a confirmed family history of Hereditary Leiomyomatosis with Renal Cell Cancer (HLRCC). The patient and several family members tested positive for a pathogenic variant of fumarate hydratase (FH) gene implicated in HLRCC and undergo annual MRIs for cancer surveillance. The loss of SDH-B suggests underlying mutation. Germline SDH mutations occur in 20% of patients with pheochromocytoma and PGLs, predisposing to hereditary syndromes. PGLs are catecholamine-secreting neuroendocrine tumors with carotid body and jugular PGLs accounting for 80% of head and neck PGLs (HNPGLs). Thyroid PGLs originate from the inferior laryngeal paraganglia. They are very rare, often non-secretory, and commonly present as asymptomatic solitary nodules. For these reasons, FNA, while contraindicated, is frequently performed. If FNA is considered, pre-procedural alpha-adrenergic blockade is recommended, although catecholamine secretion triggered by FNA is uncommon. Thyroid PGLs are misdiagnosed on FNA as other thyroid neoplasms. Awareness of the more unique cytopathology of thyroid PGLs and a comprehensive IHC can aid in accurate diagnosis. Interestingly, SDH (complex 2) and FH are closely linked enzymes in the Krebs cycle. Emerging evidence correlates germline FH mutations and hereditary pheochromocytoma-paraganglioma. PGLs are less commonly associated with MEN 2A and 2B, NF type 1, VHL, and Carney-Stratakis syndrome and Carney triad. Therefore, additional testing for SDH, RET, VHL and MAX genes was recommended in this case. Total thyroidectomy or lobectomy with or without elective lymph node dissection remains the treatment of choice. Annual 24-hour urine and plasma metanephrine testing will help screen for potential recurrence. Use of GLP1 agonists for weight loss in this patient warrants further genetic and safety evaluation. Clinical Lesson/Conclusion: Often misdiagnosed on FNA, thyroid paragangliomas are rare, with multiple genetic predispositions. FNA is contraindicated and if considered, must be performed after alpha-blockade. Germline SDH mutations are implicated in PGLs and increasing evidence links FH mutations to hereditary PGLs. Presentation: 6/3/2024

New progress in the diagnosis and treatment of jugular paragangliomas

Jugular paraganglioma is the most common neoplasms in the jugular foramen. It is a slow-growing wiht abundant blood supply, and is intimately associated with critical neurovascular structures at the skull base. In this paper, the latest advance in pathophysiology, surgical treatment, radiotherapy were reviewed based on previous literature, providing reference for clinical diagnosis, treatment and future research.

Management of bilateral head and neck paragangliomas at a single-institution across four decades.

Bilateral head and neck paragangliomas (HNPGLs) require nuanced management to balance tumor control with functional preservation. All patients seen at a single-institution for bilateral paraganglioma between 1983 and 2023 were retrospectively reviewed. Demographics, genetic testing results, and tumor characteristics were analyzed and compared to treatment modality and cranial nerve outcomes. There were 49 patients with 116 tumors (90 carotid body tumors [CBTs], 15 vagal paragangliomas [VPs], and 11 jugular paragangliomas [JPs]). Twenty-six patients had SDH pathologic variants (PV). Surgical management was more commonly utilized in younger patients (OR: 0.97, 95% CI: 0.950-0.992) and for JPs (OR: 9, 95% CI: 1.386-58.443). In surgical cases, CBTs had a lower risk of postoperative cranial nerve deficits compared to JPs and VPs (OR: 0.095, 95% CI: 0.013-0.692). Younger patients with bilateral HNPGLs, especially those with JP and CBT, are more often treated with surgery. CBTs have lowest risk of cranial nerve deficits after surgery.

Somatostatin Receptor-Directed PET/CT Can Differentiate Between Different Subtypes of Head and Neck Paragangliomas.

Given their neuroendocrine origin, head and neck paragangliomas (HNPGLs) can be imaged with somatostatin receptor (SSTR)-directed PET/CT. We aimed to determine whether the in vivo PET signal can differentiate between varying HNPGL subtypes. Fourteen patients with HNPGL received pretherapeutic SSTR-PET/CTs using 68 Ga-DOTATOC. Six (42.9%) patients had a jugular paraganglioma (PGL-J), 5 (35.7%) were diagnosed with carotid paraganglioma (PGL-Cs), and the remaining 3 patients (21.4%) had PGL-C with pathogenic SDHx germline variants (PGL-C-SDH). A visual and quantitative assessment of the primary tumor on SSTR-PET was performed, including SUV max and target-to-background ratio (TBR). Quantitative values were then compared between subgroups of patients affected with different HNPGL entities. On visual assessment, all primary HNPGLs could be identified on SSTR-PET/CT. Quantification of HNPGL revealed substantially elevated SUV max in PGL-J (101.7 ± 58.5) when compared with PGL-C-SDH (13.4 ± 5.6, P < 0.05), but not when compared with PGL-C (66.7 ± 27.3, P = 0.4; PGL-C vs PGL-C-SDH, P = 0.2). TBR of PGL-J (202.9 ± 82.2), however, further differentiated between PGL-C (95.7 ± 45.4, P < 0.05) and PGL-C-SDH (20.4 ± 12.2, P < 0.01; PGL-C vs PGL-C-SDH, P = 0.3). Moreover, whole-body readout revealed metastases in 2/3 (66.7%) of PGL-C-SDH patients, with a single SSTR-expressing skeletal lesion in one subject and bipulmonary lesions in the other patient. In patients with HNPGL, SSTR-PET/CT identified the primary and metastatic disease and provides substantially elevated TBR, indicating excellent image contrast. PET-based quantification can also differentiate between varying HNPGL subtypes.

Comparison of surgical outcomes between early and advanced class of jugular paragangliomas following application of our modified surgical techniques

To compare the safety and effectiveness of surgical treatment of jugular paragangliomas (JPs) following the application of our modified surgical techniques. Fifty-six patients with JPs were analyzed for tumor classification, surgical outcomes, and intratumor blood vessels. The gross total resection in C1–2 (100%) was significantly greater than that in C3 and D (66.7%). Good postoperative facial nerve (FN) function (House–Brackmann I–II) was achieved in 89.5% C1–2 cases, which was not significantly different from C3 and D (93.3%) (P = 0.694). Preoperative and postoperative lower cranial nerve (LCN) deficits correlated with the Fisch’s classification of tumors (P < 0.05), and intraoperative blood loss was greater in advanced tumors (P = 0.050). Further study showed that the cross-sectional area of intratumor blood vessels was positively associated with intraoperative blood loss (P < 0.001). Surgical excision of JPs is a safe and effective strategy, and early surgical treatment is a good option for patients with C1–2 tumors without surgical contraindications.

Systematic Review and Meta-analysis for Surgery Versus Stereotactic Radiosurgery for Jugular Paragangliomas.

Comprehensively analyze tumor control and treatment complications for jugular paraganglioma patients undergoing surgery versus stereotactic radiosurgery (SRS). EMBASE, Medline, and Scopus. The databases were searched for English and Spanish articles from January 1, 1995, to January, 1, 2019, for studies reporting tumor control and treatment side effects regarding patients with jugular paraganglioma treated with surgery or SRS. Main outcome measures included short-term and long-term tumor recurrence, as well as postintervention complications. We identified 10,952 original abstracts, 705 eligible studies, and 107 studies for final data extraction. There were 3,498 patients-2,215 surgical patients and 1,283 SRS patients. Bayesian meta-analysis was applied to the extracted data, with tau measurements for study heterogeneity. SRS tumors were larger (3.9 cm 3 versus 8.1 cm 3 ). Meta-analysis results demonstrated low rates of long-term recurrence for both modalities (surgery, 15%; SRS, 7%), with SRS demonstrating lower rates of postintervention cerebrospinal fluid leak, dysphagia, and cranial nerve Vll, lX, X, Xl, or Xll palsies. This study demonstrates excellent control of jugular paragangiomas with both surgery and SRS, with higher rates of lower cranial neuropathies, dysphagia, and cerebrospinal fluid leaks among surgical patients.

Headache with Cerebrospinal Fluid Hypovolemia after Radiotherapy for Jugular Paraganglioma.

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Management of Complex Jugular Paragangliomas: Surgical Resection and Outcomes.

This study aimed to review tumor control and cranial nerve function outcomes in patients with complex jugular paragangliomas and to refine the surgical strategies for complex jugular paragangliomas. We describe our experience with 12 patients with complex jugular paragangliomas diagnosed in our institution from January 2013 to June 2020. The main outcomes included tumor control, complications, and function of facial nerve and lower cranial nerves, postoperatively. Gross-total resection was achieved for 9 (75%) patients, and subtotal resection was achieved for 3 (25%) patients. The surgical tumor control rate was 100% after a mean follow-up of 45.5 months (range, 13-111 months). Postoperatively, 10 patients (83.3%) obtained unchanged or improved facial nerve function. However, new lower cranial nerve deficits occurred in 2 patients (16.7%) due to surgical removal of the concurrent vagal paraganglioma and scar tissue enclosing the IX and XII nerves. Our refined surgical techniques, including tension-free anterior facial nerve rerouting, sigmoid sinus tunnel-packing, and pushpacking techniques, could be a choice for the treatment of complex jugular paragangliomas to achieve tumor control and cranial nerves preservation. A 2-stage surgery should be applied to minimize the risk of bilateral cranial neuropathies and the influence on cerebral circulation in patients with bilateral paragangliomas. The preoperative endovascular intervention such as coil embolization or internal carotid artery stenting can be employed for the management of paragangliomas with internal carotid artery-associated lesions.

Application of internal carotid artery stent in skull base surgery

Objective: To report the experience of the application of internal carotid artery stent in skull base surgery, and to clarify the important role of internal carotid artery stent in skull base surgery. Methods: A retrospective study of 22 cases with skull base neoplasms implanted with internal carotid artery stents in the Department of ENT Head and Neck Surgery at the Sixth People's Hospital affiliated with Shanghai Jiao Tong University between July 2019 and January 2021 was conducted. Among them, 17 were male and 5 were female, aged between 33 and 75 years. There were 5 cases on the left, 16 cases on the right, and 1 case on both sides. Of these, there were 4 cases of jugular paraganglioma, 1 case of chondrosarcoma in the jugular foramen, 1 case of carotid body paraganglioma, and 16 cases of nasopharyngeal carcinoma after radiotherapy. Results: The degree of internal carotid artery erosion was assessed by computed tomography angiography (CTA), magnetic resonance imaging and digital subtraction angiography (DSA) images in 22 patients before surgery. It was found that the internal carotid artery was involved to varying degrees in all patients, so internal carotid artery stents were implanted before surgery. Tumor tissue was found to surround the internal carotid artery to varying degrees. Total or subtotal tumor resection was performed in all patients, and no intraoperative and postoperative complications occurred. The postoperative follow-up was 5 months to 2 years, and all patients had no complications such as spontaneous bleeding and pseudo aneurysm. There were no signs of stenosis or occlusion of the internal carotid artery stent segment in all cases. Conclusions: For patients with skull base tumors, preoperative imaging indicates the limited involvement of the internal carotid artery, and internal carotid artery stent implantation before surgery is a safe and effective treatment.

T147 Catecholamine-secreting jugular paraganglioma presenting as vocal cord palsy

T147 Catecholamine-secreting jugular paraganglioma presenting as vocal cord palsy

Linear Accelerator Based External Beam Radiotherapy in Glomus Jugulare Tumour: A Retrospective Review from a Tertiary Cancer Hospital in Kenya

Objective: Tumours originating from jugular bulb, carotid bifurcation, Vagus nerve are collectively called Paragangliomas. They are slow growing, essentially benign tumours, but can be detrimental if untreated. There is limited evidence on the effectiveness of fractionated radiotherapy in the management ofs Glomus jugulare tumours. The aim of this study is to determine the efficacy of Linear accelerator based fractionated external beam radiotherapy on unilateral inoperable Glomus jugulare paragangliomas. Method: This is a retrospective analysis of all the 12 cases of inoperable, unilateral Glomus jugulare tumours treated during the period 2011-2016 at a tertiary cancer centre in Kenya. Minimum follow up duration was 3 years. Patient characteristics, disease staging, immediate complications and therapeutic efficacy were analysed from the case files. Results: The 12 patients diagnosed with inoperable Glomus jugulare tumours reported in this period were treated with external beam radiotherapy to a tumour dose of 54 Gy in 30 fractions over a period of 6 weeks using IMRT technique in 6 MV Linear accelerator. 2/3rd of the patients were females in 5th and 6th decade of life. Onset of first symptom to initiation of treatment was found to be 1.7 years. Headache, earache, and tinnitus were the main complaints. No major side effects were recorded during therapy. Mean length of the tumour in its maximum dimension at the time of diagnosis was 4.5 cm. At the end of one-year post therapy, a mean reduction of 6.5 mm in the tumour length was observed, (Range: 0 - 15 mm). Tumour size remained static for a year and thereafter a slow growth pattern of 1mm per year was observed. Conclusion: Fractionated external beam radiotherapy is an effective and non-invasive treatment for advanced, inoperable Glomus jugulare paragangliomas. Clinical stability through tumour control was observed. Though newer radiation techniques like Cyberknife, Proton therapy offer better tumour control, conventional external beam radiotherapy is an effective tool in disease containment in resource limited countries.

Head and Neck Paragangliomas in the Czech Republic: Management at the Otorhinolaryngology Department

Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, comprising only 3% of all head and neck tumors. Early diagnosis forms an integral part of the management of these tumors. The two main aims of any treatment approach are long-term tumor control and minimal cranial nerve morbidity. The scope of this article is to present our case series of HNPGLs to stress most important clinical aspects of their presentation as well as critical issues of their complex management. Thirty patients with suspected HNPGLs were referred to our otorhinolaryngology clinic for surgical consultation between 2016–2020. We assessed the demographical pattern, clinicoradiological correlation, as well as type and outcome of treatment. A total of 42 non-secretory tumors were diagnosed—16.7% were incidental findings and 97% patients had benign tumors. Six patients had multiple tumors. Jugular paragangliomas were the most commonly treated tumors. Tumor control was achieved in nearly 96% of operated patients with minimal cranial nerve morbidity. Surgery is curative in most cases and should be considered as frontline treatment modality in experienced hands for younger patients, hereditary and secretory tumors. Cranial nerve dysfunction associated with tumor encasement is a negative prognostic factor for both surgery and radiotherapy. Multifocal tumors and metastasis are difficult to treat, even with early detection using genetic analysis. Detecting malignancy in HNPGLs is challenging due to the lack of histomorphological criteria; therefore, limited lymph node dissection should be considered, even in the absence of clinical and radiological signs of metastasis in carotid body, vagal, and jugular paragangliomas.

Pulsatile tinnitus as the first manifestation of a jugular paraganglioma

We present the case of a 59 year old male patient with pulsate tinnitus, referred as the first manifestation of a jugular parganglioma. The patient examined at the outpatient ENT Department of our hospital with a left lateral cervical swelling, difficulty in swallowing and pulsatile tinnitus. Tinnitus was the first reported symptom that appeared one month before. The patient had no medical history. The clinical examination showed an asymmetric swelling of the left tonsil, a left vocal cord paralysis, a retrotympanic mass otoscopically and conductive hearing loss in the left ear. The patient underwent a head-and-neck computed tomography that raised the suspicion of a paraganglioma. The magnetic resonance imaging and the magnetic angiography with the administration of a contrast agent set the diagnosis of a jugular paraganglioma. After the tumor embolization, the patient unerwent primary resection of the tumor. This is the first case of a patient with a jugular paraganglioma and pulsatile tinnitus as the first reported symptom.

Facial Paresis and Pulsatile Middle Ear Mass.

Head and neck paragangliomas are uncommon pathologies that present with common symptoms such as pulsatile tinnitus and aural pressure. This article highlights an unusual presentation of a patient with facial paresis who was found to have a jugular paraganglioma. Emphasis is placed on how the otologic examination showed a pulsatile middle ear mass that led to the diagnosis. This case illustrates the importance of maintaining a healthy degree of clinical suspicion when encountering common complaints.

Diameter-Based Volumetric Models May Inadequately Calculate Jugular Paraganglioma Volume Following Sub-Total Resection.

As gross total resection of jugular paragangliomas (JPs) may result in cranial nerve deficits, JPs are increasingly managed with subtotal resection (STR) with postoperative radiological monitoring. However, the validity of commonly used diameter-based models that calculate postoperative volume to determine residual tumor growth is dubious. The purpose of this study was to assess the accuracy of these models compared to manual volumetric slice-by-slice segmentation. A senior neuroradiologist measured volumes via slice-by-slice segmentation of JPs pre- and postoperatively from patients who underwent STR from 2007 to 2019. Volumes from three linear-based models were calculated. Models with absolute percent error (APE) > 20% were considered unsatisfactory based on a common volumetric definition for residual growth. Bland-Altman plots were used to evaluate reproducibility, and Wilcoxon matched-pairs signed rank test evaluated model bias. Twenty-one patients were included. Median postoperative APE exceeded the established 20% threshold for each of the volumetric models as cuboidal, ellipsoidal, and spherical model APE were 63%, 28%, and 27%, respectively. The postoperative cuboidal model had significant systematic bias overestimating volume (p = 0.002) whereas the postoperative ellipsoidal and spherical models lacked systematic bias (p = 0.11 and p = 0.82). Cuboidal, ellipsoidal, and spherical models do not provide accurate assessments of postoperative JP tumor volume and may result in salvage therapies that are unnecessary or inappropriately withheld due to inaccurate assessment of residual tumor growth. While more time-consuming, slice-by-slice segmentation by an experienced neuroradiologist provides a substantially more accurate and precise measurement of tumor volume that may optimize clinical management.

Preoperative embolization of jugular paraganglioma tumors using particles is safe and effective.

Jugular paragangliomas represent a surgical challenge due to their vascularity and proximity to vital neurovascular structures. Preoperative embolization aids in reducing intraoperative blood loss, transfusion requirements, and improves surgical visualization. Several embolization agents have been used. The aim of this study is to evaluate the safety and efficacy of PVA in pre-operative embolization of jugular paragangliomas. A retrospective review of all patients who underwent jugular paraganglioma resection with pre-operative embolization between 2000 and 2020 was performed. Pre-operative data including baseline patient and tumor characteristics were documented. Outcomes of preoperative embolization including extent of devascularization and post-embolization complications were recorded. Early and long-term postoperative outcomes were reported. Twenty-nine patients met study criteria with a median age of 38 years. Average tumor size was 3.4±1.8 cm. The most commonly encountered arterial feeder was the ascending pharyngeal artery followed by the posterior auricular artery. More than 50% reduction in tumor blush was achieved in 25 patients (86.2%). None of the patients experienced new or worsening cranial neuropathy following embolization. Gross total or Near total resection was achieved in 13 patients (44.8%). A STR or NTR was chosen in these patients to preserve cranial nerve function or large vessel integrity. Average intraoperative estimated blood loss was 888 ml, 9 patients (31%) required intra-operative transfusion of blood products. Extent of resection and post-operative complications did not correlate with extent of devascularization. Pre-operative embolization of jugular paraganglioma tumors with PVA particles is an effective strategy with a high safety profile.

Contemporary Management of Jugular Paragangliomas With Neural Preservation.

Management of jugular paragangliomas (PGL) has evolved toward subtotal resection (STR). The purpose of this study is to analyze neural preservation and adjuvant treatment for long-term local control. Retrospective chart review. Tertiary neurotology practice. Adults undergoing surgical treatment of jugular PGL between 2006 and 2019. Patients, disease, and treatment variables were collected retrospectively. Single predictor logistic regression was used to ascertain predictors of regrowth or need for salvage radiation. A total of 41 patients (median age, 47 years; 76% female) were identified. Most patients presented with advanced-stage disease (Glasscock-Jackson stage III-IV = 76%). Subtotal resection (STR) was performed in 32 (78%) patients. Extended STR (type 1) was the most commonly performed conservative procedure (n = 19, 59%). Postoperative new low cranial neuropathy (LCN) involving CN X and XII was rare (n = 3 and n = 1, respectively). Seventeen patients (41%) underwent postsurgical therapy for tumor regrowth or recurrence, including 15 patients who underwent adjuvant (n = 4) or salvage (n = 11) radiation. Overall tumor control of 94.7% was achieved at a mean follow-up of 35 months. All patients treated with combined modality treatment had local control at last follow-up. Logistic regression identified no single predictor for postsurgical radiation treatment or salvage-free survival. Management of jugular PGL with a conservative approach is safe and effective with a low rate of new LCN deficit. Active surveillance of residual tumor with salvage radiation for growth results in excellent long-term tumor control.

In Reply to the Letter to the Editor Regarding “Safety and Efficacy of Primary Mulitsession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

In Reply to the Letter to the Editor Regarding “Safety and Efficacy of Primary Mulitsession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Letter to the Editor “Regarding Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Letter to the Editor “Regarding Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Involvement of the Cochlear Aqueduct by Jugular Paraganglioma Is Associated With Sensorineural Hearing Loss.

The etiology of sensorineural hearing loss (SNHL) in patients with jugular paraganglioma (JP) whose tumors lack inner ear fistulae or vestibulocochlear nerve involvement is unknown. Recent literature has proposed that occlusion of the inferior cochlear vein may be causative. Herein, we assess the association between radiologic involvement of the cochlear aqueduct (CA) and the development of SNHL. Blinded, retrospective review of imaging and audiometry. Tertiary center. Adults with JP. None. Asymmetric SNHL was assessed continuously as the difference in bone conduction pure-tone average (BCPTA) between ears and as a categorical variable (≥15 dB difference at two consecutive frequencies, or a difference in speech discrimination score of ≥15%). Involvement of the CA was considered present if there was evidence of medial T2 fluid signal loss, contrast enhancement, or bony erosion/expansion. Of 30 patients meeting inclusion criteria, 15 (50%) had asymmetric SNHL. CA involvement was observed in 87% of patients with asymmetric SNHL compared with 13% in those with symmetric hearing (p = 0.0001). Univariate analysis demonstrated that age, sex, and tumor volume were not associated with asymmetric SNHL. The median difference in BCPTA between ears in patients with CA involvement was 21.3 dB HL compared to 1.2 dB HL in those without CA involvement (p < 0.0001). Regression analysis demonstrates that enhancement within the CA is associated with a BCPTA difference of 19.4 dB HL (p = 0.0006). Cochlear aqueduct involvement by JP is associated with SNHL in the absence of inner ear fistula, vestibulocochlear nerve involvement, or brainstem compression. Correlation with operative findings or histopathologic evidence of tumor involvement may validate this intriguing imaging finding.