Combined underwater endoscopic and microscopic surgery for tympanic paraganglioma: A case report.

The resection of middle ear paragangliomas can be challenging given their vascular nature and the small volume of the tympanic cavity, particularly when the tumor in the hypotympanum is close or attached to the internal carotid artery (ICA). We performed combined underwater endoscopic and microscopic surgery for a Class B1 middle ear paraganglioma according to the modified Fisch classification. The suspicious bone in the hypotympanum and around the petrous ICA was drilled with underwater endoscopy. The feeding arteries, the caroticotympanic and inferior tympanic arteries, were suctioned and cauterized under microscopy. To the best of our knowledge, no case of middle ear paraganglioma treated with underwater endoscopy has been reported. Underwater endoscopy, providing a clear operative field with blood and bone dust irrigation, is a good indication for middle ear paragangliomas. In contrast, microscopic preparation for unexpected bleeding is important, particularly when the tumor closely extends to vital structures, such as the ICA or the jugular bulb.

Analysis of clinical and pathological characteristics of retroperitoneal paraganglioma and associated prognostic factors.

BACKGROUND AND OBJECTIVES: The aim of this study is to explore the long-term prognostic risk factors associated with patients diagnosed with retroperitoneal paraganglioma (RPGL) and examine their clinical and pathological characteristics. METHODS: Expressions of biomarkers were identified using immunohistochemistry (IHC) and case databases were retrospectively searched. Survival analysis was performed using Kaplan-Meier and Cox risk regression to identify the factors that influence the postoperative progression-free survival of patients with RPGL. RESULTS: A total of 105 patients, most of whom had tumors situated in the paraaortic region, and whose average tumor size was 8.6 cm, were enrolled in this study. The average follow-up duration was 51 months, with a mortality rate of 19% and a recurrence and metastasis rate of 41.9%. Tumors were assessed using the modified Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), and SDHB, S-100, and Ki-67 were stained using IHC in all cases. Out of the total cases examined, negative in SDHB expression were observed in 18.1% of cases, S-100 expression was negative in 36.2% of cases, and endovascular tumor enboluswas present in approximately 25.7% of cases. The results of the univariate analysis indicated that several factors significantly influenced the progression-free survival of patients with PGL as follow: maximum tumor diameter (>5.5 cm), tumor morphological features, tumor grading (modified GAPP score > 6), SDHB negative, S-100 negative, and expression of proliferation index Ki-67 (>3%) (X2 = 4.217-27.420, p < 0.05). The results of the multivariate analysis indicated that negative of S-100 (p = 0.021) and SDHB (p = 0.038), as well as intravascular tumor thrombus (p = 0.047) expression were independent risk factors for progression-free survival in patients. CONCLUSION: RPGL is characterized by diverse biological features and an elevated susceptibility to both recurrence and metastasis. Both SDHB and S-100 can be employed as traditional IHC indicators to predict the metastatic risk of PGL, whereas the tumor histomorphology-endovascular tumor enbolus assists in determining the metastasis risk of RPGL.

[Paragangliomas of the head and neck]. / Paragangliome im Kopf-Hals-Bereich.

Paragangliomas represent a heterogeneous group of rare neuroendocrine tumors with marked variability in symptoms and disease course. Due to the close proximity to neurovascular structures, paragangliomas of the head and neck region can cause a variety of symptoms. To this day, there are no reliable prognostic factors that can predict a potentially malignant course. All patients with newly diagnosed paragangliomas should undergo an early diagnostic workup and regular follow-up examinations in specialized centers. While radical resection was previously regarded as standard treatment for paragangliomas, radiotherapy and active surveillance (watch-and-scan strategy) have become equally important over the years. Low-threshold techniques for molecular pathology analysis of the mutation-specific behavior of paragangliomas are nowadays available.

Two sisters diagnosed with familial paraganglioma syndrome type 1 (FPGL1) and multiple endocrine neoplasia type 2A (MEN2A).

BACKGROUND: In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1). CASE PRESENTATION: After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases. CONCLUSION: To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual.

Jugular Foramen Paragangliomas.

Paragangliomas are the most common tumors at jugular foramen and pose a great surgical challenge. Careful clinical history and physical examination must be performed to adequately evaluate neurological deficits and its chronologic evolution, also to delineate an overview of the patient performance status. Complete imaging evaluation including MRI and CT scans should be performed, and angiography is a must to depict tumor blood supply and sigmoid sinus/internal jugular vein patency. Screening for multifocal paragangliomas is advisable, with a whole-body imaging. Laboratory investigation of endocrine function of the tumor is necessary, and adrenergic tumors may be associated with synchronous lesions. Preoperative prepare with alpha-blockage is advisable in norepinephrine/epinephrine-secreting tumors; however, it is not advisable in exclusively dopamine-secreting neoplasms. Best surgical candidates are young otherwise healthy patients with smaller lesions; however, treatment should be individualized each case. Variations of infratemporal fossa approach are employed depending on extensions of the mass. Regarding facial nerve management, we avoid to expose or reroute it if there is preoperative function preservation and prefer to work around facial canal in way of a fallopian bridge technique. If there is preoperative facial nerve compromise, the mastoid segment of the nerve is exposed, and it may be grafted if invaded or just decompressed. A key point is to preserve the anteromedial wall of internal jugular vein if there is preoperative preservation of lower cranial nerves. Careful multilayer closure is essential to avoid at most cerebrospinal fluid leakage. Residual tumors may be reoperated if growing and presenting mass effect or be candidate for adjuvant stereotactic radiosurgery.

Paraganglioma of the urinary bladder: A case report.

It is very un comm on to discover Paraga ngliomas in the uri nar y bladder. Thes e tu mo ur s origina te from the sympathetic nerves which supp ly chromaffin cells in the bladde r wall. They can be classified as functional or nonfunctional. If functional, the most common presentations are with hypertensive crisis or post-micturition syncope. A si lent pa raganglioma of th e bl adder ca n be easily m isdiagnosed w hich can resu lt in severe pe ri- oper ative morbidity. We pre sent a ca se of a male pati ent who was being m a naged fo r hype rt ension for 2-3 ye ars. He presented at The Indus Hospital, Karachi o n 7th August 2022 with gross painless haematuria. An ultrasound scan revealed an echogenic lesion aris ing from base of the urinar y bladder, wh ic h was trea ted via Transurethral Resection o f Bladde r Tumour (TURBT). Histopathological report revealed Paraganglioma of the Bladder. He was later scheduled for Partial Cystectomy (PC) and has been doing well ever since.

Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report.

For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.

[Analysis of the effect of different facial nerve managements applied to tumor resection in the jugular foramen region].

Objective:To summarize the results of different facial nerve management modalities applied to tumor resection in the jugular foramen region. Methods:The clinical data of 54 patients with tumors in the jugular foramen region who underwent surgery from January 2015 to March 2023 were retrospectively analyzed: 18 males and 36 females; Age ranges from 21 to 67 years, with an average age of 44.4 years; and median follow-up time: 12 months. The House-Brackmann（HB） grading system was applied to assess the patients' facial nerve function before surgery, 1-2 weeks after surgery and at the final follow-up （HBⅠ-Ⅱ grade for good function）: 42 cases with preoperative HB grades Ⅰ-Ⅱ; partial facial nerve transposition（9 cases）, complete facial nerve transposition（28 cases）, and facial nerve excision and re-construction（17 cases） were used, respectively（stage Ⅰor Ⅱ）. Relevant factors affecting postoperative facial nerve function were analyzed. Results:Postoperative pathology confirmed 39 cases of paraganglioma, 9 cases of nerve sheath tumor, 3 cases of meningioma, and 1 case each of fibromucinous sarcoma, chondrosarcoma, and intravascular myofibroma. Facial nerve function after partial facial nerve transposition was HB grade Ⅰ-Ⅱ in 89%（8/9）; after complete facial nerve transposition was HB grade Ⅰ-Ⅱ in 86%（24/28） in 28 cases; after facial nerve severance and reconstruction was HB grade Ⅰ-Ⅱ in 2/7（Stage Ⅰ） and 0/3（Stage Ⅱ）, respectively. Tumor size and surgical approach were correlated with postoperative facial nerve function in patients with facial nerve transposition（P<0.05）. There was no statistically significant difference in facial nerve function after complete and partial facial nerve transposition（P>0.05）. Conclusion:Intraoperative stretching of the facial nerve may be an important factor affecting facial nerve function during surgical treatment of tumors in the jugular venous foramen region; for patients with facial nerve dissection, facial nerve reconstruction should be adopted according to the situation, aiming at the recovery of facial nerve function.

Management of Abdominal Paraganglioma: A Single Center's Experience.

Background and Objectives: Paragangliomas (PGLs) are rare neuroendocrine extra-adrenal tumors that could be secreting mass. The symptoms are the typical triad of paroxysmal headache, hypertension and sweating, but could also be accompanied by symptoms involving multiple organs. Surgery is the gold standard treatment for both PGLs and pheochromocytomas (PHEOs). Material and Methods: We used a computerized endocrine surgery registry to record the demographic and clinical data of 153 patients who underwent surgery for PPGL between 2010 and 2023 at our hospital. Results: Thirteen patients (8.43%) with paragangliomas underwent surgery at our institute. Five patients presented symptomatic syndrome. Preoperative investigations included enhanced abdominal CT (nine patients) and enhanced MRI (seven patients). In cases of suspicious mass, we performed 131I-MIBG scans (two patients) or 68GA-DOTATOC PET-CT scans (11 patients). Laparoscopic approach was used in four cases (30.7%) and abdominal laparotomy in the other nine (69.3%). Biochemical tests were performed on all patients. Conclusions: In this retrospective study, we discuss the multidisciplinary management in our institute of this rare disease, from its challenging diagnosis to the surgical strategy for PGLs. Laparoscopic surgery is the gold standard, but a tailored approach should be adopted for each patient.

Unrecognised paraganglioma of the urinary bladder precipitating hypertensive crisis.

Bladder paragangliomas (bPGLs) account for only 0.06% of all bladder tumours, most commonly presenting with post-micturition syncope and hypertensive crisis. Silent paragangliomas are very rare, and failure to recognise them in the perioperative setting can precipitate a hypertensive crisis in the absence of sufficient alpha-blockade. Here, we describe a case of unrecognised bPGL in a woman with pre-existing hypertension and a single prior episode of haematuria thought to be related to urothelial carcinoma. She was found to have a low-grade non-invasive papillary urothelial carcinoma (potentially the cause of her haematuria) and an unrelated vascular-appearing tumour causing hypertensive crisis and broad complex tachycardia on resection. This was confirmed to be a bPGL on histology for which she underwent definitive management with a partial cystectomy following blood pressure management.

Retroperitoneal venous malformation mimics paraganglioma on triple imaging modalities.

Here, we report a case of a woman in her 50s who was referred for an incidentally discovered lesion anterior to the origin of inferior vena cava suspicious for a paraganglioma following a CT scan for vaginal bleeding. A follow-up 68Ga-DOTATATE PET-CT and MRI of the abdomen reinforced the radiological impression of an extra-adrenal paraganglioma (EAP). The EAP was deemed non-functional given normal urine biogenic amine, supine plasma fractionated metanephrines and chromogranin A levels. The mass was resected laparoscopically without perioperative blockade. Histological examination revealed a venous malformation. Extrahepatic abdominal venous malformations are rare and can be indistinguishable from an EAP on imaging preoperatively. Although benign, the lesion nevertheless warrants excision as it is associated with a risk of haemorrhage.

Functional vagal paraganglioma developing 15 years after resection of a retroperitoneal paraganglioma.

The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.

Laryngeal Paraganglioma-A Case Report.

Background and Objectives: Paragangliomas of the head and neck are rare neuroendocrine tumors originating from the paraganglia, which might be sympathetic or parasympathetic. Laryngeal paragangliomas are the rarest subtype of these tumors, with only 1.41% of all paragangliomas, arising from the supraglottic or subglottic paraganglia of the larynx. The vast majority of them are benign, but there are some cases in which they turn out to be malignant, and the only way to know with certainty the difference between them is when we identify distant metastases. The aim of this article is to share our experience with a rare case of laryngeal paraganglioma and review the clinical characteristics, methods of diagnostic, necessary investigation prior to the operation, and surgical management of this type of tumor. Materials and Methods: We present the case of a 68-year-old female patient, a non-smoker, who accused dysphagia, dysphonia, foreign body sensation, chronic cough, and hoarseness for six months. We performed a tracheostomy prior to biopsy to secure the airways in case of bleeding and then took a few biopsy samples. The histopathological exam revealed the presence of a laryngeal paraganglioma. An enhanced CT scan was performed in order to describe the localization, size, and invasion of the tumor. We also measured the vanillylmandelic acid from the urine to determine if the tumor produced catecholamines alongside a full cardiology and endocrinology examinations. In order to prevent massive bleeding during the operation, chemoembolization was attempted before surgery, but it was unsuccessful due to an anatomical variation of the left superior thyroid artery. She underwent surgery, first through transoral endoscopic microsurgery; however, we decided to undertake an external approach because of poor bleeding control, even though we had ligated both the superior thyroid artery and the external carotid artery, with a thyrotomy and laryngofissure achieving the complete resection of the tumor. Results: The patient was discharged 10 postoperative days later, with the recommendation of introducing food step-by-step from liquids to solids. She was decannulated after 30 days, with no complications regarding breathing, phonation, or deglutition. Twelve months after the surgery, we did not identify any local relapses of distant metastases. Conclusions: Laryngeal paragangliomas are rare neuroendocrine tumors that arise from the laryngeal paraganglia. Surgery is the best treatment option available, and it can be done by either an external approach or by transoral endoscopy. Enhanced CT or MRI, as well as full cardiological and endocrinological evaluation are mandatory prior to the operation. Measuring the catecholamines levels show the if the tumor is secretory. Controlling the bleeding poses the biggest challenge in performing the resection of the tumor, especially when a transoral endoscopic approach is chosen. Further standardized follow-up guidelines are required in the future.

Intraoperative hybrid technique for excision of temporal bone paraganglioma: A case report.

BACKGROUND: Temporal bone paragangliomas are vascularized neoplasms. Although preoperative angioembolization serves as a valuable approach to reduce intraoperative blood loss, it comes with an elevated risk of cranial neuropathies, offers no assurance of complete hemostasis, and precludes real-time adjustments during surgery. METHODS: A 74-year-old patient presented with recurrent episodes of ear bleeding. On examination, a vascular lesion obstructed her external auditory canal. It had the clinical and radiological characteristics of a paraganglioma. Angiography revealed that it had three feeding vessels. RESULTS: The patient was successfully scheduled for hybrid, intraoperative angiography and temporary balloon occlusion of the feeding vessels supplying the lesion instead of preoperative angioembolization. CONCLUSIONS: Utilizing hybrid intraoperative angiography with temporary balloon occlusion during the surgical removal of temporal bone paragangliomas represents an innovative technique that reduces the risk of permanent cranial neuropathies while providing the capacity for real-time adjustments and improved hemostasis.

The Radiosurgery Society Case-Based Discussion of the Management of Head and Neck or Skull Base Paragangliomas with Stereotactic Radiosurgery and Radiotherapy.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used for the treatment of head and neck or skull base paraganglioma for a considerable time, demonstrating promising local control rates and a favorable safety profile compared with surgical approaches. Nevertheless, the choice of treatment must be carefully tailored to each patient's preferences, tumor location, and size, as well as anticipated treatment-related morbidity. This case-based review serves as a practical and concise guide for the use of SRS and FSRT in the management of head and neck or skull base paragangliomas, providing information on the diagnosis, treatment, follow-up considerations, and potential pitfalls.

Novel alternative tools for metastatic pheochromocytomas/paragangliomas prediction.

OBJECTIVE: The existing prediction models for metastasis in pheochromocytomas/paragangliomas (PPGLs) showed high heterogeneity in different centers. Therefore, this study aimed to establish new prediction models integrating multiple variables based on different algorithms. DESIGN AND METHODS: Data of patients with PPGLs undergoing surgical resection at the Peking Union Medical College Hospital from 2007 to 2022 were collected retrospectively. Patients were randomly divided into the training and testing sets in a ratio of 7:3. Subsequently, decision trees, random forest, and logistic models were constructed for metastasis prediction with the training set and Cox models for metastasis-free survival (MFS) prediction with the total population. Additionally, Ki-67 index and tumor size were transformed into categorical variables for adjusting models. The testing set was used to assess the discrimination and calibration of models and the optimal models were visualized as nomograms. Clinical characteristics and MFS were compared between patients with and without risk factors. RESULTS: A total of 198 patients with 59 cases of metastasis were included and classified into the training set (n = 138) and testing set (n = 60). Among all models, the logistic regression model showed the best discrimination for metastasis prediction with an AUC of 0.891 (95% CI, 0.793-0.990), integrating SDHB germline mutations [OR: 96.72 (95% CI, 16.61-940.79)], S-100 (-) [OR: 11.22 (95% CI, 3.04-58.51)], ATRX (-) [OR: 8.42 (95% CI, 2.73-29.24)] and Ki-67 ≥ 3% [OR: 7.98 (95% CI, 2.27-32.24)] evaluated through immunohistochemistry (IHC), and tumor size ≥ 5 cm [OR: 4.59 (95% CI, 1.34-19.13)]. The multivariate Cox model including the above risk factors also showed a high C-index of 0.860 (95% CI, 0.810-0.911) in predicting MFS after surgery. Furthermore, patients with the above risk factors showed a significantly poorer MFS (P ≤ 0.001). CONCLUSIONS: Models established in this study provided alternative and reliable tools for clinicians to predict PPGLs patients' metastasis and MFS. More importantly, this study revealed for the first time that IHC of ATRX could act as an independent predictor of metastasis in PPGLs.

The combination of doxazosin and metyrosine as a preoperative treatment for pheochromocytomas and paragangliomas.

PURPOSE: Preoperative medical management is critical to prevent intraoperative cardiovascular complications in patients with pheochromocytomas and paragangliomas (PPGLs). Initial treatment involves α-adrenergic receptor blockers. However, while the routine use of metyrosine alongside these blockers is not strongly recommended due to a lack of evidence supporting its efficacy and associated safety concerns, there are previous studies on combination therapy with phenoxybenzamine and metyrosine. There are few reports on combination therapy with the selective α1-adrenergic receptor blocker doxazosin. Therefore, we investigated this combination treatment, which theoretically can affect perioperative outcomes in patients with PPGLs. To our knowledge, this is the first such study. METHODS: This retrospective single-center observational study involved 51 patients who underwent surgical resection of PPGLs at Kobe University Hospital between 2014 and 2022. All patients received doxazosin at maximum doses. Fourteen patients received concomitant metyrosine, while 37 received doxazosin alone. Their perioperative outcomes were compared. RESULTS: No severe event, such as acute coronary syndrome, was observed in either group. Intraoperatively, the doxazosin + metyrosine group exhibited a lower median minimum systolic blood pressure (56 [54-60] vs. 68 [59-74] mmHg, P = 0.03) and required lower median remifentanil (P = 0.04) and diltiazem (P = 0.02) doses than the doxazosin-alone group. CONCLUSION: The combination of metyrosine and doxazosin as a preoperative treatment for PPGLs affects intraoperative circulatory hemodynamics, such as a reduced occurrence of blood pressure elevation during surgery. Further research is necessary to identify patients who will benefit most from this combination treatment.

Cauda equina neuroendocrine tumors: A single institutional imaging review of cases over two decades.

Cauda Equina Neuroendocrine Tumors (CE-NET), previously referred to as paragangliomas are a rare subset of spinal tumors, with limited data on imaging. Herein, we present a retrospective review of clinical and imaging findings of CE-NETs in ten patients who were evaluated at our institution over the past two decades. All patients had well-defined intradural lesions in the lumbar spine which demonstrated slow growth. A review of imaging findings revealed the presence of an eccentric vascular pedicle along the dorsal aspect of the tumor in 8 of the 10 patients (eccentric vessel sign), a distinctive finding that has not previously been reported with this tumor and may help improve the accuracy of imaging-based diagnosis. In all cases, a gross-total resection was performed, with resolution of symptoms in most of the cases.