Paragangliomas of the head and neck.

Paragangliomas are rare neuroendocrine tumors that can be found from the skull base to the pelvis. Head and neck paragangliomas have been historically treated with surgery. However, surgical resection adds risk of injury to vascular structures and cranial nerves that can lead to morbidity such as hoarseness, dysarthria, dysphagia, or aspiration. Recently, improved understanding of the behavior of these tumors and increasing experience in non-surgical treatments, such as observation and radiation therapy, have changed the paradigms of management of this entity. Multiple series now show a trend toward a more conservative management, with a higher percentage of patients being observed or treated with radiotherapy. Several factors should be taken into consideration when deciding the most appropriate treatment for head and neck paragangliomas, starting by differentiating carotid body tumors from non-carotid body tumors. In general, surgical resection is normally recommended for carotid body tumors as the complications from treatment are usually minimal. In contrast, for non-carotid body tumors, surgery is often associated with significant functional impairment due to cranial nerve paralysis. As such, non-surgical treatment is now usually recommended for this subset of head and neck paragangliomas. In young patients with no comorbidities and a small to medium carotid body tumors, surgery should be considered. Moreover, surgery should be offered for secreting tumors, malignant tumors, tumors with rapid growth or increase in symptomatology, and when radiotherapy cannot be performed. Conversely, conservative management with active surveillance or radiotherapy can be offered in the remaining cases in order to avoid unnecessary morbidity while still providing acceptable tumor control.

Glomuvenous malformations: dual PDL-Nd:YAG laser approach.

Glomuvenous malformations are uncommon simple vascular malformations that might be present at birth or appear during childhood that have been classically classified as a subtype of venous malformations. Sclerotherapy and surgery have been used in the past as treatments for this condition although with disappointing results in large glomangiomas. The treatment of these lesions has still not been standardized. We conducted a retrospective study of 17 patients treated with dual wavelength PDL-Nd:YAG. The majority of the patients experience a reduction of at least a 60% in their glomuvenous malformations. Treatment was well-tolerated, and adverse effects were rare.

Radiotherapy for benign head and neck paragangliomas: a 45-year experience.

BACKGROUND: Paragangliomas of the head and neck are rare, slow-growing, generally benign tumors of neuroendocrine cells associated with the peripheral nervous system that commonly involve the carotid body, jugular bulb, vagal ganglia, and temporal bone. Treatment options include surgery, radiotherapy (RT), stereotactic radiosurgery (SRS), and observation. This article briefly reviews our 45-year institutional experience treating this neoplasm with RT. METHODS: From January 1968 through March 2011, 131 patients with 156 benign paragangliomas of the temporal bone, carotid body, jugular bulb, or glomus vagale were treated with RT at a median dose of 45 Gy in 25 fractions. The mean and median follow-up times were 11.5 years and 8.7 years, respectively. RESULTS: Five tumors (3.2%) recurred locally after RT, all within 10 years of treatment. The overall local control rates at 5 and 10 years were 99% and 96%, respectively. The cause-specific survival rates at 5 and 10 years were 98% and 97%, respectively. The distant-metastasis free survival rates at 5 and 10 years were 99% and 99%, respectively. The overall survival rates at 5 and 10 years were 91% and 72%, respectively. There were no severe complications. CONCLUSION: RT for benign head and neck paragangliomas is a safe and efficacious treatment associated with minimal morbidity. Surgery is reserved for patients in good health whose risk of associated morbidity is low. SRS may be suitable for patients with skull base tumors <3 cm where RT is logistically unsuitable. Observation is a reasonable option for asymptomatic patients with a limited life expectancy.

Experiences in the treatment of patients with multiple head and neck paragangliomas.

PURPOSE: To analyze treatment results in the multidisciplinary management of patients with multiple head and neck paragangliomas (HNPs). METHODS: Retrospective analysis including all patients with multiple HNPs (VP, vagal paraganglioma; JTP, jugulotympanic paraganglioma; CBT, carotid body tumor) treated between 2000 and 2013 at a tertiary referral center. RESULTS: Ten patients (three men, seven women) had 25 HNPs (two VPs, eight JTPs, and 15 CBTs). The age range at diagnosis was 31-71 years (mean 40.9 years, median 37 years). Nine tumors (four CBTs, three JTPs, two VPs) were treated only with stereotactic radiotherapy (SRT; 50.4-56Gy, mean 55.3Gy) or in one case intensity-modulated radiotherapy (60 Gy). Nine tumors were treated with surgery alone (eight CBTs, one JTP) and three JTPs with subtotal surgery combined with adjuvant SRT. A "wait and scan" strategy was used in three cases (two CBTs, one JTP). The mean follow-up period was 4.3 years (range 0.1-13 years, median 4 years). The rate of tumor control with surgery and/or SRT was 100% (21/21). One patient with a wait-and-scan strategy for CBT had slow asymptomatic progression during a 13-year follow-up. CONCLUSIONS: The treatment results in this series of patients with multiple HNPs show that a very high rate of long-term tumor control with low morbidity can be achieved using tailored and individualized approaches. All of the different treatment strategies available should be discussed with the patient. In particular, the treatment should involve a multidisciplinary team of experts in the fields of nuclear medicine, genetics, pathology, radiology, radio-oncology, and surgery.

Malignant pheochromocytoma and paraganglioma: a population level analysis of long-term survival over two decades.

BACKGROUND AND OBJECTIVES: Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare tumors. Aims of this study were to describe and to compare demographic, clinical, pathologic, and survival characteristics of malignant PHEO and PGL. METHODS: Patients were identified in SEER, 1988-2009. Analyses included chi-square, ANOVA, Kaplan-Meier, and Cox proportional hazard regression. RESULTS: Gender distribution and mean age were similar for PHEO and PGL. Surgery was performed in 74.3% of PHEO and 78.9% of PGL; external beam radiation was administered in 8.0% of PHEO and 28.1% of PGL (P < 0.001). Compared to PGL, PHEO were larger (mean size 7.7 vs. 4.5 cm PGL, P = 0.001) and more were SEER-staged as localized (17.3% vs. 49.6%, respectively, P < 0.001). PGLs were more often located in the trunk than in the head/neck (53.8% vs. 38.0%, P < 0.001). PHEO had lower overall and disease-specific survival than PGL (54.0% and 73.5% vs. 73.3% and 80.5% for PGL, respectively, P < 0.001 and P = 0.118). Independent factors associated with mortality for PHEO included not undergoing surgery and metastases at diagnosis; for PGL, these were age 61-75 years, size ≥5 cm, and presenting with metastases. CONCLUSIONS: Malignant PHEO has a more aggressive course than malignant PGL; long-term survival has not improved over the last two decades. Multi-institutional efforts should be pursued to seek novel treatments.

Hereditary paraganglioma syndrome associated with SDHD gene mutations: a patient with multicentric presentation treated with radiotherapy. Case report.

INTRODUCTION: Extra-adrenal paragangliomas are rare tumors arising from neuroendocrine cells. Sporadic and hereditary forms have been recognized. Among the latter, the PGL1 and PGL4 syndromes are associated with a high risk of multiple localizations. The treatment of choice for paragangliomas is surgical resection, but in some cases surgery can be difficult due to particular or multiple tumor sites or may result in severe neurological deficits. In such cases radiotherapy can be an effective alternative. In this paper we describe the case of a patient affected by hereditary paraganglioma syndrome with multicentric presentation who was treated at our center by external radiotherapy. CASE REPORT: A 55-year-old man presented in April 2008 with multiple paragangliomas: one in the left pontocerebellar angle, two in the middle neck, one mediastinal paraaortic mass, and an abdominal paraaortic lesion. The left pontocerebellar and mediastinal tumors were treated with three-dimensional conformal radiotherapy (3D-CRT) at total doses of 50.40 Gy and 55.80 Gy, respectively. The neck lesions were treated with intensity-modulated radiotherapy (IMRT) at a total dose of 55.80 Gy. The abdominal paraaortic lesion was surgically resected. RESULTS: No severe acute or late toxicity as evaluated with the EORTC-RTOG scale was observed. Fourteen months after the end of radiotherapy a whole body CT scan showed that the tumor lesions were stable in size and in their relations to contiguous structures. The arterial pressure was controlled by medical therapy and urine catecholamine levels were within the normal range. CONCLUSIONS: We believe that in patients affected by unresectable paragangliomas radiotherapy is a safe and effective alternative to surgery. The use of high-dose conformity techniques such as 3D-CRT and IMRT will allow higher local control rates with relatively few side effects thanks to the possibility of dose escalation and reduction of the amount of irradiated healthy tissues.

Multidisciplinary approach in the treatment of malignant paraganglioma of the glomus vagale: a case report.

Malignant paraganglioma of the glomus vagale is a rare tumor entity originating from paraganglia or glomus cells. It typically affects middle age. It differs from benign paraganglioma because of its rapid growth and more aggressive clinical behavior. We report the case of a 40-year-old man presenting with a 5 cm lesion in the upper right cervical region detected by computed tomography (CT) and magnetic resonance imaging (MRI), which also showed enlargement of ipsilateral spinal and jugulodigastric lymph nodes with contrast enhancement. Clinical manifestations at diagnosis included a partial neurological deficit involving the right cranial nerves X, XI and XII. Tumor vascularization was assessed by digital angiography. The tumor mass was entirely removed by a right cervical approach with en-bloc resection with the regional lymph nodes. Histopathological examination showed a paraganglioma with cellular pleomorphism, necrotic microfoci, perineural infiltration and angiogenesis. Massive metastases in two of three jugulodigastric and one spinal lymph nodes on the right side were also detected. Postoperative workup included MRI, positron emission tomography (PET)/CT, meta-iodine-benzyl-guanidine (MIBG) scan, liver ultrasound and chest radiography. Subsequently, the patient underwent conformal radiotherapy with concomitant cisplatin administration. At the last clinical and radiological follow-up examination 5 years after completion of treatment, the patient was free of tumor recurrence. The integrated treatment by surgery and chemoradiation was feasible and effective in the management of this rare case of malignant paraganglioma of the glomus vagale. Multicenter studies should be done to increase the knowledge of tumor presentation and natural history and to analyze the possible treatment options.

[Nonchromaffin paragangliomas (chemodectoma) of the middle ear in the material of the ENT Department Medical University of Gdansk]. / Przyzwojaki niechromochlonne (chemodectoma) ucha srodkowego w materiale Kliniki Gdanskiej.

INTRODUCTION: Nonchromaffin paraganglioma (chemodectoma) is the most common neoplasm of the middle ear. The diagnosis and treatment is one of the most challenging in otolaryngology. THE AIM OF THE STUDY: was clinical and epidemiological analysis of patients with nonchromaffin paraganglioma of the middle ear. MATERIAL AND METHODS: The material consisted of 13 patients (10 females, 3 males), age 19-62 years, treated for paraganglioma of the middle ear in the ENT Department Medical University of Gdansk between 1968 and 2009. We analyzed the symptoms and results of additional diagnostic tests necessary to establish the diagnosis. RESULTS: We have diagnosed 12 cases of benign chemodectoma (92.3%) and 1 case of chemodectoma malignum (7.7%). The surgical treatment was applied in 6 patients (46.1%), 4 patients (30.8%) received complementary radiotherapy and 3 patients (23.1%) were treated only with radiotherapy. CONCLUSIONS: The diagnosis of paragangliomas of the ear is difficult and should be based on clinical data, audiometric tests, CT, MRI and histological examination. Surgical treatment of paragangliomas is limited to early stages of the disease. The results of the research show that the best therapeutic method in advanced cases is surgical treatment with complementary radiotherapy.

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

An 11-year-old female French Bulldog was presented with a mass at the base of the heart, detected by X-ray and echocardiography. Clinical abnormality included abdominal retention by ascites. Radiation therapy was performed for 5 weeks. The mass volume didn't change during the radiotherapy. The condition became worse and the dog died 6 months after the initial presentation and necropsy was performed. Grossly, the mass, 12.5 × 6.5 × 6.0 cm in size, was found at the base of the heart. Histopathological examination revealed that cardiac mass was composed of alveolar, bundle and diffuse proliferation of neoplastic cells. Most of the neoplastic cells showed a spindle morphology; in some areas small round or polyhedral neoplastic cells were observed. Occasional cartilage metaplasia was seen multifocal in the mass, and it was surrounded by the sarcomatoid proliferation. Electron microscopy revealed a few neuroendocrine granules in the cytoplasm of spindle and polyhedral neoplastic cells. Metastatic cells in the lungs which had not irradiated demonstrated typical morphology of aortic body tumors. Based on these findings, the case was diagnosed as an aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia.

Radiotherapy for benign head and neck paragangliomas.

PURPOSE: To update our experience treating benign head-and-neck paragangliomas (PGs) with radiotherapy (RT). METHODS: A total of 149 patients with 176 PGs received curative-intent RT; 126 received RT to 1 PG and 23 to 2 or more PGs. The most common dose fractionation schedule was 45 Gy/25 once-daily fractions/5 weeks which was used to treat 147 PGs (83.5%) in 123 patients (82.6%). Patients were followed with physical examination and CT/MRI. The median follow-up for all patients was 10.6 years (range, 0.2-50.4 years); the median follow-up for surviving patients was 11.1 years (range, 0.2-50.4). RESULTS: The 5-year, 10-year, and 15-year outcomes were: local control, 99%, 96%, and 95%; distant metastasis-free survival, 99%, 99%, and 99%; cause-specific survival, 98%, 98%, and 98%; and overall survival, 90%, 75%, and 64%, respectively. No patient developed a moderate or severe complication, or a radiation-induced second tumor or malignant transformation of the benign PG. CONCLUSION: RT is an effective treatment for head-and-neck PGs with a low risk of complications.

Stereotactic body radiation therapy for heart-base tumors in six dogs.

INTRODUCTION: Heart-base tumors are increasingly treated with radiotherapy, yet safety and efficacy are incompletely understood. This case series describes outcomes after stereotactic body radiation therapy (SBRT) for presumed chemodectoma. ANIMALS: Six pet dogs. METHODS: A retrospective study was performed, including dogs with a clinical diagnosis of chemodectoma and treatment with three-fraction SBRT (30 Gy total). RESULTS: Heart-base tumors, presumed or confirmed to be chemodectomas, were diagnosed via histopathology or imaging. Treatment was delivered with intensity modulation and cone-beam computed tomography-based image guidance, using a linear accelerator and robotic couchtop. Intrafraction respiratory motion was managed with either neuromuscular blockade and breath-holding (n = 3) or high-frequency jet ventilation (n = 3); mean total anesthesia times for each technique were 165 and 91 min per fraction, respectively. Four tumors were assessed after SBRT; tumor volume decreased by 30-76%. Possible treatment-related complications included cough, tachyarrhythmias, and congestive heart failure. Two dogs experienced sudden death 150 and 294 days after SBRT. Three dogs are alive 408-751 days after SBRT, and one dog died of unrelated disease 1,228 days after SBRT. CONCLUSIONS: This SBRT protocol resulted in rapid tumor volume reduction, and jet ventilation effectively reduced treatment delivery times. However, cardiac arrhythmias (presumably tumor or treatment associated) and sudden death were common after SBRT. Therefore, SBRT is a potentially useful treatment but may not be appropriate for dogs with incidentally diagnosed, slowly growing tumors, which are not causing cardiovascular disturbances. Longer follow-up and larger case numbers are needed to more completely define safety and impact of treatment on long-term survivability.

Four generations of SDHB-related disease: complexities in management.

SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4), which is associated with predominantly extra-adrenal disease and has high metastatic rates. Despite the lower penetrance rates in carriers of SDHB mutations compared to mutations in other paraganglioma susceptibility genes, the aggressive behavior of SDHB-linked disease warrants intensive surveillance to identify and resect tumors early. Patients with similar SDHB genotypes in whom the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors can arise in various locations, and management can be considerably different, depending on tumor site and pathology. We present a case series of five SDHB mutation carriers over four generations from the same family to illustrate the complexities in management.

Less common indications for stereotactic radiosurgery or fractionated radiotherapy for patients with benign brain tumors.

Microsurgical resection remains the mainstay of treatment for truly benign brain tumors that can be safely resected because of the potential for permanent cure with most histologic findings, including most of the histologic findings discussed in this article. Physicians must keep in mind the indolent nature of many of the benign brain tumors and realize that many patients are likely to live out normal life spans if tumor control is achieved. Therefore, it is not sufficient simply to consider local tumor control rates and short-term toxicity risks when choosing between surgery, stereotactic radiosurgery, and fractionated radiotherapy. Patients need to be apprised of all therapeutic options and to make their decisions with all information required to evaluate the risks and benefits. For benign brain tumors, these decisions may have consequences that last for decades.

Management of multicentric paragangliomas: Review of 24 patients with 60 tumors.

BACKGROUND: The purpose of this study was to reflect our experience in the management of multicentric head and neck paragangliomas, including genetic study and counseling, diagnostic tools, types of treatment, and the need for monitoring. METHODS: A retrospective review of 24 patients with multicentric paraganglioma, including a total of 60 paragangliomas: 37 carotid body tumors, 13 jugulotympanic paragangliomas, and 10 vagal paragangliomas. RESULTS: A total of 26 surgical procedures were performed, including the resection of 36 paragangliomas. Four tumors were pending surgery at the time of this review. Radiotherapy was administered in 7 patients with 9 tumors. A "wait-and-scan" policy with periodic MRI imaging tests was instituted for 9 patients with 12 paragangliomas. CONCLUSION: The knowledge of the different modalities of management is especially relevant in patients with multicentric paragangliomas. In every case, benefits and potential risks of all treatment options may be taken into consideration for every individual patient.

Radiation therapy, an important mode of treatment for head and neck chemodectomas.

Between 1970 and 1990, 22 patients with 44 chemodectomas in the head and neck region were seen at the Netherlands Cancer Institute in Amsterdam. All patients were treated with radiation therapy (17 patients with radiation therapy only and 5 in combination with surgery). One patient was treated two times with an interval of 12 years at each side of the neck. Standard dose was 50 Gy in 25 fractions over 5 weeks. A radiation portal arrangement with oblique fields with paired wedges was used most frequently. The follow-up period ranged from 1 year to 20 years. Two recurrences at 2 and 9 years after treatment were observed. The actuarial local control rate was 88% at 10 years follow-up. Comparison of the results of surgery and radiotherapy demonstrates that radiation therapy is an effective treatment modality without mutilation or severe late morbidity for chemodectomas in the head and neck region.

Twenty year experience with radiation therapy for temporal bone chemodectomas.

Between 1965 and 1984, 20 patients with chemodectomas of the temporal bone were seen at The Methodist Hospital in Houston, Texas and at the Cancer Therapy and Research Center in San Antonio, Texas, Ten patients were treated with radiation therapy alone, seven with surgery and post-operative radiation, one with pre-operative radiation, and two with radiation therapy following surgical recurrence. Most patients had advanced tumors at presentation. Radiation doses ranged from 22.5 Gy to 50.0 Gy. The most frequent dose was 45.0 Gy, given in 225 cGy fractions, 9.0 Gy per week. The most common radiation portal arrangement was oblique fields with paired wedges. There were no local failures or significant radiation induced complications among the patients with benign chemodectomas. The follow-up period ranged from 3 to 23 years (mean 11 years). Only one patient developed systemic metastases and progression of the primary temporal bone chemodectoma. These results and a review of the literature demonstrate that radiation therapy alone is a safe and effective treatment modality for chemodectomas of the temporal bone.

Chemodectoma of the carotid body and ganglion nodosum treated with radiation therapy.

A total of six chemodectomas of the carotid body or ganglion nodosum in four patients were treated with radiation therapy. The purpose of this paper is to present the results of treatment in these patients. One patient experienced complete regression of her bilateral carotid body tumors over the ensuing 2.5 years and the other 3 patients have had no evidence of disease progression of their chemodectomas for 2, 3, and 4.5 years, respectively.

Chemodectoma of the temporal bone: a comparison of surgical and radiotherapeutic results.

Between January 1950 and December 1981, 32 patients with chemodectomas of the temporal bone were treated at the University of Iowa Hospitals and Clinics. Thirteen patients were treated with surgery alone, 15 with radiation therapy alone, one with preoperative radiation therapy and surgery, and three with surgery and postoperative radiation therapy. In general, the patients treated with radiotherapy alone or combined therapy (radiotherapy group) had more advanced tumors than those treated with surgery alone (surgery group). For the surgery group, the initial local control rate was 46% and the ultimate local control rate 84% following salvage with additional surgery, 31% developed complications, and 78% survived 10 years. For the radiotherapy group, 84% had local tumor control, 11% developed complications, and 77% survived 10 years. These results demonstrate that radiation therapy is an effective treatment modality for chemodectomas of the temporal bone.

Fractionated stereotactic conformal radiotherapy in the management of large chemodectomas of the skull base.

PURPOSE: To evaluate the role of fractionated stereotactic conformal radiotherapy (FSRT) as a noninvasive method in the management of large chemodectomas of the skull base. METHODS AND MATERIALS: Twenty-two patients with chemodectomas of the skull base were treated with FSRT at our institution. Ten patients received primary RT, and 12 patients were treated for recurrent or progressive disease after primary surgery (8 patients) or embolization (4 patients). The median total dose was 57.6 Gy, with a median of 1.8 Gy/fraction. The median target volume was 71.8 cm3 (range, 10.5-212.2 cm3). The most common symptoms at the initial diagnosis were pulsatile tinnitus (16 patients), hearing loss (14 patients), and balance disturbance (14 patients). Twelve patients had additional cranial nerve deficits. RESULTS: The median follow-up was 5.7 years (range, 19-177 months). The actuarial overall survival rate was 89.5% at 5 and 10 years. The actuarial local control rate was 90.4% at 5 and 10 years. Seven patients (32%) had a partial response and 13 (59%) had stable disease of the irradiated chemodectoma. Two symptomatic patients developed recurrence after 19 and 32 months. Neurologic dysfunction improved or completely resolved in 59% and stabilized in 32%; 9% of patients experienced impairment of preexisting neurologic dysfunction. No patient developed new neurologic deficits after FSRT. RT was interrupted in 1 patient because of a maxillary bone abscess. In all other patients, no acute or late adverse reactions greater than Common Toxicity Criteria Grade 2 were seen. CONCLUSION: Fractionated stereotactic conformal radiotherapy is an effective and well-tolerated noninvasive treatment for chemodectomas, with excellent tumor control rates and a low risk of morbidity. It is an option for patients at greater risk of microsurgical resection or with residual and recurrent tumors.