Malignant carotid paraganglioma. A case report

The most common sites of paragangliomas occurring in the head and neck region are the carotid body and vagal glomus. The clinical course of carotid body paragangliomas is characterized by two modes of development: locoregional growth and distant metastatic dissemination. Few cases of malignant carotid body paraganglioma have been reported in the literature. We report a case managed in the ENT Department of Grenoble university hospital in 1993. A 53-year-old woman presented a bilateral functional (dopamine secretion) carotid tumor, stage II on the right side and stage I on the left side according to the Shamblin classification. Two successive excisions with complete resection were performed without complication. Two years after the second surgical excision, bone and liver metastases were diagnosed and visualized with a Ostreoscan scintigraphy. Clinical course was rapidly unfavorable and the patient died a few weeks later. Malignant forms of carotid paraganglioma are very uncommon and there is no cellular or histological appearance significantly contributing to the diagnosis of malignancy. Clinical findings are the most reliable criteria for malignancy, with the development of distant metastases usually after about 9 years. Long follow-up is essential. Histology in needed to establish the diagnosis of metastasis. A histology specimen may not be possible for a functional paraganglioma. In this case scintigraphy can provide the diagnosis. Malignant forms are more frequent in case of functional paraganglioma, more particularly in case of dopamine secretion.     

Malignant pheochromocytoma. A case report and comments on a rare pathology

Pheochromocytomas and functioning paragangliomas are rare tumors arising from the primitive neural crest, and found in the adrenal medulla or elsewhere within the sympathetic paraganglion axis. Clinical symptoms are related to catecholamine production or less frequently to dopamine or other neuropeptides secretion. Malignant pheochromocytomas are very rare tumors comprising between 5-35%, but this value is uncertain because the usual criteria for malignancy, such as mitotic activity, nuclear pleomorphism, are not suitable to discern benign from malignant pheochromocytomas. A specific diagnosis of malignancy requires evidence of invasion of the adjacent organs and the occurrence of metastases. Personal experience is presented with 92 patients affected by: adrenal pheochromocytomas (51 cases), cervical paragangliomas (32 cases), and extra-adrenal paragangliomas (9 cases). Malignant forms were observed in a 23-year-old young woman affected by malignant pheochromocytoma with lymphatic para-aortic metastases (1.9%), and in 2 patients affected by cervical paragangliomas (1 CBT, 1 VBT) with lymph nodal metastases. Careful follow-up of all patients with measurement of the urinary catecholamine is necessary to detect metachronous neoplasm and later metastases, identified with RMN and 131I-MIBG scintiscan.     

Cervical paragangliomas-tumor control and long-term functional results after surgery.

Objective: To report long-term functional results of the surgical treatment of cervical paragangliomas. Patients and Methods: A retrospective review of 22 patients with 34 head and neck paragangliomas of which 27 were resected between 1981 and 2004. Of these, 16 were carotid body tumors and 11 were vagal paragangliomas. There were 13 women and 9 men with an average age of 48.6 years (range, 26 to 75 years; median, 49 years) and the mean follow-up period was 82 months (range, 3 to 184 months; median, 61 months). Results: There were 13 solitary tumors of which 5 were carotid body tumors and 8 vagal paragangliomas. Multiple head and neck paragangliomas were seen in 9 patients (41%). The incidence of associated multiple tumors was 64.3% for carotid body tumors and 38.5% for vagal paragangliomas. Complete tumor resection was achieved in all but 1 patient in whom a small intradural residual vagal paraganglioma had to be left. The internal carotid artery was preserved in all carotid body tumor resections. Lower cranial nerve deficits were sustained in 1 carotid body tumor resection only, but in all cases with multiple tumors. All patients with vagal paragangliomas had or developed a vagal nerve paralysis. In 4 cases minor complications developed postoperatively. No recurrent tumors were seen during the follow-up period. Conclusions: Even in large head and neck paragangliomas surgical treatment provides excellent tumor control with low postoperative morbidity. A wait-and-scan policy may be more appropriate for those patients with multiple tumors, advanced age, or high operative risk and for those whose tumors have recurred following radiotherapy.     

Sporadic Paraganglioma

Paraganglioma are rare chromaffin cell tumors that develop from the neural crest cells. Parasympathetic ganglia-derived tumors are found almost exclusively in the neck and skull base and typically do not secrete catecholamines. In contrast, most sympathetic ganglia-derived tumors are found in the abdomen and produce an excess of catecholamines. Those grow within the adrenal medulla and are known as pheochromocytoma. Other sympathetic paragangliomas are also known as extra-adrenal pheochromocytomas. They arise outside of the adrenal gland and can be found anywhere along the sympathetic chain from the base of the skull and neck (5% of cases) to the bladder and prostate gland (10%). We use the term paraganglioma to refer to extra-adrenal tumors and pheochromocytoma to refer to intra-adrenal tumors. The majority of sympathetic paragangliomas are familial, commonly associated with the SDHB and SDHD gene mutations. Many are malignant. Medical management of catecholamine-secreting paraganglioma is the same as for pheochromocytoma. Favorably located abdominal paragangliomas can be safely resected laparoscopically, but the operation is technically more challenging than that for adrenalectomy. Presented at the International Association of Endocrine Surgeons (IAES) Symposium: Paraganglioma, extra-adrenal, and malignant pheochromocytoma, 29 August 2007, Montreal, Canada.     

Carotid body paraganglioma: review and surgical management

The term paraganglia best defines the spread in the body of clusters of cells with histological and cytochemical characteristics of neuroendocrine cells originating from the neural crest, with either sympathetic or parasympathetic function. Carotid body hyperplasia is associated with long-standing hypoxia as in native inhabitants in high altitude or in patients with chronic pneumonopathies, while carotid body paraganglioma is a rare parasympathetic tumor with significant morbidity. Tumor extension per se, associated cranial nerve involvement, and the estimated 3-10% malignant potential, particularly at a young age, make early diagnosis and treatment of carotid body paraganglioma mandatory. Biopsy should be avoided, because of the accompanying incidence of hemorrhage, while it is essential in all cases to investigate both sides of the neck to exclude bilateral tumors. The modalities of therapy include preoperative embolization, preoperative and postoperative radiation with ambiguous results of both, and complete surgical removal which constitutes the definite therapy. The current stroke rate is less than 5%. The histological appearance of a carotid body paraganglioma is not a reliable guide to its propensity for malignant behavior and recurrences are most likely to appear in patients who have multiple paragangliomas or a family history of carotid body paraganglioma.     

Laryngeal paraganglioma in a patient with multiple head and neck paragangliomas.

Paragangliomas of the larynx are rare neuroendocrine tumors, with fewer than 70 cases reported in the literature. 1 Typically, laryngeal paragangliomas are not found in patients with multicentric or familial paragangliomas. Only 1 case of laryngeal paraganglioma has been reported in a patient with a synchronous lesion elsewhere (carotid body tumor). 2 We report an additional case of a patient with a laryngeal and multiple other paragangliomas.     

The current surgical management of carotid body paragangliomas.

To determine if recent trends in evaluation and therapy have contributed to the successful surgical management of carotid body paragangliomas, we reviewed our experience over the past decade. Nineteen carotid body paragangliomas were identified in 17 patients. Eleven patients underwent complete, preoperative embolization of their afferent arteries with one complication. Calculated carotid body paragangliomas surface areas did not differ between the embolized 64.6 +/- 43.3 cm2 and nonembolized 63.0 +/- 57.9 cm2 lesions. Intraoperative blood loss was lower (p = 0.02) in the patients treated with embolization (372 +/- 213 ml) compared with their cohorts (609 +/- 564 ml). However, the operative times were equivalent 4.1 hours versus 4.5 hours in both groups. Intraoperative electroencephalographic (EEG) monitoring was used in 10 patients; in one patient the EEG indicated intraoperative thrombosis of the carotid artery, which was successfully treated by thrombectomy without complications. Two patients required carotid bifurcation resection and vascular reconstruction to remove the entire tumor; a late stroke manifested by contralateral hand weakness developed in one of these patients. The incidence of cranial nerve injury was low at 16%, with one transient ramus mandibularis paresis and two instances of vocal cord dysfunction. Two additional patients had a postoperative Horner's syndrome. We conclude that by diminishing intraoperative blood loss through complete and careful preoperative embolization and use of intraoperative EEG monitoring along with careful surgical technique, the complications associated with this challenging operation are facilitated and diminished.     

Bilateral carotid body tumor resection in a female patient

IntroductionCarotid body tumors also called carotid paragangliomas are rare neuroendocrine neoplasms derived from neural crest cells, approximately 3% of all paragangliomas occur in the head and neck area (Xiao and She, 2015); although they represent 65% of the head and neck paragangliomas (Georgiadis et al., 2008).Presentation of caseWe present the therapeutic management of a 65-year-old woman with bilateral carotid body tumors. The patient presented to medical clinic for unrelated signs and symptoms of weight loss, dyspepsia, and epigastric pain. Physical examination showed bilateral non-tender neck masses for which imaging studies were ordered resulting in the diagnosis of bilateral carotid tumor. Surgical resection was staged with one week of distance between each tumor resection.DiscussionCarotid Body Tumors can arise from the paraganglia located within the adventitia of the medial aspect of the carotid bifurcation.Resection is the only curative treatment. Carotid body tumors resection represents a special challenge due to potential neurovascular complications.ConclusionsSurgical resection of carotid body tumors represents a special challenge to the surgeon because of the complex anatomical location of the tumor, including close relationship with the cranial nerves, involvement of the carotid vessels and large vascularization of the tumor. With the advance of diagnosis and improvement in surgical techniques as well as the understanding of biological behavior of tumors, surgical treatment has become a safer alternative for treating these tumors.     

Familial multiple cervical paragangliomas: report of a kindred and review of the literature

Heredofamilial paragangliomas account for less than 10% of those arising in the head and neck. Multiplicity, multicentricity, and bilaterality is roughly three times more common than in the spontaneous variety. Not unlike other hereditary neuroendocrine tumor syndromes, familial paragangliomas appear to follow an autosomal dominant transmission, with variable penetrance and expressivity. This article describes a surgical experience with nine bilateral, multicentric cervical paragangliomas (7 carotid body, 1 vagal, and 1 sympathetic) occurring in four siblings less than 35 years of age. The literature on familial paragangliomas of the head and neck is reviewed. The postulated genetic mechanisms accounting for these and other hereditary tumors are discussed. The clinical and surgical aspects of spontaneous and familial paragangliomas are compared.     

Familial carotid body paragangliomas and sensorineural hearing-loss: a new syndrome

BACKGROUND: Carotid body paragangliomas are rare tumors that are sometimes familial, the transmission of which is thought to be by genomic imprinting. We have treated a family who exhibited co-inheritance of carotid body paraganglioma and sensorineural hearing-loss, a relationship that has not been previously reported. METHODS: We studied a large Australian family who exhibited familial carotid body paragangliomas, many of whose members also suffered tinnitus or hearing-loss. This relationship was examined by reviewing the medical records of family members with confirmed tumors, carrying out neck ultrasonic scanning or computed tomography on their relatives to look for previously unrecognized tumors, and arranging audiometric testing. This information was used to characterize the type of hearing-loss present in this family and to construct a pedigree for the two traits. RESULTS: The hearing-loss observed in this family was sensorineural in character. Of 15 family members studied over four generations, eight were confirmed positive for both carotid body paraganglioma and sensorineural hearing-loss, two for the tumor only (one of whom did not have his hearing assessed) and one for hearing-loss alone. Four family members were negative for both traits. CONCLUSIONS: The pedigree provides evidence of a previously undescribed association between familial carotid body paraganglioma and sensorineural hearing-loss, a combination that appears to be co-inherited in this family.     

The significance of the carotid bifurcation angle in carotid body tumours

This is a retrospective report on 22 patients with carotid body tumours (intercarotid paragangliomas or carotid chemodectomas) treated by excision using either the dissection technique or en bloc resection. The type of operation to be carried out can be predicted pre-operatively by measuring the carotid bifurcation angle or degree of splaying of the carotid arteries. An angle of less than 90 degrees implies that the tumour can be dissected off the internal carotid artery. An angle of more than 90 degrees implies that it will probably require en bloc resection, including the carotid bifurcation, followed by carotid reconstruction.     

Multiple simultaneous paragangliomas of the head and neck in association with multiple retroperitoneal pheochromocytomas

A patient in whom multiple, familial, catecholamine-secreting head and neck paragangliomas and retroperitoneal pheochromocytomas were identified is reported. There were at least nine primary and possibly five recurrent neoplasms, the most reported in a single patient. In patients with family history of pheochromocytoma or paraganglioma or with multiple tumors, careful laboratory and angiographic studies are indicated to discover additional lesions.     

Paraganglioma of the neck. Analysis of 32 operated cases]

Between january 1965 and november 1990, 32 operations for neck paraganglioma were performed: 29 chemodectomas (carotid body tumors) and 3 paragangliomas of the vagus nerve. Seven subjects were affected with bilateral chemodectomas and one of them showed concurrent unilateral vagal paraganglioma. Two paragangliomas were malignant, with invasion of the latero-cervical lymphnodes revealed at operation. Four individuals came to observation from two different families, suggesting familiarity. Preoperative diagnosis was correctly made in 12 of 18 asymptomatic chemodectomas (66.6%), ten of whom observed during the last decade: angiography is the gold standard for diagnosis but CT scan, ultrasound and NMR imaging are going to earn the confidence of physicians for precise evaluation of latero-cervical masses. Surgery is to date the treatment of choice, and the results are dependent on the size of the tumor and the involvement of the neighbouring vascular, nervous and visceral structures. According to the majority of the literature, the 29 chemodectomas were classified in the three groups of Shamblin: I: 4 cases; II: 10; III: 15. Twenty out of the 24 transient or permanent postoperative complications took place in the third group: in five instances some procedures of internal carotid artery reconstruction were needed. Fourteen complications for chemodectomas and 2 for vagal paragangliomas affected the cranial nerves; three transient and one permanent ischemic central neurological deficits occurred in the group III chemodectomas. Not any operative mortality was registered in this series.     

Successful patient outcome following surgery of carotid body tumor and temporary hypoglossal nerve dysfunction

Carotid body tumors, also known as paragangliomas or chemodectomas, are rare tumors. They are mostly benign slow-growing tumors arising from neural crest cells, but can give rise to complications because of their location and close relation to carotid vessels and cranial nerves. A 40-year male patient diagnosed with a carotid body tumor is discussed along with a review of cranial nerve complications associated with the management of carotid body tumors. This case highlights the complete recovery after a temporary hypoglossal nerve deficit following surgery. Another important aspect is that syncopal attacks might occur in carotid body tumors and early surgery is required to prevent complications.     

Catecholamine-secreting paragangliomas of the base of the skull. Report of two cases

Two cases of catecholamine-secreting paragangliomas of the base of the skull are described. The patients presented with uncontrollable hypertension and, after investigation, tumors were discovered in the regions of the glomus jugulare and pterygopalatine ganglion, respectively. After cardiovascular stabilization and tumor embolization, the tumors were surgically removed, with subsequent resolution of hypertension. The incidence of these tumors is discussed.     

Subglottic paraganglioma

Paragangliomas are uncommon neuroendocrine tumors. In the head and neck region they are most commonly associated with the carotid body, vagus nerve, jugulotympanic paraganglia, and occasionally the superior and inferior laryngeal paraganglia. Laryngeal paragangliomas and subglottic paragangliomas are rare. There have been nine reported cases in the English literature of subglottic paragangliomas. We present a case of this unusual lesion and discuss histologic characteristics and surgical treatment. © 1997 John Wiley & Sons, Inc. Head Neck 19 : 54–56, 1997.     

Classification and management of cervical paragangliomas

INTRODUCTION

Cervical paragangliomas are slow-growing tumours that eventually cause lower cranial nerve palsies and infiltrate the skull base. Surgical treatment may cause the same deficits and, in some, risks more serious neurological deficits. We describe a classification used to guide investigation, consent and management of cervical paragangliomas based on extensive experience.

METHODS

The case notes of patients managed by the senior author at a tertiary referral skull base unit between 1987 and 2010 were reviewed retrospectively. A total of 87 cervical paragangliomas were identified in 70 patients (mean age: 46 years, range: 13–77 years). Of these, 35 patients had 36 vagal paragangliomas, 43 patients had 50 carotid body paragangliomas and 8 had both. One cervical paraganglioma arose from neither the carotid body nor the nodose ganglion. The main outcome measures were death, stroke, gastrostomy and tracheotomy.

RESULTS

All tumours were classified pre-operatively based on their relationship to the carotid artery, skull base and lower cranial nerves. Type 1 tumours were excised with a transcervical approach, type 2 with a transcervical-parotid approach and type 3 with a combined transcervical-parotid and infratemporal fossa approach. Type 4 patients underwent careful assessment and genetic counselling before any treatment was undertaken. There were no peri-operative deaths; two patients had strokes, one required a long-term feeding gastrostomy and none required a tracheotomy.

CONCLUSIONS

The use of a pre-operative classification system guides management and surgical approach, improves accuracy of consent, facilitates audit and clarifies which patients should be referred to specialised centres.     

Combined endovascular and surgical treatment of head and neck paragangliomas--a team approach

BACKGROUND: Paragangliomas are highly vascular tumors of neural crest origin that involve the walls of blood vessels or specific nerves within the head and neck. They may be multicentric, and they are rarely malignant. Surgery is the preferred treatment, and these tumors frequently extend to the skull base. There has been controversy concerning the role of preoperative angiography and embolization of these tumors and the benefits that these procedures offer in the evaluation and management of paragangliomas. METHODS: Forty-seven patients with 53 paragangliomas were treated from the period of 1990-2000. Initial evaluation usually included CT and/or MRI. All patients underwent bilateral carotid angiography, embolization of the tumor nidus, and cerebral angiography to define the patency of the circle of Willis. Carotid occlusion studies were performed with the patient under neuroleptic anesthesia when indicated. The tumors were excised within 48 hours of embolization. RESULTS: Carotid body tumors represented the most common paraganglioma, accounting for 28 tumors (53%). All patients underwent angiography and embolization with six patients (13%), demonstrating complications (three of these patients had embolized tumor involving the affected nerves). Cerebral angiography was performed in 28 patients, and 5 of these patients underwent and tolerated carotid occlusion studies. The range of mean blood loss according to tumor type was 450 to 517 mL. Postoperative cranial nerve dysfunction depended on the tumor type resected. Carotid body tumor surgery frequently required sympathetic chain resection (21%), with jugular and vagal paraganglioma removal frequently resulting in lower cranial nerve resection. These patients required various modes of postoperative rehabilitation, especially vocal cord medialization and swallowing therapy. CONCLUSIONS: The combined endovascular and surgical treatment of paragangliomas is acceptably safe and effective for treating these highly vascular neoplasms. Adequate resection may often require sacrifice of one or more cranial nerves, and appropriate rehabilitation is important in the treatment regimen.     

Carotid body tumor. The Lahey Clinic experience

We believe that paragangliomas of the carotid body should be excised in all patients unless formidable medical conditions prohibit the use of general anesthesia. If these tumors are left unresected, they will eventually grow to invade the skull and kill the patient. With definitive diagnostic modalities available, in addition to comparatively low-risk anesthesia, autotransfusion, and replacement of the carotid artery, there are few patients who cannot be surgically treated. The important point is that although such a tumor is rare, its presence must always be considered when dealing with a lateral neck mass. Carotid arteriography should be performed when a carotid body tumor is suspected.     

Synchronous carotid body and thoracic paraganglioma associated with a germline SDHC mutation

Paraganglionic tumors are rare. A germline mutation responsible for a familial pattern of paragangliomas (PGLs) has been identified on the genes encoding for the subunits of succinate dehydrogenase (SDH). Manifestations of those with a succinate dehydrogenase subunit C (SDHC) germline mutation have been almost exclusively reported as single head and neck paragangliomas (HNPGLs). We present a 32-year-old man with a familial SDHC mutation who manifests synchronous PGLs of the carotid body and the thoracic aortopulmonary window. To our knowledge, this is the first report of such a presentation for this mutation.