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World J Surg OncolWorld Journal of Surgical Oncology1477-7819BioMed Central London 1477-7819-3-101570750010.1186/1477-7819-3-10ResearchDiagnosis and treatment of carotid body paraganglioma: 21 years of experience at a clinical center of Serbia Davidovic Lazar B 1lazard@EUnet.yuDjukic Vojko B 2vojko@ptt.yuVasic Dragan M 1dr_vasic@ptt.yuSindjelic Radomir P 1sindjelicpr@sezam.proDuvnjak Stevo N 1duvnjak@net.yu1 Institute for Cardiovascular Diseases, Clinical Center of Serbia, Belgrade, Serbia and Montenegro2 Institute for Otorhinolaringology and Maxillofacial Surgery, Clinical Center of Serbia, Belgrade, Serbia and Montenegro2005 12 2 2005 3 10 10 28 6 2004 12 2 2005 Copyright © 2005 Davidovic et al; licensee BioMed Central Ltd.2005Davidovic et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background
The carotid body paraganglioma (chemodectoma) is a relatively rare neoplasm of obscure origin. These are usually benign and commonly present as asymptomatic cervical mass.

Patients and methods
Records of 12 patients (9 female and 3 male) with carotid body tumors treated between 1982 and 2003, treated at our center were retrospectively reviewed. Data on classification, clinical presentation, and surgical treatment were extracted from the case records. Surgical complications and treatment outcome were noted and survival was calculated by actuarial method. The literature on carotid body paraganglioma was reviewed.

Results
The average age of the patients was 52 years (range 30–78 years). Eight of these cases presented as a large asymptomatic non-tender neck mass, and two each presented with dysphagia, and hoarseness of voice. As per Shamblin classification seven of tumors were type II and 5 were types III. In 7 cases subadventitial tumor excision was performed, while in 5 associated resection of both external and internal carotid arteries was carried out. The artery was repaired by end-to-end anastomosis in one case, with Dacron graft in one case, and with saphenous vein graft in 3 cases. There was no operative mortality. After a mean follow-up of 6.2 years (range 6 months to 20 years), there were no signs of tumor recurrence in any of the cases.

Conclusions
Surgical excision is the treatment of choice for carotid body paragangliomas although radiation therapy is an option for patients who are not ideal candidates for surgery. For the tumors that are in intimate contact with carotid arteries, the treatment by vascular surgeon is recommended.
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Background
Paraganglioma arising from the carotid body are relatively rare tumors but constitute majority of head and neck paragangliomas (60–70%) [1-6]. The term paraganglia was first used by Kohn in the early twentieth century and is the most appropriate nomenclature from an embryologic standpoint [3-5]. Other terms such as carotid body tumor, glomus tumor, chemodectomas, and nonchromaffin tumor are less accurate terms and therefore should be best avoided [7-13]. The neoplasm present as asymptomatic neck mass. We report our experience with surgically treated carotid body tumors.

Patients and methods
Between 1982 and 2003, 12 patients (9 female and 3 male) with carotid body paraganglioma were surgically treated at the Institute for Cardiovascular Diseases, Serbian Clinical Centre. Mean age of the patients was 52 years (range 30–78 years). The records of these patients were retrospectively reviewed for clinical presentation, diagnostic work-up, surgical treatment, and outcome. Descriptive data was presented as frequency and percentage. Survival was calculated by actuarial method. World literature on carotid body paraganglioma was reviewed. The articles were extracted using the key words carotid body and paraganglioma.

All the patients were followed-up periodically every 6 months for the first year, yearly for next 5 years, thereafter only select patients were followed. The patients who had undergone carotid artery repair were followed-up with yearly duplex scanning; two patients were followed by a computerized tomography (CT) scan, and one by regular magnetic resonance (MR) imaging.

Results
Eight cases presented as large non-tender neck masses located just anterior to the sternocleidomastoid muscle, two patients presented with dysphagia due to hypoglossal nerve compression, while two other had hoarseness of voice. The duplex ultrasonography and selective carotid angiography were used for diagnosis in the eleven cases, CT in five, and MR imaging in three cases (Figure 1 and 2). In one case the diagnosis was established on intraoperative exploration.

Figure 1 Selective carotid angiography showed carotid body paraganglioma. The typical separation (''lyre sign") of external and internal carotid arteries, are presented.

Figure 2 Selective carotid angiography showed hypervascularization of the carotid body paraganglioma mostly from the external carotid artery.

Intraoperatively on exploration of the neck seven of the cases showed a medium size tumor intimately associated and compressing carotid vessels (Shamblin II), and a large tumor involving carotid vessels in five cases (Shamblin III). In 7 cases of Shamblin II carotid body paraganglioma a subadventitial tumor excision was performed while in other 5 cases both external and internal carotid arteries were resected. One of these was repaired by end-to-end anastomosis, one with interposition of Dacron® graft, and other 3 were repaired with reversed saphenous vein graft.

The histological examination showed no signs of malignancy in any of the tumors. In two cases transient hypoglossal nerve palsy was noticed. Another patient had unexpected postoperative hoarseness of voice due to the transient vagus nerve palsy. All these three cases subsequently recovered. There was no operative mortality. The patients were followed-up from the 6 months to 20 years (mean 6.2 year) no local, regional or distant metastasis was noticed. The actuarial survival was 100%.

Discussion
The carotid body was first described by von Haller in 1743 [14]. It is highly specialized organ located at the common carotid artery bifurcation. Its feeding vessels run primarily from the external carotid artery. The function of the carotid body is related to autonomic control of the respiratory and cardiovascular systems, as well as blood temperature [3,10,12,15-23]. Paraganglioma is a relatively rare neoplasm occurring in carotid body [1-6].

The carotid body paraganglioma is more common in women [2-5,20,25-28]. The incidence of bilateral carotid body lesions is approximately 10%. Most of these lesions are benign however malignant behavior is often encountered. For diagnosis of malignant carotid body paraganlioma there are no clear histological characteristics that differentiate it from benign lesions. This diagnosis is reserved for the tumors with local, regional and distant metastasis. The rate of malignancy is reported to be 6–12.5% of all cases [3-5,9,11,29-35]. The 7–9% of the cases are hereditary [2,4,20,25-28,36]. None of our cases were bilateral or hereditary.

Carotid body paraganglioma often present as slow growing, non-tender neck masses located just anterior to the sternocleidomastoid muscle at the level of the hyoid. The tumor is mobile in the lateral plane but its mobility is limited in the cephalocaudal direction [3-5,13-15,21,26,36-38]. Occasionally the tumor mass may transmit the carotid pulse or demonstrate a bruit or thrill [39]. Because of its location in close approximation to carotid vessels and X-XII cranial nerves, tumors enlargement causes progressive symptoms such as dysphagia (two of our cases), odynophagia, hoarseness of voice (two of our cases) or other cranial nerve deficits [2-5,14,26,27,32,37,40]. The patients may give a history suggestive of symptoms associated with catecholamine production such as fluctuating hypertension, blushing, obstructive sleep apnea and palpitations [3-5,10,14,15,21-23,37].

Size of the tumor has a great importance not only for its clinical manifestations but also for treatment. In 1971, Shamblin introduced a classification system based on tumors size [41]. They classified small tumors that could be easily dissected away from the vessels as group I. Group II (7 of our cases) included paragangliomas of medium size that were intimately associated and compressed carotid vessels, but could be separated with careful subadventitial dissection. Group III consisted of (5 of our cases) tumors that were large and typically encased the carotid artery requiring partial or complete vessel resection and replacement. Histologically, carotid body paraganglioma resemble the normal architecture of the carotid body. The tumors are highly vascular, and between the many capillaries are clusters of cells called Zellballen [41].

The carotid angiography is the most useful diagnostic test for paragangliomas. The angiography demonstrates tumor blood supply and widening of the carotid bifurcation by a well-defined tumor blush ("lyre sign"), which is classic pathognomonic angiographic finding [5,8,37-39,42,43]. MR and contrast CT are more effective non-invasive imagining modalities comparing with duplex ultrasonography, especially for small tumors [3,37-39,42-45]. Radioimmunodetection of carotid body paraganglioma by 111In labeled anti-CEA antibody is also described in literature [9,46]. The differential diagnosis includes other tumors in this area, carotid artery aneurysms and elongation. For this reason using of precutaneous fine-needle aspiration for preoperative diagnosis of carotid body paraganglioma, can be very dangerous [47].

Resection of carotid body paraganglioma carries inherent risks of injury to the cranial nerves, carotid arteries as well excessive blood loss. Reigner first attempted resection of a carotid body paraganglioma in 1880, but the patients did not survive [48]. Maydel was the first to remove a carotid body paraganglioma successfully in 1886, but the patient became aphasic and hemiplegics due to internal carotid artery ligature [49]. In 1903, Scudder performed the first successful removal of carotid body paraganglioma [50]. The surgical excision with careful subadventitial dissection is treatment of choice for most carotid body paragangliomas (Shamblin I and II) [2-6,14-18,34,37-40,43]. The Shamblin III of carotid body paraganglioma requires resection of the external and/or internal carotid artery. If the internal carotid is encased in tumor or damaged during resection, immediate repair/replacement should be performed [15,37,39,40,42,43,51,52]. The second problem during tumor excision is bleeding, which sometimes can be massive. In such cases clamping of all carotid arteries is useful, with placement of internal carotid shunt [18,35,37]. Having in mind our experience with surgical treatment of both carotid body gangliomas as well as carotid stenosis, we recommend Pruitt-Inahara double balloon occlusive internal carotid shunt [37]. The placement of this shunt through incision on the common carotid artery contributes to the adequate bleeding control from the common and internal carotid arteries, as well as brain protection. This procedure gave a clean and dry operative field during tumor removal [3,37]. Some other articles recommend angiographic embolization preoperatively [3,23,37,42,53-55]. The Preoperative embolization of a carotid body paraganglioma can be performed by ethanol or polyvinyl alcohol. The finally result is a complete devascularization [55]. Earlier the carotid body paragangliomas were considered radioresistant [34]. However, more recent studies indicate good responses to radiation therapy [11,30]. Most authors recommend radiotherapy for giant and recurrent carotid body paragangliomas, and with malignant carotid body paragangliomas metastatic to the regional lymph nodes [8,33-36].

The modern surgical techniques have reduced the risk of postoperative stroke in carotid body paraganglioma resection to less than 5% [37,40,56]. However, the incidence of cranial nerve injury remains strikingly high, ranging from 20% to 40% [37,38,48,56,57]. In 20% of patients the neurological deficits is permanent. We found two (18%) transient hypoglossal, and one transient vagus nerve damage. recurrence after complete resection occurs in approximately 6% of patients [15,37,39,40,42,43,51,52]. In our study however, there were no recurrences. The patients with internal carotid artery reconstruction should undergo duplex scanning periodically to identify graft stenosis.

Conclusion
Early operative management is warranted to avoid the possibility of eventual metastasis and progressive local invasion to the point of inoperability. In case of tumors intimately contact with carotid arteries, the treatment by vascular surgeon is recommended.

Competing interests
The author(s) declare that they have no competing interests.

Funding source
Nil

Authors' contributions
LBD: Preperation of draft manuscript

VBD: Literature search, data collection

DMV: Study design, data analysis, interpretation, preparation of draft

RPS: Study coordination, data interpretation, manuscript preperation

SND: Manuscript editing, preparation of final manuscript for publication

All authors read and approved the manuscript.
==== Refs
Sykes JM Ossoff RH  Paragangliomas of the Head and Neck Otolaryngol Clin North Am 1986 19 755 767 3797012 
Sobol SM Dailey JC  Familial multiple cervical paragangliomas: report of a kindred and review of the literature Otolaryngol Head Neck Surg 1990 102 382 390 2113266 
Myers EN Johnson JT  Cummings, CW, Fredrickson JM, Harker LA, Krause CJ, Schuller DE  Neoplasms Otolaryngology-Head and Neck Surgery 1993 St Louis; Mosby Year Book 1590 1597 
Kyriakos M  Thawley SE, Panje WR  Pathology of selected soft tissue tumors of the head and neck Comprehensive Management of Head and Neck Tumors 1987 Philadelphia PA. W.B. Saunders 1261 1264 
Maves MD  Bailey BJ, Johnson JT, Kohut RI, Pillsbury HC, Tardy ME  Vascular tumors of the head and neck Head and Neck Surgery-Otolaryngology 1993 Philadelphia JB Lippincott 1397 1409 
Rush Bf Jr Current concepts in the treatment of carotid body tumors Surgery 1962 52 679 14495345 
Balatsouras DG Eliopoulos PN Economou CN  Multiple glomus tumors J Laryngol Otol 1992 106 538 543 1320657 
Mayer R Fruhwirth J Beham A Groell R Poschauko J Hackl A  Radiotherapy as adjunct to surgery for malignant carotid body paragangliomas presenting with lymph node metastases Strahlenther Onkol 2000 176 356 360 10987018 
Pacheco-Ojeda L  Malignant carotid body tumors: report of three cases Ann Otol Rhinol Laryngol 2001 110 36 40 11201806 
Kairemo KJA Hopsu EVM  Radioimmunodetection of Chemodectoma by In-111 labeled anti-CEA antibody Clin Nucl Med 1990 15 900 903 2177386 
Saldana MJ Salem LE Travezan R  High altitude hypoxia and chemodectomas Hum Pathol 1973 4 251 263 4706179 
Heath D  The human carotid body in health and disease Journal of Pathology 1991 164 1 8 2056385 
Dickinson AM Trauer CA  Carotid body tumors: Review of the literature with the report of two cases Am J Surg 1945 60 9 10.1016/S0002-9610(45)90344-8 
Milewski C  Morphology and clinical aspects of paragangliomas in the area of head-neck HNO 1993 41 526 531 8282577 
Boyd JD  The development of human carotid body contributions to embryology Surgery 1937 152 1 
Gordon-Taylor G  On carotid tumors Br J Surg 1990 28 163 172 
Anderson R Scarcella JV  Carotid body tumors Am J Surg 1963 106 856 859 14078744 
Eyzaguirre C  Neurobiology and Cell Physiology of Chemoreception 1993 New York: Plenum Press 123 129 
McCaffrey TV Meyer FB Michels VV Piepgras DG Marion MS  Familial Paragangliomas of the head and neck Arch Otol Head Neck Surg 1994 120 1211 1216 
Boyle JR London NJ Tan SG Thurston H Bell PR  Labile blood pressure after bilateral carotid body tumor surgery Eur J Vasc Endovasc Surg 1995 9 346 348 7620963 
Metersky ML Castriotta RJ Elnaggar A  Obstructive sleep apnea due to a carotid body paraganglioma Sleep 1995 18 53 54 7761743 
Roncorony AJ Montiel GC Soweniac GB  Bilateral carotid body paraganglioma and central alveolar hypoventilation Respiration 1993 60 243 246 8265882 
Shedd DP Arias JD Glunk RP  Familial occurrence of carotid body tumors Head and Neck 1990 12 496 499 2258288 
Rush BF Jr Familial bilateral carotid body tumors Ann Surg 1963 157 633 636 13975591 
Ridge BA Brewster DC Darling RC Cambria RP LaMuraglia GM Abbott WM  Familial carotid body tumors: incidence and implications Ann Vasc Surg 1993 7 190 194 8518138 
Katz AD  Carotid body tumors in a large family group Am J Surg 1964 108 570 573 14211450 10.1016/0002-9610(64)90157-6 
Strauss M Nicholas GG Abt AB Harrison TS Seaton JF  Malignant catecholamine-secreting carotid body paraganglioma Otolaryngol Head Neck Surg 1983 91 315 321 6410337 
Valdagni R Amichetti M  Radiation therapy of carotid body tumors Am J Clin Oncol 1990 13 45 48 2154923 
Fanning JR Woods FM Christian HJ  Metastatic carotid body tumor. Report of the case with the review of the literature JAMA 1963 185 49 
Voorda AL Jacobson N Anttmen J  Slowly growing pulmonary metastases of malignant cervical chemodectoma Acta Oncol 1994 33 77 78 8142132 
Morris GC JrBalas PE Cooley DA Crawford ES Debakey ME  Surgical treatment of benign and malignant carotid body tumors: clinical experience with sixteen tumors in twelve patients Am Surg 1963 29 429 437 14042575 
Patetsios P Gable DR Garrett WV Lamont JP Kuhn JA Shutze WP Kourlis H Grimsley B Pearl GJ Smith BL Talkington CM Thompson JE  Management of carotid body paragangliomas and review of a 30-year experience Ann Vasc Surg 2002 16 331 338 11957009 10.1007/s10016-001-0106-8 
Zabel A Milker-Zabel S Huber P Schulz-Ertner D Schlegel W Wannenmacher M Debus J  Fractionated stereotactic conformal radiotherapy in the management of large chemodectomas of the skull base Int J Radiat Oncol Biol Phys 2004 58 1445 1450 15050322 10.1016/j.ijrobp.2003.09.070 
Elshaikh MA Mahmoud-Ahmed AS Kinney SE Wood BG Lee JH Barnett GH Suh JH  Recurrent head and-neck chemodectomas: a comparison of surgical and radiotherapeutic results Int J Radiat Oncol Biol Phys 2002 52 953 956 11958888 10.1016/S0360-3016(01)02751-1 
Hinerman RW Mendenhall WM Amdur RJ Stringer SP Antonelli PJ Cassisi NJ  Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body, and glomus vagale Head Neck 2001 23 363 371 11295809 10.1002/hed.1045 
Evenson LJ Mendenhall WM Parsons JT Cassisi NJ  Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale Head Neck 1998 20 609 613 9744460 10.1002/(SICI)1097-0347(199810)20:7<609::AID-HED5>3.0.CO;2-8 
Defraigne JO Sakalihassan N Antoine P Thiry A Limet R  Carotid chemodectomas. Experience with nine cases with reference to preoperative embolization and malignancy Acta Chir Belg 1997 97 220 228 9394963 
Por YC Lim DT Teoh MK Soo KC  Surgical management and outcome of carotid body tumours Ann Acad Med Singapore 2002 31 141 144 11957547 
Mall J Saclarides T Doolas A Eibl-Eibestfeld B  First report of hepatic lobotomy for metastatic carotid body tumor J Cardiovas Surg 2000 41 759 761 
Pandey M Chandramohan K Sebastian P Ramachandran K  An unusual bilateral cervical paraganglioma: a case report Int J Oral Maxillofac Surg 2002 31 335 337 10.1054/ijom.2001.0196 
Lotina S Davidoviæ L Havelka M Vojnoviæ B Neškoviæ V Petar Stojanov Kecman N  Carotid body tumors J Serbian Med Soc 1997 125 278 284 
Johnson JT  Paparella, MM, Shumrick DA, Gluckman JL, Meyerhoff WL  Parapharyngeal space masses: diagnosis and management Otolaryngology 1991 Philadelphia, W B Saunders 2584 2585 
Laube HR Fahrenkamp AG Backer W Scheld HH  Glomus tumors: A diagnostic and surgical challenge? J Cardiol 1994 83 373 380 
Javid H Dye WS Hunter JA Najafi H Julian OC  Surgical management of carotid body tumor Arch Surg 1967 95 771 779 6053959 
Shamblin WR ReMine WH Sheps SG Harrison EG Jr Carotid body tumor (chemodectoma): Clinicopathologic analysis of ninety cases Am J Surg 1971 122 732 739 5127724 10.1016/0002-9610(71)90436-3 
Devuyever D Mathurin P Dooms G Hamoir M  Lateral neck paraganglioma: diagnostic imaging and preoperative embolization J Belge Radiol 1993 76 15 19 8391528 
Matticari S Credi G Pratesi C Bertin D  Diagnosis and surgical treatment of the carotid body tumors J Cardiovasc Surg 1995 36 233 239 7629206 
Miselli A Bresciani P Soana G Bianchi E Cocchi S Marchini L  Carotid glomus tumors. Study of 2 cases using color Duplex ulstrasonography Radiol Med (Torino) 1994 88 877 880 7878253 
Carriero A Tonni AG D'Ettorre L Iezzi A Tartaro A Bonomo L  Neoplasms of the glomus caroticum: magnetic resonance angiography versus magnetic resonance Radiol Med (Torino) 1994 87 71 75 8128036 
Kwekkeboom DJ van Urk H Pauw BK Lamberts SW Kooij PP Hoogma RP Krenning EP  Osteroid scintigraphy for detection of paragangliomas J Nucl Med 1993 34 873 878 8389841 
Fleming MV Oertel YC Rodriguez ER Fidler WJ  Fine-needle aspiration of 6 carotid body paragangliomas Diagn Cytopath 1993 9 510 515 
Lahey FA Warren KW  A long term appraisal of carotid body tumors with remarks on their removal Surg Gynecol Obstet 1951 92 481 491 14835205 
Byrned JJ  Carotid body and allied tumors Am J Surg 1958 95 371 384 13508967 10.1016/0002-9610(58)90537-3 
Scudder CL  Tumor of the intercarotid body. A report of one case, together with all cases in literature Am J Med Sci 1903 126 1384 
Anand VK Alemar GO Sanders TS  Management of the internal carotid artery during carotid body tumor surgery Laryngoscope 1995 105 231 235 7877408 
Rabl H Friehs I Gutschi S Pascher O Koch G  Diagnosis and treatment of carotid body tumors Thorac Cardiovasc Surg 1993 41 340 343 8128461 
Eskridge JM Harris AB Finch L Altois MA  Carotis synus syndrome and embolization procedures Am J Neuroradiol 1993 14 818 820 8352151 
Higo R Asai M Sugasawa M Takeuchi N Nemoto S  Preoperative embolization for paraganglioma Aurits Nasus Larynx 1994 21 122 125 
Horowitz M Whaismant RE Jungreis C Syderman C Levy EI Kassam A  Temporary balloon occlusion and ethanol injection for preoperative embolization of carotid-body tumor Ear Nose Throat J 2002 81 536 538 12199171 
Hallett JW JrNora JD Hollier LH Cherry KJ JrPairolero PC  Trends in neurovascular complications of surgical management for carotid body and cervical paragangliomas: A 50-year experience with 153 tumors J Vasc Surg 1988 7 284 291 2828696 10.1067/mva.1988.avs0070284 
Wang SJ Wang MB Barauskas TM Calcaterra TC  Surgical management of Carotid body tumors Otorynogol Head Neck Surg 2000 123 202 206 10.1067/mhn.2000.106709

