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Carotid body tumor
International Journal of Cardiology 143 (2010) e7 – e10 www.elsevier.com/locate/ijcard
Letter to the Editor
Carotid body tumor Raghotham Patlola a , Agostino Ingraldi a , Craig Walker a , David Allie a , Ijaz A. Khan b,⁎ a
Cardiovascular Institute of the South, Lafayette, Louisiana, USA b Good Samaritan Hospital, Baltimore, Maryland, USA Received 29 November 2008; accepted 3 December 2008 Available online 19 January 2009
Abstract Carotid body tumors are the most common paragangliomas of head and neck. Most of these tumors are benign with a small malignant potential. Although newer non-invasive diagnostic modalities have significantly enhanced the diagnostic capabilities, controversy exists over adequate management of these rare tumors. In younger, healthy patients with no comorbidities, the best therapeutic strategy is a complete excision of the tumor. However, in less than ideal patient population modalities such as radiation and tumor embolization can be considered. Surgical advances have greatly decreased the mortality rates, but the morbidity rates secondary to cranial nerve injuries remain high. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Carotid body tumor; Paraganglioma; Chemodectoma; Glomus tumor; Lyre sign; Fontaine sign
The carotid body tumor (Glomus tumor) is the most common paraganglioma in the head and neck. These tumors arise from accumulation of chemoreceptor cells in the neck, which develop from neural crest region during embryogenesis [1]. They are uncommon tumors representing about 0.6% of head and neck neoplasms and about 0.03% of all neoplasms. The higher prevalence of carotid body tumors has been related to chronic hypoxemia from chronic obstructive pulmonary disease and high altitudes [2,3]. The sporadic form of carotid body paraganglioma is more common than the inherited variety and tends to occur slightly more often in women. 1. Index case A 65-year-old female presented with a palpable mass in the left side of her neck associated with hoarseness of voice
⁎ Corresponding author. Good Samaritan Hospital, Russell Morgan Building, Suite 206, 5601 Loch Raven Boulevard, Baltimore, Maryland 21239, USA. Tel.: +1 443 444 5607; fax: +1 443 444 4606. E-mail address: [email protected] (I.A. Khan). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.020
and mild dysphagia (Fig. 1). An ultrasonogram of the neck demonstrated a hypervascular mass within the left carotid bifurcation with B-Mode and color Doppler. These features were mostly consistent with a carotid body tumor. Computed tomographic angiography (CTA) was subsequently performed pre-operatively using a 64 slice spiral CT scanner, after injecting 80 cm3 of nonionic iodinated contrast. The CTA scanning was performed using high-resolution, 1 mm slice thickness protocol, and post-acquisition processing was performed on a 3D workstation. This demonstrated a large carotid body tumor within the left carotid bifurcation (Fig. 2). In view of the relatively large symptomatic tumor and since the patient had no significant co-morbid conditions; surgical excision of the tumor was recommended. A selective carotid angiogram was performed pre-operatively aiming to define the anatomy, delineate the feeding artery and to perform tumor embolization to shrink the tumor prior to surgical excision (Fig. 3). With selective balloon occlusion angiography, it was evident that the tumor was possibly deriving blood supply from internal carotid and vertebral arteries. Hence tumor embolization was deemed to be impossible. The patient successfully underwent surgical
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R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
Fig. 1. A large palpable mass on the left antero-lateral aspect of the neck.
excision of the carotid body tumor. There was no major intraoperative blood loss or neurological injuries. Patient was discharged home in a stable condition, and was followed up 1 month post-operatively with a CT scan (Fig. 4). There was complete resolution of her voice hoarseness and there was no cranial nerve or cerebral neurological injury.
Fig. 3. Lyre sign — typical splaying of the external and internal carotid arteries by the carotid body tumor.
The neoplasms originating from the neural crest cells, referred to as paragangliomas, are associated with para-
sympathetic nervous system and are found near arteries and cranial nerves of the branchial arches, with a cervicocephalic distribution [4–7]. Paragangliomas are named after their site of origin. They most commonly occur at the carotid bifurcation where they are known as carotid body tumors. Additional sites of origin include the jugular bulb (jugular paraganglioma), the vagus nerve (vagal paraganglioma) and within the middle ear mucosa (tympanic paraganglioma).
Fig. 2. Multislice spiral CT-angiography with 3D volume rendered reconstruction of the left carotid system demonstrating marked widening of the carotid bifurcation with and extremely hypervascular carotid body tumor.
Fig. 4. One month status-post-surgical excision of the carotid body tumor — multislice spiral CT-angiography with 3D volume rendered reconstruction.
2. Discussion
R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
The carotid body as described by von Haller in 1743, is a highly specialized organ located at the common carotid bifurcation. The function of the carotid body is related to autonomic control of the respiratory and cardiovascular systems, as well as blood temperature. Carotid body tumor is the most common variety of paraganglioma of the head and neck, and is the only pathology to affect the carotid body [4,5]. The etiology of the carotid body tumors is unknown. There have been reports of increased incidence of carotid body tumors in patients with chronic obstructive pulmonary disease and in people living at high altitudes because the cells in the carotid body typically detect changes in partial pressure of oxygen, partial pressure of carbon dioxide, and pH levels [2]. Carotid body tumors may be sporadic or familial. The familial tumors account for about 10% of all carotid body tumors, have an autosomal dominant mode of transmission with variable penetrance, and are characterized by a high incidence of bilateral tumors [8–10]. The sporadic form of carotid body paraganglioma is slightly more common in women [2]. Carotid body tumor often presents as a slow growing, non-tender neck mass located just anterior to the sternocleidomastoid muscle at the level of the thyroid. The differential diagnosis includes cervical lymphadenopathy, carotid artery aneurysm, brachial cleft cyst, laryngeal carcinoma and metastatic tumor. The tumor is typically mobile in the lateral plane but its mobility is restricted in the cephalocaudal direction (Fontaine sign). Occasionally the tumor may transmit the carotid pulse or demonstrate a bruit or thrill [11]. Because of its close proximity to carotid vessels and X–XII cranial nerves, enlargement of the tumor may cause progressive neurologic symptoms such as dysphagia, odynophagia, or hoarseness of voice. The patients with carotid body tumors may give a history of symptoms suggestive of excessive catecholamine production such as fluctuating hypertension, flushing and palpitations. The reported rates of malignancy in carotid body tumors range from 2–50% [12–17]. Histologically, carotid body tumors resemble the normal architecture of the carotid body. The tumors are highly vascular, and between the capillaries are clusters of tumor cells resulting in formation of pseudoalveolar pattern of Zellballen (cell balls) [14]. These cells have a finely granular eosinophilic cytoplasm and small round or oval nuclei. The malignant potential of these tumors cannot be predicted by histological studies. The diagnosis of malignancy is made when there is invasion of lymph nodes, vessels, nerves, airway and the base of the skull, and not by the size or histological features [15,18]. These tumors may rarely metastasize to the kidney, thyroid, pancreas, brain and lungs but majority of the metastatic disease from cervical paragangliomas is usually confined to the neck [12,19]. Contrast computed tomography and magnetic resonance imaging have evolved as effective non-invasive imaging modalities for detection of the carotid body tumors. They commonly demonstrate tumor blood supply and widening of the carotid bifurcation by a well-defined tumor blush called Lyre sign (Fig. 3), which is a classic pathognomonic contrast
e9
angiographic finding. Carotid angiography also plays an important role in the evaluation and management of these tumors. Angiography demonstrates the vascular extent of the tumor, the carotid artery involvement, size and location of the tumor-feeding vessels for possible tumor embolization and coexisting atherosclerotic disease of the carotid arteries. The management of carotid body tumors has been controversial because of lesion's low malignant potential and high rates of operative complications. Early experiences with carotid body tumor resections were associated with operative mortality rates in the range of 5–13%, postoperative cranial nerve palsy in the range of 32–44% and other postoperative neurological complications in the range of 8–20%. However, most recent experiences have demonstrated the safety of surgical approach, with mortality rates of 1–2% but a high 40% morbidity rates, attributed to cranial nerve injuries and cerebral ischemic events [20]. Surgical treatment has been the standard approach to symptomatic carotid body tumors for many years with high cure rates [21]. The standard surgical principles for carotid body tumor excision include wide surgical exposure, proximal and distal vascular control, identification and preservation of the neurovascular structures, subadventitial tumor dissection, dissection of the tumor from the external and internal carotid arteries, ligation of the external carotid arteries when necessary, and vascular shunting and grafting wherever necessary [22]. These modern principles of carotid body surgery have contributed significantly to lower the perioperative morbidity and mortality. Size of the carotid body tumor has a great importance in defining the treatment strategy. Generally, tumors larger than 4–5 cm tend to have partial or complete encirclement of the carotid arteries [13]. Larger tumor sizes have been associated with higher risk of bleeding and cranial nerve injury complications with surgery. Pre-operative tumor embolization has been employed to shrink the tumor size and thereby decreasing the complications. Shamblin classification system based on tumor size was proposed in 1971 [12]. According this classification, group I tumors are relatively small tumors minimally attached to carotid vessels; the surgical excision is not difficult. The group II tumors are large tumors with moderate attachment to the carotid vessels; these tumors are amenable to careful surgical excision. The group III tumors are very large tumors, encasing the carotid vessels and often require arterial resection and grafting. Radiation therapy is commonly employed in patients who are poor candidates for surgical excision or embolization, secondary to their age or co-morbid conditions [23–25]. The complications of radiotherapy include inflammation of the external auditory canal and middle ear, osteoradionecrosis, cranial nerve neuropathies, and direct injury to the brain tissue. Radiotherapy also makes subsequent head and neck surgeries highly challenging. Despite limited experience, radiotherapy for paragangliomas appears to be helpful in cases with unresectable lesions, in high-risk patients, and as an adjunct to surgery for incompletely excised tumors or metastases.
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R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
Acknowledgment The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [26]. References [1] Pelliteri PK, Rinaldo A, Myssiorek D, et al. Paragangliomas of the head and neck. Oral Oncol 2004;40:75–563. [2] Saldana MJ, Salen LE, Travezan R. High altitude hypoxemia and chemodectomas. Hum Pathol 1973;4:63–251. [3] Rodriguez CS, Lopez GJ, Labastida AS, et al. Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level. Head Neck 1998;20:8–374. [4] Dickenson PH, Griffin SM, Guy AJ, et al. Carotid body tumors: 30 year experience. Br J Surg 1986;73:6–14. [5] Lack E, Cubilla A, Woodruff J, et al. Paragangliomas of the head and neck region. Cancer 1977;39:397–409. [6] Rao AB, Koeller KK, Adair CF, et al. Paragangliomas of the head and neck: radiologic–pathologic correlation. Arch Armed Forces Inst Pathol 1999;19:32–1605. [7] Pelliteri PK, Rinaldo A, Myssiorek D, et al. Paragangliomas of the head and neck. Oral Oncol 2004;34:36–829. [8] Pratt LW. Familial carotid body tumors. Arch Otol 1973;97:6–334. [9] Grufferman S, Gillman MW, Pasternak LR, et al. Familial carotid body tumors: case report and epidemiological review. Cancer 1980;46: 22–2116. [10] Gardner P, Dalsing M, Weisbarger E, et al. Carotid body tumors, inheritance and a high incidence of associated cervical paragangliomas. Am J Surg 1996;172:9–196. [11] Mall J, Saclarides T, Doolas A, et al. First report of hepatic lobotomy for metastatic carotid body tumor. J Cardiovasc Surg 2000;41:61–759. [12] Shamblin WR, ReMine WH, Sheps SG, et al. Carotid bodu tumor, (Chemodectoma): clinocopathological analysis of ninety cases. Am J Surg 1971;122:9–732.
[13] Kaman L, Singh RR, Aggarwal R, et al. Diagnostic and therapeutic approaches to carotid body tumors: report of three cases and review of literature. Aust N Z Surg 1999;69:5–852. [14] Grimley PM, Glenner CG. Histology and ultrastructure of carotid body paragangliomas: comparison with the normal gland. Cancer 1967;20: 88–1973. [15] Gaylis H, Mieny CJ. The incidence of malignancy in carotid body tumors. Br J Surg 1977;64:9–885. [16] Lees CD, Levine HL, Beven EG, et al. Tumors of the carotid body: experience with 41 operative cases. Am J Surg 1981;142:5–362. [17] Chambers RG, Mahoney WD. Carotid body tumors. Am J Surg 1968;116:554. [18] Farr HW. Carotid body tumors: a 40 year study. Cancer 1980;30: 5–260. [19] Lee JH, Barich F, Karnell LH, et al. National cancer data base report on malignant paragangliomas of the head and neck. Cancer 2002;94:7–730. [20] McPherson GAD, Holliday AW, Mansfield AO. Carotid body tumors and other cervical paragangliomas: diagnosis and management in 25 patients. Br J Surg 1989;76:6–33. [21] Persky MS, Setton A, Niimi Y, et al. Combined endovascular and surgical treatment of head and neck paragangliomas — a team approach. Head Neck 2002;24:31–423. [22] Sykes JM, Ossoff RH. Paragangliomas of the head and neck. Otolaryngol Clin North Am 1986;19:67–755. [23] Hinerman RW, Mendenhall WM, Amdur RJ, et al. Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body and glomus vagale. Head Neck 2001;23: 71–363. [24] Cole JM, Beiler D. Long-term results of treatment for glomus jugulare and glomus vagale tumors with radiotherapy. Laryngoscope 1994;04: 5–1461. [25] Evenson LJ, Mendenhall WM, Parsons JT, et al. Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale. Head Neck 1998;20:13–609. [26] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.
Letter to the Editor
Carotid body tumor Raghotham Patlola a , Agostino Ingraldi a , Craig Walker a , David Allie a , Ijaz A. Khan b,⁎ a
Cardiovascular Institute of the South, Lafayette, Louisiana, USA b Good Samaritan Hospital, Baltimore, Maryland, USA Received 29 November 2008; accepted 3 December 2008 Available online 19 January 2009
Abstract Carotid body tumors are the most common paragangliomas of head and neck. Most of these tumors are benign with a small malignant potential. Although newer non-invasive diagnostic modalities have significantly enhanced the diagnostic capabilities, controversy exists over adequate management of these rare tumors. In younger, healthy patients with no comorbidities, the best therapeutic strategy is a complete excision of the tumor. However, in less than ideal patient population modalities such as radiation and tumor embolization can be considered. Surgical advances have greatly decreased the mortality rates, but the morbidity rates secondary to cranial nerve injuries remain high. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Carotid body tumor; Paraganglioma; Chemodectoma; Glomus tumor; Lyre sign; Fontaine sign
The carotid body tumor (Glomus tumor) is the most common paraganglioma in the head and neck. These tumors arise from accumulation of chemoreceptor cells in the neck, which develop from neural crest region during embryogenesis [1]. They are uncommon tumors representing about 0.6% of head and neck neoplasms and about 0.03% of all neoplasms. The higher prevalence of carotid body tumors has been related to chronic hypoxemia from chronic obstructive pulmonary disease and high altitudes [2,3]. The sporadic form of carotid body paraganglioma is more common than the inherited variety and tends to occur slightly more often in women. 1. Index case A 65-year-old female presented with a palpable mass in the left side of her neck associated with hoarseness of voice
⁎ Corresponding author. Good Samaritan Hospital, Russell Morgan Building, Suite 206, 5601 Loch Raven Boulevard, Baltimore, Maryland 21239, USA. Tel.: +1 443 444 5607; fax: +1 443 444 4606. E-mail address: [email protected] (I.A. Khan). 0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.020
and mild dysphagia (Fig. 1). An ultrasonogram of the neck demonstrated a hypervascular mass within the left carotid bifurcation with B-Mode and color Doppler. These features were mostly consistent with a carotid body tumor. Computed tomographic angiography (CTA) was subsequently performed pre-operatively using a 64 slice spiral CT scanner, after injecting 80 cm3 of nonionic iodinated contrast. The CTA scanning was performed using high-resolution, 1 mm slice thickness protocol, and post-acquisition processing was performed on a 3D workstation. This demonstrated a large carotid body tumor within the left carotid bifurcation (Fig. 2). In view of the relatively large symptomatic tumor and since the patient had no significant co-morbid conditions; surgical excision of the tumor was recommended. A selective carotid angiogram was performed pre-operatively aiming to define the anatomy, delineate the feeding artery and to perform tumor embolization to shrink the tumor prior to surgical excision (Fig. 3). With selective balloon occlusion angiography, it was evident that the tumor was possibly deriving blood supply from internal carotid and vertebral arteries. Hence tumor embolization was deemed to be impossible. The patient successfully underwent surgical
e8
R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
Fig. 1. A large palpable mass on the left antero-lateral aspect of the neck.
excision of the carotid body tumor. There was no major intraoperative blood loss or neurological injuries. Patient was discharged home in a stable condition, and was followed up 1 month post-operatively with a CT scan (Fig. 4). There was complete resolution of her voice hoarseness and there was no cranial nerve or cerebral neurological injury.
Fig. 3. Lyre sign — typical splaying of the external and internal carotid arteries by the carotid body tumor.
The neoplasms originating from the neural crest cells, referred to as paragangliomas, are associated with para-
sympathetic nervous system and are found near arteries and cranial nerves of the branchial arches, with a cervicocephalic distribution [4–7]. Paragangliomas are named after their site of origin. They most commonly occur at the carotid bifurcation where they are known as carotid body tumors. Additional sites of origin include the jugular bulb (jugular paraganglioma), the vagus nerve (vagal paraganglioma) and within the middle ear mucosa (tympanic paraganglioma).
Fig. 2. Multislice spiral CT-angiography with 3D volume rendered reconstruction of the left carotid system demonstrating marked widening of the carotid bifurcation with and extremely hypervascular carotid body tumor.
Fig. 4. One month status-post-surgical excision of the carotid body tumor — multislice spiral CT-angiography with 3D volume rendered reconstruction.
2. Discussion
R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
The carotid body as described by von Haller in 1743, is a highly specialized organ located at the common carotid bifurcation. The function of the carotid body is related to autonomic control of the respiratory and cardiovascular systems, as well as blood temperature. Carotid body tumor is the most common variety of paraganglioma of the head and neck, and is the only pathology to affect the carotid body [4,5]. The etiology of the carotid body tumors is unknown. There have been reports of increased incidence of carotid body tumors in patients with chronic obstructive pulmonary disease and in people living at high altitudes because the cells in the carotid body typically detect changes in partial pressure of oxygen, partial pressure of carbon dioxide, and pH levels [2]. Carotid body tumors may be sporadic or familial. The familial tumors account for about 10% of all carotid body tumors, have an autosomal dominant mode of transmission with variable penetrance, and are characterized by a high incidence of bilateral tumors [8–10]. The sporadic form of carotid body paraganglioma is slightly more common in women [2]. Carotid body tumor often presents as a slow growing, non-tender neck mass located just anterior to the sternocleidomastoid muscle at the level of the thyroid. The differential diagnosis includes cervical lymphadenopathy, carotid artery aneurysm, brachial cleft cyst, laryngeal carcinoma and metastatic tumor. The tumor is typically mobile in the lateral plane but its mobility is restricted in the cephalocaudal direction (Fontaine sign). Occasionally the tumor may transmit the carotid pulse or demonstrate a bruit or thrill [11]. Because of its close proximity to carotid vessels and X–XII cranial nerves, enlargement of the tumor may cause progressive neurologic symptoms such as dysphagia, odynophagia, or hoarseness of voice. The patients with carotid body tumors may give a history of symptoms suggestive of excessive catecholamine production such as fluctuating hypertension, flushing and palpitations. The reported rates of malignancy in carotid body tumors range from 2–50% [12–17]. Histologically, carotid body tumors resemble the normal architecture of the carotid body. The tumors are highly vascular, and between the capillaries are clusters of tumor cells resulting in formation of pseudoalveolar pattern of Zellballen (cell balls) [14]. These cells have a finely granular eosinophilic cytoplasm and small round or oval nuclei. The malignant potential of these tumors cannot be predicted by histological studies. The diagnosis of malignancy is made when there is invasion of lymph nodes, vessels, nerves, airway and the base of the skull, and not by the size or histological features [15,18]. These tumors may rarely metastasize to the kidney, thyroid, pancreas, brain and lungs but majority of the metastatic disease from cervical paragangliomas is usually confined to the neck [12,19]. Contrast computed tomography and magnetic resonance imaging have evolved as effective non-invasive imaging modalities for detection of the carotid body tumors. They commonly demonstrate tumor blood supply and widening of the carotid bifurcation by a well-defined tumor blush called Lyre sign (Fig. 3), which is a classic pathognomonic contrast
e9
angiographic finding. Carotid angiography also plays an important role in the evaluation and management of these tumors. Angiography demonstrates the vascular extent of the tumor, the carotid artery involvement, size and location of the tumor-feeding vessels for possible tumor embolization and coexisting atherosclerotic disease of the carotid arteries. The management of carotid body tumors has been controversial because of lesion's low malignant potential and high rates of operative complications. Early experiences with carotid body tumor resections were associated with operative mortality rates in the range of 5–13%, postoperative cranial nerve palsy in the range of 32–44% and other postoperative neurological complications in the range of 8–20%. However, most recent experiences have demonstrated the safety of surgical approach, with mortality rates of 1–2% but a high 40% morbidity rates, attributed to cranial nerve injuries and cerebral ischemic events [20]. Surgical treatment has been the standard approach to symptomatic carotid body tumors for many years with high cure rates [21]. The standard surgical principles for carotid body tumor excision include wide surgical exposure, proximal and distal vascular control, identification and preservation of the neurovascular structures, subadventitial tumor dissection, dissection of the tumor from the external and internal carotid arteries, ligation of the external carotid arteries when necessary, and vascular shunting and grafting wherever necessary [22]. These modern principles of carotid body surgery have contributed significantly to lower the perioperative morbidity and mortality. Size of the carotid body tumor has a great importance in defining the treatment strategy. Generally, tumors larger than 4–5 cm tend to have partial or complete encirclement of the carotid arteries [13]. Larger tumor sizes have been associated with higher risk of bleeding and cranial nerve injury complications with surgery. Pre-operative tumor embolization has been employed to shrink the tumor size and thereby decreasing the complications. Shamblin classification system based on tumor size was proposed in 1971 [12]. According this classification, group I tumors are relatively small tumors minimally attached to carotid vessels; the surgical excision is not difficult. The group II tumors are large tumors with moderate attachment to the carotid vessels; these tumors are amenable to careful surgical excision. The group III tumors are very large tumors, encasing the carotid vessels and often require arterial resection and grafting. Radiation therapy is commonly employed in patients who are poor candidates for surgical excision or embolization, secondary to their age or co-morbid conditions [23–25]. The complications of radiotherapy include inflammation of the external auditory canal and middle ear, osteoradionecrosis, cranial nerve neuropathies, and direct injury to the brain tissue. Radiotherapy also makes subsequent head and neck surgeries highly challenging. Despite limited experience, radiotherapy for paragangliomas appears to be helpful in cases with unresectable lesions, in high-risk patients, and as an adjunct to surgery for incompletely excised tumors or metastases.
e10
R. Patlola et al. / International Journal of Cardiology 143 (2010) e7–e10
Acknowledgment The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [26]. References [1] Pelliteri PK, Rinaldo A, Myssiorek D, et al. Paragangliomas of the head and neck. Oral Oncol 2004;40:75–563. [2] Saldana MJ, Salen LE, Travezan R. High altitude hypoxemia and chemodectomas. Hum Pathol 1973;4:63–251. [3] Rodriguez CS, Lopez GJ, Labastida AS, et al. Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level. Head Neck 1998;20:8–374. [4] Dickenson PH, Griffin SM, Guy AJ, et al. Carotid body tumors: 30 year experience. Br J Surg 1986;73:6–14. [5] Lack E, Cubilla A, Woodruff J, et al. Paragangliomas of the head and neck region. Cancer 1977;39:397–409. [6] Rao AB, Koeller KK, Adair CF, et al. Paragangliomas of the head and neck: radiologic–pathologic correlation. Arch Armed Forces Inst Pathol 1999;19:32–1605. [7] Pelliteri PK, Rinaldo A, Myssiorek D, et al. Paragangliomas of the head and neck. Oral Oncol 2004;34:36–829. [8] Pratt LW. Familial carotid body tumors. Arch Otol 1973;97:6–334. [9] Grufferman S, Gillman MW, Pasternak LR, et al. Familial carotid body tumors: case report and epidemiological review. Cancer 1980;46: 22–2116. [10] Gardner P, Dalsing M, Weisbarger E, et al. Carotid body tumors, inheritance and a high incidence of associated cervical paragangliomas. Am J Surg 1996;172:9–196. [11] Mall J, Saclarides T, Doolas A, et al. First report of hepatic lobotomy for metastatic carotid body tumor. J Cardiovasc Surg 2000;41:61–759. [12] Shamblin WR, ReMine WH, Sheps SG, et al. Carotid bodu tumor, (Chemodectoma): clinocopathological analysis of ninety cases. Am J Surg 1971;122:9–732.
[13] Kaman L, Singh RR, Aggarwal R, et al. Diagnostic and therapeutic approaches to carotid body tumors: report of three cases and review of literature. Aust N Z Surg 1999;69:5–852. [14] Grimley PM, Glenner CG. Histology and ultrastructure of carotid body paragangliomas: comparison with the normal gland. Cancer 1967;20: 88–1973. [15] Gaylis H, Mieny CJ. The incidence of malignancy in carotid body tumors. Br J Surg 1977;64:9–885. [16] Lees CD, Levine HL, Beven EG, et al. Tumors of the carotid body: experience with 41 operative cases. Am J Surg 1981;142:5–362. [17] Chambers RG, Mahoney WD. Carotid body tumors. Am J Surg 1968;116:554. [18] Farr HW. Carotid body tumors: a 40 year study. Cancer 1980;30: 5–260. [19] Lee JH, Barich F, Karnell LH, et al. National cancer data base report on malignant paragangliomas of the head and neck. Cancer 2002;94:7–730. [20] McPherson GAD, Holliday AW, Mansfield AO. Carotid body tumors and other cervical paragangliomas: diagnosis and management in 25 patients. Br J Surg 1989;76:6–33. [21] Persky MS, Setton A, Niimi Y, et al. Combined endovascular and surgical treatment of head and neck paragangliomas — a team approach. Head Neck 2002;24:31–423. [22] Sykes JM, Ossoff RH. Paragangliomas of the head and neck. Otolaryngol Clin North Am 1986;19:67–755. [23] Hinerman RW, Mendenhall WM, Amdur RJ, et al. Definitive radiotherapy in the management of chemodectomas arising in the temporal bone, carotid body and glomus vagale. Head Neck 2001;23: 71–363. [24] Cole JM, Beiler D. Long-term results of treatment for glomus jugulare and glomus vagale tumors with radiotherapy. Laryngoscope 1994;04: 5–1461. [25] Evenson LJ, Mendenhall WM, Parsons JT, et al. Radiotherapy in the management of chemodectomas of the carotid body and glomus vagale. Head Neck 1998;20:13–609. [26] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.