C A S R E P O R E T Color Doppler Sonography of the Neck in a Patient with Bilateral Carotid Body Tumors Hsin-Ju Cheng , Chih-Hsun Chu2, Chih-Chen Lu1, Po-Chin Wang 3, Shyh-Jer Lin4, Chun-Chin Sun, Mei-Chun Wang, Jenn-Kuen Lee1,5, Ming-Ju Chuang , Han-Kai Tsai, Hing-Chung Lam1,6* Paragangliomas are rare cases Carotid body tumor (CBT) is the most common paraganglioma of the head and neck Embryologically derived from neural crest cells, paraganglioma and pheochromocytoma are similar in histology But unlike pheochromocytoma, almost all paragangliomas are nonfunctional Duplex sonography is increasingly used as the first noninvasive diagnostic tool for neck mass However, for more detail of soft tissue nearby, magnetic resonance imaging (MRI) and computed tomography (CT) with 3D reconstruction are preferred Herein we report a patient having bilateral CBT concomitant with bilateral pheochromocytomas Duplex sonography clearly demonstrates the tumor and surrounding carotid arteries Compared with CT, duplex sonography is a more rapid, convenient, safe, and economic measurement for the first diagnostic step KEY WORDS — carotid body tumor, paraganglioma, sonography, ultrasound ■ J Med Ultrasound 2009;17(2):114–119 ■ Introduction Carotid body tumor (CBT) is the most common paraganglioma of the head and neck Other paraganglioma in the head and neck include jugular, vagal, nasal, orbital, laryngeal, and tympanic tumors [1] Embryologically derived from neural crest cells of the autonomic nervous system, paragangliomas are similar to the pheochromocytomas histologically But unlike pheochromocytoma, paragangliomas are mainly nonfunctioning, and only 1–3% of paragangliomas are hyperfunctioning [2] Symptoms and signs such as palpitations, tremors, tachycardia, and hypertension may indicate possible endocrine activity of these tumors [3] Paragangliomas grow along the parasympathetic nervous system CBT is a paraganglioma originating in the chemoreceptors of the carotid body High altitude hypoxia-induced hyperplasia of chemoreceptor tissues is assumed to be the cause of CBT Received: September 17, 2008 Accepted: November 24, 2008 Division of Endocrinology and Metabolism, Kaohsiung Veterans General Hospital, 1National Yang-Ming University and 2Tzuhui Institute of Technology, 3Department of Radiology, Kaohsiung Veterans General Hospital, 4Division of Hematology, Kaohsiung Veterans General Hospital, 5Laboratory of Biochemistry, Kaohsiung Veterans General Hospital, 6Yuh-Ing Junior College of Health Care & Management *Address correspondence to: Prof Hing-Chung Lam, Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Veterans General Hospital, No 386, Ta-Chung 1st Road, Kaohsiung, Taiwan E-mail: hclam@vghks.gov.tw 114 J Med Ultrasound 2009 • Vol 17 • No ©Elsevier & CTSUM All rights reserved Sonographic Diagnosis of Carotid Body Tumor The prevalence of CBT at high altitude is ten times more frequent than that at sea level [1] The weight of a combined carotid body at sea level is around 20 mg, and that at high altitude is about 60 mg [4] The female to male ratio of CBT is around 2:1 at sea level, but elevated to 8:1 at high altitude [5] A lower baseline hemoglobin level accounts for the higher sensitivity of females to hypoxia Additionally, genetic defects contributed to familial paragangliomas have also been proposed [6] About 10–50% of paragangliomas are familial type [7] and the genetic defects may involve the oxygen-sensing and signaling pathway [6] Furthermore, neovascularization due to the hypoxia-activated vascular endothelial growth factor may also be involved in the pathogenesis of CBT [8] Contrastingly there are some conflicts to the stance that low hemoglobin levels or high altitude are related to hypersensitivity of a carotid body Luna-Ortiz et al have shown that there were no significant differences in the mean hemoglobin and hematocrit between residents living at high altitude or low altitude [9] Hence they suggested that ethnicity may play a role Though angiography was commonly performed in the diagnosis of a carotid body tumor in the past [3], the rapidity, convenience, and safety of color duplex sonography means it is performed more frequently as the first diagnostic tool Some papers have mentioned sonography in the diagnosis of carotid body tumors, but few have shown the sonographic images [10,11] In this report we submit images of carotid body tumors using 2D imaging, duplex sonography, and multidetector computed tomography (CT) with 3D reconstruction studies including CT and MRI of the neck and CT of the abdomen were performed However only tumors in bilateral carotid spaces as well as over bilateral adrenal glands were disclosed Biopsy of the left-sided neck mass was performed which revealed a pheochromocytoma-like tumor The level of urine vanillylmandelic acid (VMA) of this patient in 24 hours was 22.13 mg/day He was referred to our institution for further management Physical examination disclosed a slim build with a low body mass index (BMI) (height 178 cm, weight 51.2 kg, BMI 16.12 kg/m2), blood pressure of 115/ 82 mmHg, a heart rate of 100 beats per minute, a respiratory rate of 18/min, and a body temperature of 36.1°C A bilateral pulsatile and painless mass of about × cm2 in size was noted below the angle of the mandible Otherwise, there were no significant findings and his blood pressure remained normal during hospitalization Endocrine tests including serum thyroid hormones, parathyroid hormones, prolactin, cortisol, adrenocorticotropin (ACTH), and aldosterone levels were unremarkable Neck sonography (Figs and 2), neck to abdominal CT (Fig 3), and whole abdominal MRI (not shown) revealed only the presence of bilateral CBT concomitant bilateral adrenal tumors An otolaryngologist did not suggest surgical management of his carotid body tumors due to a high risk of neurological complications The patient was referred to a urologist to consider adrenalectomy Six months after he was discharged from our hospital, he visited our clinic again There was no further body weight loss during the months and he had still not decided to receive adrenalectomy Case Report Discussion A 36-year-old man was referred to our institution with a bilateral palpable neck mass and rapid body weight loss He had found bilateral neck mass over submandibular area years beforehand However, he felt two neck masses grow rapidly with a body weight loss of about kg in the last months He visited a local hospital where a series of imaging Although some suggest that CBT is present more in people living at high altitude and in females with relatively low hemoglobin, our patient was a previously healthy man who lived at sea level, and his hemoglobin was 13.2 g/dL on admission A painless cervical mass may be the initial presentation of CBT [3,5,9] The duration of symptoms J Med Ultrasound 2009 • Vol 17 • No 115 H.J Cheng, C.H Chu, C.C Lu, et al A B CBT D C CBT Fig Neck sonography of the right-sided CBT (A) Right-sided neck mass, transverse view CBT was partially surrounded by internal carotid artery (thick arrow) and external carotid artery (thin arrow), compatible with Shamblin class II tumor (B) Right-sided neck mass, transverse view with Doppler scan Blue confirmed these vessels were arteries, an internal (thick arrow) and an external (thin arrow) carotid artery Red confirmed the internal jugular vein (double arrow) (C) Right-sided neck mass, longitudinal view CBT presented as a mass lesion surrounded by the internal (thick arrow) and external (thin arrow) carotid artery (D) Right-sided neck mass, longitudinal view with Doppler scan may range from to years prior to the diagnosis due to the slow progression of the tumor [5,7] This patient noticed bilateral painless cervical masses years beforehand but had paid no attention to it due to a lack of initial symptoms Only 3% of paraganglioma may transform into malignancy [12] There are no histological characteristics for distinguishing malignant changes in paraganglioma Malignancy is defined as paraganglioma with distant metastases The most reported sites of metastases include the liver, bone, kidney, lung, breast, pancreas, retroperitoneum and thyroid [13,14] Systemic symptoms like malaise, weight loss or weakness may suggest metastatic disease [3] 116 J Med Ultrasound 2009 • Vol 17 • No Although the patient had a weight loss of about kg in months, he did not report any other discomfort He visited our clinic again months after discharge and we noticed that there was no further body weight loss during that period Image surveys and laboratory examinations during hospitalization favored bilateral CBT and bilateral pheochromocytomas without significant metastasis Angiography was previously the preferred method for the diagnosis of carotid body tumors [3] As technology progressed, noninvasive procedures like MRI and CT offered 3D reconstruction and thus provided more information of soft nearby tissue [10,15] Nevertheless, color duplex sonography is Sonographic Diagnosis of Carotid Body Tumor A B CBT C D Fig Neck sonography of the left-sided carotid body tumor (CBT) scanning from upper to lower portion (A) Left-sided neck mass, transverse view, 2D image CBT between the internal (thick arrow) and external (thin arrow) carotid artery (B) The internal and external artery was partially embedded in the CBT, which is compatible with a Shamblin class II tumor (C) The internal and external arteries became closer together (D) The carotid artery bifurcation site A B Fig Neck CT, 3D reconstruction, oblique sagittal view (A) Shows the patient’s left CBT, surrounded by an internal and external carotid artery (B) The right CBT J Med Ultrasound 2009 • Vol 17 • No 117 H.J Cheng, C.H Chu, C.C Lu, et al still recommended as the first diagnostic step by some authors [10], and a high diagnostic rate of around 90% has been proposed by Jansen et al [16] and Kapfer et al [17] This is due to the fact that hypervascularity has been considered a specific criterion for diagnosing a CBT by color duplex sonography [18] and hence color Doppler studies are helpful differential tools in patients with neck lesions that are difficult to diagnose Nevertheless, MRI or CT with 3D reconstruction are still necessary to provide more information on soft nearby tissue for further surgical planning Treatment choices include surgical resection, radiation, stereotactic radiosurgery, embolization, 131 I-MIBG (metaiodobenzylguanidine) and combination therapy Surgical management is the first choice if the tumor is resectable The therapeutic goal of CBT is complete surgical resection of the tumor with preservation of adjacent neurovascular structures Incomplete excision is associated with a significant local recurrence rate [3] However, the size, extension, and localization of the tumor all influence the possibility of tumor resection and acceptable morbidity Shamblin et al proposed a three-stage classification in 1971 to grade difficulty of resection in CBT [19] Class I tumors are defined as localized and easily resected tumors Class II tumors are those partially surrounding the blood vessels Class III tumors are those completely encased the carotids Most cases are class II or class III tumors when diagnosed [3,9,20] and the morbidity related to the surgical resection increases for these class II and class III tumors In order to avoid neurological deficits, early surgical management for class III tumors is recommended by Luna-Ortiz et al [9] However, because of the high morbidity rate, some authors have not suggested surgical treatment for those over 60 years of age unless malignancy is suspected [21] Our case had Shamblin class II CBT tumors on both sides of the neck We consulted an otolaryngologist, but surgical management was not considered due to the high risk of neurological complications The use of radiotherapy is still controversial for CBT management For unresectable tumors, 118 J Med Ultrasound 2009 • Vol 17 • No radiotherapy with fractionated doses of 1.8– 2.0 Gy/day (total dose 45 Gy) may be considered for local control [22–24] As well as the ablation of local tumor, radiotherapy could also be performed for distant metastases with good symptom control [13] Recently, stereotactic radiosurgery which allows cellular damage within a sharply defined treatment volume has been employed to stabilize tumor growth [25] 131I-MIBG, either used alone or in combination therapy for metastatic paragangliomas, has been reported to result in clinical improvement and complete remission, respectively [26,27] Finally, due to the rich vascular nature of these tumors, preoperative conventional endovascular transarterial embolization [28] and direct puncture embolization with cyanoacrylate glue or ethanol [29,30] have been described as useful adjuvants prior to surgery How long should we leave it before we follow up imaging of a patient with CBT ? René van den Berg suggested a follow-up interval of approximately years, or even more in stable paraganglioma [13] Of course, this would depend on changes in the clinical situation of the patient In conclusion, CBT are rare tumors of the head and neck and color duplex sonography can be used as the first-line diagnostic tool for the detection of CBT References Saldana MJ, Salem LE, Travezan R High altitude hypoxia and chemodectomas Human Pathol 1973;4: 251–63 Manolidis S, Shohet JA, Jackson CG, et al Malignant glomus tumors Laryngoscope 1999;109:30–4 Patetsios P, Gable DR, Garrett WV, et al Management of carotid body paragangliomas and review of a 30-year experience Ann Vasc Surg 2002;16:331–8 Heath D The human carotid body in health and disease J Pathol 1991;16:1–8 Rodriguez-cuevas H, Lau I, Rodriguez PH, et al Highaltitude paragangliomas diagnostic and therapeutic considerations Cancer 1986;57:672–6 Baysal BE, Ferrell RE, Willett-Brozick JE, et al Mutations in SDHD, a mitochondrial complex II Sonographic Diagnosis of Carotid Body Tumor 10 11 12 13 14 15 16 17 18 gene, in hereditary paraganglioma Science 2000;287: 848–51 Pellitteri PK, Rinaldo A, Myssiorek D, et al Paragangliomas of the head and neck Oral Oncology 2004;40: 563–75 Forsythe JA, Jiang BH, Iyer NV, et al Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor Mol Cell Biol 1996;16: 4604–13 Luna-Ortiz K, Rascon-Ortiz M, Villavicencio-Valencia V, et al Carotid body tumors: review of a 20-year experience Oral Oncology 2005;41:56–61 Alkadhi H, Schuknecht B, Stoeckli SJ, et al Evaluation of topography and vascularization of cervical paragangliomas by magnetic resonance imaging and color duplex sonography Neuroradiology 2002;44: 83–90 Stoeckli SJ, Schuknecht B, Alkadhi H, et al Evaluation of paragangliomas presenting as a cervical mass on color-coded Doppler sonography Laryngoscope 2002;112:143–6 Johnston F, Symon L Malignant paraganglioma of the glomus jugulare: a case report Br J Neurosurg 1992; 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