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Carotid body tumor in a 13-year-old child: Case report and review of the literature
Carotid body tumor in a 13-year-old child: Case report and review of the literature George S. Georgiadis, MD,a Miltos K. Lazarides, MD, EBSQvasc,a Aggelos Tsalkidis, MD,b Paraskevi Argyropoulou, MD,c and Alexandra Giatromanolaki, MD,d Alexandroupolis, Greece Carotid body tumor (CBT), an extra-adrenal paraganglioma, represents an uncommon entity arising in chemoreceptor tissue located at the carotid bifurcation. Only a few cases have been reported in the literature in the pediatric age group less than 14 years of age, primarily as case reports. Surgical excision is advisable in almost all ages, however, in childhood, it is known to carry risks and difficulties due to the smaller size of the involved anatomical structures. We report an unusual case of a large (50 ⴛ 43 ⴛ 30 mm) carotid paraganglioma of Shamblin type III in a 13-year-old female, living at high altitude until the age of 9 years. This cervical mass was present, but smaller in size, several years before admission. However, an intense hypoxic stimulus at high altitude for 2 months at the age of 13 years probably induced a fast growing period of the lesion. The tumor was removed en bloc with the involved carotid segments and vascular continuity was restored by means of a common carotid to internal carotid saphenous vein interposition graft. No malignant behavior or regional metastatic spread of the resected mass was demonstrated. Furthermore, no inheritance pattern between family members was confirmed. A clinical update on CBTs in childhood a propos of this case report is undertaken. ( J Vasc Surg 2008;47:874-80.)
Carotid body tumors (CBT) are distinctly uncommon hypervascular neck tumors.1-3 They arise from glomus bodies (paraganglia) located in the crotch of the external and internal artery, at the level of carotid bifurcation. Carotid paraganglia are composed of chemoreceptor cells derived from the carotid primitive neural crest.1,4 In general, tumors arising from any paraganglionic tissue, are best called paragangliomas (PGs) and are arbitrarily classified by their relationship to the adrenal gland (adrenal medullary tumors or pheochromocytomas and extra-adrenal PGs). Of all extra-adrenal PGs in adults, only 3% are reported to occur in the head and neck region, while up to 85% occur in the abdomen, the latter with a metastatic behavior present in 50% of patients.5,6 In children, PGs are more commonly found at extra-adrenal sites and can occur anywhere in the autonomic nervous system.7 Those tumors associated with arterial vessels and cranial nerves of the ontogenetic brachial arches, usually nonchromaffin and nonfunctioning, like carotid body PGs, are rare in childhood.7 PGs appear to have gender predilection (boys ⬎ girls) before adolescence.8 CBT is the most frequent paraganglioma in the neck9-12 accounting for almost 60% of head and neck PGs.9 Principal clinical manifestations of CBT include a slow growing pulsatile upper cervical mass with possible vagal or hypoglossal neuropathy in large tumors.1,11,13,14 Surgical excision at presentation is advisable in almost all From the Department of Vascular Surgery,a the Department of Pediatrics,b the Department of Radiology,c and the Department of Pathology,d “Demokritos” University Hospital. Competition of interest: none. Additional material for this article may be found online at www.jvascsurg.org. Reprint requests: George S Georgiadis, MD, University Hospital of Alexandroupolis, Alexandrou Papanastasiou 7 str., Alexandroupolis, Greece, 68100 and (e-mail: [email protected]). 0741-5214/$34.00 Copyright © 2008 by The Society for Vascular Surgery. doi:10.1016/j.jvs.2007.10.040
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cases,6,11,15-18 since not treating it may destroy glossopharyngeal, hypoglossal, vagal or recurrent laryngeal nerve,19 or invade carotid vessels with risk of stenosis, occlusion, or even rupture.1,20 Even sympathetic chain may be involved in large CBTs.13,14,17,20 The potential of malignant local behavior or metastasis,1,2,4,12,16-18,20-24 although of low grade, should also not be overlooked. On the basis of tumor size and involvement of the carotid vessels, three types may be recognized according to Shamblin, with type III reserved for tumors that encircle the carotid vessels, invading the media, and thus, excluding the possibility of subadventitial resection.1,12,23 CBT is uncommon in the pediatric population.6,7,25,26 Among 89 patients with CBTs, Shamblin et al reported only one case in a 12-year-old child.1 Similarly, Dickinson et al reported only one case of a young 12-year-old girl, complicated by XII nerve permanent paralysis in a review of 37 CBTs.25 Recently, Takutz et al found only one 8-yearold boy having CBT in a large population of patients younger than 21 years, with nonhematologic malignancies (0.004 %).6 To the best of our knowledge, only 16 cases of surgically excised CBTs in childhood (age at operation ⱕ14 years) have been reported in the literature, most of them sporadic in type. We report a case of Shamblin type III carotid body tumor resection in a 13-year-old girl. Review of the English literature on similar cases in childhood is also undertaken. CASE REPORT A 13-year-old girl presented in the pediatric department of our hospital with a painless pulsatile slow-growing mass in the right upper neck. History revealed that this mass was present, but smaller in size, several years before admission (first appeared at the age of 9 years) and was considered lymph node hyperplasia. Of interest, this neck lump had a fast growing period after a 2-month visit to a
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location at an altitude about 1500 m above sea level. On clinical examination this mass was located in the upper part of the anterior triangle, 1.5 cm below the mandible. Mobility was noted only in the lateral direction (positive Fontaine’s sign)13,27 while no bruit was heard above the mass. Although large in size, dysphagia and hoarseness were absent indicating no pressure on the pharynx or vagal involvement, respectively. Vocal cord paralysis was also excluded after laryngeal examination. Furthermore, no signs of hypoglossal neuropathy were detected. The patient was normotensive while hypercatecholaminemia was not present. Bilateral ultrasound scanning excluded the presence of lymph nodes or carotid aneurysm, suggesting a tumor in the right anterior triangle of the neck. This tumor, oval in shape, had a heterogeneous hypoechoic appearance. The next day, a magnetic resonance imaging (MRI) of the neck, revealed an enhanced mass with a vertical diameter of 50 mm (measured 50 ⫻ 43 ⫻ 30 mm), at the level of carotid bifurcation. The mass encased and constricted the external (ECA) and internal carotid arteries (ICA). ECA and ICA were splayed (Fig 1). Magnetic resonance angiography showed the location of the mass at the angle between the ECA and ICA while encircling both vessels (Fig 2). The base of the skull was not involved. The diagnosis of carotid body tumor of type III Shamblin was suspected. Contralateral carotid body was free of disease while chest and abdominal computer tomography (CT) were negative for other PGs. The tumor was removed en bloc with the involved carotid segments, and vascular continuity was restored by means of a common carotid to internal carotid interposition saphenous vein graft (see surgical details in Appendix, online only). The child had an uneventful recovery and was discharged on postoperative day five. Histopathological examination confirmed the preoperative diagnosis of CBT. Lymph node examination proved negative for disease. Ultrasonographic studies of all her brothers (three males and one female) were tested negative for similar lesions. Similarly, neither of siblings, or parents of the child had so far evidence of disease. On 9-month follow-up, the vein conduit remains patent with no evidence of anastomotic stenosis or aneurysmal dilatation, while neurological examination revealed no cranial nerve palsies.
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Fig 1. T1-weighted MRI gradient echo (GRE) of the neck with fat saturation, after administration of gadolinium, demonstrates a mass within the right carotid space, centered in the crotch of the carotid bifurcation, with intense enhancement. The mass encases and constricts the external carotid artery (ECA) and internal carotid artery (ICA). ECA and ICA are splayed.
DISCUSSION CBTs, also referred to as chemodectomas, glomus tumors or paragangliomas, represent the most common PGs of head and neck12,16,17 after glomus jugulare.9 However, PGs comprise only 0.6% of all neoplasms in the head and neck region.3 These extra-adrenal PGs are infrequent in the pediatric population and occur most commonly in the retroperitoneum and head and neck.6 As all types of PGs, have a propensity for multicentricity,3,11,15,19,20,28 the most common association be between intravagal PGs and CBTs.28 CBTs are often bilateral,2,11,13,18,20,24,25,29-31 and usually sporadic in form, but rarely can have familial inheritance,4,15,17 related to mutations in any of the specific susceptibility genes.32 In the familial form, there is an incidence of multiple tumors, up to 25% to 48% of cases, both synchronous and metachronous15,21,33; This later type is more likely to be malignant.34 There is also evidence, that chronic hypoxic medical conditions like chronic obstructive pulmonary disease (COPD) or chronic hypoxic
Fig 2. MRA (3D/TOF/SPGR) of the neck shows a mass in the carotid bifurcation that splays internal and external carotid artery. Internal jugular vein is pushed out. (Image rotated).
stimulation in patients living at high altitudes, can lead to an overburden of the carotid body chemoreceptor cells to compensate for the lower levels of PO2. As a consequence, hypertrophy and subsequent hyperplasia/and neoplasia of the chief cells develops (hyperplastic type of CBT).32 It has been stated that individuals harboring mutations in CBT susceptibility genes and suffering chronic hypoxemia, may develop a CBT in earlier ages than otherwise.12
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Table. Review of surgically resected CBTs in children under 14 years old (at diagnosis and operation) 1st Author, Year
No of patients, CBTs (children)
Gender (age at operation)
Chambers, 1968
38, 40 (3)
Shamblin, 1971
89, 90 (ⱖ1)
M (12) M (14) F (9) NS (12)
none none none NS
⫺/25 ⫻ 25 ⫺/60 ⫻ 60 ⫺/15 ⫻ 20 NS/NS
Newland, 1980
1 (1)
F (13)
None
NS/25 ⫻ 80, functional CBT
24 (1)
F (12)
None
NS/NS
F (12) NS (12)
None NS
NS (I or II)/NS NS/NS
Carney, 1983
Other paragangliomas
Shamblin type/size (in mm)
Dickinson, 1986 Hallett, 1988
32, 37 (1) 139, 153 (ⱖ1)
Thompson, 1989
1 (1)
F (14)
unilateral glomus jugulare
R: I/20 ⫻ 20 L: III/large
Gunnot, 1990 Ophir, 1991
1 (1) 1 (1)
M (14) F (12)
II/35 ⫻ 25 ⫻ 15 R: III/30 ⫻ 40 L: II (L⬍30 ⫻ 30, estimation from CT)
Varudkar, 1993 Hajnzic, 1999
1 (1) 1 (1)
M (6) M (9)
None unilateral jugular (familial type-mother with a posterior mediastinum paraganglioma) Pheochromocytoma none, CBT resection 20 mo before
NS/50, recurrent CBT
Wang, 2000
29, 36 (ⱖ1)
NS (10)
NS
NS/15 to 60 for all CBTs
Plukker, 2001
35, 41 (ⱖ1)
NS (11)
NS
8 (1) 1 (1)
M (8.2) F (13)
None None
NS (mean: 30, 41, 66 for I, II and III respectively NS (possibly I or II), 25 III/50 ⫻ 43 ⫻ 30
Tekautz, 2003 Present case, 2007
IJV, Internal jugular vein; NS, not stated for the specific case; R, right; L, left (in bilateral CBTs); CBT, carotid body tumor.
CBTs as sole lesions, occur at any age,1,14,29,30 but most commonly in the fourth to sixth decades of life, the incidence being equal between men and women.3,5,6,20,21,25 In patients under 14 years old, the disease represents a rarity. Surprisingly, a recent review analyzing the experience of CBT management of 21 out of 33 vascular units of the Joint Vascular Research Group, reported, that CBT disease is an adult disease, since the age of the patients studied varied from 18 to 94 years, giving the message that CBTs cannot emerge in childhood.34 This is not the case, and the literature reveals that CBTs may occur also in younger6,35,36 or older1,8,15,20,25,29,37-39 children and adolescents.6-8,11,19,24,40 Only few cases of CBTs have been reported in the pediatric age according to this review (Table),1,6,15,20,25,29,30,35-39,41,42 mostly sporadic in form. In some large reports (not included in the Table), the type of glomus tumor in patients under 14 years old, was not clearly stated.19,43 Bilaterality of CBTs was observed in two patients, while three children had simultaneous PG at other site (one adrenal). Carney reported in 1983 that when the paraganglion system is involved in a tumorous syndrome, the adrenal medulla is affected almost exclusively.42 Neither child was involved in such syndromes in this review. To our knowledge, the
first case of CBT in a 7-year-old child, was first mentioned in a report by Harrington et al in 1941 (not included in the Table).44 CBTs present as slowly enlarging pulsatile cervical masses extending up to the angle of mandible.14,27 Error in the initial clinical diagnosis, as in our case, is not infrequent,25,27 and most patients are thought to have cervical lymphadenopathy, salivary gland, neurofibroma, brachial cyst, or lipoma.27 As disease progresses, lower cranial nerves and adjacent pharynx may be involved.6,10,11,21,45 Takautz et al reported an adolescent presented with a 6-month history of deficits of III, IV, V, and VI cranial nerves ipsilateral to a CBT.6 Occasionally a bruit is heard over the lesion12,17,25,45,46 suggesting significant compression of the carotid arteries.9 If small, they are usually asymptomatic, however, local pain, dysphagia, hoarseness, jaw stiffness, soar throat, or tongue numbness are not rare in larger tumors.3,13,16,17,21 Infrequently, a clinical syndrome characterized by hypertension, headache, and sweating may be present in functional tumors secreting catecholamines.13,41 Although 20% of head and neck PGs have antecedent or subsequent malignant behavior,5,6 malignancy is not the rule in CBTs.1,17 However, if present, the malignant character is justified only by
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Table. Continued Local involvement or distant metastasis/treatment (for CBTs only)
Outcome
Follow-up with no evidence of disease
none for all/totally excised
0% mortality, 0% hemiparesis for all study cases
10 y for both M 1 y for the F
all patients: one distant, one regional node metastasis/biopsy or excision only or excision ⫹ ligation of carotid vessels (in various combinations) extension into the calvarium along the IJV/partial resection plus radiotherapy and chemotherapy invasion of submaxillary gland/resection
all patients: 17 cerebrovascular events, 4 deaths
NS
NS
NS
NS
none/excision and ECA ligation (no shunt) NS/biopsy, partial or total excision (plus arterial repair and/or ECA ligation in some, especially large, tumors) R: none/subadventitial, resection, IJV ligated L: extension to skull base/resection and reconstruction with saphenous vein none/subadventitial resection R: none/ICA ligated and removed en block with the tumor, L: none/subadventitial resection (6 mo later) none/surgical excision of both tumors metastatic chest paraganglioma, metastatic lung disease/surgical excision, chemotherapy all patients: none/surgical resection, in 17 patients preoperative embolization all patients: none/complete resection
XII permanent paralysis all patients: 39.9% cranial nerve deficit, 13.7% stroke, 3.3% mortality
epithelioid myosarcoma (5) ⫹ chondroma (5) at age of 24 y, two nodules in left lung at 30 y, well at age 31 NS NS
none/gross total resection none/complete excision
right facial nerve paralysis no complications
NS NS
complete recovery R: paralysis of IXth to XIIth cranial nerves L: complete recovery persistent hypertension no surgical complications
1y 8y
all patients: 41% neurological deficits
mean: 2.9 for all patients
all patients: ICA injured in 7, neurological complications in 8 (5 temporary) complete response complete response
NS (metastatic disease in 2 patients)
metastatic disease predominantly to cervical nodes but infrequently to distant organs.1,22 Histological appearance is virtually never predictive of the metastatic behavior of the tumor.1,4,14,17,27 Most large reports quote CBT malignant transformation of 0% to 11.1%,1,2,12-14,16,18,20,24,27 with the risk of malignant degeneration greatest in young patients with heritable tumors.12,36 Considering the vasoformative nature of CBTs, incisional biopsy is not recommended since it may result in profuse bleeding and/or cranial nerve injury.13,14,23 However, fine-needle aspiration biopsy can be helpful only when the radiologic diagnosis is unclear.14 Ultrasound studies in both sides of the neck, may exclude the presence of lymph nodes, thyroid, or brachial cysts. In most cases, color-coded Doppler sonography evaluates the hypervascularity and upward intratumoral blood flow in a neck mass at carotid angle, suggesting a CBT.45 This modality is also a useful tool in the follow-up of CBTs3 and for screening of sporadic and familial cases.13,27 Accurate diagnosis is based on angiographic criteria,13,22,31 the most reliable of these being the separation and splaying of internal and external carotid arteries (known as the lyre sign).3,45 On CT scanning, CBT is easily recognized as hypervascular mass located at the carotid bifurcation, changing the
NS death 4 mo later
9.8 y 9 mo
architecture of the angle between the internal and external carotid artery, bringing them apart from each other resembling a saddle. Arterial anatomy of carotid vessels and their relationship to an enhancing lesion of the neck can also evaluated by CT angiography.3,10,23 MRI is the most important imaging modality in evaluating CBTs14 in relation to surrounding soft tissue and vascular structures9,15 and does not employ ionizing radiation or nephrotoxic contrast agents,23 the former raising concerns in young people regarding the potential for the development of radiationinduced malignancies. Axial T1- and T2-weighted MR images reveal well defined carotid space lesions.14 In children, MRI may be more helpful for evaluation and characterization of CBTs, since small tumors may be less easily depicted in angiographic or CT studies. Furthermore, MRI is more sensitive than CT to evaluate possible invasion of the base of the skull,14,15 if preoperative clinical examination suggests this may be. 111In octreotide scintigraphy also been investigated in the head and neck, has shown great promise in its ability to identify occult PGs23 and to detect metastases in patients with malignant tumors.16 Newer evidence suggests that positron emission tomography scanning may be more accurate than MRI in detecting primary tumors of less than 10 mm.45 Perhaps both aforemen-
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tioned investigations could be considered as diagnostic work-up of suspected CBTs in children, especially those with positive family history. Surgical treatment is mandatory12,13,14,16,20,23 even at presentation11,12,17,23,27 for definite cure. Another option for these tumors is radiotherapy but for benign neoplasms, is not usually advocated.14 Only one case of radiation therapy in pediatric population has been presented so far in the literature,36 possibly because children with CBTs usually of small size are candidates of complete surgical excision and therefore complete response to treatment. However, Takautz et al support that postoperative eradication of microscopic residual disease, often performed with encouraging results in adults, can also be considered as treatment approach in pediatric patients.6 Smith et al reported that, of those patients requiring vascular repair after CBT resection, 25% had evidence of malignant tumor histology.18 This finding, however, was not confirmed in our case. Our review, found only one child (male, 9 years old) with malignant CBT suffering massive metastatic pulmonary disease. Of those cases with available follow-up, only one case of CBT recurrence with metastatic lung disease was observed.36 Thus, early, upon diagnosis of a CBT, complete surgical excision is also recommended in children and adolescents, mainly because of unpredictable malignant potential, but also because any considerable delay allows the tumor to increase in size, with a tendency to show a locally aggressive and infiltrative growth pattern. Furthermore, early excision of CBTs in children under 14 years old, in appropriate hands, inevitably reduces the risk of devastating injuries, mainly cranial nerve damage, because small tumors, usually asymptomatic, have better outcome with almost zero morbidity.20,27 Nora et al.47 reported that when surgical resection of head and neck PGs is complete, recurrence is not an issue. However, in children of parents with cervical PGs, especially of those with recurrence or metachronous development of disease, there is a need of close follow-up for early documentation of similar lesions.15 Different patient demographics, tumor characteristics, and also surgical expertise, yield great variation of the results, of perioperative complications after surgical CBT resection, cited in the adult literature. An extending review reported an operative mortality of 5% to 13%, postoperative cranial nerve injury ratio of 32% to 44% and postoperative stroke rate of 8% to 20%.4 Few surgical and follow-up data of CBTs in patients under 14 years old are available in the literature, according to this review. For this reason, it is unclear if postoperative complications, especially cranial nerve dysfunction, have lower incidence in childhood (in this review: cranial nerve deficits in 3 CBTs, 15.8% including our case). Preoperative selective angiographic embolization leading to shrinkage of tumor vascularity and size, has been proposed to facilitate surgery and to diminish blood requirements,2,11,16,27,30,48 or even prepare the lesion for palliative radiotherapy. Although a matter of debate in the adult literature,2,9-11,13,17,20,27,30,31,48,49 in children, no
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case has been reported. Recently, Zaupa and Höllwarth, successfully embolized prior to surgery (after temporary balloon occlusion test of the anterior communicans artery), a CBT in a 15-year-old adolescent boy.40 It remains unclear if preoperative embolization may be advocated in older children (12 to 14 years old) with larger tumors, but cranial nerve palsies or stroke still remain a concern. The ease of a CBT resection depends on the size of the tumor.1,11,15,27,31,37 However, the degree of the tumor attachment to carotid vessels is not necessarily related to tumor dimensions.1 According to the Shamblin classification, the risk for cranial nerve injury and vascular injury increases, as the disease progresses and CBT enlarges.1 Complete CBT resection combined with vascular reconstruction is more frequently needed in Shamblin type II/III.18 Furthermore, longer mean duration of operation and excessive mean blood loss are more likely to occur in patients with type III CBTs.20 ECA ligation, as in our case, is not associated with any permanent sequelae.11,13,17,22,24,27,30 ICA should be spared if at all possible,14 but in young patients with growth potential, if it cannot be saved due to artery invasion, as in our case, interposition saphenous vein graft should be used.37,38 Type III CBTs in children necessitate the presence of a team with experience in carotid shunting and vascular reconstrunction.38 This review confirmed that CBTs are indeed extremely rare in childhood. However, unlike others,31 we believe that, no age cut-off point must be set for aggressively pursuing the diagnosis of CBT. Although most CBTs in children are of the sporadic type as was the case with the subject of this case report, there is a strong history of exposure to high altitudes in this patient that is a known risk factor for the development of CBTs in adults (hyperplastic form).50 As in most CBTs, a certain amount of time has to elapse before the clinical diagnosis can be made. This suggests that some cases, which developed in adolescent, might have been present early in childhood, and therefore a high index for suspicion is needed for diagnosis. This article suggests also that CBTs in children behave differently compared with that diagnosed in adults. Nodal involvement is infrequently found at the first clinical examination. Furthermore, larger tumors possibly appear more often in children since smaller ones can be mistaken for lymph nodes or other benign lesions. For this reason, early diagnosis of CBTs is fundamental in children under 14 years old, for the purpose of subadventitial resection that has the lowest morbidity and mortality rates. Local or distant metastatic behavior is not the rule for CBTs in children under 14 years old. Only one case of metastatic (pulmonary) paraganglioma has been reported so far in the literature.36 Furthermore, recurrent rates are definitely lower (in this review 5.9%) compared with those in adults. Only one case developed malignancies in other organs (Carney triad), on late follow-up. Close follow-up is advisable for all family members especially in familial CBT type.31 A proposed algorithm for the evaluation and treatment of CBTs in childhood is presented in Fig 3 (online only).
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AUTHOR CONTRIBUTIONS Conception and design: GS, ML Analysis and interpretation: GS, AT, PA, AG Data collection: GS, ML, AT, PA, AG Writing the article: GS, PA, AG Critical revision of the article: GS, ML, AT Final approval of the article: GS, ML, AT, PA, AG Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: GS REFERENCES 1. Shamblin WR, ReMine WH, Sheps SG, Harrison EG Jr. Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg 1971;122:732-9. 2. LaMuraglia GM, Fabian RL, Brewster DC, Pile-Spellman J, Darling RC, Cambria RP, et al. The current surgical management of carotid body paragangliomas. J Vasc Surg 1992;15:1038-44. 3. Lustrin ES, Palestro C, Vaheesan K. Radiographic evaluation and assessment of paragangliomas. Otolaryngol Clin North Am 2001;34: 881-906. 4. Dimakakos PB, Kotsis TE. Carotid body paraganglioma: review and surgical management. Eur J Plast Surg 2001;24:58-65. 5. Patel S, Winchester D, Benjamin R. A 15-year experience with chemotherapy of patients with paraganglioma. Cancer 1995;76:1476-80. 6. Takautz TM, Pratt CB, Jenkins JJ, Spunt SL. Pediatric extraadrenal paragaglioma. J Pediatr Surg 2003;38:1317-21. 7. Deal JE, Sever PS, Barratt TM, Dillon MJ. Pheochromocytoma-investigation and management of 10 cases. Arch Dis Child 1990;65: 269-74. 8. Stackpole RH, Melicow MM, Uson AC. Pheochromocytoma in children. Report of nine cases and review of the first 100 published cases with follow-up studies. J Pediatr 1963;63:313-30. 9. Pellitteri PK, Rinaldo A, Myssiorek D, Gary Jackson C, Bradley PJ, Devaney KO, et al. Paragangliomas of the head and neck. Oral Oncol 2004;40:563-75. 10. Rao AB, Koeller KK, Adair CF. Paragangliomas of the head and neck: radiologic-pathologic correlation. Radiographics 1999;19:1605-32. 11. Dardik A, Eisele DW, Williams GM, Perler BA. A contemporary assessment of carotid body tumor surgery. Vasc Endovasc Surg 2002;36: 277-83. 12. Knight TT Jr, Gonzalez JA, Rary JM, Rush DS. Current concepts for the surgical management of carotid body tumor. Am J Surg 2006;191: 104-10. 13. Patetsios P, Gable DR, Garrett WV, Lamont JP, Kuhn JA, Shutze WP, et al. Management of carotid body paragangliomas and review of a 30-year experience. Ann Vasc Surg 2002;16:331-8. 14. van der Mey AG, Jansen JC, van Baalen JM. Management of carotid body tumors. Otolaryngol Clin North Am 2001;34:907-24. 15. Ophir D. Familiar multicentric paragangliomas in a child. Familial multicentric paragangliomas in a child. J Laryngol Otol 1991;105:376-80. 16. Liapis CD, Evangelidakis EL, Papavassiliou VG, Kalisis JD, Gougoulakis AG, Polyzos AK, et al. Role of malignancy and preoperative embolization in the management of carotid body tumors. World J Surg 2000;24:1526-30. 17. Bastounis E, Maltezos C, Pikoulis E, Leppaniemi AK, Klonaris C, Papalambros E. Surgical treatment of carotid body tumors. Eur J Surg 1999;165:198-202. 18. Smith JJ, Passman MA, Dattilo JB, Guzman RJ, Naslund TC, Netterville JL. Carotid body tumor resection: does the need for vascular reconstruction worsen outcome? Ann Vasc Surg 2006;20:435-9. 19. van der Mey AG, Frijns JH, Cornelisse CJ, Brons EN, van Dulken H, Terpstra HL, et al. Does intervention improve the natural course of glomus tumors? A series of 108 patients seen in a 32-year period. Ann Otol Rhinol Laryngol 1992;101:635-42.
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20. Plukker JT, Brongers EP, Vermey A, Krikke A, van den Dungen JJ. Outcome of surgical treatment for carotid body paraganglioma. Br J Surg 2001;88:1382-6. 21. Bishop GB Jr, Urist MM, el Gammal T, Peters GE, Maddox WA. Paragangliomas of the neck. Arch Surg 1992;127:1441-5. 22. Dias da Silva A, O’Donnell S, Gillespie D, Goff J, Shriver C, Rich N. Malignant carotid body tumor: a case report. J Vasc Surg 2000;32: 821-3. 23. Iafrati MD, O’Donnell TF Jr. Adjuvant techniques for the management of large carotid body tumors. A case report and review. Cardiovasc Surg 1999;7:139-45. 24. Luna-Ortiz K, Rascon-Ortiz M, Villavicencio-Valencia V, GranadosGarcia M, Herrera-Gomez A. Carotid body tumors: review of a 20-year experience. Oral Oncol 2005;41:56-61. 25. Dickinson PH, Griffin SM, Guy AJ, McNeill IF. Carotid body tumor: 30 years experience. Br J Surg 1986;73:14-6. 26. Lees CD, Levine HL, Beven EG, Tucker HM. Tumors of the carotid body. Experience with 41 operative cases. Am J Surg 1981;142:362-5. 27. Westerband A, Hunter GC, Cintora I, Coulthard SW, Hinni ML, Gentile AT, et al. Current trends in the detection and management of carotid body tumors. J Vasc Surg 1998;28:84-92. 28. Borba LA, Al-Mefty O. Intravagal paragangliomas: report of four cases. Neurosurgery 1996;38:569-75. 29. Chambers RG, Mahoney WD. Carotid body tumors. Am J Surg 1968; 116:554-8. 30. Wang SJ, Wang MB, Barauskas TM, Calcaterra TC. Surgical management of carotid body tumors. Otolaryngol Head Neck Surg 2000;123: 202-6. 31. Kohn JS, Raftery KB, Jewell ER. Familial carotid body tumors: a closer look. J Vasc Surg 1999;29:649-53. 32. Baysal BE, Myers EN. Etiopathogenesis and clinical presentation of carotid body tumors. Microsc Res Tech 2002;59:256-61. 33. Isik AC, Erem C, Imamoglu M, Cinel A, Sari A, Maral G. Familial paraganglioma. Eur Arch Otorhinolaryngol 2006;263:23-31. 34. Sajid MS, Hamilton G, Baker DM, and on behalf of Joint Vascular Research Group. A multicenter review of carotid body tumor management. Eur J Vasc Endovasc Surg 2007;34:127-30. 35. Varudkar AS, Kokandkar HR, Gumaste GG, Bhople KS, Kumbhakarna NR. Carotid body paraganglioma with coexistent pheochromocytoma in childhood. Indian J Cancer 1993;30:109-12. 36. Hajnzic TF, Kruslin B, Belicza M. Carotid body paraganglioma in a 9-year-old boy with extensive pulmonary metastases. Med Pediatr Oncol 1999;32:399-400. 37. Hallett Jr JW, Nora JD, Hollier LH, Cherry Jr KJ, Pairolero 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;7:284-91. 38. Thompson JW, Cohen SR. Management of bilateral carotid body tumors and a glomus jugulare tumor in a child. Int J Pediatr Otorhinolaryngol 1989;17:75-87. 39. Gounot E, Couillault G, Maingueneau C, Autissier JM. Paraganglioma of the carotid body. A propos of a case in a 14-year-old child. Chir Pediatr 1990;31:125-6. 40. Zaupa P, Höllwarth ME. Carotid body paraganglioma: rare tumor in a 15-year-old adolescent boy. J Pediatr Surg 2007;42:E13-7. 41. Newland MC, Hurlbert BJ. Chemodectoma diagnosed by hypertension and tachycardia during anesthesia. Anesth Analg 1980;59:388-90. 42. Carney JA. The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review. Medicine (Baltimore) 1983;62:159-169. 43. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extraadrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc 1999;74: 543-52. 44. Harrington SW, Clagett OT, Dockerty MD. Tumors of carotid body; cIinica1 and pathological considerations of twenty tumors affecting nineteen patients (one bilateral) Ann Surg 1941;114:820-33.
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45. Gujrathi CS, Donald PJ. Current trends in the diagnosis and management of the head and neck paragangliomas. Curr Opin Otolaryngol Head Neck Surg 2005;13:339-42. 46. Liapis C, Gougoulakis A, Karydakis V, Verikokos C, Doussaitou B, Skandalakis P, et al. Changing trends in management of carotid body tumors. Am Surg 1995;61:989-93. 47. Nora JD, Hallett JW, O’Brien PC, Naessens JM, Cherry KJ, Pairolero PC. Surgical resection of carotid body tumors: long-term survival, recurrence, and metastasis. Mayo Clin Proc 1988;63:348-52. 48. Smith RF, Shetty PC, Reddy DJ. Surgical treatment of carotid paragangliomas presenting unusual technical difficulties. The value of preoperative embolization. J Vasc Surg 1988;7:631-7.
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49. DuBois J, Kelly W, McMenamin P, Macbeth GA. Bilateral carotid body tumors managed with preoperative embolization: a case report and review. J Vasc Surg 1987;5:648-50. 50. Rodriguez-Cuevas S, Lopez-Garza J, Labastida-Almendaro S. Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level. Head Neck 1998;20:374-8.
Submitted Aug 17, 2007; accepted Oct 22, 2007.
Additional material for this article may be found online at www.jvascsurg.org.
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APPENDIX, ONLINE ONLY Surgical details Under loop magnification, surgical approach was performed through a standard linear incision along the anterior border of the sternocleidomastoid muscle with the distal end ascending behind the lobe of the ear. Initial control was obtained via exposure of the common carotid artery 2 cm below the tumor. While mobilizing the tumor, no invasion into surrounding structures was found, however, the internal jugular vein and hypoglossal nerve were found adherent to the tumor. Although we tried to find a subadventitial dissection plane, this was impossible because of penetration of the media. Additionally, the internal and external carotid arteries were hardly recognized. Only their undiseased distal segments were eventually exposed. During this stage, the hypoglossal and vagus nerve were safeguarded but the ansa hypoglossi was sacrificed. A small regional lymph node was resected at this stage. Considering the above findings, we decided en bloc resection of the mass with the carotid bifurcation. A 7-cm long segment of saphenous vein was harvested initially from the proximal thigh of the ipsilateral leg. After heparinization, the common and internal carotid arteries were clamped. Then, the common carotid artery was sectioned immediately below the tumor and the carotid bifurcation
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ligated. Placing an Inahara shunt soon after clamping, the vein graft was attached first to the distal internal carotid artery in an end-to-side fashion. Once the distal anastomosis was completed, the Inahara shunt was removed. Using now, a Javid shunt inserted to the distal internal artery through the vein graft, flushing was achieved via the cut vein stump. Then, the proximal part of the Javid shunt was inserted to the common carotid artery stump and the proximal anastomosis of the vein bypass was performed in an end-to-end fashion while still maintaining cerebral flow. Leaving the last three anterior sutures untied, the Javid shunt was removed. Via this site, antegrade and retrograde flushing was achieved after which the sutures are tightened and finally tied with flow running through the graft. At a final stage, the tumor was resected starting from the carotid bifurcation and extended distally. At that point, both external and internal carotid arteries were ligated with the latter being ligated just below the anastomotic heel (Fig 4, online only). The whole procedure was performed with the use of bipolar diathermy, which was found useful to control bleeding on the tumor surface, mainly in the initial stages of the operation. Furthermore, some local papaverine was used to avoid internal carotid artery (ICA) spasm. Intraoperative blood loss was limited to 300 ml, and all was transfused via a blood saver machine. No neurological or cranial nerve deficits were observed postoperatively.
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Fig 3, online only. Proposed management algorithm for carotid body tumors (CBTs) in childhood.
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Fig 4, online only. Common carotid to internal carotid artery bypass with reversed great saphenous vein. External carotid artery ligated just below the anastomotic heel.
Carotid body tumors (CBT) are distinctly uncommon hypervascular neck tumors.1-3 They arise from glomus bodies (paraganglia) located in the crotch of the external and internal artery, at the level of carotid bifurcation. Carotid paraganglia are composed of chemoreceptor cells derived from the carotid primitive neural crest.1,4 In general, tumors arising from any paraganglionic tissue, are best called paragangliomas (PGs) and are arbitrarily classified by their relationship to the adrenal gland (adrenal medullary tumors or pheochromocytomas and extra-adrenal PGs). Of all extra-adrenal PGs in adults, only 3% are reported to occur in the head and neck region, while up to 85% occur in the abdomen, the latter with a metastatic behavior present in 50% of patients.5,6 In children, PGs are more commonly found at extra-adrenal sites and can occur anywhere in the autonomic nervous system.7 Those tumors associated with arterial vessels and cranial nerves of the ontogenetic brachial arches, usually nonchromaffin and nonfunctioning, like carotid body PGs, are rare in childhood.7 PGs appear to have gender predilection (boys ⬎ girls) before adolescence.8 CBT is the most frequent paraganglioma in the neck9-12 accounting for almost 60% of head and neck PGs.9 Principal clinical manifestations of CBT include a slow growing pulsatile upper cervical mass with possible vagal or hypoglossal neuropathy in large tumors.1,11,13,14 Surgical excision at presentation is advisable in almost all From the Department of Vascular Surgery,a the Department of Pediatrics,b the Department of Radiology,c and the Department of Pathology,d “Demokritos” University Hospital. Competition of interest: none. Additional material for this article may be found online at www.jvascsurg.org. Reprint requests: George S Georgiadis, MD, University Hospital of Alexandroupolis, Alexandrou Papanastasiou 7 str., Alexandroupolis, Greece, 68100 and (e-mail: [email protected]). 0741-5214/$34.00 Copyright © 2008 by The Society for Vascular Surgery. doi:10.1016/j.jvs.2007.10.040
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cases,6,11,15-18 since not treating it may destroy glossopharyngeal, hypoglossal, vagal or recurrent laryngeal nerve,19 or invade carotid vessels with risk of stenosis, occlusion, or even rupture.1,20 Even sympathetic chain may be involved in large CBTs.13,14,17,20 The potential of malignant local behavior or metastasis,1,2,4,12,16-18,20-24 although of low grade, should also not be overlooked. On the basis of tumor size and involvement of the carotid vessels, three types may be recognized according to Shamblin, with type III reserved for tumors that encircle the carotid vessels, invading the media, and thus, excluding the possibility of subadventitial resection.1,12,23 CBT is uncommon in the pediatric population.6,7,25,26 Among 89 patients with CBTs, Shamblin et al reported only one case in a 12-year-old child.1 Similarly, Dickinson et al reported only one case of a young 12-year-old girl, complicated by XII nerve permanent paralysis in a review of 37 CBTs.25 Recently, Takutz et al found only one 8-yearold boy having CBT in a large population of patients younger than 21 years, with nonhematologic malignancies (0.004 %).6 To the best of our knowledge, only 16 cases of surgically excised CBTs in childhood (age at operation ⱕ14 years) have been reported in the literature, most of them sporadic in type. We report a case of Shamblin type III carotid body tumor resection in a 13-year-old girl. Review of the English literature on similar cases in childhood is also undertaken. CASE REPORT A 13-year-old girl presented in the pediatric department of our hospital with a painless pulsatile slow-growing mass in the right upper neck. History revealed that this mass was present, but smaller in size, several years before admission (first appeared at the age of 9 years) and was considered lymph node hyperplasia. Of interest, this neck lump had a fast growing period after a 2-month visit to a
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location at an altitude about 1500 m above sea level. On clinical examination this mass was located in the upper part of the anterior triangle, 1.5 cm below the mandible. Mobility was noted only in the lateral direction (positive Fontaine’s sign)13,27 while no bruit was heard above the mass. Although large in size, dysphagia and hoarseness were absent indicating no pressure on the pharynx or vagal involvement, respectively. Vocal cord paralysis was also excluded after laryngeal examination. Furthermore, no signs of hypoglossal neuropathy were detected. The patient was normotensive while hypercatecholaminemia was not present. Bilateral ultrasound scanning excluded the presence of lymph nodes or carotid aneurysm, suggesting a tumor in the right anterior triangle of the neck. This tumor, oval in shape, had a heterogeneous hypoechoic appearance. The next day, a magnetic resonance imaging (MRI) of the neck, revealed an enhanced mass with a vertical diameter of 50 mm (measured 50 ⫻ 43 ⫻ 30 mm), at the level of carotid bifurcation. The mass encased and constricted the external (ECA) and internal carotid arteries (ICA). ECA and ICA were splayed (Fig 1). Magnetic resonance angiography showed the location of the mass at the angle between the ECA and ICA while encircling both vessels (Fig 2). The base of the skull was not involved. The diagnosis of carotid body tumor of type III Shamblin was suspected. Contralateral carotid body was free of disease while chest and abdominal computer tomography (CT) were negative for other PGs. The tumor was removed en bloc with the involved carotid segments, and vascular continuity was restored by means of a common carotid to internal carotid interposition saphenous vein graft (see surgical details in Appendix, online only). The child had an uneventful recovery and was discharged on postoperative day five. Histopathological examination confirmed the preoperative diagnosis of CBT. Lymph node examination proved negative for disease. Ultrasonographic studies of all her brothers (three males and one female) were tested negative for similar lesions. Similarly, neither of siblings, or parents of the child had so far evidence of disease. On 9-month follow-up, the vein conduit remains patent with no evidence of anastomotic stenosis or aneurysmal dilatation, while neurological examination revealed no cranial nerve palsies.
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Fig 1. T1-weighted MRI gradient echo (GRE) of the neck with fat saturation, after administration of gadolinium, demonstrates a mass within the right carotid space, centered in the crotch of the carotid bifurcation, with intense enhancement. The mass encases and constricts the external carotid artery (ECA) and internal carotid artery (ICA). ECA and ICA are splayed.
DISCUSSION CBTs, also referred to as chemodectomas, glomus tumors or paragangliomas, represent the most common PGs of head and neck12,16,17 after glomus jugulare.9 However, PGs comprise only 0.6% of all neoplasms in the head and neck region.3 These extra-adrenal PGs are infrequent in the pediatric population and occur most commonly in the retroperitoneum and head and neck.6 As all types of PGs, have a propensity for multicentricity,3,11,15,19,20,28 the most common association be between intravagal PGs and CBTs.28 CBTs are often bilateral,2,11,13,18,20,24,25,29-31 and usually sporadic in form, but rarely can have familial inheritance,4,15,17 related to mutations in any of the specific susceptibility genes.32 In the familial form, there is an incidence of multiple tumors, up to 25% to 48% of cases, both synchronous and metachronous15,21,33; This later type is more likely to be malignant.34 There is also evidence, that chronic hypoxic medical conditions like chronic obstructive pulmonary disease (COPD) or chronic hypoxic
Fig 2. MRA (3D/TOF/SPGR) of the neck shows a mass in the carotid bifurcation that splays internal and external carotid artery. Internal jugular vein is pushed out. (Image rotated).
stimulation in patients living at high altitudes, can lead to an overburden of the carotid body chemoreceptor cells to compensate for the lower levels of PO2. As a consequence, hypertrophy and subsequent hyperplasia/and neoplasia of the chief cells develops (hyperplastic type of CBT).32 It has been stated that individuals harboring mutations in CBT susceptibility genes and suffering chronic hypoxemia, may develop a CBT in earlier ages than otherwise.12
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Table. Review of surgically resected CBTs in children under 14 years old (at diagnosis and operation) 1st Author, Year
No of patients, CBTs (children)
Gender (age at operation)
Chambers, 1968
38, 40 (3)
Shamblin, 1971
89, 90 (ⱖ1)
M (12) M (14) F (9) NS (12)
none none none NS
⫺/25 ⫻ 25 ⫺/60 ⫻ 60 ⫺/15 ⫻ 20 NS/NS
Newland, 1980
1 (1)
F (13)
None
NS/25 ⫻ 80, functional CBT
24 (1)
F (12)
None
NS/NS
F (12) NS (12)
None NS
NS (I or II)/NS NS/NS
Carney, 1983
Other paragangliomas
Shamblin type/size (in mm)
Dickinson, 1986 Hallett, 1988
32, 37 (1) 139, 153 (ⱖ1)
Thompson, 1989
1 (1)
F (14)
unilateral glomus jugulare
R: I/20 ⫻ 20 L: III/large
Gunnot, 1990 Ophir, 1991
1 (1) 1 (1)
M (14) F (12)
II/35 ⫻ 25 ⫻ 15 R: III/30 ⫻ 40 L: II (L⬍30 ⫻ 30, estimation from CT)
Varudkar, 1993 Hajnzic, 1999
1 (1) 1 (1)
M (6) M (9)
None unilateral jugular (familial type-mother with a posterior mediastinum paraganglioma) Pheochromocytoma none, CBT resection 20 mo before
NS/50, recurrent CBT
Wang, 2000
29, 36 (ⱖ1)
NS (10)
NS
NS/15 to 60 for all CBTs
Plukker, 2001
35, 41 (ⱖ1)
NS (11)
NS
8 (1) 1 (1)
M (8.2) F (13)
None None
NS (mean: 30, 41, 66 for I, II and III respectively NS (possibly I or II), 25 III/50 ⫻ 43 ⫻ 30
Tekautz, 2003 Present case, 2007
IJV, Internal jugular vein; NS, not stated for the specific case; R, right; L, left (in bilateral CBTs); CBT, carotid body tumor.
CBTs as sole lesions, occur at any age,1,14,29,30 but most commonly in the fourth to sixth decades of life, the incidence being equal between men and women.3,5,6,20,21,25 In patients under 14 years old, the disease represents a rarity. Surprisingly, a recent review analyzing the experience of CBT management of 21 out of 33 vascular units of the Joint Vascular Research Group, reported, that CBT disease is an adult disease, since the age of the patients studied varied from 18 to 94 years, giving the message that CBTs cannot emerge in childhood.34 This is not the case, and the literature reveals that CBTs may occur also in younger6,35,36 or older1,8,15,20,25,29,37-39 children and adolescents.6-8,11,19,24,40 Only few cases of CBTs have been reported in the pediatric age according to this review (Table),1,6,15,20,25,29,30,35-39,41,42 mostly sporadic in form. In some large reports (not included in the Table), the type of glomus tumor in patients under 14 years old, was not clearly stated.19,43 Bilaterality of CBTs was observed in two patients, while three children had simultaneous PG at other site (one adrenal). Carney reported in 1983 that when the paraganglion system is involved in a tumorous syndrome, the adrenal medulla is affected almost exclusively.42 Neither child was involved in such syndromes in this review. To our knowledge, the
first case of CBT in a 7-year-old child, was first mentioned in a report by Harrington et al in 1941 (not included in the Table).44 CBTs present as slowly enlarging pulsatile cervical masses extending up to the angle of mandible.14,27 Error in the initial clinical diagnosis, as in our case, is not infrequent,25,27 and most patients are thought to have cervical lymphadenopathy, salivary gland, neurofibroma, brachial cyst, or lipoma.27 As disease progresses, lower cranial nerves and adjacent pharynx may be involved.6,10,11,21,45 Takautz et al reported an adolescent presented with a 6-month history of deficits of III, IV, V, and VI cranial nerves ipsilateral to a CBT.6 Occasionally a bruit is heard over the lesion12,17,25,45,46 suggesting significant compression of the carotid arteries.9 If small, they are usually asymptomatic, however, local pain, dysphagia, hoarseness, jaw stiffness, soar throat, or tongue numbness are not rare in larger tumors.3,13,16,17,21 Infrequently, a clinical syndrome characterized by hypertension, headache, and sweating may be present in functional tumors secreting catecholamines.13,41 Although 20% of head and neck PGs have antecedent or subsequent malignant behavior,5,6 malignancy is not the rule in CBTs.1,17 However, if present, the malignant character is justified only by
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Table. Continued Local involvement or distant metastasis/treatment (for CBTs only)
Outcome
Follow-up with no evidence of disease
none for all/totally excised
0% mortality, 0% hemiparesis for all study cases
10 y for both M 1 y for the F
all patients: one distant, one regional node metastasis/biopsy or excision only or excision ⫹ ligation of carotid vessels (in various combinations) extension into the calvarium along the IJV/partial resection plus radiotherapy and chemotherapy invasion of submaxillary gland/resection
all patients: 17 cerebrovascular events, 4 deaths
NS
NS
NS
NS
none/excision and ECA ligation (no shunt) NS/biopsy, partial or total excision (plus arterial repair and/or ECA ligation in some, especially large, tumors) R: none/subadventitial, resection, IJV ligated L: extension to skull base/resection and reconstruction with saphenous vein none/subadventitial resection R: none/ICA ligated and removed en block with the tumor, L: none/subadventitial resection (6 mo later) none/surgical excision of both tumors metastatic chest paraganglioma, metastatic lung disease/surgical excision, chemotherapy all patients: none/surgical resection, in 17 patients preoperative embolization all patients: none/complete resection
XII permanent paralysis all patients: 39.9% cranial nerve deficit, 13.7% stroke, 3.3% mortality
epithelioid myosarcoma (5) ⫹ chondroma (5) at age of 24 y, two nodules in left lung at 30 y, well at age 31 NS NS
none/gross total resection none/complete excision
right facial nerve paralysis no complications
NS NS
complete recovery R: paralysis of IXth to XIIth cranial nerves L: complete recovery persistent hypertension no surgical complications
1y 8y
all patients: 41% neurological deficits
mean: 2.9 for all patients
all patients: ICA injured in 7, neurological complications in 8 (5 temporary) complete response complete response
NS (metastatic disease in 2 patients)
metastatic disease predominantly to cervical nodes but infrequently to distant organs.1,22 Histological appearance is virtually never predictive of the metastatic behavior of the tumor.1,4,14,17,27 Most large reports quote CBT malignant transformation of 0% to 11.1%,1,2,12-14,16,18,20,24,27 with the risk of malignant degeneration greatest in young patients with heritable tumors.12,36 Considering the vasoformative nature of CBTs, incisional biopsy is not recommended since it may result in profuse bleeding and/or cranial nerve injury.13,14,23 However, fine-needle aspiration biopsy can be helpful only when the radiologic diagnosis is unclear.14 Ultrasound studies in both sides of the neck, may exclude the presence of lymph nodes, thyroid, or brachial cysts. In most cases, color-coded Doppler sonography evaluates the hypervascularity and upward intratumoral blood flow in a neck mass at carotid angle, suggesting a CBT.45 This modality is also a useful tool in the follow-up of CBTs3 and for screening of sporadic and familial cases.13,27 Accurate diagnosis is based on angiographic criteria,13,22,31 the most reliable of these being the separation and splaying of internal and external carotid arteries (known as the lyre sign).3,45 On CT scanning, CBT is easily recognized as hypervascular mass located at the carotid bifurcation, changing the
NS death 4 mo later
9.8 y 9 mo
architecture of the angle between the internal and external carotid artery, bringing them apart from each other resembling a saddle. Arterial anatomy of carotid vessels and their relationship to an enhancing lesion of the neck can also evaluated by CT angiography.3,10,23 MRI is the most important imaging modality in evaluating CBTs14 in relation to surrounding soft tissue and vascular structures9,15 and does not employ ionizing radiation or nephrotoxic contrast agents,23 the former raising concerns in young people regarding the potential for the development of radiationinduced malignancies. Axial T1- and T2-weighted MR images reveal well defined carotid space lesions.14 In children, MRI may be more helpful for evaluation and characterization of CBTs, since small tumors may be less easily depicted in angiographic or CT studies. Furthermore, MRI is more sensitive than CT to evaluate possible invasion of the base of the skull,14,15 if preoperative clinical examination suggests this may be. 111In octreotide scintigraphy also been investigated in the head and neck, has shown great promise in its ability to identify occult PGs23 and to detect metastases in patients with malignant tumors.16 Newer evidence suggests that positron emission tomography scanning may be more accurate than MRI in detecting primary tumors of less than 10 mm.45 Perhaps both aforemen-
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tioned investigations could be considered as diagnostic work-up of suspected CBTs in children, especially those with positive family history. Surgical treatment is mandatory12,13,14,16,20,23 even at presentation11,12,17,23,27 for definite cure. Another option for these tumors is radiotherapy but for benign neoplasms, is not usually advocated.14 Only one case of radiation therapy in pediatric population has been presented so far in the literature,36 possibly because children with CBTs usually of small size are candidates of complete surgical excision and therefore complete response to treatment. However, Takautz et al support that postoperative eradication of microscopic residual disease, often performed with encouraging results in adults, can also be considered as treatment approach in pediatric patients.6 Smith et al reported that, of those patients requiring vascular repair after CBT resection, 25% had evidence of malignant tumor histology.18 This finding, however, was not confirmed in our case. Our review, found only one child (male, 9 years old) with malignant CBT suffering massive metastatic pulmonary disease. Of those cases with available follow-up, only one case of CBT recurrence with metastatic lung disease was observed.36 Thus, early, upon diagnosis of a CBT, complete surgical excision is also recommended in children and adolescents, mainly because of unpredictable malignant potential, but also because any considerable delay allows the tumor to increase in size, with a tendency to show a locally aggressive and infiltrative growth pattern. Furthermore, early excision of CBTs in children under 14 years old, in appropriate hands, inevitably reduces the risk of devastating injuries, mainly cranial nerve damage, because small tumors, usually asymptomatic, have better outcome with almost zero morbidity.20,27 Nora et al.47 reported that when surgical resection of head and neck PGs is complete, recurrence is not an issue. However, in children of parents with cervical PGs, especially of those with recurrence or metachronous development of disease, there is a need of close follow-up for early documentation of similar lesions.15 Different patient demographics, tumor characteristics, and also surgical expertise, yield great variation of the results, of perioperative complications after surgical CBT resection, cited in the adult literature. An extending review reported an operative mortality of 5% to 13%, postoperative cranial nerve injury ratio of 32% to 44% and postoperative stroke rate of 8% to 20%.4 Few surgical and follow-up data of CBTs in patients under 14 years old are available in the literature, according to this review. For this reason, it is unclear if postoperative complications, especially cranial nerve dysfunction, have lower incidence in childhood (in this review: cranial nerve deficits in 3 CBTs, 15.8% including our case). Preoperative selective angiographic embolization leading to shrinkage of tumor vascularity and size, has been proposed to facilitate surgery and to diminish blood requirements,2,11,16,27,30,48 or even prepare the lesion for palliative radiotherapy. Although a matter of debate in the adult literature,2,9-11,13,17,20,27,30,31,48,49 in children, no
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case has been reported. Recently, Zaupa and Höllwarth, successfully embolized prior to surgery (after temporary balloon occlusion test of the anterior communicans artery), a CBT in a 15-year-old adolescent boy.40 It remains unclear if preoperative embolization may be advocated in older children (12 to 14 years old) with larger tumors, but cranial nerve palsies or stroke still remain a concern. The ease of a CBT resection depends on the size of the tumor.1,11,15,27,31,37 However, the degree of the tumor attachment to carotid vessels is not necessarily related to tumor dimensions.1 According to the Shamblin classification, the risk for cranial nerve injury and vascular injury increases, as the disease progresses and CBT enlarges.1 Complete CBT resection combined with vascular reconstruction is more frequently needed in Shamblin type II/III.18 Furthermore, longer mean duration of operation and excessive mean blood loss are more likely to occur in patients with type III CBTs.20 ECA ligation, as in our case, is not associated with any permanent sequelae.11,13,17,22,24,27,30 ICA should be spared if at all possible,14 but in young patients with growth potential, if it cannot be saved due to artery invasion, as in our case, interposition saphenous vein graft should be used.37,38 Type III CBTs in children necessitate the presence of a team with experience in carotid shunting and vascular reconstrunction.38 This review confirmed that CBTs are indeed extremely rare in childhood. However, unlike others,31 we believe that, no age cut-off point must be set for aggressively pursuing the diagnosis of CBT. Although most CBTs in children are of the sporadic type as was the case with the subject of this case report, there is a strong history of exposure to high altitudes in this patient that is a known risk factor for the development of CBTs in adults (hyperplastic form).50 As in most CBTs, a certain amount of time has to elapse before the clinical diagnosis can be made. This suggests that some cases, which developed in adolescent, might have been present early in childhood, and therefore a high index for suspicion is needed for diagnosis. This article suggests also that CBTs in children behave differently compared with that diagnosed in adults. Nodal involvement is infrequently found at the first clinical examination. Furthermore, larger tumors possibly appear more often in children since smaller ones can be mistaken for lymph nodes or other benign lesions. For this reason, early diagnosis of CBTs is fundamental in children under 14 years old, for the purpose of subadventitial resection that has the lowest morbidity and mortality rates. Local or distant metastatic behavior is not the rule for CBTs in children under 14 years old. Only one case of metastatic (pulmonary) paraganglioma has been reported so far in the literature.36 Furthermore, recurrent rates are definitely lower (in this review 5.9%) compared with those in adults. Only one case developed malignancies in other organs (Carney triad), on late follow-up. Close follow-up is advisable for all family members especially in familial CBT type.31 A proposed algorithm for the evaluation and treatment of CBTs in childhood is presented in Fig 3 (online only).
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AUTHOR CONTRIBUTIONS Conception and design: GS, ML Analysis and interpretation: GS, AT, PA, AG Data collection: GS, ML, AT, PA, AG Writing the article: GS, PA, AG Critical revision of the article: GS, ML, AT Final approval of the article: GS, ML, AT, PA, AG Statistical analysis: Not applicable Obtained funding: Not applicable Overall responsibility: GS REFERENCES 1. Shamblin WR, ReMine WH, Sheps SG, Harrison EG Jr. Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg 1971;122:732-9. 2. LaMuraglia GM, Fabian RL, Brewster DC, Pile-Spellman J, Darling RC, Cambria RP, et al. The current surgical management of carotid body paragangliomas. J Vasc Surg 1992;15:1038-44. 3. Lustrin ES, Palestro C, Vaheesan K. Radiographic evaluation and assessment of paragangliomas. Otolaryngol Clin North Am 2001;34: 881-906. 4. Dimakakos PB, Kotsis TE. Carotid body paraganglioma: review and surgical management. Eur J Plast Surg 2001;24:58-65. 5. Patel S, Winchester D, Benjamin R. A 15-year experience with chemotherapy of patients with paraganglioma. Cancer 1995;76:1476-80. 6. Takautz TM, Pratt CB, Jenkins JJ, Spunt SL. Pediatric extraadrenal paragaglioma. J Pediatr Surg 2003;38:1317-21. 7. Deal JE, Sever PS, Barratt TM, Dillon MJ. Pheochromocytoma-investigation and management of 10 cases. Arch Dis Child 1990;65: 269-74. 8. Stackpole RH, Melicow MM, Uson AC. Pheochromocytoma in children. Report of nine cases and review of the first 100 published cases with follow-up studies. J Pediatr 1963;63:313-30. 9. Pellitteri PK, Rinaldo A, Myssiorek D, Gary Jackson C, Bradley PJ, Devaney KO, et al. Paragangliomas of the head and neck. Oral Oncol 2004;40:563-75. 10. Rao AB, Koeller KK, Adair CF. Paragangliomas of the head and neck: radiologic-pathologic correlation. Radiographics 1999;19:1605-32. 11. Dardik A, Eisele DW, Williams GM, Perler BA. A contemporary assessment of carotid body tumor surgery. Vasc Endovasc Surg 2002;36: 277-83. 12. Knight TT Jr, Gonzalez JA, Rary JM, Rush DS. Current concepts for the surgical management of carotid body tumor. Am J Surg 2006;191: 104-10. 13. Patetsios P, Gable DR, Garrett WV, Lamont JP, Kuhn JA, Shutze WP, et al. Management of carotid body paragangliomas and review of a 30-year experience. Ann Vasc Surg 2002;16:331-8. 14. van der Mey AG, Jansen JC, van Baalen JM. Management of carotid body tumors. Otolaryngol Clin North Am 2001;34:907-24. 15. Ophir D. Familiar multicentric paragangliomas in a child. Familial multicentric paragangliomas in a child. J Laryngol Otol 1991;105:376-80. 16. Liapis CD, Evangelidakis EL, Papavassiliou VG, Kalisis JD, Gougoulakis AG, Polyzos AK, et al. Role of malignancy and preoperative embolization in the management of carotid body tumors. World J Surg 2000;24:1526-30. 17. Bastounis E, Maltezos C, Pikoulis E, Leppaniemi AK, Klonaris C, Papalambros E. Surgical treatment of carotid body tumors. Eur J Surg 1999;165:198-202. 18. Smith JJ, Passman MA, Dattilo JB, Guzman RJ, Naslund TC, Netterville JL. Carotid body tumor resection: does the need for vascular reconstruction worsen outcome? Ann Vasc Surg 2006;20:435-9. 19. van der Mey AG, Frijns JH, Cornelisse CJ, Brons EN, van Dulken H, Terpstra HL, et al. Does intervention improve the natural course of glomus tumors? A series of 108 patients seen in a 32-year period. Ann Otol Rhinol Laryngol 1992;101:635-42.
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20. Plukker JT, Brongers EP, Vermey A, Krikke A, van den Dungen JJ. Outcome of surgical treatment for carotid body paraganglioma. Br J Surg 2001;88:1382-6. 21. Bishop GB Jr, Urist MM, el Gammal T, Peters GE, Maddox WA. Paragangliomas of the neck. Arch Surg 1992;127:1441-5. 22. Dias da Silva A, O’Donnell S, Gillespie D, Goff J, Shriver C, Rich N. Malignant carotid body tumor: a case report. J Vasc Surg 2000;32: 821-3. 23. Iafrati MD, O’Donnell TF Jr. Adjuvant techniques for the management of large carotid body tumors. A case report and review. Cardiovasc Surg 1999;7:139-45. 24. Luna-Ortiz K, Rascon-Ortiz M, Villavicencio-Valencia V, GranadosGarcia M, Herrera-Gomez A. Carotid body tumors: review of a 20-year experience. Oral Oncol 2005;41:56-61. 25. Dickinson PH, Griffin SM, Guy AJ, McNeill IF. Carotid body tumor: 30 years experience. Br J Surg 1986;73:14-6. 26. Lees CD, Levine HL, Beven EG, Tucker HM. Tumors of the carotid body. Experience with 41 operative cases. Am J Surg 1981;142:362-5. 27. Westerband A, Hunter GC, Cintora I, Coulthard SW, Hinni ML, Gentile AT, et al. Current trends in the detection and management of carotid body tumors. J Vasc Surg 1998;28:84-92. 28. Borba LA, Al-Mefty O. Intravagal paragangliomas: report of four cases. Neurosurgery 1996;38:569-75. 29. Chambers RG, Mahoney WD. Carotid body tumors. Am J Surg 1968; 116:554-8. 30. Wang SJ, Wang MB, Barauskas TM, Calcaterra TC. Surgical management of carotid body tumors. Otolaryngol Head Neck Surg 2000;123: 202-6. 31. Kohn JS, Raftery KB, Jewell ER. Familial carotid body tumors: a closer look. J Vasc Surg 1999;29:649-53. 32. Baysal BE, Myers EN. Etiopathogenesis and clinical presentation of carotid body tumors. Microsc Res Tech 2002;59:256-61. 33. Isik AC, Erem C, Imamoglu M, Cinel A, Sari A, Maral G. Familial paraganglioma. Eur Arch Otorhinolaryngol 2006;263:23-31. 34. Sajid MS, Hamilton G, Baker DM, and on behalf of Joint Vascular Research Group. A multicenter review of carotid body tumor management. Eur J Vasc Endovasc Surg 2007;34:127-30. 35. Varudkar AS, Kokandkar HR, Gumaste GG, Bhople KS, Kumbhakarna NR. Carotid body paraganglioma with coexistent pheochromocytoma in childhood. Indian J Cancer 1993;30:109-12. 36. Hajnzic TF, Kruslin B, Belicza M. Carotid body paraganglioma in a 9-year-old boy with extensive pulmonary metastases. Med Pediatr Oncol 1999;32:399-400. 37. Hallett Jr JW, Nora JD, Hollier LH, Cherry Jr KJ, Pairolero 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;7:284-91. 38. Thompson JW, Cohen SR. Management of bilateral carotid body tumors and a glomus jugulare tumor in a child. Int J Pediatr Otorhinolaryngol 1989;17:75-87. 39. Gounot E, Couillault G, Maingueneau C, Autissier JM. Paraganglioma of the carotid body. A propos of a case in a 14-year-old child. Chir Pediatr 1990;31:125-6. 40. Zaupa P, Höllwarth ME. Carotid body paraganglioma: rare tumor in a 15-year-old adolescent boy. J Pediatr Surg 2007;42:E13-7. 41. Newland MC, Hurlbert BJ. Chemodectoma diagnosed by hypertension and tachycardia during anesthesia. Anesth Analg 1980;59:388-90. 42. Carney JA. The triad of gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma: a five-year review. Medicine (Baltimore) 1983;62:159-169. 43. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extraadrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc 1999;74: 543-52. 44. Harrington SW, Clagett OT, Dockerty MD. Tumors of carotid body; cIinica1 and pathological considerations of twenty tumors affecting nineteen patients (one bilateral) Ann Surg 1941;114:820-33.
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45. Gujrathi CS, Donald PJ. Current trends in the diagnosis and management of the head and neck paragangliomas. Curr Opin Otolaryngol Head Neck Surg 2005;13:339-42. 46. Liapis C, Gougoulakis A, Karydakis V, Verikokos C, Doussaitou B, Skandalakis P, et al. Changing trends in management of carotid body tumors. Am Surg 1995;61:989-93. 47. Nora JD, Hallett JW, O’Brien PC, Naessens JM, Cherry KJ, Pairolero PC. Surgical resection of carotid body tumors: long-term survival, recurrence, and metastasis. Mayo Clin Proc 1988;63:348-52. 48. Smith RF, Shetty PC, Reddy DJ. Surgical treatment of carotid paragangliomas presenting unusual technical difficulties. The value of preoperative embolization. J Vasc Surg 1988;7:631-7.
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49. DuBois J, Kelly W, McMenamin P, Macbeth GA. Bilateral carotid body tumors managed with preoperative embolization: a case report and review. J Vasc Surg 1987;5:648-50. 50. Rodriguez-Cuevas S, Lopez-Garza J, Labastida-Almendaro S. Carotid body tumors in inhabitants of altitudes higher than 2000 meters above sea level. Head Neck 1998;20:374-8.
Submitted Aug 17, 2007; accepted Oct 22, 2007.
Additional material for this article may be found online at www.jvascsurg.org.
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APPENDIX, ONLINE ONLY Surgical details Under loop magnification, surgical approach was performed through a standard linear incision along the anterior border of the sternocleidomastoid muscle with the distal end ascending behind the lobe of the ear. Initial control was obtained via exposure of the common carotid artery 2 cm below the tumor. While mobilizing the tumor, no invasion into surrounding structures was found, however, the internal jugular vein and hypoglossal nerve were found adherent to the tumor. Although we tried to find a subadventitial dissection plane, this was impossible because of penetration of the media. Additionally, the internal and external carotid arteries were hardly recognized. Only their undiseased distal segments were eventually exposed. During this stage, the hypoglossal and vagus nerve were safeguarded but the ansa hypoglossi was sacrificed. A small regional lymph node was resected at this stage. Considering the above findings, we decided en bloc resection of the mass with the carotid bifurcation. A 7-cm long segment of saphenous vein was harvested initially from the proximal thigh of the ipsilateral leg. After heparinization, the common and internal carotid arteries were clamped. Then, the common carotid artery was sectioned immediately below the tumor and the carotid bifurcation
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ligated. Placing an Inahara shunt soon after clamping, the vein graft was attached first to the distal internal carotid artery in an end-to-side fashion. Once the distal anastomosis was completed, the Inahara shunt was removed. Using now, a Javid shunt inserted to the distal internal artery through the vein graft, flushing was achieved via the cut vein stump. Then, the proximal part of the Javid shunt was inserted to the common carotid artery stump and the proximal anastomosis of the vein bypass was performed in an end-to-end fashion while still maintaining cerebral flow. Leaving the last three anterior sutures untied, the Javid shunt was removed. Via this site, antegrade and retrograde flushing was achieved after which the sutures are tightened and finally tied with flow running through the graft. At a final stage, the tumor was resected starting from the carotid bifurcation and extended distally. At that point, both external and internal carotid arteries were ligated with the latter being ligated just below the anastomotic heel (Fig 4, online only). The whole procedure was performed with the use of bipolar diathermy, which was found useful to control bleeding on the tumor surface, mainly in the initial stages of the operation. Furthermore, some local papaverine was used to avoid internal carotid artery (ICA) spasm. Intraoperative blood loss was limited to 300 ml, and all was transfused via a blood saver machine. No neurological or cranial nerve deficits were observed postoperatively.
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Fig 3, online only. Proposed management algorithm for carotid body tumors (CBTs) in childhood.
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Fig 4, online only. Common carotid to internal carotid artery bypass with reversed great saphenous vein. External carotid artery ligated just below the anastomotic heel.