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Surgical management of cervical ganglioneuromas in children
International Journal of Pediatric Otorhinolaryngology (2006) 70, 287—294
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Surgical management of cervical ganglioneuromas in children Steven B. Cannady a, Brian J. Chung a, Keiko Hirose a, Noel Garabedian b, Thierry Van Den Abbeele c, Peter J. Koltai d,* a
The Head and Neck Institute, A71, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA b Armand-Trousseau Children’s Hospital, University of Paris, University Paris VI, 26 Ave du Dr. Arnold Netter, 75012 Paris, France c Department of Otolaryngology, Robert Debre Hospital, University Paris VII, UFR Bichat, 48 Boulevard Serurier, 75019 Paris, France d Department of Otolaryngology, Division of Pediatric Otolaryngology, Stanford University, School of Medicine, 801 Welch Rd., Stanford, CA 94305, USA Received 7 April 2005; accepted 24 June 2005
KEYWORDS Ganglioneuroma; Neurogenic tumor; Sympathetic chain
Summary Objective: To review the experience with ganglioneuromas in the head and neck of children including presentation, diagnostic testing, treatments, and outcomes. Design: Case series. Retrospective chart review. Setting: Tertiary care hospital. Patients or other participants: All patients with a history of ganglioneuroma of the neck in each authors practice were reviewed. All pathologically confirmed occurrences were eligible for inclusion, and five patients met these criteria. Results: Five patients underwent surgical excision of head and neck ganglioneuromas between 1988 and 2004. There were no occurrences of secretory tumors, therefore all of the patients presented with enlarging masses. In all cases, the tumor arose from the cervical sympathetic chain, and thus, patients had subsequent ipsilateral Horner’s Syndrome following resection. No synchronous tumors were noted, nor has a recurrent tumor been observed to this point. Complete excision was possible in all cases via a transcervical, or transoral approach, without mandibulotomy. Conclusions: Ganglioneuroma of the neck is a rare tumor that most commonly presents as an enlarging neck mass. Complete surgical excision is the treatment of
* Corresponding author. Tel. +1 650 725 6500; fax: +1 650 725 6685. E-mail address: [email protected] (P.J. Koltai). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.06.020
288
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choice, and in this series of children was possible with transcervical approach, and once via transoral approach. This tumor may be suspected in children who are otherwise asymptomatic, and present with long history of enlarging neck masses. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Ganglioneuromas, ganglioneuroblastomas, and neuroblastomas form a rare group of tumors termed neurogenic or neuroblastic. Ganglioneuromas are benign tumors that arise from peripheral derivatives of sympathoblasts, a cell line of neural crest-cell origin [1]. Neuroblastic tumors constitute 6% of tumors in children and are most frequently located in the abdomen (65—80%) or thorax (10%), with only about 5% arising in the head and neck [2]. In the reported cases of cervical ganglioneuroma, the sympathetic chain is the most common source. The average age at presentation for ganglioneuromas is 11 years, with a slightly higher incidence in girls [3]. Ganglioneuromas are typically very slowgrowing tumors and noninvasive, and therefore present as an enlarging mass of the neck [2]. Symptoms usually stem from mass effect or represent sympathetic activity from secretory components within the tumor. The position of the sympathetic chain affords the tumor opportunity to readily spread into the parapharyngeal or retropharyngeal space. Mass effect from growth into these areas can cause compression of the pharyngeal wall, cranial nerves, eustachian tubes, or vascular structures. Patients may report dysphagia, globus sensation, dyspnea, or snoring and obstructive sleep apnea, prompting inaccurate diagnosis [4,5]. Functional tumors result in systemic symptoms such as hypertension, diarrhea, sweating, flushing, and renal acidosis secondary to sympathetic response [4,6]. However, few patients will present with clinically detectable production of adrenergic byproducts [6]. Computed tomography (CT) most commonly reveals a well-encapsulated tumor with low attenuation and possible central densities. Magnetic resonance imaging (MRI) demonstrates intermediate signal intensity and nonhomogeneous contrast enhancement. Ganglioneuroma is differentiated from salivary gland tumors in the parapharyngeal space by the presence of a fatty streak medial to the parotid gland, demarcating an anatomic boundary between tumor and gland [7]. If there is no fatty streak to demarcate the tumor, then the tissue of origin is likely to be the parotid. Histologically, neuroblastic tumors exhibit varying degrees of differentiation, from the immature neuroblastoma to the mature ganglioneuroma.
Neuroblastic tumors with characteristics of both malignant and benign cell growth are termed ganglioneuroblastomas [8]. Ganglioneuromas represent the most mature form, consisting of mature ganglion cells within a fibrous matrix [9]. We present the cases of five children; a 6-year-old boy with a history of an enlarging cervical mass, who underwent surgical resection of a parapharyngeal ganglioneuroma, a 7-year-old boy who underwent transoral excision of a parapharyngeal space ganglioneuroma, the case of 6-year-old girl who presented with an enlarging neck mass, a 7-year-old girl who presented with an enlarging cervical mass that was excised, and finally, 7-year-old girl with an enlarging cervical mass in which diagnosis was complicated by coincident TB.
2. Case report 1 A 6-year-old boy with a 1-year history of an enlarging right cervical mass presented to his pediatrician for evaluation. The mass was painless and was not associated with any systemic symptoms or local symptoms of obstruction. In the workup, CT demonstrated a large mass with areas of heterogeneity (Fig. 1A). T1-weighted coronal and axial MRI with contrast showed findings similar to those of CT (Fig. 2). Urine studies for byproducts of sympathetic response (including VMA and HVA) were negative; therefore, the working diagnosis of lymphatic malformation was made. The patient was taken to the interventional radiology suite for sclerotherapy to be performed on his lesion. Upon placing a syringe into the substance of the mass, it was noted that no fluid could be aspirated, and sclerotherapy was aborted. A fine-needle aspirate (FNA) taken at this time was read by the pathologist as consistent with ganglioneuroma. The patient presented to our institution for a second opinion regarding his surgical options. The patient underwent a right neck exploration through a neck dissection approach. Upon raising skin flaps, a 6 cm 2.1 cm 1.7 cm mass of matted lymph nodes in level II was found, and was dissected and removed. Frozen sections were consistent with reactive lymphadenopathy with follicular hyperplasia. Upon dissection of the carotid sheath, the substance of the neck mass was encountered. The
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Fig. 1 Cat scan (CT) and magnetic resonance imaging (MRI) of selected patient ganglioneuromas in axial view. (A) Case report 1: Parapharyngeal ganglioneuroma CT scan. (B) Case report 2: Parapharyngeal ganglioneuroma CT scan. (C) Case report 3: Cervical ganglioneuroma CT scan. (D) Case report 5: Cervical ganglioneuroma MRI scan. (E) Case report 5: Cervical ganglioneuroma CT scan.
internal jugular vein, common carotid artery, and cranial nerves IX—XII were identified and preserved. The mass was found deep to cranial nerve X, displacing the common carotid artery and inter-
nal jugular vein anteromedially. The distal sympathetic chain was identified inferiorly as it disappeared into the mass (Fig. 3). Blunt dissection was used to free the mass circumferentially, and
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Fig. 2 T1-weighted MRI image with contrast of a ganglioneuroma in coronal view. Note line of demarcation suggestive of cystic or nonhomogeneous nature.
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Fig. 4 Representative histology of a ganglioneuroma. Note the mature and immature ganglion cells, and neurites accompanied by schwann cells and fibrous tissue.
the nerve chain was ligated superiorly and transected to free the mass. The excised mass was consistent with the common histology of ganglioneuroma. The gross appearance of the lesion revealed a 6 cm 4 cm 2.8 cm encapsulated mass of tan—white tissue. Microscopic exam of the tissue was characterized by mature and immature ganglion cells and by neurites accompanied by schwann cells and fibrous tissue (Fig. 4). With the exception of an expected Horner’s syndrome from division of the sympathetic chain, the postoperative course of this patient was uneventful. The patient was extubated in the operating room, and had no clinical signs of respiratory distress. The following day he was advanced to a regular diet and, and was therefore discharged. All cranial nerves were normal in the immediate postoperative course. The patient has been seen in follow-up and continues to have a residual Horner’s syndrome but has otherwise recovered completely. There has been no recurrence of his tumor in 2 years of follow-up.
3. Case report 2
Fig. 3 (A and B) Intraoperative photo of the sympathetic chain insertion into a ganglioneuroma proximally. Schematic demonstrating anatomical relationships seen once the tumor is isolated.
A 7-year-old boy was evaluated as a second opinion for a right-sided slowly enlarging intraoral mass. He had difficulty with dysphagia and on exam he had a mass displacing his posterior oropharyngeal wall on the right. CT scan revealed a heterogeneous mass measuring 6 cm 3 cm 2 cm, within the right parapharyngeal space that resulted in significant mass effect on the oropharynx (Fig. 1B). In this patient, the primary presentation of the mass was within the oropharynx. Given the safety of
Surgical management of cervical ganglioneuromas in children
the great vessels based on CT findings, and, drawing from experience in surgical management of pediatric parapharyngeal space infection, it was felt that a transoral approach to excision would be successful. After incision was made in the oropharyngeal mucosa, the substance of the mass was encountered. Blunt dissection was performed until the mass was freed circumferentially. The mass was successfully delivered transorally (Fig. 5). Similar to Patient 1, the gross appearance of the mass was that of a well-encapsulated mass of tan— white tissue. Histologic findings were consistent with the above described appearance of ganglioneuroma. This patient did well postoperatively requiring a nasogastric tube for only four days post-operatively to administer nutrition. This patient also developed
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an expected Horner’s Syndrome. In 13 years of followup, the patient has not had a recurrence of his tumor.
4. Case report 3 A 6-year-old girl was referred by her primary care physician for evaluation of a gradually enlarging right sided neck mass. The parents had photographs documenting the presence of the mass for at least the past 3 years. Although the mass had grown considerably in size, the patient had remained asymptomatic. On physical exam a large right sided mass was readily palpable in level III. The thyroid and laryngeal landmarks were well demarcated and appeared separate from this mass. Cranial nerves II—XII were intact. CT scan of the neck revealed a large homogeneous low-density mass measuring 4.0 cm 3.3 cm 8.3 cm. There was marked displacement of the trachea and the vessels of the carotid space. The patient subsequently underwent complete excision of the neck mass through a transcervical approach. The mass was immediately apparent after incising the platysma musculature. It appeared to arise from the cervical sympathetic chain. The carotid artery and internal jugular vein were found displaced anterolaterally. They were dissected free and preserved as were cranial nerves X and XI. The mass was smooth and well-encapsulated with a gelatinous texture. Gross sections revealed a homogeneous tan—brown internal appearance. Sampled lymph nodes were unremarkable. Histologic findings were consistent with ganglioneuroma. Now 1 year from her surgery at this writing, the patient remains free of recurrence.
5. Case report 4
Fig. 5 Transoral excision of ganglioneuroma. (A) Exposure with red-rubber catheters to retract soft palate. (B) Incised posterior pharyngeal wall with mass apparent. (C) Mass excised and pharyngeal wall closed.
A 7-year-old child was diagnosed with a cervical and right parapharyngeal clinical mass evolving over a 3month period. Medical work up included [123I]metaiodobenzylguanidine (MIBG) which was negative. A quantitative analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA) was normal. A CT scan was obtained and demonstrated the same characteristics of the above cases. The patient underwent surgery under general anesthesia in 2003. A cutaneous incision along the anterior edge of the sternocleidomastoid (SCM) muscle was made. The lesion was identified posterior to the carotid sheath with consequent anterior displacement. The tumor extended from the jugular foramen to the supraclavicular area with several smaller linear extensions. The lesion was soft and smooth with a
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yellowish consistency on gross examination. Pathology revealed findings consistent with ganglioneuroma. The post-operative course was without postoperative sequelae and the patient remains asymptomatic to date.
6. Case report 5 ML was born in 1989 after a normal pregnancy and normal delivery. At the age of 7 years (October 1995), she was diagnosed with tuberculosis after pulmonary tuberculosis was diagnosed in her father. She was treated with a four drug regimen [isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB)] until April 1996 and then two drugs (INH-RIF) until August 1996. During this period, she presented with a right-sided parapharyngeal mass slightly bulging behind the posterior tonsillar pillar together with bilateral lymphadenopathy (right > left). Ultrasonography (US) revealed a hypodense mass (2.5 cm 4.5 cm). An FNA under general anesthesia failed to diagnose the pathology. Ultrasonographic follow-up showed no tumor growth. She was lost to follow-up for 2 years until October 1998 when she presented with intermittent dysphagia, night coughing, and a large tumor of the right peritonsillar space. Repeat US and CT revealed a much larger retropharyngeal mass (5 cm 6 cm) (Fig. 1D and E) with a heterogeneous pattern. The tumor reached the foramen ovale superiorly and enlarged the carotid bifurcation. She presented without cranial nerve palsy or Horner’s syndrome. Transoral biopsy showed a whitish surrounding envelope with fibrous tissue within it and histopathology revealed schwann cells and ganglion cells, suggesting the diagnosis of ganglioneuroma. MIBG scintiscan identified the tumor and no other foci of uptake, urine, and blood catecholamines were negative. Complete removal of the tumor was accomplished via a transcervical approach. She had a postoperative Horner syndrome and transient IX and XII incomplete paralysis. Partial Horner’s syndrome remained after 6 months (anisocoria). Definitive histology revealed a ganglioneuroma with very few immature cells. Since then, no recurrence has occurred in 9 years since initial neck mass presentation.
7. Discussion These five children had ganglioneuromas of the deep neck and parapharyngeal space. This rare tumor of childhood that infrequently arises in
S.B. Cannady et al.
the head and neck [2] and most commonly presents as a slowly enlarging mass between 10 and 29 years [1,4—6,10,11]. Diagnosis of neck masses or parapharyngeal space tumors in children requires thorough evaluation beginning with physical examination. These tumors commonly present as incidentally recognized asymmetries of the external neck or intraorally as asymmetries of the soft palate, as in Case report 2 [1,4,5,12]. However, a mass must reach a substantial size before it will be noted in the external neck; therefore, they are more frequently first noted as an asymmetry of the pharyngeal wall or soft palate. The resultant physical findings may lead to a false diagnosis of tonsillitis or peritonsillar abscess, and subsequent tonsillectomy. Associated symptoms relate to local mass effect or sympathetic byproduct release. Our patients presented with asymptomatic enlarging masses of the cervical neck and posterior pharynx. As the tumor enlarges, compression of the pharyngeal wall can result in dysphagia or a globus sensation, dyspnea, voice change, or nasal congestion [4]. With further growth superiorly, the nerves of the parapharyngeal space can become dysfunctional and a palsy of cranial nerve IX, X, XI, or XII may be noted on the affected side, resulting in neurogenic dysphagia, dysphonia, or aspiration. A Horner’s syndrome may ensue from compression of the cervical sympathetic chain. Systemic symptoms, although rare, can be alarming to patients, parents, and practitioners [13]. Once a mass has been detected, both CT and MRI of the head and neck are typically ordered. CT can be helpful in illuminating the fatty streak between the parotid gland and the mass, indicating an origin outside the substance of the parotid [7]. Location of the carotid sheath vessels may also provide diagnostic clues as anterior displacement is often seen in neurogenic tumors within the parapharyngeal space. This is in contrast to the posterior displacement typical of salivary gland tumors. Similarly, the presence of fat separation between a mass and parotid may be useful in MRI studies to help determine the source of a mass. One difficulty arising from imaging studies stems from the presence of cystic or nonhomogeneous appearing components on MRI. Although nonhomogeneous ganglioneuroma has previously been described, it can pose a diagnostic dilemma as evidenced in Case report 1 in which an erroneous diagnosis of lymphatic malformation was initially made [7]. Therefore, definitive diagnosis should involve tissue sampling. Tissue diagnosis of parapharyngeal space masses has traditionally involved FNA or open biopsy. Open
Surgical management of cervical ganglioneuromas in children
biopsy is often preferred because the facial nerve often transgresses the area in which tumors arise; however, with the availability of skilled cytopathologists, an FNA can be safely performed and interpreted accurately. Transoral biopsy has traditionally been contraindicated due to the risk of significant bleeding; however, it can be successfully performed in experienced hands as seen in Case reports 2 and 5 [1,11]. FNA can be a powerful diagnostic tool in the work up of pediatric head and neck masses although sedation is often required. In Case report 1, FNA was performed with the patient already sedated for intended sclerotherapy for a presumed lymphatic malformation. Occasionally, a mandibulotomy has been advocated for complete exposure of the skull base in surgical extirpation of lesions arising in this space. However, in children, the relatively short length and pliability of the mandibular ramus allows for adequate access to the skull base without mandibulotomy. As evidenced by Case reports 1 and 3—5, a complete transcervical excision is possible without the additional comorbity of mandibulotomy. These key differences allow for successful resection of benign parapharyngeal masses by transcervical approach alone. As in the case of Patient 2, a transoral approach can be indicated in specific scenarios. In this patient, the mass was clearly medial to the great vessels of the neck, and a fat plane was evident dividing its margins from deeper neck structures. Drawing from experience with parapharyngeal space and retropharyngeal space infection, it was felt that this lesion could be excised safely via a transoral approach. If a ganglioneuroma is confirmed by pathology, surgical excision alone is curative. The patient requires no further treatment. Debulking procedures can relieve a patient’s symptoms if complete excision is not possible. However, should the mass show any signs of poor differentiation suggestive of neuroblastoma, referral should be made to a pediatric oncologist and careful discussion of management of the tumor should take place prior to plans for surgical resection are made. In addition to isolated ganglioneuromas, this tumor can occur in association with multiple endocrine neoplasia type 2B (MEN2B), and neurofibromatosis 1 (NF1) [14,15]. Any family history of MEN2B in a child diagnosed with a ganglioneuroma should prompt a careful review of their history for the typical manifestations of this syndrome: medullary thyroid carcinoma (MTC), pheochromocytoma, gastrointestinal (GI) disorders, marfanoid facies, or multiple ganglioneuromas [14]. If suspected, a molecular analysis for the RET proto-oncogene should be performed, as diagnosis can lead to early
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detection of MTC and prevention of mortality. There have also been case reports that have linked ganglioneuroblastoma and ganglioneuroma to NF1, although rare. It is prudent to assess a child diagnosed with either tumor for cafe ´-au-lait spots, or neurofibromas to aid in the diagnosis of this disorder if present.
8. Conclusions Ganglioneuromas are rare childhood tumors that are usually first noted as enlarging parapharyngeal or cervical masses in the oropharynx or neck. They have the potential to secrete adrenergic byproducts, although those found in our series in the head and neck did not. They are cured via surgical excision, and can be readily removed transcervically. Both CT and MRI offer anatomical information that may be useful at the time of surgery. Characteristic pathology confirms the benign tumor. On very rare occasion, one may encounter this tumor in the setting of a syndrome such as MEN2B or NF1, and therefore must be prepared to assess for signs thereof. Follow-up is suggested both clinically, and with repeat imaging if recurrence is suspected.
References [1] M.R. Kaufman, J.S. Rhee, L.J. Fliegelman, et al. Ganglioneuroma of the parapharyngeal space in a pediatric patient, Otolaryngol. Head Neck Surg. 124 (2001) 702—704. [2] R.T. Cotton, E.T. Ballard, J.A. Going, et al. Tumors of the head and neck in children, in: S.E. Thawley, W.R. Panje, J.B. Batsakis, R.D. Lindberg (Eds.), Comprehensive Management of Head and Neck Tumors, WB Saunders Co., Philadelphia, 1987, pp. 1792—1794. [3] J.P. Hamilton, C.E. Koop, Ganglioneuroma in childhood, Surg. Gynaecol. Obstet. 21 (1965) 803—812. [4] K.D. Olsen, Tumors and surgery of the parapharyngeal space, Laryngoscope 104 (1994) 1—28. [5] K.V. Hughes, K.D. Olsen, T.V. McCaffrey, Parapharyngeal space neoplasms, Head Neck 17 (1995) 124—130. [6] F.M. Enzinger, S.W. Weiss, Soft Tissue Tumors, Mosby, St. Louis, 1988, pp. 828—831. [7] K.W. Preidler, G. Ranner, D. Szolar, Ultrasonography, CT, and MRI of retropharyngeal ganglioneuroma: a very rare neoplasm in adults, Neuroradiology 38 (1996) 378—380. [8] V.V. Joshi, A.B. Cantor, G. Altshuler, et al. Recommendations for modification of terminology of neuroblastic tumors and prognostic significance of Shimada classification. A clinicopathologic study of 213 cases from the pediatric oncology group, Cancer 69 (1992) 2183—2196. [9] A. Maitra, V. Kumar, Disease of infancy and childhood, in: V. Kumar, H. Robbins, S. Cotran (Eds.), Pathologic Basis of Robbins Pathologic Basis of Disease, Elsevier, Philadelphia, PA, 2005, pp. 469—508. [10] P.L. Friedlander, J.P. Hunt, E. Palacios, Ganglioneuroma of the neck, JENT 81 (2002) 435.
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[11] C. Walch, W. Anderhuber, K. Preidler, et al. Retro- and parapharyngeal ganglioneuroma, J. Laryngol. Otol. 110 (1996) 87—90. [12] S.M. Shoss, D.T. Donovan, B.R. Alford, Tumors of the parapharyngeal space, Arch. Otolaryngol. 111 (1985) 753—755. [13] G.J. Lonergan, C.M. Schwab, E.S. Suarez, et al. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation, Radiographics 22 (4) (2002) 911— 934.
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[14] M. Torre, G. Martucciello, I. Ceccherini, et al. Diagnostic and therapeutic approach to multiple endocrineneoplasia type 2B in pediatric patients, Pediatr. Surg. Int. 18 (2002) 378—383. [15] A.P. Geraci, J. de Csepel, E. Shlasko, et al. Ganglioneuroblastoma and ganglioneuroma in association with neurofibormatosis type 1: report of three cases, J. Child. Neurol. 13 (1998) 356—358.
www.elsevier.com/locate/ijporl
Surgical management of cervical ganglioneuromas in children Steven B. Cannady a, Brian J. Chung a, Keiko Hirose a, Noel Garabedian b, Thierry Van Den Abbeele c, Peter J. Koltai d,* a
The Head and Neck Institute, A71, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, USA b Armand-Trousseau Children’s Hospital, University of Paris, University Paris VI, 26 Ave du Dr. Arnold Netter, 75012 Paris, France c Department of Otolaryngology, Robert Debre Hospital, University Paris VII, UFR Bichat, 48 Boulevard Serurier, 75019 Paris, France d Department of Otolaryngology, Division of Pediatric Otolaryngology, Stanford University, School of Medicine, 801 Welch Rd., Stanford, CA 94305, USA Received 7 April 2005; accepted 24 June 2005
KEYWORDS Ganglioneuroma; Neurogenic tumor; Sympathetic chain
Summary Objective: To review the experience with ganglioneuromas in the head and neck of children including presentation, diagnostic testing, treatments, and outcomes. Design: Case series. Retrospective chart review. Setting: Tertiary care hospital. Patients or other participants: All patients with a history of ganglioneuroma of the neck in each authors practice were reviewed. All pathologically confirmed occurrences were eligible for inclusion, and five patients met these criteria. Results: Five patients underwent surgical excision of head and neck ganglioneuromas between 1988 and 2004. There were no occurrences of secretory tumors, therefore all of the patients presented with enlarging masses. In all cases, the tumor arose from the cervical sympathetic chain, and thus, patients had subsequent ipsilateral Horner’s Syndrome following resection. No synchronous tumors were noted, nor has a recurrent tumor been observed to this point. Complete excision was possible in all cases via a transcervical, or transoral approach, without mandibulotomy. Conclusions: Ganglioneuroma of the neck is a rare tumor that most commonly presents as an enlarging neck mass. Complete surgical excision is the treatment of
* Corresponding author. Tel. +1 650 725 6500; fax: +1 650 725 6685. E-mail address: [email protected] (P.J. Koltai). 0165-5876/$ — see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2005.06.020
288
S.B. Cannady et al.
choice, and in this series of children was possible with transcervical approach, and once via transoral approach. This tumor may be suspected in children who are otherwise asymptomatic, and present with long history of enlarging neck masses. # 2005 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Ganglioneuromas, ganglioneuroblastomas, and neuroblastomas form a rare group of tumors termed neurogenic or neuroblastic. Ganglioneuromas are benign tumors that arise from peripheral derivatives of sympathoblasts, a cell line of neural crest-cell origin [1]. Neuroblastic tumors constitute 6% of tumors in children and are most frequently located in the abdomen (65—80%) or thorax (10%), with only about 5% arising in the head and neck [2]. In the reported cases of cervical ganglioneuroma, the sympathetic chain is the most common source. The average age at presentation for ganglioneuromas is 11 years, with a slightly higher incidence in girls [3]. Ganglioneuromas are typically very slowgrowing tumors and noninvasive, and therefore present as an enlarging mass of the neck [2]. Symptoms usually stem from mass effect or represent sympathetic activity from secretory components within the tumor. The position of the sympathetic chain affords the tumor opportunity to readily spread into the parapharyngeal or retropharyngeal space. Mass effect from growth into these areas can cause compression of the pharyngeal wall, cranial nerves, eustachian tubes, or vascular structures. Patients may report dysphagia, globus sensation, dyspnea, or snoring and obstructive sleep apnea, prompting inaccurate diagnosis [4,5]. Functional tumors result in systemic symptoms such as hypertension, diarrhea, sweating, flushing, and renal acidosis secondary to sympathetic response [4,6]. However, few patients will present with clinically detectable production of adrenergic byproducts [6]. Computed tomography (CT) most commonly reveals a well-encapsulated tumor with low attenuation and possible central densities. Magnetic resonance imaging (MRI) demonstrates intermediate signal intensity and nonhomogeneous contrast enhancement. Ganglioneuroma is differentiated from salivary gland tumors in the parapharyngeal space by the presence of a fatty streak medial to the parotid gland, demarcating an anatomic boundary between tumor and gland [7]. If there is no fatty streak to demarcate the tumor, then the tissue of origin is likely to be the parotid. Histologically, neuroblastic tumors exhibit varying degrees of differentiation, from the immature neuroblastoma to the mature ganglioneuroma.
Neuroblastic tumors with characteristics of both malignant and benign cell growth are termed ganglioneuroblastomas [8]. Ganglioneuromas represent the most mature form, consisting of mature ganglion cells within a fibrous matrix [9]. We present the cases of five children; a 6-year-old boy with a history of an enlarging cervical mass, who underwent surgical resection of a parapharyngeal ganglioneuroma, a 7-year-old boy who underwent transoral excision of a parapharyngeal space ganglioneuroma, the case of 6-year-old girl who presented with an enlarging neck mass, a 7-year-old girl who presented with an enlarging cervical mass that was excised, and finally, 7-year-old girl with an enlarging cervical mass in which diagnosis was complicated by coincident TB.
2. Case report 1 A 6-year-old boy with a 1-year history of an enlarging right cervical mass presented to his pediatrician for evaluation. The mass was painless and was not associated with any systemic symptoms or local symptoms of obstruction. In the workup, CT demonstrated a large mass with areas of heterogeneity (Fig. 1A). T1-weighted coronal and axial MRI with contrast showed findings similar to those of CT (Fig. 2). Urine studies for byproducts of sympathetic response (including VMA and HVA) were negative; therefore, the working diagnosis of lymphatic malformation was made. The patient was taken to the interventional radiology suite for sclerotherapy to be performed on his lesion. Upon placing a syringe into the substance of the mass, it was noted that no fluid could be aspirated, and sclerotherapy was aborted. A fine-needle aspirate (FNA) taken at this time was read by the pathologist as consistent with ganglioneuroma. The patient presented to our institution for a second opinion regarding his surgical options. The patient underwent a right neck exploration through a neck dissection approach. Upon raising skin flaps, a 6 cm 2.1 cm 1.7 cm mass of matted lymph nodes in level II was found, and was dissected and removed. Frozen sections were consistent with reactive lymphadenopathy with follicular hyperplasia. Upon dissection of the carotid sheath, the substance of the neck mass was encountered. The
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Fig. 1 Cat scan (CT) and magnetic resonance imaging (MRI) of selected patient ganglioneuromas in axial view. (A) Case report 1: Parapharyngeal ganglioneuroma CT scan. (B) Case report 2: Parapharyngeal ganglioneuroma CT scan. (C) Case report 3: Cervical ganglioneuroma CT scan. (D) Case report 5: Cervical ganglioneuroma MRI scan. (E) Case report 5: Cervical ganglioneuroma CT scan.
internal jugular vein, common carotid artery, and cranial nerves IX—XII were identified and preserved. The mass was found deep to cranial nerve X, displacing the common carotid artery and inter-
nal jugular vein anteromedially. The distal sympathetic chain was identified inferiorly as it disappeared into the mass (Fig. 3). Blunt dissection was used to free the mass circumferentially, and
290
Fig. 2 T1-weighted MRI image with contrast of a ganglioneuroma in coronal view. Note line of demarcation suggestive of cystic or nonhomogeneous nature.
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Fig. 4 Representative histology of a ganglioneuroma. Note the mature and immature ganglion cells, and neurites accompanied by schwann cells and fibrous tissue.
the nerve chain was ligated superiorly and transected to free the mass. The excised mass was consistent with the common histology of ganglioneuroma. The gross appearance of the lesion revealed a 6 cm 4 cm 2.8 cm encapsulated mass of tan—white tissue. Microscopic exam of the tissue was characterized by mature and immature ganglion cells and by neurites accompanied by schwann cells and fibrous tissue (Fig. 4). With the exception of an expected Horner’s syndrome from division of the sympathetic chain, the postoperative course of this patient was uneventful. The patient was extubated in the operating room, and had no clinical signs of respiratory distress. The following day he was advanced to a regular diet and, and was therefore discharged. All cranial nerves were normal in the immediate postoperative course. The patient has been seen in follow-up and continues to have a residual Horner’s syndrome but has otherwise recovered completely. There has been no recurrence of his tumor in 2 years of follow-up.
3. Case report 2
Fig. 3 (A and B) Intraoperative photo of the sympathetic chain insertion into a ganglioneuroma proximally. Schematic demonstrating anatomical relationships seen once the tumor is isolated.
A 7-year-old boy was evaluated as a second opinion for a right-sided slowly enlarging intraoral mass. He had difficulty with dysphagia and on exam he had a mass displacing his posterior oropharyngeal wall on the right. CT scan revealed a heterogeneous mass measuring 6 cm 3 cm 2 cm, within the right parapharyngeal space that resulted in significant mass effect on the oropharynx (Fig. 1B). In this patient, the primary presentation of the mass was within the oropharynx. Given the safety of
Surgical management of cervical ganglioneuromas in children
the great vessels based on CT findings, and, drawing from experience in surgical management of pediatric parapharyngeal space infection, it was felt that a transoral approach to excision would be successful. After incision was made in the oropharyngeal mucosa, the substance of the mass was encountered. Blunt dissection was performed until the mass was freed circumferentially. The mass was successfully delivered transorally (Fig. 5). Similar to Patient 1, the gross appearance of the mass was that of a well-encapsulated mass of tan— white tissue. Histologic findings were consistent with the above described appearance of ganglioneuroma. This patient did well postoperatively requiring a nasogastric tube for only four days post-operatively to administer nutrition. This patient also developed
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an expected Horner’s Syndrome. In 13 years of followup, the patient has not had a recurrence of his tumor.
4. Case report 3 A 6-year-old girl was referred by her primary care physician for evaluation of a gradually enlarging right sided neck mass. The parents had photographs documenting the presence of the mass for at least the past 3 years. Although the mass had grown considerably in size, the patient had remained asymptomatic. On physical exam a large right sided mass was readily palpable in level III. The thyroid and laryngeal landmarks were well demarcated and appeared separate from this mass. Cranial nerves II—XII were intact. CT scan of the neck revealed a large homogeneous low-density mass measuring 4.0 cm 3.3 cm 8.3 cm. There was marked displacement of the trachea and the vessels of the carotid space. The patient subsequently underwent complete excision of the neck mass through a transcervical approach. The mass was immediately apparent after incising the platysma musculature. It appeared to arise from the cervical sympathetic chain. The carotid artery and internal jugular vein were found displaced anterolaterally. They were dissected free and preserved as were cranial nerves X and XI. The mass was smooth and well-encapsulated with a gelatinous texture. Gross sections revealed a homogeneous tan—brown internal appearance. Sampled lymph nodes were unremarkable. Histologic findings were consistent with ganglioneuroma. Now 1 year from her surgery at this writing, the patient remains free of recurrence.
5. Case report 4
Fig. 5 Transoral excision of ganglioneuroma. (A) Exposure with red-rubber catheters to retract soft palate. (B) Incised posterior pharyngeal wall with mass apparent. (C) Mass excised and pharyngeal wall closed.
A 7-year-old child was diagnosed with a cervical and right parapharyngeal clinical mass evolving over a 3month period. Medical work up included [123I]metaiodobenzylguanidine (MIBG) which was negative. A quantitative analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA) was normal. A CT scan was obtained and demonstrated the same characteristics of the above cases. The patient underwent surgery under general anesthesia in 2003. A cutaneous incision along the anterior edge of the sternocleidomastoid (SCM) muscle was made. The lesion was identified posterior to the carotid sheath with consequent anterior displacement. The tumor extended from the jugular foramen to the supraclavicular area with several smaller linear extensions. The lesion was soft and smooth with a
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yellowish consistency on gross examination. Pathology revealed findings consistent with ganglioneuroma. The post-operative course was without postoperative sequelae and the patient remains asymptomatic to date.
6. Case report 5 ML was born in 1989 after a normal pregnancy and normal delivery. At the age of 7 years (October 1995), she was diagnosed with tuberculosis after pulmonary tuberculosis was diagnosed in her father. She was treated with a four drug regimen [isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB)] until April 1996 and then two drugs (INH-RIF) until August 1996. During this period, she presented with a right-sided parapharyngeal mass slightly bulging behind the posterior tonsillar pillar together with bilateral lymphadenopathy (right > left). Ultrasonography (US) revealed a hypodense mass (2.5 cm 4.5 cm). An FNA under general anesthesia failed to diagnose the pathology. Ultrasonographic follow-up showed no tumor growth. She was lost to follow-up for 2 years until October 1998 when she presented with intermittent dysphagia, night coughing, and a large tumor of the right peritonsillar space. Repeat US and CT revealed a much larger retropharyngeal mass (5 cm 6 cm) (Fig. 1D and E) with a heterogeneous pattern. The tumor reached the foramen ovale superiorly and enlarged the carotid bifurcation. She presented without cranial nerve palsy or Horner’s syndrome. Transoral biopsy showed a whitish surrounding envelope with fibrous tissue within it and histopathology revealed schwann cells and ganglion cells, suggesting the diagnosis of ganglioneuroma. MIBG scintiscan identified the tumor and no other foci of uptake, urine, and blood catecholamines were negative. Complete removal of the tumor was accomplished via a transcervical approach. She had a postoperative Horner syndrome and transient IX and XII incomplete paralysis. Partial Horner’s syndrome remained after 6 months (anisocoria). Definitive histology revealed a ganglioneuroma with very few immature cells. Since then, no recurrence has occurred in 9 years since initial neck mass presentation.
7. Discussion These five children had ganglioneuromas of the deep neck and parapharyngeal space. This rare tumor of childhood that infrequently arises in
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the head and neck [2] and most commonly presents as a slowly enlarging mass between 10 and 29 years [1,4—6,10,11]. Diagnosis of neck masses or parapharyngeal space tumors in children requires thorough evaluation beginning with physical examination. These tumors commonly present as incidentally recognized asymmetries of the external neck or intraorally as asymmetries of the soft palate, as in Case report 2 [1,4,5,12]. However, a mass must reach a substantial size before it will be noted in the external neck; therefore, they are more frequently first noted as an asymmetry of the pharyngeal wall or soft palate. The resultant physical findings may lead to a false diagnosis of tonsillitis or peritonsillar abscess, and subsequent tonsillectomy. Associated symptoms relate to local mass effect or sympathetic byproduct release. Our patients presented with asymptomatic enlarging masses of the cervical neck and posterior pharynx. As the tumor enlarges, compression of the pharyngeal wall can result in dysphagia or a globus sensation, dyspnea, voice change, or nasal congestion [4]. With further growth superiorly, the nerves of the parapharyngeal space can become dysfunctional and a palsy of cranial nerve IX, X, XI, or XII may be noted on the affected side, resulting in neurogenic dysphagia, dysphonia, or aspiration. A Horner’s syndrome may ensue from compression of the cervical sympathetic chain. Systemic symptoms, although rare, can be alarming to patients, parents, and practitioners [13]. Once a mass has been detected, both CT and MRI of the head and neck are typically ordered. CT can be helpful in illuminating the fatty streak between the parotid gland and the mass, indicating an origin outside the substance of the parotid [7]. Location of the carotid sheath vessels may also provide diagnostic clues as anterior displacement is often seen in neurogenic tumors within the parapharyngeal space. This is in contrast to the posterior displacement typical of salivary gland tumors. Similarly, the presence of fat separation between a mass and parotid may be useful in MRI studies to help determine the source of a mass. One difficulty arising from imaging studies stems from the presence of cystic or nonhomogeneous appearing components on MRI. Although nonhomogeneous ganglioneuroma has previously been described, it can pose a diagnostic dilemma as evidenced in Case report 1 in which an erroneous diagnosis of lymphatic malformation was initially made [7]. Therefore, definitive diagnosis should involve tissue sampling. Tissue diagnosis of parapharyngeal space masses has traditionally involved FNA or open biopsy. Open
Surgical management of cervical ganglioneuromas in children
biopsy is often preferred because the facial nerve often transgresses the area in which tumors arise; however, with the availability of skilled cytopathologists, an FNA can be safely performed and interpreted accurately. Transoral biopsy has traditionally been contraindicated due to the risk of significant bleeding; however, it can be successfully performed in experienced hands as seen in Case reports 2 and 5 [1,11]. FNA can be a powerful diagnostic tool in the work up of pediatric head and neck masses although sedation is often required. In Case report 1, FNA was performed with the patient already sedated for intended sclerotherapy for a presumed lymphatic malformation. Occasionally, a mandibulotomy has been advocated for complete exposure of the skull base in surgical extirpation of lesions arising in this space. However, in children, the relatively short length and pliability of the mandibular ramus allows for adequate access to the skull base without mandibulotomy. As evidenced by Case reports 1 and 3—5, a complete transcervical excision is possible without the additional comorbity of mandibulotomy. These key differences allow for successful resection of benign parapharyngeal masses by transcervical approach alone. As in the case of Patient 2, a transoral approach can be indicated in specific scenarios. In this patient, the mass was clearly medial to the great vessels of the neck, and a fat plane was evident dividing its margins from deeper neck structures. Drawing from experience with parapharyngeal space and retropharyngeal space infection, it was felt that this lesion could be excised safely via a transoral approach. If a ganglioneuroma is confirmed by pathology, surgical excision alone is curative. The patient requires no further treatment. Debulking procedures can relieve a patient’s symptoms if complete excision is not possible. However, should the mass show any signs of poor differentiation suggestive of neuroblastoma, referral should be made to a pediatric oncologist and careful discussion of management of the tumor should take place prior to plans for surgical resection are made. In addition to isolated ganglioneuromas, this tumor can occur in association with multiple endocrine neoplasia type 2B (MEN2B), and neurofibromatosis 1 (NF1) [14,15]. Any family history of MEN2B in a child diagnosed with a ganglioneuroma should prompt a careful review of their history for the typical manifestations of this syndrome: medullary thyroid carcinoma (MTC), pheochromocytoma, gastrointestinal (GI) disorders, marfanoid facies, or multiple ganglioneuromas [14]. If suspected, a molecular analysis for the RET proto-oncogene should be performed, as diagnosis can lead to early
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detection of MTC and prevention of mortality. There have also been case reports that have linked ganglioneuroblastoma and ganglioneuroma to NF1, although rare. It is prudent to assess a child diagnosed with either tumor for cafe ´-au-lait spots, or neurofibromas to aid in the diagnosis of this disorder if present.
8. Conclusions Ganglioneuromas are rare childhood tumors that are usually first noted as enlarging parapharyngeal or cervical masses in the oropharynx or neck. They have the potential to secrete adrenergic byproducts, although those found in our series in the head and neck did not. They are cured via surgical excision, and can be readily removed transcervically. Both CT and MRI offer anatomical information that may be useful at the time of surgery. Characteristic pathology confirms the benign tumor. On very rare occasion, one may encounter this tumor in the setting of a syndrome such as MEN2B or NF1, and therefore must be prepared to assess for signs thereof. Follow-up is suggested both clinically, and with repeat imaging if recurrence is suspected.
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[11] C. Walch, W. Anderhuber, K. Preidler, et al. Retro- and parapharyngeal ganglioneuroma, J. Laryngol. Otol. 110 (1996) 87—90. [12] S.M. Shoss, D.T. Donovan, B.R. Alford, Tumors of the parapharyngeal space, Arch. Otolaryngol. 111 (1985) 753—755. [13] G.J. Lonergan, C.M. Schwab, E.S. Suarez, et al. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation, Radiographics 22 (4) (2002) 911— 934.
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[14] M. Torre, G. Martucciello, I. Ceccherini, et al. Diagnostic and therapeutic approach to multiple endocrineneoplasia type 2B in pediatric patients, Pediatr. Surg. Int. 18 (2002) 378—383. [15] A.P. Geraci, J. de Csepel, E. Shlasko, et al. Ganglioneuroblastoma and ganglioneuroma in association with neurofibormatosis type 1: report of three cases, J. Child. Neurol. 13 (1998) 356—358.