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Ganglioneuroma of the parapharyngeal space in a pediatric patient
Ganglioneuroma of the parapharyngeal space in a pediatric patient MATTHEW R. KAUFMAN, MD, JOHN S. RHEE, MD, LAWRENCE J. FLIEGELMAN, MD, and PETER D. COSTANTINO, MD, New York,
New York, and Milwaukee, Wisconsin
Ganglioneuromas are rare, benign, neurogenic tumors arising from central or peripheral components of the sympathetic nervous system. They most commonly present in patients younger than 20 years of age in the posterior mediastinum or retroperitoneum.1 When these tumors present in alternative locations, a definitive clinical diagnosis is difficult because of a paucity of specific signs and symptoms. It has been reported that in a majority of cases these tumors exhibit clinically detectable evidence of production of adrenergic hormones, however, few patients actually manifest a sympathetic response.1 Ganglioneuromas are slow growing, noninvasive lesions that are often only detectable incidentally as a painless mass or because of a mass effect on neighboring structures. Evaluation with CT imaging can reveal the size, extent, and composition of such tumors; however, a biopsy is necessary for definitive diagnosis. The most characteristic histologic feature of ganglioneuromas is the presence of mature ganglion cells. Approximately 25% of ganglioneuromas will also have histologic elements of immature neurogenic tumors; it has been hypothesized that tumors of neural crest origin have the propensity to mature from malignant forms (ie, neuroblastoma) into the benign ganglioneuroma.3 Complete cure is possible with surgical excision, depending on the location of the tumor. Significant morbidity may occur as a result of the intraoperative sacrifice of structures intimately associated with the tumor such as neural structures or vasculature. We report on the case of a 21/2-year-old female patient with a parapharyngeal space ganglioneuroma,
From the Department of Otolaryngology (Drs Kaufman, Fliegelman, and Costantino), The Mount Sinai Medical Center, and the Department of Otolaryngology (Dr Rhee), Medical College of Wisconsin. Reprint requests: Matthew R. Kaufman, MD, Department of Otolaryngology, The Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1189, New York, NY 10029; e-mail, [email protected] Otolaryngol Head Neck Surg 2001;124:702-4. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/4/115371 doi:10.1067/mhn.2001.115371 702
including diagnosis and management of these rare tumors. CASE REPORT A 21/2-year-old female with a 1-year history of snoring and intermittent apnea presented to her pediatrician with right cervical adenopathy. The patient was initially diagnosed with chronic tonsillitis and was treated with a course of antibiotics. An additional work-up for mononucleosis was negative. Over the next month, the patient’s condition worsened with episodes of apnea, odynophagia, fever, and ultimately stridor, for which she was admitted to an outside hospital and intubated to secure her airway. A CT was performed that revealed a well-encapsulated right parapharyngeal space mass with medial displacement of the right lateral pharyngeal wall (Fig 1A). T2-weighted coronal and axial MRI with contrast demonstrated an enhancing mass extending superiorly to the level of the skull base, posteriorly into the retropharyngeal space, and across the midline. There was anterolateral displacement of the internal carotid artery and internal jugular vein. Preservation of the soft tissue planes surrounding the tumor was suggestive of a noninvasive lesion (Fig 1B). The patient underwent a right neck exploration with incisional biopsy of the mass and an elective tracheostomy for airway control. The biopsy specimen was a bilobed, grey, glistening tissue portion measuring 1.2 × 0.7 × 0.4 cm, which was consistent with a ganglioneuroma. The patient was subsequently transferred to our institution for definitive treatment. The patient underwent surgical excision of the mass that involved a transcervical dissection approach. On raising the skin flaps, there was noted to be some reactive adenopathy along the Level II nodes. The internal jugular vein and the internal carotid artery were noted to be splayed out laterally due to the mass of the tumor. The tumor was encountered arising from the sympathetic chain with the sympathetic chain ramifying into the mass. With careful sharp and blunt dissection, the mass was dissected from the contents of the neck in anterior, posterior, and medial margins. The sympathetic trunk was clipped and divided at the point at which it was ramifying into the mass. All the cranial nerves including IX, X, XI, XII were identified and preserved in continuity, and all were stimulatable with a nerve stimulator. The mass was then freed from surrounding tissue at the skull base and taken out in toto. The gross pathology revealed a lobulated, encapsulated mass of pink-tan soft tissue, measuring 6 × 4.5 × 2.5 cm.
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A Fig 2. High-power (×40) microscopy revealing the presence of mature ganglion cells.
The patient has subsequently been decannulated and has done well from both a swallowing and an airway standpoint. DISCUSSION
B Fig 1. A, Contrast-enhanced CT scan reveals a right parapharyngeal space mass medially displacing the right lateral pharyngeal wall. B, T2-weighted MRI demonstrates an enhancing lesion extending to the skull base and crossing the midline.
Histologically, mature ganglion cells within a fibrous matrix are well represented throughout the specimen and appear as well-differentiated cells with abundant cytoplasm, and large, euchromatic nuclei (Fig 2). S-100 immunostain enhances the neuronal elements present in the specimen and provides evidence that this was indeed a tumor of neurogenic origin. The postoperative course of the patient was complicated by a Horner’s syndrome and significant dysphagia with aspiration of thin liquids. A modified barium swallow revealed right hypopharyngeal dysmotility with pooling in the pyriform sinuses and intermittent aspiration. Decannulation was deferred, and she was nutritionally managed on nasogastric tube feeds. On postoperative day 36, she was discharged with outpatient speech therapy to restore pharyngeal muscle function.
Ganglioneuromas are benign tumors arising from neural crest cell derivatives. The cells of the neural crest migrate ventrally from the primordial spinal cord early in embryologic development forming the primitive cells, or sympathogonia, of the adrenal medulla and paraganglia. The sympathogonia differentiate into 2 cell lines: the sympathoblast that results in the production of mature ganglion cells, and the pheochromoblast that leads to pheochromocyte production. Tumors arising from the former include the immature neuroblastoma or the mature ganglioneuroma. A tumor exhibiting significant histologic evidence of both immature and mature elements is termed a ganglioneuroblastoma. A hypothesis exists whereby tumors of neural crest derivative undergo a maturational process or spontaneous regression from neuroblastoma to ganglioneuroma.3 This is an age-related phenomenon in that the rate of spontaneous regression of neuroblastomas to ganglioneuromas is highest in infants less than 6 months of age, with an accordingly higher rate of survival in this age group. Among benign tumors of neural origin, ganglioneuromas are rare in comparison to such entities as schwannomas or neurofibromas. Ganglioneuromas were first described by Loretz in 1870 and first reported as occurring in the neck by DeQuervain in 1899. Sixty percent of patients with ganglioneuromas are less than 20 years of age; the average age of presentation is approximately 11 with a slight preponderance of cases in females.1 The cervical sympathetic chain is the most common
704
Otolaryngology– Head and Neck Surgery June 2001
KAUFMAN et al
structure of origin, with other sites including the larynx, pharynx, and nodose ganglion of the vagus nerve. Correspondingly, the most common location of these tumors is the posterior mediastinum, followed by the retroperitoneum. Ganglioneuromas can infrequently be found in the neck, including the parapharyngeal space; however, this is seen predominantly in the adult population. Parapharyngeal space ganglioneuromas in the pediatric population are exceedingly rare. Because ganglioneuromas are slow growing, they often go clinically unrecognized for an extended period of time. As with any tumor arising in the parapharyngeal space, an incidental diagnosis is often made based on the presence of a cervical or intraoral mass with continuity on bimanual palpation. Symptoms are the result of compression of vital structures after the mass has become especially large, or when the tumor is functioning. Expansion of the mass results in compression of the lateral pharyngeal wall, which produces a downward and medial displacement of the tonsils and palatal arches. A patient may have dyspnea, dysphagia, and foreign body sensation, prompting a diagnosis of tonsillitis or peritonsillar abscess. Pulsations over the mass may occur as a result of intrinsic tumor vascularity or transmission from the internal carotid artery. The concurrence of serous otitis or conductive hearing loss with a palpable neck mass may suggest eustachian tube obstruction. When a tumor is functioning, a patient with a palpable neck mass may also have hypertension, diarrhea, sweating, flushing, and renal acidosis. Diarrhea as an associated symptom has been related to vasoactive intestinal peptide, which has been found in the cytoplasm of the mature ganglion cell. Although it has been reported that a majority of patients with ganglioneuromas have elevated urine vanillylmandelic acid levels, few actually manifest symptoms.1 Finally, patients may exhibit Horner’s syndrome based on the origination of the tumor within the cervical sympathetic chain. Ganglioneuromas will appear as a well-defined mass with low or intermediate attenuation on CT imaging with contrast. The pattern of calcification apparent on these studies may facilitate a distinction between ganglioneuromas and the malignant counterpart, neuroblastoma. Whereas ganglioneuromas often show discrete calcifications, the calcification pattern of neuroblastomas is more likely to be coarse.2 On T2-weighted MRI, ganglioneuro-
mas exhibit inhomogeneous but high-intensity signaling. Findings atypical to suspected ganglioneuromas should raise suspicion for malignant or more aggressive elements, such as neuroblastoma, ganglioneuroblastoma, or pheochromocytoma. Although it is difficult to diagnose a parapharyngeal space ganglioneuroma radiologically, these studies are helpful in ruling out other pathologic conditions. A tumor of the deep lobe of the parotid is unlikely with preservation of the fat planes between the mass and the parotid gland. In addition, the lack of high attenuation on contrast imaging decreases the likelihood of other varieties of neurogenic tumors, especially paragangliomas. For tumors of the parapharyngeal space, an incisional biopsy is the preferred method of tissue diagnosis, reserving open neck or transoral biopsies for when there is a high suspicion of lymphoma. On gross appearance they are encapsulated tumors that have a mucinous appearance on sectioning. Microscopically, the most prominent feature is the presence of mature ganglion cells. These tumors also display a cytologic architecture consistent with mature axonal bundles; however, the structural organization of these elements is somewhat disorganized. Up to 25% of tumors exhibit some histologic evidence of less well-differentiated structures, such as the small basophilic cells seen in more aggressive neurogenic tumors. Ganglioneuromas are benign tumors for which surgical excision is the appropriate treatment. No further therapy is needed if complete resection is possible. If complete resection is impossible, a debulking procedure is the indicated therapy. In a majority of patients with incomplete resections, residual ganglioneuroma will not regrow or produce symptoms. There have been rare instances in which ganglioneuromas have undergone malignant transformation to a malignant schwannoma or malignant peripheral nerve sheath tumor. REFERENCES 1. Hamilton JP, Koop CE. Ganglioneuromas in childhood. Surg Gynaecol Obstet 1965;21:803-12. 2. Ichikawa T, Ohtomo K, Araki T. Ganglioneuroma: computed tomography and magnetic resonance features. Br J Radiol 1996;69:11421. 3. Bolande RP. Benignity of neonatal tumors and concept of cancer repression in early life. Am J Dis Child 1971;22:12-4. 4. Kumar A, Hazarika P, Kapadia RP. Neurogenic tumors of the parapharyngeal space in the pediatric age group. Int J Ped Otorhinolaryngology 1991;22:195-200. 5. Som PM, Biller HF, Lawson W. Tumors of the parapharyngeal space: preoperative evaluation, diagnosis and surgical approaches. Ann Otol Rhinol Laryngol (Suppl) 1981;80:3-15.
New York, and Milwaukee, Wisconsin
Ganglioneuromas are rare, benign, neurogenic tumors arising from central or peripheral components of the sympathetic nervous system. They most commonly present in patients younger than 20 years of age in the posterior mediastinum or retroperitoneum.1 When these tumors present in alternative locations, a definitive clinical diagnosis is difficult because of a paucity of specific signs and symptoms. It has been reported that in a majority of cases these tumors exhibit clinically detectable evidence of production of adrenergic hormones, however, few patients actually manifest a sympathetic response.1 Ganglioneuromas are slow growing, noninvasive lesions that are often only detectable incidentally as a painless mass or because of a mass effect on neighboring structures. Evaluation with CT imaging can reveal the size, extent, and composition of such tumors; however, a biopsy is necessary for definitive diagnosis. The most characteristic histologic feature of ganglioneuromas is the presence of mature ganglion cells. Approximately 25% of ganglioneuromas will also have histologic elements of immature neurogenic tumors; it has been hypothesized that tumors of neural crest origin have the propensity to mature from malignant forms (ie, neuroblastoma) into the benign ganglioneuroma.3 Complete cure is possible with surgical excision, depending on the location of the tumor. Significant morbidity may occur as a result of the intraoperative sacrifice of structures intimately associated with the tumor such as neural structures or vasculature. We report on the case of a 21/2-year-old female patient with a parapharyngeal space ganglioneuroma,
From the Department of Otolaryngology (Drs Kaufman, Fliegelman, and Costantino), The Mount Sinai Medical Center, and the Department of Otolaryngology (Dr Rhee), Medical College of Wisconsin. Reprint requests: Matthew R. Kaufman, MD, Department of Otolaryngology, The Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1189, New York, NY 10029; e-mail, [email protected] Otolaryngol Head Neck Surg 2001;124:702-4. Copyright © 2001 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2001/$35.00 + 0 23/4/115371 doi:10.1067/mhn.2001.115371 702
including diagnosis and management of these rare tumors. CASE REPORT A 21/2-year-old female with a 1-year history of snoring and intermittent apnea presented to her pediatrician with right cervical adenopathy. The patient was initially diagnosed with chronic tonsillitis and was treated with a course of antibiotics. An additional work-up for mononucleosis was negative. Over the next month, the patient’s condition worsened with episodes of apnea, odynophagia, fever, and ultimately stridor, for which she was admitted to an outside hospital and intubated to secure her airway. A CT was performed that revealed a well-encapsulated right parapharyngeal space mass with medial displacement of the right lateral pharyngeal wall (Fig 1A). T2-weighted coronal and axial MRI with contrast demonstrated an enhancing mass extending superiorly to the level of the skull base, posteriorly into the retropharyngeal space, and across the midline. There was anterolateral displacement of the internal carotid artery and internal jugular vein. Preservation of the soft tissue planes surrounding the tumor was suggestive of a noninvasive lesion (Fig 1B). The patient underwent a right neck exploration with incisional biopsy of the mass and an elective tracheostomy for airway control. The biopsy specimen was a bilobed, grey, glistening tissue portion measuring 1.2 × 0.7 × 0.4 cm, which was consistent with a ganglioneuroma. The patient was subsequently transferred to our institution for definitive treatment. The patient underwent surgical excision of the mass that involved a transcervical dissection approach. On raising the skin flaps, there was noted to be some reactive adenopathy along the Level II nodes. The internal jugular vein and the internal carotid artery were noted to be splayed out laterally due to the mass of the tumor. The tumor was encountered arising from the sympathetic chain with the sympathetic chain ramifying into the mass. With careful sharp and blunt dissection, the mass was dissected from the contents of the neck in anterior, posterior, and medial margins. The sympathetic trunk was clipped and divided at the point at which it was ramifying into the mass. All the cranial nerves including IX, X, XI, XII were identified and preserved in continuity, and all were stimulatable with a nerve stimulator. The mass was then freed from surrounding tissue at the skull base and taken out in toto. The gross pathology revealed a lobulated, encapsulated mass of pink-tan soft tissue, measuring 6 × 4.5 × 2.5 cm.
Otolaryngology– Head and Neck Surgery Volume 124 Number 6
KAUFMAN et al
703
A Fig 2. High-power (×40) microscopy revealing the presence of mature ganglion cells.
The patient has subsequently been decannulated and has done well from both a swallowing and an airway standpoint. DISCUSSION
B Fig 1. A, Contrast-enhanced CT scan reveals a right parapharyngeal space mass medially displacing the right lateral pharyngeal wall. B, T2-weighted MRI demonstrates an enhancing lesion extending to the skull base and crossing the midline.
Histologically, mature ganglion cells within a fibrous matrix are well represented throughout the specimen and appear as well-differentiated cells with abundant cytoplasm, and large, euchromatic nuclei (Fig 2). S-100 immunostain enhances the neuronal elements present in the specimen and provides evidence that this was indeed a tumor of neurogenic origin. The postoperative course of the patient was complicated by a Horner’s syndrome and significant dysphagia with aspiration of thin liquids. A modified barium swallow revealed right hypopharyngeal dysmotility with pooling in the pyriform sinuses and intermittent aspiration. Decannulation was deferred, and she was nutritionally managed on nasogastric tube feeds. On postoperative day 36, she was discharged with outpatient speech therapy to restore pharyngeal muscle function.
Ganglioneuromas are benign tumors arising from neural crest cell derivatives. The cells of the neural crest migrate ventrally from the primordial spinal cord early in embryologic development forming the primitive cells, or sympathogonia, of the adrenal medulla and paraganglia. The sympathogonia differentiate into 2 cell lines: the sympathoblast that results in the production of mature ganglion cells, and the pheochromoblast that leads to pheochromocyte production. Tumors arising from the former include the immature neuroblastoma or the mature ganglioneuroma. A tumor exhibiting significant histologic evidence of both immature and mature elements is termed a ganglioneuroblastoma. A hypothesis exists whereby tumors of neural crest derivative undergo a maturational process or spontaneous regression from neuroblastoma to ganglioneuroma.3 This is an age-related phenomenon in that the rate of spontaneous regression of neuroblastomas to ganglioneuromas is highest in infants less than 6 months of age, with an accordingly higher rate of survival in this age group. Among benign tumors of neural origin, ganglioneuromas are rare in comparison to such entities as schwannomas or neurofibromas. Ganglioneuromas were first described by Loretz in 1870 and first reported as occurring in the neck by DeQuervain in 1899. Sixty percent of patients with ganglioneuromas are less than 20 years of age; the average age of presentation is approximately 11 with a slight preponderance of cases in females.1 The cervical sympathetic chain is the most common
704
Otolaryngology– Head and Neck Surgery June 2001
KAUFMAN et al
structure of origin, with other sites including the larynx, pharynx, and nodose ganglion of the vagus nerve. Correspondingly, the most common location of these tumors is the posterior mediastinum, followed by the retroperitoneum. Ganglioneuromas can infrequently be found in the neck, including the parapharyngeal space; however, this is seen predominantly in the adult population. Parapharyngeal space ganglioneuromas in the pediatric population are exceedingly rare. Because ganglioneuromas are slow growing, they often go clinically unrecognized for an extended period of time. As with any tumor arising in the parapharyngeal space, an incidental diagnosis is often made based on the presence of a cervical or intraoral mass with continuity on bimanual palpation. Symptoms are the result of compression of vital structures after the mass has become especially large, or when the tumor is functioning. Expansion of the mass results in compression of the lateral pharyngeal wall, which produces a downward and medial displacement of the tonsils and palatal arches. A patient may have dyspnea, dysphagia, and foreign body sensation, prompting a diagnosis of tonsillitis or peritonsillar abscess. Pulsations over the mass may occur as a result of intrinsic tumor vascularity or transmission from the internal carotid artery. The concurrence of serous otitis or conductive hearing loss with a palpable neck mass may suggest eustachian tube obstruction. When a tumor is functioning, a patient with a palpable neck mass may also have hypertension, diarrhea, sweating, flushing, and renal acidosis. Diarrhea as an associated symptom has been related to vasoactive intestinal peptide, which has been found in the cytoplasm of the mature ganglion cell. Although it has been reported that a majority of patients with ganglioneuromas have elevated urine vanillylmandelic acid levels, few actually manifest symptoms.1 Finally, patients may exhibit Horner’s syndrome based on the origination of the tumor within the cervical sympathetic chain. Ganglioneuromas will appear as a well-defined mass with low or intermediate attenuation on CT imaging with contrast. The pattern of calcification apparent on these studies may facilitate a distinction between ganglioneuromas and the malignant counterpart, neuroblastoma. Whereas ganglioneuromas often show discrete calcifications, the calcification pattern of neuroblastomas is more likely to be coarse.2 On T2-weighted MRI, ganglioneuro-
mas exhibit inhomogeneous but high-intensity signaling. Findings atypical to suspected ganglioneuromas should raise suspicion for malignant or more aggressive elements, such as neuroblastoma, ganglioneuroblastoma, or pheochromocytoma. Although it is difficult to diagnose a parapharyngeal space ganglioneuroma radiologically, these studies are helpful in ruling out other pathologic conditions. A tumor of the deep lobe of the parotid is unlikely with preservation of the fat planes between the mass and the parotid gland. In addition, the lack of high attenuation on contrast imaging decreases the likelihood of other varieties of neurogenic tumors, especially paragangliomas. For tumors of the parapharyngeal space, an incisional biopsy is the preferred method of tissue diagnosis, reserving open neck or transoral biopsies for when there is a high suspicion of lymphoma. On gross appearance they are encapsulated tumors that have a mucinous appearance on sectioning. Microscopically, the most prominent feature is the presence of mature ganglion cells. These tumors also display a cytologic architecture consistent with mature axonal bundles; however, the structural organization of these elements is somewhat disorganized. Up to 25% of tumors exhibit some histologic evidence of less well-differentiated structures, such as the small basophilic cells seen in more aggressive neurogenic tumors. Ganglioneuromas are benign tumors for which surgical excision is the appropriate treatment. No further therapy is needed if complete resection is possible. If complete resection is impossible, a debulking procedure is the indicated therapy. In a majority of patients with incomplete resections, residual ganglioneuroma will not regrow or produce symptoms. There have been rare instances in which ganglioneuromas have undergone malignant transformation to a malignant schwannoma or malignant peripheral nerve sheath tumor. REFERENCES 1. Hamilton JP, Koop CE. Ganglioneuromas in childhood. Surg Gynaecol Obstet 1965;21:803-12. 2. Ichikawa T, Ohtomo K, Araki T. Ganglioneuroma: computed tomography and magnetic resonance features. Br J Radiol 1996;69:11421. 3. Bolande RP. Benignity of neonatal tumors and concept of cancer repression in early life. Am J Dis Child 1971;22:12-4. 4. Kumar A, Hazarika P, Kapadia RP. Neurogenic tumors of the parapharyngeal space in the pediatric age group. Int J Ped Otorhinolaryngology 1991;22:195-200. 5. Som PM, Biller HF, Lawson W. Tumors of the parapharyngeal space: preoperative evaluation, diagnosis and surgical approaches. Ann Otol Rhinol Laryngol (Suppl) 1981;80:3-15.