Parapharyngeal Space Ganglioneuroma: Clinical Experience and Review of the Literature

Abstract

Ganglioneuroma is a rare benign tumor originating in the sympathetic ganglia, composed of differentiated ganglion cells, nerve sheath cells, and nerve fibers, which tend to occur in the posterior mediastinum, adrenal gland, retroperitoneal, and other locations, occurring in the head and neck is relatively rare, and parapharyngeal space involvement is extremely rare. In our report, we present 2 adult male patients whose preoperative imaging and fine needle cytology did not confirm the diagnosis of a parapharyngeal space mass and who completely resected the tumor through a combined cervical and oral approach. Finally, pathology confirmed ganglioneuroma; we also reviewed the English articles on parapharyngeal ganglioneuroma over the past 40 years, and summarized the diagnostic and treatment characteristics of parapharyngeal ganglioneuroma in combination with our cases to improve understanding of the disease.

Keywords

Head and neck tumor ganglioneuroma neurogenic tumor parapharyngeal space surgery

Introduction

Ganglioneuroma is a rare benign tumor originating in the sympathetic ganglia, consisting of well differentiated ganglion cells, nerve sheath cells, and nerve fibers, and its general incidence only accounts for 2% to 3% of neurogenic tumors.¹ Ganglioneuroma can be found anywhere along the sympathetic chain, but its most common locations are the posterior mediastinum, adrenal gland, retroperitoneum, etc. The appearance of the head and neck is relatively rare, and the involvement of the parapharyngeal space is extremely rare.² Ganglioneuromas grow slowly, are often found by imaging techniques, or are large enough to have an effect on surrounding structures. For ganglioneuromas in the parapharyngeal space, it is difficult to establish a definitive clinical diagnosis without biopsy. Imaging tests are used to assess the extent of the tumor and can even help narrow the differential diagnosis. Excisional biopsy is the most definitive way to obtain tissue for diagnosis. Ganglioneuromas are usually treated with surgical removal. However, resection of these tumors can cause serious complications, especially in the parapharyngeal space and the skull base, where complex neurovascular structures are present.

Here, we present two cases of postoperative pathologically confirmed ganglioneuroma and review the nearly 40 year literature on the diagnosis and management of this rare parapharyngeal space tumor.

Case 1

A 58 year-old man without a special medical history was admitted to our hospital, with the principal complaint that he had a foreign body sensation in the pharynx for more than 4 months, accompanied by mild pain, without cough and expectoration, swallowing obstruction, dyspnea, and other discomfort. The patient was treated with anti-inflammatory drugs in the local clinic. After remission, no further treatment was performed until the symptoms had recently worsened, with limited mouth opening and a palpable mass in the left neck, and finally he was admitted to our hospital.

Physical examination revealed that the mouth was opened about 2 fingers apart, the tongue was not deviated, oral hygiene was poor, and the left side of the soft palate bulged with a smooth surface mucosa. Tenderness is evident on the surface of the mass and hypertrophy of the lingual tonsils is observed. In the left submandibular, a round mass of about 2 cm in diameter can be palpable, tough in texture, not easy to push, no redness, and swelling of the surface skin, slight tenderness, no fluctuation.

Contrast-enhanced CT and 3D reconstruction of the neck showed that there was a round mass shadow on the left wall of the nasopharynx-oropharynx-pharynx, about 88 × 48 × 48 mm in size, eggshell-shaped calcification at the edge, and multiple small nodules inside, and the left internal carotid artery and the external carotid artery were slightly displaced by compression. There was no obvious improvement in the lesion in each stage of the enhanced scan.

Contrast-enhanced MRI of the neck revealed an oval-shaped mixed signal mass in the left parapharyngeal region with clear borders. T1W1 showed a slightly mixed high signal, and T2W1 showed a mixed and low signal, with a patchy and nodular high signal inside. The T2W1 fat suppressing sequence showed mixed and high signal, and some strips and flocculent enhancement shadows were observed in enhanced scan lesions.

Fine needle biopsy of the soft palate showed that all were necrotic substances and tumor necrosis should be excluded first. After excluding surgical contraindications, the patient underwent transcervical combined endoscopic-assisted transoral parapharyngeal tumor resection. The KARL Storz display system and the 0° endoscope were used for intraoperative visualization, and low temperature plasma was used for tissue separation and hemostasis.

Pathology of tumor contents similar to fungal mass after operation: many inflammatory necrosis with calcification; no definite fungal hyphae and spores, surrounding fibrous tissue hyperplasia and vitreous degeneration forming encapsulation, with nodes on the necrotic tissue wall cells and nerve fibers; pathology of the outer cyst wall of the tumor: fibrous tissue, striated muscle, and adipose tissue. Many ganglion cells and nerve fibers were found in it, but no definite fungal hyphae or spores were found, and the morphology was consistent with ganglioneuroma (Figure 1).

Figure 1.

Axial (A) and coronal (B) contrast-enhanced CT scan; axial (C) and coronal (D) contrast-enhanced MRI scan; intraoperative tumor capsule was smooth and gross specimen after excision (E); the contents were dark brown , sediment-like and similar to fungal infection (F); postoperative pathology 40 × (G) and 200× (H).

At 1 year follow-up, there are no signs of tumor growth.

Case 2

A 22-year-old male patient was admitted to our hospital with the main complaint of “discovering a right neck mass for half a year.” Physical examination: A mass of 6 × 4 cm in size can be palpated on the right neck, with clear borders, tough texture, and good mobility.

The contrast-enhanced CT: A type of round soft tissue mass was observed in the space of the right carotid sheath, the size was about 66 × 40 × 35 mm, the mass reached slightly below the hard palate of the oropharynx, down to the level of the laryngopharyngeal glottis, with uneven internal density, and patchy necrosis of liquefaction and low density shadows were observed, the boundary is clear, the surrounding tissue is obviously pushed and compressed, and the enhanced scan is obviously unevenly enhanced.

Fine needle biopsy of the neck mass indicated that a small amount of tumor-like proliferative spindle cells were seen under the microscope and the possibility of schwannoma was high.

Taking into account the diagnosis of parapharyngeal neurogenic tumor, we performed tumor resection in the parapharyngeal space using the lateral cervical approach, explored the location of the tumor and the boundary of the surrounding great blood vessels in the right parapharyngeal space, and then completely removed the tumor. Postoperative pathology: right parapharyngeal space ganglioneuroma (Figure 2). There has been no recurrence during the 7 year follow-up.

Figure 2.

Intraoperative tumor capsule was smooth (A) and gross specimen after excision (B); postoperative pathology 40× (C) and 200× (D).

Review of the literature

We reviewed Ganglioneuroma cases located in the parapharyngeal space that were reported in the literature during the past 40 years. A total of 23 papers and 25 cases were included, plus the 2 patients we reported. The epidemiological and clinical features are summarized in Table 1.

Table1.

Epidemiological and Clinical Features of Parapharyngeal Ganglioneuroma are Reported in the Literature, Including Our Case Reports.

Authors of case reports	Age/gender	Size, (mm)	Symptoms	FNAB	Operative approach	Preoperative neurological symptoms	Postoperative neurological symptoms	Follow up
Danosos DA et al. (1980)³	42 Y/F	100 × 60 × 30 mm	Sore throat	NA	Transcervical	NA	Horner's syndrome and vocal cord paralysis	4 M
Sohma S et al. (1985)⁴	57 Y/M*	30 × 25 × 20 mm	Hoarseness and pharyngeal foreign body sensation	NA	Transcervical	IX X XII palsy	IX X XII palsy	—
Kittel K et al. (1999)⁵	19 Y/-	100 × 60 × 40 mm	Neck swelling and dysphagic	NA	—	NA	Myosis	—
Kaufman MR et al. (2001)⁶	11 Y/F	20 mm in diameter	Suprahyoid region swelling	Consistent	Transcervical	NA	Horner’s syndrome	6 M
Albonico G et al. (2001)⁷	27 Y/F	40 × 30 mm	Throat pain and with a neck mass	Inadequate	—	NA	NA	—
Califano L et al. (2001)⁸	2Y6 M/F	60 × 45 × 25 mm	Snoring and intermittent apnea	NA	Transcervical	NA	Horner's syndrome and significant dysphagia	24 M
Müller A et al. (2002)⁹	35 Y/F	35 × 30 × 15 mm	Retro auricular and occipital regions pain	Misleading	Transoral	NA	Horner’s syndrome	—
Leonardis M et al. (2003)¹⁰	50 Y/M*	100 × 70 × 40 mm	Neck mass	Inadequate	Transcervical	NA	palpebral ptosis	—
Stárek I et al. (2004)¹¹	2 Y/F	50 × 35 × 25 mm	Neck mass	NA	transcervical	NA	Vocal cord paralysis	24 M
Cannady SB et al. (2005)¹²	6 Y/M*	60 × 40 × 28 mm	Enlarging neck mass	Consistent	Transcervical	NA	Horner syndrome	24 M
	7 Y/M*	60 × 30 × 20 mm	Enlarging intraoral mass	NA	Transoral	NA	Horner’s Syndrome	156 M
	9 Y/F	60 × 50 mm	Intermittent dysphagia	consistent	Transcervical	NA	IX and XII incomplete paralyses	108 M
Ponce-Camach M et al. (2008)¹³	5 Y/F	40 × 30 mm	Parapharyngeal region mass	consistent	Transcervical	NA	Horner’s Syndrome	—
Parul S et al. (2011)¹⁴	22 Y/M*	90 × 70 × 40 mm	Neck swelling	consistent	Transcervical	NA	NA	36 M
Hallur N et al. (2012)¹⁵	4 Y/F	(100 × 64 × 57 mm) and (41 × 26 × 50 mm)	Slow-growing, painless mass	NA	Transcervical	NA	Myosis in the right eye	18 M
Yokoi H et al. (2012)¹⁶	19 Y/F	72 × 33 × 11 mm	A mass in the middle of the pharynx	inadequate	Transoral	NA	Horner’s syndrome	60 M
Ma J et al. (2012)¹⁷	4 Y/F	54 × 37 × 33 mm	Enlarging neck mass, dysphagia	Misleading	Transcervical	hypoglossal nerve involvement	Hypoglossal nerve involvement	1 M
Deepak D et al. (2016)¹⁸	25 Y/M*	50 × 30 mm	Neck swelling and hoarseness	Misleading	Transcervical	X paralysis	X paralysis	—
Bakshi J et al. (2016)¹⁹	10 Y/F	40 × 50 mm	Slowly progressive swelling	NA	Transcervical	NA	Hypoglossal nerve and vocal fold palsy	12 M
Garzorz N et al. (2016)²⁰	3 Y/M*	60 × 28 × 17 mm	Enlarging neck mass	NA	Transcervical	NA	NA	36 M returned
Salimov A et al. (2016)²¹	13 Y/F	115 × 55 × 40 mm	Neck swelling	inadequate	Transcervical + Transparotid	NA	Horner syndrome	12 M
Lima AF et al. (2018)²²	13 Y/F	60 × 35 mm	Enlarging neck mass	NA	Transcervical	NA	Horner’s syndrome	24 M
Bach J et al. (2018)²³	17 Y/M*	Maximum diameter 86 mm	Throat pain, d dysphagia and right throat mass	NA	Transoral and Transcervical	NA	NA	—
Ma HM et al. (2019)²⁴	35 Y/F	—	Headache	NA	Transoral	NA	NA	18 M
Aslan M, et al. (2021)²⁵	41 Y/M*	100 × 50 × 40 mm	Enlarging neck mass	NA	Transcervical	NA	Myosis developed in the left eye.	12 M
Our cases	58 Y/M*	88 × 48 × 48 mm	Pharyngeal foreign body sensation	Misleading	Transoral and transcervical	NA	NA	12 M
Our cases	22 Y/M*	60 × 40 × 35 mm	Neck mass	Inadequate	Transcervical	NA	NA	84 M

FNAB: fine-needle aspiration biopsy; Y: year; F: female; NA: not available; M: month; M*: man.

Discussion

Ganglioneuroma is a rare, benign, noninvasive tumor that originates in the sympathetic nervous system and consists of well-differentiated ganglion cells, nerve sheath cells, and nerve fibers. It occurs in the posterior mediastinum, adrenal gland, retroperitoneal, and other positions, occurs in the head and neck and is relatively rare, and parapharyngeal space involvement is extremely rare.

Ganglioneuroma is a benign tumor in peripheral nerve disease, which grows slowly, and the appearance of clinical symptoms depends on the size and location of the tumor. The parapharyngeal space starts from the base of the skull and descends to the hyoid bone. Therefore, benign tumors that occur there are usually asymptomatic and have a long course of disease. They are mostly discovered incidentally during physical examination. A small number of patients may experience neurological damage such as dysphagia, hoarseness, choking after drinking water, and Horner syndrome after compression of the peripheral nerves and tissues due to large tumors.²⁶ The largest tumor in the reviewed cases was 115 × 55 × 40 mm in size, but only manifested as symptoms of neck swelling, some ganglioneuromas, with low levels of neuroendocrine activity, can experience increased blood pressure, sweating, and diarrhea.⁵ In the reviewed literature in this study, no clinical symptoms related to neuroendocrine activity were reported, except for a large parapharyngeal mass that caused foreign body sensation, dysphagia, neck swelling, and mass.

Current advanced imaging techniques may be helpful in assessing the extent and differential diagnosis of the tumor. A judicious combination of USG, FNAB, CT, MRI, and angio-CT delineates the location, nature, and extent of the tumor and facilitates treatment planning. The imaging manifestations of ganglioneuroma have certain characteristics. For example, tumors have clear borders, regular morphology, pseudopodia or embedded growth, and CT scans show low or medium density shadows and calcifications; Or MRI scan shows “vortex sign,” enhanced scan shows mild cord-like or flocculent enhancement, T2WI shows high signal, etc. However, these features are not specific and are seen in other neurogenic tumors, such as schwannomas and neurofibromas. Wan-Ling Yi found that PET-CT is helpful in the diagnosis of neurogenic lesions in the parapharyngeal space.²⁷

It is difficult to make a precise preoperative histological diagnosis of ganglioneuromas. Fine needle aspiration biopsy is not always decisive for ganglioneuromas as a diagnostic procedure.

Of the cases we reviewed, 14 patients underwent oral or cervical fine needle biopsy, among them, the results of 5 patients (35.7%) were consistent with their final pathology, 5 patients (35.7%) had unknown results and 4 patients (28.6%) were misdiagnosed as other types of tumor or disease.

In an encapsulated appearance, they appear as mucinous tumors in section. Microscopically, the most prominent feature is the presence of mature ganglion cells and schwannian stroma.

In our case 1, the preoperative fine needle aspiration biopsy showed necrosis tissues and the tumor capsule was incised during the operation. The contents were dark brown and sediment-like, like fungal infection, but no fungal spores were found on the pathological examination, PAS(-) and PASM(-). We analyzed the reasons, which may be due to the large tumor size and central necrotic tissue, resulting in tumor contents that are morphologically similar to fungal spheres.

Surgery is the main method for the treatment of parapharyngeal space tumors. The parapharyngeal space is one of the most complex anatomical regions in the head and neck, containing many important vascular and neural structures, making the surgical management of this region very challenging. To incorporate the objectives of as complete tumor resection as possible, less damage to normal structures, and hidden and aesthetic incisions, different surgical approaches have been developed, that is, transoral, transcervical, transparotid, transmandibular, and combinations of these approaches.²⁸ The transoral approach has the advantages of a short path, less damage and no skin incision, and is gradually being respected.²⁹ Currently, the most widely used approach is the lateral cervical approach, mainly because the lateral cervical approach has the advantages of a wide surgical field and better exposure to the great vessels and important nerves in the neck.³⁰ In the cases we reviewed, except for 2 patients who did not explain the surgical method, the remaining 18 patients (72%) were treated with a transcervical approach to tumor resection. In our reported case 1, the tumor was resected using the combined transcervical transoral approach, the nasal endoscope helped provide a clear and good surgical field, and the tumor was cut and separated by a low temperature plasma surgical system.

The prognosis for GN is generally good and the risk is mainly related to the sacrifice of tumor-related neural structures during surgery. Of the cases we reviewed, Horner syndrome developed postoperatively in 10 patients and corresponding neurological deficits in 4 patients, but these symptoms usually resolve completely within a few months, and one patient recurred 3 years after surgery.¹⁸

Conclusions

Parapharyngeal ganglioneuroma is a rare peripheral neurogenic tumor that grows slowly, and its clinical manifestations are related to the size and location of the tumor. Imaging examinations can clarify the extent of the tumor and its relationship with peripheral blood vessels and nerves and provide a reference and basis for the surgical method and the extent of resection. Pathology remains the gold standard for diagnosing the disease. Because the positive rate of fine-needle aspiration biopsy is low, if the tumor location is relatively safe, fine-needle aspiration biopsy may be considered. Surgical resection is the main treatment method and the most used is the transcervical approach. The endoscopic-assisted transoral approach has been gradually promoted due to its advantages of a clear field of view, a short path, less damage, and no need for skin incision. Horner syndrome and neurological dysfunction often appear after surgery, and most of them disappear gradually after a few months. Ganglioneuroma has a better prognosis and a low recurrence rate after surgery.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval

We have obtained the consent and the local research ethics committee approved the study.

Consent Statement

We have obtained the consent.

Data Availability

All data generated or analyzed during this study are included in this published article.

ORCID iD

Fei Li

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