Composite Ganglioneuroma and Schwannoma of the Cervical Sympathetic Chain: A Case Report

Abstract

Neurogenic tumors are benign tumors arising from nerve sheath or autonomic ganglion cells. Tumors arising from autonomic ganglion cells include neuroblastomas, ganglioneuromas, and ganglioneuroblastomas. Ganglioneuroma (GN) is a rare entity (1 per million). Composite ganglioneuromas with schwannomas are extremely rare in the head and neck. We report one such case.

Introduction

Ganglioneuromas (GN) are rare benign tumors of neurogenic origin. Most commonly seen in the mediastinum or abdomen, its occurrence in head and neck is rare. It is more common in young adult females and often arises from the cervical sympathetic chain. It can also arise from the vagus nerve. The patients with this entity present with a single long-standing slowly growing neck swelling (29.3%), which often is the only presenting symptom [1]. The presence of neurological deficit is a relatively late presentation which can include Horner’s syndrome or vocal cord palsy. Management includes observation or surgical excision. The tumor is slow-growing and no recurrences were reported post-surgical excision in a systematic review of 58 cases of cervical ganglioneuromas [1]. This paper aims to report a rare clinical entity of composite cervical ganglioneuroma and schwannoma.

Case Report

A gentleman in his early 50’s presented to us with left-sided neck swelling for 1½ years. It was insidious in onset and was visually noted by a bystander and gradually progressed to its current size. His family history was unremarkable. He had an addiction history of smoking (25 pack years) and tobacco chewing (20 years). The swelling was not associated with pain or any systemic manifestation such as palpitations or flushing. There were no compressive symptoms and no signs of neurological involvement.

On examination, a single, firm, mobile, non-tender, non-fluctuant, non-pulsatile swelling (measuring 3 × 3 cm) was present at the left level II. The overlying skin was normal with no local rise in temperature. A contrast-enhanced computed tomography showed a well-defined, lobulated iso to hypodense mass lesion with smooth margins in the left carotid space from C2 to C4 levels, measuring 3.3 × 3.8 × 4.9 cm. The lesion pushed the vessels anteriorly and compressed the internal jugular vein with maintained fat planes. Following multiple inconclusive cytology, a guided biopsy showed sheets of spindle cells with oval nuclei, inconspicuous nucleoli, and nuclear palisading (Verocay bodies). The IHC was non-contributory because of inadequate tissue. The possibility of Schwannoma was considered. (Fig. 1)

Fig. 1.

Pre-operative Clinico-radiological appearance. Clinical photo (a) showing the presentation with left-side neck swelling (black arrows). Contrast-enhanced computed tomography (b and c) shows a homogenous non-enhancing isodense lesion with smooth margins (yellow arrow), pushing the carotid vessels (red arrow) anteriorly on axial (b) and sagittal sections (c)

Transcervical excision was done by exposing the carotid sheath. The common carotid artery, internal jugular vein, vagus nerve, spinal accessory nerve and the hypoglossal nerve were identified and preserved. A firm, well-encapsulated tumor measuring 5 × 4 cm, was seen arising posterior to the carotid sheath and pushing the vessels anteriorly. Post-operative period was uneventful with no neurological deficits. The patient was disease free at one year of follow up.

On gross examination, a well-encapsulated tumor measuring 3.8 × 2.5 × 2 cm was seen. The cut surface was soft and homogenous with focal areas of hemorrhage. Microscopic examination revealed a mesenchymal tumor which was composed of hyper and hypocellular areas. The tumor cells were arranged in fascicles with oval and elongated hyperchromatic nuclei. Focal nuclear palisading was seen. The stroma was edematous with cystic changes. There was marked perivascular hyalinisation. Some areas showed mature ganglion cells in a schwannian background. These areas were intermixed with cellular areas. No immature neuroblast cells were seen. (Fig. 2A)

Fig. 2.

Intra-operative and histopathological examination. (A) Intra-operative image showing a smooth, oval, well-encapsulated tumor measuring 5 × 4 cm, pushing the carotid artery anteriorly. Gross examination shows a single globular tumor measuring 4 × 3 × 2 cm well-encapsulated tumor. The sliced tumor shows a yellow, soft and homogenous tumor with few foci of hemorrhage. (B) Hematoxylin and eosin (H&E) stained sections show a relatively hypocellular (a, H&E x20) and adjacent cellular area (arrows) (b, H&E x20). The hypocellular area shows an admixture of mature ganglion cells with compact, granular eosinophilic cytoplasm, distinct cell borders, and an eccentric nucleus (arrows) and Schwann cells. Stroma shows loose collagen fibres (c, H&E x100). The cellular area shows a hypercellular Antoni A area with nuclear palisading around fibrillar collagen processes (Verocay bodies) (d, H&E x200)

The spindle cells were diffusely positive for S100 protein, SOX-10, and negative for PHOX2B. H3K27me3 immunoexpression was retained. The ganglion cells were positive for chromogranin. While chromogranin, S100, and SOX-10 positivity indicate the component of Schwannoma, the negative PHOX2B rules out Paraganglioma. The loss of expression of H3K27me3 is typically seen in the Malignant Peripheral Nerve Sheath Tumor (MPNST), which was ruled out given the retained expression of H3K27me3 in our case (Fig. 2B) [2–4].

Discussion

Neurogenic tumors can present in one of the three ways (Ganglioneuromas-GN, neuroblastomas-NB, and ganglioneuroblastomas-GNB) based on their differentiation. While GN is a benign well-differentiated tumor, GNB represent the other end of the spectrum, being highly aggressive and undifferentiated.

GN occurs most commonly in the posterior mediastinum (60 to 80%), followed by the abdominal cavity (10 to 15%). The cervical region represents only 1 to 5% of all the GN. Rare sites of this entity have been reported such as the orbit, the parapharyngeal space, and the middle ear [5, 6].

Cervical GN is a rare entity. Xu et al. published a literature review (2019) of 27 cases reported in 21 articles, and 58 cases were reported in another systematic review (Saadat et al.) [1, 6]. The majority of cases were young females, however, our patient was a male in his early 50’s. The most common site was the parapharyngeal space (69%) [1].

Paraskevopoulos et al. [7] reported a case of synchronous ganglioneuroma and schwannoma which mimicked carotid body tumor in a 17-year-old female who presented with neck swelling.

The most common clinical presentation is painless neck swelling (29.3%), dysphagia (17.2%) and hoarseness of voice (10.3%). These are almost always not secretory. However, secretory cervical ganglioneuroma (Sinha et al.) [8] and schwannoma (Singh et al.) [7] have been reported.

Schwannoma pushes the carotid artery anteriorly. The distance between the carotid and the internal jugular vein is increased in vagal schwannoma, whereas it remains the same in cervical sympathetic chain schwanomas (as in our case).

The presence of immature ganglion cells in cytology is characteristic of these tumors, however FNAC may not always be conclusive. Sinha et al. found FNAC’s diagnostic value to be 40% in review of 37 parapharyngeal space GN [8].

Very limited literature exists on the concurrent existence of schwannoma along with ganglioneuroma [9, 10]. A differential of these tumors must be kept in mind while evaluating a repeatedly inconclusive benign neck swelling. Management includes observation or surgical excision (nerve transection, enucleation, or debulking). Tumor size, location and symptoms must guide the management keeping in mind the functional morbidity associated with surgery.

Funding

Not applicable.

Declarations

Competing Interests

Not applicable.