Perineural spread of head and neck cancer to the great auricular nerve: a case series

Introduction

Head and neck cancers encompass malignancies of the oral cavity, pharynx, larynx, nasal cavity and sinuses, and the thyroid and salivary glands. Although a diverse range of tumours can develop in this region, most head and neck cancers are squamous cell carcinomas (SCC) (1). Additionally, skin cancers arise in the head and neck region and are treated as part of the head and neck cancer spectrum. Keratinocyte cancers make up the majority of cutaneous cancers, including basal cell carcinoma (BCC) and cutaneous SCC (cSCC) (2,3).

High-risk tumour features include anatomical site, size, growth pattern, lymphovascular infiltration (LVI) and perineural invasion (PNI) (3). Perineural spread (PNS) is defined as radiological evidence of tumour spread along a nerve and/or a clinical neurological deficit (4-7). This is closely related to PNI which is a histopathological diagnosis of tumour invasion into a nerve (3,4,6,7). Rates of PNI in cSCC range from 2.5–14% and in BCC range from 0.18–10% (3). Higher rates are seen in non-cSCC with ranges of 14.2–63.2% (4). In the head and neck, PNS can be associated with increased rates of recurrence, progression, and poorer outcomes (4).

PNS usually affects the trigeminal (CN V) and facial (CN VII) nerves, but the great auricular nerve (GAN) can be involved (3,4,6). The GAN branches from the cervical plexus originating from the anterior rami of nerve roots C2 and C3 (5,8,9). The GAN exits the cervical plexus at Erb’s point along the posterior border of sternocleidomastoid (SCM) and courses anteriorly, dividing into two branches superiorly (5,9). The anterior branch provides sensory innervation to skin over the parotid and lower preauricular region, while the posterior branch innervates skin over the mastoid process and lower pinna, including the lobule (5).

PNS to the GAN in head and neck cancer is a rare occurrence that impacts disease and survival outcomes. PNS to the GAN should be specifically examined both clinically and radiologically. The pre-operative identification of PNS to the GAN is important as this finding alters treatment, including surgical and radiotherapy management. Few cases have been reported on the involvement of the GAN in PNS of head and neck cancers. We present five cases of PNS of head and neck cancer to the GAN and a review of the literature.

Cases were identified from Innoforce, the regional head and neck cancer database for the northern region of New Zealand between 2017 and 2022, using the search terms “perineural”, “squamous cell carcinoma”, “basal cell carcinoma”, and “great auricular nerve”. Inclusion criteria were a head and neck cancer diagnosis with clinical or radiological evidence of PNS to GAN. Clinical information was obtained from electronic health records and radiological imaging was reviewed by a head and neck specialist radiologist.

A literature search was performed in PubMed using the terms ‘great auricular nerve’ or ‘greater auricular nerve’ and ‘perineural’. The search returned 12 results between 1981 and 2025. Six results were excluded as they were not relevant. The remaining six papers, involving seven cases, were reviewed. A search was performed in MEDLINE using the same terms, identifying nine results which were all identified in the initial PubMed search. A third search was performed in Google Scholar using the term “great auricular nerve perineural spread”, which identified 11 results. This search identified one further case report to include. A total of eight cases were reviewed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports. Following assessment of each case with the JBI Critical Appraisal Checklist for Case Reports, seven previously published case reports were included in the results. As the aim of this study was to report on clinical and radiological detection of GAN PNS, case reports in the literature were still included if they did not qualitatively describe intervention, treatment or outcome. This study is reported according to the AME Case Series reporting guidelines (available at https://www.theajo.com/article/view/10.21037/ajo-25-47/rc).

Case presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients or their families for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Case 1

A 78-year-old male presented with 1 year of left jaw pain, facial pain, and headaches with no cause found on examination and magnetic resonance imaging (MRI) scan. Relevant history included immunosuppression with intermittent prednisone for temporal arteritis, type two diabetes mellitus (T2DM), and previous melanoma in situ. Concurrent skin cancer history includes an incompletely excised left lower cheek moderately differentiated, infiltrative cSCC without LVI or PNI, which was re-excised 1 month after review. Local re-excision found no evidence of residual tumour. Repeat clinical review 4 months later identified worsening facial pain and a palpable parotid mass. Examination revealed left cheek scar ulceration, left earlobe paraesthesia, and a palpable left level II neck mass. Fine-needle aspiration (FNA) of the neck mass confirmed metastatic SCC. Computed tomography (CT) and MRI scans showed thickening and enhancement of the left GAN as shown in Figure 1. After discussion at the regional head and neck cancer multidisciplinary meeting (HNC MDM), the patient proceeded to wide local excision (WLE) of left cheek skin, superficial parotidectomy, left modified radical neck dissection (ND) Ib-V, resection of GAN to the spinal foramina, and local cervicofacial rotation flap, followed by adjuvant radiotherapy. Histology revealed invasive SCC involving left preauricular skin and parotid gland with extensive PNI and 0/21 node involvement. The GAN specimen from the spinal foramina was positive for tumour involvement. MRI 1-year post-surgery revealed changes at the neural foramina of C2/C3, which could not be differentiated between recurrence and post-operative change. As the patient had completed radiotherapy, was not a candidate for further surgery or palliative chemotherapy due to side effects, the HNC MDM opinion was for follow-up. MRI 6 months later confirmed recurrent disease in the left neck as shown in Figure 1. The patient was referred to palliative care and passed away 29 days later.

Figure 1 Case 1. Axial (A) and coronal (B) CT scans showing thickening of the left GAN (arrows). Pre-treatment fat-suppressed T1-weighted axial (C) and coronal (D) MRI with contrast showing enhancement of GAN entering the vertebral column (arrows). Follow-up fat-suppressed T1-weighted axial (E) and coronal (F) MRI with contrast after treatment showing a 50×35×35 mm spiculated mass (arrows) encasing the vertebral artery and involving bone at the neural foramen of left C2/3 and C3/4. CT, computed tomography; GAN, great auricular nerve; MRI, magnetic resonance imaging.

Case 2

A 76-year-old male was referred with a right level IIa neck mass with no associated symptoms. Relevant medical history includes prostate adenocarcinoma and T2DM with stage IV chronic kidney disease. Skin cancer history includes an incompletely excised right pinna infiltrative BCC 3 years prior with subsequent re-excision negative for malignancy. FNA of the right neck mass confirmed metastatic BCC. CT showed the right level II neck mass deep to SCM and thickening of the GAN as shown in Figure 2. The case was discussed at the regional HNC MDM. The patient had a right modified radical ND including resection of macroscopically involved spinal accessory nerve and cervical plexus. Histology showed metastatic BCC in tissue around the GAN, SCM and in 5/15 lymph nodes. After further HNC MDM discussion, the patient received adjuvant radiotherapy 50 Gy in 20 Fr with no loco-regional recurrence on follow-up for 16 months. The patient subsequently passed away due to unrelated causes.

Figure 2 Case 2. (A) Axial CT showing mass deep to the right sternocleidomastoid muscle (arrow). (B) Axial CT showing thickening of great auricular nerve (arrow). CT, computed tomography.

Case 3

A 59-year-old female with 2 years of intermittent right facial pain, headaches, and 5 months of an evolving right lower motor neuron facial nerve palsy was referred to otorhinolaryngology (ORL) by neurology. Examination found a right partial facial nerve palsy, reduced right GAN sensation, and a tender mass at the tail of parotid. FNA confirmed SCC. Positron emission tomography CT (PET-CT) and MRI revealed enhancement of the intra-parotid facial nerve with proximal extension to the stylomastoid foramen, and subtle asymmetry of the right trigeminal nerve within the foramen rotundum without clinical evidence of involvement. GAN did not appear thickened or enhancing. After HNC MDM discussion, the patient proceeded to right radical parotidectomy, partial temporal bone resection, facial nerve resection to the mastoid segment, GAN resection and right Ib-V ND with radial forearm free flap reconstruction and static facial sling suspension, followed by adjuvant chemoradiotherapy for metastatic cSCC. Intraoperatively, the mastoid antrum was exposed and a section of the mastoid segment of the facial nerve was sent for frozen specimen analysis. This returned clear of disease involvement and facial nerve resection was continued distal to this. The auriculotemporal nerve was cleared as part of the deep parotid tissue clearance. There was a suspicious focus in the inferior branch of the GAN as well as involvement of the facial nerve (frontal, orbital and zygomatic branches) on frozen section, resulting in further intraoperative clearance of soft tissue and facial nerve branches to the orbital rim. Histology showed invasive SCC with extensive PNI and 0/13 nodal involvement. Follow-up MRI showed enhancement of the facial nerve to the geniculate ganglion, tympanic segment, and anterior genu, fluorodeoxyglucose negative on PET-CT. Following repeat HNC MDM discussion, the patient underwent a right cortical mastoidectomy and facial nerve excision biopsy to the geniculate ganglion showing no evidence of malignancy. The patient has ongoing periauricular pain, with no evidence of disease recurrence on serial imaging, thorough pain specialist review, and is undergoing further clinical observation.

Case 4

A 58-year-old male was referred with a three-month history of a right parotid mass and altered sensation over the pinna, mid-face, and lateral nasal wall. Examination showed a right level IIb neck mass, a right complete facial nerve palsy, and altered sensation in the right auriculotemporal, infraorbital, and GAN distributions. CT and MRI showed a superficial parotid lobe mass with widening of the distal aspect of the mastoid segment of the facial canal. After HNC MDM discussion, the patient underwent a right parotidectomy with lateral temporal bone resection, facial nerve sacrifice, GAN resection, ND, and left anterolateral thigh flap reconstruction with adjuvant radiotherapy. Histological diagnosis revealed a high-grade carcinoma ex-pleomorphic adenoma of the right parotid gland. There was peri-parotid soft tissue extension with gross PNI frequently affecting nerves within the tumour and at the advancing tumour front. Frozen section was used intraoperatively to confirm negative involvement of peripheral margins including branches of the facial nerve and/or GAN. None of the 46 nodes examined were involved. The patient remains free of disease recurrence 55 months following completion of radiotherapy.

Case 5

An 84-year-old female was referred with a right mid-neck mass. Comorbidities include atrial fibrillation, stroke with right hemiparesis and aphasia, T2DM, chronic lymphoid leukaemia, and an ex-smoking history. Two years prior to the current presentation, the patient was treated for a metastatic right temple moderately differentiated cSCC and level I neck mass. At that time, prior to referral to ORL, the patient underwent WLE of the temple lesion and excisional biopsy of the jaw mass after ultrasound scan, which showed moderately differentiated SCC. They were referred to the HNC MDM with recommendation for extended parotidectomy, ND and reconstruction. After extensive discussion and consideration, the patient and family elected to proceed with palliative radiotherapy due to comorbidities and surgical and anaesthetic risks. The patient received radiotherapy of 32 Gy in 5 Fr.

One year after completion of radiotherapy, the current presentation, the patient presented with a new right neck lesion. CT showed a 34 mm node adjacent to the external jugular vein, invading SCM, with a thickened cord of tissue coursing cranially to the vertebral foramen of C2/3, as shown in Figure 3. FNA confirmed metastatic SCC. Further recommendation from the HNC MDM was for palliative radiotherapy, however, due to patient frailty, the patient did not undergo further treatment and subsequently passed away.

Figure 3 Case 5. Coronal computed tomography scan showing a mass in the right neck node with a thickened cord of tissue extending to C2/C3 vertebral foramen.

Case series critical appraisal

There are fewer than ten reported cases of GAN PNS on a literature search of PubMed, MEDLINE and Google Scholar (4,5,9-13). Eight previously reported cases were assessed using the JBI Critical Appraisal Checklist for case reports. Seven of these cases were included for discussion, summarised in Table 1. Of the seven cases, five were due to spread of cSCC, one due to mucosal SCC and one due to melanoma. All cases reported imaging findings where the modality included CT, PET-CT and/or MRI. Treatment was described in six cases, of which two underwent surgical excision and radiotherapy, two underwent surgical excision alone, one underwent radiotherapy alone, and one received immunotherapy on a background of previously resected melanoma disease prior to recurrence involving the GAN. The surgical approach to GAN resection varied in each case, ranging from resection of GAN to the cervical plexus, to C2/3 foraminotomy (5,10,11,13). In the case of C2/3 foraminotomy, a primary resection of C2 and C3 occurred, where these nerves were followed into the prevertebral musculature (10). Frozen sections of C3 remained positive. A delayed C2/3 foraminotomy was performed one week post-operatively by a neurosurgical team. Formal histology demonstrated clear margins at the proximal end of C3.

Discussion

This case series describes five patients with head and neck cancer demonstrating PNS to the GAN, summarised in Table 2. Three cases involved the spread of SCC, one case of BCC, and one case of carcinoma ex-pleomorphic adenoma of the parotid gland with squamous transformation. Three of the five cases had altered sensation in the GAN distribution on clinical examination. Three cases had radiological changes of GAN on CT and/or MRI scans. All cases were discussed at a regional head and neck cancer meeting, and four cases proceeded to surgical resection. Three patients underwent post-operative radiotherapy, while one received combined chemoradiotherapy. One patient was unable to complete palliative radiotherapy.

PNS is defined as clinically or radiologically evident tumour involvement along a nerve, in contrast to PNI, which is a histopathological finding of tumour cell infiltration into a nerve (4,6,7). Clinical features of PNS include pain, paraesthesia or sensory nerve dysfunction, paralysis, and motor nerve dysfunction (2,7,10,11). Detection of GAN involvement requires comprehensive clinical and radiological investigation. A history of unexplained pain, paraesthesia, and/or sensory or motor nerve dysfunction should alert the clinician to perineural disease (2,7,10,11). Cranial nerves are routinely examined to assess for CN V and CN VII involvement in a head and neck cancer workup. Our cases demonstrate the importance of examining all cranial nerves as well as spinal contributions to the head and neck region. Radiological findings can be subtle and include nerve enlargement or abnormal enhancement (5-7). Up to 40% of patients with PNS may be clinically asymptomatic, leaving imaging as the only method of identifying PNS prior to treatment (5,6,9). MRI is the imaging modality of choice to detect PNS due to excellent soft tissue definition (7,12-14). Detection of GAN involvement is important as retrograde spread could extend to the cervical plexus and spinal nerve roots (5,8). This may necessitate more extensive surgical excision or alter the field of adjuvant radiotherapy (8,9). Preoperative imaging detection of PNS is also important as extensive spread may limit surgical resectability. Features that suggest unresectability include vascular encasement, prevertebral space involvement, mediastinal extension, skull base or bony involvement, PNS or evidence of distant metastasis (14). GAN resection can be extended retrograde to the C2/3 spinal foramina; however, PNS proximal to this indicates unresectable disease. Specific to GAN is the potential for PNS to spread to C2/3 spinal nerve roots and leptomeningeal spread. For primary or adjuvant radiotherapy in trigeminal and facial nerve PNS, clinical PNI imaging zones are used to guide the radiation field. However, equivalent parameters for GAN PNS are not defined and currently rely on the radiographic findings of PNS (7).

The key clinical findings, radiological findings specific to the GAN, treatment, and follow-up are summarised for our five cases and previously published cases in the literature in Tables 1,2. Of these 12 cases, nine presented with a mass in the parotid region or overlying the SCM and eight described an altered sensation, pain and/or paraesthesia in the GAN distribution. Ten cases had radiological findings of abnormalities of the GAN. Radiology descriptors include “cylindrical structure”, “superficial to the SCM”, “tubular enhancing structure”, “passing from the posterior aspect of the parotid gland posteroinferiorly to the posterior margin of the sternocleidomastoid” (4,5,10,13). Of 11 treatment options described, nine cases were treated with primary surgery and seven of these received adjuvant treatment in the form of radiotherapy, chemoradiotherapy or immunotherapy in the case of metastatic melanoma. One case was treated with radiotherapy only and the final case did not receive active treatment and was referred for palliative care. The presence of these shared clinical findings and unique radiological signs should lead to consideration of GAN involvement.

While none of our patients received immunotherapy, recent studies suggest it may have a role in the management of perineural disease (15,16). Immunotherapy [anti-programmed death-1 checkpoint inhibitor (anti-PD-1)] is a novel treatment to consider, particularly in cases of unresectable disease or where there are contraindications to radiotherapy (15,16). Immune checkpoint inhibitors were approved for use in cSCC in 2018 (16). Early case studies for anti-PD-1 therapy report favourable rates of sustained disease control and objective response on imaging for PNS involvement (15,16). Further investigation into the use of immunotherapy for treatment of PNS in head and neck cancer is required.

Strengths of this study include full access to health data, radiological imaging and specialist radiologist review of included Figures. No patients were lost to follow up. Limitations of this study include a small population size which allows descriptive analysis of cases only and does not provide external validation.

Conclusions

PNS involving the GAN, though rare, has significant implications for disease recurrence, resectability, progression, and survival (4). PNS of disease to GAN may not present with clinical signs or symptoms, and so involvement of this nerve should be specifically analysed in radiological investigations, with particular use of MRI to detect PNS (5-7). Pre-operative identification of PNS to the GAN can alter treatment including surgical and radiotherapy management (8,9). Prognostic implications of GAN PNS arise from the potential for retrograde spread through C2/3 spinal foramina.

Acknowledgments

We would like to acknowledge each of the patients and their families who gave their consent for their information to be shared in this case series. Results of this study have been presented in poster format at the 2022 NZSOHNS conference.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://www.theajo.com/article/view/10.21037/ajo-25-47/rc

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-25-47/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-25-47/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patients or their families for the publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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