Evaluation of facial nerve perineural spread from cutaneous squamous cell carcinoma using 3T MR neurography.

INTRODUCTION: Perineural spread (PNS) is a rare but potentially fatal consequence of cutaneous squamous cell carcinoma (cSCC) of the head and neck. We aimed to evaluate the accuracy of 3T MR neurography in detecting and defining the extent of facial nerve (VII) PNS from cSCC, and highlight characteristic radiological features in peripheral branches to improve early diagnosis. METHODS: Single-institution retrospective review of 38 patients with clinical, radiological, and/or histopathological findings consistent with VII PNS from cSCC who underwent pre-operative 3T MR neurography. RESULTS: Compared to histopathology (gold standard), 3T MR neurography had a sensitivity of 89% and positive predictive value of 97%. In true-positive cases (n = 33), zonal extent was correctly identified in 100%. Seventy-nine% had simultaneous trigeminal nerve (V) PNS, mostly involving the auriculotemporal branch of the mandibular nerve (64%). When the causative lesion was absent (n = 23), the extra-temporal VII demonstrated asymmetrical enhancement alone (n = 6), bulky expansion (n = 8), or extra-neural spread (n = 9). Peripheral VII branch involvement, particularly the buccal and zygomatic, was readily identified using known anatomical landmarks. CONCLUSION: 3T MR neurography is highly accurate in evaluating VII PNS from cSCC, and thus should be specifically requested by physicians if suspicious for disease. Coexistent V PNS was common, highlighting the need to examine V branches to allow complete treatment planning. The unique radiological patterns identified showcases disease progression. As early detection improves patient outcomes, the radiologist must look for peripheral VII involvement in specific anatomical areas, which is within the capabilities of 3T MR neurography.

Clinical outcomes in perineural spread of cutaneous squamous cell carcinoma via the ophthalmic nerve.

BACKGROUND: There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. OBJECTIVE: To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. MATERIALS AND METHODS: Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment. RESULTS: Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival. DISCUSSION: Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. CONCLUSION: Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1.

Long-term outcomes in advanced anterior skull base malignancy: a single quaternary institution experience.

BACKGROUND: Advanced skull base malignancies are a heterogenous subset of head and neck cancers, and management is often complex. In recent times, there has been a paradigm shift in surgical technique and the advent of novel systemic options. Our goal was to analyse the long-term outcomes of a single quaternary head and neck and skull base service. METHODS: A retrospective review of 127 patients with advanced anterior skull base malignancies that were treated at our institution between 1999 and 2015 was performed. Multiple variables were investigated to assess their significance on 5 and 10-year outcomes. RESULTS: The mean age was 60.9 (± 12.6 SD). Sixty-four percent were males and 36% were females. Ninety percent of patients had T4 disease. Median survival time was 133 months. The 5-year overall survival (OS) was 66.2%, disease-specific survival (DSS) was 74.7%, and recurrence-free survival (RFS) was 65.0%. The 10-year OS was 55.1%, DSS was 72.1%, and RFS was 53.4%. Histological type and margin status significantly affected OS & DSS. CONCLUSION: Surgical management of advanced skull base tumours has evolved over the last few decades at our institution with acceptable survival outcomes and complication rates. Histological diagnosis and margin status are the main predictors of survival. The addition of neoadjuvant systemic agents in current trials may improve outcomes.

Patterns of spread and anatomical prognostic factors of pre-auricular cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Improvements can be made in the management and staging of advanced pre-auricular cutaneous squamous cell carcinoma (cSCC). We aimed to analyze radiological patterns of spread and clinico-anatomical prognostic factors. METHODS: Retrospective review of 54 patients with pre-auricular cSCC (cutaneous/nodal) who underwent temporal bone resection with curative intent. RESULTS: Involvement of the cartilaginous external auditory canal (EAC) (79.6%) and retromandibular space (63.0%) was common. Styloid process/anterior carotid sheath (ACS) (11.1%) and bony EAC (7.4%) involvement were rare. ACS involvement resulted in high rates of involved surgical margins (100%) and poor outcomes on univariable analysis. Negative prognostic factors on multivariable analysis included salvage surgery and invasion of the bony EAC, mandible, pterygoid muscle(s), and dura. CONCLUSION: The bony EAC and ACS can form temporary barriers to tumor spread, with the latter representing a potential limit of resectability. Prognostic factors revealed can lead to the development of a more appropriate staging tool.

Fascial layers encountered in the lateral skull base region: A cadaveric and radiological analysis.

BACKGROUND: In our experience, the anterior carotid sheath forms an important plane of dissection when excising temporal bone region cancers. However, its anatomical composition, relationships, and radiological appearance remains unclear. METHODS: Eight sides of cadaveric heads were dissected. Anatomical findings were correlated with a high-resolution baseline T1 MRI. RESULTS: The anterior carotid sheath was formed by the tensor-vascular-styloid fascia, stylopharyngeal fascia, buccopharyngeal fascia (BPF), and longus capitis fascia (LCF), and appeared as a hypointense line on MRI. Not previously described, the glossopharyngeal nerve pierced the sheath 9.0 mm (SD 2.1 mm) below the skull base and traveled through its LCF and BPF layers to exit near the pharynx. CONCLUSION: Multiple fascial layers formed the anterior carotid sheath at the skull base, and this was radiologically identifiable. Further studies are required to validate findings and investigate the role this fascial plane has in forming an effective barrier to spread of malignancy.

Facial nerve perineural spread from cutaneous squamous cell carcinoma of the head and neck: A single institution analysis of epidemiology, treatment, survival outcomes, and prognostic factors.

BACKGROUND: This study aimed to examine patients with facial nerve (VII) perineural spread (PNS) from cutaneous squamous cell carcinoma of the head and neck. METHODS: Retrospective analysis of patients managed by an Australian tertiary center between 2000 and 2019. RESULTS: Seventy three patients were included. Most presented with recurrent disease (89.0%) and simultaneous trigeminal nerve (V) involvement (67.1%). Of the 55 patients (75.3%) who received curative intent treatment, 48 received surgery plus/minus post-operative radiotherapy. In these patients, 5-year disease-free survival, disease-specific survival, and overall survival was 50.7%, 68.7%, and 58.1%, respectively. Pathological nodal disease, involved margins, increasing VII zonal extent, and concurrent zone 2 V PNS significantly worsened outcomes. CONCLUSION: High rates of recurrent disease reflects the importance of adequate treatment of the primary. Surgery and post-operative radiotherapy remains the mainstay treatment. Outcomes are improved in early-stage disease and with clear surgical margins, reinforcing the need for prompt diagnosis and intervention.

Epidemiology and treatment outcomes of cutaneous squamous cell carcinoma extending to the temporal bone.

BACKGROUND: Accurate epidemiological and outcomes data regarding cutaneous squamous cell carcinoma (cSCC) extending to the temporal bone is lacking. METHODS: Retrospective analysis of 167 Australian patients with primary and peri-temporal bone cSCC. RESULTS: cSCC extending from secondary subsites (93.4%) was 14 times more frequent than primary temporal bone SCC (6.6%). For patients who underwent curative surgery ± post-operative radiotherapy (n = 146, 87.4%), 5-year disease-free survival, locoregional recurrence-free survival, disease-specific survival, and overall survival was 53.0%, 59.4%, 67.9%, and 44.7%, respectively. External ear and pre-auricular tumors, salvage surgery, tumor size (≥40 mm medial-lateral), nodal disease, and involved margins were negative predictors of survival in multivariable analysis. CONCLUSION: In regions of high sun exposure, cSCCs extending to the temporal bone are more common than primary cancers. Outcomes are improved with clear margins, justifying the need for radical resection. Further research regarding pre-auricular cancers is required given poorer associated survival outcomes.

Immunotherapy for the treatment of perineural spread in cutaneous head and neck squamous cell carcinoma: Time to rethink treatment paradigms.

BACKGROUND: Immune checkpoint inhibitors have shown promising antitumour activity. Application in head and neck cutaneous squamous cell carcinoma (cSCC) large nerve perineural spread (PNS) is limited. METHODS: Retrospective review of 13 patients with PNS receiving anti-PD-1 therapy from September 2017 to May 2021 is presented. Primary endpoints were objective response (complete or partial response) and median time to progression, determined by Head and Neck Multi-Disciplinary Team (MDT) and independent radiology review of magnetic resonance imaging (MRI) and/or computed tomography/positron emission tomography (CT/PET). RESULTS: Objective response was observed in 9/13 patients (69%), with complete response in 6 (46%) and partial response in 3 patients (23%). Median time to response was 2.1 months (IQR 1.8-2.7 months). There were 3 (23%) patients with progressive disease, with median time to progression of 3.5 months. There were no grade 3-4 treatment related adverse events. CONCLUSIONS: This case series supports developing evidence for anti-PD-1 checkpoint inhibitor therapy for perineural spread, supporting future prospective clinical trials in this patient population.

Malignancies requiring temporal bone resection: An Australian single-institution experience.

BACKGROUND: Malignancies in and around the temporal bone are aggressive and difficult to manage. In Queensland (Australia), where skin cancer rates are exceedingly high, tumours extending to the temporal bone from surrounding structures occur more commonly than primary cancers. Yet, a paucity of evidence exists as to their management and outcomes. This study aimed to review an Australian centre's experience of managing temporal and peritemporal bone malignancies, reporting on patient and tumour characteristics, treatment, and survival outcomes. METHODS: Retrospective analysis of patients with primary temporal bone cancer and cancers extending to the temporal bone managed by the Queensland Skull Base Unit (Princess Alexandra Hospital) between 2000 and 2019. RESULTS: A total of 222 patients were identified, of which 203 (91.4%) had cutaneous primaries, with 167 (75.2%) being squamous cell carcinoma (SCC). 73.9% presented with locoregionally recurrent or residual disease. Secondary tumours (92.8%) were 12 times more frequent than primary malignancies (7.2%), with the preauricular subsite the most common (45.5%). In the 201 patients (90.5%) who underwent curative intent surgery, 5-year overall survival, disease-free survival (DFS), and disease-specific survival was 46.6%, 52.2%, and 65.9%, respectively. The preauricular subsite (p = 0.004), melanoma (vs. SCC, p = 0.027), involved margins (p < 0.001), and pathologically involved nodes (p < 0.001) were associated with significantly worse DFS. CONCLUSION: This is one of the largest studies of temporal bone malignancy in the literature, comprised primarily of secondary cutaneous malignancies. Although clear differences in epidemiological characteristics exist around the world, survival remains poor. Treatment should focus on achieving a clear margin of resection to optimize outcomes.

Cerebral Venous Sinus Thrombosis After Translabyrinthine Vestibular Schwannoma-A Prospective Study and Suggested Management Paradigm.

OBJECTIVE: To prospectively evaluate the incidence, risk factors and natural history of postoperative cerebral venous sinus thrombosis (pCVST) in translabyrinthine vestibular schwannoma microsurgical resection and propose a potential management paradigm. STUDY DESIGN: Prospective, single cohort, multicenter study. SETTING: State-wide academic tertiary referral centers. PATIENTS: Fifty-four consecutive patients who underwent translabyrinthine vestibular schwannoma resection. MAIN OUTCOME MEASURES: Incidence of pCVST on postoperative imaging on Day 7, Day 28, and 12 months postoperatively. Patients and tumor characteristics, risk factors, length of stay, intraoperative parameters, complications, and follow-up were analyzed. RESULTS: pCVST was demonstrated in 21 patients (38.9%) on postoperative imaging. All patients with pCVST were treated conservatively and remained asymptomatic in the immediate postoperative period and long-term follow-up. There were no instances of venous infarction, intracranial hemorrhage, or neurological deficits. A majority (61.1%) of pCVST recannalised on long-term follow up with conservative management. There was a statistical association with pCVST and surgery on the side of the non-dominant cerebral venous drainage (n = 17, 80.1%, p = 0.034). Patients with pCVST were significantly more likely to have a postoperative cerebrospinal fluid (CSF) leak (n = 5, 23.8%, p = 0.017). CONCLUSION: The incidence of pCVST following translabyrinthine vestibular schwannoma resection is much higher than previously recognized. pCVST is more likely to occur when surgery is performed on tumors situated on the side of non-dominant cerebral venous drainage. Despite the high prevalence of this iatrogenic phenomenon, all patients were asymptomatic and a majority resolved, thereby suggesting that conservative management is safe. Correlation between pCVST and increased incidence of CSF leak requires further investigation.

Utility of a repeat PET/CT scan in HPV-associated Oropharyngeal Cancer following incomplete nodal response from (chemo)radiotherapy.

OBJECTIVES: To assess the utility of a repeat positron emission tomography/computed tomography (PET/CT) instead of immediate neck dissection (ND) for incomplete nodal response (IR) in Human Papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC) following chemoradiotherapy/radiotherapy [(chemo)RT]. MATERIALS AND METHODS: Patients with non-distant metastatic, node positive (N+) disease treated between Jan/2005 to Jan/2016, achieved complete response at the primary with no distant relapse on a 12-week re-staging PET/CT were evaluated. Patients underwent surveillance after complete nodal response (CR). Patients with IR underwent repeat PET/CT at 16 weeks to direct neck management. Primary endpoints were CR conversion rate and subsequent regional failure following a 16-week PET/CT directed ND. Secondary endpoints were predictive values (PV) of the 12- and 16-week PET/CT for residual nodal disease, predictors for requiring the 16-week PET/CT, 5 year regional, locoregional failure free survival (FFS) and overall survival (OS). RESULTS: 235 patients were evaluated. Median follow up was 56 (range 19-60) months. 41 patients underwent 16-week re-staging PET/CT, 29 (71%) converted to CR. No subsequent regional failures occurred following a 16-week PET/CT directed ND. Positive and negative PV of the 12- and 16-week PET/CT for residual nodal disease was 12% & 98%, and 33% & 97%, respectively. N-category (AJCC/UICC 7th edition) predicted for requiring a 16-week PET/CT on univariate analysis (P-value 0.02). 5 year regional, locoregional FFS and OS was 95.8%, 93.4% and 90.8%, respectively. CONCLUSION: For N+ HPV-associated OPC achieving IR on the 12-week re-staging PET/CT following (chemo)RT, a repeat 16-week PET/CT can spare patients from unnecessary surgery.

Primary lymphoepthelial carcinoma of the parotid gland, pictorial review of a rare entity.

Lymphoepithelial carcinoma (LEC) is a rare malignancy of the salivary gland arising from the parotid in 80% of cases. LEC is indistinguishable histologically from more common non-keratinising undifferentiated nasopharyngeal carcinoma (NPC). Up to 40% of patients with primary LEC present with a cervical metastasis and histological assessment of the primary lesion or nodal metastasis may be reported as NPC. The absence of a nasopharyngeal lesion on imaging and endoscopic assessment together with a parotid mass strengthens the case for a LEC. A retrospective review of three cases of primary parotid LEC presenting to a tertiary head and neck clinic was performed. Clinical information, imaging and histopathology findings are presented in the form of a pictorial review. Two female and one male patient with an average age of 42 years presented with a neck lump. Initial pathology results were poorly differentiated carcinoma (2/3) and possible NPC (1/3). MR neck revealed unilateral parotid masses with ipsilateral cervical lymphadenopathy and assessment of the nasopharynx was negative (3/3). Resection occurred in all patients and consensus was metastatic LEC with parotid primary in all cases (3/3). 2 patients are disease free, and 1 patient is deceased (as a result of disease) at the time of this report. Lymphoepithelial carcinoma is identical histologically to NPC, this pictorial review highlights the need for clinical and radiological correlation to establish the diagnosis.

Fossa navicularis in a pediatric patient: anatomical skull base variant with clinical implications.

The fossa navicularis is an anatomical variant of the skull base thought to be a rare finding. It represents a bony depression in the skull base. The authors here report the case of a fossa navicularis magna in a 9-year-old female who had been treated for recurrent episodes of meningitis.A literature review was also done to highlight the unique features and clinical importance of this distinctive radiological skull base finding. The literature search covered papers from the 19th century up to 2018. Earlier authors described "fossa navicularis" as a very rare skull base finding. So far, only three cases of fossa navicularis with associated clival or intracranial infection have been reported in the literature. This is the fourth reported case, and the defect was closed endoscopically via a transnasal route. This morphological skull base anomaly should be considered in the differential diagnoses for an unexplained skull base infective pathology.Skull base surgeons should be aware of the existence of the fossa navicularis because of its clinical importance in rendering a prompt diagnosis and appropriate treatment.

Sphenoid sinus fungal balls.

OBJECTIVES: We sought to examine the nature of fungal balls of the sphenoid sinus, in particular the exposure of adjacent skull base structures and the potential for surgical morbidity. METHODS: We retrospectively reviewed our series of 17 cases of sphenoid sinus fungal balls seen between 1998 and 2005 with reference to their diagnosis, radiologic changes, histopathology, and surgical management. RESULTS: Exposed structures included the pituitary fossa, cavernous sinus, and cavernous internal carotid artery, but this exposure did not result in an increase in perioperative complications. Sclerotic thickening of the sinus walls persisted, probably representing a chronic osteitis in response to concurrent bacterial infection. This appeared to be protective against further sinus wall erosions. Wall erosions did not heal. One patient demonstrated what appeared to be invasive fungal disease from a fungal ball. CONCLUSIONS: Sphenoid sinus fungal balls can occur with minimal symptoms in a mainly elderly population and require surgical removal. Sphenoid sinus fungal balls have a low rate of operative morbidity and should be effectively managed by transnasal endoscopic sphenoidotomy alone.

The Imaging of Large Nerve Perineural Spread.

We present a review of the imaging findings of large nerve perineural spread within the skull base. The MRI techniques and reasons for performing different sequences are discussed. A series of imaging examples illustrates the appearance of perineural tumor spread with an emphasis on the zonal staging system.

Postoperative Imaging and Surveillance in Large Nerve Perineural Spread.

We present a review of the imaging surveillance following treatment for large nerve perineural spread in the skull base. The expected appearance and possible complications following surgery and radiotherapy are discussed. Imaging examples of the possible sites of disease recurrence are also presented.

Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma.

BACKGROUND: Queensland, Australia, has the highest rates of cutaneous squamous cell carcinoma (SCC). Perineural invasion (PNI) is associated with reduced local control and survival. METHODS: A retrospective review of a prospective database of patients with clinical PNI from cutaneous SCC of the head and neck (SCCHN) treated with surgery and postoperative radiotherapy (PORT) between 2000 and 2011 and a minimum of 24 months follow-up. Patients were excluded if immunosuppressed, had non-SCC histology, or were treated palliatively. RESULTS: Fifty patients (mean age, 60 years) with median follow-up of 50 months were included in this study. A total of 54.8% of known primary tumors had incidental PNI. Ten percent had nodal disease at presentation. MRI neurogram was positive in 95.8%. Recurrence-free survival (RFS) at 5-years was 62%. Five-year disease-specific survival (DSS) and overall survival (OS) were 75% and 64%, respectively. There were no perioperative deaths. CONCLUSION: This report demonstrates that long-term survival is achievable in patients with clinical PNI from cutaneous SCCHN after surgery and PORT. © 2015 Wiley Periodicals, Inc. Head Neck 38: 824-831, 2016.

Pneumopericardium and pneumothorax due to right atrial permanent pacemaker lead perforation.

A 75-year-old man presented with a spontaneous right pneumothorax and pneumopericardium following right atrial pacemaker lead perforation, which is a rare complication, with only two case reports being documented in the literature to the authors' knowledge. It is important that radiologists be aware of cardiac lead perforations, as they may be the first to diagnose this complication.

3T MRI evaluation of large nerve perineural spread of head and neck cancers.

INTRODUCTION: Accurate definition of the presence and extent of large nerve perineural spread (PNS) is a vital component in planning appropriate surgery and radiotherapy for head and neck cancers. Our research aimed to define the sensitivity and specificity of 3T MRI in detecting the presence and extent of large nerve PNS, compared with histologic evaluation. METHODS: Retrospective review of surgically proven cases of large nerve PNS in patients with preoperative 3T MRI performed as high resolution neurogram. RESULTS: 3T MRI had a sensitivity of 95% and a specificity of 84%, detecting PNS in 36 of 38 nerves and correctly identifying uninvolved nerves in 16 of 19 cases. It correctly identified the zonal extent of spread in 32 of 36 cases (89%), underestimating the extent in three cases and overestimating the extent in one case. CONCLUSION: Targeted 3T MRI is highly accurate in defining the presence and extent of large nerve PNS in head and neck cancers. However, there is still a tendency to undercall the zonal extent due to microscopic, radiologically occult involvement. Superficial large nerve involvement also remains a difficult area of detection for radiologists and should be included as a 'check area' for review. Further research is required to define the role radiation-induced neuritis plays in the presence of false-positive PNS on MRI.

Study of Mimusops elengi bark in experimental gastric ulcers.

The present study was designed to investigate the effect of Mimusops elengi (Sapotaceae) against experimental gastric ulcers. The 50% alcoholic extract of Mimusops elengi (Ext E) and its different fractions namely ethyl acetate (Ext E1), n-butanol (Ext E2), methanol (Ext E3) and aqueous (Ext E4) were studied (p.o.) against ethanol-induced gastric damage. Ext E1 was also studied in ethanol-induced, pylorus-ligated and water-immersion plus stress-induced gastric ulcer models. Ranitidine HCl (80 mg kg(-1)) was used as a reference standard. In ethanol-induced gastric ulcer model, pantoprazole (20 mg kg(-1)) was also used as a reference standard. Ext E1 tested in mice up to the dose of 5000 mg kg(-1) (p.o.) did not produce any sign of toxicity. Ext E at the doses of 50, 100, 300 and 500 mg kg(-1) and its different fractions (100 mg kg(-1)) showed reduction in gastric ulceration (P < 0.05). Ext E1 at the doses of 10, 50 and 100 mg kg(-1) showed dose-dependent inhibition of gastric lesions against ethanol-induced gastric damage. In 19 h pylorus-ligated animals, Ext E1 at 50 and 100 mg kg(-1) doses showed significant reduction in ulcer index (P < 0.05). Significant reduction was also observed in total acidity, volume of gastric acid secretion, total acid output and pepsin activity (P < 0.05) when compared with the control group. Besides, Ext E1 showed increase in the mucosal glycoproteins that was evident from significant rise in total carbohydrates to protein ratio (TC:PR ratio) (P < 0.05), which is an indication of mucin activity. Ext E1 also showed protection against water-immersion plus stress-induced gastric lesions that was evident from dose-dependent decrease in ulcer index (P < 0.05), score for intensity (P < 0.05) and total lesion area (P < 0.05) when compared with the control group. It can be concluded from our study that Ext E1 possesses anti-ulcer activity against experimental gastric ulcers. The mechanism of anti-ulcer activity can be attributed to decrease in gastric acid secretory activity along with strengthening of mucosal defensive mechanisms.