Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process.

Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.

Insight into the epidemiology of cutaneous squamous cell carcinoma with perineural spread.

BACKGROUND: Perineural spread (PNS) of cutaneous squamous cell carcinoma of the head and neck (SCCHN) can be associated with poor outcomes. Disease understanding and awareness is limited leading to delayed diagnosis and treatment. The purpose of this study was to identify epidemiological features of patients with PNS of cutaneous SCCHN. METHODS: Tumor characteristics and demographics of patients with PNS of cutaneous SCCHN managed through a single institution were collected between 1998 and 2013. RESULTS: One hundred twenty patients were included in this study. The majority had a history of skin cancer (85.8%). The median time from primary tumor treatment to PNS symptom onset was 16 months (range, 1-86 months). A total of 34.2% had no perineural invasion (PNI) detected in the primary, and 22.5% had no known primary tumor. Only 5.8% of the patients had nodal involvement at presentation. CONCLUSION: Patients can present with PNS from cutaneous SCCHN with no known primary tumor or with primary tumors without PNI. The majority of patients presented without regional nodal involvement. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1416-1420, 2016.

The Natural History and Treatment Outcomes of Perineural Spread of Malignancy within the Head and Neck.

Understanding the natural history of diseases enables the clinician to better diagnose and treat their patients. Perineural spread of head and neck cancers are poorly understood and often diagnosis is delayed resulting in poorer outcomes and more debilitating treatments. This article reviews a large personal series of head and neck malignancy presenting with perineural spread along almost exclusively the trigeminal and/or facial nerves. A detailed analysis of squamous cell carcinoma of cutaneous origin is presented including an analysis of likely primaries, which most often have occurred months to years prior. The importance of early detection is reinforced by the highly significant (p < 0.0001) differences in disease specific survival, which occur, depending on how far along a cranial nerve the disease has been allowed to spread.

Galectin-1 is associated with poor prognosis in patients with cutaneous head and neck cancer with perineural spread.

Spread of head and neck cancer along the cranial nerves is often a lethal complication of this tumour. Current treatment options include surgical resection and/or radiotherapy, but recurrence is a frequent event suggesting that our understanding of this tumour and its microenvironment is incomplete. In this study, we have analysed the nature of the perineural tumour microenvironment by immunohistochemistry with particular focus on immune cells and molecules, which might impair anti-tumour immunity. Moderate to marked lymphocyte infiltrates were present in 58.8% of the patient cohort including T cells, B cells and FoxP3-expressing T cells. While human leukocyte antigen (HLA) class I and more variably HLA class II were expressed on the tumour cells, this did not associate with patient survival or recurrence. In contrast, galectin-1 staining within lymphocyte areas of the tumour was significantly associated with a poorer patient outcome. Given the known role of galectin-1 in immune suppression, the data suggest that galectin inhibitors might improve the prognosis of patients with perineural spread of cancer.

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.

Histopathological features of clinical perineural invasion of cutaneous squamous cell carcinoma of the head and neck and the potential implications for treatment.

BACKGROUND: Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. METHODS: The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. RESULTS: No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. CONCLUSION: Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications.

Pictorial review: Vascular anomalies of the head and neck.

Vascular anomalies encompass a broad spectrum of tumours and malformations as classified by the International Society for the Study of Vascular Anomalies. Despite being one of the most common congenital abnormalities, they are often misunderstood in clinical practice: use of the term 'haemangioma' to denote any vascular anomaly still occurs. They are found frequently in the head and neck, often as complex lesions that require multidisciplinary management which necessitates an accurate diagnosis. Precise radiological assessment is therefore crucial. This pictorial review will briefly discuss the current classification system of vascular anomalies and the optimal radiological tools for their evaluation.