Defining incidental perineural invasion: the need for a national registry

Abstract

This article by the Perineural Invasion (PNI) Registry Group aims to clarify clinical and histopathological ambiguities surrounding PNI in non-melanoma skin cancer (NMSC). PNI is reportedly present in approximately 2-6% of cases of NMSC and is associated with greater rates of morbidity and mortality. The distinction between clinical PNI and incidental PNI is somewhat unclear, especially in regard to management and prognosis. One important objective of the PNI Registry is to develop a standardised method of classifying perineural invasion. Hence, in this article we propose a definition for PNI and for its sub-classification. This article also provides a critical analysis of the current literature on the treatment of incidental PNI by evaluating the key cohort studies that have investigated the use of surgery or radiotherapy in the management of incidental PNI. At present, there are no universal clinical guidelines that specify the acceptable treatment of NMSC exhibiting incidental PNI. Consequently, patients often receive surgery with varying wider margins, or radiotherapy despite the limited evidence substantiating such management options. It is evident from the existing literature that current opinion is divided over the benefit of adjuvant radiotherapy. Certain prognostic factors have been proposed, such as the size and depth of tumour invasion, nerve diameter, the presence of multifocal PNI and the type of tumour. The PNI Registry is a web-based registry that has been developed to assist in attaining further data pertaining to incidental PNI in NMSC. It is envisaged that this information will provide the foundation for identifying and defining best practice in managing incidental PNI.

Molecular mechanisms of perineural spread of cutaneous carcinoma: a potential role for receptor tyrosine kinases and other biomarkers

“…However, in borderline cases where there is clinical suspicion yet no obvious PNI, staining for broad-spectrum keratin (AE1/AE3) or cytokeratin to label epithelial tumour cells or for S-100 to label myelin secreting Schwann cells, can assist in defining the pathology. (27) Several studies have used a single immunostain to enhance nerve detection and thus Either way, it is considered most likely that in cases of clinical perineural spread it is the intraneural involvement that causes the characteristic symptoms and signs. (20) In the aforementioned study, only 3.9% of specimens demonstrated epineural involvement, which is thought to reflect the multilayer barrier function of the perineurium beyond the superficial fascia, effectively limiting tumour cell migration beyond the nerve compartment into surrounding soft issue.…”

“…(20,27) There is also likely variation in awareness levels and rates of detection across different geographical regions. PNI occurs in 2.5% to 14% of cases of cSCC, with most studies reporting rates < 5%.…”

Epidemiological and molecular features of cutaneous squamous cell carcinoma with perineural spread

“…10 An accurate incidence of cutaneous SCC with PNI is unavailable as neither cutaneous SCC nor PNI are reportable diseases. 11 The detection of PNI in cutaneous SCC is associated with more aggressive behaviour and a worse prognosis. [12][13][14][15][16][17][18][19][20] A recent systematic review and meta-analysis comprising 36 studies with 17,248 patients analysed the risk factors for poor outcomes with cutaneous SCC.…”

“…28 PNI is classified into two subtypes, incidental PNI and clinical PNI. 11,19,29 PNI that is incidentally detected on microscopy in a tumour excised from an asymptomatic patient is known as incidental PNI. 11 This is estimated to occur in approximately 2-6% of NMSCs and is the most common subtype.…”

“…11,19,29 PNI that is incidentally detected on microscopy in a tumour excised from an asymptomatic patient is known as incidental PNI. 11 This is estimated to occur in approximately 2-6% of NMSCs and is the most common subtype. 11 Incidental PNI is typically treated with complete surgical excision and consideration given to post-operative radiotherapy (PORT) when other high-risk features of the patient and/or primary tumour are present (see Table 1.1).…”