{"entity":{"id":"perineural-invasion","kind":"term","name":"Perineural invasion (PNI)","aka":["PNI","perineural","nerve invasion","neural invasion"],"tldr":"Cancer cells growing along the sheath of a nerve. Nerves act as tracks for spread, so this finding predicts recurrence, especially in pancreatic, prostate and head and neck cancers.","summary":"Nearly universal in pancreatic cancer (explaining its pain and local recurrence), common in prostate cancer biopsies and in cutaneous squamous and salivary cancers, PNI is an adverse pathological feature that can trigger adjuvant radiotherapy or wider margins. Biologically, nerves and tumours signal to each other (adrenergic and cholinergic signalling drive proliferation), which underpins the cancer neuroscience field and trials of beta-blockers and denervation. It is recorded in nearly every pathology report as present or absent.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Perineural_invasion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Perineural_invasion"},{"label":"Schmults et al., factors predictive of recurrence and death from cutaneous squamous cell carcinoma: 10-year, single-institution cohort study of 985 patients (JAMA Dermatology 2013)","url":"https://doi.org/10.1001/jamadermatol.2013.2139"},{"label":"Morecroft et al., immunotherapy and radiation for clinical perineural invasion in cutaneous squamous cell carcinoma (Cancers 2025)","url":"https://doi.org/10.3390/cancers17243921"}],"tags":[],"related":["lymphovascular-invasion","resection-margins","surgical-margins-keratinocyte-cancer","radiotherapy-for-skin-cancer"],"cancers":["pancreatic","prostate","head-and-neck","cutaneous-scc","skin-cancer","bowens-disease"],"sections":["diagnostics"],"technologies":["nerve-tumour-denervation"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["tnm-skin-carcinoma","skin-cancer-high-risk-features"],"trials":["c-post","trog-05-01"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In cutaneous squamous cell carcinoma this is the finding that changes the plan, and it comes in two forms. Clinical perineural invasion is evident from symptoms such as pain, altered sensation or a motor deficit, or from imaging; incidental perineural invasion is found only on the slide, with no symptoms and nothing on a scan. The clinically evident form carries the worse outlook.","In the ten-year cohort of 985 patients with 1,832 cutaneous squamous cell carcinomas, perineural invasion was associated with death from the cancer with a subhazard ratio of 3.6 (95 percent confidence interval 1.1 to 12.0), alongside a diameter of at least 2 cm, poor differentiation, invasion beyond the fat, and an ear or temple location.","In skin carcinoma it has a threshold, and the threshold moved. UICC TNM 9 defines perineural invasion in cutaneous carcinoma as tumour within the nerve sheath of a nerve lying deeper than the dermis, or measuring 0.1 mm or more in calibre, or involvement of five or more nerves in a section; meeting the definition upstages a tumour to pT3 whatever its size. The eighth edition had the nerve-calibre and nerve-depth criteria without the count."],"category":"Pathology"},"route":"/terms/perineural-invasion/","neighbours":{"term":[{"id":"depth-of-invasion","kind":"term","name":"Depth of invasion (DOI)","route":"/terms/depth-of-invasion/"},{"id":"extranodal-extension","kind":"term","name":"Extranodal extension (ENE)","route":"/terms/extranodal-extension/"},{"id":"extraprostatic-extension","kind":"term","name":"Extraprostatic extension and seminal vesicle invasion","route":"/terms/extraprostatic-extension/"},{"id":"tnm-skin-carcinoma","kind":"term","name":"How skin carcinoma is staged in Britain: UICC TNM, and why it is not the American system","route":"/terms/tnm-skin-carcinoma/"},{"id":"lymphovascular-invasion","kind":"term","name":"Lymphovascular invasion (LVI)","route":"/terms/lymphovascular-invasion/"},{"id":"radiotherapy-for-skin-cancer","kind":"term","name":"Radiotherapy for skin cancer","route":"/terms/radiotherapy-for-skin-cancer/"},{"id":"resection-margins","kind":"term","name":"Resection margins (R0 / R1 / R2)","route":"/terms/resection-margins/"},{"id":"bwh-staging-cscc","kind":"term","name":"The Brigham and Women's Hospital staging system, and why squamous cell carcinoma has two","route":"/terms/bwh-staging-cscc/"},{"id":"surgical-margins-keratinocyte-cancer","kind":"term","name":"The margin in skin cancer surgery","route":"/terms/surgical-margins-keratinocyte-cancer/"},{"id":"cscc-subtype-and-grade","kind":"term","name":"The subtype and grade on a cutaneous squamous cell carcinoma report","route":"/terms/cscc-subtype-and-grade/"},{"id":"skin-cancer-high-risk-features","kind":"term","name":"What makes a skin cancer high risk: the UK feature lists","route":"/terms/skin-cancer-high-risk-features/"}],"cancer":[{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"bowens-disease","kind":"cancer","name":"Bowen's disease (squamous cell carcinoma in situ)","route":"/cancers/bowens-disease/"},{"id":"cutaneous-scc","kind":"cancer","name":"Cutaneous squamous cell carcinoma","route":"/cancers/cutaneous-scc/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"gallbladder-neuroendocrine-carcinoma","kind":"cancer","name":"Neuroendocrine carcinoma of the gallbladder","route":"/cancers/gallbladder-neuroendocrine-carcinoma/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"}],"technology":[{"id":"nerve-tumour-denervation","kind":"technology","name":"Cancer neuroscience: cutting the nerve supply","route":"/technologies/nerve-tumour-denervation/"}],"trial":[{"id":"c-post","kind":"trial","name":"C-POST (cemiplimab after surgery and radiotherapy for high-risk skin squamous cell carcinoma)","route":"/trials/c-post/"},{"id":"trog-05-01","kind":"trial","name":"TROG 05.01 (chemotherapy added to radiotherapy after surgery for high-risk skin squamous cell carcinoma)","route":"/trials/trog-05-01/"}]}}