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Eye (London, England) Apr 2023Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a... (Review)
Review
Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) of the periocular region is a prognostic marker of adverse tumour outcomes. PNI carries a well-established risk of tumour recurrence, regional metastasis and higher likelihood of mortality. This review will explore and stratify the risks conferred by histological PNI parameters. The radiological features of perineural spread (PNS) and the imaging sequences that delineate these findings will also be highlighted. Surgical excision with en face margin control is the preferred technique for achieving histological clearance. Adjuvant radiotherapy improves treatment outcomes in the setting of concomitant high-risk features. For locally advanced or metastatic cutaneous SCC, immunotherapy represents a novel treatment alternative. This review will provide an algorithm for the diagnosis and management of periocular SCC with PNI and PNS.
Topics: Humans; Carcinoma, Squamous Cell; Skin Neoplasms; Neoplasm Recurrence, Local; Treatment Outcome; Radiotherapy, Adjuvant; Neoplasm Invasiveness; Prognosis; Retrospective Studies
PubMed: 36400852
DOI: 10.1038/s41433-022-02306-w -
Scientific Reports Jul 2022Surgical management of head and neck cancer requires a careful balance between complete resection of malignancy and preservation of function. Surgeons must also...
Surgical management of head and neck cancer requires a careful balance between complete resection of malignancy and preservation of function. Surgeons must also determine whether to resect important cranial nerves that harbor perineural invasion (PNI), as sacrificing nerves can result in significant morbidity including facial paralysis. Our group has previously reported that Dynamic Optical Contrast Imaging (DOCI), a novel non-invasive imaging system, can determine margins between malignant and healthy tissues. Herein, we use an in vivo murine model to demonstrate that DOCI can accurately identify cancer margins and perineural invasion, concordant with companion histology. Eight C3H/HeJ male mice were injected subcutaneously into the bilateral flanks with SCCVIISF, a murine head and neck cancer cell line. DOCI imaging was performed prior to resection to determine margins. Both tumor and margins were sent for histologic sectioning. After validating that DOCI can delineate HNSCC margins, we investigated whether DOCI can identify PNI. In six C3H/HeJ male mice, the left sciatic nerve was injected with PBS and the right with SCCVIISF. After DOCI imaging, the sciatic nerves were harvested for histologic analysis. All DOCI images were acquired intraoperatively and in real-time (10 s per channel), with an operatively relevant wide field of view. DOCI values distinguishing cancer from adjacent healthy tissue types were statistically significant (P < 0.05). DOCI imaging was also able to detect perineural invasion with 100% accuracy compared to control (P < 0.05). DOCI allows for intraoperative, real-time visualization of malignant and healthy tissue margins and perineural invasion to help guide tumor resection.
Topics: Animals; Disease Models, Animal; Head and Neck Neoplasms; Male; Margins of Excision; Mice; Mice, Inbred C3H; Neoplasm Invasiveness; Optical Imaging
PubMed: 35896579
DOI: 10.1038/s41598-022-16975-w -
Frontiers in Genetics 2022Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell... (Review)
Review
Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion's extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors.
PubMed: 35571032
DOI: 10.3389/fgene.2022.848557 -
Cancers Aug 2022Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI,... (Review)
Review
Perineural invasion (PNI) is a common indication of tumor metastasis that can be detected in multiple malignancies, including prostate cancer. In the development of PNI, tumor cells closely interact with the nerve components in the tumor microenvironment and create the perineural niche, which provides a supportive surrounding for their survival and invasion and benefits the nerve cells. Various transcription factors, cytokines, chemokines, and their related signaling pathways have been reported to be important in the progress of PNI. Nevertheless, the current understanding of the molecular mechanism of PNI is still very limited. Clinically, PNI is commonly associated with adverse clinicopathological parameters and poor outcomes for prostate cancer patients. However, whether PNI could act as an independent prognostic predictor remains controversial among studies due to inconsistent research aim and endpoint, sample type, statistical methods, and, most importantly, the definition and inclusion criteria. In this review, we provide a summary and comparison of the prognostic significance of PNI in prostate cancer based on existing literature and propose that a more standardized description of PNI would be helpful for a better understanding of its clinical relevance.
PubMed: 36077602
DOI: 10.3390/cancers14174065 -
Journal of Neurological Surgery. Part... Apr 2016Perineural invasion (PNI) is the neoplastic invasion of nerves. PNI is widely recognized as an important adverse pathological feature of many malignancies, including... (Review)
Review
Perineural invasion (PNI) is the neoplastic invasion of nerves. PNI is widely recognized as an important adverse pathological feature of many malignancies, including pancreatic, prostate, and head and neck cancers and is associated with a poor prognosis. Despite widespread acknowledgment of the clinical significance of PNI, the mechanisms underlying its pathogenesis remain largely unknown. Recent theories of PNI pathogenesis have placed a significant emphasis on the active role of the nerve microenvironment, with PNI resulting from well-orchestrated reciprocal interactions between cancer and host. Elucidating the mechanisms involved in PNI may translate into targeted therapies for this ominous process.
PubMed: 27123385
DOI: 10.1055/s-0036-1571835 -
Oral Oncology Jan 2015Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor... (Review)
Review
Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor cells inside the neural space seen on histological or imaging evaluations. Little is known about molecular mechanisms involved in the growth and spread of tumor cells in neural spaces. The poor prognosis associated with perineural growth and lack of targeted approaches necessitates the study of molecular factors involved in communication between tumor and neural cells. Perineural growth rates, shown to be as high as 63% in head and neck squamous cell carcinoma (HNSCC), correlate with increased local recurrence and decreased disease-free survival. Here we describe the literature on perineural growth in HNSCC. In addition, we discuss factors implicated in perineural growth of cancer. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 and -4, glial cell-line derived neurotrophic factor (GDNF), the neural cell adhesion molecule (NCAM), substance P (SP), and chemokines. We also explore the literature on membrane receptors, including the Trk family and the low-affinity nerve growth factor receptor. This review highlights areas for further study of the mechanisms of perineural invasion which may facilitate the identification of therapeutic targets in HNSCC.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Neoplasm Metastasis
PubMed: 25456006
DOI: 10.1016/j.oraloncology.2014.10.004 -
Anaesthesia Jul 2021Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the... (Meta-Analysis)
Meta-Analysis
Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the effects of dexamethasone and dexmedetomidine based on their administration routes have not been directly compared, and the relative extent to which each adjunct prolongs sensory blockade remains unclear. This network meta-analysis sought to compare and rank the effects of perineural and intravenous dexamethasone and dexmedetomidine as supraclavicular block adjuncts. We sought randomised trials investigating the effects of adding perineural and intravenous dexamethasone or dexmedetomidine to long-acting local anaesthetics on supraclavicular block characteristics, including time to block onset and durations of sensory, motor and analgesic blockade. Data were compared and ranked according to relative effectiveness for each outcome. Our primary outcome was sensory block duration, with a 2-h difference considered clinically important. We performed a frequentist analysis, using the GRADE framework to appraise evidence. One-hundred trials (5728 patients) were included. Expressed as mean (95%CI), the control group (local anaesthetic alone) had a duration of sensory block of 401 (366-435) min, motor block duration of 369 (330-408) min and analgesic duration of 435 (386-483) min. Compared with control, sensory block was prolonged most by intravenous dexamethasone [mean difference (95%CI) 477 (160-795) min], followed by perineural dexamethasone [411 (343-480) min] and perineural dexmedetomidine [284 (235-333) min]. Motor block was prolonged most by perineural dexamethasone [mean difference (95%CI) 294 (236-352) min], followed by intravenous dexamethasone [289 (129-448)min] and perineural dexmedetomidine [258 (212-304)min]. Analgesic duration was prolonged most by perineural dexamethasone [mean difference (95%CI) 518 (448-589) min], followed by intravenous dexamethasone [478 (277-679) min] and perineural dexmedetomidine [318 (266-371) min]. Intravenous dexmedetomidine did not prolong sensory, motor or analgesic block durations. No major network inconsistencies were found. The quality of evidence for intravenous dexamethasone, perineural dexamethasone and perineural dexmedetomidine for prolongation of supraclavicular sensory block duration was 'low', 'very low' and 'low', respectively. Regardless of route, dexamethasone as an adjunct prolonged the durations of sensory and analgesic blockade to a greater extent than dexmedetomidine. Differences in block characteristics between perineural and intravenous dexamethasone were not clinically important. Intravenous dexmedetomidine did not affect block characteristics.
Topics: Adjuvants, Anesthesia; Administration, Intravenous; Anesthetics, Local; Brachial Plexus Block; Dexamethasone; Dexmedetomidine; Humans; Network Meta-Analysis
PubMed: 33118163
DOI: 10.1111/anae.15288 -
International Journal of Rheumatology 2012Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related...
Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related disease identified 21 peripheral nerve lesions in 7 patients. Clinicopathological and radiological features were examined. Results. Peripheral nerve lesions were commonly identified in orbital or paravertebral area, involving orbital (n = 9), optic (n = 4), spinal (n = 7), and great auricular nerves (n = 1). The predominant radiological feature was a distinct perineural soft tissue mass, ranging 8 to 30 mm in diameter. Histologically, the epineurium was preferentially involved by massive lymphoplasmacytic infiltration rich in IgG4(+) plasma cells. All lesions were neurologically asymptomatic and steroid-responsive at the first presentation, but one recurrent lesion around the optic nerve caused failing vision. Conclusion. IgG4-related disease of the peripheral nervous system is characterized by orbital or paravertebral localization, perineural mass formation, and rare neurologic symptoms. The term "IgG4-related perineural disease" seems appropriate to describe this entity.
PubMed: 22523496
DOI: 10.1155/2012/401890 -
The British Journal of Radiology Aug 2022Acetabular paralabral cysts are common and are almost always associated with labral tears. Uncommonly, they extend into the periacetabular soft tissues or may propagate...
OBJECTIVE
Acetabular paralabral cysts are common and are almost always associated with labral tears. Uncommonly, they extend into the periacetabular soft tissues or may propagate along peripheral nerves causing pain and hip dysfunction. The aim was to evaluate the clinical and MRI presentations of such cases including perineural propagation.
METHODS
Retrospective cross-sectional study with a search of electronic health records for cases of acetabular paralabral cysts demonstrating perineural propagation was performed. Clinical and MR imaging features were tabulated after re-review by experienced musculoskeletal radiologists, and available outcomes were recorded. Descriptive statistics were performed.
RESULTS
14 cases were recorded. The mean age was 56.9 years (range = 30-79 years) and female:male ratio was 1:2.6. The commonest presenting complaint was hip pain (10/14, 71.4%). Other complaints included groin pain, perineal pain and hip dysfunction. No symptoms were attributed to the acetabular paralabral cyst in 3/14 patients (21.4%). None had foot drop. The cysts were multilocular in all cases and were homogenously T2 hyperintense in 13/14 (92.9%). Labral tears were identified in 11/14 cases (78.6%). The sciatic nerve was most commonly involved in 5/14 cases (35.7%) with the obturator, medial femoral cutaneous nerve, femoral nerve, superior and inferior gluteal nerves also affected.No intervention was undertaken in 9/14 cases (64.3%). 5/14 (35.7%) underwent image guided aspiration and corticosteroid injection. 4/5 such patients reported reduced pain following the procedure.
CONCLUSION
Paralabral cysts demonstrating perineural propagation are uncommon and exhibit varied presentations. Most patients who underwent image-guided or surgical interventions reported an improvement in symptoms.
ADVANCES IN KNOWLEDGE.
This is the first description of a series of patients with acetabular paralabral cysts demonstrating perineural propagation in the literature. A comprehensive description of their clinical and imaging characteristics and interventions/outcomes where relevant is provided.
Topics: Acetabulum; Adult; Aged; Arthralgia; Arthroscopy; Cross-Sectional Studies; Cysts; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies
PubMed: 35762342
DOI: 10.1259/bjr.20211306 -
Cell & Bioscience Jun 2021The perineural invasion (PNI), which refers to tumor cells encroaching on nerve, is a clinical feature frequently occurred in various malignant tumors, and responsible... (Review)
Review
The perineural invasion (PNI), which refers to tumor cells encroaching on nerve, is a clinical feature frequently occurred in various malignant tumors, and responsible for postoperative recurrence, metastasis and decreased survival. The pathogenesis of PNI switches from 'low-resistance channel' hypothesis to 'mutual attraction' theory between peripheral nerves and tumor cells in perineural niche. Among various molecules in perineural niche, microRNA (miRNA) as an emerging modulator of PNI through generating RNA-induced silencing complex (RISC) to orchestrate oncogene and anti-oncogene has aroused a wide attention. This article systematically reviewed the role of microRNA in PNI, promising to identify new biomarkers and offer cancer therapeutic targets.
PubMed: 34187567
DOI: 10.1186/s13578-021-00630-4