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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 -
The Laryngoscope Jun 2022To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor...
OBJECTIVES/HYPOTHESIS
To describe outcomes of advanced head and neck cutaneous squamous cell carcinoma (cSCC) with clinical perineural invasion (cPNI) treated with immune checkpoint inhibitor (ICI) therapy, and to describe post-treatment radiographic findings in the context of clinical response to treatment using a new grading system.
STUDY DESIGN
Retrospective chart review.
METHODS
Retrospective chart review was performed for 11 patients treated with ICI for head and neck cSCC with cPNI of large named nerves. The primary outcome was response to treatment as defined by radiographic and clinical evidence. Clinical responses were defined as improvement in symptoms of neuropathic pain, hypoesthesia, nerve weakness, or decrease in visible tumor. Imaging studies were graded based on a new classification system for perineural invasion and reviewed by two neuroradiologists since RECISTv1.1 is inadequate to adjudicate response in these patients.
RESULTS
Nine (82%) patients had radiographic perineural disease control on ICI. Eight patients had improved radiographic perineural disease and one had stable disease. Of these, complete resolution of radiographic evidence of perineural disease was seen in only one patient. Seven (64%) patients had clinical responses, with either improved or stable radiographic disease.
CONCLUSIONS
ICI therapy is a viable treatment option for head and neck cSCC with cPNI. Radiographic and clinical evidence of response correlate well, with improvement in neuropathic pain being the most sensitive clinical marker of response. Even with favorable findings on repeat imaging and stable clinical course, complete resolution of perineural thickening and enhancement is rare. A grading system for classifying changes in perineural disease over time is proposed.
LEVEL OF EVIDENCE
4 Laryngoscope, 132:1213-1218, 2022.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Immunotherapy; Neoplasm Invasiveness; Neuralgia; Retrospective Studies; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 34797598
DOI: 10.1002/lary.29953 -
Pathology, Research and Practice Mar 2024Perineuriomatous melanocytic nevi are rare and this may indicate the similar embryological source of melanocytes and peripheral nerves in the neural crest. Neurotized...
BACKGROUND
Perineuriomatous melanocytic nevi are rare and this may indicate the similar embryological source of melanocytes and peripheral nerves in the neural crest. Neurotized melanocytic nevi may resemble nerve sheath tumors histologically, and show schwannian differentiation. However, literature on whether neurotized nevi differentiate into perineural cells is controversial. We examined our cases of neurotized nevi for evidence of perineural differentiation.
MATERIALS AND METHODS
A total of 100 benign nevi with large neurotized component (microscopically involved a low power field 4.2 mm in diameter) were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for EMA, Claudin1, Glut1 and neurofilament were performed.
RESULTS
Perineural differentiation was immunohistochemically detected in the neurotized component of the nevi in 61% of the cases with EMA and in all the cases with Glut1 and Claudin1. Axonal differentiation was not detected with neurofilament. The expression pattern, especially with Glut1, was usually in form of partial or complete staining surrounding the Meissner's corpuscle-like structure (MCLS). Also, a linear/curvilinear staining pattern was observed particularly with Claudin1. A diffuse staining pattern with EMA, Glut1 and Claudin1 was detected in a case with a microscopically distinct whorl structure, and in which spindle cells are separated from the superficial epithelioid melanocytes with an abrupt transition histologically. These findings of the case are compatible with previous reports of perineuromatous nevus.
CONCLUSION
Perineural differentiation is not uncommon and immunohistochemically observed in all nevi with a relatively large component of neurotization. To prevent misdiagnosing desmoplastic melanoma and overtreating patients, it is crucial to be aware of perineuromatous nevi.
Topics: Humans; Skin Neoplasms; Glucose Transporter Type 1; Immunohistochemistry; Nevus; Nevus, Pigmented; Melanocytes
PubMed: 38324967
DOI: 10.1016/j.prp.2024.155184 -
Journal of Neurological Surgery. Part... Sep 2021A perineural (Tarlov) cyst is a fluid-filled lesion occurring between the perineurium and the endoneurium of spinal nerve roots. The aim of the study was to evaluate...
BACKGROUND
A perineural (Tarlov) cyst is a fluid-filled lesion occurring between the perineurium and the endoneurium of spinal nerve roots. The aim of the study was to evaluate the prevalence and morphology of perineural cysts, detected incidentally in patients with symptomatic degenerative disk disease.
MATERIALS/METHODS
The study was based on the retrospective data gathered during magnetic resonance imaging (MRI) examinations.
RESULTS AND CONCLUSIONS
Out of 3,128 spinal MRI examinations, perineural cysts were detected in 286 patients (9%). The cysts were most commonly observed in the sacral region, followed by thoracic, cervical, and lumbar regions. Cysts were more common in women than in men and the average age of patients was 54.8 years. In the majority, a single cyst was found. The average longest dimension of the lesion was 11.72 mm.
Topics: Female; Humans; Lumbosacral Region; Magnetic Resonance Imaging; Male; Middle Aged; Retrospective Studies; Spinal Nerve Roots; Tarlov Cysts
PubMed: 33822351
DOI: 10.1055/s-0040-1722194 -
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 -
Oral and Maxillofacial Surgery Clinics... Aug 2023Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are... (Review)
Review
Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.
Topics: Humans; Cranial Nerve Neoplasms; Neoplasm Invasiveness; Head and Neck Neoplasms; Skull Base; Magnetic Resonance Imaging
PubMed: 37005170
DOI: 10.1016/j.coms.2023.02.004 -
Journal of Maxillofacial and Oral... Jun 2022Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of...
The Interrelation Among Triad of Depth of Invasion, Perineural Invasion and Tumor Size in Squamous Cell Carcinoma of Tongue and Floor of the Mouth: An Analytical Appraisal.
BACKGROUND
Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of the head and neck region Squamous cell carcinoma of tongue has a peculiar behavior of occult and skips metastasis to regional lymph nodes. It occasionally occurs along with floor of the mouth. The purpose of this study is to evaluate the significance of correlation between, depth of invasion of the primary tumor, its proximity with the neurovascular bundle and subsequent perineural invasion and cervical lymph node metastasis in squamous cell carcinoma tongue and floor of the mouth and the sites involving both.
MATERIALS AND METHODS
A total of 108 patients with carcinoma tongue (59), floor of the mouth (20) and involving both together (29) who underwent treatment during January 2015 to June 2017 that were followed up until December 2019 were assessed. Out of 108 patients that were included in the study, 71 patients underwent primary surgery and 37 patients were inoperable (tongue-17, floor of the mouth-9 and involving both together-11).
RESULTS
Perineural invasion was seen in 15 cases of pT1-2 where depth of invasion was less than 1 cm and in 28 cases of pT3-4 where depth of invasion was more than 1cm (-0.075). Skip metastasis was accounted for 61.9% overall.
CONCLUSION
The triad of perineural invasion, depth of invasion and tumor size is interrelated and was responsible for cervical lymph node metastasis and prognosis of the disease. Obtaining clear deep margins of the tumor from the mucosal margin and removal of lympho-fatty tissue at the floor of the mouth is an important aspect which gives the indication about prognostic factors like depth of invasion, tumor size, cervical nodal metastasis and recurrence of the disease. High-grade tumors (T3-4), depth of invasion of tumor at 1 cm or > 1 cm, increase the propensity of perineural invasion highly.
PubMed: 35712423
DOI: 10.1007/s12663-022-01685-7 -
Survey of Ophthalmology 2023Periocular squamous cell carcinoma is a common cutaneous malignancy with generally favorable outcomes; however, the periocular region is intrinsically a high-risk... (Review)
Review
Periocular squamous cell carcinoma is a common cutaneous malignancy with generally favorable outcomes; however, the periocular region is intrinsically a high-risk location, and there exist a subset of lesions with a propensity for poor outcomes. Orbital invasion, intracranial perineural spread, nodal and distant metastasis are feared complications. There are several staging systems for eyelid carcinoma and cutaneous squamous cell carcinoma, but the definition of high-risk lesions remains heterogeneous. It is unclear exactly which lesions can be safely deescalated, and which require nodal evaluation and adjuvant multimodal therapy. We seek to answer these questions by summarizing the literature on clinicopathologic variables, molecular markers, and gene profiling tests in periocular squamous cell carcinoma, with the extrapolation of data from the cutaneous squamous cell carcinoma literature. Standardized pathology reports with information on tumor dimensions, histological subtype and grade, perineural invasion, and lymphovascular invasion should become uniform. Integration with gene expression profiling assessments will individualize and improve the predictive accuracy of risk stratification tools to ultimately inform multidisciplinary decision-making.
PubMed: 37172747
DOI: 10.1016/j.survophthal.2023.05.001 -
Actas Dermo-sifiliograficas 2019Cutaneous squamous cell carcinoma is sometimes characterized by an increased risk of locoregional recurrence and occasionally distant metastasis. Several clinical and... (Review)
Review
Cutaneous squamous cell carcinoma is sometimes characterized by an increased risk of locoregional recurrence and occasionally distant metastasis. Several clinical and pathological factors, including perineural invasion, have been shown to have prognostic value in this setting. Perineural invasion, that is, the spread of tumor cells into the space surrounding a nerve, is usually an incidental finding. In the presence of symptoms or radiographic evidence of perineural spread, the diagnosis is clinical perineural invasion, which is associated with an increased risk of local recurrence and mortality.
Topics: Carcinoma, Squamous Cell; Facial Neoplasms; Facial Nerve; Humans; Incidental Findings; Magnetic Resonance Imaging; Mohs Surgery; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Peripheral Nerves; Prognosis; Risk Factors; Skin Neoplasms; Trigeminal Nerve
PubMed: 31000135
DOI: 10.1016/j.ad.2018.10.006 -
Cellular Signalling Oct 2023Perineural invasion and radioresistance are the main determinants of treatment outcomes in oral squamous cell carcinoma (OSCC), but the exact mechanism is still unknown....
Perineural invasion and radioresistance are the main determinants of treatment outcomes in oral squamous cell carcinoma (OSCC), but the exact mechanism is still unknown. We conducted an in vitro experiment to evaluate the role of integrin β1 (ITGB1) in the perineural invasion, radioresistance, and tumor aggressiveness of OSCC. Two OSCC cell lines (SCC25, SCC15) and radiation-induced radioresistant OSCC cell lines were used in this study. The expression of ITGB1 was compared between control radiosensitive and radioresistant OSCC cell lines. ITGB1 was inhibited by small hairpin RNA, and then the adhesion to neuronal cells, responsiveness to radiation, and aggressiveness of both OSCC cell lines were evaluated. Expression of ITGB1 and adhesion to neuronal cells were increased in radioresistant OSCC compared with control radiosensitive OSCC, and increased ITGB1 expression was more prominent in cancer stem cell-like cells. When the expression of ITGB1 was inhibited, the adhesion to neuronal cells, resistance to radiation, and invasion and migration of radioresistant OSCC were significantly reduced. Moreover, the expression of cancer stem cell markers and size of spheroid formations were also significantly attenuated by inhibiting ITGB1. These findings suggest that ITGB1 may be a significant contributor to perineural invasion and the maintenance of radioresistance in OSCC cells, and is associated with cancer stem cell-like cells. Furthermore, our results suggest a possible relationship between perineural invasion and radioresistance of OSCC. More detailed research is warranted to evaluate the role of ITGB1 as a novel emerging therapeutic target for radioresistant OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Integrin beta1; Cell Line, Tumor; Squamous Cell Carcinoma of Head and Neck; Cell Proliferation; Cell Movement; Head and Neck Neoplasms
PubMed: 37481218
DOI: 10.1016/j.cellsig.2023.110808