-
Life (Basel, Switzerland) Jun 2023Basal cell carcinoma (BCC) is a malignant tumor with a rising incidence and is the beneficiary of several innovative evaluation techniques. Histopathology remains the...
Basal cell carcinoma (BCC) is a malignant tumor with a rising incidence and is the beneficiary of several innovative evaluation techniques. Histopathology remains the gold standard for assessment, having the possibility of addressing multiple high-risk factors such as perineural invasion (PNI). The current study included a number of 244 BCC patients and targeted the identification of positive PNI and its suggestive signs, and whether they correlated or not with other high-risk tumor signs. PNI was found in 20.1% of patients, with 30.7% of patients having perineural chronic inflammation (PCI), which is a suggestive sign of PNI. PNI was also found in larger tumors, with deeper Clark levels, in high-risk BCCs and high-grade tumors. PNI and PCI are both important for pathology reporting, aiding in treatment choice and further patient management, with possibly positive outcomes concerning morbidity and mortality.
PubMed: 37374188
DOI: 10.3390/life13061406 -
Advanced Biology Feb 2023Squamous cell carcinoma of the oral cavity (OSCC) is the most common type of head and neck cancer; survival is poor, and response to treatment varies. Metastasis or... (Review)
Review
Squamous cell carcinoma of the oral cavity (OSCC) is the most common type of head and neck cancer; survival is poor, and response to treatment varies. Metastasis or recurrence in the regional lymph nodes is associated with poor survival. Consequently, overt or occult spread to the lymph nodes is used to identify patients who will receive adjuvant radiation therapy. Perineural invasion and the diameter of nerves exhibiting perineural invasion have also been suggested to be of prognostic significance. The explosion of interest in cancer neuroscience in the last two decades has led to novel biological insights into interactions between nerves and tumor cells. However, the criteria for defining perineural invasion have lagged behind current knowledge. It is important to re-evaluate the concept of perineural invasion and identify other neural phenotypes in OSCC that can impact treatment selection and prognosis. In addition to perineural invasion, neural phenotypes that are of potential relevance to tumor progression include nerve-tumor distance, nerve diameter, and nerve density. This manuscript discusses the translational significance of recent mechanistic studies on the progression of oral cancer.
Topics: Humans; Neoplasm Invasiveness; Mouth Neoplasms; Prognosis; Head and Neck Neoplasms; Lymph Nodes
PubMed: 36373694
DOI: 10.1002/adbi.202200188 -
Journal of Neurological Surgery. Part... Apr 2016This article provides an overview of perineural spread of head and neck malignancy. It defines the problem and explores some of the unique features, which occur with... (Review)
Review
This article provides an overview of perineural spread of head and neck malignancy. It defines the problem and explores some of the unique features, which occur with this pathology. The expectation is for a better understanding of this extraordinary disease, hopefully leading to earlier diagnosis and for a more consistent reporting of results. It summarizes the topics to be covered in this special edition, which should leave the reader with a fairly complete understanding of the contemporary issues of perineural spread.
PubMed: 27123383
DOI: 10.1055/s-0036-1579778 -
Current Oncology (Toronto, Ont.) Sep 2023Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to... (Review)
Review
Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI.
Topics: Humans; Peripheral Nerves; Neoplasm Invasiveness
PubMed: 37887547
DOI: 10.3390/curroncol30100647 -
International Journal of Molecular... May 2023Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of...
Perineural invasion is a prevalent pathological finding in head and neck squamous cell carcinoma and a risk factor for unfavorable survival. An adequate diagnosis of perineural invasion by pathologic examination is limited due to the availability of tumor samples from surgical resection, which can arise in cases of definitive nonsurgical treatment. To address this medical need, we established a random forest prediction model for the risk assessment of perineural invasion, including occult perineural invasion, and characterized distinct cellular and molecular features based on our new and extended classification. RNA sequencing data of head and neck squamous cell carcinoma from The Cancer Genome Atlas were used as a training cohort to identify differentially expressed genes that are associated with perineural invasion. A random forest classification model was established based on these differentially expressed genes and was validated by inspection of H&E-stained whole image slides. Differences in epigenetic regulation and the mutational landscape were detected by an integrative analysis of multiomics data and single-cell RNA-sequencing data were analyzed. We identified a 44-gene expression signature related to perineural invasion and enriched for genes mainly expressed in cancer cells according to single-cell RNA-sequencing data. A machine learning model was trained based on the expression pattern of the 44-gene set with the unique feature to predict occult perineural invasion. This extended classification model enabled a more accurate analysis of alterations in the mutational landscape and epigenetic regulation by DNA methylation as well as quantitative and qualitative differences in the cellular composition in the tumor microenvironment between head and neck squamous cell carcinoma with or without perineural invasion. In conclusion, the newly established model could not only complement histopathologic examination as an additional diagnostic tool but also guide the identification of new drug targets for therapeutic intervention in future clinical trials with head and neck squamous cell carcinoma patients at a higher risk for treatment failure due to perineural invasion.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Epigenesis, Genetic; Risk Assessment; RNA; Neoplasm Invasiveness; Tumor Microenvironment
PubMed: 37240283
DOI: 10.3390/ijms24108938 -
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 -
Prilozi (Makedonska Akademija Na... Dec 2023: Lymphovascular Invasion (LVI) and Perineural Invasion (PNI) represent undesirable but still realistic pathological features of rectal cancer, associated with poor... (Observational Study)
Observational Study
: Lymphovascular Invasion (LVI) and Perineural Invasion (PNI) represent undesirable but still realistic pathological features of rectal cancer, associated with poor prognosis and worse survival. The aim of this study is to assess the incidence of LVI and PNI in patients treated for rectal cancer and the impact of LVI and PNI on patient survival. : This retrospective single center observational study, conducted in the period of 2016-2019, includes patients with rectal cancer treated with/without long-course neoadjuvant chemoradiotherapy (nCRT). Data collection encompassed demographics, tumor characteristics, type of surgery (abdominal perineal rectal resection - APR and low anterior rectal resection - LAR), and LVI/PNI presence. Survival during follow-up was estimated and compared for patients with/without LVI and PNI involvement. : A total number of 234 patients (77 females and 157 males) with mean age of 61.3 enrolled in the study. Neoadjuvant CRT was conducted in 170 patients. APR procedure was performed in 67 of them and LAR in 167. LVI presence was noted in 55 (24.4%) and PNI in 77 (34.2%) patients. Mean survival during follow-up was 42.07 months. The use of nCRT influenced on survival (p < 0.033). Patients treated with LAR had better survival outcomes (p = 0.001). Presence of LVI and PNI was associated with a worse prognosis (p < 0.001). : PNI was more frequent than the LVI in this study. Patients with nCRT conduction had better overall survival. LVI and PNI presence was associated with poor prognosis in terms of overall survival in patients with rectal cancer.
Topics: Male; Female; Humans; Middle Aged; Retrospective Studies; Incidence; Neoplasm Invasiveness; Rectal Neoplasms; Chemoradiotherapy; Neoplasm Staging
PubMed: 38109451
DOI: 10.2478/prilozi-2023-0049 -
Scientific Reports Mar 2023This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received...
This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received surgery-based treatment at our institution between January 2013 and December 2020. Patients were divided into four groups based on the presence of perineural (P-/P +) and lymphovascular invasions (V-/V +): P-V-, P-V + , P + V-, and P + V + . Log-rank and Cox proportional hazard models were used to evaluate the association between perineural /lymphovascular invasion and overall survival (OS). Altogether, 127 patients were included, and 95 (74.8%), 8 (6.3%), 18 (14.2%), and 6 (4.7%) cases were classified as P-V-, P-V + , P + V-, and P + V + , respectively. Pathologic N stage (pN stage), tumor stage, histological grade, lymphovascular invasion, perineural invasion, and postoperative radiotherapy were significantly associated with OS (p < 0.05). OS was significantly different among the four groups (p < 0.05). Significant between-group differences in OS were detected for node-positive (p < 0.05) and stage III-IV (p < 0.05) cases. OS was the worst in the P + V + group. Lymphovascular and perineural invasions are independent negative prognostic factors for squamous cell carcinoma of the tongue. Patients with lymphovascular and/or perineural invasion may have significantly poorer overall survival than those without neurovascular involvement.
Topics: Humans; Prognosis; Carcinoma, Squamous Cell; Tongue; Health Facilities
PubMed: 36882521
DOI: 10.1038/s41598-023-30939-8 -
Journal of Neurological Surgery. Part... Apr 2016We present a review of the imaging findings of large nerve perineural spread within the skull base. The MRI techniques and reasons for performing different sequences are... (Review)
Review
We present a review of the imaging findings of large nerve perineural spread within the skull base. The MRI techniques and reasons for performing different sequences are discussed. A series of imaging examples illustrates the appearance of perineural tumor spread with an emphasis on the zonal staging system.
PubMed: 27123387
DOI: 10.1055/s-0036-1571836 -
Biomedical Papers of the Medical... Dec 2019Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One...
Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One of the most important factors affecting the risk of tumor recurrence and overall prognosis is perineural invasion and bone invasion. Perineural invasion is defined as a tumor spreading and the ability of tumor cells to penetrate around or through the nerve tissue. Perineural invasion can cause the tumor to spread to distant areas from the primary tumor location. One possible explanation for this is the formation of microenvironment in the perineural space which may contain cellular factors that act on both nerve tissue and some types of tumor tissues. Bone invasion by OSCC has major implications for tumor staging, choice of treatment, outcome and quality of life. Oral SCCs invade the mandibular or maxillary bone through an erosive, infiltrative or mixed pattern that correlates with clinical behavior. Bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. Some cytokines (e.g. TNFα and PTHrP) lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression in oral SCC cells and in cancer stromal cells to induce osteoclastogenesis. Oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. A more molecular-based clinical staging and tailor-made therapy would benefit patients with bone invasion by OSCC.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Carcinoma, Squamous Cell; Cytokines; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nerve Sheath Neoplasms; Predictive Value of Tests; Prognosis
PubMed: 31435075
DOI: 10.5507/bp.2019.032