Worst Pattern Of Invasion Research Articles

WPOI-4/5 Correlates With Lymph Node Recurrence and Poor Prognosis in Early-stage Tongue Squamous Cell Carcinoma.

Neck management in patients with early-stage tongue cancer remains controversial. The worst pattern of invasion (WPOI) of the primary tumor has been associated with the incidence of regional metastasis. We investigated the prognostic role of WPOI, especially in relation to regional lymph node recurrence and disease-specific survival (DSS). We retrospectively reviewed medical records and evaluated tumor specimens of 38 patients with early-stage tongue cancer who underwent primary tumor resection without elective neck dissection. Regional lymph node recurrence rates were significantly higher in patients with WPOI-4/5 compared with WPOI-1 to -3. The 5-year DSS rates were significantly higher for WPOI-1 to -3 than for WPOI-4/5. Notably, patients with WPOI-1 to -3 achieved a 100% 5-year DSS rate with salvage neck dissection and postoperative treatment, even those with cervical lymph node recurrence, whereas patients with WPOI-4/5 had a poorer prognosis. Patients with WPOI-1 to -3 tumors can be followed up without neck dissection until regional lymph node recurrence is detected, with a good course after salvage treatment. In contrast, patients with WPOI-4/5 tumors who are followed up until the appearance of regional lymph node recurrence have a poor prognosis, even with adequate treatment for recurrent disease.

Incidence of Perineural Invasion of Oral Squamous Cell Carcinoma and Its Association with Worst Pattern of Invasion and Staging of Tumor: A Retrospective Study

Background: Histological parameters are the most reliable factors in diagnosis, management and prognosis of oral squamous cell carcinoma (OSCC). The incidence of perineural invasion (PNI) and its association with staging of tumor and worst pattern of invasion (WPOI) have influenced the outcome of the disease. This retrospective study was conducted to determine the association of PNI with staging of tumor and WPOI.
 Methodology: Sixty-six cases of histopathologically confirmed OSCC treated surgically without neo-adjuvant chemo-radiotherapy between 2019 Jan -2020 June were included in the study. The subjects were divided into group A with PNI negative subjects and Group B with PNI positive subjects.
 Results: Out of 66 cases, 42 patient were PNI negative (63.6%) and 24 patients were PNI positive (36.4%). WPOIIV-V was present in 38 (57.6 %) of the cases and I-III was seen in 28 (42.4%) of the 66 patients.
 Conclusion: WPOI and PNI are significantly important risk factors for predicting LN metastasis in all stages of Oral squamous cell carcinoma and are associated with a poorer outcome in early-stage tumors.

WPOI-5: Accurately Identified at Intraoperative Consultation and Predictive of Occult Cervical Metastases.

Frozen section analysis of oral cancer specimens is ideal for assessing margin distances and depth of invasion (DOI); the latter impacts intraoperative decisions regarding elective neck dissection (END). Here, we show that intraoperative determination of worst pattern of invasion (WPOI), specifically WPOI-5, has a high level of accuracy. This relates to our demonstration herein that WPOI-5 predicts occult cervical metastases (OCM) for pT1 oral squamous carcinoma (OSC). The presence of OCM was correlated with WPOI in 228 patients with primary T1/T2/cN0 OSC undergoing resection and END. Concordance between intraoperative and final pathology WPOI determination was assessed on 51 cases of OSC. WPOI-5 predicts OCM in pT1 patients, compared with WPOI-4/WPOI-3 (p < 0.0001). Most pT1 WPOI-5 tumors had DOI of 4-5mm (24/59 or 40.7%). Only two pT1 WPOI-5 tumors had DOI < 4mm (3.0 and 3.5mm). If END were performed in this pT1 cohort for all WPOI-5 OSC patients regardless of DOI, OR all OSC patients with DOI ≥ 4mm regardless of WPOI, then no OCM would be missed (p = 0.017, 100% sensitivity, 29% specificity, 77% positive predictive value, 23% negative predictive value). With respect to intraoperative WPOI-5 determination, the accuracy, sensitivity, and specificity was 92.16, 73.33, and 100.0%, respectively. DOI ≥ 4mm is the dominant predictor of OCM. For the rare WPOI-5 OSC with DOI < 4mm, it is reasonable to suggest that surgeons perform END. WPOI-5 may be accurately determined intraoperatively. As microscopic instruction is needed to accurately assess WPOI-5, a teaching link is included in this manuscript.

A Clinicopathological Evaluation of the Correlation of Carcinoma Oral Tongue (Anterior Two Thirds) with Cervical Nodal Metastasis to Assess the Level of Neck Dissection: A Hospital Based Prospective Study.

Being an important prognostic predictor in carcinoma oral tongue, neck metastasis poses an adverse impact on prognosis.The management of neck is still controversial. Neck metastasis depends on features like tumor thickness, depth of invasion, lymphovascular invasion and perineural invasion. Thus by correlating these features with the level of nodal metastasis and by correlating clinical and pathological staging, a preoperative assumption for a more conservative neck dissection may be done. To correlate clinical staging, pathological staging and depth of invasion (DOI) of tumor with cervical nodal metastasis, for a preoperative assumption of a more conservative neck dissection.To study the correlation of additional prognostic features like lymphovascular invasion, perineural invasion, positive resection margin, worst pattern of invasion, lymphocytic infiltration and presence of necrosis with that of cervical nodal metastasis. The study was conducted on 24 patients of carcinoma oral tongue who underwent resection of the primary with an appropriate neck dissection and their clinical, imaging, and postoperative histopathological findings were correlated. We found a significant association of the CC (craniocaudal) dimension and radiologically determined DOI (depth of invasion) with the pN also significant association of clinical and radiological DOI with histological DOI. The probability of occult metastasis was found to be more when the MRI-DOI is > 5mm. The sensitivity and specificity of cN staging were 66.67% and 73.33% respectively. The accuracy of cN was 70.8%. In the present study a good sensitivity, specificity and accuracy of cN (clinical nodal stage) was found. Craniocaudal (CC) dimension and DOI of the primary tumor measured by MRI is a strong predictor of the disease extension and nodal metastasis. MRI-DOI > 5mm warrants an elective neck dissection of level I-III. For tumors MRI DOI < 5mm observation can be recommended with adherence to a strict follow-up.

Significant association of Yamamoto-Kohama classification and pathological depth of invasion with cervical lymph node metastasis in early-stage tongue squamous cell carcinoma (Stage I/II)

Background/purposeTongue squamous cell carcinoma (SCC) has a poor prognosis due to a high rate of cervical lymph node metastasis (CLNM). We aimed to determine clinicopathological features related to the prediction of CLNM in tongue carcinomas (Stage Ⅰ/Ⅱ). Materials and methodsData from 89 patients with tongue SCC (Stage I/II) were analyzed retrospectively. Patients were treated only with partial glossectomy and not with chemotherapy or radiotherapy until CLNM was observed. No cervical lymph node metastasis survival (NCLNMS) was estimated using the Kaplan–Meier method. The difference in NCLNMS between the groups with and without CLNM was compared using the log-rank test. The Cox regression model was used to estimate hazard ratios and the associated 95% confidence interval. ResultsClinical T2, clinical and pathological depth of invasion (cDOI and pDOI, respectively) > 5 mm, Yamamoto-Kohama (YK)-4c, tumor budding ≥5, worst pattern of invasion −4/5, muscle invasion, perineural invasion, and grade of differentiation 3 were found to be significant CLNM risk factors. ConclusionCLNM was observed in 25.8% of early-stage tongue carcinomas (Stage I/II). YK-4c and pDOI >5 mm were the most important CLNM risk factors identified. Close follow-up is needed after partial glossectomy when patients with tongue SCC have other risk factors, particularly YK-4c and pDOI >5 mm.

Relationship Between Worst Pattern of Invasion and Extranodal Extension in Oral Tongue Squamous Cell Carcinomas.

Oral tongue squamous cell carcinoma (OTSCC) is a common malignancy of the oral cavity with poor survival rates. The aim of this project is to investigate the relationship between certain histopathological factors such as Worst Pattern of Invasion (WPOI) and Extranodal Extension (ENE) in patients with oral tongue squamous cell carcinoma (OTSCC) who underwent surgical resection at Loyola University Medical Center. This was a retrospective cohort study at a tertiary care academic medical center. All patients that underwent primary surgical resection of OTSCC between 1/1/2015 and 1/1/2022 were reviewed. Patients were identified using the Cerner CoPath Laboratory Information System. A total of 82 patients met inclusion criteria and were included in the study. Higher grades of WPOI (WPOI 5) were not significantly associated with the presence of ENE in our study (P = 0.82), regardless of the presence of major or minor ENE. WPOI 5 was associated with a higher incidence of local recurrence (P = 0.011). Higher grades of WPOI were not found to correlate with the presence of ENE, a common histopathological factor that is used as an important prognostic indicator in OTSCC. It is important for clinicians to consider these factors separately when determining whether a patient is high-risk and would benefit from aggressive multimodal treatment.

Worst pattern of invasion and other histopathological features in oral cancer as determinants of prognosis and survival rate: A retrospective cohort analysis.

Oral cavity squamous cell carcinoma (OCSCC) is a well-recognized malignancy of the head and neck. Studies on patients with early-stage oral cancer have shown that they develop locally recurring and/or regional lymph node metastasis, which results in disease-associated mortality. Thus, early-stage oral cancer does not always present good prognoses. The present study aimed to determine the efficacy of using worst pattern of invasion (WPOI) and other histopathological features, such as prognostic factors in OCSCC, and analyze the impact of resection margin status and histopathological prognostic indicators on local recurrence (LR) and overall survival (OS) in patients with OCSCC. A retrospective cohort study was conducted by reviewing the charts of 63 patients with OCSCC treated with primary surgery at King Abdulaziz University Hospital between 2012 and 2019. An author and an experienced pathologist reviewed pathology slides. Associations of histopathological factors, including differentiation, stage, lymphovascular invasion, extracapsular extension, perineural invasion (PNI), WPOI and surgical margins, with LR or disease-free survival (DFS) were evaluated. Univariate analysis identified WPOI and PNI, and multivariate analysis identified the WPOI as predictive factors for LR and DFS. Kaplan-Meier analysis identified the WPOI and PNI as predictive factors for OS and WPOI as a predictive factor for DFS. Therefore, it may be concluded that WPOI and PNI are significant independent prognostic factors for local tumor control and DFS in patients with OCSCC.

Association of worst pattern of invasion in oral squamous cell carcinoma with clinicopathological parameters

There is a paucity of literature regarding the association of various clinicopathological parameters with the different patterns of invasion including the worst pattern of invasion (WPOI). The current study aimed to evaluate the association of WPOI in oral squamous cell carcinoma (SCC) with clinicopathological factors. This was a retrospective study conducted on all newly diagnosed cases of oral SCC patients, who underwent resection surgery. The cases were evaluated for the WPOI, tumor budding, extra-nodal extension, perineural invasion (PNI), lympho-vascular emboli (LVE), depth of invasion (DOI), nodal metastasis, closest surgical margin and histological grade. The association between WPOI and clinicopathological parameters was evaluated using the Fischer exact/Chi-square test. Out of 71 patients, 61.9% (n = 44) and 38.1% (n = 27) had WPOI I-III and IV-V respectively. A significant association was seen between WPOI and tumor stage, nodal involvement, histological grade, LVE, PNI, DOI and tumor budding. However, no association was observed with extra-nodal extension and margin status. The patients with WPOI IV and V had nodal metastasis, a higher histological grade, a high tumor budding and lympho-vascular invasion. The pattern of invasion is an easily recognizable histopathological variable which must be included in routine reporting of oral SCCs. An infiltrative pattern has a worse clinical outcome and is associated with nodal metastasis, PNI and LVE.

Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Worst Pattern of Invasion as an Independent Predictor of Lymph node Metastasis and Prognosis in oral Cavity Squamous cell carcinoma - A Retrospective Cohort Study.

Although Worst pattern of invasion (WPOI) is one of the histopathological (HP) markers that has been utilized in risk stratification of oral squamous cell carcinoma (OSCC) patients, its potential as an independent predictive factor for lymph node metastasis (LNM) and prognosis is least analyzed. Aim of the study is to analyze the relationship of various HP parameters to WPOI, their propensity for lymph node metastasis and prognostic value. This retrospective study included 140 patients diagnosed with resectable OSCC who underwent definitive surgery. Multiparametric HP risk assessment was done on the postoperative specimen and patients were categorized as low-risk WPOI (Type 1-3), and high-risk group (type 4 and 5). After categorization, 36.1% patients had low-risk WPOI and 63.9% had high-risk WPOI. Significant association was noted between WPOI and patient's age (p = 0.001), nodal stage (p = 0.001), lymphovascular invasion (LVI) (p = 0.006) and neural invasion (p = 0.001). 87% patients with nodal metastasis had high risk WPOI. LVI (p = 0.014) and WPOI (p < 0.001) had significant predictive role in LNM. High-risk WPOI and bone involvement were found to be predictive factors for overall survival, and only high risk WPOI had strong correlation with disease free survival having significant poor prognosis. Analyzing WPOI is essential in reporting HP specimens in OSCC. High-risk WPOI can act as an independent predictor for LNM, early recurrence and poor prognosis. Incorporation of WPOI into TNM staging is recommended to improve clinician's ability to prognosticate and individualize treatment strategies.

Early-Stage Oral Tongue Squamous Cell Carcinoma and a Positive Sentinel Lymph Node Biopsy: Description of a Prognostic Correlation between Pre-Treatment Inflammatory Biomarkers, the Depth of Invasion and the Worst Pattern of Invasion.

The aim of this study was to investigate the correlation between pre-treatment inflammatory biomarkers and the post-operative depth of invasion (DOI) and worst pattern of invasion (WPOI) in early-stage oral tongue squamous cell carcinoma (OTSCC) by means of positive sentinel lymph node biopsy (SLNB). A retrospective analysis of patients affected by cN0 T1-T2 OTSCC who had undergone an SLNB at the National Cancer Institute of Naples was performed. The patients were studied using an evaluation of the pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), and a histopathological analysis of the DOI and WPOI. The statistical analysis showed that among the prognostic biomarkers, the NLR was a significant predictor of high WPOI values (p = 0.002). The cut-off NLR value was 2.52 with a probability of developing a positive sentinel lymph node biopsy (SLNB) of 30.3%. In contrast, the DOI value was 5.20 with a probability of developing a positive SLNB of 31.82%. Regarding the WPOI, increasing the WPOI class increased the likelihood of a positive SLNB occurrence, and a positive significant correlation was found between the WPOI and SLNB (Csp = 0.342; p &lt; 0.001). Pre-treatment NLR, together with post-surgical DOI and WPOI, can be a reliable predictor of occult neck metastasis in patients affected by early-stage OTSCC with a clinically negative neck. Further prospective studies with a larger series will be needed to confirm the results obtained and to better define the NLR, WPOI and DOI cut-off values in order for elective neck dissection to be recommended in relation to a clinically negative neck.

Prognosis of tongue squamous cell carcinoma associated with individual surgical margin and pathological features

The specific muscular structure of the tongue greatly affects margin shrinkage and tumor invasion, making the optimal surgical margin controversial. This study investigated surgical margin correlated prognosis of TSCC (tongue squamous cell carcinoma) according to margin location and its value, and the histopathologic factors which are suggestive of tumor invasion. And we would like to propose defining of the surgical margin for TSCC via prognosis according to location and margin values. We reviewed 45 patients diagnosed with TSCC who visited Seoul National University Dental Hospital (SNUDH) (Seoul, Republic of Korea) from 2010 to 2019, who were managed by a single surgical team. Patient clinical and pathological data of patients were retrospectively reviewed, and in 36 out of 45 patients, the pathologic parameters including the worst pattern of invasion (WPOI) and tumor budding were investigated via diagnostic histopathology slide reading. When standardized with as 0.25 cm anterior margins, as 0.35 cm deep margin, there was no significant difference in disease specific survival (DSS) or loco-regional recurrence-free survival (LRFS). Additionally, there was a non-significant difference in DSS and LRFS at the nearest margin of 0.35 cm (PDSS=0.276, PLRFS=0.162). Aggressive WPOI and high tumor budding showed lower survival and recurrence-free survival, and there were significant differences in close margin and involved margin frequencies. In TSCC, the value and location of the surgical margin did not have a significant relationship with prognosis, but WPOI and tumor budding suggesting the pattern of muscle invasion affected survival and recurrence-free survival. WPOI and tumor budding should be considered when setting an optimal surgical margin.

Impact of Depth of Invasion Tumor Budding and Worst Pattern of Invasion on Clinical Outcome in Post-Operative Oral Cavity Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> Definitive treatment for oral cavity squamous cell carcinoma (OCSCC) is surgery followed by post-operative radiotherapy (PORT) with or without chemotherapy. Risk factors for PORT are T3/T4, node positive, lympho-vascular space invasion (LVI) or perineural invasion (PNI), close margin etc. Depth of invasion (DOI), tumor budding (TB) and worst pattern of invasion (WPOI) and tumor infiltrating lymphocytes (TILS) may have prognostic implications. We aim to report the incidence of these factors and its association with clinical outcome post-operative OCSCC patients treated at our institute. <h3>Materials/Methods</h3> 150 post-operative patients of OCSCC undergoing curative oncological resection were analyzed with median follow up time 18 months from year 2019 to 2021. WPOI (WPOI-5) was defined as tumor dispersion of ≥1mm between tumor satellites. High risk WPOI was defined as (WPOI 4/5). Tumor budding is defined as the presence of single cancer cell or cluster of <5 cancer cells at the invasive front. DOI and staging were used as per AJCC 8^th edition. Disease free survival (DFS) and overall survival (OS) were estimated with Kaplan- Meier method. <h3>Results</h3> Median age was 50 years with M:F ratio of 135:15. Tumor site was buccal mucosa: tongue:alveolus:others as 84 (56%):49 (32%):13 (8.6%):4 (2.6%). LVI:PNI: close/positive margin: extra nodal extension was seen in 57 (38%):52 (34%):35 (23%):33 (22%) patients respectively. DOI=>10, DOI<10, high risk WPOI, tumor budding and TILS were observed in 79(52.6%), 71(47.3%), 102(72.8%), 97(71.3%) and 30(21.5%) patients respectively. Association of these have been listed in Table 1. AJCC eighth stage was I:II:III:IV as 30 (20%):32 (21.3%):38 (25.3%):50 (33.3%). Median RT Dose was 60 Gray. Sixty-four patients received CTRT (Median 5 cycles). Median Overall Treatment Time (OTT) was 98 (95-120) days. 2-year OS and DFS for the entire cohort was 81% and 67% respectively. 2-year DFS for patient with TILS was 86% vs.64% without TILS (p=0.07). PNI (60% vs. 72%; p=0.06) and bone invasion (47% vs 84%; p=0.04) portended poorer DFS. TB, WPOI and DOI did not statistically impact DFS in our cohort. <h3>Conclusion</h3> TB, WPOI and DOI are often associated in post-operative OCSCC with other adverse risk features. Patients with TILS tend to have a better clinical outcome

Epithelial PD-L1 expression at tumor front predicts overall survival in a cohort of oral squamous cell carcinomas from Sudan.

We recently described the tumor immune microenvironment (TIME) in oral squamous cell carcinomas (OSCC) from Sudan by assessing the core of the lesions. However, the invasive tumor front (ITF) is the most active part of OSCC lesions;thus,TIME should also be characterized at theITF in this patient cohort. We aimed to evaluate patterns of immune cell infiltration at theITF in a cohort of OSCC patients from Sudan previously investigated at the tumor centerand their association with clinicopathological parameters. This study was performed on a prospective cohort of 22 OSCC patients attending Khartoum Dental Teaching Hospital with a median follow-up of 48 months. Inflammatory infiltrate densities of CD4-, CD8-, FoxP3-, CD20-, CD66b-, M1 (CD80/CD68)-, M2 (CD163/CD68)-, and PD-L1-positive cells were assessed at the ITF by immunohistochemistry, followed by digital quantitative analysis at the stromal and epithelial compartments separately. Histopathological parameters such as the worst pattern of invasion, differentiation, and tumor budding (TB) were also assessed. Correlations between clinicopathological parameters and survival analysis were investigated using SPSS. All inflammatory cell subsets investigated were found to be higher in the stromal compartment as compared to the epithelial one, except for the PD-L1+ subset. Stromal infiltration with the CD8+ cell subset was associated with low TB. Kaplan-Meier analyses identified higher epithelial and stromal CD4+ cell subsets.The presence ofPD-L1 was found to be associated with unfavorable overall survival. Further, Cox's regression analysis using an age- and tumor-stage-adjusted model identified epithelial PD-L1 expression at theITF as the only independent prognosticator. Epithelial PD-L1 expression at theITF was found to be an independent prognostic biomarker for OSCC in a cohort of Sudanese patients.

Worst Pattern of Invasion as a Predictor of Nodal Metastasis in Early-Stage Oral Squamous Cell Carcinoma.

About one-third of early stage oral cancer patients have occult nodal metastasis. High grade worst pattern of invasion (WPOI) is associated with an increased risk of nodal metastasis and poor prognosis. However, it still remains unanswered whether to perform an elective neck dissection for clinically node-negative disease or not. This study aims to evaluate the role of histological parameters including WPOI in predicting nodal metastasis in early-stage oral cancers. This analytical observational study comprised 100 patients of early-stage, node-negative, oral squamous cell carcinoma, admitted in the Surgical Oncology Department from April, 2018 till the sample size was reached. The socio-demographic data, clinical history, and findings of clinical and radiological examination were noted. The association of nodal metastasis with various histological parameters like tumour size, degree of differentiation, depth of invasion (DOI), WPOI, perineural invasion (PNI), lymphovascular invasion (LVI) and lymphocytic response was determined. SPSS 20.0 statistical tool; student's 't' test and chi-square tests were applied. While the buccal mucosa was the commonest site, the rate of occult metastasis was highest in the tongue. Nodal metastasis was not significantly associated with age, sex, smoking and primary site. While the nodal positivity was not significantly associated with tumour size, pathological stage, DOI, PNI and lymphocytic response, it was associated with LVI, degree of differentiation and WPOI. Increasing WPOI grade correlated significantly with the nodal stage, LVI and PNI, but not with DOI. WPOI is not only a significant predictor of occult nodal metastasis but can also be a novel therapeutic tool in the management of early-stage oral cancers. In patients with an aggressive WPOI pattern or other high-risk histological parameters, the neck can be addressed with either elective neck dissection or radiotherapy after wide excision of the primary tumor; otherwise, an active surveillance approach can be followed.

Worst pattern of invasion in oral squamous cell carcinoma is an independent prognostic factor.

IntroductionBiologic aggressiveness of OSCC (Oral Cavity Squamous Cell Carcinoma), has intrigued research in various prognosticating histopathological markers over past few decades. DOI (Depth of Invasion) is one such histopathological factor which affects outcomes and was included in the AJCC 8th edition TNM staging. Pattern of Invasion (POI) has been widely reported as an adverse prognostic factor associated with higher locoregional failure and poor prognosis. However, these factors are not utilized for treatment decision making and for outcome assessment.Materials and methodsThis is a retrospective analysis of 320 patients with OSCC who underwent treatment, from October 2018–February 2020. Clinic demographic details were extracted from electronic medical records. Univariate and multivariate analysis was done for the parameters. WPOI (Worst Pattern of Invasion) was correlated with all histopathological prognostic factors. Survival analysis was done using Kaplan Meier for WPOI type's I–V. DFS (Disease free Survival) was evaluated for different grades of WPOI.ResultsWe analyzed the results comparing, early and advanced T (Tumor) stages, cohesive WPOI I-III, non-cohesive WPOI IV-V. Univariate analysis showed a significant association of T-stage (p = 0.001), N (Nodal) -stage (p = 0.002), DOI (p = 0.008), PNI (Peri-neural invasion) (0.001) and Tumor differentiation Grade (p = 0.001). On multivariate analysis, non-cohesive WPOI (IV & V) showed significant association with grade, PNI, DOI (0.002, 0.033 & 0.033 respectively). Non-cohesive WPOI had significantly higher locoregional failures and short DFS.ConclusionPresence of invasive WPOI is associated with advanced T stage, poor differentiation, PNI, greater depth of invasion, and higher chances of nodal metastasis. WPOI is associated with poor DFS, treatment intensification in early stage disease with WPOI type IV & V may improve survival.

OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling

The Pattern Of Invasion (POI) of tumor cells into adjacent normal tissues clinically predicts postoperative tumor metastasis/recurrence of early oral squamous cell carcinoma (OSCC), but the mechanisms underlying the development of these subtypes remain unclear. Focusing on the highest score of POIs (Worst POI, WPOI) present within each tumor, we observe a disease progression-driven shift of WPOI towards the high-risk type 4/5, associated with a mesenchymal phenotype in advanced OSCC. WPOI 4-5-derived cancer-associated fibroblasts (CAFsWPOI4-5), characterized by high oxytocin receptor expression (OXTRHigh), contribute to local-regional metastasis. OXTRHigh CAFs induce a desmoplastic stroma and CCL26 is required for the invasive phenotype of CCR3+ tumors. Mechanistically, OXTR activates nuclear ERK5 transcription signaling via Gαq and CDC37 to maintain high levels of OXTR and CCL26. ERK5 ablation reprograms the pro-invasive phenotype of OXTRHigh CAFs. Therefore, targeting ERK5 signaling in OXTRHigh CAFs is a potential therapeutic strategy for OSCC patients with WPOI 4-5.

Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma.

This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC). Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence. One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence. TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

Relationship of histamine expression with chemokine balance in the tumor microenvironment of squamous cell carcinoma of the tongue.

Tumor-associated macrophages in the tumor microenvironment (TME), as a factor affecting lymphocytes, have received much attention. Both lymphocytes and macrophages can switch the expression of histamine receptors. In this study, we investigated the role of histamine in the TME of tongue squamous cell carcinoma (SCC). Sixty-seven patients with stage I tongue SCC were studied. Histamine was evaluated by the expression of L-histidine decarboxylase (HDC). Macrophages, T lymphocytes, and lymph vessel density, as well as the Ki-67 labeling index (LI) and depth of invasion (DOI), were compared with HDC expression. HDC expression was significantly affected by the TME. The DOI, worst pattern of invasion, and Ki-67 LI were associated with histamine expression. C-C motif chemokine ligand (CCL) 2 and CCL22 were co-expressed with histamine H1 and H2 receptors. Histamine expression was most affected by the DOI. Tongue SCC expressing histamine affected the TME via histamine receptors and chemokines.

Emerging histopathologic markers in early-stage oral tongue cancer: A systematic review and meta-analysis.

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin‐based histopathologic markers. Our meta‐analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease‐specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease‐free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost‐effective and can be incorporated in daily practice.