Pattern of invasion of oral squamous cell carcinoma and its relation to the presence of nodal metastases - a review.

Squamous cell carcinomas of the oral cavity represent the largest group of malignancies in this area. Currently, there are many prognostic histopathological factors, according to which the maxillofacial surgeon in collaboration with the oncologist is able to determine the prognosis and subsequently also set an appropriate therapy. Nowadays, the squamous cell carcinoma invasion pattern in the area of the "invasive tumor front" seems to be a very important prognostic factor. The invasion pattern is connected to metastatic potential (and to the presence of subclinical microscopic metastases) and may well be the answer to why even early-stage tumors do not respond to standard therapy. That is to say, based on varying invasion pattern, oral cavity squamous cell carcinomas with identical TNM manifest varying clinical behavior and growth tendencies and a varying metastatic potential.

Prognostic Role of Tumor Budding and Worst Pattern of Invasion in Lymph Node Metastasis and Disease-Free Survival in Oral Squamous Cell Cancer Patients: Result from Central India's Regional Cancer Centre.

Aim: To study the role of pattern of invasion, tumor budding and other clinicopathological parameters in determining the risk of nodal metastases and disease-free survival in oral squamous cell cancer patients. Method: The data of 90 patients with oral squamous cell carcinoma who underwent surgery as their primary modality of treatment were retrospectively analysed. Predictive significance of clinicopathological parameters was assessed with Univariate analysis with Fisher exact test and unpaired t-test. The factors which were significant on Univariate analysis were then analysed with multivariate analysis using logistic regression model to find independent predictors. P value < 0.05 was considered significant. Disease free survival analysis was performed using Kaplan-Meier method and comparison done using the log-rank test for each group. Result: The age of the patients ranged from 22yrs to 72 years with male predominance (81.1%). The most common site of involvement was buccal mucosa. Significant factors predicting nodal metastases on univariate analysis were site (p = 0.031), grade (p = 0.012), T stage (p = < 0.001), Depth of invasion (p = < 0.001), perineural invasion (p = < 0.001), lymphovascular emboli (p = 0.018), tumor budding (p = < 0.001), pattern of invasion (p = < 0.001) and stroma (p = 0.037). On multivariate analysis tumor budding (p = 0.016), depth of invasion (p = 0.016) and perineural invasion (p = 0.044) were predictive of nodal metastasis. A statistically significant difference in 3year disease free survival was seen in infiltrative pattern of invasion and tumor budding which showed a p-value of 0.0372 and 0.0489 respectively. Conclusion: Based on the findings of the present study and review of previous articles tumor budding, worst pattern of invasion, host lymphocyte response should also be included in routine histopathology reporting of OSCC.

Assessment of Bone Invasion and Its Correlation With Brandwein-Gensler Criteria in Oral Squamous Cell Carcinoma.

Background The most prevalent form of head-neck cancer is squamous cell carcinoma (SCC). Apart from all sites like the tongue, labial mucosa, and buccal mucosa, the prevalence of oral squamous cell carcinoma (OSCC) is more common in gingivobuccal sulcus due to the habit of keeping tobacco quid. With regards to anatomical relationships in the mouth and proximity to bone, OSCC invades the maxilla and mandible. However, bone invasion significantly influences the pathological staging of OSCC. Histological parameters such as Brandwein-Gensler worst pattern of invasion (WPOI), lymphocytic host response (LHR), and perineural invasion (PNI) hold significance for determining the need for adjuvant therapy. This study aims to correlate Brandwein-Gensler Criteria (BGC) with bone invasion and also to include the bone invasion criteria as a prognostic parameter in OSCC. This study aimed to assess bone invasion and correlate it with Brandwein-Gensler criteria in OSCC. Methods The research was conducted retrospectively, analyzing 65 cases of OSCC that underwent surgical intervention. Data was gathered from the Oral Pathology department's archives at Sharad Pawar Dental College (SPDC), Wardha. Pathologists assessed bone invasion without the knowledge of other factors to minimize bias. Subsequently, the cases were classified into well-differentiated (WDSCC), moderately differentiated (MDSCC), and poorly differentiated squamous cell carcinomas (PDSCC) based on histological grading, followed by the evaluation of WPOI, LHR, and PNI using the Brandwein-Gensler risk scoring system. Results This study found a notable association between bone invasion and BGC, with a calculated significance level of p = 0.047. LHR shows patterns as 1, 2, and 3. There were five (7.6%) cases with pattern III, 45 (69.23%) cases with pattern II, and 15 (23.08%) cases with pattern I. Similarly, PNI is scored as 0, 1, and 3. There were seven (10.77%) cases with score 3, 17 (26.15%) with score 1, and 41 (63.03%) with score 0. In the case of the WOPI, which is classified as patterns I to V, there were seven (10.77%) cases with pattern V, 27 (41.54%) cases with pattern IV, 23 (35.38%) cases with pattern III, and eight (12.231%) cases with pattern II, whereas no cases were noted with pattern I. Conclusion Although bone invasion and BGC are independent parameters, the BGC score should be considered in treatment planning. Patients with bone invasion and those with a higher BGC score should be strongly considered for adjuvant treatment.

Significance of Worst Pattern of Invasion-5 in Early-Stage Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: There is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC. METHODS: This was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. RESULTS: On univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95% CI 2.83-15.44, p < 0.0001) and extratumoural LVI (odds ratio 9.97, 95% CI 2.19-45.35, p = 0.003) were independently associated with OS. Postoperative radiotherapy (odds ratio 0.40, 95% CI 0.19-0.87, p = 0.02) and non-tongue subsite (odds ratio 3.03, 95% CI 1.70-5.39, p = 0.0002) were also significantly associated with OS on multivariate analysis. CONCLUSION: Satellite nodules and extratumoural LVI correlated significantly with survival outcomes in our early-stage OSCC cohort. Further study is required to investigate the benefit of adjuvant treatment in these cases and to ascertain if WPOI-5 parameters including satellite nodules should be mandatory reporting data elements.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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

BACKGROUND/AIM: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Impact of worst pattern of invasion on prognosis of oral squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The relationship between the worst pattern of invasion (WPOI) and the prognosis of oral squamous cell carcinoma (OSCC) remains controversial. This systematic review and meta-analysis was performed to determine the impact of the WPOI on the prognosis of OSCC. METHODS: Studies from six databases were assessed for quality using the Newcastle-Ottawa Scale, and data were analyzed using Stata software. RESULTS: Eighteen studies involving 3954 patients showed that patients with a WPOI of 4 to 5 had significantly worse overall survival, disease-specific survival, and disease-free survival than patients with a WPOI of 1 to 3. Significant associations of the WPOI with locoregional recurrence and mortality were found. CONCLUSION: A higher WPOI was significantly associated with a worse prognosis of OSCC across various outcomes. Incorporating the WPOI into standard histopathological assessments may guide personalized treatments and improve outcomes.

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

BACKGROUND: 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). METHODS: 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. RESULTS: WPOI-5 predicts OCM in pT1 patients, compared with WPOI-4/WPOI-3 (p < 0.0001). Most pT1 WPOI-5 tumors had DOI of 4-5 mm (24/59 or 40.7%). Only two pT1 WPOI-5 tumors had DOI < 4 mm (3.0 and 3.5 mm). If END were performed in this pT1 cohort for all WPOI-5 OSC patients regardless of DOI, OR all OSC patients with DOI ≥ 4 mm 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. CONCLUSIONS: DOI ≥ 4 mm is the dominant predictor of OCM. For the rare WPOI-5 OSC with DOI < 4 mm, 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.

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.

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

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

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.

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.

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 < 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.

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

Introduction: Biologic 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 methods: This 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. Results: We 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. Conclusion: Presence 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.

Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features.

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.

Biopsy pattern of invasion type to determine the surgical approach in early-stage oral squamous cell carcinoma.

Depth of invasion (DOI) and pattern of invasion (POI) indicate tumor invasiveness of oral squamous cell carcinoma (OSCC). However, preoperative DOI evaluation is challenging, and the correlations between DOI and POI are unknown. We aimed to assess DOI and worst pattern of invasion (WPOI) in early-stage OSCC, and evaluate the preoperative predictive ability of biopsy pattern of invasion (BPOI) for WPOI and DOI. This retrospective study included n = 444 OSCC patients with pT1-2N0M0. The prognostic value of DOI, WPOI, and BPOI and the predictive prognostic option for WPOI and DOI by BPOI were assessed. WPOI (1-3 vs 4-5), but not BPOI, predicted the lowest survival rate and highest DOI. To evaluate the difference between WPOI and BPOI, we conducted a POI type-matching analysis of patients with BPOI1-4 and WPOI1-5. Based on each WPOI type, the false-prediction rates (FPR) of BPOI types 1 (n = 23), 2 (n = 89), 3 (n = 252), and 4 (n = 80) were 52.17%, 52.81%, 36.90%, and 0%, respectively. BPOI4 perfectly predict WPOI 4-5. As the false-predicted BPOI 1-2 was almost WPOI2-3 (79.7%), regardless of the existed FPR, patients with BPOI1-2 have longer survival and lower DOI than those with BPOI 4. However, this phenomenon was not observed in BPOI3, because all false-predicted BPOI3 were WPOI4-5 with a high DOI. We provide an alternative predictive prognostic option for WPOI and DOI by evaluating BPOI during OSCC surgical planning, with the recommendation of conservative treatment in patients with BPOI 1-2.

Worst pattern of invasion - type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset.

BACKGROUND: A proportion of early-stage node-negative oral squamous carcinoma patients fail despite complete surgical resection. Adjuvant treatment in early oral cancer is controversial and is often individualized based on stage, depth, and margin status. AIMS: We reviewed various histological markers in pT1/T2N0 cases, resected upfront with elective nodal dissection, with an emphasis on tumor-tissue interface characteristics of the worst pattern of invasion (WPOI), tumor cell nest size (sCNS), budding and lymphocytic host response (LHR), to assess their prognostic significance. MATERIALS AND METHODS: Archived blocks of 95 cases were reviewed. Tumor stage, grade, size, depth of invasion, lymphovascular, and perineural invasion, WPOI, LHR, sCNS, and tumor bud (single cells or <5 cell clusters) score were recorded. STATISTICAL ANALYSIS: Prognostic significance was statistically analyzed using SPSS software version 20. RESULTS: Depth of invasion (P = 0.008), WPOI- 4 and 5 (P = 0.033), sCNS (<5 cells) at tumor interface (P = 0.010), high bud count (≥3 buds/40 × hpf) (P = 0.021) and poor LHR (P = 0.019) correlated significantly with poor disease-free survival on univariate analysis. However, on multivariate analysis only LHR and WPOI-4 (that is presence of small cell nests or buds) were significant, with high hazard ratio of 4.351 (95% CI 1.290-14.676, P = 0.018) and 5.019 (95% CI 1.212-20.789, P = 0.026), respectively. CONCLUSION: We propose mandatory reporting of WPOI-4 at the tumor interface and absence of LHR, as significant markers of poor prognosis in early-stage oral cavity squamous carcinoma.

Tumor Budding and Worse Pattern of Invasion Can Predict Nodal Metastasis in Oral Cancers and Associated With Poor Survival in Early-Stage Tumors.

The management and prognosis of oral squamous cell carcinoma (OSCC) depend on tumor stage and lymph node (LN) metastasis status. Early-stage (T1/T2 N0M0) OSCC comprises a heterogeneous group. We evaluated the role of histological parameters including worst pattern of invasion (WPOI) and tumor budding to determine the risk of LN metastasis in cases of OSCC and to determine the risk of recurrence and death in early-stage OSCC in north Indian patients. All cases of buccal mucosa and tongue SCC which underwent excision over 4 and half years were reviewed for histological parameters including histologic grade, WPOI, tumor budding, lymphovascular emboli (LVE), perineural invasion (PNI), depth of invasion (DOI), host lymphocyte response, and stromal response and compared to LN metastasis. Clinical follow-up of early-stage tumor was obtained and compared. A total of 126 cases of OSCC were included, of which 48 showed LN metastasis. Histological grade, WPOI, tumor budding (≥3/×40 field), LVE, and PNI were significantly associated with risk of LN metastasis. On multivariate analysis, WPOI and tumor budding were 2 most significant factors. Among the early-stage tumors with available follow up (n = 48), DOI, WPOI, tumor budding, and LVE were associated with a shorter overall survival, although it was not statistically significant. To conclude, WPOI and tumor budding are important risk factors for predicting LN metastasis in all stages of OSCC and associated with a poorer outcome in early-stage tumors. These are easy and reliable prognostic factors and should be included in the histopathological reporting guidelines.

Postoperative radiotherapy is dispensable for OSCC patients with micrometastases in lymph nodes.

Lymph node metastasis is a decisive factor for performing postoperative radiotherapy for oral squamous cell carcinoma (OSCC). However, whether OSCC patients with only micrometastasis need postoperative radiotherapy is unclear. In this study, OSCC patients (n = 311) with negative (n = 247), only micrometastasis (n = 44) and macrometastasis (n = 20) were detected and selected by HE staining. Micrometastasis was re-assessed using immunohistochemical staining of cytokeratin (CK) in HE-negative patients to find out the false negative cases. The results indicated that, among the negative lymph node cases (n = 247), the positive rate of CK was 4.94% (n = 12). Besides, the clinical features of the primary tumor in relation to the only micrometastatic status and the value of the postoperative radiotherapy on the only micrometastasis patients were evaluated. Patients with only micrometastasis had higher T stage and inferior worst pattern of invasion (WPOI) than patients without micrometastasis, but they had longer overall survival (OS), metastasis-free survival (MFS), and disease-free survival (DFS) than macrometastasis patients. However, the survival time of only micrometastasis patients with or without postoperative radiotherapy was comparable, even in patients with inferior WPOI. Radiotherapy, however, may only benefit patients with IV/V levels of micrometastasis. These data indicated that postoperative radiotherapy is dispensable for only micrometastasis OSCC patients.