In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

UNASSIGNED: The current study aimed to assess the frequency of CDH1 promoter gene hypermethylation in gastric cancer and chronic gastritis and its correlation with clinicopathological aspects.
UNASSIGNED: Methylation-specific PCR was used to detect CDH1 promoter gene hypermethylation in 53 chronic gastritis patients and 40 gastric cancer patients along with normal adjacent tissues.
UNASSIGNED: The chronic gastritis group comprised 29 males and 24 females with a mean age of 51.8 ± 12.96 years, and 49.1 % of them were positive for H. pylori infection. The frequency of CDH1 hypermethylation in gastritis lesions was 18.8 %. CDH1 hypermethylation showed a significant correlation with H. pylori infection (p = 0.039), but no significant association was observed with other clinical features. The gastric cancer group consisted of individuals with a mean age of 65.4 ± 10.6, among them, 77.5 % were male and 22.5 % were female, 62.5 % had PT3 tumors, 40 % had PN1 lymph node involvement, and the majority (47.5 %) of samples were obtained from body segment. CDH1 hypermethylation was significantly associated with depth of invasion (p = 0.017) and nodal invasion (p = 0.041) in this group. In both groups, normal adjacent specimens lacked CDH1 hypermethylation, and there was no statistically significant correlation between CDH1 hypermethylation and age at which the tumor was diagnosed, gender, activity level, or tumor location.
UNASSIGNED: This study demonstrates that E-cadherin methylation is associated with some characteristics of chronic gastritis and gastric cancer. These findings support previous research indicating that CDH1 hypermethylation may play a significant role in the development of gastric cancer.

UNASSIGNED: Magnetic resonance imaging (MRI) is a routinely used imaging modality for pre-treatment radiologic evaluation of tongue carcinoma, providing accurate information regarding the extent of the disease.
UNASSIGNED: To investigate the role of MRI-derived depth of invasion and tumor thickness evaluation in squamous cell carcinoma of the tongue, and to assess if any correlation exists between depth of invasion, tumor thickness, nodal metastasis, muscles, and space involved.
UNASSIGNED: Thirty-three patients with oral squamous cell carcinoma of the tongue who had undergone pre-treatment MRI and excisional biopsy were included. The tumor thickness (TT) and depth of invasion (DOI) were evaluated on MRI and histopathologic images.
UNASSIGNED: The relation between different methodologies for assessing showed a very high correlation for the tumor tissue thickness (r = 0.99, p < 0.05) and depth of invasion (r = 0.82, p < 0.05). The tumor thickness and the depth of invasion increased with the loss of differentiation in the carcinoma histopathologically. As the depth of invasion increases, the extent of the spread of the carcinoma to tongue musculature, lingual septum, and spaces also increases.
UNASSIGNED: The present study has depicted a high correlation between the tumor thickness and the depth of invasion between MRI and histopathological findings and is the first of its kind to correlate DOI to the invasiveness of the disease.

BACKGROUND: The accurate indication for level IV dissection is crucial for preventing complications such as phrenic nerve damage and chylous fistulas in clinically N0 tongue cancer. Although the depth of invasion is an established independent risk factor for occult lymph node metastasis in tongue cancer, its relationship with level IV metastasis has not been evaluated. This study investigated the relationship between the depth of invasion and level IV nodal metastasis in clinically N0 tongue cancer.
METHODS: We retrospectively investigated clinical N0 patients who underwent glossectomy and level I-IV neck dissection. We examined lymph node metastasis, risk factors, and the relationship between depth of invasion and metastasis.
RESULTS: Our study included 58 patients, and no patient had isolated level IV metastasis. Additionally, there was no level IV metastasis in well-differentiated tumors. Tumor size, depth of invasion, differentiation, and perineural invasion were significantly associated with level IV neck metastasis. We found a critical tumor size of 2.5 cm and depth of invasion of 8 mm for level IV neck metastasis.
CONCLUSIONS: Based on our findings, we recommend that level IV dissection should be considered for poorly differentiated tumors, tumors greater than 2.5 cm in size, and those deeper than 8 mm. This study highlights the importance of depth of invasion as a prognostic factor for predicting level IV metastasis and suggests that our findings can be used to prevent unnecessary level IV dissections that may lead to complications in tongue cancer surgery.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Oral squamous cell carcinoma (OSCC) of the tongue is the most common type of oral cavity cancer, and tumor depth of invasion (DOI) is an important prognostic factor. In this study, we investigated the accuracy of intraoral ultrasound and magnetic resonance imaging (MRI) for assessing DOI in patients with OSCC. Histopathological measurement of DOI was used as a reference standard. We conducted a prospective study including patients planned for surgical treatment of OSCC in the tongue. The DOI was measured in an outpatient setting by intraoral ultrasound and MRI, and was compared to the histopathological DOI measurements. Bland-Altman analysis compared the mean difference and 95% limits of agreement (LOA) for ultrasound and MRI, and the Wilcoxon signed-rank test was used to test for significance. The correlation was evaluated using Pearson\'s correlation coefficient. We included 30 patients: 26 with T1 or T2 tumors, and 4 with T3 tumors. The mean difference from histopathology DOI was significantly lower for ultrasound compared to MRI (0.95 mm [95% LOA -4.15 mm to 6.06 mm] vs. 1.90 mm [95% LOA -9.02 mm and 12.81 mm], p = 0.023). Ultrasound also led to significantly more correct T-stage classifications in 86.7% (26) of patients compared to 56.7% (17) for MRI, p = 0.015. The Pearson correlation between MRI and histopathology was 0.57 (p < 0.001) and the correlation between ultrasound and histopathology was 0.86 (p < 0.001). This prospective study found that intraoral ultrasound is more accurate than MRI in assessing DOI and for the T-staging of oral tongue cancers. Clinical practice and guidelines should implement intraoral ultrasound accordingly.

UNASSIGNED: Tumour budding has been recognized as a morphologic marker of tumour invasion. Invasive characteristics such as depth of invasion, mode of invasion and worst pattern of invasion are potentially powerful parameters predicting the regional metastasis.
UNASSIGNED: This study was done to understand the significance of tumour budding and various characteristics of invasion and their impact on grading of oral squamous cell carcinoma.
UNASSIGNED: An immunohistochemical study was performed on tissue sections obtained from 34 paraffin-embedded blocks of clinically and histologically diagnosed cases of oral squamous cell carcinoma. The sections were stained with pan cytokeratin and observed under high power magnification.
UNASSIGNED: Tumour budding and the invasive patterns were found to be significant in OSCC. A proposed grading system based on tumour budding and cell nest was found to have a significant correlation with the WHO grading system.
UNASSIGNED: This study demonstrated the importance of using tumour buds as an additional parameter in the grading system and also assessed the importance of invasive patterns, cellular atypia and stromal contents in OSCC.

Tongue carcinoma constitutes 10.4-46.9% of all oral squamous cell carcinomas (OSCCs) and is notoriously known for invading tissues deeper than the evident gross margins. The deeper the tumor invades, the higher are its chances of future morbidity and mortality due to extensive neck dissection and risk of recurrence. Magnetic resonance imaging (MRI) is a noninvasive diagnostic aid used for measuring a preoperative tumor\'s depth of invasion (DOI) as it can efficiently outline soft tissue tumors from adjacent normal tissue. To assess various MRI modalities used in measuring DOI in tongue carcinoma and their reliability compared with other DOI measuring modalities. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022330866), and the following Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) Diagnostic Test Accuracy guidelines were performed. PubMed electronic database was searched using a combination of keywords for relevant articles in the English language since 2016. Critical appraisal was carried out using the Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) risk-of-bias (RoB) assessment tool. A weighted mean difference (WMD) was calculated between MRI and histopathological DOI along with pooled correlation and subgroup analysis, where possible. A total of 795 records were retrieved of which 17 were included in the final review with 13 included for meta-analysis. A high RoB was found for most studies for all parameters except flow and timing. WMD showed a statistically significant MRI overestimation of 1.90 mm compared with histopathology. Subgroup analysis showed the 1.5 Tesla machine to be superior to the 3.0 Tesla machine, while imaging sequence subgroup analysis could not be performed. MRI is a viable preoperative DOI measurement modality that can help in efficient treatment planning to decrease surgical morbidity and mortality.

UNASSIGNED: To understand the approach to interpretation along with challenges encountered in assessing pathological depth of invasion (pDOI) in oral squamous cell carcinoma (OSCC) as per 8th Edition of TNM-AJCC staging among oral and maxillofacial pathologists in India.
UNASSIGNED: A cross-sectional web-based survey was conducted (May 2021-October 2021) with a pre-validated 21-item questionnaire. Responses were stored in a Microsoft Excel worksheet and analysed by descriptive statistics using SPSS v 25.0.
UNASSIGNED: About 69.7% of the 267 respondents correctly defined pDOI while 13.1% measured the same from tumour surface. Among those not reporting pDOI, one-third of respondents (36.6%) lacked requisite awareness about 8th edition staging while more than half of them (55.4%) lacked proper tools to measure. The vst majority of the oral pathologists found pDOI measurement practically challenging (85.8%), mostly with difficulty in obtaining adjacent normal mucosa (77.9%). Selection of reference points of adjacent normal mucosa was divided between deepest point of rete ridge (43.1%), the closest rete ridge (28.8%) and the tip of highest submucosal papilla (15%).
UNASSIGNED: Underreporting of pDOI was observed owing to inherent challenges in measurement, thus ostensibly substituted with tumour thickness. Elaboration on reference points of adjacent normal mucosa is awaited.

The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.