Depth of invasion versus tumour thickness in early oral tongue squamous cell carcinoma: which measurement is the most practical and predictive of outcome?

Abstract

Aims: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging introduced depth of invasion (DOI) into the pT category of oral cavity squamous cell carcinoma. However, we noted multiple practical obstacles in accurately measuring DOI histologically in our daily practice.

Methods and results: To compare the prognostic effects of DOI and tumour thickness (TT), a meticulous pathology review was conducted in a retrospective cohort of 293 patients with AJCC 7th edition pT1/T2 oral tongue squamous cell carcinoma. Overall survival (OS) and nodal metastasis rate at initial resection were the primary and secondary outcomes, respectively. We found that TT and DOI were highly correlated with a correlation coefficient of 0.984. The upstage rate was only 6% (18 of 293 patients) when using TT in the pT stage compared with using DOI. More importantly, DOI and TT, as well as pT stage using DOI and pT stage using TT, performed identically in predicting risk of nodal metastasis and OS.

Conclusions: We therefore propose to replace DOI, a complicated measurement with many challenges, with TT in the pT staging system.

Keywords: AJCC staging; depth of invasion; oral tongue squamous cell carcinoma; prognosis; tumour thickness.

Figure 1.. Definition of tumor thickness (TT) and depth of invasion (DOI) using AJCC staging manual 7^th and 8^th editions ^, in tumor with a flat surface (A), an ulcerated endophytic surface (B), and a polypoid/exophytic architecture (C and D).

TT (green line) is measured from the surface of the tumor to the deepest point of invasion. In ulcerated tumor, an alternative definition of TT (blue line) measuring TT from ulcer bed to deepest point of invasion is also proposed by AJCC 7^th edition. DOI (black lines) is measured from an imaginary line connecting the basement membrane of normal squamous mucosa on both sides of the tumors perpendicularly to the deepest point of invasion. In panel C: the DOI is 0 mm as the tumor is entirely exophytic. However, high power view shown in panel D clearly demonstrates invasion of the carcinoma into skeletal muscle (M). In scenarios A and B, TT is slightly greater than DOI. The alternative measurement of TT is much less than DOI in ulcerated lesions. In exophytic lesions, TT is much greater than DOI.

Figure 2.. Pathologic challenges in measuring depth of invasion (DOI) in oral tongue squamous cell carcinoma.

(A) The normal tongue mucosa has a curved (convex) surface with a wavy and curved basement membrane (green contour). (B-C) and DOI measured perpendicularly from the imaginary straight line connecting the basement membrane of the rete of adjacent normal squamous mucosa (black lines) results in marked underestimation of the actual DOI for a lateral tongue tumor (B) and an anterior tongue tumor (C). Note the elongated retes of papillae of the dorsum of the tongue (DO) compared to the rete of the ventral tongue (V). (D) A carcinoma with normal mucosa limited to one side of the tumor. The other side does not contain normal mucosa due to positive surgical resection margin. DOI measured perpendicularly from the straight line of basement membrane of normal mucosa results in an oblique measurement (black lines). Green line: tumor thickness measured perpendicular to the tumor surface. (E) DOI cannot be measured in this tumor as there is no adjacent normal mucosa within the section. (F) The adjacent normal squamous mucosa has elongated rete ridges. Measuring DOI from the very end of the rete as defined by AJCC 8^th edition disregards the invasive carcinoma located between the upper boundary (blue line) and lower boundary (black line) of basement membrane.

Figure 3.

Correlation between tumor thickness and depth of invasion.

Figure 4.

Staging of the study cohort using AJCC 7^th, AJCC 8^th and proposed pT categories, Alluvial flow diagram .

Figure 5.

Kaplan Meier curves for overall survival. Shaded areas represent 95% Hall-Wellner Bands.