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. 2021 May 14;41(2):108–119. doi: 10.14639/0392-100X-N1056

Table I.

Pathological markers predictive of loco-regional recurrence and prognosticators.

Marker Definition Notes
Depth of Invasion (DOI) DOI is measured from the level of the basement membrane of the closest adjacent normal mucosa. A “plumb line” is dropped from this plane to the deepest point of tumour invasion 38,42 Included in T1-3 Categories for Oral Cavity Cancer, TNM Staging Manual 8th Edition 37
The T category increases with every interval of 5 mm
Tumour Thickness (TT) TT is measured from the surface of the tumour to the deepest point of invasion. In exofitic and ulcerated lesions TT is measured from the imaginary line reconstructing the intact mucosa to the deepest point of invasion 42,48
TT1 is measured from the level of adjacent mucosa to the deepest point of tumour invasion 49
TT2 is the distance from the bottom of most adjacent dysplastic abnormal rete pegs to the deepest point of invasion 49
TT3 is measured as distance from the epithelial junction of the most adjacent dermal papillae to the deepest point of tumour invasion 49
As defined before publication of the 8th TNM Edition 42,48 or defined as an alternative to the proposed classification 49
Rete pegs: epithelial extensions in the connective tissue underlying the mucosa 49
Radiological Depth of Invasion (rDOI) rDOI is measured by drawing a perpendicular line from the reference line to the deepest point of the tumour 50 Radiological definition of DOI is also reported in TNM 8th Edition 37. The reference line connects the junction of the tumour surfaces and of the normal mucosa on both sides 50
Tumour Budding (TB) TB is defined as the presence of either isolated single cells or small-cell clusters comprising fewer than five cells scattered in the stroma ahead of the invasive tumour front 15,45,48,51-54 TB is speculated to be the result of interactions between cancer cells and tumour microenvironments. It is expression of loss of cohesion and active invasive cellular movement 55. It is considered the first step in metastasis of a solid tumour
Pattern of Invasion (POI) POI at the tumour-host interface of oral cancer is graded 1 to 5. Tumour dispersion is assessed at the advancing tumour edge.
The most common WPOI-5 phenotype is tumor dispersion through soft tissue. Dispersed extratumoral peri-neural invasion, or extratumoral lymphovascular invasion, also can qualify for classification as WPOI-5 37
Worst Pattern of Invasion (WPOI) WPOI-5 (POI Grade 5) consists of dispersed, discontinuous growth pattern, with a defined tumour dispersion cutoff of 1 mm 37,54
Tumour-Stroma Ratio (TSR) TSR defines the interactions between cancer cells and intra-tumoural stroma, which is the main component of the microenvironment 46,56,57 These interactions are important for both cancer initiation and progression: the proportion of this stroma acts as a key regulator in cancer biology and could provide strategies for biological cancer treatment
Peri Neural Invasion (PNI) PNI is defined as the tumour cell infiltration in any layer of the nerve sheath or tumour in close proximity involving more than one-third of the nerve circumference 49 PNI should be subclassified as either intratumoral or extratumoral, and as focal or multifocal. Extensive multifocal PNl is usually extratumoral and frequently associated with a “strand-like” tumour phenotype 37
Lympho Vascular Invasion (LVI) LIV is defined as the detection of tumour epithelial cells within or attached to the endothelial cell lining of the vascular space 49 LIV should be reported as either intratumoral or extratumoral, as well as focal or multifocal 37