Cutaneous SCC Grading

Qualitative 4-tier feature-checklist grading plus the Broders % quantitative system, with a combined 2-tier risk summary.

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Grading of cutaneous SCC is not standardized, and grade is prognostically important despite weak-to-moderate interobserver concordance in the literature. This tool is an educational and documentation-support aid only and does not replace professional pathologist judgment, institutional protocols, or the current edition of the applicable classification.

Reference

Two independent systems

Grading of cutaneous SCC is not standardized. Two approaches are offered side by side, as in the source protocol: a classic 4-tier qualitative system based on histologic features, and the Broders quantitative system based on the percentage of undifferentiated tumor. Neither is mandatory nor mutually exclusive, and they are not guaranteed to agree on every case.

Classic qualitative grading (4-tier)

Grade	Criteria
G1	Well-differentiated tumors characterized by squamous epithelium that frequently shows easily recognizable and often abundant keratinization. Intercellular bridges are readily apparent. There is minimal pleomorphism, and mitotic figures are mainly basally located.
G2	Moderately differentiated tumors show more structural disorganization in which squamous epithelial derivation is less obvious. Nuclear and cytoplasmic pleomorphism are more pronounced, and mitotic figures may be numerous. Keratin formation is typically limited to keratin pearls, horn cysts, and scattered individually keratinized cells.
G3	In poorly differentiated tumors it may be difficult to establish squamous differentiation, usually by identification of rare intercellular bridges or small foci of keratinization.
G4	Used to denote anaplastic or undifferentiated tumors.

Grade 4 is an override

The source frames G4 as a distinct anaplastic/undifferentiated category, so any G4 finding is treated as sufficient on its own for a Grade 4 result. Grade 3 is decisive only if no Grade 4 feature is present, and Grade 2 only if neither Grade 3 nor Grade 4 applies. Grade 1 is the default when none of the higher-grade feature sets apply.

Broders classification (quantitative, % undifferentiated)

A single-parameter quantitative grading system, described as a popular alternative to the qualitative 4-tier system.

Practical estimation technique: the source defines Broders grade by % undifferentiated tumor but does not specify a field-counting protocol. The HPF method estimates that percentage as the proportion of HPFs in which undifferentiated morphology predominates, out of total representative HPFs assessed — mathematically equivalent to comparing the summed HPF area of each category, since all fields share the same area. Apply it per your laboratory's validated sampling practice, or use direct % entry instead.

Grade	% undifferentiated tumor
G1	Less than 25% is undifferentiated
G2	≥25% but <50% is undifferentiated
G3	≥50% but <75% is undifferentiated
G4	≥75% is undifferentiated

Prognostic significance & management relevance

Grade has remained a key independent prognosticator in cutaneous SCC despite limited data showing weak-to-moderate interobserver concordance.

From a management perspective, grade is typically reduced to two tiers, with poorly differentiated tumors (Grades 3 and 4) constituting the high-risk category. However, limited evidence suggests that even moderately differentiated tumors (Grade 2) may show a higher risk for subclinical spread requiring more layers of clearance by Mohs micrographic surgery. Of note, it is this grade of tumors that appears to show the highest interobserver variability.

The application of grading to subtypes in cutaneous SCC is not well studied, though some subtypes (e.g., verrucous SCC) have a well-established intrinsic biologic behavior. It is thus reasonable to use the "not applicable" category when a subtype comprises the bulk of the tumor.

Sources

McKee PH, Calonje E, Brenn T, Lazar AJ, Billings SD. Tumors of the surface epithelium. In: McKee's Pathology of the Skin with Clinical Correlations. 5th ed. Philadelphia, PA: Elsevier Mosby; 2020.

Broders AC. Squamous cell epithelioma of the lip. J Am Med Assoc. 1920;74:656-664.

Prezzano JC, Scott GA, Lambert Smith F, Mannava KA, Ibrahim SF. Concordance of Squamous Cell Carcinoma Histologic Grading Among Dermatopathologists and Mohs Surgeons. Dermatol Surg. 2021 Nov 1;47(11):1433-1437.

Kyrgidis A, Tzellos TG, Kechagias N, Patrikidou A, Xirou P, Kitikidou K, Bourlidou E, Vahtsevanos K, Antoniades K. Cutaneous squamous cell carcinoma (SCC) of the head and neck: risk factors of overall and recurrence-free survival. Eur J Cancer. 2010 Jun;46(9):1563-1572.

Lohmann CM, Solomon AR. Clinicopathologic variants of cutaneous squamous cell carcinoma. Adv Anat Pathol. 2001;8(1):27-36.

Eversman A, Tracey EH, Michalik D, Rodriguez M, Varra V, Briskin IN, Vidimos AT, Poblete-Lopez CM. Moderate differentiation is a risk factor for extensive subclinical spread of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2021 Dec;85(6):1606-1608.

Source document: CAP Cancer Protocol, HN.Skin_Cutaneous_1.2.0.0.REL_CAPCP.