Table 1.
Risk factors for high-risk cSCC in current guidelines are summarized. The presence of any high-risk factor places the patient in the high-risk category.
| High-Risk Factors | European 2020 [1] | US NCCN 2022 [12] | UK BAD 2020 [13] | ||
|---|---|---|---|---|---|
| High Risk for Recurrence (Local or Metastatic) | High-Risk Factor for Local Recurrence, Metastasis, or Disease-Specific Death | Very High Risk for Local Recurrence, Metastasis, or Disease-Specific Death | High Risk for Local Recurrence, Nodal Metastasis, Or Disease-Specific Death | Very High Risk for Local Recurrence, Nodal Metastasis, Or Disease-Specific Death | |
| Tumor-Related High-Risk Factors | |||||
| Tumor diameter | >20 mm | Trunk, extremities >2 cm–≤4 cm | >4 cm any location | >20–40 mm | >40 mm |
| Localization | On temple/ear/lip | Head, neck, hands, feet, pretibial, and anogenital (any size) | On ear/lip | - | |
| Thickness | Thickness > 6 mm or Invasion beyond subcutaneous fat |
- | >6 mm or Invasion beyond subcutaneous fat |
Thickness > 4–6 mm | Thickness > 6 mm |
| Invasion | Invasion into subcutaneous fat | Invasion beyond subcutaneous fat | |||
| Differentiation | Poor grade differentiation | - | Poor grade differentiation | Poor grade differentiation | - |
| Histological feature | Desmoplasia | Acandtholytic (adenoid), adenosquamous, or metaplastic (carcinosarcomatous) | Desmoplasia | Lymphovascular invasion | High-grade histological subtype—adenosquamous, desmoplastic, spindle/sarcomatoid/metaplastic |
| Perineural invasion (PNI) | Histological/symptomatic/radiological PNI | Yes | PNI of a nerve lying deeper than the dermis or measuring ≥ 0.1 mm | Perineural invasion—dermal only; nerve diameter < 0.1 mm | Perineural invasion present in named nerve; nerve ≥0.1 mm; or nerve beyond dermis |
| Lymphatic or vascular involvement | - | - | Yes | - | - |
| Bone erosion/invasion | Bone erosion | - | - | - | Any bone invasion |
| Tumor on scar/chronic inflammation/RT | - | Site of prior RT or chronic inflammation | - | Tumor arising within scar or area of chronic inflammation | - |
| In-transit metastasis | - | - | - | - | In-transit metastasis |
| Borders | - | Poorly defined | - | - | - |
| Primary vs recurrent | - | Recurrent | - | - | - |
| Rapidly growing tumor | - | Yes | - | - | - |
| Neurologic symptoms | - | Yes | - | - | - |
| Patient-Related Risk Factors | |||||
| Immunosuppression | Yes | Yes | - | Iatrogenic IS or biological therapies, frailty and co-morbidities, HIV, HAART | As for high risk, especially SOTRs, hematological malignancies, such as CLL or myelofibrosis, other significant IS |
| Extrinsic Risk Factors | |||||
| Positive margins | Yes | - | - | One or more involved or close margin in a pT1 tumor. Close margins in a pT2 tumor. | One or more involved or close margin in a high-risk tumor. |
| Grade of recommendation | B (recommendation) | - | Category 2A (lower-level evidence, uniform NCCN consensus) | GPP (informal consensus) | GPP (informal consensus) |