Tumour budding
Tumour budding; intratumoral / peritumoral budding; cell budding; small-cell budding
Tumour budding is the presence of single tumour cells or small clusters of ≤ 4 cells at the invasive front (or within the tumour body, depending on definition). It is best established as an adverse prognostic feature in colorectal cancer, where it predicts nodal metastasis and survival independent of conventional staging. Increasing evidence supports its prognostic role in cutaneous squamous cell carcinoma — high-grade tumour budding (≥ 10 buds in a 0.785 mm² high-power field at the invasive front) is associated with nodal metastasis, disease-specific death and locoregional recurrence in multiple cohorts. Reporting is increasingly incorporated into RCPath cSCC datasets but standardisation is still evolving; expect tumour budding to feature more prominently in future cSCC staging systems.
Definition
- Tumour bud — single tumour cell or small cluster of ≤ 4 cells at the invasive front (peritumoral budding) or within the tumour body (intratumoral budding).
- Counted in a single 0.785 mm² (or equivalent) high-power field at the invasive front "hotspot".
- Grading (International Tumor Budding Consensus Conference 2016, for colorectal but adopted for cSCC):
- Bd1 (low) — 0–4 buds.
- Bd2 (intermediate) — 5–9 buds.
- Bd3 (high) — ≥ 10 buds.
- Reflects epithelial-mesenchymal transition activity at the tumour front — a biological correlate of metastatic potential.
Role in cSCC
- Multiple cohort studies — high-grade tumour budding (Bd3) in cSCC associated with:
- Significantly higher nodal-metastasis risk.
- Higher disease-specific death.
- Higher locoregional recurrence.
- Independent of established BWH / AJCC 8 T-stage in multivariable analyses.
- Particularly informative in lip cSCC and head-and-neck cSCC.
- RCPath cSCC dataset — tumour budding is a desirable / increasingly reported item.
- Not yet incorporated into BWH or AJCC 8 staging — but candidate for future iterations.
Clinical implications
- High-grade tumour budding (Bd3) in an otherwise low-stage cSCC — discuss at MDT for upstaging considerations.
- May influence:
- Decision for adjuvant radiotherapy.
- Threshold for sentinel-node consideration (selected cases).
- Surveillance intensity.
- Not yet a stand-alone treatment-decision criterion in UK practice but supports overall risk assessment.
- Specialist dermatopathology review recommended for budding assessment — inter-observer variability moderate.
Broader context
- Tumour budding originated as a concept in colorectal cancer where it is part of formal pathology reporting.
- Adopted in oral / head-and-neck SCC pathology — significant prognostic value demonstrated.
- Increasing adoption in cSCC; standardisation efforts ongoing.
- Related concepts:
- Epithelial-mesenchymal transition (EMT) — the biology underlying tumour budding.
- Worst Pattern of Invasion (WPOI) — alternative invasive-front grading system used in oral SCC.
- Stroma-immunoscore / TILs — see TILs.
- Likely to be incorporated into future cSCC staging revisions.
References
- Lugli A et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod Pathol; 2017.
- Brinkman D et al. Tumor budding is an adverse prognostic factor in cutaneous squamous cell carcinoma — meta-analysis. Br J Dermatol; 2021.
- Royal College of Pathologists. Dataset for histopathological reporting of primary invasive cutaneous squamous cell carcinoma and regional lymph nodes. G124. London: RCPath; February 2019.
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