Immunohistochemical Comparison of Salivary Gland SCC and Cutaneous SCC of the Face
The key distinguishing immunohistochemical markers between salivary gland squamous cell carcinoma (SG-SCC) and cutaneous squamous cell carcinoma (cSCC) of the face are p63/p40 and CK5/6 positivity in both, but SOX10 negativity in cSCC and Ber-EP4 positivity in cSCC but not SG-SCC.
Comparative Immunohistochemical Profile
| Marker | Salivary Gland SCC | Cutaneous SCC (Face) |
|---|---|---|
| p63/p40 | Positive (>80%) | Positive (>80%) |
| CK5/6 | Positive (>80%) | Positive (>80%) |
| SOX10 | Negative | Negative |
| Ber-EP4 | Negative | Positive (variable) |
| TTF-1 | Negative | Negative |
| CK7 | Variable/Focal | Variable/Focal |
| Cam 5.2 | Variable/Focal | Variable/Focal |
Interpretation of Key Markers
Markers Positive in Both SG-SCC and cSCC
p63/p40: Both are highly sensitive markers for squamous differentiation. p63 shows 100% sensitivity for SCC in effusion samples with 80% specificity, while p40 demonstrates 100% sensitivity with 90% specificity 1. These markers are consistently positive in both SG-SCC and cSCC.
CK5/6: This is a reliable marker for squamous differentiation with approximately 80-85% of SCCs showing CK5/6 positivity regardless of origin 2. The combination of p63 and CK5/6 positivity has a specificity of 96% for squamous cell carcinomas 2.
Distinguishing Markers
Ber-EP4: This is a critical distinguishing marker. cSCC is typically negative for Ber-EP4, while basal cell carcinomas are positive 3. However, in the context of differentiating SG-SCC from cSCC, Ber-EP4 can show variable positivity in cutaneous SCC but is typically negative in SG-SCC 4.
SOX10: While SOX10 is positive in many salivary gland tumors (including acinic cell carcinoma, adenoid cystic carcinoma, and basal cell adenoma/adenocarcinoma), it is typically negative in both SG-SCC and cSCC 5.
Diagnostic Algorithm
Initial Screening: Use p63/p40 and CK5/6 to confirm squamous differentiation in both tumors
- Strong, diffuse positivity in both markers supports SCC diagnosis regardless of origin
Distinguishing Origin:
- Test for Ber-EP4
- Positive: Favors cutaneous origin
- Negative: Favors salivary gland origin or poorly differentiated cSCC
- Test for Ber-EP4
Confirmatory Testing:
- If origin remains unclear, consider clinical context and additional markers:
- SOX10: Negative in both SG-SCC and cSCC (but positive in many other salivary gland tumors)
- CK7: Variable in both, but more commonly focal positive in SG-SCC
- TTF-1: Negative in both (useful to rule out lung primary)
- If origin remains unclear, consider clinical context and additional markers:
Clinical Implications and Pitfalls
Diagnostic Pitfall: Relying solely on p63 or CK5/6 will not distinguish between SG-SCC and cSCC as both are typically positive for these markers.
Sampling Considerations: Ensure adequate tissue sampling, as focal staining patterns can lead to false negatives, especially in poorly differentiated tumors.
Interpretation Challenges: Some cutaneous SCCs may show focal CK7 positivity, particularly those with a pagetoid pattern 6, which can cause confusion with salivary gland primaries.
Panel Approach: Always use a panel of markers rather than a single marker, as individual marker expression can vary based on tumor differentiation and sampling.
Clinical Correlation: Immunohistochemical findings should always be correlated with clinical presentation, as the location and appearance of the tumor provide critical diagnostic context.
By systematically applying this immunohistochemical panel and understanding the expected staining patterns, pathologists can more accurately distinguish between salivary gland SCC and cutaneous SCC of the face, which has important implications for treatment planning and prognosis.