What is the recommended immunohistochemistry (IHC) panel for diagnosing basal cell carcinoma in adults with a history of skin lesions or at high risk for skin cancer?

Immunohistochemistry for Basal Cell Carcinoma

Immunohistochemistry is not routinely recommended for diagnosing basal cell carcinoma when standard histological examination with hematoxylin and eosin staining provides a clear diagnosis. 1 However, when the diagnosis is uncertain or when differentiating BCC from other basaloid tumors, a specific IHC panel can be highly valuable.

When to Use IHC for BCC

IHC should be reserved for specific diagnostic challenges:

• Confirming melanocytic versus non-melanocytic nature of pigmented lesions with unusual presentations, particularly non-pigmented lesions 1
• Distinguishing BCC from squamous cell carcinoma when histologic features overlap 2
• Differentiating BCC from basosquamous carcinoma, which requires different clinical management 2
• Separating BCC from benign mimics such as trichoepithelioma 3

Recommended IHC Panel

First-Line Markers (Highest Diagnostic Value)

Ber EP4 is the single most specific marker for BCC, showing 100% positivity in basal cell carcinomas while remaining completely negative in squamous cell carcinomas. 2 This marker should be your primary choice when differentiating BCC from SCC.

• Ber EP4: Positive in 100% of BCCs, negative in all SCCs 2
• EMA (Epithelial Membrane Antigen): Negative in BCCs, positive in 96% of SCCs (22 of 23 cases) 2

Supplementary Markers

When Ber EP4 and EMA are insufficient or when broader differential diagnosis is needed:

• Bcl-2: Shows 100% positivity in BCCs versus only 3.5% in SCCs 4
• CD10: Demonstrates 75.8% positivity in BCCs versus 0% in SCCs 4
• CD34: Useful for stromal differentiation patterns 3
• Cytokeratin 15: Part of extended panels for complex cases 3
• D2-40: Contributes to differentiation models 3

Practical Diagnostic Algorithm

For suspected BCC with diagnostic uncertainty, use this two-marker approach first:

1. Order Ber EP4 and EMA simultaneously 2

   • If Ber EP4 positive AND EMA negative → Confirms BCC
   • If Ber EP4 negative AND EMA positive → Confirms SCC
   • If both positive in different areas → Suggests basosquamous carcinoma

2. Add Bcl-2 and CD10 if initial markers are equivocal 4

   • Combined Bcl-2 and CD10 positivity detects BCC with 88% accuracy and 100% specificity 4

Critical Pitfalls to Avoid

• Do not rely on CEA, CAM 5.2, or 34betaE12 as these markers lack specificity for distinguishing BCC from SCC 2
• Do not use IHC alone to establish malignancy - it cannot determine whether a lesion is benign or malignant 1
• Do not substitute IHC for adequate tissue sampling - ensure biopsy includes deep reticular dermis regardless of IHC plans 5

Special Consideration for Basosquamous Carcinoma

Basosquamous carcinomas show at least some areas of Ber EP4 positivity but typically lack EMA expression (only 1 of 13 cases showed focal EMA positivity). 2 This mixed pattern is diagnostically significant because basosquamous carcinomas should be managed as squamous cell cancers due to their metastatic potential. 6

Clinical Context Matters

Despite the availability of IHC panels, histopathological criteria combined with clinical data remain the gold standard for BCC diagnosis. 3 The overlapping immunohistochemical profiles between BCC and its mimics reflect that these tumors may represent different differentiation points of a single cell type. 3