What is the role of Immunohistochemistry (IHC) in the diagnosis and treatment of salivary gland cancer?

Role of Immunohistochemistry (IHC) in Salivary Gland Cancer Diagnosis and Treatment

Immunohistochemistry is an essential diagnostic tool for salivary gland cancer that enhances diagnostic accuracy, helps determine tumor differentiation, and identifies therapeutic targets that guide treatment decisions. 1

Diagnostic Applications of IHC

Confirming Diagnosis and Tumor Classification

• IHC serves as a critical adjunct to standard histopathological examination (H&E staining) when diagnosing salivary gland malignancies 1
• Pathologists should perform ancillary testing including immunohistochemical studies on fine needle aspiration biopsies (FNABs) and core needle biopsies to support diagnosis and assess malignancy risk 2
• IHC helps discriminate between histologically similar tumor groups that may have different prognoses and treatment approaches 1

Cell Differentiation Assessment

• IHC is particularly valuable for identifying neoplastic myoepithelial cells, which are important in the diagnosis of several salivary gland tumor types 1
• Specific markers help distinguish between epithelial and myoepithelial components in tumors like pleomorphic adenoma and adenoid cystic carcinoma 1, 3

Specific Tumor Type Identification

• IHC markers assist in diagnosing specific tumor types:
  • MYB RNA for adenoid cystic carcinoma
  • PLAG1 for pleomorphic adenoma
  • LEF1 for specific adenomas
  • NR4A3 for acinic cell carcinomas
  • Pan-TRK for secretory carcinomas 3

Differential Diagnosis from CUP

• IHC helps differentiate salivary gland carcinomas from cancer of unknown primary (CUP) by identifying tissue-specific markers 2
• Cytokeratin patterns (CK7, CK20) and site-specific markers help determine if a metastatic tumor originated from salivary glands 2

Prognostic and Predictive Applications

Malignancy Assessment

• Ki-67 and p53 expression help predict biological aggressiveness in salivary tumors 4
• High p53 and Ki-67 expression is associated with more aggressive forms, particularly in carcinoma ex pleomorphic adenoma, adenocarcinoma NOS, and mucoepidermoid carcinoma 4

Therapeutic Target Identification

• IHC identifies actionable molecular targets that guide personalized treatment:
  • Androgen receptor (AR) positivity in salivary duct carcinoma
  • HER2 overexpression in certain high-grade tumors
  • NTRK fusion detection (particularly NTRK3 in secretory carcinoma) 5, 6

Predictive Biomarkers for Immunotherapy

• PD-L1 expression assessment helps determine potential response to immune checkpoint inhibitors 2
• Combined with tumor mutational burden (TMB) assessment, IHC helps select patients who may benefit from immunotherapy 2

Comprehensive Molecular Testing Approaches

Next-Generation Sequencing Panels

• Comprehensive NGS panels like "SalvGlandDx" can detect mutations, fusions, and gene expression levels of multiple genes involved in salivary gland neoplasms 6
• These panels can identify:
  • NTRK or RET fusions that may be targetable with specific therapies
  • PRKD1 mutations in polymorphous adenocarcinomas
  • Novel fusion proteins that may have diagnostic or therapeutic implications 6

Recommended Testing Algorithm

1. Initial histopathological examination with H&E staining
2. Basic IHC panel for tumor classification (epithelial/myoepithelial markers)
3. Specific IHC markers based on morphological features
4. Advanced molecular testing (NGS) for cases with diagnostic uncertainty or to identify therapeutic targets 2, 6

Clinical Implementation Considerations

Limitations of IHC

• IHC should be considered a supportive method rather than a definitive diagnostic tool 1
• Few tumor type-specific markers are currently available, limiting the specificity of IHC alone 1
• Results should be interpreted in conjunction with clinical, radiological, and histological findings 2, 1

Best Practices

• Pathologists should report risk of malignancy using a risk stratification scheme for salivary FNABs with particular attention to high-grade features 2
• When IHC results are inconclusive, molecular testing should be considered to identify specific genetic alterations 6, 3

Future Directions

• More comprehensive genomic screening approaches using NGS-based technologies 5
• Development of combination strategies using immune checkpoint inhibitors based on IHC and molecular profiles 5
• Continued research to identify tumor type-specific markers to improve diagnostic accuracy 1, 3

IHC plays a crucial role in salivary gland cancer management by enhancing diagnostic accuracy, providing prognostic information, and identifying therapeutic targets. While it has limitations, when used in conjunction with clinical, radiological, and molecular findings, it significantly improves patient outcomes by enabling more precise diagnosis and personalized treatment approaches.