From the Guidelines
Immunohistochemistry (IHC) is a crucial diagnostic tool in salivary gland pathology, particularly for identifying targetable molecular alterations in specific tumor types, such as AR expression in salivary duct carcinoma (SDC) and ETV6-NTRK3 translocation in secretory carcinoma (SC) 1.
Significance of IHC in Salivary Gland Pathology
The significance of IHC in salivary gland pathology lies in its ability to accurately diagnose and classify various tumor types, which is essential for determining the appropriate treatment approach.
- IHC can help identify specific molecular alterations, such as AR expression and ETV6-NTRK3 translocation, which are associated with certain tumor types.
- The use of IHC can also help distinguish between different tumor types, such as pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma.
- A panel of markers, including cytokeratins (CK7, CK14), S-100 protein, p63, smooth muscle actin (SMA), and mammaglobin, can be used for optimal IHC analysis of salivary tissue.
Recommendations for IHC Analysis
For optimal IHC analysis of salivary tissue, I recommend using a panel of markers and considering the pattern of staining and distribution within different cell populations 1.
- Tissue should be fixed in 10% neutral buffered formalin for 24-48 hours, processed routinely, and sectioned at 3-5 μm thickness.
- Antigen retrieval methods vary by antibody but often include heat-induced epithelial retrieval using citrate buffer (pH 6.0) or EDTA buffer (pH 9.0).
- Proper positive and negative controls should be included with each staining run.
- The interpretation of IHC results should consider the pattern of staining (nuclear, cytoplasmic, or membranous) and the distribution within different cell populations of the salivary tissue.
Clinical Implications
The use of IHC in salivary gland pathology has significant clinical implications, particularly in terms of determining the appropriate treatment approach.
- For example, the identification of AR expression in SDC can inform the use of targeted therapies, such as androgen receptor inhibitors 1.
- Similarly, the identification of ETV6-NTRK3 translocation in SC can inform the use of targeted therapies, such as TRK inhibitors 1.
- The use of IHC can also help identify patients who may benefit from comprehensive genomic screening, such as next-generation sequencing (NGS)-based approaches 1.
From the Research
Significance of Immunohistochemistry in Salivary Gland Pathology
- Immunohistochemistry (IHC) plays a crucial role in the diagnosis of salivary gland tumors, particularly in cases where histological examination is insufficient 2.
- IHC can help assess cell differentiation, discriminate between histologically similar tumor groups, and diagnose specific tumor types, such as pleomorphic adenoma, adenoid cystic carcinoma, and salivary duct carcinoma 2, 3.
- Specific markers, like CD117, p63, and Ki67, can aid in highlighting luminal and abluminal cell components, predicting adverse outcomes, and identifying tumor types 3, 4.
- BSND immunohistochemistry has been shown to be useful in the differential diagnosis of oncocytic and Warthin-like mucoepidermoid carcinoma of the salivary gland, with a threshold of ≥10% positivity differentiating Warthin tumors from Warthin-like MECs 5.
- Immunohistochemistry can be used as an adjunct to routine H&E staining in the diagnosis of salivary gland tumors, helping to distinguish between different tumor types and providing valuable information for treatment and prognosis 4, 6.
Applications of Immunohistochemistry
- IHC can be used to evaluate the expression of specific proteins, such as alpha-smooth muscle actin (α-SMA), Ki-67, and p63, which can help diagnose and differentiate between various salivary gland tumors 3, 4.
- Fluorescence in situ hybridization (FISH) probes can also be used to detect chromosomal rearrangements and identify potential targets for therapy 6.
- Molecular techniques, such as next-generation sequencing, can provide additional information on the genetic alterations underlying salivary gland tumors, potentially leading to targeted therapies 6.
Limitations and Future Directions
- Despite the usefulness of IHC in salivary gland pathology, few tumor-type specific markers are currently available, and the results of IHC should be interpreted in conjunction with histological assessment 2.
- Further research is needed to identify new markers and develop more effective diagnostic and therapeutic strategies for salivary gland tumors 3, 6.