Start with a diagnostic question
Immunohistochemistry, or IHC, uses antibody-based staining to investigate selected proteins in tissue. In head and neck pathology, ancillary testing can help refine classification and, for certain markers and tumour types, provide information relevant to treatment. [1]
The useful question is what uncertainty a stain is expected to resolve. Ordering a long list without a defined differential diagnosis can make the result harder to interpret and consume limited material.
Morphology and context guide the panel
The following is a practical reasoning approach: describe the main morphological possibilities, select tests that distinguish them and interpret the staining pattern alongside the tissue architecture and clinical site. A positive stain should be understood within that framework rather than treated as an isolated diagnostic label.
For a small biopsy, discuss priorities before requesting further studies. Ask whether tissue must also be preserved for another clinically relevant investigation.
The anatomical site changes interpretation
p16 provides an important example. CAP guidance supports its use as a surrogate marker in appropriate oropharyngeal squamous cell carcinoma settings, with additional HPV-specific testing in defined circumstances. The same testing strategy should not be applied routinely to oral cavity squamous cell carcinomas for prognostic purposes. [2]
The oral tongue and base of tongue are different anatomical sites. Clear site information helps prevent an inappropriate assumption about what a result means.
Laboratory performance matters
CAP’s IHC validation guidance addresses the need to establish assay performance, including relevant specimen and scoring considerations. [3] Technical quality is part of interpretation, not an optional extra.
Communicate the conclusion
When a panel is requested, explain the question to the receiving laboratory. When reporting, connect the result to the diagnostic conclusion and state any remaining limitation.
For patients, a useful explanation is that extra staining may be needed to clarify the tissue findings. It does not automatically mean that the disease is more advanced.
IHC is most informative when the result answers a specific question and changes or strengthens the integrated interpretation.
References
[1] College of American Pathologists. Head and Neck Pathology. Read source
[2] College of American Pathologists. Human Papillomavirus Testing in Head and Neck Carcinomas, 2025 update. Read source[3] College of American Pathologists. Principles of Analytic Validation of Immunohistochemical Assays, 2024 update. Read source