Acid decalcification degrades both protein epitopes and nucleic acid. A bone biopsy that has been through it can return a falsely negative immunohistochemistry result, a failed fluorescence in situ hybridisation, or an inadequate sample on next-generation sequencing — and the report will often say 'negative' rather than 'unreliable'.
So when bone is the only accessible disease, plan the specimen before it is taken. Ask for a soft tissue component if the lesion has one, request that part of the core be held back undecalcified, or ask the laboratory to use a chelating agent such as EDTA, which is slower but preserves antigenicity and DNA. Where the decision hinges on a single biomarker — hormone receptors, HER2, a fusion, a targetable mutation — a repeat biopsy from another site is often faster than arguing with an uninterpretable result.
And when you receive a negative biomarker on bone, check the processing before you accept it. A patient denied targeted therapy on a decalcification artefact is a common and entirely preventable error.
- Ask how a bone specimen was decalcified before accepting a negative biomarker result.
- Request EDTA rather than acid decalcification where the laboratory can offer it.
- Where a lesion has a soft tissue component, biopsy that instead.
- Ask for part of the core to be reserved undecalcified for molecular work.
- Treat 'negative on decalcified bone' as uninterpretable, not as negative.
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