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The page below is a sample from the LabCE course Troubleshooting Guidance for Hematoxylin and Eosin (H&E) Stain. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Note the bubbling in and around the cells. This artifact is typically
caused by proteins coagulating at high temperatures, but can be caused
by high pH in formalin.

Nuclear Bubbling: Created During Processing

Nuclear bubbling occurs when the proteins in the nucleus coagulate. This artifact is often a result of poorly fixed samples that have encountered a high level of heat. A high pH fixative can also cause bubbling to be seen. The harsh environments cause the proteins to coagulate around small droplets of liquid, which is what gives them the soap bubble appearance. Unfortunately, there is no way to remove this artifact once it has occurred.