All that glitters is not gold – the importance of context in the evaluation of atypia

“It’s too atypical to be malignant.”

“It’s too atypical and so it has to be malignant.”

These are too variations on the theme of atypia, and lead the thinker to two contradictory conclusions. I am sure you have either heard or spoken at least one of these two statements. Obviously, atypia doesn’t mean the same in every situation and to every person. Or, as Shakespeare wrote (in his The Merchant of Venice): “All that glitters is not gold.” We could rephrase this for pathologists: “All that is atypical is not malignant.”

We can easily think of many examples in dermatopathology. For example, awful looking melanocytic lesions in children may simply be Spitz nevi that do not behave malignantly. I have two examples that made a deep impression on me (because they are not just examples, but mistakes I nearly made): an anaplastic large cell lymphoma I initially thought was squamous cell carcinoma and a case of Leishmaniasis I assumed was squamous cell carcinoma. In both of these cases, the squamous atypia was horrible. My mistake was that I just hadn’t paid attention to the whole slide.

The importance of reviewing every feature on the slide to evaluate atypia (in addition to evaluating the entire clinical situation) cannot be overstated. Had I paid attention to the clinical history (a woman fleeing from Ecuador and being bitten by a bug in a jungle) and had I then used that clinical history to look hard for organisms, I would have noticed the Leishmania. In the other example, had I noticed how ugly the lymphocytes looked, I wouldn’t have concluded that the pseudoepithelimatous hyperplasia was carcinoma. In other words, atypia divorced from the context can lead to errors.

This is highlighted in a recent article in the American Journal of Dermatopathology, about herpes folliculitis being misdiagnosed as lymphoma (in the August issue of this year, 2013; 35(6):663-665). Yes, there were atypical lymphocytes, but there was herpes as well, and that changed everything.