Here’s a case that I came across recently. I know I said in my last post I’d concentrate on common or exam-type diagnoses, but this one is a useful clinical pitfall to know about.
Young adult with a subconjunctival pigmented area ?melanoma
This medium power image shows fibroconnective tissue with no identifiable epithelium. Centrally, there is a structure which looks like a nerve, with some scattered pigment surrounding it.
In the annotated image, I’ve outlined the nerve in blue. I’ve also outlined in yellow a line on the section: this is an example of folding artefact, and not a diagnostic feature!
If you see brown pigment granules on an haematoxylin and eosin (H&E) stained slide, the most likely candidates are melanin and haemosiderin. There are histochemical stains you can use to tell the difference. In our lab we use Perls’ and Masson Fontana, but in this case I was happy to interpret it as melanin without the need for special stains.
We can see the pigment has two patterns. In the first (outlined in blue), it is within distinctly defined cells with modest cytoplasm (with the nuclei highlighted because of their lack of pigment). These are probably melanocytes although some may be melanophages (macrophages that have ingested melanin). In the second pattern (outlined in yellow), it is more dispersed/elongated. Some remains intracellular, within dendritic melanocytes, and some is deposited in the stroma.
This is an intrascleral nerve loop (of Axenfeld). It’s a clinical pitfall, because it can present as a pigmented nodule raising the suspicion of melanoma.
This slide is immunostained for S100 (in red), which is expressed in neural tissue. It is often expressed in melanomas as well, so a positive S100 does not exclude melanoma!
We use a red chromogen here since standard immunostaining gives a brown colour to positive material, which can be confusing if there’s already intrinsic brown pigment.
This slide is immunostained for neurofilament, which is highlights neurons (yes, the name rather gives it away): particularly their axons which you can see as long thin structures. Melanomas do not express neurofilament. Note that the pigmented cells are not highlighted with either the neurofilament or S100.
And finally, this slide is immunostained for MelanA, which highlights melanocytes (and melanomas). It is negative in the nerve, and positive in the surrounding melanocytes.
Intrascleral nerve loops aren’t uncommon although they don’t often get biopsied. Whether you’re an ophthalmologist or histopathologist, it’s worth knowing about their existence so you don’t get caught out. I wasn’t able to find many references on the entity. Here are a few links.
Clinical image from EyeRounds at the University of Iowa
Degeneration of Axenfeld nerve loop: a clinicopathologic case report by Shin et al.
Intrascleral nerve loops by D. Katz. The images aren’t the best, but it’s an interesting article on the entity’s history
And here is a rather old-looking article (maybe a book chapter?) by the renowned Algernon Reese himself.