We had an interesting conundrum a couple of days ago at our daily lunchtime 'interesting cases meeting', where we looked at a biopsy of a 'Halo Nevus' (Clinical description). H&E stains revealed a small, well circumscribed partly nested melanocytic lesion with epithelioid cells suggesting a spitzoid origin/ features. The tumour was underpinned by dense a lichenoid inflammatory reaction associated with degenerate nevus cells, in places destroying the entire epidermis, in keeping with the clinical description of a halo nevus. Given the degree of degenerate naevus cells and the inflammation, we were not sure whether to call this a Spitz nevus or not. So we tried to look for additional features i.e Kamino bodies.

There were certainly a number of eosinophilic hyaline globules in the DE Junction and the question was- were these 'Colloid bodies' associated with the lichenoid inflammation in a Halo Nevus [u]or[/u] true 'Kamino Bodies'. None of us were absolutely sure how to differentiate these 'hyaline globules', and hence I thought it would be a good idea to do some research on this topic!

[b]Basics first: This is what Weedon says about[/b]

[u]Kamino bodies: [/u]They are usually PAS-D positive and trichrome positive.On immunohistochemistry they contain various components of the basement membrane, including laminin and type IV and VII collagen, but no keratin or S100 protein.They are not an apoptotic product of keratinocytes or melanocytes.Electron microscopy shows them to be composed of bundles of filaments situated extracellularly.

[u]Colloid bodies:[/u] [i]Colloid bodies [/i]are PAS-D positive bodies, usually found in the papillary dermis, derived from degenerate keratinocytes, usually associated with the lichenoid reaction pattern. They represent tonofilament-rich bodies extruded into the dermis, but they are sometimes trapped in the epidermis and are carried upwards with normal epidermal maturation.
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[i]So essentially, these 'hyaline globules' are entirely different in composition and pathogenesis.[/i][/center]

But the literature is riddled with confusion as is evident from this [url="https://docs.google.com/file/d/0B47a2MWGC7eIeTRiUlgwVzhlWjQ/edit?usp=sharing"]snapshot[/url] from Rapini’s recent book where he describes (albeit falsely!) Kamino bodies, as apoptotic end products, similar to colloid bodies!.

[url="https://docs.google.com/file/d/0B47a2MWGC7eIOGtvdjhJMERVb3M/edit?usp=sharing"]Another book written for surgical trainees says something similar![/url]

Though in his original description Kamino et al proposed apoptosis of keratinocytes and/ or melanocytes as a possible mechanism of Kamino body formation, this was subsequently disproved (Wesselmann U, Becker LR, Bröcker EB, et al. Eosinophilic globules in spitz nevi: no evidence for apoptosis. Am J Dermatopathol 1998;20:551–4.)


I was interested to see if Ackerman had a view on Kamino bodies. He had extensively written on the 'necrotic keratocyte' (Ref: '[url="http://www.derm101.com/quandaries/civatte-bodies-colloid-bodies-hyaline-bodies-sunburn-cells-satellite-cells-and-apoptotic-cells/"]Civatte Bodies, Colloid Bodies, Hyaline Bodies, Sunburn Cells, Satellite Cells, and Apoptotic Cells?' in Resolving Quandaries in Dermatology, Pathology & Dermatopathology[/url]'), stating at the end 'Dermatology and dermatopathology are replete with examples of superfluous synonymy, i.e., many names for the same condition or phenomenon. The subject under discussion here is a riveting example of it. One name is enough for these cells: necrotic keratocytes!'. But I couldn't find a reference to his views on Kamino bodies.

However, In my readings I came across a very interesting paper by Le Boit: [url="http://www.ncbi.nlm.nih.gov/pubmed/11481532"]Kamino bodies: what they may mean[/url]. What is interesting is that Le Boit questions one of Ackerman's papers showing a Kamino body in a Spitz nevus, saying that 'the diagnosis of 'kamino bodies' in that paper is not beyond dispute, as the photomicrograph looks like it might be an apoptotic keratinocyte (read- colloid body) rather than a true Kamino body'.

[center][i]So even experts seem to be unsure about how we differentiate these entities??[/i][/center]

[center][i]Le Boit did not describe how he might have analysed the Kamino body described by Ackerman in that paper, to differentiate it from a colloid body.[/i][/center]

Apparently, both Kamino and Colloid bodies stain with PAS. However Kamino bodies also stain with the Trichrome stain (since they contain basement membrane material/ collagen). Unfortunately I could not find a reference for trichrome staining and colloid bodies. I am presuming that colloid bodies would not be expected to stain with trichrome given that they do not contain basement membrane material/ collagen.

[center][i]So can we use this as a method to differentiate between colloid & Kamino bodies? Is anyone aware of a better method to differentiate between these pink globules?[/i][/center]
What is more amusing in Le Boit's paper was that apparently Kamino et al in their original paper suggested that Kamino bodies seen in melanoma's do not stain with PAS-D and Trichrome and are thus not true Kamino bodies. [u]So this might indeed be used to differentiate Spitz nevi from melanoma![/u]

[center][i]I have never come across this before, as there is no mention in the books![/i][/center]

Le Boit himself was puzzled that no one else had taken up this very important topic since, apart for [url="http://www.ncbi.nlm.nih.gov/pubmed/6182169"]a paper by Arbuckle & Weedon[/url] showing that only half of the Kamino bodies in their melanoma's stained with PAS-D/ Trichrome; in contrast to all of the globules in their Spitz nevi, which stained positively. Le Boit did however sound quite sceptical that PAS-D/ Trichrome positivity can be used to distinguish between benign and malignant spitzoid lesions with Kamino bodies. In fact, to prove his point[i], Le Boit threw a challenge[/i] asking people to submit cases of melanoma with metastasis, where Kamino bodies are seen.

[url="http://www.ncbi.nlm.nih.gov/pubmed/11803294"]Ackerman subsequently accepted and responded to Le Boit's challenge[/url], saying that the reason Kamino bodies may not present in metastasizing melanoma's is probably because these are usually thick lesions and Kamino bodies might be a feature seen only in superficial lesions with junctional involvement.

[center][i]I do agree with that this might be true as most of thick spitzoid tumours I have seen, seldom demonstrated Kamino bodies.[/i][/center]


[url="http://www.ncbi.nlm.nih.gov/pubmed/14631194"]Le Boit responded[/url] saying that this might be true, but he was sceptical, as thin melanoma's also do metastasize and there is bound to be at least one such case in the world with kamino bodies and reiterated his challenge!



[center][i]I am astounded that this challenge has not been taken up so far!![/i][/center]

[center][i]Are colleagues aware of this challenge? Will you take it up?[/i][/center]