Trichoepithelioma: Pathophysiology

00:01 Welcome. In this talk we're going to discuss another of the benign epithelial lesions.

00:07 This one's a trichoepithelioma.

00:10 Sounds bizarre. Well tricho is actually from the Greek meaning hair or hair like epithelial g.

00:19 That's from the epithelium.

00:20 So that's epidermis. And oma means it's going to be benign.

00:24 So there you've got the entire case.

00:27 Trichoepitheliomas are benign adnexal tumors.

00:30 So they are not part of the epithelium per se but of the structures associated with the epithelium.

00:37 They originate from hair follicles.

00:39 As we'll discuss. They are not the black squares over this person's eyes. They are the lesions that are on the forehead, on the glabella, between the eyebrows and the nose and around the nose.

00:52 The epidemiology of these well, they are pretty rare.

00:56 So in one academic setting, who in that academic setting they saw perhaps 50,000 cases.

01:03 They had three cases in a year, so it's not all that common.

01:08 If you get to see one, you will be lucky.

01:12 It's autosomal dominant inheritance when there are multiple lesions.

01:15 So there are known genetic associations.

01:18 We'll talk briefly about one of the major ones.

01:21 It typically occurs more frequently in females than males, suggesting that there may be a hormonal influence on the gene expression.

01:29 And there is this familial predisposition.

01:31 It's part of the Brooke Spiegler syndrome.

01:35 And we'll discuss that briefly.

01:37 The pathophysiology. So in the familial syndrome, the Brooke Spiegler syndrome, we know that in the majority of cases that's associated with a CYLD loss of function.

01:50 So what is CYLD? It's a gene that codes a deubiquitinating enzyme. So its loss of function, meaning that we are no longer deubiquitinating a particular substrate.

02:04 It turns out that substrate.

02:05 It's important for turning off Proliferative pathways.

02:10 So the normal CYLD would be taking away the ubiquitins that would normally degrade that substrate, and allows that substrate to inhibit proliferative pathways.

02:23 Okay. Now let's get rid of CYLD or lose its function.

02:27 Now it is not activating and we are getting degradation of the substrate.

02:35 It goes away. And as a result now we get elevated expression of NF-κB and the Wnt/β-catenin proliferative pathways.

02:45 And we drive the proliferation of the cells that are going to be responsible for making the trichoepithelioma.

02:52 Cool. So where are these cells? Where are they proliferating? The trichoepithelioma is typically derived from cells of the hair follicle, not from the epidermis per se.

03:06 They typically are cells that are in the bulge area.

03:10 And you see the bulge is circled.

03:12 And that's where we have the erector muscles that are inserting.

03:17 But it's also where the stem cells of the hair shaft live.

03:21 And it's those cells where the mutations in the child, for example, will then be allowed to proliferate.

03:28 They're going to be making sort of hair like structures, not hair per se, but the epithelium around hair.

03:35 And so that's why we get the trichoepitheliomas the clinical presentation in the familial cases, the Brooke Spiegler syndrome cases, there are multiple and there is a predilection for the face, the central face, in particular.

03:50 They are flesh-colored .

03:51 They can be papules to nodules.

03:54 In sporadic cases they can occur anywhere, although the face again is the site where they typically occur. They can be anywhere from 2 to 8mm in diameter, and sometimes, because of the proliferative genes that are being activated, we can also get telangiectasias, meaning that we're getting blood vessel proliferation, The solitary trichoepithelioma, as I said, typically occur mid-face rarely in other locations such as the scalp, extremities, etc.. In the multiple or familial cases, they're symmetrical over the central face.

04:31 Rarely in other areas.

04:33 And they can grossly resemble basal cell carcinomas, so to distinguish them from a malignant tumor or basal cell carcinoma, we'll need to do a biopsy.

04:44 So the diagnosis is a combination of clinical.

04:48 When you have a lot of them in the central face you kind of know what they are.

04:52 However, if you get isolated cases, you're going to have to actually biopsy it.

04:57 You get basaloid. So cells that look like they're basal cells proliferating, they form nests, as you see there, the very dense collection of kind of bluish cells.

05:09 They will make hair-like structures but not really good hair.

05:13 So you get a board of hair, so-called horn cysts, and the overall tumors can resemble basal cell carcinomas.

05:22 Do I expect you to be able to distinguish those and diagnose it? Not yet, but when you become world famous dermatopathologists, absolutely. If we see multiple of them, we will actually do genetic studies to look for the specific mutation.

05:37 How do we manage these? So for isolated cases you can remove them by surgery.

05:44 You're removing basically the cells that are responsible for proliferating. In larger cases or the familial cases you can do more extensive surgery.

05:55 But it requires a pretty deft plastic surgery expertise to take care of all of those.

06:02 Electrodesiccation is another method and laser therapy, but basically you try to ablate them again.

06:08 Recall that these are totally benign, so if you don't mind the way they look, you can live with them.

06:14 And with that, we've covered an interesting, albeit rare entity, the Trichoepithelioma.