Eccrine Gland Tumors: Pathophysiology

00:01 Welcome. In this talk, we're going to discuss a fairly rare set of entities called eccrine gland tumors.

00:08 So the old medical joke about, you know, when you hear hoof beats initially think horses.

00:14 And if you're, you know, if you're now thinking more bizarre things, think zebras. In this particular case, if you hear hoof beats, you're thinking unicorns.

00:24 These are pretty rare.

00:26 And unless you are in a rather large dermatopathology or dermatology clinic, it's very unlikely you'll see them.

00:33 However, please stay with me because they're kind of interesting.

00:37 They're kind of fun to look at.

00:38 They have very characteristic histology, so let's get into it.

00:42 Eccrine gland tumors are rare growths.

00:45 They originate from eccrine sweat glands.

00:48 And if you go back to the the talk where we talked about general structure and function of the skin, if you remember, the eccrine glands are typically those that are responsible for making sweat, for making water and electrolyte that help to cool by evaporative cooling the body. Tumors of these particular cells are relatively rare because they don't usually have a high proliferative potential.

01:14 Yes, they're turning over a bit at a slow rate, and they rarely go bad.

01:19 There are endocrine gland tumors, benign and malignant variants, and you're seeing a whole bunch of bullet points on both sides.

01:28 We're really going to cover the three major benign variants or benign versions of eccrine gland tumors- a syringoma, a cylindroma and spiradenoma.

01:39 We're not going to get into the others because, boy, it's beyond unicorns.

01:43 And on the malignant side, we're only going to cover the major one that we see most frequently, which is adenoid cystic carcinoma.

01:50 And the others we're not going to cover just because it's probably not appropriate for medical students to have to worry about all these little, teeny tiny details.

02:01 Okay. The epidemiology.

02:03 So syringomas again, benign eccrine tumors.

02:07 It's hyperplasia essentially.

02:09 It's not even really fully a tumor.

02:11 It's just increased numbers of cells typically appears in early adulthood.

02:16 Women more common than men.

02:18 There's probably hormonal basis for driving some of the proliferation.

02:22 They can also be associated with inflammation, trauma, or autoimmune disorders.

02:26 They are often around the eye.

02:29 Even though you have eccrine glands pretty much everywhere, we tend to see the tumors of the hyperplasias around the orbits, and it can be widespread in other syndrome of things like down syndrome with certain medications or hyperthyroidism.

02:45 Cylindroma is another variation on the eccrine benign tumors are again fairly rare.

02:52 We see them much more frequently in women than in men.

02:55 Again, speaking probably to the estrogenic component that stimulates proliferation as opposed to syringomas.

03:01 They occur later in life.

03:04 Solitary lesions are typically associated with sporadic acquired mutations. Loss of function.

03:10 Mutations in CYLD that encodes for a deubiquitinating enzyme that removes Ubiquitins from a substrate that is going to regulate inflammatory states.

03:22 That same CYLD mutation is also seen in Trichoepitheliomas.

03:28 So if you want to look at another talk, Trichoepitheliomas are also associated with this same gene. When we have familial forms of cylindroma, as it's an autosomal dominant disease with those mutations in germline, and that's the Brooke Spiegler syndrome.

03:46 Spear adenomas, another oma so benign tumor of the eccrine glands, it looks similar to cylindroma as it's just a little bit different. It's also rare.

03:57 It's also again benign.

04:00 These typically have pain associated with them.

04:02 So there may be a greater association with neural input and or with making cytokines or inflammatory mediators that drive neural stimulation.

04:12 It's early adulthood. Kind of like the syringomas.

04:15 They're solitary lesions.

04:17 They're typically sporadic.

04:18 You can have these occurring also in the Brooke Spiegler syndrome. Okay. Those were the three major benign variants.

04:28 Syringoma cylindroma spiradenoma.

04:31 Now we're going to go to the malignant.

04:33 The most common malignant brain tumor.

04:36 And this is going to be the adenoid cystic carcinoma.

04:39 It's not a major public health menace.

04:42 This is a rare skin tumor typically occurs in much older individuals.

04:46 Slightly more common in females like all of the eccrine gland tumors. It typically, interestingly enough, is not on the skin but in salivary glands. But you can't have a cutaneous lesion.

05:00 It has a better prognosis than a lot of other salivary gland tumors.

05:04 So even though it's malignant, it's not a terrible actor.

05:08 And it's associated not with CYLD that deubiquitinase enzyme, but rather with MYB, which is a transcription factor.

05:18 It's a proto oncogene and you get overexpression.

05:21 So the pathophysiology of these guys syringomas again benign eccrine glands sweat gland hyperplasia, they're organized in nests.

05:30 And the histology that you see on the right is fairly characteristic.

05:35 And for us pathologists and you as a future dermatopathologist of distinction the the nests of cells have a characteristic tadpole appearance. I think someone is taking drugs.

05:48 But anyway, it looks sort of like a tadpole.

05:51 Some of them, and I have tadpoles there, for your edification, to remind you what they look like.

05:57 Syringoma. The root syrinx is Greek for a tube or a pipe.

06:02 Cylindroma have a very different look.

06:05 They derive from the hair follicle bulge.

06:08 They're not eccrine gland per se, although they are thought to have eccrine gland kind of differentiation characteristics.

06:15 Again, CYLD mutations, there are also other gene fusions that are associated with it. And they are cells that look like basaloid keratinocytes. So they don't even look like eccrine glands.

06:27 But they are arranged in clusters.

06:29 They resemble a jigsaw puzzle.

06:31 So that's again when you become a dermatopathologist, you'll look down the microscope and say, oh, clearly a cylindroma. They also do express keratin.

06:42 Spir adenomas. The third of the three benign eccrine gland tumors are very primitive sweat glands.

06:50 They can differentiate along either apocrine or eccrine.

06:53 Remember those are two different variations of glands associated with adnexal structures.

07:02 They can have a variety of mutations CYLD again comes forward.

07:06 And these are genes that affect NF-κB pathway, NF-κB is going to be important for driving proliferation.

07:15 They tend to be very sharply demarcated basophilic nodules.

07:20 So that big blue thing at the bottom.

07:22 Yeah, that's the spiradenoma.

07:24 They don't have a lot of other changes in their genetic makeup.

07:28 So they don't have genetic instability.

07:30 They have a very benign course and they just proliferate to make nodules okay. As opposed to this entity.

07:38 So now we've gone away from our three benign into our one malignant eccrine gland tumor that we're going to talk about the adenoid cystic carcinoma again associated with MYB, which is going to be that proto oncogene that is going to drive proliferation.

07:54 It's a transcriptional activator.

07:56 The cells form these kind of nests of cribiform.

08:01 So with kind of a it looks like a lace or a mesh.

08:05 And the cells are around those holes or gaps.

08:09 They often will have perineural invasion and vascular invasion.

08:13 That's why they're bad actors and have a propensity to metastasize.

08:18 The clinical presentation.

08:19 So back to benign syringomas are small.

08:23 Again. We've talked about them being mostly peri-orbital .

08:26 We're showing some here that are in another location on the legs.

08:30 They can be found in a variety of locations as indicated there, including the genital area.

08:35 Cylindroma and spiradenoma are very slow growing papules and nodules.

08:40 They can appear on the scalp or a variety of other areas, typically on the head and neck.

08:45 Small blood vessels may be present.

08:48 That again speaks to the proliferative potential, driving not only the adnexal structures to proliferate, but also the vasculature to proliferate.

08:58 So we'll get telangiectasias.

09:00 And again these are most commonly on the scalp.

09:03 Adenoid cystic carcinoma.

09:05 Again, the most common place we're going to see it is in the mouth.

09:09 But we can also see it in cutaneous locations scalp trunk and extremities.

09:14 They tend to be painless.

09:15 They're slow growing. When they get more advanced, when they are on the verge of getting nasty and metastasizing, then we may get pain and paresthesias due to perineural invasion.

09:28 So in diagnosing these lesions, it really is going to come down to biopsy to be perfectly honest.

09:34 They look like a lot of other things.

09:37 You can do a physical examination.

09:39 In fact, you should do a physical examination.

09:41 You can use your special dermoscopy device, but really it's a matter of sending things off for biopsy to the pathologist.

09:50 The syringomas remember, those are the ones that look like little tadpoles. The kind of glandular structures, the spir adenomas look like that big blue ball.

10:00 The cylindroma are going to look like those jigsaw puzzle.

10:03 So we'll be able to say that's what they are one and two.

10:07 They're benign, so don't worry about it.

10:09 It's good advice and good for the patient.

10:11 On the other hand, when we see this, we are into the malignant world. Adenoid cystic kind of describes what it is.

10:19 It looks like glandular structures that have cysts within them.

10:23 Good description. And when we see this on biopsy we get a little bit more anxious because these do have a malignant potential of spread metastatic spread. So then once we make the diagnosis we'll do CT /MR or other imaging studies to delineate how big it is and where it is and etc.. Um, management.

10:46 So for the benign versions, all those omas excision is curative. You can also blast them with lasers or you can freeze them with liquid nitrogen.

10:57 For the adenoid cystic you have to be a little bit more aggressive. So you want to get a complete surgical resection if possible.

11:04 Given a location, say around the eye, you may not be able to get it all.

11:08 So in that case, and even if you think you got it all, you would want to do post-operative radiation therapy and then therapy plus or minus systemic treatment for tumors that you can't completely resect.

11:23 And with that, we've covered a relatively rare set of unicorn type tumors of the eccrine glands.