Welcome to First Incision, the podcast about preparing for the General Surgery Fellowship exam. I'm your host, Amanda Nikolic. Welcome back to another episode of First Incision. On today's episode, we are going to cover benign breast diseases, and I'm going to try to break it down into a little bit more of an understandable format.
Let's get started with our team timeout. Our patient today is still the breast module from the surgical curriculum, and our patient or topic today is going to be benign breast diseases.
A couple of brief things to go over before we get started, just to help keep these main sort of concepts in our head throughout this topic. It'll really help you understand benign breast diseases better. The first thing is... the setup of the breast itself so remember in our breast anatomy module we talked about the ducts and lobules of the breast And these ducts and lobules are lined by two layers of cells. The inner layer lining the duct is the...
epithelial layer and the second layer which is just deep to this is the myoepithelial layer and this is often called the basal layer and outside of those two layers is the basement membrane. On the other side of that is the fibroepithelial tissue, the stromal tissue surrounding these ducts and ductules and lobules. And when we talk about benign breast diseases, we're talking about changes in the cells either lining the duct or in the... the stromal tissue around those ducts and lobules.
The other thing to remember is that the breast is constantly changing, both over a woman's lifetime as well as fluctuations with the normal hormonal cycles. So some of the main... Times that the breast will undergo change include early on in adolescence and the mid-20s, where the lobules and the stroma in the breast will respond to hormones in a sort of exaggerated fashion. And this can lead to the development of...
things like fibroadenomas. Obviously, there are a number of changes that occur when a woman is lactating, and I won't go into these in detail. And the other time that the breast undergoes change is in the fourth decade of life and leading up to menopause. During this time, the breast undergoes progressive involution, which is essentially a physiological process that occurs where the elements of the breast undergo atrophy.
progressively disappear. So basically the breast is not going to be required as a milk producing gland in the future and therefore those duct and lobular units will disappear and be reabsorbed over time causing a less dense breast. The reason I touched on that is because you might come across this term called normal breast development and involution or aberrations of normal breast development and involution when you're reading about benign breast diseases.
The reason this seems to come up is because some of these processes are aberrations or abnormalities of the normal process of the breast changing over time and therefore don't represent a neoplastic or a potentially neoplastic process.
The key example of this is when we look at cysts, cysts being fluid-filled structures within the breast, very, very common. These are thought to be... a byproduct of an involuting lobule that then... basically doesn't involute properly and gets filled with fluid and becomes a cyst and is most common in perimenopausal women when that involution is occurring most commonly. So let's get a little bit deeper into this topic of benign breast diseases. There are a few ways to break down this topic.
The best way that I've found, at least to start with, is to split these conditions into three main categories. The first of these is non-proliferative lesions. The second is proliferative lesions. And the third is proliferative lesions with atibia. Lesions that are found in these three categories can...
be thought of having a certain amount of relative risk for that patient of developing breast cancer over their lifetime. And that doesn't mean that that lesion that you've found itself is going to grow into a breast cancer. does tell you is that over that woman's lifetime, they may have an increased risk of developing cancer in the same breast and in the other breast as well. For non-proliferative lesions, these can be thought of as low turnover.
low cellular numbered lesions, so things like cysts. And they have a very low relative risk for that patient developing breast cancer in the future, between 1.2 to 1.4 times that of the general population. proliferative lesions are a little bit more concerning. You've got increased numbers of cells. And these lesions are associated with a 1.7 to 2.1 times relative risk of that patient developing breast cancer over their lifetime compared to someone in the general population.
When we look at the group of patients with a proliferative lesion with ATPR of those cells, this is more closer... along the spectrum of being a really abnormal looking lesion. And these patients have a much higher risk of developing breast cancer with a relative risk of four to five times population. Let's have a look at some lesions in each of these three categories. But before we do that, I also want to talk about another way that I've thought of differentiating these lesions.
looked at it this way was because I found there were lots of names of things that were coming up in the three different sections that looked quite similar. So for example, in non-proliferative lesions, there's something called mild duct hyperplasia. And in proliferative lesions, there is florid ductal hyperplasia. And in proliferative lesions with atibia, there is atypical ductal hyperplasia.
And when you look at it and look at what these lesions actually are, really this is a spectrum of changes of... abnormalities in the same type of cell. So I'm going to split it up into these three sections, but I'm also going to talk about themes of lesions that run through the three sections. So given we've talked about mild ductal hyperplasia, I've
put these lesions under the topic of epithelial cell-based lesions. So when we think about those linings of cells in the ducts, that inner lining is the epithelial cells. So these lesions are abnormalities of those epithelial lining cells. So for example mild ductal hyperplasia comes in under a non-proliferative lesion and when you look at that under the microscope you're looking at an increased number of epithelial cells relative to normal.
They're not atypical and there isn't a huge, huge number of extra cells, just two or three lines of cells rather than just the one line that you would be expected to see. If we look in the proliferative lesions category, we have florid ductal hyperplasia. And this is an increased number of epithelial cells, which occupy at least 70% of the duct lumen. So you're talking about fluoroductal hyperplasia. So a lot of these cells.
And under the proliferative lesions with atypia category, we have atypical ductal hyperplasia. So again, an increase in the number of cells lining the ducts. which is the hyperplasia, but with cellular atypia. So microscopically, those cells look abnormal. They might even look similar to a low-grade ductal carcinoma in situ, but...
They should be less than two to three millimeters in size. These cells shouldn't be more than two to three millimeters in size and they shouldn't completely fill two duct spaces. Moving on to another theme that I came across, we can look at fibroepithelial lesions. Fibroepithelial lesions are basically lesions that involve both stromal
and epithelial components. So a simple example of this under the non-proliferative lesion title is a fibroadenoma. It's a biphasic, so both the epithelial and the stromal cells. are proliferating and they cause a mass, which is a fibroadenoma. You might have come across that before. They're very common. Under the same topic, heading non-proliferative lesions, there's another type of fibroepithelial lesion, which is called pseudoangiomatous stromal hyperplasia, or PASH for short.
This is also a fibroepithelial lesion, but it's more weighted towards the stromal component. So it's usually sort of a dense collagen with slit-like spaces resembling blood vessels in the stroma. And that's how it would look out under the microscope. There is one type of fibroepithelial lesion that comes in under proliferative lesions, and this is a complex fibroadenoma. Basically, the way that I think of this is...
Remember that a fibroadenoma itself is both the epithelial cells and the stromal cells hypertrophying. And so in a complex fibroadenoma, you have hypertrophy and increased number of those cells. But those ductal cells, epithelial cells, will have abnormalities. So you may see other proliferative lesions that we'll talk about in a minute. in the cells inside these epithelial components that are proliferating in a fibroadenoma.
The next theme we're going to talk about is metaplasia. You might know about metaplasia when we talk about Barrett's esophagus or change of one cell type to another. In the metaplasia here, what we're talking about is a change of the normal epithelium of the ducts, which is usually a cuboid epithelium, and it's changed to a columnar epithelium.
So under the non-proliferative lesion title, there is simple columnar alteration. So just a change of the regular cuboidal epithelial cells to columnar cells. And it has to be less than two layers of these cells for it to come under simple columnar alteration. Under the proliferative lesions title, there is columnar hyperplasia.
And this is, again, a change of those regular cuboidal cells to columna epithelial cells, but with more than two layers. And the cells are starting to crowd each other and overlap. So it looks more proliferative. It looks like there's more cells growing there.
And there is another subtype of this that comes in under proliferative lesions with atibia, and this is flat epithelial atibia. So again... change of those epithelial cells into columna cells but now those cells have nuclear atypia they look abnormal
This is the one exception to that rule of proliferative lesions with atypia having an increased risk of breast cancer at four to five times the regular population. For this group, even though these cells have nuclear atypia, their relative risk is only 1.5. So this is the exception to the rule. There are another couple of themes we'll quickly touch on. One of these is sclerosing lesions. These are basically...
aberrations of the normal involution of the breast. So there may be increased scarring or areas of fibrosis or sclerosis where these ductal units would usually be involuting and being reabsorbed. So there's nothing here under non-proliferative lesions, but under proliferative lesions, we have mammary adenosis. And this is a benign proliferation of the lobular unit. So you have more glands than usual that are also enlarged.
And there's a subtype of this called the sclerosing type of mammary adenosis, where you also have a fibrosed stroma associated with these increased number and size of lobular units of the ducts.
The next sclerosing lesion that also comes under this heading of the proliferative lesions is two things, radial scars and complex sclerosing lesions. And I put these under the same heading because... A radial scar is basically an elastic or collagen stellate-shaped centre with entrapped epithelial elements throughout these kind of stromal fibrous.
area and a complex sclerosing lesion is the same thing but just more than one centimeter in size so they're the same thing but one of them the radial scar is less than one centimeter and a complex sclerosing lesion is more than one centimeter and these entrapped epithelial components can also have associated
adenosis, so increased proliferation that we just talked about, or size of the glands, or hyperplasia, so increased number of cells lining those glands. And there's no squirming lesions under... the proliferative lesions with atypia heading. And the last one to talk about or second last one is lobular lesions. These probably start... as epithelial lesions, so that mild duct hyperplasia, fluoroductal hyperplasia we were talking about, which is why...
There is nothing under this heading under the non-proliferative or proliferative lesions. But there is a couple under proliferative lesions with atypia. And basically, they come from the same cell. But once those cells lose their e-cadherin, which is... a protein that helps the cells stick together, then they are classified as lobular rather than ductal lesions. So the first thing we'll talk about is atypical lobular hyperplasia.
This is obviously a proliferative lesion with atypia because it's atypical lobular hyperplasia. And this is a proliferation of small monomorphic... because they're not sticking together cells within the ducts and lobules or terminal ductal lobular unit that don't stain for e-cadherin. And the differentiation of atypical lobular hyperplasia from the next thing we're going to talk about is that the lobular unit is less than half filled with these cells and there's no distension. The next...
Lesion we'll talk about under proliferative lesions with atypia, which is also a lobular lesion, is lobular carcinoma in situ. So this is the same as above. It's those small... discohesive monomorphic cells within the ducts and the lobules, but more than half the lobular units are filled and distended with these cells. And again, they don't stain for E-cadherin.
And the last thing we'll talk about are papillomas. Papillomas are proliferations of epithelial and myopithelial cells around a fibrovascular stalk. So they're like little polyps. There's nothing under this title in non-proliferative lesions, but under proliferative lesions, there is a simple papilloma. They often grow within the ducts. A typical presentation of these is that you get one in the peripheral duct with bloody discharge from one duct in the nipple.
And like I said, a proliferation of these epithelial myoepithelial cells around a fibrovascular stalk. I've also put under proliferative lesions with atypia and atypical papilloma. And this is a papilloma. So again, looks like a little polyp, but with atypia in the cells in the nuclei. And this has a high association with malignancy. So taking the next step then. What do you do about all these lesions? Most of these will be found incidentally for a biopsy. Some of them have classic...
Mammographic changes where they may have associated calcifications, for example, or a radial scar, for example, will look quite a lot like a cancer with distortion of the architecture because of this nidus, stellate nidus in the middle. Other things will be found when you're biopsying, for example, fibroadenoma, you may find cellular ATP or hyperplasia. And some of these do cause a mass that the patient may present with, such as a cyst.
can be felt as a mass and some of these uh lesions that cause a thickening of the The stroma can cause a mass like mammary adenosis or the pseudoangiometristromal hyperplasia. So the patients themselves may come to you with this for investigation. As with all breast lesions. Any maths should be approached with a triple assessment, which is a thorough history and examination.
imaging which typically would be a mammogram and ultrasound and a biopsy preferably a core biopsy because as you can see from the way that I've described differentiating some of those lesions you can't tell whether half a duct is filled or full duct is filled or whether duct is distended if you only have the cells. So you really need to be able to see the architecture to be able to diagnose these lesions. Along that same line...
it's very difficult to differentiate between these. And you can see that there may be some areas of a lesion that, for example, there's only the duct half filled with these abnormal cells, but then in another area, it may be more than half filled. Often, if you get a biopsy that says one thing, if you then remove the whole lesion, you may then upgrade that lesion to a more atypical or concerning lesion by taking out the whole thing and getting a better sample.
You should always make sure you're correlating whenever you get something like this on a biopsy because if you've looked at... a mammogram or an ultrasound and there's a really high, you know, BIRADS 4 or 5 of being a malignancy or something very abnormal and you have a really benign looking result in front of you. that the correlation there is not correct and that you should be concerned that you're missing a lesion. And whenever a biopsy is done or an excision is done,
especially if you're doing it for something like calcifications, there should be imaging of that specimen to make sure that those calcifications have been removed. So what should you do if you receive a pathology report with one of these lesions? For non-proliferative lesions, essentially you could leave them be, offer observation and put them back onto the normal surveillance program.
Some patients may request excision, especially if they're anxious and they can feel a lump and it's reasonable to offer these patients excision. And especially if the lump is increasing in size or associated with pain or the histology is equivocal or not clear, you can also offer these patients an excision. For patients with cysts, if it's large or they are very concerned about it, you can aspirate the fluid from the cyst. This fluid, if it's bloodstained, can be sent for cytology.
And if there's any thickening of the wall of the cyst once it's been aspirated, then you should consider doing a biopsy. Fibroadenomas also come under the title of non-proliferative lesions. However, if these increase in size over time or if they are greater than... two or three centimetres or have any complex features on biopsy, then you should consider excising these as they can be very difficult on pathology to differentiate from a phalloides tumour, which is...
Again, very similar under the microscope to a fibroadenoma but has a higher cellularity. So in order to be 100% sure that it's not a phalloides, you can offer excision to these patients in those circumstances. Moving on to the group of proliferative lesions, there is a little bit of controversy around what you should exactly do with some of these. But from what I've read, essentially...
For sclerosing mammary adenosis, you can offer these patients observation. For radial scars and complex sclerosing lesions, these... are a little complicated because they appear so abnormal and so malignant on imaging that although you may get a biopsy that says it's a radial scar or a complex sclerosing lesion, you're still left with this mammogram that looks really atypical and really can... So you'd probably offer an excision to these patients.
to be sure that you're excluding a malignancy. And there's about a 10% risk when you do excise a radial scar or complex sclerosing lesion that there will be DCIS or even an invasive ductal cancer on that final excision specimen. So it's reasonable to offer these patients. and excision. For fluoroductal hyperplasia, we would offer observation and normal surveillance for these patients. For patients with columnar hyperplasia,
5% to 15% of these are associated with another pathology when you excise these areas. So that may be atypical ductal hyperplasia, lobular carcinoma in situ. ductal carcinoma and such or even in invasive cancer.
For these lesions, you'd have to really consider about whether you're going to survey all these. If you had a specific abnormality on the mammogram and you'd excised all of that abnormality, it may be reasonable to watch. But if there are any ongoing abnormalities... or this was a large area involved, then you could consider excision.
And for papillomas, we mostly would suggest an excision for these as they are often symptomatic. And as we'll talk about in the next section, they can be atypical and difficult on biopsy to confirm, definitely just a papilloma. So our third topic heading today was proliferative lesions with atypia. What do you do with these? So a little bit more clarity on these in the literature. For atypical ductal hyperplasia, we would recommend excision.
The only real difference between this and ductal carcinoma in situ is the size of the lesion and whether or not the ducts are completely filled. So you can tell that there may be... Although you've sampled one area where it doesn't look like there's a lot of cells, that you may have missed an area where there are more cells and that could definitely be upgraded to DCIS or an invasive ductal cancer. And on about 10% to 20% of the excisions of these lesions, they'll be upgraded to one.
of those. With atypical lobular hyperplasia, again, a discussion with the patient, atypical lobular hyperplasia and lobular carcinoma in situ are not nowadays thought to be part of a process of developing interlobular cancer in the same way that DCIS is thought to be a precursor lesion to invasive ductal cancer. They themselves are not thought to turn into a cancer, but they do increase the likelihood.
sort of a patient developing a breast cancer in either breast. So you would talk to the patient about surveillance. You'd make sure that there were definitely benign imaging findings. And if you had any concerns, then you would do an excision. And same for... lobular carcinoma in situ. It is a little bit more based on the histologic subtype. So there is just plain lobular carcinoma in situ and there's another subtype called pleomorphic lobular carcinoma in situ. Pleomorphic.
lobular carcinoma in situ is a more aggressive type and behaves a lot more like DCIS. And if you had that on your biopsy, you would definitely... do excision of that lesion and probably radiotherapy post. But for plain lobular carcinoma in situ, most people, from my experience, would excise that lesion and keep the patient on a close surveillance.
For flat epithelial atypia, we discussed that that one doesn't have as high a risk as the other proliferative lesions with atypia of that patient developing cancer over their lifetime. On excision, about 5% to 15% of those will be upgraded to an atypical ductal hyperplasia or a DCIS, and therefore most people would do an excision of an area with that biopsy result.
The other layer you should consider when treating a patient with an atypical proliferative lesion is reducing their risk of breast cancer. And this may include a discussion with the patient of... starting a medication such as a selective estrogen receptor modulator. including tamoxifen or raloxifen if they're premenopausal, or an aromatase inhibitor such as XMS stain if they're at high risk, and for them to continue this for five years.
I think I have talked enough about benign breast diseases. I don't think I can say any more Bs for a while. I think I definitely stuffed a few of those up. I just briefly want to touch on a couple of topics I didn't go into too much detail about. The first is papillomas. You might also see these written as duct papillomas or intraductal papillomas. Basically, these are tumors of the major lactiferous ducts. They are very common in late reproductive or postmenopausal years.
They are typically thought to be benign. I did put them under the proliferative category because they are a proliferation of cells. And as I mentioned in the last section, they are a proliferation of both the epithelial inner layer and that myoepithelial second layer of cells. around a fibrovascular axis and they look like little polyps basically. Some may harbour a malignant potential. Definitely papillary cancer is a subtype.
or histological subtype of breast cancer that we will talk about later. And they can harbour areas of atipia or DCIS because they are a proliferation of that layer of epithelial cells. So there is some concern when you do get a biopsy of a papilloma and you find... this growth in the duct that you are concerned that maybe you're missing something more sinister. Typically, these patients present with blood-stained nipple discharge.
and it's thought that the papilloma twists around its fibrovascular pedicle and gets ischemia and necrosis, and that's why you get this bloody discharge, and it will come out of one of the ducts of the nipple. Sometime detected during breast screening as a small lump or maybe seen pretty clearly on ultrasound under the nipple areola complex. In terms of location, it is mostly in 90% of cases seen in the subareola region. But there are two types, the central.
and the peripheral types of papillomas that tell you that they can also be found more peripherally within the ducts of the breast. The central type is... thought to be more benign, more indolent than the peripheral type. Peripheral can also be associated with the syndrome of multiple papillomas.
I've seen those terms that seem to be interchanged. So I'm not really clear whether they're thought to be the same thing. That can be something we ask the specialists when we get them on the program. But within the peripheral or multiple papilloma group, you may find multiple papillomas. distally in the breast, often more than five. And these have a higher association with developing invasive cancer, probably a relative risk of about three times compared to a central papilloma.
The recommendation is that they should be removed, especially if they're large, more than one or one and a half centimetres in size, because of this associated risk of malignancy. And then there's this other subtype. called an atypical papilloma which i put under that proliferative lesions with atypia title because they, like I said, have cellular atypia abnormalities and about 67% of these will actually be a malignancy when they are removed. So they should definitely be excised.
In terms of excision, it can be difficult to find the lesion. So it may be that if it's in the subareola region, you use an imaging study or... a blue dye down that particular duct to be able to identify that duct and that papilloma, you can get the radiologist to put a hook wire into it beforehand so that you know where exactly it is in order to remove it.
And again, because these come under that proliferative lesions title, these patients have a one and a half to two times risk of developing cancer over their lifetime. So they should be closely monitored on a surveillance program. The other thing I want to talk a little bit more about is phylloides tumors. I briefly touched on them. If we think about those themes that we're running through the benign breast diseases topic, this comes under fibroepithelial lesions.
It's also known as cystosarcoma phalloides. They're very rare. Less than 1% of breast neoplasms will be a phalloides and the most common in women around 40 to 60 years of age. They're typically painless, fast-growing masses, and they are a fibroepithelial lesion, which means that they have growth of both the epithelial and stromal components of normal breast tissue. So we talked about fibroadenomas as being a benign proliferative lesion. And a phalloides is essentially a...
fibroadenoma, but with a greater amount of hypercellular stroma that is expanded out of proportion to that epithelial component. So it's both epithelial and stromal components that... increase in number and size of cells but specifically when you look under the microscope a phalloides will have a lot more cells in that stromal component and a lot less of that epithelial component and phalloides basically refers to the leaf-like growth of pattern that the stroma looks like under the microscope.
The fullitis tumour can be classified according to the WHO classification system as either benign, borderline or malignant. And the way they classify this is by looking at the border of the lesion. the cells in the stroma, and the mitoses. So in a benign phalloides tumour, the border is well-defined. It's sort of well-capsulated. The stroma will not have any atypical.
atypia in the cells. There'll be mild hypercellularity compared to a fibroadenoma and pretty uniformly these cells will be distributed through that stroma and there'll be less than five mitoses per 10 high-powered fields. By contrast, we'll go right to malignant. So malignant phalloides, the border is invasive. It's encroaching and growing into the surrounding normal tissue. There's a lot of cells.
heaps of cells and they look very atypical, different sizes and nuclei look very different. And there'll be more than 10 mitoses per high powered field. And the borderlines come in, in the middle of that. The reason this is important is because of the risk of recurrence after excision and the metastatic rate. So benign phylloides tumors.
If you excise them, and you should excise them with at least a centimetre margin, one centimetre, not one millimetre, one centimetre margin of normal tissue will have a recurrence rate of about 10%. A borderline full AIDS tumour. even with a one centimeter margin will have a 30% recurrence rate and a malignant a 35% recurrence rate.
And when we're talking about its ability to metastasize, benign and borderline are not thought to metastasize, but malignant phalloidies, about 30% of those will metastasize. And once they do metastasize, they... act a lot more like a sarcoma. So they don't typically spread to lymph nodes. So when you're excising one of these tumors, you don't need to do a sentinel lymph node biopsy, but they will spread hematogenously. So to lung, bone, central nervous system.
and they act like true sarcomas. They have very poor survival rates and you would treat them with chemotherapy as you would usually treat a sarcoma, not like a breast cancer. That is all I have time for today about benign breast diseases. I will put up on the Instagram a little summary of what I've talked about today that includes those three.
subheadings under benign breast diseases and then list the different breast diseases under each of those subheadings and I've color coded them so you can see how those different subtypes flow on from each other and hopefully you'll find that. a useful way to help get your head around this very complex topic.
I think for next week, we may move on to breast cancer, which is obviously a ginormous topic. And I don't know that I'll be able to get through it all before I'm supposed to finish this topic at the end of next week, but we will give it a red hot go. it's time to close up thanks for listening to first incision if you have any comments or feedback or follow us on Instagram at First Incision. Happy studying!