TVS of Endometrium - SD

Introduction

I am Dr. Arthur Fleischer, chief of Ultrasound at Vanderbilt University Medical Center, Nashville, Tennessee.

This talk will cover the applications of transvaginal sonography in a variety of endometrial disorders, including hyperplasia, polyps and carcinoma.

This presentation will cover the use of transvaginal sonography in evaluating the endometrium and endometrial disorders.

It will cover the technical factors including scan technique and instrumentation to optimize imaging of the endometrium.

I will cover the endometrium in premenopausal and perimenopausal women as well as postmenopausal women.

And I will discuss the sonographic findings in various endometrial disorders such as hyperplasia and cancer.

And I'll talk about the application of transvaginal sonography and evaluating women who are on hormone replacement therapy.

And just mention the application of transvaginal sonography in evaluating the endometrium using sonohysterography.

Applications in Postmenopausal Patients

Basically, the use of transvaginal sonography in post-menopausal patients who have bleeding is to evaluate those patients that need endometrial biopsy and also patients that need sonohysterography and DNC, and of course, to evaluate patients that are having bleeding in patients on a hormone replacement.

And transvaginal and or transrectal sonography provides a means for guided biopsy of endometrial disorders.

Technical Aspects

Basically, the technical aspects of providing excellent images of the endometrium focuses around understanding that the endometrium is an unusual and somewhat irregular geometry, and that we must use the probe and image the entire endometrium in different scan planes.

To assess its texture and integrity, we have to have focal areas that correspond to the level of the endometrium.

The endometrium also is affected by patient's weight.

In fact, patients that are heavier have more thick endometrium, and certainly patients with fibroids may have the endometrium that is displaced by submucosal fibroids.

I prefer doing the patient on a pelvic examination table to let their legs relax and use the non transducer hand to move the uterus to some degree to optimize imaging of the endometrium.

Endometrial Anatomy and Phases

The endometrium is basically a specialized mucus membrane.

It has both a functional layer, which is built up and shed in patients that are of childbearing age and a basal layer, which is not shed.

As you can see from this diagram in the menstrual phase, the endometrium is irregular due to sloughing, usually the first three to five days of the cycle.

After that, there's a gradual buildup of the endometrium with the glandular elements still being rather small, and the spiral vessels being rather small and confined to the functional layer.

In the secretory phase, the endometrium thickens, the glandular elements become distended, and there is a ischemic phase in the last few days of the cycle where there's decreased flow to the endometrium, which predates sloughing.

The graph on the bottom basically covers what is a typical bilayer thickness in the anterior posterior plane.

In normal endometrium, as you can see in the secretory phase, the endometrium can measure up to 12 millimeters, but typically measures between six and eight millimeters.

During this phase, now, I will be showing you the pictures of the endometrium, and I think it's important to realize that we can image the endometrium by observing the layers in the myometrium.

The myometrium is made up of three layers.

The inner myometrium is the more longitudinally oriented of these.

The middle layer of the myometrium, which runs from the inner layer to the arcuate layer, is shown here, and then the outer myometrium corresponding to these areas in the drawing inner the spiral layer in the outer layer of myometrium.

I mention these because you can use these to determine whether or not you have a complete evaluation of the endometrium.

Here in the long axis, we can see the endometrium starting here at the cervical al junction extending into the fundus, and we can measure the endometrium in the greatest anterior posterior plane.

We have an outer hypo coic area, which is the inner myometrium.

We have the spiral layer or the middle layer, followed by the outer layer of myometrium, and this is in the long plane.

When we turn the transducer 90 degrees, we can see the endometrium is a linear interface, the inner myometrium, which is hypo coic, the spiral layer, which is more echogenic, and then the outer layer of myometrium is very nicely shown here.

When we turn the probe 90 degrees to that an image in the long axis plane, we can get a more transverse image of the endometrium is shown in this diagram.

This is not the proper plane for measurement in the anterior posterior plane, since this represents the transverse dimension of the endometrium, and a lot of patients will have a uterus that is somewhat rotated, and we can see it makes a big difference in the measurement of the endometrium, whether you're measuring the transverse dimension as shown here in the same patient, we're rotating the probe and we're getting a five millimeter endometrium, which is much less than the transverse plane.

So it's very important to be attuned to these details when you measure the endometrium.

And this is another example of measuring in a retroflexed uterus, the transverse dimension of the endometrium, which is not the same as the bilayer thickness.

This is the endometrium in a patient who has a retroflex uterus, where the fundus is oriented toward this part of the screen.

And you can see here that this is the correct measurement of the bilayer thickness of the endometrium.

Now, there's about a 1.5 to two millimeter inter observer variation in measurement of the endometrium.

And I think this should be kept in mind when we say we have a seven millimeter endometrium.

That could be anywhere from five millimeters to nine millimeters.

Now, it's important to have the highest frequency probe that is focused in the area of the endometrium.

This is two examples of probes.

This is a tight curved array probe operating at a nominal frequency of five megahertz.

This is a higher frequency probe with a more compact footprint as you can see here.

And we would wanna image the endometrium with that probe.

And here visually is the difference between the older probe with a lower frequency showing an echogenic area in the endometrium with a higher frequency probe.

We can see in fact that what we have here are multiple small clots within the endometrium in a patient who had just undergone endometrial biopsy.

This is another measurement error that is not uncommon, and that is including the inner myometrium in the measurement of the endometrium.

As you can see here, this is the proper measurement.

This is a measurement including the inner myometrium.

As you can see in this patient, there's an apparent thickening of the endometrium, which was originally measured to be 22 millimeters, when in fact the endometrium is only about nine millimeters.

And what is happening is this submucosal fibroid is displacing the endometrium, making it look thick.

Another variation one can see is the C-section scar can be rather prominent in some patients.

As you can see here, this is not the endometrial interface.

Normal Thickness in Postmenopausal Women

Now, what is the normal thickness of the endometrium in post-menopausal women?

There have been many studies that have looked at this and basically they've asked different questions.

In some studies, they've asked, what is the typical measurement, which implies atrophy or tissue insufficient for diagnosis, should you do in endometrial biopsy?

And the answer there is around four millimeters.

We used a six millimeter cutoff and found a 98% true negative as a screening test for endometrial disorders.

This is an example of a thin endometrial interface that is normal.

Here's an example of an endometrium that was thought to be a few millimeters, when in fact the endometrium histologically is only a few cell layers, and sometimes mucus can give the appearance of a thickened endometrium.

It's not uncommon in post-menopausal women to see a small amount of fluid in the lumen.

And here's an example of that with the thin single layer thickness and a small amount of fluid.

We did a study where we looked at endometrial thickness and compared it to endometrial biopsy in 1,733 postmenopausal women, and we found that there was a grouping of endometrial thicknesses, typically less than six millimeters and greater than six millimeters with less than six millimeters being the most common.

When we looked at the histology in these patients, as you can see from this bar graph, that the majority of endometrial abnormalities were greater than six millimeters, but there were a few shown in this graph that were actually less than six millimeters.

And astonishingly enough, there were two cancers that were less than six millimeters.

But this is extremely rare.

And here's an example of some of these pathologies in patients with less than six millimeters thickness.

This is a three and four millimeter endometrium that turned out to be hyperplastic.

And this was an unusual case in a retroflex uterus here of a thin endometrium in a patient who had diffuse endometrial cancer that just spread around the entire surface.

When we looked at our data using six millimeters, we found the positive predictive value was not very good, but the negative predictive value that is if an endometrium is less than six millimeters, that it was negative was very high.

So it is clear that we can use the thickness of the endometrium to exclude disease.

However, there are cases when endometrial thickness is greater than six millimeters were seen in even normal cases.

So we must not just focus on the thickness of the endometrium, but look at its texture.

For example, here's a patient that has a polyp, and if one would image in this plane, you would see a totally normal endometrium.

So we need to take into account the texture and regularity of the endometrium.

3D Sonography

The use of 3D has radically improved the ability to diagnose endometrial disorders, and this is a very early example of where an endometrial polyp was seen on 3D that wasn't really that apparent on the 2D image.

Now, in 3D imaging of the endometrium, basically this is the long axis plane shown in the a plane and be due to the tipping of the image.

With the fundus being at the top, it looks like it's a retroflex uterus, where it's, that's just the display of it in the orthogonal view to a, we have this plane, which is the short axis view, and then the coronal plane is shown here with the fundus oriented to the top of the image.

And this is of course, the sample volume where we can see the entire endometrium.

And this is an example of a retroflexed uterus with a normal appearing endometrium on long axis, short axis in the coronal plane and on the sample volume, again, an example of the normal endometrium, beautifully shown in the corneal regions on this 3D coronal image.

So we can use this to evaluate uterine abnormalities.

And this is an example of a uterine delphis.

And the biggest area that we need to depict on 3D the most important area is the fundus of the uterus.

And where there's a dip in the fundal region, we know that that is a bico uterus, as opposed to where there's no dip.

This is a septated uterus or an arcu uterus.

And you can see the two endometrial interfaces in this patient with a Delphi uterus.

The 3D can also show beautifully the polyp, and not only the polyp, but the pedicle where the attachment is to the rest of the endometrium.

3D is also very helpful for depiction of a submucosal fibroid to determine, again, the attachment of the fibroid to the rest of the myometrium and the displacement of the surrounding endometrium in a patient with a submucosal fibroid.

This was lent to me by Al left, showing a beautiful 3D image after installation of fluid of a Cecile polyp.

That is very broad based as you can see here.

Sonohysterography

Well, sonohysterography or saline infusion sonohysterography is used when we can't be sure whether there in fact is a polyp.

And we used to do this much more before we had 3D sonography, because 3D sonography can answer many of these questions.

And the questions are whether the endometrial disorder is diffuse, or in fact whether it's focal.

And to answer this, we can insert a flexible thin catheter in install, instill some fluid, and depict the lumen of the uterus.

This is a normal example of sono histogram.

This is an example of a small polyp shown after installation of just a small amount of fluid.

And sonohysterography is very helpful in this regard.

In patients that have post-menopausal bleeding.

It's important to realize that this may be associated with endometrial polyps, particularly in the perimenopausal age group.

And this was a study performed by Ted Dubinsky, where he evaluated about 300 patients with a negative endometrial biopsy.

And many of these patients in fact, showed polyps.

In fact, 14 malignancies were found.

And in this same patient, I hope you can appreciate the appearance of a polyp beautifully with a little bit of fluid surrounding it.

A Dr. Bre and coworkers found that sonohysterography improves the certainty of the diagnosis, and in fact, changed the treatment in many patients, that some of the pitfalls of sonohysterography are incomplete distension, a space occupying lesion.

And in some instances where the catheter is not preloaded with fluid, you can inject some air and it may in fact make things very difficult to depict.

And this is a polyp that is actually very proximal.

One would have to slip the catheter past this, do some injection to entirely delineate this polyp.

Evaluation of Bleeding

Patients that have cycles are different than postmenopausal women, and that patients with bleeding that are of trial bearing age or perimenopausal, it's usually due to corpus lium that fails to support the endometrium.

And you can see in some of these patients, the endometrium can be up to 12 millimeters.

As I discussed earlier in the secretary phase, we're more concerned about the patient with bleeding that is post-menopausal.

But even in these patients, the most common cause is atrophy.

So sonography has a pivotal role to determine which patients undergo biopsy.

We also should be aware that there is clearly a precursor of cancer, and that is atypical hyperplasia.

And if we detect this, we know that this patient is at risk for developing endometrial cancer.

In those patients with post-menopausal bleeding, only about one in 10 or so will actually have cancer.

The vast majority will have atrophy, a very thin endometrium, which leads to erosions and bleeding.

And this is a typical thin endometrium that we can see in women with atrophy.

We also need to take into account that there are known risk factors in patients with endometrial cancer, and that is patients that are diabetic large, and some patients that take tamoxifen and endometrial cancer is a very common cancer in post-menopausal women, but luckily it has a symptom that is bleeding that leads to its workup.

This is a study that was done in Scandinavia where the endometrial thickness was plotted.

And you can see that in this receiver operating curve that most cancers were over six millimeters and that it had very high predictive value.

Hormone Replacement Therapy

Now, patients that are having that are receiving hormone replacement are decreasing ever since the Women's health Initiative showed a higher incidence of endo of breast cancer associated with this therapy.

But some patients still undergo some form of either estrogen supplementation or our on aer, which is a selective estrogen receptor modulator.

And the most common one of these is tamoxifen or r oxen.

Now, one should be aware that the endometrium in patients on HRT should be about the same in thickness as patients not on HRT.

And this, these are several studies which have shown that patients on hormone replacement have about the same thickness of the endometrium.

And this is important because patients on hormone replacement will still have bleeding.

In fact, it's not uncommon up to three months to have bleeding.

Here are a few examples of patients on hormone replacement that had abnormal endometrial.

As you can see here, this is a 13 millimeter bilayer thickness.

This patient had hyperplasia.

And after DNC, you can see a very thin endometrium.

This patient had bleeding, and the endometrium is slightly thickened, but also very irregular.

And this, the patient with an endometrial carcinoma.

This patient had endometrial carcinoma that had invaded into the inner myometrium as shown right here.

Now, it's not uncommon for patients that have bleeding and one may find a in fact, a mass on transvaginal and the pathology comes back negative.

This is typical of patients with polyps that the polyp indeed is missed by the endometrial biopsy propel.

And the surrounding area is in fact atrophic.

And here is an example where sonohysterography was very helpful in and identifying an area of abnormality in the end, in the endometrium that was actually missed by initial biopsy.

As you can see here, there's focal thickening of the endometrium and the other area of the endometrium is relatively atrophic.

Selective Estrogen Receptor Modulators (SERMs) and Tamoxifen

Now, serums or selective estrogen receptor modulators are basically a class of drugs that are used to prevent osteoporosis decreasing the possibility of fracture of bones, but they clearly do have a increased risk of deep vein thrombosis.

And we have been involved with study of these medications just for those people that are curious.

The these drugs mass the receptor sites, and the most common one of these is tamoxifen.

Tamoxifen is given to patients with breast cancer to decrease recurrence rates.

It's also been shown unfortunately to be associated with increased incidence of a very specific type of hyperplasia, as well as patients that have carcinoma.

And here's an example of a thin endometrium in a patient on Tamoxifen, and it's not uncommon in patients on tamoxifen to see these little cystic areas in the inner myometrium, which represent reactivated foci of adenomyosis.

And here's another example of these clefts associated with adenomyosis.

This is an older case where a tro Zingo Graham was done showing these divert associated with adenomyosis.

Now, tamoxifen can also be associated with a polyp.

And in this case, we have cysts inside the polyp very nicely shown on transvaginal sonography.

Now, whether or not patients are actually followed on tamoxifen is the choice the clinician has to make.

But this was a study which showed that there was a unfortunate high rate of preparation of the uterus when these polyps and endometrial thickening was worked up by endometrial biopsy.

So basically, most patients, unless they have bleeding, will not undergo sonography.

So these hypo coic areas in the inner myometrium, there's of course a differential diagnosis, but these are most commonly associated with adeno myotic foci.

Now, sometimes these cystic spaces are seen within polyps.

As shown in these slides, there is a drug called Evista that does not stimulate the postmenopausal endometrium.

And in fact, is given in patients with a history of breast cancer.

We studied a drug which was called IOx afin.

And I show these slides because there are subtle changes of the endometrium we can see on sonography that in fact are not found on pathology.

And I wanted to just show you some examples of these.

Here is a patient, the these were all patients that were followed up three months after starting this drug with endometrial biopsy.

This is a normal endometrium, and three months later you can see some thickening.

And this was a negative endometrial biopsy, even though the findings on sonography showed some thickening.

Another patient who starts out with this endometrium and ends up with some cystic changes.

So my point is that sometimes the endometrial biopsy don't show changes that we see on sonography, another patient with these little hypoechoic areas in the inner myometrium that are probably reactivated adeno myomas.

And we can see that again in this patient.

And we can see the little cystic areas associated with adenomyosis.

And this patient underwent Mr showing these adeno myotic foci in a patient.

Pitfalls and False Positives/Negatives

So there are many causes of false positive of endometrium that I wanted just to discuss.

I'm showing you some examples of adeno miotic foci that appear as cystic areas, but histologically cystic atrophy can be associated with thickening of the endometrium, primarily because of multiple interfaces produced by the microscopic cysts, false negative, incomplete delineation, poor patient cooperation, and substandard equipment.

Now, these slides were lent to me by Anna Parsons, who many years ago now looked at areas that we saw that she saw that were abnormal on transvaginal sonography and did histology in those areas.

And here is what appears to be a thickened endometrium.

When samples right here, we found these cystic areas in so-called cystic atrophy of the endometrium.

This echogenic focus right here and represented an adeno miotic oci.

So adenomyosis can give a very abnormal image in the endo, in the myometrium and displace the endometrium.

In fact, as you can see in this example and in adenomyosis, the vascular supply is different from fibroids in that it's scattered.

And on 3D we can see that the thickened endometrium myometrium can in fact displace the endometrium.

Color Doppler in Endometrial Disorders

So transvaginal sonography has an important role in evaluation of endometrial disorders.

One has to be very careful to image in scan planes that are relative to the endometrium and look at the endometrium in some cases using sonohysterography.

So I've shown you where the role of transvaginal sonography in patients with post-menopausal bleeding is to decide which patients need endometrial biopsy.

Now, sometimes this patient, I, after showing a two millimeter endometrium, underwent endometrial biopsy because the clinician was insistent and the tissue came back insufficient for diagnosis.

In a meta-analysis by Smith Bindman, she showed that when the endometrium was less than five millimeters and the patient had no real risk factors for endometrial carcinoma, this basically excludes the possibility of endometrial cancer.

And this finding did not vary in patients who underwent hormone replacement.

So, in other words, transvaginal sonography is an excellent means to screen patients for endometrial carcinoma.

Unfortunately, there's a high level of operator dependency of transvaginal sonography.

But I think if you use six millimeters as your general guideline for which patients need biopsy, which patients can be followed up, that is very helpful.

I wanna mention briefly the use of color doppler and endometrial disorders.

The endometrium is supplied by vessels coming from the arcuate, the radial vessels that come into the endometrium by the spiral vessels.

And there are some basal layer vessels, but in patients with polyps, typically the spiral vessel is enlarged.

Here's a color Doppler showing the radial vessels.

As you can see histologically, we find a few small vessels in the endometrial layer.

These represent the spiral layer spiral vessels, as shown on this image of the histology.

These are the glandular elements.

As I mentioned, most polyps will drag a feeding vessel into them.

In fact, it makes it very clear that this is a polyp, for example, that has a big vascular pedicle.

This is a big polyp with multiple vessels, as opposed to a patient with hem ometria that has little or no vessels within the center.

This is a patient who had infertility.

The polyp is shown here with its feeding vessel.

This is a patient that had fluid.

We did not instill fluid.

She presented with this amount of fluid in the lumen.

These polyps are very irregular, and as you can see, some of the large feeding vessels as shown here.

This is the scopic picture of these polyps that were found to be endometrial carcinoma.

Transrectal Sonography for Guided Biopsy

I wanna mention briefly the use of trans rectal sonography, and specifically biplane, transrectal sonography for difficult patients that may have cervical stenosis.

These probes have a linear array here and an axial orientation of the transducers at the top.

And a condom is put over the probe.

And the probe is introduced trans rectally.

And as you can see, the field of view is very limited to the cervix and part of the uterus, but it's very helpful.

For example, here's a patient that on transvaginal sonography has an ex echogenic area in the myometrium.

These are two or three image four images from a transrectal where this is posterior, this is anterior, this is inferior, this is superior.

And we could help guide the gynecologist in putting the dilator right into the area of the cervix.

And finally you can see its location within the lumen is very clear.

This is a patient with a very abnormal cervix.

The dilator is going two posteriorly, and when corrected went in beautifully.

So here's the dilator going into the cervix, and we could see that it's in the proper position.

The retractors have to be out toward the side to get a good image.

Now, the actual securage instrument is being introduced.

We could confirm that it is luminal by activating the actually oriented had a transducer.

So we're gonna do that and see.

So now this is posterior right, left, and we're moving the probe.

And here is, here will be the uterus right here.

This echogenic area is the dilator, and we could confirm that we're indeed in the lumen of this uterus.

Now we're back in long axis.

The securage instrument is now obtaining the endometrial tissue.

And I highly recommend this technique in the difficult patient.

Here's a patient that unfortunately the bladder was not distended enough.

This is the uterus.

And the dilator could be seen going right through the uterus into a bowel loop.

And when we corrected for a non distended bladder, we got into the uterus perfectly.

Conclusion

So what I've tried to do in this review is to show you that transoral and transvaginal sonography has a very important role in evaluating patients with endometrial disorders.

It's very important that one gets the entire endometrium either manually or by 3D and understand the endometrial disorders are different in premenopausal and perimenopausal women as compared to postmenopausal women, where one is thinking about endometrial cancer.

Hyperplasia cancer can be diagnosed and one can use sonohysterography for further evaluation.

Thank you.