What To Do When…Clinical Issues in Ultrasound - SD

Introduction

Hi, my name is Bill Middleton.
I'm a professor of radiology at Washington University in St. Louis at the Mallinckrodt Institute of Radiology.
I am going to talk to you today about a variety of clinical issues and ultrasound, several clinical scenarios, and what do you do when you encounter them.
Okay? So let's look at four separate clinical situations that you might encounter.

Treating Small Pseudoaneurysms

The first one is, what do you do when asked to treat a pseudoaneurysm, measuring between one and two centimeters in size?
And the index case that I'm showing is the NIC clip that you see below.
So what would you do if you were asked to treat this?
And the potential responses are recommend serial follow up waiting for thrombosis to occur spontaneously, recommend ultrasound guided compression, recommend ultrasound guided thrombin injection, recommend angiography directed treatment or recommend surgery.
Well, I can tell you that what I elected to do was to inject it with thrombin.
I injected 0.05 ccs, which translated into a dose of 50 units of thrombin, and this is the result.
So you can see that the pseudoaneurysm thrombosed, but in addition, a little bit of thrombin leaked out and produced this intraluminal thrombin plug that was attached to the neck of the pseudoaneurysm.
This was fairly disconcerting to me when I saw it.
I immediately checked the patient's pulses.
Then I checked my pulse, and everybody was doing okay.
I was a little tachycardic, but the patient was fine.
And he never developed any clinical symptoms.
He never lost pulses.
He never developed any signs of ischemia.
This is a series of scans that were done in follow up of this patient.
And you can see on the immediate post thrombin injection to the left, the little thrombin plug in the lumen of the artery.
The next day, we re-scanned him and it was still there.
We were relieved that it hadn't migrated distally.
It had gotten a little bit smaller, and then by day 20, it had completely resolved.
And this patient did fine, never had any problems whatsoever.
Now, subsequently, I've seen this two other times, and each time I've seen it, I've been very worried about the patient.
But each time the patient has done fine and never had any problems, never required any therapy.

Contraindications to Thrombin Injection

But this does bring us into a discussion about contraindications to thrombin injection of pseudoaneurysms.
And there's several that have been discussed in the literature.
One is a short neck, and the patient that I showed you certainly falls into that category.
Now, unfortunately, the articles that have been written and have listed a short neck as a contraindication never defined what a short neck is, how short is too short to inject.
So that's fairly nebulous.
However, in series of patients that have been reported in whom thrombin has been injected successfully without complications, the ranges of neck size or neck lengths that have been reported range all the way from zero to 31 millimeters.
So clearly you can inject necks that are very short without problems, and do that without too much difficulty.
Now, another contraindication is a wide neck.
Now again, how wide is too wide has not been defined in the literature.
But when reported in series of patients that have been thrombosed successfully without complications, the width of the neck has ranged from 0.3 millimeters to eight millimeters.
Problem is none of these studies describe exactly how they measured the width of the neck.
They don't say if they measured the maximum width or the minimum width.
They don't say whether they measured it during systole when it's larger or during diastole when it's smaller.
And then they also don't say whether they measure it with color or with gray scale.
And clearly the neck size is going to look bigger with color than it is with gray scale.
So although wide necks are a relative contraindication, there really is very little guidance as to how wide is too wide.
Now, another contraindication that seems fairly straightforward is poor visualization, poor visualization of either the needle or the pseudoaneurysm itself.
If you don't know exactly where the needle tip is, you should not be injecting.
And then finally, contraindication is that rare patient that has a combined pseudoaneurysm and arteriovenous fistula.
When there's a combined PSA and fistula, then there's the potential that the thrombin that you inject will leak out of the venous drainage, go right into the venous system, and cause either DVT or worse travel up to the lungs and cause a PE.
So these are some of the contraindications to thrombin injection.
Another factor that plays into your decision whether to inject or to treat pseudoaneurysms is the natural history of untreated pseudoaneurysms.
And actually, the natural history is pretty good.
This is a very nice study that came out in the late 1990s that followed a series of small pseudoaneurysms, and they defined small pseudoaneurysms that were less than three centimeters in size.
And pseudoaneurysms in that size range thrombosed spontaneously at a rate of 88%, 72 out of 88.
And the range of time that it took to thrombose ranged from one to 125 days with an average thrombosis time of 23 days.
So it may take a while for them to thrombose, but a large percentage of them will thrombose if you give them enough time.
Now, this study did discover that spontaneous thrombosis, although it occurs, it's less likely if the patient's anticoagulated or if the pseudoaneurysm is chronic and is developed a fibrous wall.
So the conclusion is that you can follow small pseudoaneurysms, and treat them only if they persist or if they enlarge.

Examples of Spontaneous Thrombosis

And here's a nice example of a small pseudoaneurysm that we followed over time.
You can see in that upper left hand image, that was when the patient first presented on 3/28.
On 4/7, we repeated a scan and it was still there.
Hadn't changed much. We repeated a scan two weeks after that on 4/21 pseudoaneurysm was still there.
You can see it's partially thrombosed, but still present.
And it wasn't until 4/28, four weeks later that the pseudoaneurysm was completely thrombosed.
So it took a little while for it to thrombose, but it did.
Here's a patient that we diagnosed a pseudoaneurysm one evening.
It was late in the day and we decided we would wait until the next morning to thrombose this pseudoaneurysm.
And you can see when the patient came back to have his thrombin injection the next morning, it had already thrombosed spontaneously.
Here's another example of a pseudoaneurysm.
This is in a patient that had just had a cardiac catheterization.
You can see that the pseudoaneurysm has a nice long neck here and has a relatively small discreet lumen.
Well, this patient also had another interesting finding.
So the image to the left shows the typical to and fro pattern of flow in the neck of the pseudoaneurysm.
But the image to the right was obtained just slightly distal to the neck of the pseudoaneurysm down near the bifurcation of the femoral artery.
And you can see that the flow in this area is very high velocity and very low resistance.
This is typical pattern of an associated arteriovenous fistula.
And for this reason, plus the fact that the pseudoaneurysm was relatively small, the person who did this case decided not to inject the pseudoaneurysm and just wait for spontaneous thrombosis.
Well, the patient was discharged, went home when he got up out of bed at night to use the restroom.
The pseudoaneurysm ruptured.
He developed a lot of pain, a lot of swelling at the site.
He came back into the emergency room and had a CT arteriogram done.
The two images up above, you can see the infiltrating hemorrhage in the groin as well as the pseudoaneurysm lumen.
And in fact, there was a second lumen of the pseudoaneurysm that had developed after it had ruptured this coronal reconstruction, you can see the two pseudoaneurysm lumens and the hemorrhage surrounding it.
And here on the 3D reconstruction, you can see both components of the pseudoaneurysm Here.
And here you can also see the early draining vein indicating the presence of an arteriovenous fistula.
So let's just review the anatomy on this patient.
He had a pseudoaneurysm with a long, slender neck and a classic to and fro pattern arising from the neck and distal to this.
He had an arteriovenous fistula with the classic low resistance, high velocity flow at the site of the fistula.
So this represents a coexistent pseudoaneurysm and AV fistula.
It really does not represent a combined pseudoaneurysm and AV fistula, and the distinction is important.
So having sorted all that out and having known that this patient had already ruptured once, we decided to thrombose him the next morning, and in fact, were successful using a hundred units of thrombin.

Coexistent vs. Combined Pseudoaneurysm and AV Fistula

Now, I mentioned the distinction between a coexistent pseudoaneurysm and AV fistula, and a combined pseudoaneurysm and AV fistula.
This is an example of a combined pseudoaneurysm and AV fistula.
The image to the left shows a typical appearing pseudoaneurysm.
But when you look at the flow pattern in the neck of the pseudoaneurysm, it is not the to and fro pattern.
It's a high velocity, relatively low resistance pattern with lots of antegrade diastolic flow throughout the cardiac cycle.
This is the type of pattern more consistent with an AV fistula.
And this suggests that this pseudoaneurysm has some sort of outflow other than the neck.
As we looked a little bit more closely, we did find this outflow tract right here.
And waveforms obtained from the outflow tract again, show low resistance, high velocity flow consistent with an AV fistula.
So the anatomy here is like this.
There is a pseudoaneurysm arising from the femoral artery, but then it connects to a channel that drains into the femoral vein.
So injection of this pseudoaneurysm would result in thrombin just spilling directly into the vein, causing, potentially causing DVT or PE.
Now, why do you get combined pseudoaneurysm and AV fistulas?
If you look at the anatomy of the common femoral artery and vein, you can see that there are a number of small branches and several of these branches, one is shown here, go in front of the femoral artery.
So this is a venous branch that travels in front of the femoral artery.
If you puncture right in this area, you can potentially get an AV fistula between the artery and that venous branch.
And if there's also a pseudoaneurysm involved, then that produces a combined pseudoaneurysm and AV fistula.
That's the sort of thing that you would not want to inject.

Primary Hyperparathyroidism with Negative Sestamibi Scan

Okay. Let's move on to the next clinical scenario.
What do you do when a patient with primary hyperparathyroidism has a negative Tc-99m sestamibi scan and a sonogram that shows suspicious nodules or nodule?
And here's our index case.
So Tc-99m sestamibi scan shown up above is negative ultrasound shown below shows a small nodule deep and along the inferior aspect of the right lobe of thyroid, and then a similar size nodule more superficial and inferior to the left lobe of the thyroid.
So in this situation, do you trust the Tc-99m sestamibi scan and assume that the nodules are lymph nodes and not parathyroid adenomas?
Do you trust the ultrasound and diagnose multi gland involvement?
Do you recommend a MRI or a CT to further evaluate these nodules?
Do you recommend aspiration of the nodule or nodules, or do you recommend angiography with venous sampling?
Well, in this case, we decided to aspirate the nodules.
The nodule on the right was relatively deep and would've been hard to get to.
The nodule on the left was superficial and relatively easy to get to.
So we aspirated the nodule on the left and we sent the specimen for PTH assay.
And you can see that the result of that assay was a PTH value of 4.9 picograms per milliliter.
That's within the normal range, indicating that this nodule is not a parathyroid adenoma.
Knowing that we assumed that the nodule on the right was the parathyroid adenoma, and this patient went for a right neck exploration, and sure enough, a right superior parathyroid adenoma was identified in a posterior inferior location just as we would've predicted.

Aspiration Technique for Parathyroid Nodules

So let's talk a little bit about aspirating parathyroid nodules and sending the specimen for PTH levels.
This was first described as best I can tell, back in 1994 by a group at Beth Israel and Harvard.
The technique that they used was they injected 0.25 ccs of saline into the nodule and then aspirated as much of that fluid as they could.
They did it one or more times, they put the specimens in separate tubes, froze them, sent them to the lab to get PTH assays.
And in their experience, most of the ones that were positive were unequivocally positive.
In other words, the PTH levels were quite high, although they did have six parathyroid adenomas that had false negatively low PTH levels.
And presumably that was because they did not adequately sample the lesion.
They did not describe what levels of PTH they obtained in the lesions that were not parathyroid adenomas.
Now, since this time, a number of institutions have started to do this, and in fact, in busy practices, it's fairly common procedure.
This report from the Cleveland Clinic describes doing one to two passes, diluting the specimen in five ccs of saline.
In other words, they do a couple of passes.
They aspirate what they can, they put the aspirate in a tube with five ccs of saline, submit that for analysis.
And in their experience, the positive results range between 44 and 13 million picograms per ml.
And 91% of their positives had a value greater than 500 in lesions that were not parathyroid adenomas.
The values range from four to 15.
And in this last study, more recently from a group in Istanbul had a fairly similar technique.
And in their experience, the positives ended up having levels between 30 and 705,000, and the negatives had levels between four and 20.
The technique that we use at Mallinckrodt is to aspirate a suspicious nodule with a 25 gauge needle.
We use suction. We take the sample and wash it with a cc of saline and inject the resulting mixture in a test tube.
Then we put the test tube on ice.
And then we repeat the aspiration and wash the needle and the connecting tube with saline from the prior aspiration.
And then we deliver it immediately to the lab for analysis.

Examples of Parathyroid Aspirations

And here's some examples of other cases that we've done.
As you can see above, there's two ultrasounds showing a complex solid and cystic mass inferior to the thyroid with readily detectable internal flow.
The Tc-99m sestamibi scan in this patient was negative.
Because this was such an unusual appearance for a parathyroid adenoma, we thought that we wanted to be sure that that's truly what it was.
So we aspirated it, and you can see the result was greater than 4 million picograms per milliliter.
We consulted our charts and in fact, that was above the normal range, and this turned out to be a complex parathyroid adenoma.
And here's the last case.
This is a patient again with primary hyperparathyroidism.
In this case, the Tc-99m sestamibi scan was positive, showed an area of persistent uptake in the region of the left lobe of the thyroid.
On the SPECT scan, you can see that it clearly looks like it's arising within the left lobe.
And they described that as increased accumulation in the left lobe of the thyroid and gave a differential of either a thyroid adenoma or a parathyroid adenoma.
So we went on and did an ultrasound on this patient confirmed that there was a solid nodule in the left lobe of the thyroid, quite vascular on color Doppler imaging.
And in our opinion, we thought that this was more consistent with a follicular thyroid neoplasm than a parathyroid adenoma.
Given that potential differential, we decided we needed to aspirate this nodule.
And the cytology from it came back as follicular cells in a background of blood.
So this was, in fact a follicular lesion.
Unfortunately, cytology cannot distinguish a follicular thyroid nodule from a parathyroid adenoma.
You can only do that with PTH aspirations.
So in this case, the PTH assay showed a result of greater than 2000, and we felt comfortable calling this a parathyroid adenoma.
And in fact, it was intra thyroidal parathyroid adenoma confirmed at surgery.

Splenic Biopsy in Patient with Lymphoma History

Let's go on to the next clinical situation.
What do you do when asked to biopsy a new focal solid splenic lesion in a patient with a history of lymphoma?
So the index case is shown below.
As you can see on the contrast enhanced CT scan.
There's a oval shaped lesion deep in the splenic parenchyma that was FDG avid on a PET scan and appeared solid and hypoechoic on the sonogram.
So the options here are to refuse violently, refuse to biopsy it, but do so politely, agree to biopsy and schedule on a partner's day, or agree to a biopsy, but only do fine needle aspirations or agree to biopsy and do core needle biopsies well.
So in this case, we agreed, as you can see, to go ahead and do a core needle biopsy.
And this is a short clip of the biopsy taking place.
This did turn out to be positive for recurrent lymphoma.
After the biopsy, you can see that there's a small hemoperitoneum that developed in the perisplenic space.
We followed this patient very closely, repeated scans a couple of times afterwards.
And this never got any bigger.
He never had any symptoms, and he was discharged from the hospital later that day.

Discussion on Splenic Biopsies

So let's just talk a little bit about splenic biopsies.
We always are taught that the spleen is a very vascular organ and that we should avoid doing biopsies whenever possible.
But this retrospective review that was published in this past year looked at 52 patients that were biopsied 62 times.
They had a fairly even mix of malignant lesions and benign lesions.
The results were that 24 of the aspirate showed a malignancy 22 showed a benign lesion, and six were non-diagnostic.
They used FNA approach with a range of needle sizes from 20 to 25 gauge and 37 instances and core needle biopsies with a range of needle sizes from 19.5 to 14 in 25 patients.
And of these biopsies, they had two episodes of hemorrhage.
One was minor, probably similar to the case that I just showed you, and one unfortunately was severe and required a splenectomy for treatment.
So complications did occur, but they were uncommon.
What about the accuracy?
Well, the accuracy was actually quite good.
Fine needle aspirations had an accuracy of 87%, and core needle biopsies had an accuracy of 92%.
Now, in the specific instance that we talked about lymphoma, this series had 22 cases and the fine needle aspirate were adequate in 80% core needle biopsies were adequate in a hundred percent.
And I would recommend that if you had the situation where you're trying to diagnose recurrent lymphoma, that you do use a core needle biopsy.
'Cause not only will that make the diagnosis of lymphoma, but it will help to characterize the subtype of lymphoma.
And we mentioned that it is possible to biopsy both malignant and benign lesions.
This is just an example of a benign lesion sarcoidosis that was diagnosed with fine needle aspiration of the spleen.

Solid Extratesticular Mass

Now the last clinical scenario that I'm going to present to you is what do you do when you identify a 1.5 centimeter solid extra testicular mass?
This is the index case here where we see a lesion that's just slightly bigger than a centimeter superior to the upper pole of the right testis.
This is a cine clip showing that the lesion is separate from the head of the epididymis as well.
This was a transverse view.
This is actually the head of the epididymis, and this is the lesion in question.
You can see that it's quite mobile.
It did not move from the superior aspect of the scrotum, but it was quite mobile.
So what do you do? Do you call this a benign lesion and recommend nothing?
Do you call it indeterminate and recommend serial clinical follow up?
Do you call it indeterminate and recommend ultrasound follow up?
Do you say it's indeterminate and recommend a percutaneous biopsy or do you pull the trigger and call it potentially malignant and recommend excision?
Well, let's just look at a few other lesions before we talk about that.
Lesion in the upper left hand corner is a solid heterogeneous hypoechoic mass superior to the testis.
This was resected and shown to represent sarcoidosis lesion.
In the upper right hand corner is a similar appearing lesion, but inferior to the testis in the region of the epididymal tail.
This was also resected shown to represent an adenomatoid tumor.
The image in the lower left hand corner just is included to remind you that there is the condition of polyorchidism and extra testicular masses can sometimes be testicular tissue themselves.
This is a case that Tom Winter loaned to me.
Now this on the other hand is a lesion superior to the testis, large solid hypoechoic, slightly heterogeneous with an area of calcification.
This looks a little bit more concerning than the other lesion that I showed you based on its size and sonographic morphology.
And sure enough, this turned out to be a malignant leiomyosarcoma.
This is a lesion that a patient that presented with a lesion just superior to the left testis.
The lesion was primarily solid, but had a prominent cystic component, readily detectable blood flow.
This was an older gentleman, and we were concerned that this might represent metastatic disease.
We actually looked around other parts of his body and did find a large supraclavicular lymph node that had not been detected clinically, although it was palpable, as well as scattered peritoneal nodules.
And this turned out to be a metastasis from a lung cancer.

Data on Solid Extratesticular Masses

So what's the data on solid extra testicular masses?
There's actually a nice study that Mary Frates from the Brigham published in 1997.
She looked at 19 surgically proven solid extra testicular masses.
And surprisingly, or at least somewhat surprisingly, three of the 19 were malignant.
All were sarcomas, a leiomyosarcoma, a liposarcoma, and a fibrosarcoma.
16 of the 19 lesions were benign.
And you can see the list of lesions.
There were six adenomatoid tumors, two lipomas, two epididymal inclusion cysts, two cases of sarcoid and four miscellaneous other lesions.
They looked closely for differences in the ultrasound findings in the malignant and benign lesions.
And unfortunately, there weren't characteristic differences in either the appearance, the size, or the location of the lesion.
Now clearly there's a selection bias to this type of a study because many benign lesions were probably not resected and did not get included in these statistics.
However, many of the benign lesions that are extra testicular, in fact, the majority are lesions that are clearly benign and you wouldn't even consider resecting.
And in that list you include things like spermatic cord cysts and hydroceles and varicocele.
Those are so easy to diagnose, you wouldn't even think about doing surgery on those.
So the lesions that we're really focusing on are the other lesions, the solid extra testicular lesions that have a slightly different differential diagnosis.
So in this case, our index case, this turned out to be a papillary cystadenoma of the appendix testis, and it was so pedunculated that explained the rotational component when we compressed it.

Conclusion

Well, that concludes this lecture on what do you do when, thank you very much for your attention.