Incidental Finding of Papillary Renal Cell Carcinoma on Renal Biopsy

In this podcast, James Matera, DO, speaks about a patient case presentation of a 41-year-old man with a recurrence of minimal change disease and an incidental finding of papillary renal cell carcinoma on renal biopsy. 

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James Matera, DO, is a practicing nephrologist, Senior Vice President for Medical Affairs, and Chief Medical Officer at CentraState Medical Center (Freehold, New Jersey).

TRANSCRIPTION:

Jessica Bard: Hello everyone, and welcome to another installment of Podcast 360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard, with Consultant360, a multidisciplinary medical information network.

Dr James Matera is here to speak with us today about a patient case presentation of a 41-year-old man with a recurrence of minimal change disease and an incidental finding of papillary renal cell carcinoma on renal biopsy. Dr. Matera is a practicing nephrologist, senior vice president of medical affairs and Chief Medical Officer at CentraState Medical Center in Freehold, New Jersey. Thank you for joining us today, Dr. Matera. Please tell us more about this patient.

Dr James Matera: Yeah, this is an interesting case. I've been in practice almost, definitely a silver back here, I've been in practice for 30 years. And first met this gentleman when he was age 18. He came to me for a second opinion when he had biopsy-proven minimal change disease; very common in children, but in an 18 year old, it's not as common, but it's certainly one of the reasons for nephrotic syndrome. So he had a biopsy done at that time, which proved minimal change disease. We actually treated him; they do respond to steroids, which was good. In this particular gentleman, he kept having some relapses. And I'll go over in a moment what the definitions are of relapse and recurrence. But once I switched him over to a different agent, in that particular case I used mycophenolate, and he did very well and went into a full remission.

Now a full remission is a reduction in his proteinuria, which at that time was about 10 grams, down to less than 300 milligrams per day with a stable serum creatinine and serum albumin greater than 3.5. So he actually achieved a complete remission. A partial remission may be a reduction in proteinuria of about 50%. In this case it would've been if he went from 10 grams down to five grams, that would certainly be a consideration.

But he had some difficulty at first, but then he went into remission at age 20. I see him in the office every six months. And now at age 42, he comes to me with a flare of nephrotic syndrome again. So 24 years or so after his initial issue, he's back up to about six grams of protein hypoalbuminemic; typical nephrotic picture. But he has normal renal function, which oftentimes they do. So, my question here was, what's going on? Does he have a recurrence after 24 years of minimal change disease, number one. Number two, did he progress as some of these people with minimal change are likely to do towards a more ominous lesion of focal sclerosis? So we see that, or number three was something else completely different.

So I decided to do another kidney biopsy. He hasn't had one in 24 years; there was no need. So I did an ultrasound beforehand; everything was normal. We proceeded to a biopsy. And I got a report from the pathologist that he had found a nest of papillary cell carcinoma along with, interestingly enough, minimal change disease again. So what we have is a recurrence of minimal change disease after 24 years, and this isolated unexpected finding of a nest of papillary cell carcinoma.

So interestingly, most of the time when we see renal cell tumors, whether it be clear cell or papillary cell, you see a mass. So I went back and I looked at the ultrasound, and there is no mass. So did we pick up a so very super early papillary cell carcinoma, and what does it mean? I still don't have the answer for you yet as to what that means, but we picked up a renal cell carcinoma or papillary cell carcinoma with no evidence of any lesions on the CAT scan.

The reason I bring this case up is if you think about minimal change disease, and now he's got minimal change disease again, but his age 42, there are some things that I would wonder about why this remission occurred. Number one would be on my mind, infection. Now in the era of COVID, we are seeing some patients who get COVID, some type of COVID-associated kidney disease, very similar to what we saw with HIV. There's actually HIV-AN, HIV-associated nephropathy. Well, I think there's also going to be a COV-AN, or COVID-associated nephropathy. This gentleman did not have any COVID. One thing you always have to remember in minimal change disease, especially in the adult, is it can often be found in association with malignancies. So a patient like him who we didn't see a nest of cells at 42, who came back minimal change disease, wasn't on medications because that can also cause it; certain medications can cause that, or he didn't have any known viral infections, I'd be worried about malignancy.

So the question I have for the audience that I'd be happy to have them email me some of their thoughts, Did we uncover recurrence or flare in this guy's minimal change disease, or is it because of the papillary carcinoma that we're seeing, and what do we do for that?

So I think my best bet when I looked at this is here's what I'm going to do in reference to both diseases. For the papillary cell carcinoma, I actually just biopsied this gentleman about three or four weeks ago, I'm going to wait for a total of six weeks, let all the hematoma subside. Then I'm going to do another thin-cut CAT scan just to make sure there's no tumor there. If I don't find a tumor, fine, we just watch him. If I do find a tumor and it's below 1.5 centimeters, I think watchful waiting is also warranted. If we do find one that's above that, then I think we have to go in and look at removal.

For the minimal change disease. I did start, again, with corticosteroids, at a dose of two milligrams per kilogram divided every other day to see if we can abate that. After three weeks he, he's gone down into a partial remission. Half of his proteinuria is gone, but I will treat him out to about 16 weeks before we start to taper.

But interestingly enough, patients can do this with minimal change disease. You can see a period of, 20 years has been reported in the literature in at least five studies that I'm aware of, where they get a flare and there's no ominous thing to it. It just happens. The take-home message is for this though is, I want you to understand that when you see minimal change in an adult, you should be thinking of some type of secondary cause, whether it be malignancy, drug-associated or viral. Number two is that even though most recurrences will occur within a year, you can see them further out with minimal change disease. And interestingly enough, we also did not see any evidence of focal sclerosis. But you have to remember that that could be part of the continuum of this disease.

Now remember when I'm doing a kidney biopsy, there's a million functioning units, glomeruli in each kidney, a good biopsy, I'm hitting 10 to 20. So maybe there is focal sclerosis and we just missed it. Sampling error, if you will. This I thought was an interesting case because I'm looking at two separate diseases. One I was not expecting whatsoever, and now I have to make that circle back. Is this an uncovering of a very, very early carcinoma that now causes minimal change disease? Part two is what I'm calling it this.

Jessica Bard: We'll have to keep an eye on this and maybe do a part two of this podcast.

Dr James Matera: Yeah. Yeah, I think as we move along. I did all my biopsies that I do down here, we sent to Columbia, which is probably the best renal pathology group in the world. So I've been in touch with them and we've been talking about this case. So we're going to look at that as well.

But I think this is a very interesting thing because number one, I have to fix his nephrotic syndrome, if we can. And number two, I have to worry about this 42-year-old with the nest of papillary carcinoma.

Jessica Bard: Did you want to talk more about the definition of relapse and recurrence?

Dr James Matera: Yeah. So when we look at nephrotic syndrome in general, a complete response I told you would be a reduction of proteinuria, basically to normal levels, under 300 milligrams per day. A partial remission would be 50% reduction. So again, first off with this gentleman, he had 10 grams. If we went down to five grams, that would be the case. But then we have other things we have to worry about. Relapse; a relapse would be a return of proteinuria to greater than three and a half grams per day, which is what this gentleman now has. So he has a relapse of what was previously a complete response. And then you have the timing of that. Frequent relapsers; frequent relapsers tend to have two or more relapses within a six-month period of time. So if you get a response, a complete or a partial response and then you taper and then they relapse again to nephrotic range levels, then of course we base, especially minimal change disease, their dependents on glucocorticoids.

We know in kids glucocorticoids work so well that we don't even biopsy kids with nephrotic syndrome because we assume they have minimal change disease. So sometimes you could be dependent on glucocorticoids; meaning every time we try to taper them down, within two weeks you'll relapse again. But you start steroids and it tapers down again. So that's glucocoid-dependent.

Then we have, what I'm worried about in this gentleman, is glucocoid-resistant, meaning that we're going to treat him with the steroids and he's going to have no response. He's going to have the persistence of proteinuria greater than three and a half grams. And he's currently at eight grams; was at eight grams, he's now down to four. So he has a partial response right now. So again, these are the things we have to look at.

When we look at glucocorticoid-resistant or steroid-dependent, that's when we start to open up the toy chest and see what we're going to use next. And there are a lot of other things that you can use, from Rituximab to ACTH to calcineurin-inhibitors. There's a lot of different things that we could use.

So right now I have a relapser and a former complete responder, and time will tell where he fits on the continual.

My email is jmatera@centrastate.com. If anybody has seen this or wants to email me. I'd be happy to engage with any of the listeners.

Jessica Bard: Thank you Dr. Matera. We really appreciate your time.

Dr James Matera: Right. Thank you.

Jessica Bard: For more chronic kidney disease content, visit the resource consultant360.com