William Morice, II, M.D., Ph.D., Chair of the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota, and President of Mayo Medical Laboratories, kicks off his new leadership podcast series with an interview with Sounak Gupta, M.B.B.S., Ph.D., an Anatomic and Clinical Pathology resident at Mayo, and Melanie Bois, M.D., a Cardiovascular Pathology resident at Mayo. Drs. Gupta and Bois received distinguished awards at this year's United States and Canadian Academy of Pathology (USCAP) annual meeting. Dr. Gupta received the Excellence in Urologic Pathology Award and a Stowell-Orbison Certificate of Merit, while Dr. Bois received the SCVP Young Investigator’s Award. In the interview, Dr. Morice discusses their awards and research.
William Morice: Well, hi, Everybody, this is Bill Morice, Dr. Bill Morice, your Department Chair, here doing the first podcast version of “Chat with the Chair.” I am pleased today to have with me Dr. Sounak Gupta. I just want to talk to him for a couple minutes about an award he received at the recent Annual Meeting of the USCAP. Welcome, Dr. Gupta.
Sounak Gupta: Thank you, Dr. Morice.
WM: So, can you just tell me a little bit about the award that you received?
SG: Yeah, recently at the USCAP Meeting, the International Society of Urologic Pathology gave me an Excellence in Research Award, and it was for a project; and for the same project, I also got a Stowell-Orbison Award.
SG: So, it turned out fantastic. And initially, it was supposed to just be a case report, but we got a little carried away with Dr. Sukov, and good things happened.
WM: Wow, so what’s . . . is it a . . . can you just give me like a brief description of the project itself?
SG: Sure, so we were looking at subclassifying renal cell carcinomas. And for renal cell carcinomas, for the most part, we think of them as very homogenous entities. We classify them morphologically, and we are just starting to break them down based on the molecular alterations. And actually, the MML really contributed to how we came up for that project because a lot of cases get sent in, in consultation for FISH studies, and we started seeing a very unusual pattern. For example, a common alteration is a TFEB rearrangement; but instead of seeing a rearrangement, we are seeing a massive amplification.
SG: And so we went and looked through close to 1600 cases, both in-house and public databases, and we found that a big portion of chromosome 6 was amplified, and this included VEGF; and as you know, most clear cell renal cell carcinomas are treated with VEGF inhibitor, so it was a very exciting project. And before we knew it, we found close to 30 cases. And so our estimate is that we almost have 3% of papillary renal cell carcinomas, maybe 4% which, on an annual basis, works out to at least maybe 200 to 500 cases just in the United States, and so these patients have very aggressive disease and are very likely to respond to targeted therapies.
WM: Wow, how cool is that? So I mean, it’s a great story #1 because, you know, it really shows that how . . . that the power of the reference lab and getting exposure to the world outside of Mayo Clinic, but at the same time with that Mayo Clinic focus on improving patient care, that kind of the real powerful synergy there. So, did you know you wanted . . . I mean, are you someone that, like when you . . . as soon as you showed up, you knew you were interested in urologic pathology and this is what you pursued or . . . ?
SG: Yeah, before I came here, I did postdoctoral research at the Cleveland Clinic and at USCD, and I was focused on bladder cancer. And when I came here, I knew I wanted to do GU pathology, but I had no specific idea or . . .
SG: . . . specific project in mind, so I just looked for anything that was available, and I remember Dr. Sukov calling me into his office saying, hey I’m seeing this really weird pattern. Do you want to write a case report? And before we knew it, we said let’s look at a few more cases, and a few more turned into close to 1600 cases.
SG: And before we knew it, we were onto something really exciting.
WM: And the world’s noticed too because you got the awards, right?
SG: Yeah, and our manuscript just got published today, in fact, in Modern Pathology, so it’s just a lot of good things have happened with this project.
WM: Wow, wow, that’s . . . well congratulations. It’s great to hear. It makes me think back to the . . . I mean there’s . . . first of all, I’m glad to hear it wasn’t your early experiences with me as a (laughs) in hematopathology that scared you away from bone marrow pathology, you know. I was all set to do hem, and then I worked with you, Dr. Morice, no (laughs). But more importantly, too, is just . . . I mean, the fact that you were able to come here and have an idea and actually see it blossom into something much bigger than you suspected. That’s happened to me in my own career with some different things and kind of fed by MML and the questions that people asked as well. For me, it was differentiating myeloma from lymphoplasmacytic lymphoma. And also, though, I have to congratulate you because I think back to when I was really just coming on staff, there was a senior faculty member who was . . . I really, really respected, and I remember he sat me down and he said . . . because someone had came up to him . . . he was a famous pulmonary pathologist . . . and said, oh I’ve seen Dr. So-and-So . . . I won’t say his name . . . I’ve seen . . . I just saw a thousand cases of X and . . . or I just looked at a thousand cases of X . . . it was like pulmonary leiomyomatosis or LAM or whatever . . . and he sat me down and said, Bill, there’s a big difference between looking at a thousand cases of something and seeing a thousand cases of something; and so the project he described as seeing . . . you know, seeing something in those renal cell tumors that really needed to be pursued . . . so congratulations; it’s great . . . it’s so gratifying for me to hear that this is happening in the department still because that’s kind of what makes this place really vibrant. Thank you for your energy in pursuing it, and congratulations on receiving the award.
SG: Thank you again. I just couldn’t have done it without all of the opportunities at Mayo Clinic.
WM: Thank you, Dr. Gupta. It’s a really great story. Also with us today is Dr. Melanie Bois, who also received an award at our USCP Meeting, and it is a pleasure to have her here today to talk to us about it. Melanie, welcome.
Melanie Bois: Thank you. Thank you for having me.
WM: Oh yeah, it’s my pleasure. So you got the Young Investigator’s Award. Could you just tell me a little bit more about that . . . what’s it about?
MB: I did, yeah. Thank you for inviting me here to talk about it. It was a really exciting award I got from the Society of Cardiovascular Pathology; so this is a group of national and international pathologists with a specialty in cardiovascular, and they are really focused on forwarding research opportunities for younger individuals within the field, and so they were . . . they bestowed upon me this particular award this year, which was really quite a great honor. It was for a particular study that I did on subaortic membranes, which is something that is an uncommon specimen (laughs).
MB: It is quite hard . . . it is something that a lot of people haven’t heard of. It’s . . . and that’s because it’s relatively uncommon around different surgical practices, but we actually see quite a bit of it here, and that’s because Mayo Clinic is a center for excellence in subaortic membranes and the diagnostic and treatment of such. So, we really focused in on #1 understanding the pathobiology of this disease process and trying to figure out if there’s any molecular underpinnings to it.
WM: Got it.
MB: And to also forwarding our diagnostic abilities for this disease and related diseases.
WM: So, what is "subaortic membrane"?
MB: It’s a confusing topic, but, essentially, it’s just a membranous or fibromembranous outgrowth right below the aortic valve just within the left ventricular outflow tract, and this can create disturbances of blood flow going through that left ventricular outflow tract, leading to aortic or subaortic stenosis, and it sometimes necessitates surgery because of the downstream effect on the left ventricle.
WM: Interesting, interesting. Who did you work with on the project?
MB: I worked with Dr. Joseph Maleszewski. He was my primary mentor on this project.
WM: What did you find? Did you find the molecular pathogenesis?
MB: We did. In a subset of our cases, we found a link to the RAS-MAPK pathway, which is a cytoplasmic signaling pathway, again a function mutation which is typically associated with Noonan’s syndrome, interestingly enough.
MB: So, we found two mutations in PTPN11 and one in SOS1, both of which participate in this pathway, and it’s a really interesting diagnostic link and association that we’re going to be following up on in future studies to try and better define this particular disease.
WM: Wow, that’s really great! You know, and it makes me think about, again, one of the advantages of being here at Mayo is that there’s a lot of things that are considered uncommon or are so uncommon that people have a hard time seeing the linkages between cases; but when we have the sufficient number of cases here and smart people and curious people, such as yourself, to look at them, we start seeing . . . you know, revealing new things and diseases that are relatively uncommon but, you know, if I’m the one person . . . if I’ve got a subaortic membrane, I don’t really care if it’s common or not; I just want someone to help me figure out whether, you know, especially if it’s going to require surgery or is my family going to get it, all those question. I mean that’s the first question now that I have kids; well, it’s not the first question I have about my kids, but if I have a . . . like when I got my DVT, the first question you want to know is: Are my kids going to be at risk for this as well? So, it’s all of this stuff is really, really important. So, I mean you’ve been here . . . did you go to medical school here as well?
MB: I did, yes, I started medical school here, just like you.
MB: And I performed my anatomic and clinical pathology residency here, and I'm now in my first fellowship in cardiovascular pathology.
WM: Got it. Are you interested in pursuing a career in CV pathology then?
MB: I am, yes. I’m very interested in that, and I’ll be doing a second fellowship in cytopathology next year also here as well.
WM: So, in cardiovascular pathology, is that . . . people tend to think of that as more of a, you know, postmortem autopsy type of practice, but it sounds like it’s got quite a surgical . . . you can have a surgical practice as well?
MB: Yeah, that’s one of the things I love about it is the ability to balance both the whole gross specimen at the time of autopsy and really give answers to patients who are . . . and decedents in their particular families when they come in with questions regarding why this patient died or what exactly happened with their heart disease, and then also the living patients and the surgical patients that we do have, being able to provide them answers as well, so it really balances both worlds, and it just makes for a fascinating practice; it really does.
WM: Wow, well you know, I’m so pleased that you got the award, that the work you did got recognized. I love this story. It’s a lot like the one we heard previously from Dr. Gupta about just having the uniqueness of Mayo and having really bright and . . . bright people who will not stop until they get an answer to a question, really digging into things, and so I congratulate you on getting the award. I’m so pleased that you did, and I really thank you for taking the time to share it with us today.
MB: Thank you so much. I appreciate it.