DIP Episode 541 - Familial Cancer Syndromes and The USMLEs (+ worksheet)

Alright, welcome to episode 541 of the Divine Intervention Podcasts. In today's podcast we're going to be addressing a pretty high-yield topic. I'm going to title this familiar cancer syndrome and the USMELIS. Familiar cancer syndrome and the USMELIS. This is one of those things that you know you're going to see on step one, step two, step three. So I would not ignore it. It's something I would know I'm no well if I were you. We're going to hit up about seven things and there's a worksheet attached to this. So you can either listen to the work, listen to the podcast first and fill out the worksheet at the end or try to follow along and then fill out the worksheet as we go one by one. And the worksheet goes in order with the way I'm going to discuss the pathologies in this question. Alright, now what if they give you a question about like a 17-year-old boy and they tell you that you know for the last like four weeks he's been having pretty significant pain in his regular extremity. Just around his knee and in detail you get an x-ray and in detail you see destructive processes around the cortex of the bone and your toe that the boy has lost some weight and whatnot. So what should you be thinking about there? I hope you're saying divine. This person probably has an osteosarcoma. This person probably has some kind of osteosarcoma. Remember for osteosarcoma you're going to see the codmin's triangle, you're going to see the sombers pattern. That's a very classic x-ray.

You want to make sure you can identify. And typically for those folks, you know, after you get the x-ray you're going to get some kind of MRI to see the lesion and then you're going to do a tissue biopsy. You're going to do a bone biopsy. But osteosarcoma is not the big crux of all of this. I guess maybe I can use that as a leading to what I want to discuss. So what are the classic things we see with osteosarcoma in terms of risk factors? Well, we know that you can get osteosarcoma from having an RB mutation, from having an RB mutation. If you have a retinoblastoma mutation, you can get osteosarcoma. Remember, typically those kids will have a white reflex at birth, things that have a right reflex. So you have a retinoblastoma, which will raise the risk of osteosarcomas. Another risk factor for osteosarcoma is going to be Pajet's disease of the bone. It's probably going to be more than an older person on your exams. Another risk factor may be a person that has been on teraparitite for osteoporosis. Remember teraparitite is a drug that we give for osteoporosis. It's a PT channel lock. When you give it in a bolstital fashion, it's going to encourage bone growth, but when you give it in a continuous fashion, it's going to resort bone. So give it in a bolstital fashion to make the bones grow. You're going to do that for about two years or less. Because if you give it more than two years, think about it.

You're literally given a stimulating factor for bone growth that can cause the presence to have cancer. And then the fourth risk factor I'm going to talk about, which leads into the topic for question one, in terms of bone cancer, osteosarcoma, especially, is going to be the leaf from an eye syndrome, leaf from an eye syndrome. These are pretty high-yield syndrome to know for your exams. And leaf from an eye syndrome, typically they don't ask about specific cancers with leaf from an eye syndrome. But if you want to know the major ones that we find here, we tend to have sarcomas, they tend to have a lot of breast cancers, a lot of brain cancers, a lot of leukemias, lymphomas, especially leukemias. And then we can have some adrenal malignancies. Some people remember it with the numonic SBLA, you know, so sarcomas, breast cancer, brain cancer, leukemias, and adrenal malignancies. But the thing is our friends at the MBM is to be honest with you, they don't usually stress too much about that. The cancer they really love to fix it on, for whatever bizarre reason with leaf from an eye syndrome is the osteosarcoma. Leaf from an eye syndrome has a strongest association with osteosarcoma. So again, we've talked about many of the risk factors for osteosarcoma, but let's talk about a few kind of weird things you should not about leaf from an eye syndrome. First things first was the pathophase. The pathophase is from a P53 mutation.

I'm telling you this for these cancer syndromes, you've got to know the pathophase. P53, remember P53 basically inhibits the transition from the G1 phase to the S phase. If it's mutated, you'll have aberrant transition from the G1 to the S phase. And if that happens, that's a problem. That's literally a problem. Because you don't want to go from the G1 to the S phase if you have like a lot of mutations that have built up that you've not fixed. So G1 to S phase, it inhibits that. So when it's mutated, you won't give it it. So even if you have a genetic mutation, the cancer cell is just going to keep progressing. So you get it from a P53 mutation. And these folks, there's a bunch of screening guidelines, but I'm going to see the critical ones to know is from birth, these kids should get abdominal ultrasounds like every three to four months. The malopeleic ultrasound every three to four months. Because the thing is these people, right, again, they can have adrenal malignancies, they can have sarcomas and all these things. And typically these people also get unobrine MR Is, unobrine MR Is because again, they can get brain cancers. Remember that being the mnemonic, they can get brain cancers, they can get brain cancers. That's actually pretty high, you know, they have all the breasts. How do we interrogate the breast in these folks? Well, the thing is starting at each 20, they should get unobraced MR Is, starting at each 20, they should get unobraced MR Is.

And then because these people can get GI malignancies, although again, this last thing I'm about to mention, they're probably never going to test it on your exams, but they should pretty much start getting colonoscopies roughly at each 25. Although I will say something here, for these high risk folks, typically, especially like these people, they should get colonoscopies about every three to five years or they're about. All right. Now, the thing is, yes, we're on this subject of P53. I think it's kind of helpful to talk about HPV. We know that HPV, especially those gnarly ones, you know, HPV 16, 18, those are the ones that really increase risk of cancer. And the increased risk of cancer because they express two proteins that are ubiquitin ligases, A6 and A7. So you may wonder, divine, what in the world is a ubiquitin ligase? Well, here's the thing, the ubiquitin ligase is something that puts a bunch of ubiquitins on something. When you put a bunch of ubiquitins on something, you're telling that thing, go to the predisome to get chopped up, go to the predisome to be destroyed, to get chopped up. That's pretty high up to no for exams. So if you put a bunch of ubiquitin on something that is good that your body needs, that's going to be problematic because you're destroying that thing that is good. So what do E6 and E7 do specifically? Well, E6 is ubiquitin ligase that polyubiquity needs P53. And then E7 is ubiquitin ligase that polyubiquity needs RB.

P53 and RB are both tumor suppressor genes. When you pull you ubiquitinize them, you target them for predisome degradation. That's going to cause the person to get into trouble because you're literally killing tumor suppressor gene products. And I guess since we're kind of talking about this whole ubiquitination thing and predisomes, I guess it will be helpful to remember that the way we treat multiple myeloma is what a drug known as bortezomeb. And multiple myeloma, one thing that happens is that you have increased predisomo degradation of pro-epaptotic proteins. Proteins that will cause those myeloma cells to die. So if you want to treat multiple myeloma, hey, maybe shut down those predisomes. Seems like a wise idea. If you shut those things down, then you're not going to be degrading those pre-epaptotic proteins. And of course, apoptosis of those plasma cells, those myeloma cells. That's literally how bortezome it works. Bortezome is a predisome inhibitor. Right? Again, make sure you can make these integrations and can leave these ideas together in your mind. All right. Now, the next thing we're going to talk about here, what if they give you a question about a family? And you see lots of CEO cancers in that family. What do I mean by CEO cancers? A lot of colon cancer. That's the C, a lot of endometrial cancer. That's the E and a lot of ovarian cancer. That's the O. When you see something like that, I want you to think of what? Of Lange Syndrome.

I absolutely, positively want you to think about Lange Syndrome. I like to think of this as the CEO's. CEO, CEO, CEO. And basically, what are the gene mutations that can cause Lange Syndrome? I want you to remember your MSS and your emels. Your emels and your MSS. So things like MLH1 and MSH2 and MSH6. Just remember a bunch of emels and a bunch of MSH. So MLH1 and MSH1. If you know those things, you're going to be pretty good to go. And the critical thing to know about Lange Syndrome are those CEO cancers. They can get many other cancers. But the one you really care about for your exam is colon cancer. That's the C, the E's endometrial cancer and the ovarian cancer. And it's actually pretty high you to know that these folks, typically, we're going to start screening them for colon cancer in their 20s. We're going to be starting at age 20. So typically they're going to get colonoscopy's everyone to two years. But honestly, that's not all. That is not all. That is absolutely not all. These people can also get endometrial cancer. They're going to start screening at age 30, at age 30. And the thing is for these folks, if, for example, someone has been diagnosed with colon cancer in the family, then you want to start two to five years younger than that. Two to five years younger than that. I'll see probably five years is a safer number to use for your exams. All right.

So let's say a person was diagnosed with colon cancer in this family at age 20, you got a start screening at like age 15. And again, remember, this will get colonoscopies roughly every one to two years. All right. So again, don't forget CE Os. Don't forget CE Os. Don't forget the pathophase. All right. Now, what if they give you a question about a little child that has tons of polyps in the colon, literally tons of polyps in the colon? And what hope you're thinking about? So that's the third pathology we're talking about. How do you think of FAP? Family, all the nomadous polyposes, FAP, FAP? Remember FAP, the big things about FAP is the APC mutation. APC mutations and all those other dominant disorder. Okay. It's an APC gene mutation and APC gene mutation. APC is a tumor suppressor gene. APC is literally a tumor suppressor gene. Make sure you know that for your exams literally. Make sure you know that for your exams. So what are the key things about FAP? Well, these people tend to get a ton of cancers, right? Literally a ton of cancers, especially colon cancer. That's kind of like the big, big, big one to know for your exams. And for these folks, remember, it's not having the APC gene mutation alone that will cause you to have cancer. There is this thing you need to know for your exams, call the adenometer carcinoma sequence, right? So this will be going to start off with an APC mutation. That's going to cause them to form all these adenomatos polyps.

And then after that, they're going to accumulate the carousam mutation. And then after that, they're going to accumulate a P53 mutation. And then that's going to take them from the adenomatos all the way to cancer. So these people, because the cancer risk is so, so, so, so, so high, you're going to start screening them at each 10, actually. At each 10, they're going to get some kind of chlorrectal cancer screening, typically every one to two years, typically every one to two years. That's pretty high you to know for, for example. And again, remember, I said for Lynch syndrome, colon cancers that are around age 20, endometrial cancers that are around age 30 for Lynch syndrome, for Lynch syndrome, kind of backtracking a little bit there. And remember, people that have FAP, remember if you see them having a little brain tumors, you want to think about turquoise syndrome, you see them having a lot of soft tissue tumors, like hostumes and fibromas, you want to think about something like, it's not turquoise syndrome, it's a gardener syndrome, gardener syndrome, gardener syndrome in those folks. All right, now next thing we're going to talk about, what if you see multiple family members having a bunch of breast cancers, bunch of varying cancers, what should you be thinking about? Actually, at the young ages, think of BRCA mutations, think of BRCA mutations, think of what? BRCA mutations, BRCA mutations. Remember, BRCA mutations, typically you're going to see BRCA one, BRCA two.

These things are associated with like double-stranded DNA break repair. So if you mess those up, if you cannot fix double-stranded DNA break, you're going to have a very high risk of accumulating mutations. And remember, people that have these BRCA mutations is actually pretty high to know what kind of screening you should do for these folks. So remember screening is a form of secondary prevention. So you're going to see things like these people, starting at each 25, they should get anobrastermaris, right? Starting at each 25, we want to hit each 30 in addition to those anobrastermaris should be doing anomamogramses as well, right? We're going to screen these people for cancer because they can get, you know, breast cancers and a bunch of ovarian cancers. And don't forget, it's actually pretty high to know that these people they can ask you a question on primary prevention. Like, how can you prevent them from developing these breast cancers and ovarian cancers? Well, basically, go ahead and do what I believe Angelina Jolie did, right? So you get a bilateral mastectomy and they get a total abdominal hysterectomy and a bilateral salpingo upherectomy. You're like, whoa, oh, oh, oh, oh, oh, oh, oh, oh, divine calm down. What are all these words? Okay, let's break it down. So bilateral mastectomy, blood breast gun. And then total abdominal hysterectomy and a bilateral salpingo upherectomy.

So you're basically, Yanke now the ovarian, the ovaries, Yanke now the phallopian tubes, Yanke now the uterus. That's pretty much what that means. It's a lot of words that you should know for your exams, but that's pretty much what that means. That's pretty much what that means. And the thing is, as a quick segue, if you love the way I make integrations, I will encourage you to consider the classes that I make, that I teach. I actually had one yesterday a testing strategy class. I'll have another one on the 23rd of this month of July. It's for Step 1, or the week of Step 3. But I also have a bio stats class today for Step 1 to 3. It's a four hour class. All these classes over Zoom have a social sciences ethics and quality improvement class tomorrow. It's five hours long. And then I have a lot. That's also for Step 1 to 3. And then I have a last minute review for Step 2 and Step 3. Obviously, complex 2 and 3 also applies for complex 1 to 3. And then next week I have a 20 hour step to Step 3 class. And the week after that I have a 25 hour Step 1 class. So I'll encourage you to check out these classes. Again, these classes are not lectures. They are pretty much all scenarios. And then I make tons of integrations. I really take time to explain pathophys. And there's lots of people that, you know, struggling, they feel the USML exam, they're struggling to pass exams, or they want to score really solid scores. And they take these classes and find it to help them meet their needs.

I've literally had people get as high as the two. I've literally had people that have failed USML, they took my classes and they passed them again. I can't offer any guarantees to anyone. But the overwhelming majority of people that have taken my classes have had very good outcomes. Right. So let's go to the next syndrome. So let's go to syndrome number five. Right. So what if they give you a question about a person that has a very high hematocrate and they tell you that they have the supposed to have four semas? What should you be thinking about? I hope you're saying old divine. That's a hematocrate. That's a hemangioblastoma. How did you get there? Okay. Let's slow down for a bit. So remember, hemangioblastomas, they tend to grow in the cerebellum on exams. So they're going to be the posterior force on your test. And hemangioblastomas have this nasty habit of producing evil. So if they make evil, they're going to cause you to have polycythemia. And that polycythemia can elevate your hematocrate. And also think about it. If you're a polycythemic, what do you think is going to happen to your blood viscosity? Let's remember, porceles law. The blood viscosity is going to jump up because your blood is thicker because you have a high hematocrate. If you have a high hematocrate, then your blood is more viscous. If your viscosity rises, think of porceles law. What's going to happen to your true peripheral resistance? Your true peripheral resistance is going to go up.

It just makes sense. Right? Remember, blood viscosity is directly related to true peripheral resistance. If your true peripheral resistance goes up, when the word is going to happen to your blood pressure, it's going to go up. That's why these people have hypertension. That can literally be a USM-Ly question. They literally go from polycythemia to high blood pressure. What's the link? Porceles law. Again, make sure you can make these integrations. Now, so what genetic syndrome is associated with this? It's actually an Ruzomodominant disorder known as VHL. Von Hippo Lendau. Von Hippo HI WPEL Lendau LINTU. So it's a VHL mutation. So Ruzomodominant. And the thing that VHL does is that it's an inhibitor of something called HIF1 alpha, HIF, hypoxia, inducible factor 1 alpha. If you have a mutation in VHL, then you cannot inhibit HIF1 alpha. And you're going to get in a lot of trouble. What kind of trouble do you get in? You're going to get in troubles with things like hemangible astomas, things like renosylcarcinomas, especially bilateral renosylcarcinomas. This people can also get in trouble with phyocromocyc tumors. And many of these tumors that these people have tend to produce EPO, for whatever bizarre reason. That's something that's absolutely, positively, high-youtu-no-forear, exact. I would certainly know these things. I just mentioned with VHL. And people that have VHL, they also have some of the risk of a pancreatic cancer. All right, let's go to pathology number six.

So let's run through real quick the water of this cost. Number one, we talked about Lyfren and Isandra. Number two, we talked about Lynch syndrome. Please don't confuse Lyfren and I with Lynch syndrome. Number three, we talked about FEP with EK53. Number four, we talked about Braka mutations. Number five, we've talked about VHL. Number six. We give you a question about a person that has, you know, a bunch of masses in the posterior medius thinum, they have a bunch of masses on the skin. They have hyperpigmented lesions on the skin. Obviously, in this case, I'm talking about NF1. We're talking about neurofibromatosis. Remember, neurofibromatosis, there's NF1 and there's NF2. The thing is, is pretty high-youtu-no, that NF1, NF1 and two are both autosomodominant disorders. They're both autosomodominant. And NF1 is a chromosome 17 problem. NF2 is a chromosome 22 problem. Remember, NF2 for chromosome 22. NF1, I believe, is also called one recline housings disease. And there's 17 letters in one recline housing. So chromosome 17. And remember, NF1 is a neurofibromine mutation. NF2 is a merlin mutation. Make sure you know these things. And make sure you know their findings. So people that have NF1, remember, they tend to have things like, you know, you know, they can get these optic nerve gliomas, they can get neurofibromas, they can get a bunch of leukemias, they can have these coffee-olise spots. Those are hyperbimented molecules on the skin.

Contrast that with NF2, we tend to have, in fact, some people call this mesmy, MSME, mesmy syndrome. Where they have like multiple schwanomas, that's the S, meningiomas, that's the M, and ependymomas, that's the E. It's super high-youtu-no, that. Multiple schwanomas, meningiomas, and ependymomas. People that have NF2, especially, if you see a person that has bilateral acoustic neuromas, those tumors are the cerebellum-pontine angle, think about that person literally has to be screened for NF2. I'm gonna say this again. Our friends at the Mb, he's the love to write some strange questions where they'll give you a disorder of a person has, and then the ask-o-way should you screen for? If a person is diagnosed with a bilateral acoustic neuroma on your test, those people absolutely positively have to be screened for what, for NF2. All right, now, the kind of weird thing to know about these NF1s and NF2s is that people that have NF1, don't forget that they're gonna get anvil-i exams. It is super high-youtu-no, that for tests. People that have NF1, they're gonna get anvil-i exams, because they have a bunch of eye problems going on, right? They can have the optic nerve to trillions, they have the lesion modules. Remember, those lesion modules are hematomas of the iris. Hematomas of the iris. And then, people that have NF2, and the screening should be get. Those people should get anvil brain MR Is. Anvil brain MR Is.

In fact, sometimes people get spinal MR Is like every two to three years, right? But you started each 10 for people that have NF2, started each 10, anvil brain MR Is, and it's spinal MR Is every two to three years. Again, some of these things I'm seeing maybe like, divine, this is super low yield, there's no way they can ever test it. Once you see them, you're exams, and then you start like, whoa, where did that come from? So make sure you know the stuff. And don't forget that people that have NF1, again, I said it's a chromosome 17 problem. To be honest with you, there's some other chromosome 17 stuff that's kind of helpful to know for exams. Might as well heat those, right? So like NF1 is a chromosome 17 problem. You know what, bracket one mutations are also from a chromosome 17 issue. You know what, leaf from an isendrom is also from a chromosome 17 issue. Again, these are high-old integrations to know for tests. And I guess another integration we can say, because I said that, oh, people that have NF1 should get anvil eye exams. Who are people that should get anvil eye exams on your exams besides people that have NF1? People that are taking hydroxychloroquine, they should get anvil eye exams. Because remember, hydroxychloroquine has this predilection for, he has this habit of damaging people's reckons. And that set of people that should get anvil eye exams on your test, where people that have oligua-ticular GRE, those people should get anvil slit lump exams of the eye. Why?

Because we want to screen them for anterior U Vitis. Remember, anterior U Vitis is a very strong association with oligua-ticular GRE. Again, all these things in this podcast, they promise you they are not low yield to know for your exams. They are absolutely not low yield to know for your exams. And then the last thing I'm going to talk about here, the last one, this is number seven, this is probably the lowest yield one of the bunch. But you may see occasionally on your exam, is cow-dine syndrome, cow-dine syndrome, cow-co-w-d-e-n syndrome. This is from a P10, P-T-E-N mutation. People that have cow-dine syndrome, this P10 mutation is going to cause them to basically have issues with the P-I-3 kinase or AKT pathway, the P-I-3 kinase with the AKT pathway. Right? But people that have cow-dine syndrome, remember the critical thing to remember is breast cancer, thyroid cancer, and endometrial cancer. Breast, thyroid, and endometrial. That's about all I'm going to say about cow-dine syndrome. Again, please make sure you know these familiar cancer syndromes. Again, this is one of these podcasts that's short, but it's super high yield. So I'm going to stop here. Again, I offer one I want you to infer all the USM-L exams, all the complex exams. I have these review classes that I teach. I have these podcasts on Apple, Google, and Spotify. I have a You Tube channel you can check out. I also have with ERA's applications, personal statements, mocking reviews, rec letters.

I edit these things. I've done that for so many years, and I've had a great success rate. Like I've literally had people match into very difficult specialties. People that have had challenging applications, match into great specialties. So if you're interested, just reach out to me by email through the website. I can give you some more information. And then, you can just shoot me an email directly at Divine Intervention Podcasts with an S at the end. Divine Intervention Podcasts at gmail.com. And then I also have another podcast called The Divine Intervention Life Lessons Podcast. Many people love my life lessons. So many of you know I'm a Christian. So I decided that hey, every week one or two podcasts from the local perspective, I'll address a life lesson. So check out Divine Intervention Life Lessons.com. There's actually an Apple Podcast associated with that called The Divine Intervention Life Lessons Podcast. So thank you for listening to me today. I will see you in episode 542. God bless you. Happy Fourth of July and bye for now. Thank you.

APC mutation.

Lynch Syndrome.

Poiseuille's Law; increased blood viscosity increases true peripheral resistance, raising blood pressure.

Screen for NF2 syndrome itself, as this finding is highly suggestive of the disorder.

Cowden Syndrome (Breast, Thyroid, and Endometrial cancers).

Annual eye exams/slit-lamp examination to screen for anterior uveitis.

Familial Adenomatous Polyposis (FAP).

Breast cancer, Thyroid cancer, and Endometrial cancer.

Neurofibromatosis type 2 (NF2).

Hemangioblastomas (cerebellum/retina), Renal Cell Carcinomas (RC Cs), and Pheochromocytoma.

P53 (by E6) and RB (by E7).

FAP requires screening starting at age 10; Lynch syndrome requires screening starting much earlier, around age 20.

Familial Adenomatous Polyposis (FAP).

Breast cancer, Thyroid cancer, and Endometrial cancer.

Neurofibromatosis type 2 (NF2).

Hemangioblastomas (cerebellum/retina), Renal Cell Carcinomas (RC Cs), and Pheochromocytoma.

P53 (by E6) and RB (by E7).

FAP requires screening starting at age 10; Lynch syndrome requires screening starting much earlier, around age 20.