Case 3: Pathology Considerations in SCLC

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Benjamin P. Levy, MD:Back to small cell because this is the case. Lonny, is there any different approach? I imagine there’s not, but is your approach different at all to a biopsy for small cell versus non—small cell? Does it require less tissue because you’re not getting molecular testing? Do you approach this any differently if you were the one getting the tissue in this patient and you thought maybe this was a small cell patient? Or your first pass showed that it looked like small cell?

Lonny Brett Yarmus, DO:I think the general approach is the same. I think the additive benefit of on-site cytologists is really important because the onsite H&E [hematoxylin and eosin] staining can be confusing.

Benjamin P. Levy, MD:Yeah.

Lonny Brett Yarmus, DO:Especially in small cell. Having that feedback should definitively figure out what you’re dealing with, and then a stop point is in place.

Benjamin P. Levy, MD:If they’re like, “This is small cell,” are you like, “OK, I don’t need that much tissue here”? Does it guide you in some ways in terms of how aggressive you’re going to be with the tissue procurement?

Lonny Brett Yarmus, DO:Yes, completely. Because as discussed earlier, I think 1 of the major benefits is using it as a complication reduction tool, so that I don’t need to move on and do additional biopsies or higher-risk biopsies. Having that safety stop point is a nice factor.

Benjamin P. Levy, MD:Sam, can you address the role that the pathologist has here for small cell, for example, IC [intracellular cytokine] staining? Do we do any other testing? How do you approach this for small cell in the context of what you usually do for non—small cell?

Samuel Caughron, MD:It’s certainly different. Once it’s small cell, which means it has neuroendocrine features, it’s going to be positive for your neuroendocrine immunohistochemical markers, that it certainly does not have the biomarker work-up like we’d have in a non—small cell. We look for any features of non–small cell. Neuroendocrine can be a component of a mixed tumor. If you see any of those features, you are going to want to go ahead and do the complete adenocarcinoma, or non–small cell biomarker work-up. But in a patient in whom it’s a pure small cell, with no evidence of anything else, I think it’s handed off to the rest of the team.

Benjamin P. Levy, MD:Do you ever get samples that are mixed non—small and small cell? Do you get a mixture of them, or you can’t determine whether it’s non–small cell or small cell because it’s just poorly differentiated? We’ve discussed this before between the adenosquamous and the squamous cell. But do you ever get that it’s tough to tell?

Samuel Caughron, MD:I should point out actually the language that’s evolved here. We now talk about these as neuroendocrine tumors, and we certainly have both large and small neuroendocrine tumors, which is what we talk about when we refer to small cell. I think as soon as you have those neuroendocrine features, which you identify by your standard immunohistochemical markers, you know you’re in that category.

If it’s a pure small cell neuroendocrine, we know what to do with those. If it’s anything outside those, a large cell neuroendocrine tumor, we would probably still not do the biomarkers. But if it has any features or the neuroendocrine staining is discontinuous, I think my perspective is having that information helps manage the patient, especially in the absence of clear data that say that they’re not going to benefit and make it part of the multidisciplinary discussion. If we don’t have the data, we don’t know what we’re looking at.

Benjamin P. Levy, MD:And 1 of my favorite questions to ask pathologists when they get a small cell case, or a neuroendocrine tumor in general, is do you get a Ki-67 staining on these patients? Does that help you determine the proliferation rate of the small cell? For medical oncologists who like getting a Ki-67 done, is that something routinely done in small cell?

Samuel Caughron, MD:We can. These are highly proliferative tumors so the Ki-67 is going to be high. But if it’s not, the neuroendocrine features make the difference. We’ll do it for you if you really want it. It’s an easy test to do.

Benjamin P. Levy, MD:It’s incorrectly stuck in my brain that it makes a difference in some way or shape. I mean, sometimes we’re trying to understand the tumor biology, and small cell is so tough because we’re grasping at straws in terms of how it behaves sometimes. We know it behaves aggressively, but for some of these neuroendocrine tumors and trying to determine what chemotherapy to give them, sometimes if they have a high Ki-67, I default more to my small cell regimens. If their Ki-67 is low and they’re in advanced stage, I default more to my non—small cell regimens based on very little data.

Samuel Caughron, MD:But, I think you make an excellent point that we have the standard guidelines with each patient. We live near personalized medicine, and each patient is each patient. There may be biologic features. For purposes of trials, we have to bucket them. But, there may be individual features a good pathologist will see that they’ll call and say, “Hey, you know I’m going to call it this, but it’s got these really unusual features, and this is how you should be thinking about the biology,” or “It’s not quite typical.” I do think if you think a Ki-67 test helps you, by all means I’m happy to do it and get it for you.

Benjamin P. Levy, MD:Yeah. I may be a one-off.

Transcript edited for clarity.