Diagnosing Lung Adenocarcinoma: Biopsying Adequate Tissue

Transcript:Gerald J. Berry, MD: So, there are a variety of ways to determine the diagnosis of cancer, and, in some cases, to establish the stage of cancer using very small samples. And 2 of the current techniques that are available are core needle biopsies, which are often done under CT guidance as a transthoracic approach, or a fine-needle aspiration, which also can be done through a transthoracic approach, or it can be also done through the endoscopic ultrasound-guided approach.

In terms of the transthoracic approach, there’s a great deal of literature as to which is better: the core needle biopsy or the fine needle aspiration. Each has its advantages and its disadvantages. What we’ve established at Stanford over the many years is that we first do a fine-needle aspiration, because that allows you to get small groups of cells and establish that there’s diagnostic material, that there is carcinoma present. We don’t try to separate adenocarcinoma from squamous cell carcinoma at that time, we’re just trying to establish that the radiologist is in the right location. And then, they’ll they proceed to the core needle biopsy.

Our folks tend to use a 20-gauge needle. At other institutions, they’ll use a larger needle: the 18-gauge. And so, I think that is, in my opinion, the optimal approach because you can establish the diagnosis—or at least you’ve got material with the fine needle aspiration—and then move on to get enough of the larger chunks of tissue for the appropriate molecular and other ancillary testing. There’s, as I say, some advantages and disadvantages to both, but I think the combination is the ideal approach.

At the time of tumor progression, there’s a variety of opportunities to obtain tissue to confirm that tumor progression has taken place. Ideally, it should be as minimally invasive as possible because many of these patients are quite ill from their cancer and sometimes from the side effects of the drugs that they’re receiving. So, in the ideal world, the least invasive approach would be the best, and I think that’s where the cell-free DNA has a great potential advantage.

I think those studies are still needing to be validated. Traditionally, the approach on the first recurrence is to get tissue of some sort to confirm the diagnosis. And if this is going to depend on the preferences of the oncologist, the feasibility of gaining tissue as to which particular technique that they’ll use, I think our folks will often use a combination of both. Certainly, they’re investigating the cell-free DNA approach.

The question is how to ideally obtain adequate tissue and mechanisms towards making sure that can take place. At our institution, what we’ve done is established protocols for the examination evaluation of these patients. And so, particularly under CT guidance, what we will do is the fine-needle aspiration. We will then make sure that there’s an immediate evaluation by a cytotechnologist or a cytopathologist to confirm that, and then obtain the additional tissue through the core or the fine-needle approaches. In terms of making sure that there’s enough to do the ancillary testing, again, a protocol approach is probably best, and what we’ve done is created a cellblock with the fine-needle aspiration or the core needle biopsy so that you can prepare paraffin-embedded formalin-fixed samples.

What we do is prepare a hematoxylin and eosin, or a H&E, stained slide. Then, we do 12 unstained slides followed by an additional H&E stained slide, which allows you to see how much tumor you’ve got at either end of the sampling. We then also make sure that we retain tissue in that block. So, the advantage of preparing these unstained slides upfront is that if you need to do immunohistochemistry to sort out whether something is squamous cell carcinoma or not, you’ve got unstained slides to do your immunohistochemical staining. You can also use those stains to do ALK studies, either by immunohistochemistry or FISH. We tend to do it by FISH. And you have unstained slides available to do PD-L1 testing.

With 12 unstained slides, in the vast majority of cases, we have enough material. And then, the tissue is retained and the block can be used for the molecular testing. So, I think it’s very important that each institution established some protocols, both in terms of how they handle the tissue up front and then once they’ve attained the tissue. How is the pathologist going to handle the material so that you can maximize and not have to repeat biopsies because you haven’t gotten enough tissue initially?

Transcript Edited for Clarity