PATHOLOGY/CORRELATIVE STUDIES SECTION - DISCOVERY OF SMALL LESIONS BY PATHOLOGICAL EXAMINATION by Douglas Flieder, MD

SLIDES & TRANSCRIPTS
Tuesday, June 19

PATHOLOGY/CORRELATIVE STUDIES SECTION - DISCOVERY OF SMALL LESIONS BY PATHOLOGICAL EXAMINATION

Douglas Flieder, MD

Slide 1: Introduction

DR. FLIEDER: For me, pathology is a little more simple. I'm not a tie person. I'm a scrubs person. And I wear a pair of gloves. And I'm fortunate that I work at a place where lung cancer screening has taken off, and it allows me to get involved, take a step back, and at a very simplistic level go back to the specimen and say, what are we dealing with? What are the questions that we now need to deal with, now that we are finding smaller and smaller lesions? Most of us in the room know that a 7 centimeter lung cancer that is diagnosed on chest x-ray or CT scan is a dismal tumor. But we don't really know about the sub-centimeter lesions. I'm not going to offer any ideas about the sub-centimeter lesions. I'm just going to show you how I handle the specimens, the things that I find, the issues that we, especially in the pathology field, and also in the medical field need to start addressing to answer some of these questions. So this is what I'm going to talk about, the small lesions that I find.

Slide 2: Pathologist's Role

The pathologist plays a very important role in this. And it is a low tech role. When the specimens are resected, the pathologist is able to correlate the tumors and the findings with the CT scans. He is responsible for honest diagnosing and staging of lung cancer. He or she needs to know about these putative precursor lesions such as atypical adenomatous hyperplasia, squamous dysplasias, and neuroendocrine cell proliferations.

Slide 3: Lung Resection Processing Protocol

And also very important for any science project is to procure the tissue for morphologic and for molecular studies. All of these very basic things fall on the shoulders of the pathologist.

Slide 4: Specimen

So over the past three years, I have been able to examine a lot of specimens, whether that means pushing the residents aside, that seems to be what I do often. And I get involved with the surgeons and with the radiologists so we are all on the same track. And that's very important as well, and will need to be. So this is a difficult area to research, but the basic steps have to be taken.

Slide 5: Fresh Tissue

If fresh tissue needs to be procured, it has to be done with minimal specimen disturbance. A lot of patients are on protocols, and tissue is required. And we are able to give away fresh tissue in some, but not in all instances.

Slide 6: Small Lesion Examination

And then after that if it's necessary, we can fill the lobectomy specimen with air, and do a specimen CT. But more often than not I fill it with formalin and I let it sit at least overnight, sometimes two nights. No one I work with seems to mind if the diagnostic report comes out in 72 hours as opposed to 48 hours.

Slide 7: Half-millimeter Section

At which point I am able to cut a section of the lung into half-millimeter sections like this lobectomy specimen. When you section it into small pieces like this, you can see things, you can feel things, and you are also able to take a lot more sections.

Slide 8: Tumor

And this is an example of a tumor. Well, it's just a lung tumor, but everything up to now has been pretty high tech with the CT images. This is the best I can do in a 5 millimeter slice to show that one tumor has three different looks.

Slide 9: Tumor

One tumor here seems to respect the interlobular septa. So a lot of information can be gleaned.

Slide 10: Tumor

This tumor has solid areas and cystic areas. So this is the start of interpreting the tumors.

Slide 11: Issues

So what can you gain by sampling a specimen very carefully? Well, you see things, you feel things, and then there are just things that you happen to find under the microscope. We see the tumors, the scars, infections, hamartomas, interparenchymal lymph nodes. These are interesting only because the incidence of these is much higher than what has been reported, but that's probably if you sample a lung, and you take 30 sections instead of two or three sections, you will find more.

Slide 12: Subpleural Scar

Here is a subpleural scar measuring 1 centimeter.

Slide 13: Lobectomy Specimen

Here is an incidental focus of active tuberculosis in the lobectomy specimen, which is of some clinical import. And just for example, can very well interfere with the patient's survival.

Slide 14: Diagnosis of Malignancy

So what about the tumors? That's really what we are up against. The issues facing the pathologist -- well, he has to be able to diagnose the cancer, which sometimes is easy, sometimes is very difficult. He needs to know enough about the cancers, and have strong enough skills to diagnose them properly. It's either adenocarcinomas, or neuroendocrine tumor, or a subtype of adenocarcinoma. He needs to be able to stage it. And he needs to identify these precursor lesions.

Slide 15: Lymph Node

Here is an intraparenchymal lymph node, a 4 millimeter lesion that in retrospect was on the cut of the CT scan.

Slide 16: Tumor

And of course, the tumor. Here is a less than a centimeter lung adenocarcinoma. These are the lesions we look for and find.

Slide 17: Adenocarcinoma

Well, this is an obvious adenocarcinoma. It's invading the pleura. It's destroying the lung parenchyma, and has just ghastly cytologic features. So that's an easy 5 millimeter adenocarcinoma to diagnose.

Slide 18: International System for Staging

However, not all of the sub-centimeter tumors are easy to diagnose. And the differential diagnosis for the pathologist often includes things such as scars, reactive processes like bronchoalveolarization secondary to a previous infection, and maybe in some instances as was alluded to in the Hopkins case, you can get an atypical adenoma that is hyperplasia that measures up to 5 centimeters. It is detected on the CT scan, but it just doesn't make it to carcinoma.
[Slides interrupted due to technical difficulties]
Here is an example. A subpleural predominantly scar, with a little pleural pucker in the beginning. Is this an adenocarcinoma?
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There is a peribronchiolar proliferation of glandular cells. Is that cancer?
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And is some more diffuse alveolar receptor proliferation. Is that cancer? These are the issues facing pathologists today.

Slide 19: Conclusions

Well, the salient points are, and I guess it is true that in a room with few pathologists, the images aren't so important, but the points are that the ability to diagnose lung cancer with these sub-centimeter lesions is becoming more and more difficult. And the pathologists need to really get together and decide on some diagnostic criteria for some of the lesions to distinguish such things as reactive atypical in a scar, versus atypical adenoma that is hyperplasia, versus indeed sub-centimeter adenocarcinomas.
The issue with adenocarcinomas relates to the new World Health Organization's subtyping of cancers. And they define the bronchoalveolar carcinoma as a tumor without invasion. It just grows along the alveolar septa without invading. Well, there is no real evidence that that lesion has a better outcome that invasive adenocarcinomas. So that's another thing that needs to be looked at by the pathology community.

And lastly, the ability of the pathologist to correctly stage lung cancer. If the pathologist looks carefully at the specimen and finds a little satellite lesion, according to the current staging, that could be stage 3B if it's in the tumor bearing lobe, or an M1 stage 4 if it's in the non-tumor bearing lobe. That needs to be looked at as well, because someone with a primary tumor measuring a centimeter, and a satellite lesion measuring a millimeter for example, does that patient have the same 7% 5 year survival as the patient with true stage IIIB disease? That needs to be looked at. That's another Pandora's box opened by screening. The putative precursor lesions, I'm not going to touch on that, aside from saying that if you sample the tissue, you collect the lesions. And collecting the tissue, and developing a repository will allow for studies to go on beyond just this initial craze in screening for CTs. So in summary, the pathologist needs to really start examining the specimens. It's no longer the days where you take two sections of a tumor, and you throw it in the incinerator. The specimens need to be grossed carefully and laboriously. Many sections have to be taken and studied. Diagnoses have to be made correctly. Staging has to be fine tuned. And the lesions all have to be catalogued for further research.

And with that, I'm just going to pass the pointer and the clicker into the garbage can.
Thank you.