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Adenocarcinoma in situ

Myths and Misconceptions About Bronchioloalveolar Carcinoma (BAC)

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GCVL_LU-AA02_Myths and Misconceptions About Bronchioloalveolar Carcinoma (BAC)

Unfortunately, there is as much misinformation as good information about the unusual subtype of lung cancer known as bronchioloalveolar carcinoma (BAC) or adenocarcinoma in situ. Dr. Jack West reviews the top 5 myths.

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One of the unusual subtypes of lung cancer is known as bronchioloalveolar carcinoma of the lung, or BAC. This is a rare type of cancer, about 2, 3, 4%, but it has its own lore about it and with that comes some misinformation and myths about managing BAC that I sometimes see causing some bad treatment decisions. I wanted to discuss some of those, as someone who has focused on BAC as a major concept in my own research over the last several years.

The first myth to address is that it is always slow growing or sometimes it may always be considered fast growing. In fact, there’s a lot of variability in how BAC behaves. Sometimes it can be the slowest growing cancer you will ever see; even when it does grow, it might grow by a millimeter or two as a single nodule every year or two.

On the other hand, it is not always an indolent or slow-growing process and you can sometimes see it lead to increasing symptoms over a course of just weeks. So, each case needs to be individually assessed and you need to see how a patient is feeling over time, how their imaging is changing over time, and treat each case individually based on what you observe.

Another myth that we sometimes see is that BAC does not respond to standard chemotherapy. One of the challenges is that BAC tends to appear on scans not as a discreet measurable spot, some solid lesion in the lungs that you can readily measure the size of as it grows or shrinks, but rather as a hazy area that might be one spot; it might be multiple nodules that are all hazy, or it might be a diffused cloudy area. But that haziness is not readily measurable — it’s kind of like trying to measure how cloudy it is one day to the next if it’s just kind of diffusely gray outside.

The problem is that measuring tumor shrinkage is how we historically graded how chemotherapy works, and if you can’t measure it shrinking, we’ve sometimes just categorically said ”treatment doesn’t work.“ However, when you look carefully at some studies that have given the same treatment to patients whether they have BAC or another form of lung cancer, particularly an adenocarcinoma, which BAC is a subtype of, you really tend to see that it responds comparably to other forms of lung cancer to the same chemotherapy. So it is really a bit of misinformation that chemotherapy does not work for BAC.

Another myth that has emerged is that EGFR inhibitors such as Iressa (gefitinib) or Tarceva (erlotinib) are the treatment of choice for BAC. Now, this myth emerged because many of the patients who have responded extremely well to these oral EGFR inhibitors have BAC, and because of that it’s been presumed that it is the treatment of choice. In fact, what we’ve seen is that patients who have an EGFR mutation are the very ones who will most likely benefit from EGFR inhibitors, and many patients with BAC will have one of these EGFR mutations, but certainly not all, and if patients don’t have one of these mutations they tend not to do that well with these agents. So, an EGFR inhibitor is not necessarily the treatment of choice.

Another issue that comes up is that if surgery could be done, it should be done. That might even apply if patents have three of four different spots. What we sometimes see is that patients may want to have surgery because you want to get it out, and many surgeons are inclined to oblige if they feel they can safely do that surgery — but it’s not always a good idea. If there is one spot of cancer, taking it out is almost always a great idea as long as a patient can tolerate it. On the other hand, if there are 3 or 4 or 6 spots, even if it’s possible to get them all out, it’s not likely that that’s all the cancer that is or will ever be. When you see multiple spots that usually means that, in addition, there are other spots likely to emerge over time just like if you take out a bunch of dandelions from your lawn, if your lawn has multiple dandelions, you can’t pull them out and expect that’s the end of that and you’ll never see them again. In addition to the visible disease, there’s invisible disease. There are little seeds, and there’s likely to be additional cancers that pop up, and at some point many patients miss the lung that got removed for the surgery when there are new BAC lesions a few years later.

And the fifth myth that I’d like to address is the idea that treatment should be started immediately or promptly. Now, I mentioned that the pace of BAC is quite variable: sometimes it’s extremely slow, sometimes it’s quite aggressive. In patients who have a very slow process, they can do very well and often have no symptoms for years on end. There are even patients who might never be affected and have their life limited by the cancer, even if it’s growing. If it’s growing by a few millimeters at a time it does not necessarily need treatment and patients might do well for 5 or 10 years or more.

So, there’s no clear incentive to starting a treatment like chemotherapy or even a pill-based therapy like an EGFR inhibitor, that has side effects associated with it and that works typically for a limited amount of time, if this is a problem that you’re going to be managing over a very chronic basis. You just don’t want to exhaust your treatments long before they are needed. So one strong idea is if a patient has a minimal amount of cancer that’s growing slowly and they don’t have symptoms, it makes good sense to think about holding off on treatment until there’s a clear need to intervene.


Bronchioloalveolar Carcinoma (BAC): What is It?

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GCVL_LU-AA01_Bronchioloalveolar Carcinoma (BAC): What is It?

Bronchioloalveolar carcinoma (BAC), also known as adenocarcinoma in situ, is an unusual subtype of lung cancer with its own appearance under a microscope and on imaging. Dr. Jack West introduces some of the basics of the unique features of BAC.

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One of the unusual sub-types of lung cancer is called bronchioloalveolar carcinoma, or BAC. In fact, it’s a pretty controversial type of cancer, with its own behavior and its own prognosis. It also goes by a few potentially different names. The older name for it is BAC, bronchioloalveolar carcinoma, but some pathologists use a new terminology and call it adenocarcinoma in situ. We’ll talk more about what that means, but the behavior tends to be quite unusual.

GCVL_LU-AA01 - BAC intro slide 1b

When you look at it under a microscope, it has its own appearance that does not invade or make solid tumors that go into the lung tissue. Instead, it has what’s called a lepidic pattern. Lepidic means scale-like, and so it really causes just a thin lining that overlies the thin air sacks for the lungs, but that interferes with the ability of the lungs to exchange air. Because of that, it causes shortness of breath and a cough in many people, at least if there is a significant size to the area involved.

GCVL_LU-AA01 - BAC intro slide 2b

BAC can be quite variable. It can be just a very tiny little nodule, it can be multiple spots throughout the lungs, or it can be very large areas of confluent involvement in one or more lungs. And of course, the more of the lung that’s involved, the more severe a patient’s symptoms tend to be.

It has a unique appearance because it tends not to grow invading into tissues and then jumping into the blood and spreading elsewhere — it’s really limited to the lungs only. We will often see a pattern of diffused haziness within the lungs on a chest x-ray or a CAT scan and sometimes you’ll see a spattering of lots of nodules within the lungs as its own pattern.

One of the newer terms for it is adenocarcinoma in situ, and this implies a pre-malignant condition. By that, it means that it is not actually a life-threatening cancer, and this speaks to the often very favorable prognosis of these lesions, at least when they’re smaller and a solitary spot in the lungs. In those cases, when they’re taken out, they have a nearly 100% survival at 5 years. However, the survival is more variable when patients have multiple nodules or when they have larger areas involved.

In addition, the term adenocarcinoma in situ really applies to a non-mucinous cancer, and there are other adenocarcinomas that make mucin, a product of what becomes phlegm or mucus, that patients will sometimes cough up. If patients have cancer that does make this mucin, it tends not to have as favorable a prognosis.

We’ll talk more about how multi-focal BAC is managed in a separate video.


How Long A Period of Follow-Up is Long Enough to Be Confident a Ground Glass Opacity Won’t Grow?

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GGO over timeAn interesting article from Japan was published out in the Journal of Thoracic Oncology that asks how long a duration of follow-up imaging of a ground-glass opacity (GGO) is really needed to be confident it’s going to remain stable and not grow.   It’s very common to see small lung nodules that are ambiguous in their significance, for which follow-up scans are typically recommended rather than diving into a biopsy, and non-solid, hazy GGOs are another form of lung lesion that might possibly represent a lung cancer but are also the way a little inflammation or small infection would appear.   Even when they turn out to be something technically called cancer based on its appearance under the microscope, it’s often a non-invasive adenocarcinoma (sometimes termed bronchioloalveolar carcinoma, or BAC, but shifting in terminology to adenocarcinoma in situ, or AIS) or minimally invasive adenocarcinoma (MIA), in which the invasive component is less than 5 mm in diameter.  Even when they grow, it can be at an extremely slow pace.

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How does the diagnosis of BAC shape systemic therapy considerations today?

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It’s not uncommon for a question here to be about the a pathologist’s terminology on a report that equivocates about whether a lesion is bronchioloalveolar carcinoma (BAC) or another form of adenocarcinoma, perhaps “well-differentiated adenocarcinoma”, especially if it has a radiographic appearance of a hazy infiltrate or many small ground glass opacities. Meanwhile, there’s a new classification of lung cancer subtypes that obliterates the term BAC, instead favoring a definition of adenocarcinoma in situ, classifying small non-invasive lesions previously called BAC as a pre-malignant condition. How have the changes over the past few years changed how we should approach BAC?

I would have to say that the new reassignment of BAC as adenocarcinoma in situ hasn’t taken the lung cancer world by storm and that I still think of the clinical entity as BAC. For the preceding decade, the definition the pathologist’s used technically excluded a lesion with even 1% or 5% of the lesion being invasive as being called BAC, even if it acted for all the world like BAC. Clinicians learned not to be too hung up on a pathologist’s technical definitions and tended to define BAC more functionally/operationally. General oncologists and expert lung cancer specialists alike managed BAC based on the overall picture of how it behaved if it looked like a BAC pattern.

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Redefining Lung Cancer: Seeing the Patterns from Individual Colors

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This month’s Journal of Thoracic Oncology includes a landmark article, written by a multidisciplinary group of lung cancer experts that features several of the leading lung cancer pathologists in the world, that is attempting to do no less than present a new categorization of the pathology of lung cancer, focusing primarily on adenocarcinomas, but also touching on other lung cancer subgroups. Among the concepts included is a proposal that the term bronchioloalveolar carcinoma (BAC) be discontinued and recategorized based on whether patients have any invasive component to their lung cancer or not, and whether is is mucinous or non-mucinous. As significant as it is to redefine an entire disease of BAC, the concepts it introduces have implications that actually lead to a fundamentally different way of thinking about lung cancer, or at least NSCLC.

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