Saturday, May 18, 2013

Seeing the Life

First of all, Dear Reader, let me apologize for the title of the last post. I just publicized the blog to a much wider audience today and what did they see when they first visited? "Hopes, Shattered." What a welcome!

Let me assure you that title was only a hyperbolic device employed for thematic effect.

I knew there was very little chance that a radiologist would mistake a sinus infection for cancer. But I thought it was interesting how my mind was willing to grasp and amplify that vanishingly small probability, as evidenced by my mild but clearly felt disappointment when it did not eventuate.

Editor: Sheesh, who is this guy using fancy words like eventuate?

I swear, that's the first time I have ever used that word. It just popped into my head. I thought I was making it up but it's a real word!


Today's topic is the biopsy. The word stems from two Greek roots: bios, meaning "life" and opsis, meaning "to see". That's exactly what it means: to remove cells from a living organism and look at them, traditionally under a microscope, to determine their type and properties. These days the tissue removed during a biopsy is used for many other purposes besides visual examination but that is still the core use.

The biopsy procedure itself can take many forms. In my case I will have two biopsies at the same time: the otolaryngologist will take samples from the growth on the back of my tongue using normal surgical instruments. And he will also perform a Fine Needle Aspiration of the adjacent Lumpy the Lymph Node: he will insert a needle into the node and then use a syringe to withdraw ("aspirate") some of the cell soup contained therein. Both tissues will then be sent to the pathology lab for analysis. It is the shape, size, location, organization, proportion and other properties of these collected cells that will tell me and my doctors exactly what is going on.

Biopsies are used in many, many illnesses to assess what is happening biologically. But I think in cancer essentially every suspected tumor is biopsied as one of the first steps in the diagnostic process.

Soon I'll write a post about "personalized medicine" and how genetic sequencing of tumors is one of the early successes that fall under that name. Lots of research institutions and hospitals have begun using sequencing of specific genes in tumors to try to understand which patients will respond or not to specific treatments based on the individual collection of mutations each patients' tumor carries. Some of the scientists I work with do exactly that in the research phase.

For now, suffice it to say that I wanted my malignancy sequenced. There's a year-old company in Cambridge named Foundation Medicine that is among the first to offer tumor sequencing as a service: in the form of a lab test that one's doctor can order like any other test. They obtain tissue from the pathology lab, extract the DNA from it and analyze it. Then they send your doctor a comprehensive report that highlights the specific mutations that have an impact on that patient's treatment, treatments that are most likely to work for that patient, and clinical trials that involve new drugs that target that patient's mutations.

One thing I like about Foundation's test is that they have identified a set of just over 200 genes that are known to be important in cancer and which are known to have specific impact on treatment. I.e. they aren't fishing for every possible mutation and trying to understand what it means. That's too noisy.

I referred my otolaryngologist, Doctor B, to Foundation's website to consult their sample requirements and requested that during the biopsy he collect extra tissue to satisfy those requirements.

But let's get back to the main purpose of the biopsy: finding out what exactly is growing in my throat and neck at a cellular level.

That work is done by a pathologist, an MD who specializes in examining tissues and making diagnoses. In my case the pathologist will take the tissue collected during the biopsy, slice it very thinly, and place the slices on microscope slides. S/he may use stains, which are chemicals applied to the slices to highlight specific aspects of structure, or the presence (or absence) of specific proteins or other molecules.

There are other more complicated tests that can be applied to tissues. For example, to look for some proteins the lab will use immunohistopathology or immunohistochemical staining. Impressive words! The immuno part means they use antibodies (which are part of the immune system). The histo part refers to tissue. You now know what pathology means (by the way, it comes from pathos, meaning "suffering" or "disease" and ology, meaning "study of" or "science of").

Immunohisto- techniques take advantage of the fact that antibodies are very specific about the proteins they will stick to, and when they find that protein they stick to it strongly. Imagine if iron came in different flavors and there were different magnets that would attract each type of iron specifically. That's what immunohistochemical staining does: the proteins whose presence you want to determine are special kinds of iron and the antibodies are the matched magnets. Chemically attach some dye to an antibody, apply the antibody to the tissue and viola! The target protein takes on a color that visually indicates its presence.

Here's an example of pathology slides stained with antibodies to indicate the presence of specific proteins:

Pathologists are trained to recognize normal tissues as well as abnormal, and to classify the abnormal tissues appropriately. In my case, since the tongue is a muscle the normal cells should be long and smooth and all lined up in the same direction (think "muscle fibers"). Cancer tends to be chaotic: mixed up wrong shapes, disorganized structure, etc. The amazing thing to me is that pathologists can make these evaluations for any cell type in the body: kidney, skin, lung, spleen - you name it.

Lumpy the Lymph Node, if normal, would contain cells that are part of the structure of the node itself, plus immune system cells that transact business in the lymph nodes: T cells, B cells, dendrocytes, etc. Since mine is swollen, it probably contains either way too many of the cells that would normally be there, or cells that shouldn't be there, or both. The pathologist will quantify and classify the cells that are aspirated and diagnose what is ailing Lumpy.

We will anxiously await the pathology report after the biopsy. It will take at least a couple of days. Everything hinges on that report as it will confirm the preliminary diagnosis of malignancy, identify the specific type of cancer and ultimately determine many aspects of the treatment that is in store for me as well as my prognosis.

I think most people know what prognosis means, but just in case let's go back to Greek: pro, meaning "before" and gnosis, "to know". So, "knowing beforehand". In cancer it means "are you going to live", and if not, "how long do you have". It's a prediction, so obviously it's not exact. But there is a lot of treatment history to go by so a cancer prognosis is based on statistical analysis of outcomes of prior cases of the same type.

Given all that is riding on the pathology report, the wait for it is going to feel long.

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