A Sunburned Man Found A Lump On His Arm. This Is What Happened To His Brain.
KC is a 45 year old man, presenting to the emergency room with a 15 minute seizure.
His wife, Jennifer, tells the admitting nurse at admission that he had been developing a
weakness on the left side of his body over the last few days.
You see, KC was a farmer in rural middle America. Every year, he was sunburned for at least
3 months from working out in the fields. Didn't really care about anything for his health
because he'd been ok his whole life.
Several months ago, a sunburned KC found an asymmetrical, pigmented lesion with irregular
borders growing rapidly on the skin of his right arm. Day after day, the lump would seem
to morph into something new, grow larger and ulcerated but without pain. He thought it
might be cancer. A doctors visit was unnecessary, he thought. Most of his farmer's life was
fixing things on his own. Whether it was parts of his home, or his farm equipment, he lived
a self-sufficient life. He always had the tools to get the job done and in the case
of his skin cancer, this is something he could fix himself.
Immediately after removing his own skin tumor, KC thought that this story was over. Nothing
more to be done here. Wrap it up with a cloth and carry on, he thought.
Over the next few months KC felt great, but noticed there was a lump growing inside his
right armpit underneath the skin. It was warm to the touch, sometimes he could feel a pulsating
sensation coming from it. Every morning he'd wake up and put his hand on the lump, and
feel his heart beat through it.
His wife suggested he see a physician, but KC joked to his wife that he's his own surgeon
now. He said he did it once, and if he has to do it for the lump in his right Armpit,
he'll do it again. Except, a PET scan revealed hypermetabolic lymph nodes in that region.
Hyper meaning high. Metabolic referring to cellular division. And lymph nodes denoting
the structures in your body where white blood cells from your immune system accumulate and
drain. These kinds of lymph nodes indicate that something is growing inside his right
armpit.
About a month ago, Jennifer started to notice KC developing irregularities in his walk.
It appeared to look like a limp that when confronted about it, KC would deny anything.
He actually couldn't see himself deteriorating. He started to develop a weakness on his left
side and began developing headaches that were so bad he'd feel as if someone were pushing
from inside his skull against his eyes..His entire family began to notice changes in his
personality. A normally patient and down to earth man, he would now get physically angry
at everything until one day while working out in the fields, he suddenly collapsed on
a 15 minute seizure.
An MRI finds multiple lesions developing in several regions of KC's Brain. Because there's
no indication of infection, cerebral bleeding and signs of radiation damage to his brain
and because these tumors don't have the characteristics of a primary tumor, it means
that KC doesn't have brain cancer, but that theres tumors in his brain that are from cancers
elsewhere in his body and they've spread to his brain.
Cells from his axillary mass lymph nodes were examined. It wasn't just a swollen red lump,
it was widespread cancer growth.
Looking at the cells under a microscope, multiple markers
were positive for a type of skin cancer based on presence of the polymer that gives tissue
color and pigmentation, something called melanin. Even though KC had removed the cancer from
the skin of his right arm, it appears that the cells from that primary tumor are now
growing en masse in his lymph nodes, and in his brain.
We can conclude here that KC has metastatic melanoma. Melan referring to melanin. Oma
meaning tumor, or irregular mass, describing the type of cancer growing on KC. And metastatic
meaning that even though he originally had cut out the cancer himself, it has transcended
its stationary site of origin, and has started spreading throughout his body.
If in a healthy person you wouldn't normally find skin cells growing in the brain, then
how is it possible that KC's skin cancer spread to his brain? Well, there's a bit
of basic cellular biology to be known here.
Cancer is a genetic disease at it's core, but its physical characteristics are something
more.
The genes in our body code for proteins, which give us our physical form, but they also signal
for our cells to do things. Proteins are made of amino acids. Amino acids are sequenced
together, dictated by our genetic sequence. Changing that sequence, either by mistake,
or from environmental damage like from radiation from the sun, cause mutations. But most mutations
are nonsense, happen less than 0.01% of the time and usually get fixed. But sometimes,
these mutations create proteins that signal to the cell to grow, and there's no signal
to stop growing. To keep reproducing with no signal to stop reproducing. To grow their
own blood supply. And to survive in the circulation and spread to other distant sites of the body.
Cancer is more than just a genetic disease, its an evolutionary step to highly successful
cellular survival, at the expense of its host. KC's case gives us more evidence of this.
A genetic test is done on his lymph node cancer cells. A single point mutation was found specifically
on chromosome 7, on the gene named BRAF, at nucleotide 1799: where there should have been
an A, there was a T, meaning for the protein made by the gene BRAF, 1 amino acid at position
600 changed, creating something called the V600E mutation. A normal functioning cell
uses RAF, which feeds into a pathway of the cell causing it to grow, with limitations,
but BRAF V600E promotes unmitigated cellular growth and uninhibited cellular division,
which gives us a necessary condition for it to be cancer, but there's more.
When you pee, some urethral cells will be in that pee. Physics tells us for any flowing
fluid, a shear stress will be produced along the surface on which it flows. For biological
systems, it means some of the cells can come off when you urinate, but cells can also can
come off when blood flows in to a tissue. As melanomas grow thicker and deeper into
the skin, the chance of metastasis becomes higher and higher. We call this high risk
disease because then melanoma cells can break off from the primary tumor and float around
in the blood.
The blood vessels going into the brain have a special biology, called the blood brain
barrier. It prevents certain substances from going in, and allows others in.
This blood brain barrier has proteins on it's surface. Melanoma cells also have an overexpression
of proteins on its surface, meaning if a skin cancer cell can break off from the tumor,
live in the blood circulation, when it gets to vasculature of the brain, it can adhere
onto the proteins at the blood brain barrier, and begin to grow and multiply, forming a
brain metastasis.
Melanomas are the 3rd most common cancer to spread to the brain. Breast and lung cancers
have a higher incidence of brain metastasis, but data shows that 40 to 50 percent of patients
who have a melanoma that spreads somewhere in the body, will eventually have it spread
to the brain. The massive headaches. The paralysis on one
side of his body. The 15 minute seizure. If this continues unchecked, the brain masses
growing inside KC will eventually rupture the blood vessels in the brain, causing fatal
damage through the cerebral cortex.
Ultraviolet radiation from the sun is known to cause cellular damage. Because the sun
doesnt shine directly on KC's brain, nor his lymph nodes, but it shines on his skin,
and skin cancer is known to spread to the brain and lymph nodes, we know where these
tumors originated from.
Case reports of people who for years, worked in an environment where the sun shined on
one half of their face revealed the extent of damage possible to skin tissue. Queensland
Australia, where the UV index is often high, and people with light colored skin who are
not genetically adapted to the harsh sun contribute to the melanoma capital of the world with
an incidence rate of 71 cases per 100,000 people, three times that of the United States.
The metastatic propensity of malignant primary tumors is a recurring theme when it comes
to causes of mortality in cancer. Colorectal and stomach cancers commonly spread to the
liver first as the shared blood supply make it one of the first organs of contact. Bone
cancers typically go to the lungs first. Breast cancers commonly spread to the lungs, liver,
bones and brain, and lung cancers typically to go the brain first as blood passes through
the lungs to be oxygenated, pick up cancer cells as the fluid produces a shear stress
along its interface, enter into the left ventricle into the aorta into the carotid arteries to
the brain. And uveal melanoma, a cancer of the melanocytes in the eyes, which is a different
kind of melanoma than the skin, typically spread to the liver first, despite the eyes
being right next to the brain.
For KC, removing his own primary tumor meant very little, because at some point either
before or after he removed it, the cancer had already started to spread all throughout
the body.
There's a few things that can be done, but the prognosis, or the predicted outcome of
his disease at this late stage is grave. Once melanoma has metastasized to the brain and
produce symptoms like a 15 minute seizure, historic data from multiple studies show that
median survival, the time at which 50% of patients are left alive, is less than 5 months.
That by 18 months after diagnosis, about 10% of patients are still alive. Throughout any
clinician's career, over the many patients one will see, statistically, there will be
those few patients who live with stable disease, but those patients are the exception and not
the rule.
At the time KC was diagnosed in early 2011, multiple treatment modalities were available
for KC. Traditional chemotherapies in metastatic melanoma had fallen by the wayside by the
time he presented to the emergency room, as they were known to have little to no effect
on brain metastases.
KC was offered brain surgery in an attempt to prevent more seizures, prevent the tumor
from causing a brain bleed, and minimize neurologic dysfunction. He declined and elected for radiation
therapy, which irradiates the cells, thereby damaging their DNA sufficiently to prevent
them from reproducing, but it appeared that KC presented to the emergency room too late
as additional seizures and intracerebral hemorrhage ensued before any treatment was initiated.
At autopsy, KC's brain masses were found to have the same V600E mutation as the mass
in his right armpit and because it's not likely that both of those sites each simultaneously
and independently mutated the exact same gene, with evidence of melanocytic immunomarkers
present, this was a case of advanced melanoma with multiple metastases to the brain.
Sunscreen is a must for anyone who spends long periods of time outside. It shields one
from the harmful UV radiation from the sun that damages the DNA of skin. Early detection,
along with going to a surgical oncologist for consultation instead of removing the skin
tumor himself, could have prevented this outcome for KC. Prevention with sunscreen, sitting
in the shade, and limiting one's sun exposure during the summer months is still the best
approach to one's health in this context.
The Ancient Chinese had a character for cancer. It is based off the word for rocks, implying
a burden carried by one's body. The character has a formality to indicate illness on the
right as it resembles a bed turned sideways, and on the left is a symbol for a primary
tumor, spreading throughout the body as multiple smaller metastases, that continue to spread,
to infinity.
Treatment modalities in early 2011 when KC presented to the emergency room were better
than what ancient humans had. The treatments today improve response rates, progression
free survival, and overall survival. But they can and will be better yet with time. And
even after all of these centuries, cancer is still a burden on humanity.
Thank you to the Griffith Family of Greenock Road, Lothian Maryland, for allowing me to
record on their farm and thank you so much for watching. Take care of yourself. And be well.
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