Looking for pictures? PathologyPics.com has plenty

Dr. Roger E. McLendon called my attention to PathologyPics.com a very good, pictorially-oriented general pathology website which includes many examples of both classic and rare brain tumors. Here, for example, is an example from the site of a chordoid glioma of the third ventricle:

Thanks, Dr. McLendon, for pointing out this helpful website.

I have discovered my ApoE status

I just got my ApoE results back from 23andMe.com.  When I ordered the test, the first question I posed to readers was whether it was wise to even find out whether or not I have the epsilon 4 allele. One commentator, "Agent 86", quoted the ancient Greek philosopher Epictetus for guidance on this issue. In 135 AD, Epictetus argued that one should emotionally separate oneself from those things which are not one's own -- i.e., those things over which one has no control. Therefore, had he known what a gene was at the time, Epictetus would have counted one's genome as among those things that is not one's own. As such, knowing his ApoE status would have been of no consequence either way to Epictetus. I do find it rather easy to take this Epictetusian attitude toward my ApoE status. But because I find it exceedingly difficult to adopt this attitude of separateness toward many other things in my life over which I have no control, I can certainly understand how others could feel emotionally affected by knowledge of their own ApoE status.

I then had a second question: Should I make my ApoE results public? I was surprised by the number of people who recommended against doing so. The main objection seemed to be the potential that an insurance company might refuse to cover me if it were known that I was at increased risk for the development of Alzheimer's disease. I agree with one commentator who stated that this is a "worst-case scenario" and continually worrying about worst-case scenarios is not a wise way to live one's life.  I might also add that it might be in an insurance company's best interest for me to get Alzheimer's disease at a relatively earlier age (in my 60's rather than in my 80's) as  I would likely die at a younger age and thereby cost the company less money over the long run. That being said, in deference to all those who weighed in on this matter, I have elected not to publicly share my ApoE status. I appreciate all those who engaged in this discussion; and I suspect that this kind of discussion will be ongoing in many circles in the decades to come as personalized medicine, based on genomic profiling, emerges in the new age of theragnostics.

What's wrong with finding out and releasing my ApoE status?

In a recent blog post, I stated that I intended to publish my ApoE status on the blog when I get the results back from 23andMe.com. I was surprised to find that some people objected to this. One associate said that by publishing information about my genetic status, I would be "normalizing" the dissemination of information that should be confidential. That sets a bad precedent for the use of personal genomic data. Another individual emailed me the following suggestion: "Instead of posting your results, maybe you would consider instead the value of not doing so at the request of an 'anonymous' reader and keeping the information private in order to stimulate debate about finding out about a disease process for which there is no cure." Finally, "jd" commented in the original post about the wisdom of getting the test done at all: "Why would you do that? If you come back 4/4 or 3/4, that'll be hanging over you the rest of your life. If there were a cure for Alzheimer's, that'd be different."

And so, I pose this question to readers: Is there not intrinsic value in knowledge about one's genome, regardless of whether or not a related disease predisposition can be treated? Also, if I am willing to release my personal genetic information to the public, what harm am I causing myself or anyone else? At this point, I intend to find out my ApoE status when the information is made available to me, and I intend to discuss the results on this blog when I get them. But, if anyone can make a convincing argument otherwise,  I am willing to be convinced. I await comment.

A 58-year-old woman presenting with headache and unsteadiness of gait

Here's a recent case of mine involving a lesion in the third ventricle of a 58-year-old woman who presented with headache and unsteadiness of gait. First, the imaging:

 

Axial CT

Sagittal T1 MRI

Axial T2 MRI

Coronal Gradient Echo

The neuroradiologist thought perhaps the lesion was a craniopharyngioma. But, the neurosurgeon was surprised that the lesion seemed to "pop out". Here's the specimen I received:

Outer Surface

Cut Surface

I smeared some of the viscous fluid from the cut surface onto a glass slide, cover-slipped it, and viewed it under polarized light:

Those cholesterol crystals certainly seem to suggest the possibility of craniopharyngioma. But, craniopharyngiomas do not have a smooth outer surface and do not just "pop out" into the neurosurgeon's hand. Here was my first glimpse of the histology the next day:

Cholesterol clefts and giant cells. Note in the upper picture that this xanthogranulomatous reaction appears to be continuous with the choroid plexus. Could this be a xanthogranuloma of the choroid plexus? I considered that, until I looked elsewhere on the slide and saw this:

This is the ciliated epithelium characteristic of a colloid cyst of the third ventricle, a tumor that can indeed "pop out" into the neurosurgeon's hand. Gross inspection did not reveal a cyst per se because the exuberant xanthogranulomatous reaction obliterated it. Cases like this have been described in the literature. For example, Dr. David Louis and colleagues wrote in a 1994 article entitled Third ventricle xanthogranulomas clinically and radiologically mimicking colloid cysts: Report of two cases (Journal of Neurosurgery. 81(4):605-9, 1994 Oct.) that "histopathologic examination revealed xanthogranulomas of the choroid plexus with only microscopic foci of colloid cyst-like structures." I would argue quite the opposite: that the xanthogranuloma derived from the colloid cyst and extended into the choroid plexus. Indeed, Dr. Peter Burger and colleagues write in the fourth edition of Surgical Pathology of the Nervous System and Its Coverings that "a xanthogranulomatous reaction occasionally supervenes in colloid cysts, largely replacing the epithelium in some cases."

Cool case.

The Link Between ApoE4 and Chronic Traumatic Encephalopathy appears to be weakening

Dr. Robert Cantu

In the current issue of Nature Medicine, Dr. Robert Cantu, co-director of the Center for Traumatic Encephalopathy at Boston University, indicates that the suggested link between ApoE4 carrier status and Chronic Traumatic Encephalopathy (CTE) might not be as strong as some earlier studies have suggested. Seeming to be referring to data that has yet to be published, Cantu is quoted in the article as saying the following: "“I must say we’re not finding a high correlation” between CTE and the e4 variant.

(Reference: Katsnelson A, Gene tests for brain injury still far from the football field. Nature Medicine. June 2011. 17:6, p. 638)

American Brain Banking Network renamed the International Brain Banking Network, with new website

Piotr B. Kozlowski, MD, PhD

From Dr. Piotr B. Kozlowski, Touro College of Osteopathic Medicine, New York City:

"The website of the brain banking network formerly known as the American Brain Banking Network (ABBN), is now renamed as the International Brain Banking Network and its website can be found at http://www.intbbn.org/ 

 "Please have a look at this website, still in a nascent state, and if the information regarding your brain/tissue bank needs to be updated, please let me know."

Dr. Kozlowski's email address is piotr.kozlowski@touro.edu

Illinois Lawmakers Pass Concussion Bill

I'm glad to see that my state's lawmakers are addressing the issue of sports-related concussions. The policies adopted by the National Football League appear to be trickling down to the high school gridiron. The bill, passed by the Illinois Legislature, now goes to Governor Pat Quinn's desk for his signature.

Population prevalence of the ApoE4 gene

Regarding the Alzheimer genotype, I just did a little research regarding the prevalence of the ApoE epsilon 4 allele (the allele that predisposes to Alzheimer disease). Depending on the study you read, about 20% of the population has at least one epsilon 4 allele, while about 2% have two epsilon 4 alleles. As you'd expect, having two is worse than having one in terms of Alzheimer risk. I should add that the epsilon 4 allele also predisposes to a worse outcome in recovery from traumatic brain injury and is also over-represented among those football players who suffer from Chronic Traumatic Encephalopathy.

 

It's important to note that this data applies only to those of European ancestry. The rates of other ethnic groups are different. I saw one study showing, for example, that the rate of epsilon 4 prevalence is much, much higher among Australian aboriginal populations.   I recently sent in a saliva specimen to 23andMe.com to have their CLIA-approved lab run a genetic profile on me, which will include a report on my ApoE status. The service has dramatically decreased in price in recent years, so I finally broke down made the purchase. I'll report those results when I get them next month.

The Timeless Dr. Adelman

Lester S. Adelman, MD

I was recently sent this 1992 essay written by Dr. Lester S. Adelman, retired neuropathologist at Tufts New England Medical Center. It amusingly illustrates the anonymity in which we pathologists toil:

Pathologists spend their time in the figurative,
and sometimes literal bowels of the hospital.
Even those of us who specialize in the pathology
of the brain occupy this nether region. The
patients who benefit from our brilliant diagnoses
are often as little aware of us as they are of
the hospital laundry.
This life of anonymity has its rewards. Frozen sections
are only rarely done on nights and weekends, and straightforward
cases are disposed of quickly. The intellectual and
visual pleasures of the job are great. Every once in a while,
however, we are reminded of the fact that we have given up
a part of doctoring, the part that has to do with knowing the
gratitude of the patients whom we help.
Some years ago, in the era before CT scans and MRIs,
a patient was admitted to our hospital with a brain tumor.
Preoperative radiologic diagnoses in those days were based
on angiography, and this patient's angiogram strongly suggested
a glioblastoma multiforme. The patient was given the
bad news, and a biopsy was done to confirm the diagnosis.
The surgeons also thought the tumor was a glioblastoma,
but when I looked at the frozen section, I discovered the
tumor was clearly a meningioma. With this diagnosis, the
surgeons were able to find a plane of dissection around the
tumor and remove it completely.
I was happy with the outcome and thought I had accepted
the fact that the patient would never know my part .
in it. It was not long after that I was to come face-to-face
with the shortcomings of my chosen medical specialty.
A week later I was at a conference with the neurosurgeons
when I noticed that one of the residents was wearing
an expensive new wristwatch. A moment later I noticed that
a senior neurosurgeon had a similar watch on his wrist. A
quick check of the audience revealed that they all had new
watches!
"What's going on?" I asked.
"You remember Mr. X, the patient with the meningioma?
He's a jeweler, and he was so happy he didn't have
a glioblastoma that he gave us all new watches."
"How about me?" I whined. "I'm the one who cured
him. If it weren't for me, you would have quit, thinking he
had a glioblastoma."
The physicians smiled graciously and conceded this was
probably the case.
Years have passed, and despite the advances in imaging,
my neurosurgical colleagues continue to consult me about
diagnoses. But when I want to know what time it is I still
consult my Timex.

Best Post of January, 2011: Retinal Changes in Inflicted Pediatric Head Trauma

The next in our "Best of the Month Series" is from January 13, 2011:

The illustrious Peter Cummings, MD recently contributed an excellent post to the Cambridge University Press medical blog on the topic inflicted pediatric head trauma.  In particular, Dr. Cummings discusses the presence of retinal hemorrhage as evidence for pediatric head trauma. Whether or not the trauma had been intentionally inflicted depends, of course, on the history provided by witnesses and law enforcement as there are no pathognomonic findings. But, as Dr. Cummings says in his post: "I treat every pediatric case as though it is a homicide until I can prove to myself that it is not."

Retinal fold with hemorrhage

Given the near ubiquity of artefactual retinal folds in extracted eye specimens, I asked Dr. Cummings whether there is a role for postmortem funduscopic examination. He responded that he has had some success with this technique, but postmortem corneal clouding often makes funduscopic exams impossible.

 

Dr. Cummings is the director of forensic neuropathology at the Office of the Chief Medical Examiner in Boston, Massachusetts. He is also first editor of Atlas of Forensic Histopathology, which has just been released by Cambridge University Press.

'Slug Nutty' Boxers, 'Head Scrambled' Football Players, and the Role of the Neuropathologist in Protecting the Public

American boxer John Heenan (1835-1873)

As part of National Lab Week activities, I delivered a presentation yesterday to staff at the College of American Pathologists headquarters in Northfield, IL on the topic of chronic brain injury among football players. Repetitive brain trauma in sport was first recognized among boxers, and thus the early-onset dementia -- and, in some cases, parkinsonian symptoms -- associated with this kind of trauma was named dementia pugilistica. Since the recognition of this phenomenon in other sports, most notably football, the entity has been renamed Chronic Traumatic Encephalopathy (CTE). Among the first papers describing repetitive traumatic brain injury in sport was one authored by neuropathologist Harrison S. Martland, MD, who published his results in the Journal of the American Medical Association in 1928 (Punch Drunk: JAMA 91:15, [1928] p. 1103-1107). Dr. Martland -- who worked in the pathology department of the City Hospital in  Newark, NJ and the office of the Chief Medical Examiner in Essex County, NJ -- wrote that "fighters in whom the early symptoms are well recognized are said by the fans to be 'cuckoo', 'goofy', 'cutting paper dolls', or 'slug nutty'." Dr. Marland concluded his report of 23 cases of dementia pugilistica with a call-to-arms to neurologists and neuropathologists:

"The condition can no longer be ignored by the medical profession or the public. It is the duty of our profession to establish the existence or non-existence of punch drunk by preparing accurate statistical data as to its incidence, careful neurologic examinations of fighters thought to be punch drunk, and careful histologic examinations of the brains of those who have died with symptoms simulating the parkinsonian syndrome. The late manifestations of punch drunk will be seen chiefly in the neurologic clinics and the asylums, and such material will practically fall to the neuropathologist connected with such institutions."

As was the case 100 years ago with boxing, chronic brain damage in "head scrambled" football players is now being widely acknowledged. It is the obligation of every blue-collar neuropathologist to advance our knowledge of CTE by recognizing it in our autopsy cases and supporting the work of the two white-collar neuropathologists most involved in bringing football-related CTE to public attention: Dr. Ann McKee of Boston Univeristy and Dr. Bennet Omalu of West Virginia University. With more than four million children and young adults playing football in this country, it is our moral obligation as neuropathologists and as citizens to become active participants in the public discussion surrounding this important social and public health issue.