Best Post of May 2015: "Bad Ass" CrossFitter and Neuropathologist Greg Fuller set to compete in kettlebell competition for brain cancer research

The next in our "Best of the Month" Series comes from Wednesday, May 20, 2015:

Elite Neuropathologist

Elite Athlete

It's no secret that Dr. Greg Fuller (pictured) is the fittest neuropathologist in the world. What his colleagues might not know is that he is the 67th fittest man in the world for his age class (60+). Greg's wife, Tina, describes him as a "bad ass CrossFitter". As a former owner of a CrossFit "box" myself, I know what it takes to achieve Greg's level in the Sport of Fitness. It requires true grit. There are many of us who would also consider Greg a "bad-ass neuropathologist" -- in the very best sense of that phrase. He's bringing together his love of fitness with his commitment to the study of CNS malignancies by participating in the Kettlebells For Brain Cells competition in Boerne, Texas on June 13. (So, he has a legitimate reason for not showing up at the concurrent AANP annual meeting. in Denver.) All proceeds from the competition will be going to the American Brain Tumor Association. The event is being organized by a brain tumor patient at MD Anderson Cancer Center, where Greg is Chief Neuropathologist. This is a shining example of a neuropathologist reaching out to a patient in a very personal way. Best of luck in the competition, Greg. Crush it!

Best Post of April 2015 - The Tumor Biomarker Series: BRAF

The next in our "Best of the Month" series comes from Tuesday, April 28, 2015:

BRAF gene (v-Raf murine sarcoma viral oncogene homolog B)

BRAF+ IHC (correlates with V600E mutation) in ganglioglioma

Aberrant constitutive activation of BRAF tends to be seen in cerebellar and midline pilocytic astrocyomas whereas the activating point mutation at BRAF V600E is more likely to be seen in cerebral examples. The V600E point mutation is also observed in other low-grade gliomas and glioneuronal neoplasms, including approximately two-thirds of pleomorphic xanthoastrocytomas, and lower percentages of ganglioglioma, desmoplastic infantile ganglioglioma, dysembrioplastic neuroepithelial tumor, and papillary craniopharyngioma. Although less common, diffusely infiltrative gliomas including glioblastoma, particularly the epithelioid variant, may also demonstrate the V600E point mutation -- making this biomarker potentially less useful as a diagnostic tool in distinguishing low-grade gliomas from high-grade ones.

Juvenile psammomatoid ossifying fibroma in 22-year-old male with eyelid droop

This lesion was arising from the nasal sinuses but was growing into the anterior skull base and pushing into the left orbitofrontal region. At first low-power glance, I thought it was a bread-and-butter psammomatous meningioma. But it revealed itself when targeted with a 20X objective lens:

Brain Tumor Rhapsody by Dr. Arie Perry

Arie Perry, MD

I have written about Dr. Arie Perry's incredible musical talent before, and how he has applied it to neuropathology education. Well, he's brought that talent to a whole new level through a collaboration with the San Francisco Bay Area's vocal ensemble Musaic.  With Virchow as his muse, Arie outlines major biomarkers in the diagnosis of CNS tumors. This magnum opus is called Brain Tumor Rhapsody, and its Dr. Perry's first-ever educational music video.This is an epic musical and neuropathological achievement! Many thanks to Dr. Gabrielle Yeaney of the Cleveland Clinic for alerting me to this remarkable video. Check it out on YouTube!

Gabrielle A. Yeaney, MD

Heterotopic neuron in a patient with epilepsy

The patient is a 22-year-old female with intractable epilepsy who underwent resection of an epileptogenic region of the left lateral temporal lobe. In addition to mild cortical dyslamination (not depicted) and Chaslin's subpial gliosis (pinkish band on top surface of brain in photomicrograph), there were an increased number of individual heterotopic neurons within the neocortical molecular layer. The heterotopic neuron pictured below is also disoriented, with its axon projecting tangentially rather than perpendicularly to the the pial surface.

Best Post of March 2015: The asinine reason why the name JCD was converted to CJD

The next in our "Best of the Month" series is from March 25, 2015.

Originally referred to as Jakob-Creutzfeldt disease (and believed by many to rightfully be called simply Jakob's disease), we now refer to this prion disease as Creutzfeldt-Jakob disease. Why? It all stems from a Dr. C. Joseph Gibbs, a colleague of D. Carleton Gajdusek's at the National Institutes of Health, who worked on this disease back in the 1960's. Here's the explanation, lifted from Nobel laureate Stanley Prusiner's Madness and Memory: The Discovery of Prions - A New Biological Principle of Disease:

"Alfons Jakob wrote a paper in 1921 describing several cases of progressive dementia with widespread neuronal loss in the brain. A year earlier, Hans Creutzfeldt had described the brain of a woman who died after a prolonged series of seizures. He found widespread vacuolation, but some medical scientists believe that his patient died of a seizure disorder complicated by hypoxic brain damage and doubt that she had what became known as CJD. So why did the named Jakob and Creutzfeldt become flipped in an important report on the disease, regarding the transmission to a chimpanzee? Twenty years passed before I found the answer, in conversation with Gibbs. 'When I was writing my first paper on the transmission of Jakob-Creutzfeldt disease to an ape,' he told me, 'I wanted to rename the disease Gibbs disease. I didn't think this would be acceptable to the scientific and medical communities, so I decided to reverse the names, because my first name is Clarence and my middle name is Joseph and my initials are C.J.' Thus did the diease become known as Creutzfeldt-Jakob disease, or CJD for short - a case of mind-boggling scientific mischief." 

Gibbs (left) and Gajdusek with a New Guinea kuru patient in 1972.

 
A remarkable case ofhubris, although from what I hear about Prusiner, he is not one to point fingers at those who grasp credit for the work of others.Gajdusek, also a Nobel prize winner, once wrote inhis diary the following about Prusiner:


""I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

But then again, Gajdusek himself, who died in 2008 at age 85, was no paragon of virtue.In the course of his research trips in the South Pacific to study kuru , Gajdusek had brought 56 mostly male children back to live with him in the United States, and provided them with the opportunity to receive high school and college education. He was later accused by one of these, now an adult man, of molesting him as a child. In fact, seven men testified in confidentiality about Gajdusek having had sex with them when they were boys.  Gajdusek was charged with child molestation in April 1996, based on incriminating entries in his personal diary and statements from a victim. He pleaded guilty in 1997 and, under a plea bargain, was sentenced to 12 months in jail. After his release in 1998, he was permitted to serve his five-year unsupervised probation in Europe. He never returned to the United States and ultimately died in Norway.

Chromothripsis!

The next edition of the World Health Organization Classification of Tumors of the Central Nervous System will feature a new, separate ependymoma subtype: RELA fusion-positive ependymoma. RELA fusion refers to the juxtaposition of the RELA gene (the principle effector of NF-кB signaling which controls DNA transcription and cell survival) to the poorly characterized C11orf95 gene. Fusion of these two genes is brought about by chromothripsis, a term first coined in 2011 that literally means "chromosome shattering". Chromothripsis occurs when chromosomal segments first fragment into many pieces and then get stitched back together in random order by DNA repair processes. Seen in the setting of some malignancies, chromothripsis in a particular segment of chromosome 11 can result in C11orf95-RELA fusion, which in turn drives oncogenic NF-кB signaling in ependymoma.

Chromothripsis (literally meaning "chromosomal shattering") can drive oncogenesis

Although chromothripsis is a novel model for oncogenesis, it does not necessarily contradict more established models of progressive cancer development as there is no definitive proof that chromothripsis has to occur as a single catastrophic event. Nevertheless, this is a fascinating area of research which will undoubtedly yield more insights into the progression of at least a subset of cancers.

The Brain -- as explained by John Cleese

Finally, it has become clear to me now:

https://m.youtube.com/watch?v=FQjgsQ5G8ug&feature=youtu.be

Thanks to Dr. Ann Thor for directing me to this concise explanation of the brain and its connections.

Guest Post: How to make your own brain cutting board

Today I am fortunate to host a guest blogger, Dr. Juan Mercado, who is a neuropathology fellow at the University of Alabama at Birmingham under the guidance of Drs. Robert Hackney and Kenneth Fallon. Dr. Mercado studied music from a young age and went to a specialized school of music in San Juan, Puerto Rico; but during college he decided to exchange music for medicine and attend the University of Puerto Rico School of Medicine. He has not, however, abandoned his creative approach to the subject matter at hand; in this case, cutting autopsy brains. His guest post follows:

Juan J. Mercado, MD (neuropathology fellow at UAB 2015-17)

A while ago, as a pathology resident, I was temporarily in charge of organizing the weekly brain cutting activity. During this event I always felt a little bothered by the unpredictability and irregularity that occurred with each cut and the variability of results with each different person trying to pursue the same goal.  I decided to do some research trying to find more information about how brain grossing examination was done in different places. To my amazement, I found out about a brain tissue bank in the United Kingdom that performed their coronal sections with the help of a tool. This tool enabled them to create perfect fine cuts every time to perform a complete meticulous evaluation. After knowing about this, I was highly motivated to perform a DIY project. As I optimistically anticipated, the results were excellent. I made the tool using materials that I could easily find in any hardware store. This new and improved tool could now be made by anyone interested in having the same results.  

Materials:

·        White durable cutting board: the bigger the better (Fig. 1)

Figure 1

·        Straight cabinet handles: they come in different diameters, meaning a different brain slice thickness can be created depending on this diameter. Also they come in different lengths. Choose a length proportionate to the size of the cutting board you select. These bars always come with the screws included. (Fig. 2)

Figure 2

·        Drill: to make four holes

·        Rubber O-ring washers: not necessary, but I use them just for the preservation of the tool, preventing liquids or tissue to enter in the drilled holes (Fig. 3)

Figure 3

·        Rubber chair legs (to elevate the board from a surface and to hold its placement) (Fig. 4)

Figure 4

With the above materials you can create the basic version that will permit you to create cuts of only one predetermined thickness based on the diameter of the bar you select. You can also have an add-on to be able to do thinner cuts with the same board, but it is not necessary. 

How it works:

After detaching the brainstem via an axial cut through the midbrain and then making the first brain coronal section cut through the middle of the mammillary bodies, proceed as usual making coronal sections but with the help of the tool

The bars aligned in the way pictured (Fig. 5) serve to hold in place any brain size firmly while cutting. Use a rigid knife sliding it above the bars as a guide. In this way the thickness of the brain sections will be the same as the diameter of the bars 

Figure 5


Advantages

·        Always the same results, not relying on the experience of the person cutting the brain -- meaning standardization.

·        Homogeneous leveled slices. Option of creating thin slices help in a more meticulous evaluation.

·        When a pathologic finding is present, such as a big intraparenchymal hemorrhage that normally disintegrates the brain slice if performed by normal technique; it does not happen with this tool.

·        Better pictures.

·        It is a lot faster and the cuts are perfect. Less time cutting, more learning and teaching.

See for yourself…

        Add-on(s): Optional (need a saw)

A thinner cutting board cut to fit within the two bars. The diameter of the bar minus the thickness of this board will be your new brain slice thickness, making the same board practical for two different thicknesses.

Thanks, Dr. Mercado. I have often thought about how nice it would be to have a tool that could simplify and standardize braincutting. I am hoping he builds a limited-edition series of these devices and sells them at the next AANP meeting. Since I am not particularly mechanically inclined, I would be the first in line to purchase what I am hereby dubbing "The Mercado Brain Cutting Device"!

Best Post of February 2015 - The Perils of Crossing Boundaries in the Interstate Practice of Neuropathology: Real or Imagined?

The next in our "Best of the Month" series comes from February 17, 2015:

A provocative article entitled Crossing Boundaries: A Comprehensive Survey of Medical Licensing Laws and Guidelines Regulating the Interstate Practice of Pathology appeared in March of last year in the American Journal of Surgical Pathology (Am J Surg Pathol 2014;38:e1–e5) which addressed recent judicial interpretations of interstate medical licensure laws. These legal developments are relevant to neuropathologists insofar as we, as a small group of sub-specialists, not uncommonly serve as consultants on surgical cases from outside of our own state. Recent legal judgements have found pathologists guilty of malpractice and even the criminal practice of medicine without a license. Given these recent developments, authors MC Hiemenz, ST Leung, and JY Park surveyed the licensure requirements and laws regulating the interstate practice of pathology. The authors then grouped states according to similarities in legislation and medical board regulations. The survey determined that states define the practice of pathology on the basis of geographic location of the patient at the time of the surgery.  Thirty-two states and the District of Columbia allow for a physician with an out-of-state license to perform limited consultation to a physician with an in-state license. However, five states prohibit physicians from consulting out of state unless they themselves hold a license in that state. Other states have limited restrictions, such as requiring that the consultation itself occur within the state.  The authors conclude that pathogists who either send cases out to consultants in other states or who serve as consultants to out-of-state pathologists should familiarize themselves with the medical licensure laws of the states from which they either send or receive cases. In a November 2014 letter to the editor, Edward O Cousineau, JD, deputy executive director of the Nevada State Board of Medical Examiners, wrote that "the representations in the article, related to how Nevada law applies to out-of-state licensed specialists, are erroneous". In the article, Nevada was represented as being in the category which allows for an out-of-state licensed physician to practice medicine in consultation with an in-state licensed physician, with the additional stipulation that the consultation must occur within the state boundaries. Mr. Cousineau, in representing the Nevada Board, stated that Nevada allows out-of-state consultations without the stipulation that the consultation must occur within state boundaries. Given Nevada's response to the survey, it may be that more states allow out-of-state consultation than the article indicates. Unfortunately, however, the article may have resulted in the unnecessary restriction of certain out-of-state consultations by cautious department chairs

Please comment if you have been impacted by these state licensure issues when either consulting out of state or seeking a consultation from an out-of-state neuropathologist. I'm sure your colleagues would be interested in hearing your story.

Neuropathology Goes Hollywood: "Concussion" Opens in Theaters December 2015

Dr. Bennet Omalu, the first neuropathologist to draw a connections between playing football and the development of Chronic Traumatic Encephalopathy, is featured in a movie starring Will Smith slated to open in December. Check out the trailer!

Will Smith portraying Bennet Omalu, MD in the movie "Concussion"

Not surprisingly, according to a New York Times report, the National Football League intervened in the making of the film so that the final cut would not vilify the nation's most-watched game.