Friday, December 25, 2015

The Pigmented Cells of Metastatic Melanoma Traveling Along Virchow Robin Spaces of Adjacent Brain


Saturday, December 19, 2015

Tuesday, December 15, 2015

Please show your gratitude to outgoing AANP Business Manager Peggy Harris

The Incomparable Peggy Harris
An important message from Mark Cohen, MD and Kathy Newell, MD:Peggy Harris needs no introduction to members of the American Association of Neuropathologists, as over the past 13 years she has supported and guided most of us (including the Executive Council and Committee Chairs) through the often confusing mechanics and byways of the society's functions, and has been instrumental in facilitating every aspect of our Annual Meetings, from abstract submission to registration to finding other members to making sure that everyone got CME credits. It would be almost impossible to list everything that Peggy has done for the AANP during her tenure with us. Pardon the neuropathological pun, but it would not be hyperbole to say that Peggy has been both our pia mater and glia during her tenure with the Association.

Peggy recently learned that she will no longer be assisting the AANP membership in the new year. Many of us will be sad to see her go, and will miss her at our Annual Meetings. For those who wish to contribute to a monetary gift of appreciation and support honoring Peggy's many contributions to the AANP, we have set up this special farewell fund.

This is not an official AANP-sponsored fundraiser. All proceeds donated to this fund will go directly to Peggy to show our gratitude to her. Please join us in showing how much we appreciate all that she has done for each of us individually and for the AANP as a whole. Thanks.

Friday, December 11, 2015

"I’m a neuropathologist with a glioblastoma": A guest post from Susan M Staugaitis, MD, PhD

I’m a neuropathologist with a glioblastoma.  How ironic is that?  For 17 years, my skill in making this diagnosis has been a major part of my job.  I know more about the biology of my disease than most of the physicians involved in my care.  And suddenly, within two weeks, my life expectancy changed from 30+ years to 2-5.  My reality has changed.

If I'm freaking you out, you are not alone.  I'm freaking everybody out.  I haven’t had such a good excuse to be so “frontal lobe” since I was a teenager.  In the past five months, I have become so accustomed to my diagnosis and disabilities that I blurt it out to store clerks when explaining why I’m seeking a particular good or service.  I know the song I want to hear over and over again as I cross to the other side.  Would you expect anything less from someone who looks a lot better than her scan?  

I cope by trying to stay realistic and in the moment.  I try to extract anything and everything that is positive from my experience today and defer to tomorrow all thoughts that won’t matter until then.  It’s not much different from the days when I lived in southern California, not worrying about the “big one” that could hit anytime, but keeping myself prepared nevertheless. 

Dr. Staugaitis wearing the Novocure Optune electric field generator as part of her treatment 
Family and friends remark on the extraordinary strength and courage I display.  Honestly, hearing this can get to be too much.  I do need the people close to me to help me fortify and reinforce the strength I am finding in myself, but quixotic sentiments don’t provide much comfort.  I’m too honest and practical to expect a miracle, to dream the impossible dream.  I’ll be satisfied with the possibility of beating the odds.

But, any gambler will tell you that the odds depend on the game.  I think sports gambling is most relevant to me and my diagnosis.  In sports gambling, it is all in the point spread.  You can win when your team loses and lose when your team wins.

Neuropathologists have inside information in this respect.  We look at the location of the lesion, at the histology in the microscope, at the molecular profile, and the combination gives us a pretty good idea of how to place our bet.  No emotions or wishful thinking here; we’ve got data.  As scientists, we are obligated to describe the data accurately and analyze it objectively.  In fact, if we are to gain and maintain the respect of our peers, we cannot ignore any data, no matter how much we dislike it, no matter how much it conflicts with our view of how the world should be.  And as writers, we find the words that communicate our interpretations as definitively and positively as possible without being incorrect.

Then it is time to sit back and watch the game, wait for the final score.  Did my bet beat the spread? 

And regardless of the game’s outcome, there will always be another game: new questions, new data to acquire.  So we pick ourselves up, dust ourselves off, and start all over again.

© 2015 Susan M. Staugaitis, M.D., Ph.D. 
Retired Consultant Staff, Departments of Pathology and Neurosciences, Cleveland Clinic
Adjunct Assistant Professor of Molecular Medicine

Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

Thursday, December 10, 2015

Renowned neuropathologist Peter Burger set to retire at the end of this month

Peter C. Burger, MD
I just got word that the illustrious Johns Hopkins neuropathologist Peter C. Burger, MD is set to retire at the end of this month. In an email yesterday, the 74-year-old professor informed me that he will continue to work on various neuropathology projects, but will not be signing out cases after December 31. He writes that he is "ready for a new phase of life without the daily responsibility of cases". His sage consultations on difficult cases will be missed, but I am sure his impact will continue to be felt in the field through his valuable publications.

Wednesday, December 9, 2015

Not allowing kids to play football is "our moral duty": Bennet Omalu, MD

In a recent New York Times opinion piece, pathologist Bennet Omalu strongly endorsed a policy that children should not play football. Here are excerpts from his essay:

"We've known since 1964 that cigarette smoking is harmful to your health. We’ve known for more than 40 years that alcohol damages the developing brain of a child. We’ve known since the mid-70s that asbestos causes cancer and other serious diseases. Knowing what we know now, we do not smoke in enclosed public spaces like airplanes; we have passed laws to keep children from smoking or drinking alcohol; and we do not use asbestos as an industrial product.

"If a child who plays football is subjected to advanced radiological and neurocognitive studies during the season and several months after the season, there can be evidence of brain damage at the cellular level of brain functioning, even if there were no documented concussions or reported symptoms. If that child continues to play over many seasons, these cellular injuries accumulate to cause irreversible brain damage, which we know now by the name Chronic Traumatic Encephalopathy, or C.T.E., a disease that I first diagnosed in 2002."

It should be noted that the CTE brain bank at Boston University found evidence of CTE in the brains of 131 out of 165 athletes who played professional, college, or high school football. In other words, based on this sample size, the risk of getting CTE from playing football for a relatively extended period is higher than the risk of getting lung cancer from smoking.

Since we have a legal age at which individuals are allowed to smoke, drink alcohol, and drive, it stands to reason that engaging in an activity that is likely to cause brain damage should also only be engaged in by individuals old enough to make an informed decision, says Omalu. 

Thanks to Dr. Chad Vanderbilt for alerting me to this article.

Tuesday, November 24, 2015

The Mercado Brain Cutting Device launched at the University of Colorado

Thanks to a hand-made gift from University of Alabama neuropathology fellow Juan Mercado, MD, our residents on autopsy rotation this month had the opportunity yesterday to inaugurate the use of The Mercado Brain Cutting Device (MBCD). Made from tools easily found at any hardware store, the device allows prosectors to make reliably even 1-cm thick coronal brain slices for optimal demonstration of gross anatomy and pathology. University of Colorado pathology residents Abby Richmond, MD (PGY-III) and Sammie Roberts, MD (PGY-I) used the device to great advantage as demonstrated by the exquisitely presented brain slices laid out for inspection.

Dr. Sammie Roberts with the MBCD 
Dr. Abby Richmond makes the first cut

Sections are even and uniform in thickness

The finished product

Drs. Moore, Richmond, and Roberts (left to right) examining the coronal sections

Much appreciation to Dr. Mercado for gifting this device, which he describes as a "limited edition (1 or 1)", to our department. We will undoubtedly have more meticulous brain cutting sessions henceforth thanks to Dr. Mercado's efforts.

Wednesday, November 18, 2015

A 60-year-old woman with a left occipitotemporal brain lesion

We were sent this case in consultation to rule out infiltrating neoplasm. The diagnosis is amyloid beta related angiitis (ABRA). In this case, no infarction was present in the specimen, but white matter rarefaction (the presumed pathologic correlate to the leukoaraiosis reported on imaging) is present.

Granulomatous vasculitis associated with pink hyaline material in vessel walls

The pink hyaline material is shown to be beta-amyloid by immunohistochemistry

White matter rarefaction (upper half of picture) correlating with leukoaraiosis seen on imaging

Tuesday, November 17, 2015

Best Post of June 2015: First Day at 2015 American Association of Neuropathologists Meeting - The Special Course

The next in our "Best of the Month" series comes from 11 June 2015, where we harken back to the first day at the American Association of Neuropathologists (AANP) annual meeting held in my newly adopted home of Denver, Colorado:


The "Special Course" which typically launches the annual AANP meeting was anything but typical this year. Rather than the usual series of research presentations which has characterized the first day of the meeting, the 2015 edition of the "Special Course" focused on need-to-know practical topics. Dr. Beatriz Lopes put together a program that offered something for everyone -- from trainee to seasoned practitioner. The morning started with a presentation by Dr. Caterina Giannini on primary CNS lymphoma, as well as its mimickers and precursors. Far from being a straightforward diagnosis, lymphoma -- particularly in the setting of corticosteroid therapy -- can be mistaken for anything from multiple sclerosis to infarct. Next, two eminent scholars from Paris, Drs. Francoise Gray and Elisabeth Tournier-Lasserve, presented a three-part lecture on the hereditary non-amyloid small vessel diseases of the brain. Then Charles Eberhart showed up from Johns Hopkins to provide a primer on ophthalmic pathology, providing a practical approach to eye specimens. For example, Dr. Eberhart discussed the significance of uveal granulomatosis in orbital exenteration specimens. The presence of this finding should be noted in the pathology report as it portends an increased risk for sympathetic ophthalmia. Dr. Arie Perry appeared next with a presentation on the molecular characterization of brain tumors using immunohistochemical surrogates -- an approach particularly appreciated by neuropathologists who work at smaller institutions which may not have the resources to perform sequencing and other more advanced laboratory tests. After lunch, the focus was redirected to neuropathology training. Drs. Marc Del Bigio and Suzanne Powell discussed the state of neuropathology training abroad and in the United States, respectively. Finally, a lively discussion was initiated by a panel featuring Drs. Jeff Golden, Dennis Dickson, Liz Cochran, and myself organized under the title "The Professional Market for Neuropathology Trainees". Several audience members talked about their view of the profession and how its many facets are reflected in the training we give fellows and how that training impacts the preparedness of trainees for the job market. Overall, it was engaging day which, as audience member John Donahue put it, was "well worth the price of admission!"

Tuesday, November 10, 2015

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!

Wednesday, October 28, 2015

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.

Friday, October 23, 2015

Psammomatoid juvenile 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:



Thursday, October 22, 2015

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

Thursday, October 15, 2015

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.


Monday, October 12, 2015

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.

Thursday, October 1, 2015

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.


Monday, September 28, 2015

Tuesday, September 22, 2015

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 FallonDr. 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 goalI 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"!

Wednesday, September 9, 2015

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.

Wednesday, September 2, 2015

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.

Sunday, August 23, 2015

Best Post of January 2015: Dr. Pierluigi Gambetti steps down as director of national prion surveillance center

The next in our "Best of the Month" series comes from January 5, 2015:


Pierluigi Gambetti, MD
Dr. Pierluigi Gambetti has stepped down as director of the National Prion Disease Pathology Surveillance Center. In a letter to members of the American Association of Neuropathologists, Dr. Gambetti writes:

"I will be resigning as Director of the National Prion Disease Pathology Surveillance Center effective January 1, 2015. I will continue to be associated with the Center in an advisory position and as consultant for special cases. Dr. Jiri Safar, Associate Professor of Pathology and Neurology at Case Western Reserve University, will be the new director."

Dr. Gambetti goes on to state that the NPDPSC "will remain unchanged", continuing to coordinate autopsies on suspected prion disease cases. Dr. Mark Cohen will continue to have primary responsibility for the histologic and immunohistochemical assessment of cases.

Saturday, August 15, 2015

College of American Pathologists Neuropathology Committee Meets this Weekend

I am delighted to be in Chicago this weekend meeting with my wonderful colleagues on the College of American Pathologists Neuropathology (CAP-NP) Committee. We are making plans for a SAM-eligible educational product that will update you on the 2015 iteration of the World Health Organization Classification of Tumors of the Central Nervous System. The new WHO book is set to be published in October of this year; and we on the committee are making plans to create a CD to be issued a year from now designed to keep you in the loop regarding the latest in CNS tumor classification. This weekend's meeting also marks the end of Dr. Dan Brat's tenure as CAP-NP chairman. Dr. Brat will  be replaced by the illustrious Dr. Eyas Hattab at the helm of the CAP-NP Committee. After a long day at work today on the CAP-NP educational product, committee members retired to Smith and Wollensky Steakhouse for some well-deserved nourishment before returning to finish up our work tomorrow. In addition to Drs. Brat, Hattab, and myself, current committee members include Drs. Bill Hickey, Joe Ma, Roger McLendon, Matthew Schneiderjan, Aaron Wagner, Cynthia Welsh, and junior member Matthew Cykowski.

Rania Hattab (wife of Dr. Eyas Hattab) and Dr. Joe Ma enjoy a morsel of chocolate cake at tonight's CAP-NP dinner

Outgoing CAP-NP committee members Dr. Dan Brat and Dr. Cynthia Welsh will be sorely missed

Wednesday, August 5, 2015

The Tumor Biomarker Series: INI1

This is the last in my tumor biomarker series -- at least until future significant biomarkers are established. I conclude this series with a short description of INI1, a marker for atypical teratoid/rhabdoid tumor (AT/RT). A clinically aggressive embryonal tumor of infancy, AT/RT is characterized by mutations in SMARCB1/INI1 (HSNF5). Immunohistochemical evaluation of AT/RT for the INI1 protein using the BAF47 antibody shows a loss of labelling in tumor cell nuclei, with retention of staining in internal positive control cells such as endothelial cells. Since AT/RT has morphologic overlap with medulloblastoma, CNS PNET, choroid plexus carcinoma, GBM, and other malignant tumors of childhood, INI1 immunohistochemistry is extremely useful in arriving at a diagnosis of AT/RT. A diagnosis of AT/RT carries implications for genetic counseling as this tumor -- in about a one-third of cases -- is a component of the rhabdoid tumor predisposition syndrome (RTPS) wherein there is a germline mutation of SMARCB1/INI1. Because of the risk associated with RTPS, the germline status of SMARCB/INI1 is typically assessed for each new case of AT/RT.

Wednesday, July 29, 2015

Best Post of December 2014: The Einstein/Rorke-Adams Connection

The next in our "Best of the Month" series comes from Tuesday, December 16, 2014:



Dr. Lucy Rorke-Adams
I'm not sure how many in the neuropathology community know this, but our renowned colleague Lucy Rorke-Adams donated slices of Albert Einstein's brain to the Mütter Museum and Historical Medical Library in Philadelphia. Rorke-Adams, a senior neuropathologist at the Children's Hospital of Philadelphia, donated the 46 slices of brain tissue to the museum in 2011. Rorke-Adams had received the slides as a gift from local doctor, who in turn had received them from his colleague, a neuropathologist who examined the slides on behalf of Thomas Harvey, the man who removed Einstein's brain during an autopsy in 1955. Guess where my first stop will be on my next visit to Philly?

Friday, July 17, 2015

The Tumor Biomarker Series: Medulloblastoma Markers

Four subgroups of medulloblastoma have been defined based on genetic alterations:

Wingless (WNT) - WNT medulloblastomas display monosomy 6 and most show nuclear accumulation of the WNT pathway protein beta-catenin, which serves as a useful immunohistochemical screen for this group. Medulloblasomas with more than 50% nuclear staining for beta-catenin have been shown to have WNT pathway activation, whereas those with only focal nuclear staining do not. Overall survival for WNT medulloblastomas are dramatically longer than those of other subtypes, and clinical practices surrounding the treatment of this subtype reflects this better prognosis.

Sonic Hedgehog (SHH) - SHH medulloblastomas often show a nodular/desmoplastic histopathology and are associated with a better prognosis in younger children and infants. 9q deletion is characteristic, and MYCN amplifications are occasionally noted. GAB1 is expressed in the cytoplasm of nearly all SHH medulloblastomas but not in other groups and can be detected imunohistochemically, making it a valuable SHH-group marker.  Targeted therapies directed at this subgroup have been established and are entering clinical practice.

"Group 3" - Group 3 medulloblastomas have the worst overall prognosis, have a high incidence of large cell/anaplastic histology, and are very frequently metastatic. This group contains the vast majority of MYC amplified tumors, with MYC amplification being a strong negative prognostic factor. It has been suggested that Group 3 tumors should perhaps be re-named MYC medulloblastomas, but wide agreement has not been reached on this designation. Group 3 tumors occur more commonly in males than females, and are found in infants and children, but almost never in adults.


"Group 4" - Group 4 medulloblastomas classically harbor isochromosome 17q; but as the molecular pathogenesis of this group is not currently clear, the generic name "Group 4" remains the consensus designation. Although isochromosome 17q is also seen in Group 3 tumors, it is much more common in Group 4. KCNA1 has been suggested as an immunohistochemical marker for this group, but this requires validation.  The only other notable cytogeneic change seen in Group 4 tumors is loss of X chromosome, which is seen in 80% of females with this tumor subtype. Group 4 patients have an intermediate prognosis, similar to patients with SHH tumors.

In conclusion, the worst prognosis is associated  with Group 3 medulloblastoma; Group 4 and SHH have an intermediate prognosis; and WNT medulloblastoma tends to have the best prognosis.