Thursday, October 1, 2015


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.  
·        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


·        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.