Thursday, December 20, 2018

The new WHO Ocular Tumour “Blue Book” is now available!

Prepared by 64 contributors from 22 countries

More than 400 tables and color photos 
The new edition of the WHO Classification of Tumours of the Eye is now on sale, just in time for Christmas! The latest edition is edited by Drs. Hans E. Grossniklaus, Charles Eberhart, and Tero Kivela. There are sections on all recognized neoplasms of the eye, lacrimal apparatus, and conjuctiva. Included are substantial changes to the classification of conjunctival neoplasia and melanoma, based on the latest molecular studies.  Information on clinical features in addition to prognostic and predictive factors for each tumour type are provided. Also included are updates to the existing ICD-O codes and new codes for use in epidemiology and cancer registration.

Chapters are as follows:
1. Conjunctiva and caruncle
2. Iris, ciliary body, and choroid
3. Retina and retinal pigment epithelium
4. Optic disc and optic nerve
5. Lacrimal gland
6. Lacrimal drainage system

Wednesday, December 19, 2018

Creating a Google Earth of the Brain

A recent New York Times article describes a $50 million project by more than a dozen research centers aiming to create a sort of Google Earth of the brain. In a series of 11 papers, published in Science and related journals, a consortium of researchers has produced the most richly detailed model of the brain’s genetic landscape to date, one that incorporates not only genes but also gene regulators, cellular data and developmental information across the human life span.

The PsychENCODE Consortium, initiated in 2015 and financed by the National Institute of Mental Health, involves more than a dozen research centers and scores of specialists in cell biology, genetics and bioinformatics. It is an all-hands, brute-force effort, coordinating top brain banks and brain scientists at major research centers, led by Yale, Mount Sinai, UCLA, and UCSF.

Dr. Matthew State, chair of the department of psychiatry at the University of California, San Francisco, and a co-author on two of the papers, said: “Essentially what these papers do is lay out cellular and molecular landscape at a resolution that’s never existed before. I see it as foundational work, and an investment that will pay off in giving us a far richer context to develop new hypotheses and study these disorders.”

Friday, December 14, 2018

Best Post of November 2018: The exquisite cellular uniformity of the central neurocytoma

The next in our "Best of the Month" series is from November 20, 2018:

Intraoperative ThinPrep smear demonstrates the striking cellular uniformity

Permanent section of the same tumor

Monday, December 10, 2018

A Pattern-Based Approach to the Interpretation of Skeletal Muscle Biopsies

Chunyu (Hunter) Cai, MD, PhD
Chunyu (Hunter) Cai, Douglas Anthony, and Peter Pytel have authored a wonderfully useful review article in Modern Pathology entitled A Pattern-Based Approach to the Interpretation of Skeletal Muscle Biopsies. Dr. Cai wrote the following to me: "In this review, we take a pathology-friendly approach and categorize muscle biopsies into 6  morphologic groups, and discuss common differential diagnoses for each group. I think this review fills a void that there is not a good quick guide for NP fellows, residents and even neuropathologists who don’t sign out muscle cases on a routine base." Thanks, Drs. Cai, Anthony, and Pytel for a review article that will be a fixture on the desks of many neuropathologists in the coming years!

Tuesday, December 4, 2018

Giant cell GBM masquerading as an anaplastic PXA

At first glance, this tumor with pleomorphic cells and prominent perivascular lymphocytic cuffing strikes one as a pleomorphic xanthoastrocytoma (PXA).

The relative circumscription, as demonstrated by the stark difference in tumor burden in adjacent gyri depicted above also suggests the possibility of  PXA.

The presence of mitotic figures (center of picture above) and a small amount of necrosis and microvascular proliferation (not pictured) suggests the possibility of anaplastic PXA.

However, perivascular lymphocytes and relative circumscription can be seen in giant cell glioblastoma (GC-GBM). Pointing away from anaplastic PXA is the fact that there was no evidence of Rosenthal fibers and eosinophilic granular bodies. Additionally, there was strong p53 immunohistochemical positivity. The final diagnosis was Glioblastoma, IDH-wildtype, WHO grade IV, giant cell variant.

Wednesday, November 28, 2018

A middle-aged patient with panhypopituitarism

The clinicoradiological suspicion in this case of a middle-aged patient with panhypopituitarism was hypophysitis.

T1 sagittal post-contrast
Transphenoidal hypohysectomy yielded the following specimen:

Two populations of cells predominate: small monomorphic cells and larger pleomorphic cells
Immunohistochemistry identified the larger pleomorphic cells as representing a large B-cell lymphoma, while the small cells were intermixed non-neoplastic T-cells.

This ACTH immunostain demonstrates the progressive obliteration of the pituitary gland by the invading lymphoma

Diffuse large B-cell lymphoma presenting as a pituitary mass is rare. A few case reports exist in the literature.

Friday, November 23, 2018

Unexpected Neuropathology Fellowship opening at Mount Sinai starting July 2019

John F. Crary, MD, PhD
Dr. John Crary just informed me that his institution, Mount Sinai, has an unexpected opening for a neuropathology fellowship starting in July 2019.  Interested candidates can contact him at

Wednesday, November 21, 2018

Tuesday, November 20, 2018

The exquisite cellular uniformity of the central neurocytoma

Intraoperative ThinPrep smear demonstrates the striking cellular uniformity

Permanent section of the same tumor

Monday, November 19, 2018

Perforating injury of globe

Ocular perforation caused by BB gun is a through-and-through injury with entrance and exit wounds in limbus and sclera, respectively. The track of the BB is marked by fresh blood. Posteriorly detached vitreous also contains ochre-colored degenerated blood.

(Source: Eagle R. Eye Pathology: An Atlas and Text. Second Edition. 2011)

Wednesday, November 14, 2018

Q&A with Dr Peter Cummings, co-author of “Brainwashed: The Bad Science Behind CTE and the Plot to Destroy Football”

Peter Cummings, MD

1.   Chronic traumatic encephalopathy has been considered by many to be a distinct nosologic entity since 1928, when Dr. Harrison Martland published the article Punch Drunk” in JAMA. Do you believe that CTE is a distinct entity? If so, what, in your opinion, defines CTE?

That's a good question! If you look at the totality of the literature in a historical context, you see the 'classic' boxers neuropathological changes followed by the Omalu cases and then the McKee cases. Looking at all of these cases you can see that there is a wide spectrum of changes considered to be "CTE". Right now I think all we can say is CTE is a pattern; we don't know what causes it and we don't know what it causes. There are cases of CTE-like pathology in people who have never been exposed to repetitive head trauma and never had a head injury. The answer is probably more complex than we're able to say right now. There are extremist views (such as that expressed in a 2015 BMJ editorial) that suggest CTE doesn't exist outside of boxing and CTE as described in football players is an American social phenomenon. There is a lot more work to do in this area and we discuss that in the book.

2.   Whats your opinion of the work of Bennet Omalu as it pertains to CTE?

It's certainly historically important. After all, it's what really launched this whole conversation. We talk a little bit about it in the book. I do think there is some debate on whether or not some of his cases are CTE, but that might be a factor related to the wide spectrum of patterns said to be present in these individuals. I've always been curious as to why none of his football player cases were examined in the process to develop a consensus diagnosis. Again, that is something we discuss in the book.

3.   What conclusions drawn by Dr. Ann McKee regarding CTE do you have issue with?

I take issue with a number of things. First, I think the way the cases are portrayed in the media is disingenuous. In the CTE Center’s scientific papers, they assert that one cannot imply or conclude prevalence but then will go on to state in the media that they think every player has this. The CTE Center has also clearly stated in their papers that findings of a study should not  be used to inform safety and/or policy decisions in youth football but then proposes publicly in the media and in testimony before state legislatures that tackle football should be banned for kids under 14. It also bothers me when they put up a photo of an atrophic brain and claim it's severe CTE without any other qualifier. Over half of the 'severe' cases of CTE have another primary neurodegenerative disease, so when you look at those nice photos of atrophic brains, you have to wonder what other disease is lurking in there. Is it also Alzheimer’s disease? As stated by their very own consensus recommendations, if another neurodegnerative disease is present, it excludes CTE as the sole diagnosis. So, when the photos are shown in the media and they don't tell you it's Alzheimer's disease with CTE, it's disingenuous at best. Science doesn't stop at the paper, it continues into the public arena where it is used to educate the public. Here, it's not educating, it's fear mongering. I also have great concerns over the lack of transparency with information coming from the CTE Center. I described some of this in great detail in the book. For example, not turning over documents when presented with a signed release from a family; requiring a subpoena and then failing to turn over all the records; when I demand the missing records I am asked 'why am I drilling so hard? The NHL didn't drill this hard,'; and when I finally get the records, the names of the clinicians who reached the diagnoses are blacked out. Why? Additionally, the public should know that there exists cases where neuropathologists have looked at brains prior to the CTE Center and failed to find CTE, but when the brain arrive at the CTE Center, they all have CTE. This diagnostic discrepancy is alarming. There are many other examples in the book.

4.   The title of your book is rather sensational (the plot to destroy football”). Are there actually people plotting a plan? If so, who are these conspirators?

I think we paint a pretty clear picture in the book of what is going on and how football has been targeted. For example, with the recent proposed legislation to ban youth tackle football in California, I found it outrageous that if the bill would have passed, an 8 year old in California wouldn't be able to play football, but could box or fight in MMA--sports designed to target the head. If this bill was really about brain health in kids, the coverage would encompass all areas of potential brain injury in all sports—not just football. The PR campaign accompanying the public release of the various CTE studies intentionally generate undue fear in parents and in the general public. The PR has intentionally tried to definitively link youth football to subsequent CTE-- and there is no scientific evidence of that. And for scientists involved in CTE research, who mind you, have no training, certification, or experience in youth football, to call out the sport for not responding is deceptive-- it's one of the reasons why I did become certified and I started to coach both flag and tackle and I would argue that no other youth sport has made a more radical transformation than youth football in response to safety concerns; I know this because I coach! Another example from the book is how some at BU have tried to silence me and discredit my opinions. 

In the end "Brainwashed" is a very optimistic book full of hope and information which we hope will empower people. We wrote it as two dads asking the same questions a lot of other parents are asking and I think people who read the book will see that and realize it’s our journey for the truth for our own kids. In the end, we really hope people will have more information and be in a better position to make an informed decision as to whether or not a particular sport is right for their family.

Monday, November 12, 2018

Dr. Fausto Rodriguez to deliver live online presentation this Wednesday

Wednesday, November 14th  - 8 AM EST

Topic: Surgical Neuropathology Pearls:
Sellar Lesions
Presented by Fausto Rodriguez, MD,
Associate Professor of Pathology, JHUSOM

This seminar can be accessed live
through the following links at 8 AM on Wednesday:

This hour-long PathCast seminar presented by Dr. Fausto Rodriguez will be broadcast live on both Facebook and YouTube.
Live chat will be available for you to discuss the presentation with Dr. Rodriguez during the seminar.

The PathCast will be archived after the live session at:

Wednesday, November 7, 2018

SF-1 immunohistochemistry for detecting gonadotroph adenomas

Adenomas driven by the transcription factor SF-1, which are exclusively gonadotroph adenomas, are a common subtype encountered by the surgical pathologist. Traditionally, gonadotroph adenomas have been defined by positive immunostaining for luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) with or without alpha-subunit (αSU). However, SF-1 alone can detect gonadotrophin adenomas. Further, the majority of previously classified "null cell" adenomas -- negative for all hormonal markers including LH, FSH and αSU -- are in fact positive for SF-1 and therefore better classified as gonadotroph adenomas.
A gonadotroph pituitary adenoma so classified based solely on SF-1 positivity

Monday, November 5, 2018

The appendix is implicated in Parkinson’s disease

Clumps of alpha-synuclein (red) in the appendix of a healthy individual suggests the possibility
that the gut plays a role in the pathogenesis of Parkinson disease
The appendix may contribute to a person’s chances of developing Parkinson’s disease. An analysis of data from nearly 1.7 million Swedes found that those who’d had their appendix removed had a lower overall risk of Parkinson’s disease. Also, samples of appendix tissue from healthy individuals revealed protein clumps similar to those found in the brains of Parkinson’s patients, researchers report online October 31 in Science Translational Medicine.

Together, the findings suggest that the appendix may play a role in the early events of Parkinson’s disease, Viviane Labrie, a neuroscientist at the Van Andel Research Institute in Grand Rapids, Mich., said at a news conference on October 30.

Symptoms related to Parkinson’s can show up in the gut earlier than they do in the brain. So Labrie and her colleagues turned their attention to the appendix. Often considered a “useless organ,” Labrie said, “the appendix is actually an immune tissue that’s responsible for sampling and monitoring pathogens.”

In the new study, Labrie’s team analyzed health records from a national registry of Swedish people, some of whom were followed for as many as 52 years. That long observation time was key: People have their appendix removed most often in their teens or 20s but, on average, don’t develop Parkinson’s disease until their 60s. More than half a million people in the registry had had an appendectomy, while a total of 2,252 people out of the 1.7 million developed Parkinson’s. Removing the appendix was associated with a 19 percent drop in the risk of developing Parkinson’s disease, the team reports.

Surgical samples from a tissue bank of appendixes from 48 people without Parkinson’s provided another link to the disease. The team discovered alpha-synuclein clumps in 46 of the samples — from both old and young patients — similar to those seen in the brains of Parkinson’s patients.

If the clumped protein in the appendix turns out to jump-start the disease, Labrie said, “preventing excessive alpha-synuclein clump formation in the appendix, and its departure from the gastrointestinal tract, could be a useful new form of therapy.”

Ongoing clinical trials are investigating different strategies to remove alpha-synuclein from the brain. If a new therapy could clear the protein from the brain, says UPenn neuropathologist John Trojanowski, perhaps it would do the same for the appendix.

B. Killinger et alThe vermiform appendix impacts the risk of developing Parkinson’s diseaseScience Translational Medicine. Published online October 31, 2018. doi:10.1126/scitranslmed.aar5280.

Friday, November 2, 2018

AANP announces Special Course topic for 2019 meeting

The Special Course topic is: Unintended Consequences: The Iatrogenic Neuropathology of Systemic Therapies.

Register for the meeting here.

Thursday, November 1, 2018

Best Post of October 2018: Young adult with an iridic mass extending into the ciliary body

The next in our "Best of the Month" series comes from October 9, 2018:

Melanoma markers were negative. Smooth muscle markers were positive. This case was determined to be an epithelioid leiomyoma. I didn't do electron microscopy to look for mitochondia, but it may well be what Ursula Schlotzer-Schredhardt et al. have called a mitochondria-rich epithelioid leiomyoma (Arch Ophthalmol, Vol 120, January 2002).

Thursday, October 25, 2018

Nowinski rebuts book which questions football's role in chronic traumatic encephalopathy

On Tuesday, I posted about a new book out which questions the conclusions drawn by Boston University researchers regarding the connections between football and chronic traumatic encephalopathy (CTE). Today, BU's Chris Nowinski responded in the pages of USA Today.

Chris Nowinski, PhD, CEO of the Concussion Legacy Foundation which has connections to Boston University researchers, said the following in the USA Today article: "I'm happy to ask Merril Hoge who to draft No. 1 next year, but we shouldn't be asking him how to design research studies."

Chris Nowinski, PhD

Tuesday, October 23, 2018

Neuropathologist teams up with former NFL player to write provocative book questioning the extent and cause of CTE among football players

Dr. Peter Cummings
In an Op-Ed piece published today on Yahoo! Sports, neuropathologist Peter Cummings and former NFL player Merril Hoge discuss their skepticism about the science behind the connection between chronic traumatic encephalopathy (CTE) and football. 

Cummings and Hoge just released a book entitled “Brainwashed: The Bad Science Behind CTE and the Plot to Destroy Football” (Amplify, Oct. 23, 2018), describing their take on the conclusions that have been drawn regarding the connection between football and CTE. "We believe that when people know what we know, they’ll start asking tougher, smarter questions, and the 'football causes CTE' connection will be revealed as the pseudoscience that it is," the authors write.

Merril Hoge
The authors later state: "The researchers, especially [Boston University], were all too willing to ride the wave of attention provided by the press without ever copping to the severe weaknesses in their work. As a result, the public is convinced that football causes CTE — and that anyone who says otherwise is a 'denier' — based on work that would not have passed muster in a graduate-level research design course."

We will be on the lookout for reaction to the provocative statements made by Cummings and Hoge. Stay tuned...

Sunday, October 14, 2018

The Ivy League reduces concussion rates in football by moving the kickoff ball just five yards toward opposing team's goalpost

Following an experimental 2016 change to kickoff rules designed to encourage more touchbacks,  Ivy League schools saw reduced rates of concussions on the football field.

A recent study in which Brown University and the seven other Ivy League institutions participated showed that reducing kickoff returns in which players actively try to advance the ball during football games could lessen the number of concussions players suffer on the field.
Results from the study, published this month in the Journal of the American Medical Association, show a sharp decrease in the rate of concussions following the Ivy League’s decision in 2016 to adopt an experimental kickoff rule in league play. Between 2013 and 2015, data show, about 11 concussions occurred for every 1,000 kickoffs. In 2016 and 2017, after the league shifted the kickoff position and the touchback line, the rate of concussions during kickoffs decreased to about 2 in 1,000.
Though the JAMA study published on Oct. 1, its preliminary data prompted the National Collegiate Athletic Association to adopt a kickoff rule change — distinct from the Ivy League’s rule, but with the same intent — for all levels of football for 2016. The study comes months after new National Football League data were released showing that the concussion rates had reached an all-time high in the 2017 season, prompting continued focus on the physical and cognitive effects of head injuries in football.
“Concussions in football are a nationwide concern,” said Phil Estes, Brown’s head football coach. “Players are bigger, faster and stronger than ever before, and that creates more collisions. We in the Ivy League recognize that the sport must adapt to reflect these changes, and we are proud to take part in research that will help make football safer.”
A team of researchers at the University of Pennsylvania, Princeton University and the Ivy League authored the JAMA study. Their data demonstrate that kickoffs are a logical place to start in the quest to reduce the rate of concussions: while kickoffs comprised less than 6 percent of plays in Ivy League games between 2013 and 2015, nearly a quarter of all concussions came during those plays. Kickoff returns, in which one team catches the other’s kick and runs up the field toward the end zone, can leave players more vulnerable to injuries largely due to their running speed upon impact, explained Matt Culp, Brown’s head athletic trainer.
“The kicking team is spread out across the field and running fast, gathering lots of speed as they head toward the receiving team,” Culp said. “In contrast, during regular line-of-scrimmage play, players tend to stay in a more compact formation and may only run 10 to 15 yards down the field.”
Talk of reducing kickoff-related concussions in Ivy League play began earlier in the decade, when a committee of coaches, medical professionals, university administrators and others reviewed nationwide concussion data and research. The investigation not only led Ivy League schools to increase the use of padding and decrease player-on-player contact during football practices, but also to more formal research on the rate of concussion.
A recent game between Brown and Harvard
When that research revealed the high rate of kickoff-return concussions, the Ivy League responded by implementing a new set of experimental rules for intraleague play. Starting in 2016, the league determined, teams would kick off from the 40-yard line rather than the 35-yard line — increasing the kicking team’s chances of landing the ball in the end zone, where returning teams often opt to kneel for a “touchback.” The league also moved the touchback line to the 25-yard line rather than the 20-yard line, providing the receiving team with more incentive to simply catch the ball and kneel rather than run the ball up the field.
Data from the JAMA study show that after 2016, about 48 percent of kickoffs resulted in touchbacks — a stark contrast to the pre-2016 touchback rate of just 17.9 percent.
Culp is glad to see that the new rules have decreased the rate of active kickoff returns and helped to curb concussions, which can be one of the most difficult football injuries to identify and treat. On the field, Culp and his colleagues use the SCAT5 test to determine whether a player has suffered a concussion. The test involves a 22-symptom checklist, a demonstration of balance, a neurological screen and a series of memory-related questions.

Friday, October 12, 2018

True rosette situated within an Embryonal Tumor with Multilayered Rosettes, C19MC-altered, WHO grade IV

This aggressive tumor was located in the frontoparietal lobe of a young child. It had alterations in the C19MC locus at 19q13.42.

Tuesday, October 9, 2018

Young adult with an iridic mass extending into the ciliary body

Melanoma markers were negative. Smooth muscle markers were positive. This case was determined to be an epithelioid leiomyoma. I didn't do electron microscopy to look for mitochondia, but it may well be what Ursula Schlotzer-Schredhardt et al. have called a mitochondria-rich epithelioid leiomyoma (Arch Ophthalmol, Vol 120, January 2002).

Monday, October 8, 2018

Best Post of September 2018: A Case of Posterior Cortical Atrophy

The next in our "Best of the Month" series is from September 7, 2018:

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that is characterised by progressive decline in visuospatial, visuoperceptual, literacy, and praxic skills. The progressive neurodegeneration affecting parietal, occipital, and occipitotemporal cortices that underlies PCA is attributable to Alzheimer's disease in most patients. However, alternative underlying causes, including dementia with Lewy bodies, corticobasal degeneration, and prion disease, have also been identified, and not all patients with PCA have atrophy on clinical imaging. (Crutch, S. J., Lehmann, M., Schott, J. M., Rabinovici, G. D., Rossor, M. N., & Fox, N. C. (2012). Posterior cortical atrophyLancet Neurology11(2), 170-178)

This is a case of a 60-year-old female with PCA:

Although there is diffuse neocortical atrophy, note the prominent occipital lobe atrophy

Tau stain of temporal lobe section highlights Alzheimer pathology

Pallor of the substantia nigra was noted, and Lewy bodies noted microscopically (see inset)

Alpha-synuclein staining showed neocortical Lewy bodies (here in the frontal lobe)

The final diagnosis was Alzheimer disease and Diffuse Neocortical Lewy Body Disease in the setting of Posterior Cortical Atrophy.

Neuropathology Blog is Signing Off

Neuropathology Blog has run its course. It's been a fantastic experience authoring this blog over many years. The blog has been a source...