Friday, July 20, 2018

A ganglion of neuropathologists spontaneously coalesces at a this week's Association of Pathology Chairs meeting

Neuropathologists serve many roles aside from signing out surgical specimens and performing brain autopsies. That fact was in full display at this week's Association of Pathology Chairs meeting where, at a reception on Monday, a group of neuropathologists found themselves standing together at an afternoon reception. (Perhaps this coalescence was not so much by chance as it occurred directly adjacent to the bar.) It was nice to see old friends.

Left to right: Drs. Douglas Miller, Kymberly Gyure, Jennifer Baccon, Eyas Hattab, and Brian Moore

Monday, July 16, 2018

What is the nodulus?

The lobule of the cerebellar vermis that, together with the flocculus of each hemisphere, forms the flocculonodular lobe.




Friday, July 13, 2018

Hyperbrain: a great resource for learning neuroanatomy

HyperBrain is an online tutorial for human neuroanatomy from the University of Utah.  HyperBrain includes thousand of images and hundreds of linked illustrated glossary terms, as well as movies, quizzes and interactive animations.

Thursday, July 12, 2018

Best Post of May 2018: Moving beyond histologic grading of IDH-wildtype diffuse astrocytic gliomas

The next in our "Best of the Month" series comes from May, 30, 2018:

Despite the fact that the most recent update of the World Health Organization (WHO) classification of central nervous system tumors was published only two years ago, the data is already showing that we are moving beyond that classification system when if comes to IDH-wildtype diffuse astrocytomas. The concept of an "integrated diagnosis" in the setting of IDH-wildtype histologic grade II and III tumors has already been eclipsed in the literature by the primacy of the genetic signature over histologic appearance in predicting outcome. In the near future, diffuse IDH-wildtype astrocytic gliomas with (1) combined whole chromosome gain of 7 and loss of 10, and/or (2) EGFR amplification will be designated as equivalent to WHO grade IV gliomas. Histologic grades for such tumors will be stricken from the top diagnostic line so as to avoid unfounded reassurance that these tumors will behave in any way other than very aggressively.

Friday, July 6, 2018

Malignant astroblastoma in a 23-year-old female


Headaches prompted imaging which showed a large right parieto-occipital tumor. Astroblastic pseudorossettes are prominent, with cells that are fairly monotonous. GFAP was only focally positive, not unusual for this diagnosis. Mitotic rate ranged up to 8 per 10 HPF, with a MIB1 cell cycling index reaching 40%.

Thursday, July 5, 2018

More on Rosenthal

Thanks to Dr. Gregg B. Wells from Texas A&M University for directing me to an article authored by Dr. Hans Goebel of Charite-Universit√§tsmedizin in Berlin regarding the life and accomplishments of neuropathologist Werner Rosenthal (1870-1942). Dr. Wells was prompted to write to me by my recent post entitled "Who was Rosenthal?". For those who are interested in Dr. Rosethal's travails as a Jew in Nazi Germany forced into exile in India, I encourage you to read Dr. Goebel's open-access article.

Dr. Werner Rosenthal with his wife and daughter in 1917.
(Taken from Dr. Goebel's article in Clinical Neuropathology)

Monday, June 25, 2018

Embryonal tumor with multilayered rosettes, C19MC-altered


Embryonal tumor with multlayered rosettes, C19MC-altered, is a WHO grade IV tumor with alterations -- including amplifications and fusions -- in the C19MC locus at 19q13.42.

Friday, June 22, 2018

Who was Rosenthal?

A Rosenthal fiber in pilocytic astrocytoma

"In 1898, the German pathologist Werner Rosenthal noted elongated inclusions within the gliotic edge of a syringeal cavity of an ependymoma. Assigned to write the case report by a senior mentor while serving as a “first assistant” at the University of Erlangen, Rosenthal colorfully described these inclusions as a “glossy formation of little bulbs or wavy sausages with one thick and one pointed end.”….  His supposition that they were related to glial fibers would prove surprisingly insightful. Not until some 20 years later did Bielschowsky and Unger use the term 'Rosenthal fibers' when describing structures in the gliotic capsule of a cystic teratoid tumor."

Quoted from:  F.J. Wippold, A. Perry and J. Lennerz. Neuropathology for the Neuroradiologist: Rosenthal Fibers. American Journal of Neuroradiology May 2006, 27 (5) 958-961.

Thursday, June 21, 2018

Pennies-on-a-plate cell in a pilocytic astrocytoma

Multinucleated astrocytes with peripherally situated nuclei like this one in a pilocytic astrocytoma
are referred to as having a "pennies-on-a-plate" configuration
This is a common "degenerative" change seen in long-standing pilocytic astrocytomas. I'm not sure from where this "pennies-on-a-plate" designation derives, but please leave a comment if you know.

Tuesday, June 19, 2018

Guest Post - Wanted: Your Opinion on Artificial Intelligence in Pathology

Today features a guest post from Dr. Phedias Diamandis of the University of Toronto:

Phedias Diamandis, MD, PhD
There is a growing body of evidence highlighting the utility of Artificial Intelligence (AI) in pathology. AI is a type of mathematical algorithm that allows computers to carry out human-like tasks considered “intelligent”, such as recognizing diagnostic histologic patterns or counting mitotic figures on digital H&E slides.  This has the potential to radically transform the clinical practice of pathologists. This anonymous survey was developed to understand the familiarity, enthusiasm, and concerns pathologists may have regarding this technology in their practice. Some anonymous demographic information is also requested to understand the relationship of these variables (e.g. specific age groups, practice types and speciality) to the responses of the variables. It is expected that findings of this study will help guide researchers to design AI workflows that meet the specific needs of the study participants.

This survey will take roughly 10-15 minutes to complete. It is anonymous and the investigators of the study have no conflicts of interest.

The survey can be accessed at the following link: https://www.surveymonkey.com/r/AIinpathology

Thank you for your participation! Please circulate to your colleagues. Everyone's opinion counts!

Automated lesion detection and classification in pathology: Upper Panels: A form of artificial intelligence known as deep convolutional neural networks (CNNs) is currently showing impressive results at pattern recognition tasks traditionally carried out by highly skilled humans. In this example, a full digital slide image is analyzed to highlight brain regions infiltrated by this oligodendroglioma. The IDH1-R132H immunostains (right upper panel) highlights where the tumor actually is for comparison. Lower panels: High power view of the same tumor showing it's infiltrative nature. The CNN clearly detects the infiltrative nature of this lesion. The right most panel shows the computer output of another metastatic lesion with a much more circumscribed border. In addition to identifying the lesions, CNNs are beginning to show promise at classifying tumors with different clinical outcomes.  

Monday, June 18, 2018

International Society of Neuropathology set to meet in Tokyo this fall

Keio Plaza Hotel in Tokyo
The 19th International Congress of Neuropathology will take place in Tokyo on September 23-27, 2018. The Congress meets every four years. The upcoming meeting will be hosted by the Japanese Society of Neuropathology with the theme ‘a gateway to modern neuroscience’.  The Congress will be held at the central Keio Plaza Hotel in Tokyo, The meeting will be held in conjunction with the Asian Congress of Neuropathology and the Japanese Societies of Neuropathology and Brain Tumour Pathology. The  programme and other details are now on the Congress website

Friday, June 15, 2018

More on the amazing word "physaliferous"

Since my post this past Wednesday about the etymology of the word "physaliferous" which designates the characteristic cells comprising chordomas, the illustrious Dr. Maria Martinez-Lage (neuropathologist at Massachusetts General Hospital), tweeted about another word which derives from the same Greek root. Here is Dr. Martinez-Lage's tweet:

Physaliferous cells resemble the fruit of the physalis plant, an edible berry that is round and surrounded by a delicate lacy husk. It goes by many names: Golden berry, cape gooseberry, edible Chinese lantern. Delicious!


Thursday, June 14, 2018

A Primer on Giant Cell (Temporal) Arteritis

Neuropathologists are often tasked with handling ophthalmic pathology at their institutions. As such, they are assigned all cases submitted by ophthalmologists -- including temporal artery biopsies for determination of the presence of active giant cell (temporal) arteritis. What follows is a quick reference on the important points to remember about giant cell arteritis. (If there are things I am forgetting, please add your comments.):

Arrow points to a giant cell in a temporal artery wall
(from Robbins Basic Pathology, 10th edition)
Refering to the condition as "temporal arteritis" is not entirely accurate as giant cell arteritis is a granulomatous inflammatory disorder that can affect a variety of large and small arteries in the head. In addition to the temporal artery, ophthalmic arteries can be affected (which is the reason ophthalmologists are often the clinicians performing biopsies in suspected cases). Additionally, vertebral arteries and even the aorta (giant cell aortitis) can be involved. Since ophthalmic arteritis can lead to sudden and irreversible blindness, affected patients must be promptly diagnosed and treated. A negative biopsy result does not entirely exclude the diagnosis as the distribution of inflammation is often patchy.

Because pathologic changes tend to be patchy, examination of several cross-sectional levels is required. Involved segments exhibit nodular intimal thickening (and occasional thromboses). Most lesions exhibit granulomatous inflammation within the inner media which disrupts the internal elastic lamina. A minority of cases do not show either granulomas or giant cells, instead exhibiting only a non-specific acute and chronic inflammatory infiltrate. Healing is characterized by intimal thickening, medial thinning, and adventitial fibrosis.

Reference: Kumar V, Abbas AK, and Aster JC (eds.) Robbins Basic Pathology, Chapter 10 "Blood Vessels", 10th Edition (2018) pp. 384-5.

Wednesday, June 13, 2018

Etymology of the word "physaliferous"

The characteristic cells seen in chordoma, physaliferous cells (which, according to the Oxford English Dictionary, can alternatively be spelled 'physaliphorous') is from the Greek physallis (meaning 'bubble') and phoros (meaning 'bearing').


The "bubble-bearing" physaliferous cells of a chordoma

Tuesday, June 12, 2018

A primary central nervous system lymphoma overwhelmed by necrosis and neutrophil infiltration

This PCNSL (later proved to be EBV-driven) biopsied from the right parietal lobe is hardly discernible among the necrotic debris and neutrophilic infiltration

Tumor cells (outlined) within and surrounding a vessel wall

Wednesday, May 30, 2018

Moving beyond histologic grading of IDH-wildtype diffuse astrocytic gliomas

Despite the fact that the most recent update of the World Health Organization (WHO) classification of central nervous system tumors was published only two years ago, the data is already showing that we are moving beyond that classification system when if comes to IDH-wildtype diffuse astrocytomas. The concept of an "integrated diagnosis" in the setting of IDH-wildtype histologic grade II and III tumors has already been eclipsed in the literature by the primacy of the genetic signature over histologic appearance in predicting outcome. In the near future, diffuse IDH-wildtype astrocytic gliomas with (1) combined whole chromosome gain of 7 and loss of 10, and/or (2) EGFR amplification will be designated as equivalent to WHO grade IV gliomas. Histologic grades for such tumors will be stricken from the top diagnostic line so as to avoid unfounded reassurance that these tumors will behave in any way other than very aggressively.

Friday, May 25, 2018

Dr. Dan Brat interviewed on Northwestern Feinberg School of Medicine Podcast

In the latest episode of the Northwestern Medicine Breakthroughs podcast, Daniel Brat, MD, PhD discusses the emerging integrated molecular-histomorphological classification of diffuse gliomas. In an episode entitled "A New Way to Diagnose Brain Tumors", Dr. Brat -- the new chairman of the Northwestern Pathology -- states that "whenever you go through a reclassification that dramatic, there's going to be gaps in knowledge and gaps in practice and we are recognizing those gaps on a
Dr. Dan Brat
daily basis, on a yearly basis.  And we as a brain tumor community internationally are working to fill those gaps in knowledge. So what we found for example, is that once you classify molecular diseases, the grading criteria that we used in the past to grade things as [World Health Organization] grade one, grade two, grade three, grade four, which really served to predict how patients are going to fair and what type of therapies they are going to need, all of those grading criteria needed to be recalibrated. And that's a significant undertaking as well. And we have certain initiatives within the international community through an organization called cIMPACT-Now [
Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy – Not Official WHO]. And we as a group, including some colleagues here at Northwestern Feinberg School of Medicine, are writing the guidelines for new grading criteria for the diffuse gliomas within the molecular era." . The podcast aired on May 15 and is available on iTunes and SoundClound.

Thursday, May 24, 2018

Best Post of April 2018: Exuberant endothelial reactive hyperplasia next to a subacute infarct biopsied to rule out neoplasia

The next is on "Best of the Month" series is from Tuesday, April 3, 2018:


Endothelial hyperplasia next to an infarct, not to be confused with microvascular proliferation in a glioma

Tuesday, May 22, 2018

The "specific glioneuronal element" of dysembryoplastic neuroepithelial tumor

A "floating neuron" is circled in this "specific glioneuronal element" of a DNT
A pathognomonic feature of dysembrioplastic neuroepithelial tumors (DNTs) is the "specific glioneuronal element" which consists of oligodendroglial-like cells lined up on either side of a paucicellular and mucinous region in which lone neurons appear to float.

Thursday, May 17, 2018

Astroblastoma


This is a rare, as yet ungraded, cerebral tumor of childhood. It is composed of cells that are GFAP positive and have broad, non-tapering processes radiating toward central blood vessels (astroblastic pseudorosettes). The border with adjacent brain is pushing, not infiltrative. Hyalinized vessels (as seen below) are a hallmark of astroblastoma. No ependymal features have been identified in studies of this unusual entity.

Wednesday, May 16, 2018

Age of First Football Tackles Tied to Neurobehavioral Symptom Onset

Younger age of exposure to tackle football predicts earlier neurobehavioral symptom onset among players with chronic traumatic encephalopathy (CTE), according to a study recently published online in the Annals of Neurology.
Michael L. Alosco, Ph.D., from Boston University, and colleagues examined the brains of 246 tackle football players donated for neuropathological examination. Of the 211 who were diagnosed with CTE, 126 were without comorbid neurodegenerative diseases. Age of first exposure and age of cognitive and behavioral/mood symptom onset were determined through informant interviews.

Monday, May 14, 2018

Understanding Neurophobia Among Medical and Other Health Care Students

Andre Toulouse, PhD, (University College,
Cork, Ireland) lead author on
article about neurophobia
Neurophobia, a trepidation among students in health-related fields when it comes to neuroanatomy, is a real thing and has been studied by several researchers in medical education. A recent paper by an Irish group appearing in Anatomical Sciences Education, entitled "Understanding neurophobia: reasons behind impaired understanding and learning of neuroanatomy in cross-disciplinary healthcare students", examines this phenomenon further. The authors write: "Neuroanatomy is perceived as a more difficult subject compared to other anatomy topics (e.g., reproductive/pelvic anatomy)...[U]nderstanding of neuroanatomy could be enhanced and neurophobia decreased by purposefully designed computer aided learning resources. This data could help curricular designers to refocus attention and guide educators to develop improved neuroanatomy web resources in future." Interestingly, when students were surveyed about what they would find most helpful in online neuroanatomy learning, blog posts were perceived as likely to be least helpful, while photographs of brain prosections and computer animations were perceived to be the most helpful.

Reference: Javaid MA, Chakraborty S, Cryan JF, Schellekens H, Toulouse A. Understanding neurophobia: reasons behind impaired understanding and learning of neuroanatomy in cross-disciplinary healthcare students. Anat Sci Educ 11:81-93 (2018).

Thursday, May 10, 2018

Best Post of March 2018 - Featured Neuropathologist: Michael Punsoni, MD

The next in our "Best of the Month" series is from March 12, 2018

On occasion, we profile a prominent or rising neuropathologist. In the past, we've featured the likes of Craig HorbinskiRoger McLendonJan Leestma, and Karra Jones. Today we feature Michael Punsoni, MD, a 2016 graduate of the Brown University Neuropathology Fellowship Program and now on faculty at the University of Nebraska in Omaha. Dr. Punsoni agreed to engage in a little Q&A:



1. Why did you decide to become a neuropathologist?
I have always had a strong interest in science and medicine, particularly the neurosciences. After college I worked in two research labs, which fueled my interest in basic neuroscience but also drove me to pursue a medical degree. During my clinical years of medical school I had a strong interest in neurology but my eagerness to be involved in all facets of medical care led me to apply for a categorical residency in Internal Medicine. While I am grateful for the skills and knowledge I acquired during my medicine internship I came to the realization (on one of my 36-hour calls if I remember correctly) that clinical medicine was not for me. I went back to the specialty drawing board and ultimately found pathology somewhat by chance. One of my patients on the medical floor needed an aspiration biopsy of a neck mass. I met the cytopathologist and watched closely as she aspirated a small amount of material and looked on in awe at the squamous cell carcinoma cells on her bedside dual-head scope. I fell for pathology hard after that and, while re-applying to the match, I went back to what I knew best, another year of neuroscience research. By the time I was in pathology residency, my interest for neuropathology was cemented and there was no going back.


2. What do you like to do outside of work?
Watching old and new movies and finding great hole-in-the-wall type restaurants. I’m always looking for/open to suggestions for either one.


3.
 Name a couple of important professional mentors. Why were they important to you?
My two PIs at Cornell Medical Center, Joe Pierce and Theresa Milner for the brilliant work they let me participate in, for teaching me to be meticulous in all things particularly bench techniques and for their good humor that stays with me today. To all four neuropathologists at Brown University who shaped the neuropathologist I would become and still hope to be one day. Dr. Suzanne de la Monte to whom I am grateful for her relentless push to make me a good presenter and for sharing her invaluable tips on manuscript writing. Dr. Douglas Anthony whose leadership skills and commitment to the scientific method were inspiring then and now. Dr. Ed Stopa who treats all his fellows like family and never stops guiding them. Dr. John Donahue who taught me that a remarkable memory is only part of what makes a good pathologist and also, that “it’s a tough job but someone’s got to do it!”.


4.
 What advice would you give to a pathology resident interested in doing a neuropathology fellowship?
Do an elective at your home institution and/or elsewhere. Try it out. It’s a fascinating field and will be for years to come. As I once heard one of my mentors say, we have our own language (when describing the structures of the brain) and we like it that way. Join the group, we’d love to have you.


5. What city (other than Omaha, of course) would you like a future American Association of Neuropathologists meeting to be held and why? 
Honolulu. I’ve never been and this would be a great reason to go. Another desirable place would be Boston, which has great restaurants and a good transit system.

Monday, May 7, 2018

The American Association of Neuropathologists Awarded R13 Conference Grant by National Institute on Aging

The American Association of Neuropathologists (AANP) today announced that it has been awarded an R13 Support for Conferences and Scientific Meetings grant through the National Institute on Aging of the National Institutes of Health. This grant will support the 94th Annual Meeting of the AANP in Louisville, KY.

Dr. Edward Lee
“We are extremely pleased to be recipients of an R13 grant to support dissemination of the critical work completed by our members and featured by our annual meeting,” said Assistant Secretary Treasurer/Chair of the Education Committee, Edward Lee, MD, PhD. “The National Plan to Address Alzheimer’s Disease calls for the prevention and treatment of Alzheimer’s disease and related dementias (ADRD) by 2025. Critical to this goal is the role of neuropathologists in describing the neuropathology associated with ADRD and aging. To this end, the annual AANP meeting provides the most direct means to disseminate the latest developments in ADRD and aging-related neuropathologies.”

The purpose of the R13 grant through the NIA is to support the ADRD and aging components of conferences and scientific meetings, to better disseminate latest developments related to pathologic heterogeneity in dementia and aging. Specific to the AANP, this grant aims to enhance the education of neuropathology trainees about ADRD and aging to attract the next-generation of ADRD neuropathologists. Notably, this grant markedly expands the support available for trainees to attend the annual meeting such that 30 trainees will receive trainee travel awards this year.

This year’s 94th Annual Meeting will kick-off on Thursday, June 7 with the first half of the Special Course: Neuropathology of Aging featuring the following speakers: Elizabeth Mormino, PhD, Stanford University; John Crary, MD, PhD, Icahn School of Medicine at Mount Sinai; Peter Nelson, MD, PhD, University of Kentucky; and Julie Schneider, MD, MS, Rush University Medical Center. The DeArmond Lecture: Dysregulated Metabolism in the Pathogenesis of Alzheimer’s Disease: Type 3 Diabetes will take place on Friday featuring Suzanne de la Monte, MD, MPH, of the Warren Alpert Medical School of Brown University. In addition, multiple platform sessions throughout the meeting will focus on aging and neurodegenerative diseases including sessions on
Alzheimer’s disease, chronic traumatic encephalopathy, frontotemporal lobar degeneration, Lewy body disease and prion disease. Lastly, this year will also include the first-ever Award for Best Neurodegenerative Disease Case Presented at the 2018 Diagnostic Slide Session.

“We are thrilled to be R13 grant recipients,” said current AANP President Elizabeth Cochran, MD. “Thank you to everyone who dedicated time and focus in developing our proposal, and thank you to the National Institute on Aging for their support.”

Friday, May 4, 2018

Dr. R. Ross Reichard and Dr. Daniel J. Brat will be giving the What Every Neuropathologist Needs to Know lectures at upcoming annual AANP meeting

The 94th Annual Meeting of the American Association of Neuropathologists will take place June 7-10 in Louisville, Kentucky. On June 9th, Dr. R. Ross Reichard and Dr. Daniel J. Brat who will be giving the What Every Neuropathologist Needs to Know lectures. Dr. Reichard will discuss ways a neuropathologist may be involved in legal proceedings. Dr. Brat will talk about the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy - Not Official WHO (cIMPACT-NOW), an initiative to address grading challenges in CNS tumors given new findings regarding the impact of molecular signatures on prognosis.

Wednesday, May 2, 2018

Pilomyxoid astrocytoma

Angiocentricity, a hallmark of pilomyxoid astroctyoma, is demonstrated here
Although thought to be related to pilocytic astrocytoma, full characterization of pilomyxoid astrocytoma has yet to yield a definitive WHO grade for these tumors (although the prior edition of the WHO book pegged this tumor as grade II). Pilomyxoid astrocytomas differ from pilocytic astrocytomas in that they tend not to be biphasic or harbor Rosenthal fibers.

Monday, April 30, 2018

Best Post of February 2018: Tau accumulations in the brains of woodpeckers

The next in our "Best of the Month" series comes from February 21, 2018


Dr. Peter Cummings makes another appearance on the blog, this time as senior author on a paper entitled: Tau Accumulations in the Brains of Woodpeckers. Eight of ten woodpeckers examined showed cerebral tau accumulations, whereas no control brains (red-winged blackbirds) were positive.This is significant in that there has been some research interest in developing football helmets based on the protective design that has evolved to protect the brains of woodpeckers.But maybe the relatively short life of the woodpecker (average less than 10 years) precludes the need for this protective adaptation. Thanks to Dr. Mark Cohen for alerting me to this study.

Thursday, April 26, 2018

Ann McKee named to Time Magazine's Annual List of the 100 Most Influential People in the World

Ann McKee, MD
Dr. Ann McKee joins Rihanna, Donald Trump, and Oprah Winfrey on the list of Time Magazines's annual list of the 100 most influential people in the world for 2018. The full list appears in the April 30 issue of Time Magazine. McKee is the chief of neuropathology at the VA Boston Healthcare System and director of the Boston University Chronic Traumatic Encephalopathy (CTE) Center.

McKee's research focuses on the long-term effects of concussion, subconcussion and blast injury in contact sports athletes and military veterans, including CTE. Her work has shifted the prevailing paradigm of scientific thought regarding head trauma; she has demonstrated that "mild" head trauma, particularly repetitive mild head trauma, is not just an acute injury - it can provoke a persistent and progressive neurodegeneration that continues long after the traumatic exposure. McKee has published more than 70 percent of the world's cases of CTE ever reported and created the Veterans Affairs - Boston University - Concussion Legacy Foundation (VA-BU-CLF) brain bank, the world's largest repository of brains from individuals exposed to traumatic brain injuries (more than 550) and neuropathologically confirmed CTE (more than 320).

Tuesday, April 24, 2018

Monday, April 16, 2018

Anaplastic Gangliocytoma in the frontal lobe of a 35-year-old female

This is the latest in several resections and follows two rounds of chemotherapy. Immunomarkers positive for neurofilament, and negative for S100, GFAP, synaptophysin, chromogranin, NeuN, HMB45, and MelanA.

Anaplastic Gangliocytoma (note the necrosis in the lower right corner)

Thursday, April 12, 2018

Colloid cyst of the third ventricle

Modified by compressive atrophy, the cyst lining cells would otherwise be columnar with obvious cilia

A different area of the same cyst which more clearly demonstrates cilia

Wednesday, April 11, 2018

There is a neuropathology museum in Lima, Peru

The Institute of Neurological Science (INCN) in Lima  houses the only "Brain Museum" in Latin America. The  collection contains over 3000 samples from which around 300 are on permanent display, including brains with diverse cerebral diseases and anomalies as well as fetal brains with abnormalities.  Unique photomicrographs and other items are also on display.

Monday, April 9, 2018

Wednesday, March 21, 2018

Best Post of January 2018: Choroidal ganglioneuronal hamartoma in an NF1 patient

The next in our "Best of the Month" series is from January 30, 2018:

Thanks to Dr. Ahmed Gilani (pediatric pathology fellow at the University of Colorado) for providing me with slides of an enucleation specimen from a patient with Von Recklinghausen Neurofibromatosis (NF-1). The specimen exhibits a region of choroidal expansion with hamartomatous neuroglial tissue. Distributed throughout this choroidal expansion are non-pigmented ovoid bodies, which have a delicately laminated appearance reflecting the presence of concentric Schwann cell processes. One might conceive of these choroidal expansions as cousins of iridic Lisch nodules.

Choroidal expansion in an enucleation specimen from a child with NF1

Ganglion-like cells within the choroidal expansion

Ovoid body within choroidal expansion

Monday, March 19, 2018

Epigenomics to Enhance Tumor Classification

The Neuropathology Department at Heidelberg University Hospital led by Professor Andreas von Deimling, have developed a new computer-based method. “We hope that our new molecular classification method will help improve diagnostic accuracy in CNS tumors and, thus, also improve the chances for successful treatment,” said von Deimling.

The researchers analyzed specific DNA methylations. Different cell types exhibit characteristic patterns of DNA methylation which enable scientists to draw conclusions about a tumor’s cellular origin. "We have developed computer-based algorithms that reliably differentiate 82 types of CNS tumors based on their methylation patterns," said Professor David Capper, who is one of the four first authors of the study. “Particularly in tumors which we cannot easily assign to a diagnostic category based solely on microscopic examination, methylation analysis is often helpful to make a precise diagnosis. The analysis of approximately 2,800 reference tumor samples additionally made it possible to classify tumors into specific subgroups that are not yet included in the classifications that have been used so far.”

In order to test whether the method is suitable for use in clinical routine diagnostics, the scientists analyzed more than 1,100 additional tumor samples. In about twelve percent of the cases, they were able to correct the initial diagnosis using the methylation patterns. In almost all cases where it was possible, further molecular-diagnostic examinations showed that molecular classification characterized the tumors even better than the initial microscopic diagnosis. 

“We are convinced that our new method is well suited to be used in the clinic,” said Stefan Pfister, one of the paper's authors. He added: “We have made our classification system available online in order to enable researchers to analyze their data at our platform.”

Reference: Capper, D., Jones, D. T. W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D., … Pfister, S. M. (2018). DNA methylation-based classification of central nervous system tumours. Nature. https://doi.org/10.1038/nature26000

Wednesday, March 14, 2018

On Einstein's Birthday, We Take a Second Look at His Brain

On this date 139 years ago, Albert Einstein was born in Ulm, Germany. We take this occasion to republish a post from November 21, 2012 entitled: Photos reveal unique features of Einstein's cerebral cortex:

Photographs taken shortly after his death, but never before analysed in detail, have now revealed that Einstein’s brain had several unusual features, providing clues about the neural basis of his extraordinary mental abilities.



Nature.com reports that, while doing Einstein's autopsy, the pathologist Thomas Harvey removed the physicist's brain and preserved it in formalin. He then took dozens of black and white photographs of it before it was cut up into 240 blocks. Now, anthropologist Dean Falk of Florida State University in Tallahassee and her colleagues have obtained 12 of Harvey’s original photographs from the National Museum of Health and Medicine in Silver Spring, Maryland, analysed them and compared the patterns of convoluted ridges and furrows with those of 85 brains described in other studies.Many of the photographs were taken from unusual angles, and show structures that were not visible in photographs that have been analysed previously. The analysis was recently published today in the journal Brain. The most striking observation, says Falk, was “the complexity and pattern of convolutions on certain parts of Einstein's cerebral cortex”, especially in the prefrontal cortex, and also parietal lobes and visual cortex.

The autopsy revealed that Einstein’s brain was smaller than average and subsequent analyses showed all the changes that normally occur with ageing. Nothing more was analysed, however. Harvey stored the brain fragments in a formalin-filled jar in a cider box kept under a beer cooler in his office. Decades later, several researchers asked Harvey for some samples, and noticed some unusual features when analysing them.
A study done in 1985 showed that two parts of his brain contained an unusually large number of non-neuronal cells called glia for every neuron2. And one published more than a decade later showed that the parietal lobe lacks a furrow and a structure called the operculum3. The missing furrow may have enhanced the connections in this region, which is thought to be involved in visuo-spatial functions and mathematical skills.
AFP/Getty Images
Einstein was a keen violinist, which may account for an overdeveloped section of his brain that deals with the left hand.
The prefrontal cortex is important for the kind of abstract thinking that Einstein would have needed for his famous thought experiments on the nature of space and time, such as imagining riding alongside a beam of light. The unusually complex pattern of convolutions there probably gave the region and unusually large surface area, which may have contributed to his remarkable abilities.
Falk and her colleagues also noticed an unusual feature in the right somatosensory cortex, which receives sensory information from the body. In this part of Einstein’s brain, the region corresponding to the left hand is expanded, and the researchers suggest that this may have contributed to his accomplished violin playing.
According to Sandra Witelson, a behavioural neuroscientist at McMaster University in Hamilton, Canada, who discovered that the parietal operculum is missing from Einstein’s brain, the study’s biggest contribution may be in encouraging further studies. “It makes clear the location and accessibility of photographs and slides of Einstein's brain,” she says. “This may serve as an incentive for other investigations of Einstein's brain, and ultimately of any consequences of its anatomical variations.”

Monday, March 12, 2018

Featured Neuropathologist: Michael Punsoni, MD

On occasion, we profile a prominent or rising neuropathologist. In the past, we've featured the likes of Craig HorbinskiRoger McLendon, Jan Leestma, and Karra Jones. Today we feature Michael Punsoni, MD, a 2016 graduate of the Brown University Neuropathology Fellowship Program and now on faculty at the University of Nebraska in Omaha. Dr. Punsoni agreed to engage in a little Q&A:



1. Why did you decide to become a neuropathologist?
I have always had a strong interest in science and medicine, particularly the neurosciences. After college I worked in two research labs, which fueled my interest in basic neuroscience but also drove me to pursue a medical degree. During my clinical years of medical school I had a strong interest in neurology but my eagerness to be involved in all facets of medical care led me to apply for a categorical residency in Internal Medicine. While I am grateful for the skills and knowledge I acquired during my medicine internship I came to the realization (on one of my 36-hour calls if I remember correctly) that clinical medicine was not for me. I went back to the specialty drawing board and ultimately found pathology somewhat by chance. One of my patients on the medical floor needed an aspiration biopsy of a neck mass. I met the cytopathologist and watched closely as she aspirated a small amount of material and looked on in awe at the squamous cell carcinoma cells on her bedside dual-head scope. I fell for pathology hard after that and, while re-applying to the match, I went back to what I knew best, another year of neuroscience research. By the time I was in pathology residency, my interest for neuropathology was cemented and there was no going back.


2. What do you like to do outside of work?
Watching old and new movies and finding great hole-in-the-wall type restaurants. I’m always looking for/open to suggestions for either one.


3.
 Name a couple of important professional mentors. Why were they important to you?
My two PIs at Cornell Medical Center, Joe Pierce and Theresa Milner for the brilliant work they let me participate in, for teaching me to be meticulous in all things particularly bench techniques and for their good humor that stays with me today. To all four neuropathologists at Brown University who shaped the neuropathologist I would become and still hope to be one day. Dr. Suzanne de la Monte to whom I am grateful for her relentless push to make me a good presenter and for sharing her invaluable tips on manuscript writing. Dr. Douglas Anthony whose leadership skills and commitment to the scientific method were inspiring then and now. Dr. Ed Stopa who treats all his fellows like family and never stops guiding them. Dr. John Donahue who taught me that a remarkable memory is only part of what makes a good pathologist and also, that “it’s a tough job but someone’s got to do it!”.


4.
 What advice would you give to a pathology resident interested in doing a neuropathology fellowship?
Do an elective at your home institution and/or elsewhere. Try it out. It’s a fascinating field and will be for years to come. As I once heard one of my mentors say, we have our own language (when describing the structures of the brain) and we like it that way. Join the group, we’d love to have you.


5. What city (other than Omaha, of course) would you like a future American Association of Neuropathologists meeting to be held and why? 
Honolulu. I’ve never been and this would be a great reason to go. Another desirable place would be Boston, which has great restaurants and a good transit system.