Friday, December 2, 2016

Guest Post: Fibrous Bodies Nicely Demonstrated in a Smear from a Somatotroph Pituitary Adenoma

Christian Davidson, MD

Dr. Christian Davidson, director of neuropathology at the Robert Wood Johnson University Hospital in New Jersey, provides today's blog post:

A 30-year-old man presented with bitemporal hemianopsia and a 3.0 cm pituitary mass was discovered upon MRI. His IGF-1 was elevated to 900, but he had no signs of acromegaly. A smear of tissue sent for frozen section evaluation (see above below) revealed that most cells had round, eosinophilic, perinuclear inclusions suggestive of fibrous bodies (some examples are circled). Dot-like CAM5.2 immunostain (not shown) confirmed my smear-based diagnostic suspicion.

Thursday, December 1, 2016

Pineal Parenchymal Tumor of Intermediate Differentiation, WHO grade III

"A tumor of the pineal gland that is intermediate in malignancy between pineocytoma and pineoblastoma and is composed of diffuse sheets or large lobules of monomorphic round cells that appear more differentiated than those observed in pineoblastoma." -- WHO Book (2016)

The particular example depicted above recurred with leptomeningeal spread.

Tuesday, November 29, 2016

Vestige of a choroidal melanoma

Only melanin and melanophages remain in an enucleation specimen from a patient successfully treated with brachytherapy for choroidal melanoma. The eye was enucleated not because of the tumor, but because it was blind and intractably painful in the aftermath of treatment.

Monday, November 28, 2016

Best Post of October 2016: Brain Cancer Surpasses Leukemia as #1 Pediatric Cancer Killer

The next in our "Best of the Month" series comes from October 18, 2016:

The following post appeared on the Johns Hopkins Neuropathology Blog last month. The author is Andrew Black:

New data from the CDC shows the mortality rates for pediatric cancers is in decline. A study published by the CDC found that during 1999–2014, the cancer death rate for patients aged 1–19 years in the United States dropped 20%. What is also changing are the type of patients dying. In 1999, leukemia was the leading killer of childhood cancer. That has been replaced by brain cancer. Numerous other trends were also observed in the study.

In both 1999 and 2014, more than one ­half of all cancer deaths among children and adolescents 1­-19 years old were attributable to either leukemia or brain cancer. 3 out of 10 cancer deaths among children and adolescents aged 1–19 years in 1999 were due to leukemia (29.7%), and 1 in 4 were due to brain cancer (23.7%). By 2014, these percentages reversed and brain cancer was the most common site, accounting for 29.9% of total cancer deaths.

Wednesday, November 23, 2016

Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas

Ganesh Shankar of Brigham and Women's Hospital and colleagues recently published an article in Neuro-Oncology entitled Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. Rhabdoid meningiomas are designated in the World Health Organization Classification of Tumours as high grade, despite the fact that only a subset follow an aggressive clinical course. To define genomic aberrations of rhabdoid meningiomas, the authors performed sequencing of cancer-related genes in 27 meningiomas from 18 patients with rhabdoid features and evaluated breast cancer [BRCA]1–associated protein 1 (BAP1) expression by immunohistochemistry in 336 meningiomas. The tumor suppressor gene BAP1 is inactivated in a subset of high-grade rhabdoid meningiomas. Patients with BAP1-negative rhabdoid meningiomas had reduced time to recurrence compared with patients with BAP1-retained rhabdoid meningiomas. A subset of patients with BAP1-deficient rhabdoid meningiomas harbored germline BAP1 mutations, indicating that rhabdoid meningiomas can be a harbinger of the BAP1 cancer predisposition syndrome. The authors conclude that BAP1-mutated rhabdoid meningiomas are clinically aggressive, requiring intensive clinical management.

Tuesday, November 22, 2016

MOC Exam Topic: Acute Hemorrhagic Leukoencephalopathy

First recognized as a discrete entity by Weston Hurst in 1941, acute hemorrhagic leukoencephalopathy (AHL) is a usually fatal disease characterized clinically by an abrupt onset of fever, neck stiffness, and neurological deficits, often progressing rapidly to seizures and coma. The presenting clinical picture is similar to that of acute disseminated encephalomyelitis (ADEM) but with a more fulminant course. At autopsy, the brain is swollen with multiple petechial hemorrhages centered in the white matter. Large foci of necrosis with cavitation may be present. The cerebral cortex and basal ganglia usually appear intact. Histologically, perivascular demyelinating lesions consist of ball or ring hemorrhages surrounding necrotic venules. There are cuffs of mononuclear cells and neutrophils. There is also substantial axonal injury in the affected areas. The lesions are indistinguishable from ADEM, but the extent of microvascular damage and therefore hemorrhage is is greater. An allergic mechanism is postulated.

FIGURE 3. A (H&E, 100×), B (LFB/PAS, 100×), and C (HAM-56 IHC, 400×). Light microscopic studies revealed thin sleeves of pallor surrounding small-caliber parenchymal blood vessels (A) which correspond to areas of demyelination on special stain (B). Macrophages stain strongly positive for macrophage marker HAM-56 (C). From Lann MA, et al.  2010 Mar;31(1):7-11.

Wednesday, November 16, 2016

Best Post of September 2016 - Featured Neuropathologist: Karra A. Jones, MD, PhD

The next in our "Best of the Month" Series is from September 6, 2016:
Karra Jones, MD, PhD
From time to time on Neuropathology Blog, we profile a prominent neuropathologist. In the past, we've featured the likes of Craig HorbinskiRoger McLendon, and Jan Leestma. Today, we feature a rising star in the field: Karra A. Jones, MD, PhD. Having just moved to the University of Iowa from UCSD, Dr. Jones is poised to do great work at her new institution. Here's a short bio followed by a Q&A with the inimitable Dr. Jones:

Karra Jones grew up in Kansas City where she completed her M.D. and Ph.D. at the University of Kansas School of Medicine. Karra’s graduate work focused on the evaluation of muscle spindle innervation by large peripheral nerve fibers and proprioceptive abnormalities in diabetes. During her time at KUMC, Karra was inspired by the strong history of neuropathology in Kansas City started by the dearly missed John Kepes and continued by her amazing mentor Kathy Newell. Karra traveled to the West Coast in 2010 to train in combined anatomic pathology/neuropathology under Lawrence Hansen, Scott VandenBerg, Subhojit Roy, and Henry Powell at the University of California, San Diego. There she focused on brain tumor research with Scott VandenBerg and Steve Gonias and developed a clinical interest in neuromuscular pathology. She was fortunate to obtain additional training in muscle pathology at UCSD with Diane Shelton in The Comparative Neuromuscular Laboratory. Karra joined the staff at UCSD in 2014 where she headed the neuromuscular service, participated in the general neurosurgical service, collaborated with molecular pathology on brain tumor molecular testing protocols/testing, supervised a biomarker laboratory, and was a co-director of the tissue biorepository. Karra very recently returned to the Midwest to join the highly talented neuropathology group at the University of Iowa where she is very excited to be practicing alongside Steve Moore, Leslie Bruch, Pat Kirby, and Gary Baumbach. 

1. Why did you decide to become a neuropathologist?

I became interested in the neurosciences after spending a year as a research assistant at Emory University in the Department of Neurology prior to medical school. Then, during graduate school at KUMC, my interest in tissue morphology was peaked after spending hours each day under a confocal microscope staring at muscle spindle innervation (what a gorgeous thing!) While at KUMC, I was extremely lucky to have Kathy Newell take me on as a mentee, and after that I was hooked. Almost everyone in my family is an artist, and I often felt like the outsider in that regard. But I realized with pathology, and in particular the beauty of neuropathology, I was a different kind of artist in my own right. Examining, classifying, and photographing brain tumors, neuromuscular diseases, and neurodegenerative diseases seemed like the most fun I could ever have at work. And I continue to have fun every day as a neuropathologist. 

2. Name a couple of important professional mentors. Why were they important to you?
I already mentioned Kathy Newell – Kathy has been an amazing mentor throughout my training and early career even though I haven’t worked with her directly since medical school. She first inspired me to pursue neuropathology with her amazing eye, calm demeanor, and kind heart. She also taught me about the importance of a “Neuropathology Family” introducing me to John Kepes and encouraging me to work with B.K. DeMasters during my last year of medical school, which helped solidify my decision to pursue combined AP/NP training. Another very important mentor is Lawrence Hansen (although he would argue that mentor means “cross-dresser” as the word is derived from Homer’s Odyssey in which Athena assumes the form of Mentor.) Larry is one of the most talented teachers and morphologists I have ever had the opportunity to work with. His “Hansen-isms” are embedded in my brain for life and as a neuropathologist and educator I will forever pass them on to my fellows, residents, students and mentees. Not only is Larry an amazing teacher and mentor, but also he is a very good friend and human being. I was also extremely lucky to be mentored by Scott VandenBerg on brain tumor diagnosis, molecular testing, and basic science research. Without Scott’s influence, I wouldn’t be where I am today. 

3. What advice would you give to a pathology resident interested in doing a neuropathology fellowship?

Do it! Neuropathology is clearly the best of all pathology specialties. But in all seriousness, Neuropathology training will give you a highly desirable skill set that will prepare you for a large variety of career paths. There are many ways to “differentiate” as a neuropathologist – academic, private practice, research, clinical, tumors, neuromuscular, neurodegenerative, etc. So, prior to your NP training, try to think about what you would like to do as a career after it’s all said and done, but remember to always be flexible and allow yourself to change your mind (it happens in medicine quite often). Neuropathology can also be a good specialty to combine with others such as pediatric pathology and forensic pathology, making you a highly desirable job candidate for varied positions. Don’t be intimidated by the 2 year commitment of the NP fellowship. One extra year in training is nothing in the grand scheme of life and only prepares you even better for the day you click “finalize” on your first case (or it gives you more time to work toward getting grant funding before the clock starts ticking). Right now, there are many job openings in neuropathology – we need bright, motivated, and enthusiastic trainees to become the next generation of neuropathologists. 

4. What city would you like a future American Association of Neuropathologists meeting to be held and why?

I would love for the meeting to be held in San Francisco again. I love visiting the city and always look for excuses to return.