CAP16 Abstract Highlights - Heterotopic Cutaneous Meningioma: An Unusual Presentation Occurring in a Patient With a History of Intracranial Meningioma

The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.

Chibuike L. Enwereuzo and Jean Henneberry at Baystate Medical Center/Tuft University School of Medicine, in Springfield, Massachusetts  discuss an unusual case of cutaneous meningioma in a patient with a history of intracranial meningioma (Poster #106):

Meningioma is a neoplasm of the meninges and typically occurs in intracranial sites. Extracranial meningioma has been reported most frequently in the sinonasal tract and skull bone, most often as extension of intracranial meningiomas. Isolated heterotopic meningioma without contiguous intracranial lesion is extremely rare. A 56-year-old woman presented in December 2015 with 2 firm subcutaneous scalp masses: one in the left lateral and the other in the left superior regions. The clinical impression was that of lipoma. Pathologic examination revealed
an ill-defined proliferation of fairly uniform meningothelial cells, infiltrating a fibroblastic stroma with interspersed adipose tissue. The 2 excised lesions had similar histologic features. Immunohistochemical stains were performed, and the tumor cells were positive for epithelial membrane antigen and negative for S100. A diagnosis of atypical meningioma, World Health Organization (WHO) grade II, was made. The patient’s medical history was significant for intracranial meningioma of the frontal lobe in October 2007, which was diagnosed as atypical meningioma, WHO grade II. Comparison of the scalp masses to her prior meningioma revealed a distinctly different morphologic pattern. Considering the 8-year interval between the scalp tumors and intracranial meningioma, it is unlikely that her most recent tumors represent a recurrence or metastasis of the intracranial tumor.

CAP16 Abstract Highlights - Extraventricular Neurocytoma: A Diagnostic Pitfall Mimicking Oligodendroglioma

The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.

Xinhai Zhang and colleagues at Loma Linda University in California discuss in Poster #198 discuss the problem of distinguishing extraventricular neurocytoma from oligodendroglioma:

Context: Extraventricular neurocytoma (EVN) mimics oligodendroglioma in terms of location and morphology. Oligodendrogliomas usually progress, while EVNs, other than atypical EVNs, typically do
not.

Design: We retrospectively analyzed studies encompassing 155 EVN cases published since 2000 for distinguishing features.

Results: Summarized differentiating features include the fact that EVNs have a peak incidence in the third and fourth decade of life, whereas the peak incidence of oligodendrogliomas is from the fourth to sixth decade. EVNs can have small areas of nucleus-free neuropil as well as thickened hyalinized blood vessels, features not seen in oligodendrogliomas. Immunohistochemically, oligodendrocyte lineage transcription factor 2 (OLIG2) is immunopositive in oligodendroglioma but negative in EVNs. In addition, EVNs are consistently positive for synaptophysin but rarely positive for GFAP, whereas oligodendrogliomas are variably positive for synaptophysin and more often positive for GFAP. Many oligodendrogliomas show loss of heterozygosity on
chromosomes 1p and 19q. These changes are not seen in EVNs except for atypical EVN with MIB-1 proliferation indices greater than 3%. IDH1/2 mutations are present in many oligodendrogliomas but not EVNs. Ultrastructurally, EVN tumor cells demonstrate numerous neuritelike cell processes as well as cell bodies with dense-core neurosecretory granules, whereas oligodendroglioma cells show plump and rounded cytoplasm without forming cellular processes, synaptic structures, or dense-core granules. Rare hypothalamic neurocytomas express TTF1 and vasopressin.

Conclusions: While clinicopathologic features are diagnostically helpful, additional molecular analyses are needed to better characterize the spectrum of EVNs and their distinction from oligodendrogliomas.

CAP16 Abstract Highlights: Accuracy of Central Nervous System Intraoperative Consultation Among Neuropathologists and General Pathologists

The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.

Timothy Harcom and Patrick Malafronte of the Walter Reed National Military Medical Center address in Poster #202 the accuracy of CNS intraoperative consultation:

Context: The reported accuracy of central nervous system (CNS) intraoperative consultation approaches 90%. Many of these studies, however, only include analysis by neuropathologists. The accuracy of diagnoses among general pathologist has not been extensively studied.

Design: All CNS intraoperative consultations during a consecutive 5-year period were evaluated. The consultations were separated into 2 groups: those consultations evaluated by a neuropathologist and those evaluated by a general pathologist. Four categories of frozen-permanent concordance were created: complete concordance, partial concordance, discordance, and deferral of diagnosis beyond the appraisal of adequate diagnostic tissue.

Results: A total of 170 CNS intraoperative consultations were identified: 91 cases with neuropathology evaluation and 79 cases with general pathologist evaluation only. The results (numbers of cases) were as follows, respectively: total concordance of 43 and 25; partial concordance of 39 and 31; discordance of 5 and 6; deferral of diagnosis of 4 and 17. Two of these comparisons produced statistically significant results (P< .05), complete concordance, showing a 72% increase, and deferral of diagnosis, showing a 76% decrease when the cases were evaluated by a neuropathologist.

Conclusions: The increased reliance on deferral of diagnosis and a reduced concordance rate among general pathologists points to a potential learning deficit that could be overcome through targeted education programs, similar to the ThinPrep Pap Proficiency Test, with the aim of increasing the quality of information provided during CNS intraoperative consultation.

CAP16 Abstract Highlights -- Pilocytic Astrocytoma: A Diagnostic Consideration in Lateral Ventricular Tumors

The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.

Caleb Graham and colleagues at the University of Colorado (Poster #193) discuss the differential diagnosis of oligodendroglioma mimickers in the lateral ventricles. Here's the updated abstract:

Context: The most common lateral ventricular tumors are choroid plexus papilloma and meningioma, with a fewer number of cases of subependymoma, subependymal giant cell astrocytoma, lymphoma, and metastasis. Lateral ventricular pilocytic astrocytomas (PAs) are uncommon, seldom reported as a series, and must be excluded from neurocytoma and glioneuronal tumors.

Design: Our brain tumor databases were reviewed to identify all lateral ventricular PAs seen from 2000 to 2016. Magnetic resonance imaging studies were reviewed to exclude cases that were primarily parenchymal with secondary protrusion into the lateral ventricles. Immunohistochemical workup for glial and neuronal markers, as well as BRAF VE1 (surrogate marker for BRAF V600E mutation), were undertaken. KIAA:BRAF fusion status and electron microscopy were performed in 2 cases. 

Results: Four cases (ages 13, 21, 28, and 43 years) were identified. By neuroimaging 2 cases displaced the septum (Figure 75, A) and 1 was near the trigone (Figure 75, B). These cases had generated wide radiologic differential diagnoses, especially central neurocytoma in the 2 cases displacing the septum. Histologically, 3 of the 4 were predominantly composed of small round cells with perinuclear halos (Figure 75,C) and showed few piloid areas or Rosenthal fibers. These cases also showed patchy synaptophysin immunohistochemical positivity, traditionally associated with neuronal tumors (Figure 75, D), but those evaluated by electron microscopy failed to show neuronal lineage.Unlike typical gangliogliomas, all 4 were BRAF VE1 negative.

Conclusions: Lateral ventricle PAs are uncommon but should be considered when encountering lateral ventricular tumors.

CAP16 Abstract Highlights: Predictive Markers for Meningioma Grading

The 2016 annual meeting of the College of American Pathlologists (CAP16) is coming up September 25-28 in Las Vegas. I'll be attending the meeting this year. In this series of posts, I'll be featuring poster abstracts of particular interest to neuropathologists.

Hussam Abu-Farakh and colleagues from Ibn Haytham Hospital in Amman, Jordan present a poster (#178) on predictive markers for meningioma grading. Here is an excerpt from the abstract:

Design: We studied 244 meningioma cases during the last 10 years at our center. All cases were studied for the following: sex, tumor size, mitotic count, the presence of small cell component (SCC), brain invasion (BRI), bone invasion (BNI), necrosis, and atypia (defined as pleomorphism, prominent nucleoli 6 large hyperchromatic nuclei). Additionally, immunohistochemistry for the percentage of progesterone receptor (PRG) expression, p53, and Ki-67 was calculated.

Results: Grade I and II meningiomas were more common in females, but grade III tumors were equally distributed (P , .05)

The poster also breaks down specific percentages for different histologic features of each of the grades in their series. For example, with regard to progesterone receptor (PR) immunohistochemical expression, 65% are positive in Grade I meningiomas, 32% are positive in grade II, and only 3% are positive in grade III.

Featured Neuropathologist: Karra A. Jones, MD, PhD

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 Horbinski, Roger 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.

Best Post of July 2016 -- The signature feature of sparsely granulated growth hormone pituitary adenoma: the fibrous body

The next in our "Best of the Month" series is from July 19, 2016:

The patient is a middle-aged female with subtle signs of acromegaly.

Arrows point to the pale balls in this pituitary adenoma  which correspond to
fibrous bodies on CAM 5.2 immunohistochemistry

The signature feature of sparsely granulated GH adenomas is the finding of widespread, ball-like, cytoplasmic ‘fibrous bodies’ on CAM5.2  in >70% of cells.

CAM 5.2 immunohistochemistry

Crooke cells in a touch preparation of a corticotroph pituitary adenoma

College of American Pathologists Neuropathology Committee meets this weekend

I am privileged to join the other members of the Neuropathology Committee of the College of American Pathologists at our biannual meeting this weekend in Chicago. Members and staff are pictured:

Back row, left to right: Amyn Rojiani, myself, Eyas Hattab (Chair), Brent Harris, Joe Ma, Bill Hickey, Matt Schneiderjan.
Front row, left to right: Cordell Jones (staff), Annabel Dizon (staff), Areli Cuevas-Ocampo (junior member), Andrea Wiens

My all-time favorite post ever: Whither the Illusory Cowdry B Inclusion?

I have put up a grand total of 619 blog posts since this site got started back on October 31, 2007. I was recently asked which was my favorite. No question, my all-time favorite is about the illusory Cowdry B body. This post has even made it into the references for the Wikipedia page on Cowdry bodies. By the way, the reward of a 10 dollar bill which I posted six years ago to the person who sends me a picture of this structure still stands! I have no fear of being parted from my Jefferson as, in my opinion, the Cowdry B body is the Sasquatch of neuropathology. Here's the post from November 13, 2008:

In a recent post about poliomyelitis, the illustrious Dr. John Donahue of Brown University (pictured) correctly pointed out that I did not mention the presence of Cowdry B inclusions in my histological description of the disease. Having never seen polio under the microscope, I went looking in textbooks and on the web for a photomicrograph of a polio-related Cowdry B inclusion. Failing in my search, I turned to the esteemed Dr. Tom Smith of the University of Massachusetts to see if he had such a picture. With his permission, I quote Dr. Smith’s email to me:

“I have the same problem you and everyone else seems to have -- I've never seen one myself and cannot find any photos of one either in my own file or anywhere in books or on the web. I remember reading a description a long time ago - I think it might have been from the old AFIP neuropath teaching slide set - that they were supposed to be small eosinophilic (?) nuclear inclusions that were sometimes seen in neurons in poliomyelitis. I don't remember actually seeing them in the slide in that teaching set. From the description, I had the impression they might have resembled Marinesco bodies or maybe even normal but prominent nucleoli... or perhaps those small inclusions seen in some neurodegenerative dementias. They don't seem to be as 'specific' as Cowdry A inclusions and perhaps they don't even exist? Frankly I think Cowdry B inclusions have reached the point where they should be relegated to the trashbin of neuropathology.” (Emphasis added.)

I recently photographed a Marinesco body (see picture, arrow points to the eosinophilic body) within the 

nucleus (outlined) of a pigmented neuron in the substantia nigra. Could the Cowdry B inclusion be an elaborate hoax perpetrated upon us by Dr. E.V. Cowdry when he first described Cowdry type A and type B inclusions in 1934? Dr. Smith’s response:

“Well, I doubt that it was a hoax but I think some of those folks were quite prone to seeing things that just the passage of time (and new information) has proved to be ‘not real’. Another case in point - how many Alzheimer type 1 astrocytes have you

seen?”

I then wrote back to the individual who got me started on this hunt for the illusory Cowdry B in the first place: John E Donahue, MD. Here’s what Dr. Donahue had to say about the issue:

“I think these descriptions are very old and go back to the day where everything was described visually, without knowing etiology. (Remember, there are eight structures of Scherer from the original 1938 article, only three of which are really relevant anymore, and maybe even the gliosarcoma being a tertiary structure may be going the way of the dinosaur since I've heard recently that the gliosarcoma arises from a single precursor cell)…”

Fuller and Goodman, in Practical Review of Neuropathology (Lippincott, 2001), define a Cowdry B purely on morphological grounds -- with no implication as to the cause (polio or otherwise) -- as being small, eosinophilic, intranuclear inclusions with no halo and causing no nuclear effacement. I quote page 20: “[T]he quotidian Marinesco bodies that are routinely observed in the neurons of the pigmented brainstem nuclei are sterling examples of the Cowdry type B beau ideal.”

Perhaps the Marinesco body, rather than a “sterling example”, may in fact be the only example of a Cowdry B inclusion! Come to think of it, I think I’ll offer a $10 reward for anyone who can send me a photomicrograph of a polio-related Cowdry B inclusion. Email me the photo at brian.moore@ucdenver.edu

I hope you have better luck finding one than I did!

Scleral invasion by uveal melanoma

Circled cells represent superficial invasion of sclera (I don't think those cells are in a vessel)