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)

Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma

Jacob J. Mandel, MD

The current issue of the Journal of Neuro-Oncology features an paper by neuro-oncologist Jacob J. Mandel and colleagues entitled Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma. The paper looks at whether patients with IDH-mutated glioblastoma have a higher 6-month progression-free survival (PFS6) or radiographic response (RR) on clinical trials for recurrence. With respect to PFS6, 24 patients were identified who had PFS6 and IDH results. Of those 24 patients, 5 had IDH-mutant GBM. A group of 24 controls without PFS6 also had 5 patients with IDH-mutant GBM. A similar result was obtained with regard to RR. Although median overall survival was 10 months better for the IDH-mutant group, the study determined that IDH mutation status was not predictive of PFS6 or RR in recurrent GBM for this data set. The authors conclude that their results "would seem to indicate that stratifying future recurrent GBM trials based on IDH1 mutation status or excluding pts with IDH1 mutated tumors may be unnecessary if including pts at various recurrences. However, our findings suggest that stratification of pts based on IDH mutation status may potentially be necessary for recurrent GBM clinical trials that limit patient enrollment to first recurrence."

A Case of Chordoid Glioma of the Third Ventricle

A man in his sixties presented with disequilibrium and hypothermia.

A 34 x 28 mm well-circumscribed 3rd ventricular mass

Chordoid architecture with myxoid background

Admixed plasma cells are characteristic

Chordoid Glioma, WHO grade II

H3-K27M immunohistochemical positivity in a case of Diffuse Midline Glioma

The utility of TTF-1 immunohistochemistry in the diagnosis of sellar region masses

Posterior pituitary cells (pituicytes) manifest nuclear TTF-1 positivity. Anterior pituitary cells are negative. Three rare neurohypophyseal neoplasms which are derived from pituicytes maintain TTF-1 nuclear positivity: pituicytoma, spindle cell oncocytoma, and granular cell tumor. At times when the neuropathologist is trying to distinguish one of these neoplasms from more common sellar tumors -- such as pituitary adenoma, meningioma, and schwannoma -- TTF-1 can be helpful.

TTF-1 immunohistochemistry in the neurohypophysis