Neuropathologist Roger Brumback found murdered in his home

Neuropathologist Roger Brumback, 65, and his wife were found murdered in their Nebraska home on Tuesday. Dr. Brumback, an active member of the neuropathology community, was the former chair of pathology at Creighton University in Omaha.

Roger Brumback, MD

The bodies of Dr. Brumback and his wife, Mary, were discovered by a piano mover who had arrived at their home to find the front door ajar. 

In addition to his work as a neuropathologist, Dr. Brumback was a clinical pediatric neurologist and was the founding Editor-in-Chief of the Journal of Child Neurology. At a memorial held at Creighton in his honor, medical students described Brumback as a kind and caring man who was devoted to teaching.

Police are looking at any link between this killing and that of the son of another Creighton pathologist back in 2008. There have been no arrests in either case.

Dr. Mark Cohen's "Wicked Clown" Mitochondrion

Inspired by the last post regarding unusual mitochondrial inclusions, the insurmountable Dr. Mark Cohen of Case Western sent in his favorite picture of an aberrant mitochondrion, which he likens to a "wicked clown":

Angulated intramitochondrial inclusions in the left leg of a man with a left-sided limp

A 59-year-old male with a one-year history of limping as well as pain, weakness, and paresthesia of the left lower extremity who underwent lumbar microdiscectomy with cord decompression. Although the patient's pain subsided post-operatively, his other symptoms persisted. Since his CPK levels were chronically elevated (around the 500's), biopsies were later performed on the quadriceps bilaterally. Light microscopic examination was underwhelming except for some denervation effect on the left. However, subsarcolemmal clumping was evident with NADH histochemisty on both the right and left. This clumping prompted me to perform an ultrastructural examination, which revealed the following angulated intramitochondrial inclusions IN THE WEAK LEG ONLY:

These inclusions were present in about 5% of mitochondria.  I reported out my findings in a descriptive manner, not certain of their significance. If anyone has seen such intramitochondrial inclusions in a specimen, please comment. As of now, the patient has no definitive diagnosis.

Annual AANP meeting is two months away

The Charleston Place Hotel in Charleston, South Carolina

Neuropathologists across the country are starting to make plans to attend the 89th Annual Meeting of the American Association of Neuropathologists, which will be held June 20-23, 2013 in Charleston, SC at the Charleston Place Hotel. The meeting with commence on Thursday the 20th with two half-day courses. There will be a morning course directed by Dr. Charles L. White entitled Practical Issues and Challenging Diagnoses in Forensic Neuropathology. The afternoon course is called Update in Frontotemporal Lobar Degenerations and is directed by Dr. Elizabeth J. Cochran. Other highlights later in the weekend include the return of Dr. Stanley Prusiner, Nobel laureate, who will talk about prion disease. (Dr. Prusiner last spoke to the AANP in 2006, when the meeting was paired with the International Society of Neuropathogy conference in San Francisco.) The inimitable Dr. Harry Vinters will speak on vascular diseases of the CNS. Looks like another great line-up of topics and speakers!

A Rich Focus

The grey arrow is pointing to a Rich focus that has hemorrhaged into the subarachoid space

A Rich focus is a tuberculoma in the cerebral cortex. Rich foci become particularly significant when they rupture into the subarachnoid space and cause tuberculous meningitis. This entity is named for Johns Hopkins pathologist Dr. Arnold Rice Rich (1893-1968), who first described it.

Best Post of September 2012: DecisionDx-GBM: Should every glioblastoma patient be getting this test?

The next in our Best of the Month Series is from September 12, 2012. It's worth revisiting the question of whether or not genetic testing of brain tumors is appropriate in patients who are not on research studies:

What does the neuropathology community think of DecisionDx-GBM? This is a product offered by Castle Biosciences, based in Phoenix, AZ. DecisionDx-GBM is a gene expression profile test developed at The University of Texas M. D. Anderson Cancer Center for the purpose of increasing the accuracy of the prognosis and predicted responsiveness of glioblastoma multiforme to first line radiation plus temozolomide. The test is able to distinguish GBM tumors with a proneural phenotype (tumor signature) from those with a mesenchymal / angiogenic phenotype. Patients with a proneural phenotype tumor who are treated with first line radiation plus temozolomide experience a significantly longer median survival (over 7 years) compared to those patients with a mesenchymal / angiogenic phenotype tumor (approximately 1 year). According to the company website, the assay has been fully validated and has been available for clinical use since 2008. A study is ongoing to determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit from the addition of bevacizumab to temozolomide and radiotherapy. DecisionDx-GBM is also currently being incorporated into a number of other prospective and retrospective studies.

Is DecisionDx-GBM covered by insurance? Castle Biosciences states that the test receives reimbursement from a number of commercial insurance companies, and appeals to the Administrative Law Judge level for Medicare have resulted in favorable decisions for full payment. Should a patient need to pay out-of-pocket for this test, I could not find on the website what the cost would be.

Should we as neuropathologists recommend the use of this profile? Here is a an example of the kind of report that is generated when one orders the panel of 12 genes (3 of which are for control) upon sending a block of paraffin-embedded fixed tissue to the company. I would be interested in hearing people's opinions regarding this product, and whether there are others on the market which might be comparable. Please post!

How do you calculate a brain tumor's MIB-1 index?

Elizabeth J. Cochran, MD

I was recently contacted by the affable Elizabeth Cochran, MD  asking if I would post a query regarding MIB-1 counts on brain tumors. Does anyone know if there is a standardized approach to this?  Please tell us your approach to MIB-1 quantification in the comment section. Dr. Cochran takes an approach based on an article she had read in Human Pathology some time ago, summarized as follows:

1. Examine control section stained with MIB-1 antibody to confirm that the stain worked.

2. Survey the slide of the case to be counted to find the area(s) that have the most stained nuclei.

3. Put reticule in right eyepiece of microscope.

4. Place the area identified in #2 under the reticule at 40x power.

5. Using the hand held counter, count all the immunoreactive nuclei within the entire grid.

6. Count all nuclei that touch the right and bottom outer border of the grid, but NOT the nuclei that touch the upper and left borders.

7. Record this number in the lab book.

8. Count all nuclei present within one vertical column of the grid.  This column should be randomly chosen.

9. Record this number in the lab book.

10. Count all nuclei present within one horizontal column of the grid.  Again this column should be randomly chosen, and recorded in the lab book.

11. Again, be sure to count all nuclei that touch the right and bottom outer border of the grid, but NOT the nuclei that touch the upper and left borders

12. Repeat this procedure for at least two more high power fields on the section that contains the most numerous immunostained nuclei and record all values in the lab book.

 13. Calculate the MIB-1 proliferative index as follows:

                a. For each of the fields counted: Add all of the nuclei counted in each row and column from each field and multiple by five.  Divide the number of the immunostained nuclei counted in that field by the calculated sum of all of the nuclei in that field.

                b. The total number of all cells counted in all fields should be > 1000.  If it is substantially less than 1000, count another field, as described above.

                c. Calculate the average of the three fields and  record the proliferative index in the lab book.