Wednesday, July 29, 2015

Best Post of December 2014: The Einstein/Rorke-Adams Connection

The next in our "Best of the Month" series comes from Tuesday, December 16, 2014:



Dr. Lucy Rorke-Adams
I'm not sure how many in the neuropathology community know this, but our renowned colleague Lucy Rorke-Adams donated slices of Albert Einstein's brain to the Mütter Museum and Historical Medical Library in Philadelphia. Rorke-Adams, a senior neuropathologist at the Children's Hospital of Philadelphia, donated the 46 slices of brain tissue to the museum in 2011. Rorke-Adams had received the slides as a gift from local doctor, who in turn had received them from his colleague, a neuropathologist who examined the slides on behalf of Thomas Harvey, the man who removed Einstein's brain during an autopsy in 1955. Guess where my first stop will be on my next visit to Philly?

Friday, July 17, 2015

The Tumor Biomarker Series: Medulloblastoma Markers

Four subgroups of medulloblastoma have been defined based on genetic alterations:

Wingless (WNT) - WNT medulloblastomas display monosomy 6 and most show nuclear accumulation of the WNT pathway protein beta-catenin, which serves as a useful immunohistochemical screen for this group. Medulloblasomas with more than 50% nuclear staining for beta-catenin have been shown to have WNT pathway activation, whereas those with only focal nuclear staining do not. Overall survival for WNT medulloblastomas are dramatically longer than those of other subtypes, and clinical practices surrounding the treatment of this subtype reflects this better prognosis.

Sonic Hedgehog (SHH) - SHH medulloblastomas often show a nodular/desmoplastic histopathology and are associated with a better prognosis in younger children and infants. 9q deletion is characteristic, and MYCN amplifications are occasionally noted. GAB1 is expressed in the cytoplasm of nearly all SHH medulloblastomas but not in other groups and can be detected imunohistochemically, making it a valuable SHH-group marker.  Targeted therapies directed at this subgroup have been established and are entering clinical practice.

"Group 3" - Group 3 medulloblastomas have the worst overall prognosis, have a high incidence of large cell/anaplastic histology, and are very frequently metastatic. This group contains the vast majority of MYC amplified tumors, with MYC amplification being a strong negative prognostic factor. It has been suggested that Group 3 tumors should perhaps be re-named MYC medulloblastomas, but wide agreement has not been reached on this designation. Group 3 tumors occur more commonly in males than females, and are found in infants and children, but almost never in adults.


"Group 4" - Group 4 medulloblastomas classically harbor isochromosome 17q; but as the molecular pathogenesis of this group is not currently clear, the generic name "Group 4" remains the consensus designation. Although isochromosome 17q is also seen in Group 3 tumors, it is much more common in Group 4. KCNA1 has been suggested as an immunohistochemical marker for this group, but this requires validation.  The only other notable cytogeneic change seen in Group 4 tumors is loss of X chromosome, which is seen in 80% of females with this tumor subtype. Group 4 patients have an intermediate prognosis, similar to patients with SHH tumors.

In conclusion, the worst prognosis is associated  with Group 3 medulloblastoma; Group 4 and SHH have an intermediate prognosis; and WNT medulloblastoma tends to have the best prognosis.

Wednesday, July 1, 2015

Neuropathologist Kevin Roth named Chair at Columbia and Pathologist-in-Chief at New York-Presbyterian

Dr.. Kevin Roth, MD, currently chair of pathology at the University of Alabama at Birmingham, has been named chair of the Columbia's Department of Pathology & Cell Biology and pathologist-in-chief at NewYork-Presbyterian, effective September 1, 2015.  Dr. Roth succeeds Michael Shelanski, MD, PhD, also a neuropathologist, following his 28-year tenure as chair of the department.

Although Dr. Shelanski is stepping down, his is remaining on staff at the department. Dr. Roth's addition will therefore bring to seven the number of neuropathologists practicing at Columbia, including Drs. Jim Goldman, Peter Canoll, Phyllis Faust, Jean-Paul Vonsattel, and Andy Teich.  


Kevin A. Roth, MD, PhD

Dr. Roth’s professional training included a combined anatomic pathology and neuropathology residency at Washington University in St. Louis, where he was later appointed an assistant professor in the Department of Pathology.  Dr. Roth rose through the faculty ranks to become a tenured professor in the Departments of Pathology and Immunology and Molecular Biology and Pharmacology there before moving to the University of Alabama at Birmingham, where he was named chair of the Department of Pathology in 2008.
Dr. Roth serves as president of the American Society for Investigative Pathology, chair of the Neural Oxidative Metabolism and Death (NOMD) Study Section, and editor-in-chief of the American Journal of Pathology, which is devoted to elucidating the cellular and molecular mechanisms of disease pathogenesis.