Best Post of October 2012: IDH1 Mutations in Oligodendrogliomas: PNA-clamping PCR is best analytic method

Time for the next in our "Best of the Month" series.. At the time of it's original publication, Dr. Craig Horbinski had this to say about a study which had recently been published in Brain Pathology: "Only catch is whether the method is TOO sensitive. After all, if all oligos are positive for IDH1, why do the "inferior" IDH tests effectively stratify prognosis? I'll be keen to see if anyone else can replicate this work."

Here's the original post from October 22, 2012:

Although direct sequencing of mutations in isocitrate dehydrogenase 1 (IDH1) has been considered to be the gold standard method to detect this mutation, the sensitivity of this technique has been questioned especially because specimens from glial tumors may contain large numbers of non-tumor cells. The group screened 141 cases of oligodendroglial tumors for IDH1 mutations using peptide nucleic acid (PNA)-mediated clamping PCR and compared the results with the results of direct sequencing, pyrosequencing, and immunohistochemistry (IHC). Nested PCR was only performed in cases having mutant IDH1 only discovered by clamping PCR. Using dilution experiments mixing IDH1 wild-type and mutant DNA samples, clamping PCR detected mutations in samples with a 1% tumor DNA composition. Using PNA clamping PCR, the group detected 138 of 141 (97.9%) cases with mutant IDH1 in the series, which is significantly higher (P = 0.016; PNA clamping vs. direct sequencing) than those of direct sequencing (74.5%), pyrosequencing (75.2%), and IHC (75.9%). From these results, it appears that almost all oligodendroglial tumors have IDH1 mutations, suggesting that IDH1 mutation is an early and common event especially in the development of oligodendroglial tumors.

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.