Case Study 24Craig Horbinski, M.D., Ph.D.

You receive a consult case from an outside hospital on a brain biopsy from a 51 y/o male with a left sided brain tumor, with accompanying MRI scans.  No other clinical information is provided.  Describe the scan.

Question 1

The scans show a large left-sided tumor with mass effect, edema, and only a slight focus of enhancement at the inferior aspect of the tumor just above the hippocampus, near the posterior end of the basal ganglia.

Answer

Question 2Describe the biopsy.

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AnswerThere are fragments of hypercellular brain tissue infiltrated by atypical glial-appearing cells.  These cells have moderate amounts of pink process-rich cytoplasm, enlarged slightly pleomorphic nuclei that are mostly oval or angulated, with a few rounded nuclei.  A few scattered angulated neoplastic nuclei are present.  Extensive microcalcification is seen, as well as rare apoptotic, pyknotic and karyorrhectic nuclei.  No necrosis, mitosis, or endothelial proliferation is seen.

Question 3What is your differential?  Are there any additional studies that could help you make the diagnosis?

AnswerClearly this is a low grade glioma.  The differential includes a grade 2 oligodendroglioma, grade 2 diffuse astrocytoma, or a grade 2 oligoastrocytoma.  If there were any mitoses in a biopsy this small it would be a grade 3, and if there was necrosis or microvascular proliferation it would be a grade 4.  In cases like this it is best to wait for molecular diagnostic tests (in particular 1p/19q FISH) before signing it out.

Question 4Does your diagnosis correlate with the radiology?

AnswerMostly, since there is only a small amount of contrast enhancement at the inferior aspect of the large tumor.  Still, contrast enhancement is a sign that the blood-brain barrier is breaking down, which in gliomas is usually due either to blood vessel proliferation or necrosis.  Thus, it is a red flag for progression to a higher grade.  But this biopsy does not meet the WHO criteria for a grade 3 or 4 glioma, so it cannot be diagnosed as anything other than a grade 2 glioma.  A diagnostic comment might be in order, mentioning that the focal area of enhancement does not appear to have been represented in this biopsy material.

Question 51p/19q FISH results are in:The ratio of 1p36/1q25 =0.95 with 9.6% of the cells showing loss of 1p.The ratio of 19q13/19p13 =0.97 with 6.5% of cells showing loss of 19q.

How do you interpret these findings?  What is the diagnosis?

AnswerThere is no 1p/19q loss via FISH, so the evidence favors a grade 2 astrocytoma over an oligodendroglioma.  The key here is to realize that, although calcifications are more common in an oligodendroglioma, in fact calcifications are more often seen in an astrocytoma just because astrocytomas are far more common.  Plus, for this to be an oligodendroglioma the vast majority of the nuclei should be rounded, not just a minority.  Furthermore, while oligodendrogliomas can have a fair amount of pink cytoplasm in some cases, they don’t show the amount of processes that are seen here.