Thursday, March 25, 2010
Best Post of November '09" Finally, a simple cartoon depicting the anatomic location of the transentorhinal cortex
online presentation by Prof. Jillian Kril of the Pathology Department at the University of Sydney, NSW. Prof. Kril kindly emailed me a copy of the illustration, which is depicted above with the addition of a label for the presubiculum. Feel free to use this cartoon for teaching purposes with the following credit: Adapted from Harding AJ, Halliday GM, Kril JJ. Variation in hippocampal neuron number with age and brain volume. Cerebral Cortex (December, 1998) 8:710-718.
Friday, March 19, 2010
Thursday, March 11, 2010
This is an example of dysplastic cerebellar gangliocytoma, otherwise known as Lhermitte-Duclos disease (LDD). Dr. Peter Burger and colleagues, in their Surgical Pathology of the Nervous System and Its Coverings (4th edition, page 274), make this comment about LDD: "In the parlance of bird-watching, an endeavor with many similarities to surgical pathology, Lhermitte-Duclos disease is an entity not likely to be found on the 'life-list' of most pathologists." Well, this rara avis is now on my life-list!
When I came upon this tumor, I immediately thought of Dr. Ty Abel (pictured to the left), neuropathologist at Vanderbilt, who in 2005 authored an immunohistochemical study of 31 cases of Lhermitte Duclos disease. I emailed him this question: "What is the current thinking on LDD? Is it a hamartoma or a neoplasm or something in between?"
Ty's response: "Something in between may be the best answer. We suggested in our paper that it was a 'hypertrophic phenomenon superimposed upon a developmental malformation'. Our observations, as well as those in Suzie Baker's mouse model of this, suggest that aberrant signaling in the pathway disrupts granule cell migration as well as leading to their hypertrophy. Histologically, there is little proliferation, so the increase in tumor size over time may be due to cellular hypertrophy or to the abnormal myelinization of the molecular layer or both.Still, they do grow and sometimes come back after resection, making them tumor-like. Does your patient have evidence of Cowden's?"
Cowden syndrome. But Ty put me in touch with a leading authority on Cowden syndrome at the Cleveland Clinic, Dr. Charis Eng (pictured to the right) who emailed me this comment: "What we found in our initial series is that adult-onset LDD is almost always associated with germline PTEN mutations, i.e., has Cowden syndrome."
Whether or not this patient gets germline PTEN testing, she should be closely surveilled for breast, thyroid, and endometrial cancer, as there is a high incidence of these tumors in patients with Cowden syndrome.
And now a recut slide of this rare bird gets filed away in my teaching set, only to be let out of its cage again by the eager inquiry of a resident.
Monday, March 8, 2010
What is the relative prevalence of CNS metastases versus primary tumors?: Simple question, complex answer
During the pre-exam pathology review session at my medical school, one of the students asked about the relative incidence of metastases to the CNS versus primary CNS neoplasms. I answered that metastases are ten times more common than primary tumors. After the presentation, a colleague in the audience pointed out to me that the current issue of Robbins and Cotran (p. 1330) says: "about half to three quarters are primary tumors, and the rest are metastatic." I said, "No way!" and produced another textbook (the current edition of "Greenfield's Neuropathology"), which states the following on page 2116: "Metastatic tumors to the brain are approximately 10 times more common than primary intracranial neoplasms."
As we investigated the issue further, it became clear that the two textbooks were starting with a completely different denominator in arriving at their proportions. In Robbins and Cotran, the authors were looking at incidence rates of metastases in patients presenting with brain tumors. In Greenfield's Neuropathology, the authors appear to be extrapolating from autopsy series which included patients who never had a pre-mortem brain biopsy because metastasis was presumed. You might say that none of this matters too much. And, in a way, you would be right to say that. The bottom line is that a significant proportion of brain tumors are metastatic lesions. But, this discussion does matter in that it is a nice example of how statistical estimates of the prevalence of disease can vary widely depending on what denominator the author chooses to use. It is incumbent upon the author to be crystal clear about the denominator; but, unfortunately, that is not always the case – in which case it is incumbent upon the reader to beware.