Answer 1: B. Glioblastoma multiforme.
Answer 2: A. APC.
A 20-year-old HIV positive male presents with headache, nausea, and vomiting following a seizure. History is notable for 3 surgeries to remove colonic polyps. Subsequent MRI brain scan with contrast reveals a mass in the left frontal lobe which is removed. The image above is an H&E stained section of the mass.Comment: Key clinical features of Turcot syndrome (also called mismatch repair cancer syndrome) include both colonic polyps and CNS malignancies. Interestingly, patients with Turcot syndrome have a 92% higher incidence of medulloblastomas and gliomas than occur spontaneously. About 2 to 3 spontaneous cases of glioma occur per 100,000 people in both the European and North American populations. Turcot syndrome has been described as having either an autosomal recessive or dominant inheritance pattern. Either the APC gene or the mismatch repair genes (MLH1, MLH2, MLH6 or PMS2) have been implicated. These genes also are thought to underlie a disease similar to Turcot syndrome called syndrome of hereditary nonpolyposis colorectal cancer. Brain malignancies seen in these uncommon diseases with APC mutations are usually medulloblastomas, but if they have mutated mismatch repair genes they usually are glioblastomas.
Click here for the comparative pathology.
Click here to see the whole slide image.
This Image IQ has been provided by the Center for Genomic Pathology
Reference:
1. Turcot J, Despres JP, St-Pierre F. Malignant tumors of the central nervous system associated with familial polyposis of the colon: report of two cases. Dis Colon Rectum. 1959;2:465-468. PMID: 13839882
2. Hamilton SR, Liu B, Parsons RE, et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995;332:839-847. PMID: 7661930
3. Digilio MC. Turcot syndrome. Atlas Genet Cytogenet Oncol Haematol. August 2005. Available from: http://atlasgeneticsoncology.org/Kprones/TurcotID10026.html
4. De Rosa M, Fasano C, Panariello L, et al. Evidence for a recessive inheritance of Turcot's syndrome caused by compound heterozygous mutations within the PMS2 gene. Oncogene. 2000 Mar 23;19(13):1719-23. PMID: 10763829
5. Lucci-Cordisco E, Zito I, Gensini F, Genuardi M. Hereditary nonpolyposis colorectal cancer and related conditions. Am J Med Genet A. 2003;122A:325-334. PMID: 14518071
6. Marumoto T, Tashiro A, Friedmann-Morvinski D, et al. Development of a novel mouse glioma model using lentiviral vectors. Nat Med. 2009;15:110-116. PMID: 19122659
