Turcot Syndrome (medulloblastoma with familial adenomatous polyposis)
Stephen J. Qualman, M.D. Children's Hospital Columbus, Ohio
A nine-year-old girl who presented with a mass in the posterior cranial fossa underwent suboccipital
decompression and C1 laminectomy with tumor resection. Rectal bleeding developed after surgical resection
of the tumor and chemotherapy, five-and-a-half months after initial brain tumor biopsy. Two colon biopsies
were collected during proctoscopy, which revealed a friable, granular and exudative mucosa.
Resection of the posterior fossa tumor yielded a total of 1 X 1 X 0.5 cm of tissue which was diagnosed as
medulloblastoma ("primitive neuroectodermal tumor"). One of the two biopsies taken from the proctoscopy was
found to be normal; the other was markedly abnormal. Much of the glandular epithelium was denuded and the
glands were cystically dilated. Neutrophils were present in the glands and interstitium. The remaining
epithelium showed cytologic atypia thought consistent with attempted regeneration. The clinical impression
at this point was one of possible pseudomembranous colitis. Stools were sent for bacterial and viral
culture. The patient was maintained on Flagyl therapy.
Nine years later, the patient presented again with rectal bleeding (hemoglobin decreased to 8 g/DL) with
history of intervening stroke and recurrent bleeding thought secondary to hemorrhoids. Upper endoscopy and
colonoscopy now revealed multiple nodules in the stomach, duodenum and colon. Polypectomies from the upper
endoscopy and colonoscopy revealed adenomatous polyps in the duodenum and ascending colon (part C) with the
latter displaying focal high grade dysplasia. The gastric biopsies (part A) showed polyps with a
hamartomatous mixture of gastric fundic gland cells and mucinous columnar gland cells with cystic change.
Cystic glandular change with atypia and inflammation, colon
Fundic gland polyp
Tubular adenoma with focal high-grade dysplasia
This case illustrates two differential diagnostic considerations which offer valuable learning experiences
to both the general and pediatric pathologist. The first is the differential diagnosis of cystic glandular
dilation with acute inflammation in an immunocompromised brain tumor patient. One obvious consideration,
infectious colitis, was ruled out. However, another more obscure relationship, that of a coincidental brain
tumor and intestinal polyposis, was not considered at the time of initial gastrointestinal biopsy (biopsies
were not multifocal or widespread as to site), nor in the ensuing nine years when the patient's rectal
bleeding was ascribed to hemorrhoids without re-biopsy. Initial biopsy of the upper gastrointestinal tract
might also have helped clarify this diagnosis. The patient actually has a combination of Familial
Adenomatous Polyposis (FAP) with medulloblastoma; a variant of so-called Turcot Syndrome.
Turcot's Syndrome is defined by development of colorectal carcinomas and adenomas and primary central
nervous system tumors. In one series, two-thirds of the brain tumors seen were medulloblastomas1 but
other studies2 report the occurrence as closer to one-third. Medulloblastomas tend to arise in younger
patients and are usually associated with familial adenomatous polyposis (FAP). Adenomas usually develop in
the second decade of life. It is typical for hundreds or thousands of polyps to develop. Nearly all cases
will eventually progress into colon cancer, most by the age of 40. Adenomas also develop in the upper GI
tract with nearly all patients developing duodenal adenomas sometime in their life. Fundic gland polyps are
also characteristic of FAP.
Eighty percent (80%) of FAP cases have a germ-line mutation, usually a truncation, in the adenomatous
polyposis coli (APC) gene3 located on chromosome 5q21-22. The inheritance pattern is autosomal dominant
but 30% of cases appear tomr There is genetic evidence that Turcot Syndrome is not
allelic to FAP.5
Nearly all of the residual Turcot syndrome cases are comprised of hereditary non-polyposis colon cancer
(HNPCC) and glioblastomas or astrocytomas. HNPCC is also autosomal dominant arising from mutations in one
of five DNA mismatch repair genes. The majority of HNPCC cases (50-70%) have mutations in hMSH2 and hMLH1,
but mutations also occur in hPMS1, hPMS2 and hMSH6.1 Mutations in hPMS2 or hMLH1 have been noted in
glioblastomas of two Turcot cases6 and hMSH2 mutations in all three Turcot cases7 studied by another
group. Ninety-five percent (95%) of HNPCC cases have microsatellite instability caused by errors in
mismatch repair as opposed to 15% amongst unselected colon cancers. Microsatellite instability is also
exhibited by gliomas in Turcot's syndrome.6 Women with HNPCC, as determined by mutations in mismatch
repair genes, also have a higher chance of developing endometrial cancer.
At least 95 cases of Turcot's Syndrome have been reported in the literature2 with associated brain tumors
including: 31 cases with glioblastoma, 31 cases with astrocytoma and 27 cases with medulloblastoma.
Dividing this syndrome in two components according to the presence of FAP versus HNPCC and the type of brain
tumors leaves one with the intriguing observation8 that the original cases described by Turcot9 were
siblings, both with polyps, one with glioblastoma and the other a medulloblastoma. New candidate genes to
consider in Turcot syndrome include the DMBT1 gene10 or the PTC gene.11
Turcot Syndrome (medulloblastoma with familial adenomatous polyposis)
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