Dysembryoplastic neuroepithelial tumor
Dysembryoplastic neuroepithelial tumors are rare, indolent, low-grade tumors found in children and young adults. Most commonly affecting the temporal
Mar. 22, 2021
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This article includes discussion of Turcot syndrome, brain tumor polyposis syndrome, glioma-polyposis syndrome, familial adenomatous polyposis coli, and hereditary nonpolyposis colorectal cancer. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Turcot syndrome is a genetic disorder clinically comprised of an association of primary neuroepithelial tumors of the central nervous system with familial adenomatous polyposis coli (APC) or hereditary nonpolyposis colorectal cancer. This article describes the pathogenesis and diagnosis of this syndrome. The management of patients with Turcot syndrome takes into consideration both the CNS lesions and colorectal lesions. Early detection of brain tumors in patients with familial adenomatous polyposis coli might improve outcome. Therefore, surveillance for brain tumors is considered worthwhile in these patients.
• Turcot syndrome is an association of primary neuroepithelial tumors of the central nervous system with familial adenomatous polyposis coli or hereditary nonpolyposis colorectal cancer.
• Turcot syndrome is a genetic disorder associated with mutations of 2 germline genes in each individual.
• An important differential diagnosis is metastatic brain tumor in cases with colorectal carcinoma.
• Early detection of brain tumors in patients with familial adenomatous polyposis coli might improve outcome.
• Prognosis in advanced cases is poor, and death is usually due to malignant brain tumor, but some patients die due to colorectal malignancy.
• An understanding (and classification) of the disease at the genetic level is likely to lead to the most impactful advances in its management.
Turcot syndrome has been described as the association of primary malignant tumors of the CNS with adenomatous polyposis coli. The first case of polyposis coli associated with a medulloblastoma, as well as thyroid carcinoma, was described in a case report in 1949 (07). In 1959, Turcot described 2 teenaged siblings with multiple adenomatous polypi of the colon that developed into adenocarcinoma and malignant CNS tumors, medulloblastoma involving the spinal cord in 1 sibling and glioblastoma multiforme in the other (60). The gene for adenomatous polyposis coli was mapped and cloned in 1991 (17; 44). Familial adenomatous polyposis coli, Turcot syndrome, Gardner syndrome, and a few other syndromes were later considered to be associated with mutations in adenomatous polyposis coli gene. Another type of germline genetic defect, the mutation of a mismatch repair gene usually found in hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome, was demonstrated in 1995 in the family originally described by Turcot (19). Controversy persists regarding the mode of inheritance and whether Turcot syndrome constitutes a distinct genetic disorder. One common feature of these syndromes is association with inheritance of germline mutations in the DNA mismatch repair genes. It is now proposed that inheritance of 2 mismatch repair mutations in an individual along with the unique tumor spectrum should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir-Torre and termed Lynch III, to identify individuals with constitutively compromised mismatch repair associated with biallelic mutations (10). Turcot syndrome overlaps with “constitutional mismatch repair deficiency (CMMRD) syndrome”, a genetic disorder that results from biallelic germline mutations in 1 of the 4 MMR genes -- MLH1, MSH2, MSH6 or PMS2 – and manifests in childhood with a broad spectrum of cancer including mainly hematological, brain, and intestinal tract tumors. It includes cases of Lynch syndrome, and it is likely that the original 2 cases described by Turcot in 1959 were the first cases of constitutional mismatch repair deficiency and many cases described subsequently as Turcot syndrome should retrospectively be considered constitutional mismatch repair deficiency patients (65). The spectrum of tumors in constitutional mismatch repair deficiency is distinct from Lynch syndrome because malignant brain tumors are at least as frequent as gastrointestinal tumors, and in more than one third of cases, hematological malignancies have also been reported (02). Patients with constitutional mismatch repair deficiency may also show clinical features like those of neurofibromatosis type 1, especially café au lait spots.
At least 180 cases resembling Turcot syndrome have been reported in the literature to date. In some cases, the histological confirmation of the lesions is not available. Some of the case reports also include reviews of previously reported cases (51; 24; 23; 66; 05; 18; 58). Several classification systems have been proposed. Lewis proposed 3 groups (35):
(1) Cases in which siblings are affected and there is family history of brain tumors
A classification of glioma-polyposis syndrome based on a review of 127 cases is as follows (22):
(1) Cases of Turcot syndrome that had characteristic colonic and brain manifestations
A simple classification based on molecular evidence and genetic background divides Turcot into 2 entities (54):
(1) True Turcot syndrome (autosomal recessive). Intestinal polyps are large, fewer in number than 100, and are apt to undergo a malignant change. Associated brain tumor is usually a glioblastoma or an astrocytoma. Mismatch repair genes might be involved.
(2) Familial adenomatous polyposis-associated type (autosomal dominant). There is a predisposition to development of medulloblastoma.
Definition. The earlier cases of Turcot syndrome included only brain tumors of neuroepithelial origin, but some authors have reported other tumors as well. One of the original cases of Turcot had a 3 mm chromophobe adenoma of the pituitary in addition to the glioblastoma multiforme. Several other tumors of organs besides the colon and brain have been reported in some cases of Turcot syndrome. It is difficult to define the exact components of this syndrome. The synonym “glioma-polyposis complex,” sometimes used to describe the syndrome, does not adequately describe it because it restricts the brain tumor to glioma and the colon lesions to polyposis. Because neuroepithelial tumors other than gliomas and nonpolyposis colorectal cancer are recognized as components of Turcot syndrome, the following definition of Turcot syndrome would be more appropriate: Turcot syndrome is an association of primary neuroepithelial tumors of the central nervous system with familial adenomatous polyposis coli or hereditary nonpolyposis colorectal cancer. It is generally agreed that CNS tumors of nonneuroepithelial origin such as meningiomas, pituitary tumors, craniopharyngioma, and CNS lymphoma should not be included as components of Turcot syndrome.
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