GENETIC PREDISPOSITION IN
NON-MEDULLARY THYROID CANCER
Non-medullary
thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and
is classified into 4 groups: papillary, follicular, Hurthle and anaplastic. In NMTC
there is a small, but clinically significant, percentage of patients (ranging
from 5% to 15 %) with a genetic predisposition for the development of the
disease. In contrast to familial medullary thyroid carcinoma (FMTC), which is
associated with well-known genetic alterations, the case for a familial predisposition
of NMTC is only now beginning to emerge. In the absence of high-penetrance
Mendelian-type causative genes, the genetic factors can likely be attributed to
many low-penetrance DNA variants in the human genome. Familial NMTC (FNMTC) is
characterized ty three or more first-degree relatives with follicular-derived
NMTC, and includes two groups: (a) syndromes characterized by a predominance of
non-thyroidal tumors (such as familial adenomatous polypis and PTEN-hamartoma
tumor syndrome), and (b) familial
syndromes characterized by predominance of papillary thyroid carcinoma (PTC),
such as pure familial PTC (FPTC), FPTC associated with papillary renal cell carcinoma,
and FPTC with multinodular goiter. Some characteristic morphologic findings should alert the pathologist of
a possible familial cancer syndrome, which may lead to further molecular
genetics evaluation. For example, the presence of multifocal, multinodular,
and bilateral thyroid neoplasms is suggestive of a familial disease. The risk
for NMTC development is significantly increased (up to eightfold) among
first-degree relatives. Interestingly, this risk is also increased among
second-degree relatives (x 2.5), and in third-degree relatives (x 1.7). This information
has obvious clinical implications for the screening of members of families with
a strong family history of NMTC
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