FINDINGS NECESSITATING GENETIC TESTING IN PATIENTS
WITH THYROID CANCER.
1.
Coexistance of numerous (thousands) of polyps in the
colon and rectum.
a.
Familial adenomatous polyposis (FAP) should be
suspected.
b.
The risk of papillary thyroid cancer (PTC) is 160
times higher in women with FAP than that in the general population
c.
PTC occurs with a frequency about 10 times higher than
sporadic PTC. PTC is often bilateral and multifocal.
d.
FAP is caused by a germline mutation of the APC gene.
2.
Coexistance of numerous adenomatous polyps in the
colon / rectum in association with extracolonic manifestations such as fibrous
dysplasia of the skull, osteomas of the mandible, desmoid tumors etc.
a.
Gardner’s syndrome (a variant of the FAP, see above)
should be suspected.
b.
The risk of thyroid cancer development ranges from 2
to 12 %.
c.
Gardner’s syndrome is due to a germline mutation of
the APC gene.
3.
Macrocephaly
a.
Coweden’s syndrome and Bannayan-Riley-Ruvalcaba
syndrome (PTEN-Hamartoma Tumor Syndrome) should be suspected.
b.
Thyroid lesions are often bilateral (typically follicular
cancer, often multicentric).
c.
Coweden’ syndrome is due to germline mutations in the
PTEN (phosphatase and tensin homolog) gene
4.
Premature aging (progeria)
a.
Werner syndrome should be suspected
b.
Increased risk for papillary or follicular thyroid
cancer and osteosarcoma/soft tissue sarcoma development
c.
Werner syndrome is due to mutations in the WNR gene
5.
Medullary thyroid cancer (MTC) (especially in
children)
a.
Multiple endocrine neoplasia type 2 (MEN2) should be
suspected
b.
MEN2A: parathyroid hyperplasia + MTC +
pheochromocytoma
c.
MEN2B: MTC + pheochromocytoma + mucosal neuromas +
marfanoid body habitus
d.
MEN2 syndrome is due to RET proto-oncogene mutations
6.
Tumors of the central nervous system (mainly
medulloblastoma) and polyps of the colon
a.
Turcot’s syndrome should be suspected
b.
Increased risk for papillary thyroid cancer
development
c.
Turcot’s syndrome is due either to a mutation in APC
associated with FAP or a mutation in one of the mismatch repair genes
associated with Lynch syndrome (MLH1
and PMS2).
7.
Spotty skin pigmentation, endocrine overactivity
(acromegaly, ACTH-dependent Cushing syndrome due to primary pigmented nodular
adrenocortical disease), cardiac myxomas, schannomas, adrenal and pituitary
tumors
a.
Carney’s complex type 1 should be suspected
b.
Associated with the presence of thyroid nodules (very
common)
c.
Risk of thyroid cancer (papillary / follicular):
ranges widely (between 4 % and 60 %)
d.
Carney’s complex type 1 is due to a mutation in the
PPRKAR1alpha gene
8.
Café-au-lait spots, polyostic fibrous dysplasia,
hyperfuctioning endocrinopathies (precocious puberty, hyperthyroidism, GH
excess, Cushing’s syndrome)
a.
McCune-Albright syndrome should be suspected
b.
Associated with thyroid nodules and thyroid cancer
(typically papillary)
c.
McCune-Albright syndrome is due to a postzygotic activating mutation of the
GNAS gene, coding
for the G protein subunit Gs alpha in the affected tissues
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