Familial Non-Medullary Thyroid Carcinoma
Familial Non-Medullary Thyroid Carcinoma (FNMTC)
Thyroid carcinomas can be sporadic or familial. Familial thyroid cancer syndromes are classified into familial medullary thyroid carcinoma (MTC), derived from calcitonin-producing C cells, and familial non-medullary thyroid carcinoma, derived from follicular cells. Familial Non-Medullary Thyroid Carcinoma (FNMTC) referred to papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) that have genetic component and develop within the same family. FNMTC develops with PTC in 90% - 95% of patients and in the remaining 5% - 10% with FTC. FNMTC tumors account for about 5% of cases of all non-medullary thyroid cancers. FNMTC is more aggressive than sporadic non-medullary differentiated thyroid cancer. It tends to affect younger patients, the tumors are often multifocal and bilateral, with higher rate of extrathyroidal invasion and lymph node metastasis.
There are following genetic syndromes that characterized by increased incidence of PTC and FTC: Familial Adenomatous Polyposis (FAP), Gardner's Syndrome, Cowden's Syndrome (or PTEN hamartoma tumor syndrome), Carney's Complex, Werner's Syndrome, Papillary Renal Neoplasia, McCune-Albright Syndrome. FNMTC is divided into two groups. The first includes familial syndromes characterized by a predominance of non-thyroidal tumors, such as familial adenomatous polyposis (FAP), PTEN hamartoma tumor syndrome (PHTS), Carney's complex type 1, and Werner's syndrome. The second group includes familial syndromes characterized by a predominance of FNMTC, such as pure familial PTC, familial PTC with papillary renal cell carcinoma, and familial PTC with multinodular goiter. These syndromes are described on this page.
In order to be diagnosed with FNMTC syndrome, other genetic syndromes, such as Gardner's Syndrome, Cowden's Syndrome, Carney's Complex, Werner's Syndrome and so on, should be ruled out. The risk of developing thyroid cancer is 5 to 10 times higher in individuals with a first-degree relative who has thyroid cancer than in the general population. That risk is higher when the family member is a sibling and even higher when a sister is affected, especially for early-onset thyroid cancers, such as papillary thyroid cancer. When three or more first-degree family members are affected a familial predisposition is highly likely in over 94% of cases.
Diagnosis of FNMTC is established when two or more first-degree family members are affected by thyroid cancer. All patients being evaluated for a thyroid disorder or tumor should have a comprehensive history to identify a family history of thyroid cancer. Relatives of the patient with thyroid cancer should be screened for thyroid nodules with neck ultrasound, and if thyroid nodule(s) detected, biopsy is recommended. At present time, the predisposing genetic factors and the optimal screening criteria are unclear and the genetic abnormality leading to FNMTC is unknown. Despite on lack of strong evidence, the screening of unaffected family members has been suggested to initiate at age 20 (or 10 years earlier than the youngest age of diagnosis within the family) with thyroid ultrasonography.
At minimum a total thyroidectomy is recommended to remove all the thyroid tissue, which harbors the genetic defect responsible for the disease, even in low-risk patients, due to the predisposition to develop thyroid cancer and the more aggressive nature of the disease. Total thyroidectomy with a routine prophylactic central neck lymph node dissection (epecially for tumor bigger than 1 cm) is the best surgical treatment for patients with FNMTC because these patients have predisposition to tumor formation in any remaining follicular cells and have increased risk of lymph nodes metastases. They have a high rate of multicentric disease, and they may have more aggressive disease with extra thyroidal invasion, lymph node metastasis, and higher recurrence rates. If lymph node involvement is present in the lateral neck by preoperative neck ultrasound or by physical examination, a therapeutic lymph node dissection should also be performed. The advantage of such an aggressive approach is similar to that observed for patients with sporadic disease because it allows for more effective treatment with radioiodine ablation, allows serum thyroglobulin levels to be used to detect persistent/recurrent disease, and may be associated with a lower risk of recurrent or persistent disease. Some experts are recommending to perform a prophylactic total thyroidectomy in patients with thyroid nodules and two affected family members (Mazeh et al.).
Prognosis and Survival
Patients with FNMTC have cancer recurrences more common than with sporadic PTC or FTC. There are not enough data to suggest that survival is worse in patients with FNMTC, but there are some literature that describes worsened survival in patient with FNMTC if three or more family members are affected (Mazeh et al.).
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