Other syndromes associated with thyroid cancer

1) Familial Adenomatous Polyposis (FAP)

Familial adenomatous polyposis is inherited as an autosomal dominant trait caused by a germline mutation in the adenomatous polyposis coli (APC) gene. Patients typically have thousands of adenomas that are primarily located in the colon and rectum. Virtually all patients will progress to colorectal cancer. Patients may have extraintestinal manifestations that include osteomas, dental abnormalities, epidermal cysts, desmoids tumors, congenital hypertrophy of the retinal pigment epithelium (CHRPE), hepatoblastoma, medulloblastoma, and thyroid cancers.

Patients with FAP are at risk for developing papillary thyroid carcinoma (PTC). Young women with FAP are at particular risk of developing thyroid cancer, with risk approximately 160 times higher than that of normal individuals, and PTC occurs with a frequency about 10 times that expected for sporadic PTC. It is typically bilateral and multifocal. The overall prognosis for FAP-associated-PTC is similar to that of classical variants of PTC.

Thyroid tumors: PTC with cribriform pattern

2) Gardner's Syndrome

It is autosomal dominant inherited syndrome. As with FAP, Gardner's Syndrome is caused by a germline mutation in the adenomatous polyposis coli (APC) gene. In this variant of FAP, polyposis of the large bowel is associated with the extracolonic manifestations of supernumerary teeth, fibrous dysplasia of the skull, osteomas of the mandible, fibromas, desmoid tumors, epithelial cysts, hypertrophic retinal pigment epithelium, upper gastrointestinal tract hamartomas, hepatoblastomas, and thyroid tumors. Thyroid neoplasms occur at a young age (below 30 years) and in women. The overall risk of developing thyroid cancer is 2% to 12%.

Thyroid tumors: PTC

3) Cowden's Syndrome (PTEN-Hamartoma Tumor Syndrome)

Cowden's syndrome is an autosomal dominant disorder caused by a germline mutation in PTEN (phosphatase and tensin homolog, deleted on chromosome 10) and characterized by the development of multiple hamartomas and carcinomas of the thyroid, breast, and uterus.

The most frequent extracutaneous manifestations of this disease are thyroid neoplasms, both benign neoplasms and follicular thyroid cancers, occurring in approximately two-thirds of the subjects. The majority of thyroid lesions are multicentric, bilateral, benign, and malignant. Up to 66% of patients have thyroid involvement. Follicular thyroid carcinoma is the most common thyroid malignant tumor in patients with PTEN-hamartoma tumor syndrome. It is multicentric, and progress from a preexisting follicular adenoma. PTC is very rarely associated Cowden syndrome.

Thyroid tumors: FTC and PTC

4) Carney's Complex

Carney's Complex is an autosomal dominant inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity, (cardiac) myxomas, schwannomas, adrenal and pituitary tumors. Skin pigmentation anomalies include lentigines and blue nevi. Myxomas can occur at multiple sites such as the heart, skin or soft tissue, external auditory canal, and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. These patients may also present with testicular tumors. Carney's Complex type 1 is associated with a mutation in the PPRKAR1alpha gene.

The most common endocrine gland involvements are growth hormone (GH)-secreting pituitary adenomas (acromegaly), thyroid tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome due to primary pigmented nodular adrenocortical disease. The presence of thyroid nodules is very common. The thyroid is multinodular with multiple adenomatous nodules and follicular adenomas. The risk of thyroid cancer has been reported between 4% and 60%. Both PTC and follicular thyroid carcinomas (FTC) are reported.

Thyroid tumors: PTC, FTC

5) Werner's Syndrome

Werner's syndrome is inherited autosomal recessive connective tissue disease. It is result of mutation in the WRN gene. It is a rare premature aging syndrome that begins in the third decade of life. It is characterized by elderly thin skin appearance with wrinkles, alopecia, and muscle atrophy in proportion to the patient’s age. The patients with this syndrome have short stature. Patients also may have diabetes, osteoporosis, cataracts, peripheral vascular disease, or different types of malignant tumors (sarcomas and osteosarcomas). Malignancy and cardiac disease are the most common causes of death in these patients, who have a median life expectancy of 54 years. Patients present at a younger age and have approximately a threefold increased risk for follicular carcinoma and six times increased risk for developing anaplastic thyroid carcinoma. The risk of PTC is increased, specifically in Caucasian populations. The prevalence of thyroid cancer in Werner's syndrome is in up to 18% of the patients and a routine thyroid screening in these patients is advisable.

Thyroid tumors: FTC, PTC, anaplastic

6) Papillary Renal Neoplasia

Papillary Renal Neoplasia is rare disease characterized by presence of the combination of PTCs, benign thyroid nodules, and papillary renal neoplasia (genetic mutation of PRN1 locus on chromosome 1q21).

Thyroid tumors: classical variant of PTC

7) McCune-Albright Syndrome

The McCune-Albright syndrome is characterized by cafe-au-lait skin spots, polyostotic fibrous dysplasia and hyperfunctioning endocrinopathies, such as precocious puberty, hyperthyroidism, GH excess, and Cushing's syndrome. It is due to mutations in the gene encoding the Gs protein alpha subunit coupling 7-transmembrane-domain receptors to adenylate cyclase, leading to constitutive adenylate cyclase activation and cAMP overproduction. Involvement of the thyroid gland in the McCune-Albright Syndrome (MAS) is a common and sometimes overlooked feature of this disorder. Thyroid cancer has been described with MAS.

Thyroid tumors: PTC, clear cell

8) Turcot’s Syndrome

Turcot's syndrome (glioma-polyposis) is a rare hereditary disorder characterized by association of colonic polyposis (large intestine polyps) with primary tumors of the central nervous system (brain tumors, predominantly medulloblastoma). Gene APC on 5q21

Thyroid tumors: PTC


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