Familial thyroid carcinoma: a diagnostic algorithm

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Thyroid carcinomas, particularly papillary thyroid carcinoma (PTC), are common endocrine malignancies.
• While mostly sporadic, familial forms of thyroid cancer exist, classified as familial medullary thyroid carcinoma and familial nonmedullary thyroid carcinoma.
• Multifocal papillary thyroid carcinoma is a frequent presentation of familial nonmedullary thyroid carcinoma.

Purpose of the Study:

• To review the classification and clinico-pathologic features of familial thyroid cancer syndromes.
• To highlight morphologic findings that suggest a familial cancer syndrome.
• To emphasize the importance of molecular genetic evaluation in suspected cases.

Main Methods:

• Review of existing literature on familial thyroid cancer syndromes.
• Classification of familial syndromes based on associated nonthyroidal tumors or predominance of non-medullary thyroid carcinoma (NMTC).
• Description of characteristic morphologic findings for pathologists.

Main Results:

• Familial nonmedullary thyroid carcinoma (FNMTC) is divided into two groups: those with nonthyroidal tumors and those with NMTC predominance.
• Familial medullary thyroid carcinoma (FMTC) accounts for 20-25% of cases and is linked to MEN IIA, IIB, or pure familial syndromes.
• C-cell hyperplasia is the precursor lesion for heritable medullary thyroid carcinoma syndromes.

Conclusions:

• Recognizing morphologic features suggestive of familial thyroid cancer is crucial for early diagnosis.
• Familial thyroid cancer syndromes require careful clinico-pathologic evaluation and consideration for genetic testing.
• Prompt identification can guide further molecular genetic evaluation and management.