Cancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past... Show moreCancer derived from thyroid follicular epithelial cells is common; it represents the most common endocrine malignancy. The molecular features of sporadic tumors have been clarified in the past decade. However the incidence of familial disease has not been emphasized and is often overlooked in routine practice. A careful clinical documentation of family history or familial syndromes that can be associated with thyroid disease can help identify germline susceptibility-driven thyroid neoplasia. In this review, we summarize a large body of information about both syndromic and non-syndromic familial thyroid carcinomas. A significant number of patients with inherited non-medullary thyroid carcinomas manifest disease that appears to be sporadic disease even in some syndromic cases. The cytomorphology of the tumor(s), molecular immunohistochemistry, the findings in the non-tumorous thyroid parenchyma and other associated lesions may provide insight into the underlying syndromic disorder. However, the increasing evidence of familial predisposition to non-syndromic thyroid cancers is raising questions about the importance of genetics and epigenetics. What appears to be "sporadic" is becoming less often truly so and more often an opportunity to identify and understand novel genetic variants that underlie tumorigenesis. Pathologists must be aware of the unusual morphologic features that should prompt germline screening. Therefore, recognition of harbingers of specific germline susceptibility syndromes can assist in providing information to facilitate early detection to prevent aggressive disease. Show less
This thesis, describes investigations of the genetic background of a wide variety of rare endocrine tumors, including those of the thyroid, parathyroid, adrenal and paraganglia. In the first part,... Show moreThis thesis, describes investigations of the genetic background of a wide variety of rare endocrine tumors, including those of the thyroid, parathyroid, adrenal and paraganglia. In the first part, our studies focus on the role of molecular testing in diagnostics and treatment decision making in patients with DICER1 syndrome or advanced radioactive iodine refractory thyroid cancer. In the second part, we investigated the of genetic background of pediatric non-medullary thyroid carcinoma. In the third part we focused on genetic counseling in the following endocrine tumor predisposition syndromes: CDC73-related disorder, SDHA-associated paraganglioma and MEN2a syndrome. Our studies contributed to the debate on accurate estimation of disease penetrance. In order to provide answers to the questions - “Why do I have cancer? Are other relatives at risk? And if so, can we prevent cancer?” - patient- and family centered endocrine cancer care encourages active collaboration between the departments of endocrinology, oncology, surgery, pathology, chemistry, radiology, nuclear medicine and clinical genetics. Show less
