Natural History Study of Children and Adults With Medullary Thyroid Cancer

Background: \- Medullary thyroid cancer (MTC) is a rare cancer of the thyroid gland. In children and adults, it is often part of a condition called Multiple Endocrine Neoplasia 2 (MEN2). MEN2 is usually caused by a genetic mutation, and it can cause a number of problems in addition to MTC. These problems include adrenal gland tumors, hormone changes, and problems with the bones and other organs. Not much is known about how MTC develops over time, especially in people with MEN2. Researchers want to study MTC in children and adults and see how it affects their growth and development. Objectives: \- To study how medullary thyroid cancer affects children and adults over time. Eligibility: \- Children and adults who have medullary thyroid cancer. Design: * Participants will be screened with a brief physical exam and medical history. Blood and tissue samples will be collected to see whether participants have the MEN2 genetic mutation. * Treatment will not be provided as part of this study. However, participants will be receiving standard care for MTC. They may be eligible for other clinical trials at the National Institutes of Health. * Participants will have regular study visits every 6 to 12 months to evaluate their MTC and any treatment. Blood tests, imaging studies, and other tests may be performed as needed to monitor the disease. * Participants and their parents/guardians will also complete questionnaires about their health and emotions during the study.

Background: * Medullary Thyroid Carcinoma (MTC) is a calcitonin producing tumor arising from the parafollicular C cells of thyroid. In children and adults, MTC is usually seen in association with Multiple Endocrine Neoplasia (MEN) 2A and 2B, which are rare cancer syndromes resulting from germline mutations of Rearranged during Transfection (RET) proto-oncogene. MTC develops in virtually all patients with MEN 2, and is the leading cause of death in these patients. Patients with MEN 2 may have other characteristic manifestations such as pheochromocytoma and hyperparathyroidism in MEN 2A and pheochromocytoma, ganglioneuromatosis, and skeletal deformities in MEN 2B. * Complete surgical resection is the only current curative treatment for MTC, and the tumor is unresponsive to standard chemotherapy and conventional doses of radiation therapy. However, more than half the patients present with advanced or metastatic disease and cannot be cured surgically. Novel agents are currently under investigation for treatment of MTC, and vandetanib, an oral RET and receptor tyrosine kinase (RTK) inhibitor was recently approved by the FDA for adults with advanced or metastatic MTC. Vandetanib also has activity in children with hereditary MTC. * However, complete responses to RTKs have not been observed, and some patients develop resistance to the treatment with RET and RTK inhibitors or have primary refractory disease. The natural history of MTC, particularly in patients with MEN 2, the molecular pathways involved in tumorigenesis, and the development of resistance to targeted therapies are not well understood. Objectives: -The overall objective of this longitudinal study is to develop a better understanding of the biology and natural history of MEN2 with or without MTC, particularly in children and adults with MEN 2A and 2B, as well as study non-tumor manifestations of MEN 2. This will hopefully allow for developing more effective treatment interventions for tumor and non-tumor related manifestations, and more sensitive endpoints in clinical trials. Eligibility: * Patients, must have histologically or cytologically confirmed MTC, confirmed by the Laboratory of Pathology, NCI or who have MEN2 (regardless of MTC status). * Parent or primary caregiver of patient participant (\<= 21) * Participants may be undergoing standard care or receiving treatment on a clinical trial while participating in this study. Design: This study will allow for longitudinal evaluations of MTC and MEN2 and non-tumor related manifestations of MEN 2A and 2B in children and adults. Evaluations will consist of the following (summarized): 1. Clinical and radiological evaluations 2. Detailed pathologic and molecular analysis of tumor specimens will be performed, including immunohistochemistry (IHC), comparative genomic hybridization (CGH), and genome sequencing. CGH and genome sequencing will be performd with co-enrollment on protocol 10-C-0086 Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of a Repository for Related Biological Studies.