Pediatric Medullary Carcinoma of the Thyroid With Point Mutation of RET Proto-Oncogene Associated With Multiple Endocrine Neoplasia and Initially Diagnosed by Fine-Needle Aspiration Biopsy

Chiling Chai, MD, Luciano B. Lemos, MD, Margot Kaelbling, PHD, Mithra Baliga, MD


South Med J. 2003;96(3) 

In This Article

Abstract and Introduction

A 7-year-old girl presented with a thyroid mass, elevated serum levels of calcitonin and carcinoembryonic antigen, as well as multiple mucosal nodules in the upper lip and tongue. Cytologic material obtained by fine-needle aspiration biopsy from the thyroid mass was diagnosed as medullary carcinoma and confirmed by immunohistochemical studies in the cell-block sections. Subsequent histopathologic examination showed involvement of both thyroid lobes by medullary carcinoma, and electron microscopic studies further confirmed the diagnosis. Molecular studies showed a point mutation in amino acid 918 in exon 16 of the RET proto-oncogene. Biopsies from the upper lip and tongue showed mucosal neuromas. Fine-needle aspiration biopsy is frequently used in the initial evaluation of thyroid nodules. This case illustrates the value of fine-needle aspiration biopsy as a safe and accurate diagnostic modality in the workup of pediatric thyroid nodules. Fine-needle aspiration biopsy should always be considered for the investigation of thyroid nodules in pediatric patients.

Medullary carcinoma of the thyroid (MCT) is an uncommon malignant neoplasm arising from the parafollicular cells that produce calcitonin and carcinoembryonic antigen (CEA). It accounts for up to 10% of thyroid malignancies.[1] It may occur sporadically (70-80% of cases) or as a familial form (20% of cases) associated with multiple endocrine neoplasia (MEN) type 2. Sporadic MCT occurs primarily in middle-aged adults (aged 36 to 51 years) as unilateral enlargement of the gland. The familial form is seen in a younger population (aged 15 to 20 years); it is often multicentric, involving both lobes, and coexists with T-cell hyperplasia.[1] The combination of elevated serum calcitonin level plus a thyroid nodule is virtually pathognomonic of MCT.[2] The biologic behavior of MCT is ranked between the well-differentiated thyroid neoplasms and aggressive anaplastic carcinoma. The treatment approach is also more aggressive, with radical neck dissection recommended in all cases.

MCT is also disproportionately important because of its strong association with other neuroendocrine tumors and familial occurrence. Recently, molecular studies have demonstrated that patients with MEN 2A, MEN 2B, and familial MCT have specific sequence changes within the coding region of the RET proto-oncogene.[3] It has been recommended that thyroidectomy be performed as early as possible in children with the clinical manifestations of MEN 2B, such as the mucosal neuroma syndrome. Analysis of RET proto-oncogene mutation at codon 918 should be performed in all children born to parents with MEN 2B, as well as in children with ambiguous clinical features suggestive of MEN 2B.[4]

In pediatric patients, a thyroid nodule should always arouse suspicion of carcinoma, and the mass must be promptly investigated. Although the risk of relapse exists for young patients with thyroid carcinomas, the prognosis is very good when the disease is diagnosed early and properly treated.[5] Fine-needle aspiration biopsy (FNAB) has become a mandatory diagnostic tool in the preoperative diagnosis of thyroid nodules.[2] This safe, economic, and highly accurate technique has not been used as widely in children as it has been in adults.


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