ABSTRACT
OBJECTIVE: We report the case of a female patient with multiple endocrine neoplasia type 2A (MEN2A) who was found to have a double mutation in the RET (rearranged during transfection) proto-oncogene. METHODS: RET mutational analysis was performed by Sanger DNA sequencing. RESULTS: The proband was a compound heterozygote for the RET germline mutations Val648Ile and Val804Leu on exons 11 and 14, respectively. Genetic analysis of family members showed the presence of the Val648Ile mutation in all except 1 daughter who carried the Val804Leu mutation. However, none of them showed any clinical, biochemical, or histologic signs of neoplastic disease either in the thyroid or adrenal gland. Furthermore, a daughter and the proband's sister who underwent a prophylactic thyroidectomy did not show pathologic evidence of C-cell disease. CONCLUSIONS: We hypothesize that the combined effect of the 2 mutations may have induced the development of pheochromocytoma (PHEO) in our patient. Thus, in the presence of single RET-induced mild medullary thyroid cancer (MTC) phenotype, the search for additional genetic anomalies may lead to the discovery of rare but potentially more aggressive double mutation genotypes.
Subject(s)
Adrenal Gland Neoplasms/genetics , Amino Acid Substitution , Germ-Line Mutation , Multiple Endocrine Neoplasia Type 2a/genetics , Pheochromocytoma/genetics , Proto-Oncogene Proteins c-ret/genetics , Adrenal Gland Neoplasms/pathology , Base Sequence , DNA Mutational Analysis , Female , Humans , Isoleucine/genetics , Leucine/genetics , Middle Aged , Molecular Sequence Data , Multiple Endocrine Neoplasia Type 2a/pathology , Pedigree , Pheochromocytoma/pathology , Proto-Oncogene Mas , Valine/geneticsSubject(s)
Carcinoma/pathology , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Thyroid Neoplasms/pathology , Carcinoma/drug therapy , Carcinoma/surgery , Carcinoma, Papillary , Female , Goiter/surgery , Humans , Middle Aged , Thyroid Cancer, Papillary , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/surgeryABSTRACT
OBJECTIVE: To describe a rare case of ectopic intrathyroidal parathyroid cyst (PC) in a 29-year-old woman who had been referred to us because of a multinodular goiter. METHODS: We review the clinical, laboratory, and radiographic findings as well as the treatment in our patient and provide a brief discussion of the associated literature. RESULTS: Ultrasonography of the neck showed the presence of 2 thyroid nodules in the left lobe, the larger of which was solid and the smaller of which had a cystic appearance. A small nodular area was also found in the right thyroid lobe (diameter, less than 8 mm). A thyroid scan performed with technetium showed the absence of uptake by both left lobe nodules. Fine-needle aspiration biopsy (FNAB) of the 2 major nodular lesions revealed that the larger thyroid nodule was benign and the smaller was a cyst with clear fluid. Measurement of parathyroid hormone in the FNAB fluid showed a high concentration, suggestive of the diagnosis of PC. Normal serum levels of parathyroid hormone and calcium indicated that it was a nonfunctioning intrathyroidal PC. The PC disappeared after FNAB, but the lesion recurred 3 months later. Therefore, the patient underwent near-total thyroidectomy. Histologic examination confirmed the diagnosis of intrathyroidal PC, and a papillary microcarcinoma (6 mm in diameter) was found in the right lobe of the thyroid. CONCLUSION: Although an ectopic intrathyroidal PC is rare, the frequency of occult papillary microcarcinoma of the thyroid is high. The association we describe, however, should be considered incidental. To our knowledge, this is the first report of an association of an intrathyroidal PC with papillary microcarcinoma of the thyroid.
