Endocrinol Metab.  2010 Dec;25(4):354-359. 10.3803/EnM.2010.25.4.354.

A Case of Concurrent Papillary Thyroid Carcinoma in Familial Medullary Thyroid Microcarcinoma with a Germline C634W Mutation

• Kim JH
• Park JH
• Park TS
• Baek HS
• Chung MJ
• Hong KH

• KMID: 1497762
• DOI: http://doi.org/10.3803/EnM.2010.25.4.354

Abstract

The origins of medullary carcinoma (MTC) and papillary carcinoma (PTC) of the thyroid are embryologically different. Tumors showing concurrent medullary and papillary features are rare and they represent less than 1% of all thyroid malignancies. Hereditary MTC is an autosomal dominantly inherited disease which is genetically determined as part of the MEN 2A, MEN 2B, or variants of MEN 2A such as familial MTC. Germline mutations of the RET gene are the underlying cause of the majority of cases of hereditary medullary carcinomas. The pathogenesis of concurrent PTC with familial MTC has rarely been known. Genetic analysis of the RET oncogene has so far provided conflicting results. Here we describe a family whose sibling was affected by both PTC & MTC, and the family carried a germ-line point mutation in the RET extracellular domain that converted cysteine 634 into tryptophan (C634W).

Keyword

Concurrent; Medullary; Papillary

MeSH Terms

Carcinoma
Carcinoma, Medullary
Carcinoma, Papillary
Cysteine
Factor IX
Germ-Line Mutation
Humans
Multiple Endocrine Neoplasia Type 2a
Multiple Endocrine Neoplasia Type 2b
Oncogenes
Point Mutation
Siblings
Thyroid Gland
Thyroid Neoplasms
Tryptophan
Carcinoma
Cysteine
Factor IX
Thyroid Neoplasms
Tryptophan

Figure

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  Fig. 1 Family pedigree.

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  Fig. 2 Computed tomography scan showed 2.2 cm sized hypodense enhancing mass (arrows) in right lobe.

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  Fig. 3 Direct sequence analysis of the RET gene in the patient. A heterozygous missense mutation (c.1902C > G;p.Cys634Trp) was identified in the patient (arrow).

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  Fig. 4 Histology of the resected thyroid gland. (A) Papillary carcinoma. The tumor shows papillary fronds lined by cells with the nuclear characteristics of papillary carcinoma (H&E, × 200). (B) Medullary carcinoma. The tumor shows trabecular pattern composed of cells with ill-defined granular cytoplasm (H&E, × 200). (C) Immunochemical staining (× 400). The tumor cells of the smallest mass are calcitonin positive.

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