Papillary Thyroid Carcinoma Associated with Primary Light-Chain Amyloidosis and RET codon 691 and 982 Polymorphisms: Evolution after Autologous Stem-Cell Transplant

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 414-428-Thyroid Neoplasia & Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-422
Beatriz Lecumberri*, Jesús Solera, Dolores Hernández, Paola Parra, Miguel Angel Canales, Manuel Nistal and Luis Felipe Pallardo
La Paz University Hospital, Madrid, Spain
Introduction: Medullary thyroid cancer (MTC) is the type of thyroid cancer usually associated with amyloidosis (AA) either primary or secondary. There are only ten reported cases of papillary thyroid carcinoma (PTC) associated with AA, and only in two a primary origin was confirmed. We report the first patient diagnosed with PTC and primary systemic light-chain amyloidosis (LA-AA) that has been treated with an autologous stem-cell transplant (ASCT) and in whom RET genetic study has been performed. Clinical Case: A 55-year-old female patient with a history of a follicular variant of PTC operated in 2001 after a Graves' disease (GD), was referred to us. Her 3 children had suffered GD, the daughter also a follicular thyroid carcinoma, and 2 sons displayed coagulopathies, one being a Von Willebrand disease. Her sister was operated for a lingual osteoma. She had nephrotic syndrome, atrial fibrillation and a hemostatic dysfunction showing hypercoagulability. Monoclonal lambda chain was detected in serum and a biopsy of subcutaneous fat confirmed amyloidotic infiltration. An autologous stem-cell transplantation (ASCT) performed after Dexametasone/Bortezomib treatment significantly improved her renal and cardiac dysfunction with disappearance of the nephrotic syndrome. RET oncogene genetic study revealed that the index patient was homozygous for the SNP c.2071 G>A (p.Gly691Ser) that alters the primary structure of the protein, and heterozygous for the SNP c.2994 C>T (p.Arg982Cys) at RET exon 18. Her sister, 2 sons and one of her 3 grandchildren were heterozygous for both polymorphisms, but her daughter was only heterozygous for the 691 variant and had not inherited the 982 one. The 691 variant has been described more frequently in patients with radiation-induced human thyroid tumours and it's been proposed that the 982 variant could raise the risk for Hirschsprung's disease. Conclusion: Based on this case and her excellent response to ASCT with almost complete recovery of her renal amyloidotic dysfunction, we conclude that the presence of a PTC is not incompatible with LA-AA, and that an early diagnosis and correct treatment of both are critical to achieve the best possible outcome in each patient. More research is needed to define the specific roles of the RET codon 691 and 982 polymorphisms in the pathogenesis of PTC, their relationship, if any, with LA-AA, and their potential value in genetic counselling.

Nothing to Disclose: BL, JS, DH, PP, MAC, MN, LFP

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