Exp Clin Endocrinol Diabetes 2014; 122 - P093
DOI: 10.1055/s-0034-1372110

Impact of integrated molecular diagnostics of air-dried Fine Needle Aspiration (FNA) smears of patients with nodular thyroid disease in a routine diagnostic setting

M Eszlinger 1, M Neustadt 1, I Ruschenburg 2, A Neumann 3, C Franzius 4, C Landvogt 5, S Adam 6, R Hammoser 7, T Molwitz 8, A Hach 9, B Feldmann 10, S Gratz 11, W Braun 12, D Graf 13, B Amro 14, R Niemann 15, R Santen 16, R Paschke 1
  • 1Universitätsklinikum Leipzig AöR, Klinik für Endokrinologie und Nephrologie, Leipzig, Germany
  • 2MVZ wagnerstibbe für Gynäkologie, Reproduktionsmedizin, Zytologie, Pathologie und Innere Medizin GmbH, Einbeck, Germany
  • 3MVZ wagnerstibbe für Laboratoriumsmedizin, Gynäkologie, Humangenetik und Pathologie GmbH, Hannover, Germany
  • 4Zentrum für Nuklearmedizin und PET/CT, Bremen, Germany
  • 5Praxis für Nuklearmedizin und PET/CT-Zentrum in der Deutschen Klinik für Diagnostik, Wiesbaden, Germany
  • 6Radiologie Hoheluft, Nuklearmedizin, Hamburg, Germany
  • 7Schilddrüsenpraxis Kantstraße, Berlin, Germany
  • 8Klinik Dr. Hancken, Stade, Germany
  • 9Institut für Radiologie und Nuklearmedizin, Bremerhaven, Germany
  • 10Praxis Endokrinologie und Diabetologie im Zentrum, Stuttgart, Germany
  • 11Radiologie Zentrum, Stuttgart, Germany
  • 12Schilddrüsenpraxis Nuklearmedizin, Augsburg, Germany
  • 13Praxisgemeinschaft auf dem Meere, Lüneburg, Germany
  • 14Praxis für Nuklearmedizin, Oldenburg, Germany
  • 15Praxis Steen und Partner, Radiologie, Oldenburg, Germany
  • 16Endokrinologische Gemeinschaftspraxis, Frankfurt/Main, Germany

After a first retrospective study we now report the first 12 month results of molecular diagnostics analyzing BRAF, RAS, RET/PTC, and PAX8/PPARG mutations in routine air-dried FNA smears instead of fresh FNA material.

RNA and DNA was extracted from 321 consecutive routine air-dried FNA cytology smears (75 FNA smears with follicular neoplasia (FN), 195 FNA smears with microfollicular proliferation (MFP), 48 FNA smears with the cytological diagnosis of papillary carcinomas (PTC) and 3 FNA smears with the cytological diagnosis suspicious for malignancy (MAL). 3 PAX8/PPARG, 2 RET/PTC1 and 3 RET/PTC3 rearrangements were detected by qPCR, while 33 BRAF and 16 RAS point mutations were detected by pyrosequencing.

For the 75 FN-FNA, 195 MFP-FNA, 48 PTC-FNA and 3 MAL-FNA, NRAS mutations could be detected in 2/9/1/0 FNA samples, respectively. HRAS mutations were detected in 1/2/0/0 samples, respectively. A KRAS mutation was detected in 1/0/0/0 sample. BRAF mutations were detected in 1/3/29/0 samples, respectively. The corresponding histologic results for 26 surgeries showed 24 PTC, 2 follicular Variant PTCs. PAX8/PPARG was detected in 0/3/0/0 samples. RET/PTC1 was detected in 0/0/2/0 samples. RET/PTC3 was detected in 0/3/0/0, respectively. In total, 6.7% FN-FNA, 10.3% MFP-FNA, 66.7% PTC-FNA and 0% MAL-FNA samples harbored a mutation, respectively.

These results confirm the feasibility of molecular diagnostics of air-dried FNA smears in a routine diagnostic setting. BRAF positive FNA smears with the cytological diagnosis PTC can result in more primary total thyroidectomies instead of diagnostic lobectomies followed by completion thyroidectomy after histologic diagnosis. The molecular analysis of borderline cases with MFP can lead to important additional information with likely clinical consequences, whereas the molecular analysis of FN samples provided further specific arguments for a diagnostic surgery for mutation positive samples.