Medullary thyroid carcinoma diagnosed with liquid-based cytology and immunocytochemistry

J Immunoassay Immunochem. 2022 Sep 3;43(5):502-515. doi: 10.1080/15321819.2022.2070025. Epub 2022 Apr 27.


Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy that arises from the parafollicular cells (C cells) secreting calcitonin. This study summarizes our experience in the diagnosis of MTC with ultrasound-guided thyroid FNA, subsequently processed with liquid-based cytology (LBC) and immunocytochemistry (ICC). We searched our laboratory archives for thyroid FNA cases with an interpretation of positive or suspicious for MTC, during the period 2004-2018. A total of 20 cases (18 thyroid FNAs; two lymph node FNAs) were selected and included in this study. These displayed high cellularity and a discohesive pattern, with a few loose syncytial groups. There was some variation in the cell size and shape both across and within our cases. Most MTCs (n = 15) exhibited a predominant plasmacytoid/epithelioid cell morphology, whereas five of our cases showed a spindle cell pattern. Of interest, none of eight MTC microcarcinomas (≤1 cm) showed a spindle cell morphology. Amyloid was found in 11/20 cases (55%), while binucleation/multinucleation in 17/20 (85%), and nuclear pseudoinclusions in 3/20 MTC cases (15%). Nuclei exhibited a granular, "salt and pepper" chromatin in all cases. ICC was performed in 18/20 cases (90%). Calcitonin, CEA, TTF1, and Chromogranin were positive wherever applied, whereas thyroglobulin and CK19 were negative. In conclusion, ultrasound-guided thyroid FNA - processed with LBC and ICC - is a reliable modality to detect MTC preoperatively, facilitating the management of such patients.

Keywords: Medullary thyroid carcinoma; biomarkers; calcitonin; cytopathology; fine-needle aspiration (FNA); immunohistochemistry; neuroendocrine tumor; thyroid cancer.

MeSH terms

  • Biopsy, Fine-Needle
  • Calcitonin*
  • Carcinoma, Neuroendocrine
  • Humans
  • Immunohistochemistry
  • Thyroid Neoplasms* / diagnosis


  • Calcitonin

Supplementary concepts

  • Thyroid cancer, medullary