Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods

Abstract

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.

Keywords: cytology; fine-needle aspiration; medullary thyroid carcinoma; sensitivity; specificity; thyroid.

Figure 1

Cytomorphologic features of MTCs in the discordant group. (A) Round cells formed loosely cohesive clusters, making a diagnosis of FLUS or SFN (Romanowsky, ×400). (B,C) Polygonal tumor cells with abundant cytoplasm or cytoplasmic granules ((C); arrowhead), making a diagnosis of Hurthle cell neoplasm or FLUS ((B) Papanicolaou, ×400; (C) Liu, ×400). (D,E) Intranuclear cytoplasmic pseudoinclusion (center) mimicking papillary thyroid carcinoma ((D) Papanicolaou, ×400; (E): Liu, ×400). (F) A few plasmacytoid cells with preserved background colloid prompted an indeterminate diagnosis of AUS/FLUS (Papanicolaou, ×200).

Figure 2

The receiver operating characteristic (ROC) curve of the cytomorphologic scoring. The performance of discrimination was satisfied, with an area under the ROC curve (AUC) of 75.4% (95% CI, 68.1–81.7%).