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每月一例 2015 December • A 32-year-old woman was healthy and denied any systemic disease. • Multiple thyroid nodules were found incidentally during a routine healthy check. Ultrasound examination revealed multiple nodules in both lobes of the thyroid, with a hypoechoic one, 0.8 cm, in the left lobe. • Thyroid function was within normal limits. No other lesions were identified in the head and neck area. Clinical presentation • Fine needle aspiration of the nodule was performed and the aspirate was submitted to the cytology laboratory as one ethanol-fixed smear for Papanicolaou stain, one airdried smear for Liu’s stain, and one SurePath BD CytoRichTM vial for liquid-based preparation (Becton, Dickinson and Company). Your interpretation ? PTC ? Variant ? Cytology findings • The smears showed moderate cellularity in a clean background devoid of colloid and blood. It consisted of loosely cohesive three-dimensional and mono-layer clusters of cells. • Occasional papillary fragments with vascular cores were present. • Pseudostratified epithelium composed of cigar-shaped, elongated hyperchromatic nuclei in a picket-fence-like arrangement was apparent. • Nuclear grooves and intranuclear pseudoinclusions were found in very limited area. Diagnosis Papillary thyroid carcinoma (PTC), columnar cell variant Differential diagnosis • Papillary thyroid carcinoma, tall cell variant • Metastatic endometrioid or colorectal adenocarcinoma • Upper respiratory epithelial cells contamination from the aspiration procedure DDx: Papillary thyroid carcinoma, tall cell variant • The criteria of tall cell variant PTC was recently lowered to over 50% of cancer cells with 2-3:1 height/width ratio. • The nuclei frequently have the characteristic classic PTC features showing oval and optically clear nuclei with nuclear grooves and pseudoinclusions. • Therefore, it is easy to be interpreted as a PTC. • However, you will find loosely cohesive clusters of cells with rows or parallel cords of tall cells, which raises the possibility of the tall cell variant. Columnar cell vs Tall cell variant • On the contrary, the characteristic PTC nuclear features are not apparent in the columnar cell variant. • Although both subtypes will have tall or columnar cell features, the differential is not very difficult. DDX: Metastatic endometrioid or colorectal adenocarcinoma • The elongated overlapping and stratified nuclei with occasional supranuclear and/or subnuclear cytoplasmic vacuoles of columnar cell variant PTC will resemble those of metastatic endometrioid or colorectal adenocarcinoma. • However, these cancers seldom metastasize to the thyroid. If it is a metastatic lesion in the thyroid, usually it will happen in an advanced stage of disease. So, the differential diagnosis could be easily made by the clinical presentation and history. DDX: Metastatic endometrioid or colorectal adenocarcinoma • The immunocytochemical stains for ER and CDX2 are not useful; because they have been found to be positive in up to two thirds and 55% of columnar cell variant PTC, respectively. DDx: Upper respiratory epithelial cells contamination from the aspiration procedure • The pseudostratification pattern of columnar cell variant PTC may show a resemblance to the upper respiratory epithelial cells which are sometimes inadvertently aspirated during the thyroid aspiration procedure. • However, no cilia could be identified in any of these cells. • In addition, the presence of vague PTC nuclear features or background colloid material would help a lot in the differential diagnosis Discussion & Conclusions • Columnar cell variant PTC is a rare thyroid cancer (accounting for 0.2% of PTC) and characterized by columnar cells with hyperchromatic elongated nuclei in pseudostratified arrangement. • The classic nuclear features of conventional PTC are not frequent. • The differential diagnoses, including tall cell variant PTC, metastatic endometrioid or colorectal cancers, and contaminated respiratory epithelial cells, are not problematic after consideration of clinical presentation, past history, and overall cytomorphology. Discussion & Conclusions • Columnar cell variant was previously thought to be more aggressive than conventional PTC. However, recent studies showed that the behavior was more related to tumor size and extra-thyroid involvement rather than histologic subtype per se. • Better prognosis was found in small sized circumscribed or encapsulated tumor in younger female patients. • The V600E BRAF mutation was identified in approximately one third of this variant, which is similar to that in conventional PTC. • More studies are needed for further evaluation of the prognosis and behavior of this tumor in the future.