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LEF-1 is a Sensitive Marker of Cribriform Morular Variant of Papillary Thyroid Carcinoma

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Abstract

Cribriform morular variant of PTC (CMV-PTC) frequently shows activation of the CTNNB1/Wnt pathway with nuclear accumulation of beta catenin. The utility of LEF-1, also in the CTNNB1/WNT pathway, in the diagnosis of CMV-PTC has not been previously studied. LEF-1 immunohistochemistry was performed on seven CMV-PTC, 52 benign cases and 101 malignant thyroid neoplasms. LEF-1 was scored by stain intensity (0 = no nuclear stain, 1 = weak nuclear stain, less than lymphocyte and 2 = strong nuclear stain, intense as lymphocyte) and percentage of positive cells at each intensity, for a maximum total score of 200. Sensitivity and specificity of LEF-1 stain for all cases and to differentiate between regular PTC and CMV-PTC was also calculated. Six of the seven CMV-PTCs showed ≥ 30% strong (2+) nuclear LEF-1 staining and a total score over 100. Beta catenin also showed strong and diffuse nuclear staining in these cases. One CMV-PTC was negative for both LEF-1 and beta catenin and did not have a history of FAP. All control PTC cases uniformly lacked LEF-1 staining at 2+ intensity. LEF-1 had a sensitivity of 86% and specificity of 98% for the diagnosis of CMV-PTC. LEF-1 is highly sensitive and specific marker for CMV-PTC, especially when used in the setting of a PTC neoplasm. The pattern of staining is important with ≥ 30% of cells showing strong 2+ nuclear staining having the highest combined sensitivity and specificity.

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Authors and Affiliations

  1. Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, L25, Cleveland, OH, 44195, USA

    Shalini Mohindra, Hany Sakr, Charles Sturgis & Deborah J. Chute

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  1. Shalini Mohindra
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  2. Hany Sakr
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  3. Charles Sturgis
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  4. Deborah J. Chute
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Correspondence to Deborah J. Chute.

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Mohindra, S., Sakr, H., Sturgis, C. et al. LEF-1 is a Sensitive Marker of Cribriform Morular Variant of Papillary Thyroid Carcinoma. Head and Neck Pathol 12, 455–462 (2018). https://doi.org/10.1007/s12105-017-0873-3

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  • DOI: https://doi.org/10.1007/s12105-017-0873-3

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