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Clinical and Morphologic Features of ETV6-NTRK3 Translocated Papillary Thyroid Carcinoma in an Adult Population Without Radiation Exposure

Seethala, Raja R. MD; Chiosea, Simion I. MD; Liu, Cheng Z. MD, PhD; Nikiforova, Marina MD; Nikiforov, Yuri E. MD, PhD

The American Journal of Surgical Pathology: April 2017 - Volume 41 - Issue 4 - p 446–457
doi: 10.1097/PAS.0000000000000814
Original Articles

The ETV6-NTRK3 translocation characterizes a subset of radiation associated and pediatric papillary thyroid carcinomas (PTCs). We now describe the clinicopathologic features of ETV6-NTRK3 translocated PTC in an adult population without radiation exposure. Twelve cases were identified by next-generation sequencing (ThyroSeq version 2). The mean patient age was 37 years with a female predilection (10:2). Preoperative fine needle aspiration was performed on 6 patients of which 4 were classified as “malignant,” whereas 2 were classified as “follicular lesion of undetermined significance.” One third (4/12) of patients demonstrated extrathyroidal extension and one half of patients (5/10) demonstrated lymph node metastases. One patient presented with brain metastasis. Tumors typically (8/12) demonstrated an admixture of follicular and papillary patterns and were usually infiltrative and multinodular (6/12 cases). Tumors often showed clear cell or oncocytic foci and demonstrated overt nuclear features of PTC, though characteristically, interspersed bland areas were common, even in metastases. Cytoplasmic vacuolization resembling that of mammary analog secretory carcinoma was also common but focal. TTF-1 was positive and S100 was negative in all tested cases confirming a thyroid phenotype. Unique morphologies included glomeruloid follicles, reverse polarization of nuclei. Survey of the TCGA datasets revealed similar findings. Thus, ETV6-NTRK3 translocated PTC are locoregionally aggressive and can metastasize distantly. They are characterized by mixture of papillary and follicular architecture and may show cytoplasmic vacuolization akin to other ETV6 translocated carcinomas. Although nuclear features are typically overt, interspersed bland regions may cause diagnostic difficulty in metastatic sites, and may explain discordance on fine needle aspiration.

*Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA

Department of Pathology and Laboratory Medicine, New York University Langone Medical Center, New York, NY

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Supported in part by NIH grant CA88041 (Y.E.N.).

Correspondence: Raja R. Seethala, MD, A614.X, Presbyterian University Hospital, 200 Lothrop Street, Pittsburgh, PA 15213 (e-mail:

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