A thyroid EIF1AX story: how clinical, cytologic, and molecular surveillance led to appropriate management

Daniel L Geisler; Esra Karslioglu French; Linwah Yip; Marina N Nikiforova; Yuri E Nikiforov; Karen E Schoedel; Raja R Seethala; N Paul Ohori

doi:10.1016/j.jasc.2022.11.002

A thyroid EIF1AX story: how clinical, cytologic, and molecular surveillance led to appropriate management

J Am Soc Cytopathol. 2023 Mar-Apr;12(2):105-111. doi: 10.1016/j.jasc.2022.11.002. Epub 2022 Nov 18.

Authors

Daniel L Geisler¹, Esra Karslioglu French², Linwah Yip³, Marina N Nikiforova¹, Yuri E Nikiforov¹, Karen E Schoedel¹, Raja R Seethala¹, N Paul Ohori⁴

Affiliations

¹ Department of Pathology, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania.
² Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania.
³ Division of Endocrine Surgery, Department of Surgery, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania.
⁴ Department of Pathology, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania. Electronic address: ohorinp@upmc.edu.

PMID: 36504010
DOI: 10.1016/j.jasc.2022.11.002

Abstract

Introduction: Indeterminate thyroid cytology diagnoses are associated with intermediate risks of malignancy. Application of molecular testing (MT) to indeterminate specimens provides additional diagnostic and prognostic information. While a positive or suspicious MT result may prompt surgery, a negative MT result is associated with a low probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features and approximates that of a benign cytology diagnosis. Furthermore, ThyroSeq v3 MT has a "currently negative" result for findings with the probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear feature that is slightly greater than that for the negative ThyroSeq v3 MT result but less than 10%, suggesting active surveillance. In this report, we discuss a case of a patient for whom clinical, cytologic, and molecular surveillance led to timely surgery and management.

Clinical details: A 53-year-old man with a thyroid isthmus nodule had a fine-needle aspiration cytology diagnosis of atypia of undetermined significance and a subsequent ThyroSeq v3 MT, which revealed an EIF1AX mutation and a "currently negative" MT result. Surveillance with additional fine-needle aspiration samples demonstrated concerning genomic alterations (fluctuating EIF1AX allelic frequency and a non-V600E BRAF mutation), culminating in the conversion to a positive MT result 3 years later. Resection revealed an encapsulated noninvasive, oncocytic solid subtype of papillary thyroid carcinoma with increased mitotic activity.

Conclusion: The case is notable for clinical, cytologic, and molecular surveillance demonstrating sequential pathologic alterations in an indeterminate thyroid nodule with EIF1AX mutation, leading to timely resection of the neoplasm before invasion manifested.

Keywords: EIF1AX; Indeterminate thyroid nodules; Molecular testing; Papillary carcinoma; ThyroSeq.

Publication types

Case Reports

MeSH terms

Biopsy, Fine-Needle
Humans
Male
Middle Aged
Thyroid Cancer, Papillary / diagnosis
Thyroid Cancer, Papillary / genetics
Thyroid Neoplasms* / diagnosis
Thyroid Neoplasms* / genetics
Thyroid Neoplasms* / surgery
Thyroid Nodule* / diagnosis
Thyroid Nodule* / genetics
Thyroid Nodule* / pathology