Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and CREB3L2::PPARγ Fusion

A 58-year-old woman presented with an asymptomatic, soft-to-palpation, mobile, right thyroid mass. Subsequent ultrasonography revealed numerous, bilateral, mildly heterogenous, cystic and solid nodules, including a hypoechoic, 1.7 × 1.0 × 1.6 cm, solid, left superior pole nodule of intermediate morphologic suspicion, meeting ATA criteria for FNA biopsy. Cytopathologic diagnosis was suspicious for papillary thyroid carcinoma and ThyroSeq molecular testing revealed an underlying CREB3L2::PPARγ fusion, implying a high risk for "malignancy or non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)". A left thyroid lobectomy was performed. Gross examination revealed a 1.1 × 0.7 × 1.0 cm, white-tan, firm, well-circumscribed nodule lacking gross evidence of invasion, which was entirely submitted for histologic examination. Microscopically, the nodule was fully enveloped by a thin fibrous capsule and composed entirely of microfollicles. Follicular epithelial cells featured moderate amounts of pale, eosinophilic, cytoplasm, and enlarged, wrinkled or irregular nuclei with chromatin clearing, grooves, and occasional intranuclear cytoplasmic pseudoinclusions. Papillary or solid growth patterns, psammoma bodies, increased mitoses, necrosis, or invasion were absent. As anticipated, immunostaining using the BRAF V600E mutant specific antibody (VE1) was negative. However, the intranuclear pseudoinclusions were negative for ubiquitin. Here, we report the clinical, radiologic, cytologic, histologic, and molecular characteristics of an example of NIFTP harboring a rare CREB3L2::PPARγ fusion.