Expanding the histologic spectrum of thyroid neoplasms with NTRK1/2/3 or ALK translocation: a single-center retrospective study of 82 cases.

Thyroid tumors with NTRK1/2/3 or ALK translocation are rare, accounting for < 2% of all thyroid neoplasms. Yet, the presence of these fusions makes patients eligible for targeted therapy. Most reported cases harboring NTRK1/2/3 or ALK fusion are papillary thyroid carcinoma (PTC). A detailed pathologic review was conducted on a large retrospective cohort of 82 thyroid neoplasms with NTRK1/2/3 (n = 62) or ALK (n = 20) translocations, focusing specifically on their histologic classification and pathologic features. Pan-TRK or ALK immunohistochemistry was performed in 59 cases. The histologic classification included noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP, n = 2), PTC (n = 59), poorly differentiated thyroid carcinoma (n = 3), high-grade differentiated thyroid carcinoma (n = 8), anaplastic thyroid carcinoma (n = 3), and secretory carcinoma (n = 3). Common histologic features included multinodular invasive growth pattern (63%), dense fibrosis around nodules/follicles (54%), oncocytic changes (41%), a mixture of papillary and follicular architecture (79%), and (focal) solid growth with or without glomeruloid appearance (40%). The sensitivity of pan-TRK and ALK immunohistochemistry was 98% and 88%, respectively, although staining can be focal and/or weak. We herein expanded the histologic spectrum of NTRK1/2/3 or ALK-translocated thyroid neoplasms to include the first two reported cases of NIFTP. Although these tumors often show a multinodular invasive growth pattern, oncocytic changes, internodular fibrosis, and a mixture of follicular, papillary, and solid architecture, their histologic spectrum and classification are broad. Pan-TRK and ALK immunohistochemistry are sensitive screening tools, with the caveat that any focal or weak staining should prompt confirmatory molecular testing.