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<p>Thyroid tumors with <i>NTRK1/2/3</i> or <i>ALK</i> translocation are rare, accounting for &lt; 2% of all thyroid neoplasms. Yet, the presence of these fusions makes patients eligible for targeted therapy. Most reported cases harboring <i>NTRK1/2/3</i> or <i>ALK</i> fusion are papillary thyroid carcinoma (PTC). A detailed pathologic review was conducted on a large retrospective cohort of 82 thyroid neoplasms with <i>NTRK1/2/3</i> (<i>n</i> = 62) or <i>ALK</i> (<i>n</i> = 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, <i>n</i> = 2), PTC (<i>n</i> = 59), poorly differentiated thyroid carcinoma (<i>n</i> = 3), high-grade differentiated thyroid carcinoma (<i>n</i> = 8), anaplastic thyroid carcinoma (<i>n</i> = 3), and secretory carcinoma (<i>n</i> = 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 <i>NTRK1/2/3</i> or <i>ALK</i>-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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年5月30日

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  • Ronald Ghossein,
  • Ryan Instrum,
  • Snjezana Dogan,
  • Neha Chongtham,
  • Kerry Mullaney,
  • Dibisha Roy,
  • Ashok Shaha,
  • R. Michael Tuttle,
  • Ian Ganly,
  • Luc Morris,
  • Bin Xu

摘要

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.