# Proceedings of the 2026 North American Society of Head and Neck Pathology Companion Meeting, San Antonio, TX, March 22, 2026: It’s a Trap! Pitfalls in Thyroid Pathology: Mets or Not Mets?

**Authors:** Yu-Che Chuang, Jen-Fan Hang

PMC · DOI: 10.1007/s12105-026-01901-7 · Head and Neck Pathology · 2026-03-14

## TL;DR

This paper reviews common diagnostic challenges in thyroid pathology, focusing on distinguishing metastatic tumors from primary thyroid neoplasms.

## Contribution

The paper highlights key scenarios and diagnostic strategies to avoid misclassification in thyroid pathology.

## Key findings

- Intranodal thyroid inclusions can mimic metastatic papillary thyroid carcinoma in lymph nodes.
- Metastatic tumors to the thyroid may resemble primary thyroid neoplasms across various malignancy grades.
- Combining histologic, clinical, and radiologic data improves diagnostic accuracy in thyroid pathology.

## Abstract

Similar to other head and neck organs, thyroid pathology encompasses a broad spectrum of diagnostic entities. The significant overlap in architectural or cytological features across these entities presents a unique set of diagnostic challenges.

This review focuses on diagnostic pitfalls related to metastasis in thyroid pathology, with particular emphasis on morphologic assessment and differential diagnosis.

Key scenarios discussed include (1) intranodal thyroid inclusions, which may closely mimic metastatic papillary thyroid carcinoma in cervical lymph nodes, and (2) metastatic tumors to the thyroid that can simulate primary thyroid neoplasms across the full histologic spectrum, from low-grade to high-grade malignancies, especially in the absence of a known concomitant primary malignancy or when the clinical history is not provided. Awareness that both benign thyroid tissue and metastatic tumors may exhibit atypical architectural or cytologic features is critical to avoiding overdiagnosis or misclassification. Rigorous morphological assessment remains the first step in the diagnostic workup. Immunohistochemistry serves as a valuable adjunct when used judiciously, particularly mutation-specific markers such as BRAF VE1 and lineage-associated markers including TTF-1, PAX8, and thyroglobulin, with careful consideration of their sensitivity and specificity.

Integration of histologic findings with clinical history and radiologic information ultimately enables accurate distinction between metastatic and non-metastatic lesions in thyroid pathology.

## Linked entities

- **Proteins:** TTF1 (transcription termination factor 1), PAX8 (paired box 8)
- **Diseases:** papillary thyroid carcinoma (MONDO:0005075)

## Full-text entities

- **Genes:** Cdh1 (cadherin 1) [NCBI Gene 12550] {aka ARC-1, E-cad, Ecad, L-CAM, UVO, Um}, TP53BP1 (tumor protein p53 binding protein 1) [NCBI Gene 7158] {aka 53BP1, TDRD30, p202, p53BP1}, INSM1 (INSM transcriptional repressor 1) [NCBI Gene 3642] {aka IA-1, IA1}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, RET (ret proto-oncogene) [NCBI Gene 5979] {aka CDHF12, CDHR16, HSCR1, MEN2A, MEN2B, MTC1}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, ALK (ALK receptor tyrosine kinase) [NCBI Gene 238] {aka ALK1, CD246, NBLST3}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}, NTRK1 (neurotrophic receptor tyrosine kinase 1) [NCBI Gene 4914] {aka MTC, TRK, TRK1, TRKA, Trk-A, p140-TrkA}, SATB2 (SATB homeobox 2) [NCBI Gene 23314] {aka C2DELq32q33, DEL2Q32Q33, GLSS}, CDX2 (caudal type homeobox 2) [NCBI Gene 1045] {aka CDX-3, CDX2/AS, CDX3}, Ttf1 (transcription termination factor, RNA polymerase I) [NCBI Gene 22130] {aka TTF-1, TTF-I}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, TTF1 (transcription termination factor 1) [NCBI Gene 7270] {aka TTF-1, TTF-I}
- **Diseases:** Graves' disease (MESH:D006111), ITIs (MESH:D003586), oncocytic thyroid carcinoma (MESH:C535584), inflammatory (MESH:D007249), Head and Neck Tumors (MESH:D006258), head and neck squamous cell carcinoma (MESH:D000077195), follicular (MESH:D005497), thymic-type neoplasms (MESH:D013953), MTC (MESH:C536914), thymic carcinoma (MESH:D013945), SCC (MESH:D002294), hyperplasia (MESH:D006965), necrosis (MESH:D009336), chronic lymphocytic thyroiditis (MESH:D050031), RCC (MESH:D002292), benign thyroid tissue (MESH:D013966), Metastatic (MESH:D000092182), PTC (MESH:D000077273), lymph node metastasis (MESH:D008207), invasive lobular carcinoma of the breast (MESH:D001943), primary thyroid tumor (MESH:D001932), anterior neck mass (MESH:D019547), lung carcinomas (MESH:D008175), fibrosis (MESH:D005355), primary (MESH:D010538), follicular nodular disease (MESH:D008224), lung carcinoids (MESH:D002276), laryngeal or pharyngeal cancer (MESH:D010610), benign thyroid tumors (MESH:D009369), disease (MESH:D004194), follicular adenoma (MESH:D000236), Metastasis to the thyroid (MESH:D009362), pulmonary and extrapulmonary neuroendocrine carcinomas (MESH:D018278), SDC (MESH:D012465), abnormalities in the thyroid gland (MESH:D013959), Lesions of the Neck and Lymph Nodes (MESH:D000072717), neuroendocrine tumor (MESH:D018358), FTC (MESH:D018263), hemorrhage (MESH:D006470), non-thyroid malignancy (MESH:D005067), ATC (MESH:D065646), Metastatic lung adenocarcinoma (MESH:D000077192), heterotopia (MESH:D054091), adenocarcinoma (MESH:D000230), PDTC (MESH:D013964)
- **Chemicals:** lipids (MESH:D008055), glycogen (MESH:D006003), Napsin A (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** Q61R, V600E

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12988945/full.md

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Source: https://tomesphere.com/paper/PMC12988945