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Abstract
Background: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive form of thyroid cancer that presents as a rapidly enlarging neck mass with compressive symptoms. Its malignancy and mortality rates approach nearly 90% and is a feared transformation of papillary thyroid cancer (PTC). A contributor to its increased mortality is its predilection for metastasis, which by nature, is less documented in medical literature. The study of ATC’s diagnostic algorithm, which classically utilizes cytological and histological confirmation, is crucial in enhancing early recognition and atypical presentations.
Methods: This systematic review catalogs the diagnosis, clinical properties, and metastasis sites of anaplastic thyroid cancer between the Surveillance, Epidemiology, and End Results Database (SEER), the National Cancer Database (NCDB), and published case reports between the years 2013-2024. The less established protocol of ATC’s diagnostic workup is discussed, and commonalities within clinical descriptors of thyroid scintigraphy and fine-needle aspiration cytology are explored.
Results: Out of the 15 papers reviewed, the 12 chosen case reports involved either cytological or histological assessment of metastatic ATC from 2013 to 2024. In decreasing order, the most common metastasis sites were the lungs, lymph nodes, and serous membranes (pleura and pericardium), with half being bilateral. With one-third of cases having a prior diagnosis of PTC, reduced diagnostic reliance on fine needle aspiration (FNA) for initial malignancy confirmation likely resulted in several IMH-diagnosed cases bypassing the test. Still, half of the cases presented concurrently with PTC, requiring additional histological testing following FNA to identify the primary source of metastatic disease.
Across cases that used IMH (n=11), paired box gene 8 (PAX-8) was the most consistent protein marker, expressed in 87.5% of metastatic ATC. This was followed by limited use of Cytokeratin AE1/AE3, Ki-76, and Thyroglobulin markers which were positive in 64.3% of observed metastatic ATC. Rarely used markers frequently associated with thyroid origin, including thyroid transcription factor-1 (TTF-1) and p63, showed marginal differences between positive and negative expression rates. One case of ATC was diagnosed solely through (FNA) and cytological analysis due to direct access to the thyroid nodule and cytological similarity observed in pleural fluid.
Conclusions: Our findings reinforce the role of histopathological evaluation, particularly IHC, in identifying primary tumor origin in suspected ATC cases, most notably when FNA cytological assessment yields limited results. Given the rarity and aggressiveness of ATC, there is little research into diagnostic protocols, much less in metastasized cases. Concurrent and past presentations with PTC further complicate ATC identification. Among IHC markers, PAX-8 demonstrated the highest diagnostic utility in confirming ATC, supporting its continued use in differentiating ATC from other thyroid cancers. Cytokeratin AE1/AE3 and Ki-67 had the next greatest differences in positive and negative expression, potentially serving as supportive markers. Overall, these findings support a multimodal diagnostic approach that prioritizes histological confirmation and emphasizes the careful selection and interpretation of IHC markers in metastatic ATC diagnoses.
Presentation Type
Poster
Recommended Citation
Yang, Phyllis; Cauba, John Nicholas; and Mito, Shizue, "Comparison of Cytology and Histology Diagnosis Methods in Metastatic Anaplastic Thyroid Cancer" (2025). Research Colloquium. 84.
https://scholarworks.utrgv.edu/colloquium/2025/posters/84
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Diagnosis Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Oncology Commons
Comparison of Cytology and Histology Diagnosis Methods in Metastatic Anaplastic Thyroid Cancer
Background: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive form of thyroid cancer that presents as a rapidly enlarging neck mass with compressive symptoms. Its malignancy and mortality rates approach nearly 90% and is a feared transformation of papillary thyroid cancer (PTC). A contributor to its increased mortality is its predilection for metastasis, which by nature, is less documented in medical literature. The study of ATC’s diagnostic algorithm, which classically utilizes cytological and histological confirmation, is crucial in enhancing early recognition and atypical presentations.
Methods: This systematic review catalogs the diagnosis, clinical properties, and metastasis sites of anaplastic thyroid cancer between the Surveillance, Epidemiology, and End Results Database (SEER), the National Cancer Database (NCDB), and published case reports between the years 2013-2024. The less established protocol of ATC’s diagnostic workup is discussed, and commonalities within clinical descriptors of thyroid scintigraphy and fine-needle aspiration cytology are explored.
Results: Out of the 15 papers reviewed, the 12 chosen case reports involved either cytological or histological assessment of metastatic ATC from 2013 to 2024. In decreasing order, the most common metastasis sites were the lungs, lymph nodes, and serous membranes (pleura and pericardium), with half being bilateral. With one-third of cases having a prior diagnosis of PTC, reduced diagnostic reliance on fine needle aspiration (FNA) for initial malignancy confirmation likely resulted in several IMH-diagnosed cases bypassing the test. Still, half of the cases presented concurrently with PTC, requiring additional histological testing following FNA to identify the primary source of metastatic disease.
Across cases that used IMH (n=11), paired box gene 8 (PAX-8) was the most consistent protein marker, expressed in 87.5% of metastatic ATC. This was followed by limited use of Cytokeratin AE1/AE3, Ki-76, and Thyroglobulin markers which were positive in 64.3% of observed metastatic ATC. Rarely used markers frequently associated with thyroid origin, including thyroid transcription factor-1 (TTF-1) and p63, showed marginal differences between positive and negative expression rates. One case of ATC was diagnosed solely through (FNA) and cytological analysis due to direct access to the thyroid nodule and cytological similarity observed in pleural fluid.
Conclusions: Our findings reinforce the role of histopathological evaluation, particularly IHC, in identifying primary tumor origin in suspected ATC cases, most notably when FNA cytological assessment yields limited results. Given the rarity and aggressiveness of ATC, there is little research into diagnostic protocols, much less in metastasized cases. Concurrent and past presentations with PTC further complicate ATC identification. Among IHC markers, PAX-8 demonstrated the highest diagnostic utility in confirming ATC, supporting its continued use in differentiating ATC from other thyroid cancers. Cytokeratin AE1/AE3 and Ki-67 had the next greatest differences in positive and negative expression, potentially serving as supportive markers. Overall, these findings support a multimodal diagnostic approach that prioritizes histological confirmation and emphasizes the careful selection and interpretation of IHC markers in metastatic ATC diagnoses.
