Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases

Kun-Ping Shih ¹, Yu-Cheng Lee ², Jia-Jiun Tsai ³

¹Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Shipai Rd, No. 201, Sec. 2, Taipei, 11217, Taiwan.
²Department of Pathology, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan.
³Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan.
⁴Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁵Division of Pathology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
⁶School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
⁷Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.
⁸Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan.
⁹Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
¹⁰National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
¹¹Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Shipai Rd, No. 201, Sec. 2, Taipei, 11217, Taiwan. jfhang@vghtpe.gov.tw.
¹²School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. jfhang@vghtpe.gov.tw.
¹³Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. jfhang@vghtpe.gov.tw.

⁰Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Shipai Rd, No. 201, Sec. 2, Taipei, 11217, Taiwan.

Endocrine Pathology +

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April 20, 2024

View abstract on PubMed

Summary

Anaplastic lymphoma kinase (ALK) gene fusions in papillary thyroid carcinoma (PTC) present with subtle cytologic features, often leading to indeterminate fine-needle aspiration diagnoses. These rare fusions may represent a therapeutic target despite atypical nuclear morphology.

Area Of Science

Oncology
Cytopathology
Molecular Pathology

Background

Anaplastic lymphoma kinase (ALK) gene fusions are uncommon in papillary thyroid carcinoma (PTC).
Identifying ALK-rearranged PTCs is crucial as they represent potential therapeutic targets.
Preoperative diagnosis of ALK-rearranged PTC can be challenging due to subtle cytologic features.

Purpose Of The Study

To evaluate the preoperative cytologic findings and clinicopathologic features of ALK-rearranged PTCs.
To correlate cytologic findings with histologic subtypes and molecular alterations.
To assess the impact of ALK rearrangements on diagnostic accuracy in fine-needle aspiration (FNA) cytology.

Main Methods

Retrospective review of eight ALK-rearranged PTC cases.
Confirmation of ALK rearrangements using D5F3 immunohistochemistry.
Targeted RNA-based next-generation sequencing (NGS) for fusion identification.
Analysis of original fine-needle aspiration (FNA) cytology diagnoses and revised interpretations.

Main Results

Cytologic review revealed microfollicular architecture with reduced nuclear elongation and chromatin alterations in all cases.
Nuclear grooves and pseudoinclusions were infrequent or absent.
Two cases initially diagnosed as Bethesda System category II were revised to category III due to architectural atypia.
Histologic subtypes included follicular variant, classic, and solid/trabecular PTC.
ALK fusions identified by NGS included EML4::ALK, STRN::ALK, and ITSN2::ALK.
ALK-rearranged PTCs exhibited reduced nuclear features compared to
BRAF-like
PTCs, often showing
RAS-like
features.

Conclusions

ALK-rearranged PTCs frequently display subtle nuclear features, mimicking less atypical lesions.
The
RAS-like
nuclear morphology in ALK-rearranged PTC can lead to indeterminate preoperative FNA diagnoses.
Accurate preoperative identification of ALK-rearranged PTC is challenging but important for potential targeted therapy.

Keywords:

Anaplastic lymphoma kinase Fine needle aspiration Papillary thyroid carcinoma The Bethesda System