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Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms

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Abstract

Background

Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results. The aim of this study is to further explore the morphologic, immunohistochemical, and genetic profile of CC-PTC, as well as to correlate these features with clinical outcomes.

Methods

CC-PTC cases were identified from 3 institutions. Immunohistochemistry (ER, CDX2) and molecular testing (DNA and RNA sequencing) were performed. Clinicopathologic parameters and patient outcomes were recorded.

Results

Twelve cases (2006–2023) were identified, all in adults (age 45–91). Two presented with disease outside the thyroid gland (neck and mediastinum) and two presented with distant metastasis. Four were high-grade differentiated thyroid carcinomas (necrosis or mitoses), one of which died of disease. Four were noninvasive or minimally invasive, one of which locally recurred. Three patients had lymph node metastases. ER and CDX2 were positive in 73% and 50%, respectively. Pathogenic mutations were found in TERT promoter (n = 3), RAS (n = 2), ATM, NOTCH1, APC, and ESR1, along with cases bearing AGK::BRAF fusion (n = 1), BRAF VE1 expression (n = 1), and NF2 loss (n = 1).

Conclusions

This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

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No additional data or materials are available outside this manuscript. Specific requests for data can be made to the corresponding author(s) if necessary.

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Funding

This study was not supported by any funding.

Author information

Authors and Affiliations

  1. College of Dentistry, The University of Oklahoma Health Sciences Center, Oklahoma City, USA

    Kathleen E. Higgins

  2. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Peter M. Sadow

  3. Pathology, Little Company of Mary Hospital, Evergreen Park, USA

    Daniel N. Johnson

  4. Division of Molecular Pathology, Department of Pathology, The University of Chicago, Chicago, USA

    Peng Wang & Pankhuri Wanjari

  5. Division of Anatomic Pathology, Department of Pathology, The University of Chicago, Chicago, USA

    Nicole A. Cipriani

Authors
  1. Kathleen E. Higgins
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  2. Peter M. Sadow
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  4. Peng Wang
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  5. Pankhuri Wanjari
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  6. Nicole A. Cipriani
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Contributions

KEH and NAC wrote the main manuscript text and tables. NAC prepared figures. PMS, DNJ, PW, and PW contributed data and manuscript revision. All authors reviewed the manuscript.

Corresponding author

Correspondence to Nicole A. Cipriani.

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Conflict of Interest

Peter M. Sadow is co-editor of the journal and Nicole A. Cipriani is an officer of the North American Society of Head and Neck Pathology, a sponsor of the journal and an ad hoc editorial board member.

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IRB approval from Northwestern, UChicago, and MGH have been obtained. For this type of study, formal consent is not required.

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For this type of study, consent for publication is not required. No statistical analysis was performed in the preparation of this manuscript.

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Higgins, K.E., Sadow, P.M., Johnson, D.N. et al. Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms. Head and Neck Pathol 18, 39 (2024). https://doi.org/10.1007/s12105-024-01645-2

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