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Cytopathology of the Thyroid

Staats, Paul N. MD

doi: 10.1097/PCR.0000000000000085

From the Department of Pathology, University of Maryland School of Medicine, Baltimore, MD

Reprints: Paul N. Staats, MD, Department of Pathology, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201. E-mail:

The author has no funding or conflicts to declare.



The thyroid is the most common source of fine-needle aspiration specimens in most cytology laboratories in the developed world. Fine-needle aspiration of the thyroid is the key triage test for thyroid nodules, and its use has markedly decreased the rate of unnecessary thyroid surgery for benign disease.

However, these cases remain among the more diagnostically challenging ones encountered on a daily basis. The lack of standardized terminology was for years a major obstacle to better understanding of this area, but the publication of the Bethesda System for Reporting Thyroid Cytopathology in 2009 provided a standardized framework that will allow for better definition of diagnostic criteria for pathologists, clearer communication between clinicians and pathologists, and a common base for research into better diagnosis and treatment of thyroid neoplasia.1 We will devote 2 issues of Pathology Case Reviews to this topic, with the overall outline approximately following the Bethesda system terminology.

The present issue is devoted to the most common diagnostic entities: follicular pattern nodules and papillary thyroid carcinoma (PTC). A subsequent issue will address less common entities in thyroid cytopathology, including medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, anaplastic (undifferentiated) thyroid carcinoma, secondary tumors of the thyroid, and lymphomas of the thyroid, as well as aspirations of the parathyroid glands.

Nodules composed of cells with follicular (or Hürthle cell) cytology are perhaps the most challenging routinely encountered cases, in part because definitive classification as malignant is not possible on cytology, and these cases are rather categorized based on the likelihood of malignancy, with even the category of “follicular neoplasm” expected to have only a 15% to 30% risk of malignancy on surgical excision. First, Kanber and Auger provide a through survey of the “benign” category, including the cytologic features associated with the various types of thyroiditis, as well as the cytologic features of benign follicular nodules. Next, Chang and Krane discuss the “atypia of undetermined significance/follicular lesion of undetermined significance” category, emphasizing the potential for its overuse and suggesting approaches to appropriately limit the use of this term. Next, Ocal and Ghofrani review follicular neoplasms, and Bernadt and Collins review Hürthle cell neoplasms.

The “positive for malignancy” category contains a variety of neoplasms that can be definitively diagnosed based on cytologic features and is expected to have an associated 97% to 99% risk of malignancy. By far the most common tumor in this category is PTC. The features of the classic PTC are well known to any pathologist who reviews thyroid cytology specimens routinely; however, certain variants are quite challenging cytologically. In the next review, Marshall takes on one of these, the diffuse sclerosing variant of PTC.

Finally, Rossi and colleagues review the current state of molecular testing on thyroid cytology specimens. Molecular testing has become part of the routine diagnostic algorithm at many centers and is likely to hold the key to further improvements in patient care.

Although fine-needle aspiration cytology has significantly reduced the rate of unnecessary surgery, the majority of thyroid nodules removed are still benign, and the consequences of these surgeries for patients can be quite significant. Moreover, as a recent review of thyroid management practices in South Korea strikingly demonstrates, increased identification of thyroid nodules has had no identifiable effect on the rate of thyroid cancer mortality.2 Thus, a critical focus of research going forward must be on identifying, by molecular or other means, the lesions that are truly malignant, so as to treat only those lesions. Similarly, the everyday focus of practicing cytopathologists should be on preventing harm to our patients by limiting the overdiagnosis of benign changes as atypia of undetermined significance or worse, just as much as on identifying malignancy. For now, that balance remains the prime challenge of thyroid cytopathology, and I hope that this issue of Pathology Case Reviews will offer the reader some guidance toward that goal.

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1. Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132: 658–665.
2. Ahn HS, Kim HJ, Welch HG. Korea’s thyroid-cancer “epidemic”—screening and overdiagnosis. N Engl J Med 2014; 371: 1765–1767.
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