Fine Needle Aspiration Acta Cytologica 2014;58:145–152 DOI: 10.1159/000358264

Received: May 21, 2013 Accepted after revision: December 30, 2013 Published online: February 13, 2014

Fine-Needle Aspiration Cytology of Thyroid Nodules with Hürthle Cells: Cytomorphologic Predictors for Neoplasms, Improving Diagnostic Accuracy and Overcoming Pitfalls K.A. Kasper J. Stewart III K. Das Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wis., USA

Abstract Objectives: Hürthle cells (HCs) are follicular-derived oncocytic cells seen in a variety of neoplastic and nonneoplastic pathologic entities of the thyroid gland. This study was to report our experience of the surgical outcome on the finding of HCs on fine-needle aspiration biopsies (FNABs) of thyroid nodules, to identify cytologic predictors of HC neoplasms and an attempt to overcome diagnostic pitfalls. Study Design: This was a retrospective study of all FNAB of thyroid nodules with findings of HCs with subsequent surgical resection. The FNAB slides of 70 thyroid nodules were blindly reviewed for specific cytomorphologic characteristics. The cytologic findings were correlated with the corresponding final surgical pathology diagnosis. Results: The patients ranged in age from 25 to 78 years with a male:female ratio of 1:2. There were 19 false-negative and 4 false-positive cases. Overall high cellularity, scant colloid and >90% HCs on FNAB are consistently seen in a neoplastic HC process. All cases of Hashimoto’s thyroiditis were associated with prominent nucleoli and 92% of cases demonstrating transgressing vessels were neoplastic. Conclusion: Diagnostic accuracy can be improved by following the current Bethesda classification sys-

© 2014 S. Karger AG, Basel 0001–5547/14/0582–0145$39.50/0 E-Mail [email protected]

tem. A constellation of cytomorphologic features in conjunction with clinical findings can be considered a strong predictor of a neoplastic process. © 2014 S. Karger AG, Basel


Hürthle cells (HCs) are follicular-derived oncocytic cells [1] seen in a variety of pathologic entities of the thyroid gland. These cells are frequently seen in nonneoplastic conditions such as nodular goiters, dominant adenomatous nodules and lymphocytic (Hashimoto’s) thyroiditis, where they are considered to be metaplastic in nature [1, 2]. They can also be found in benign or malignant neoplasms, i.e. HC adenoma (HCA) and HC carcinoma (HCC). It is imperative to distinguish between a reactive HC lesion and a neoplastic process because HC neoplasms (HCNs) are surgically resected whereas reactive nodules do not necessarily undergo resection [3]. There are studies describing cytomorphologic features that are more often seen in HCC than all HCNs [4–6]. In spite of

This study was presented as a poster at the 60th Annual Meeting of the American Society of Cytopathology (ASC) in Las Vegas, 2012.

Correspondence to: Assoc. Prof. Kasturi Das, MD Department of Pathology and Laboratory Medicine Hofstra North Shore - LIJ School of Medicine 6 Ohio Drive, Suite 202, Lake Success, NY 11042 (USA) E-Mail kasturiikens @

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Key Words Hürthle cell · Fine-needle aspiration biopsy · Thyroid

Material and Methods A search of our database for ‘Hürthle cells’ in thyroid specimens was performed from January 2005 to March 2012. The approval of the institutional review board at the University of Wisconsin was obtained. There were 1,916 aspiration biopsies performed in this period with the finding of ‘Hürthle cells’ on cytologic specimens. Sixty-eight patients (70 thyroid nodules) who underwent FNAB with a finding of ‘Hürthle cells’ with subsequent surgical resection were included in this study. Ethanol-fixed Papanicolaou-stained smears and air-dried Romanowsky-stained slides were available for all cases. Pathology reports were reviewed for the age, gender, size, number and laterality of the aspirated thyroid nodules. The FNAB diagnoses were divided into ‘negative for neoplasm’, ‘suspicious for Hürthle cell neoplasm’ and ‘Hürthle cell neoplasm’. The ‘negative for neoplasm’ category included all nonneoplastic entities, e.g. multinodular goiters (MNGs) and cysts. The FNAB diagnoses were correlated with the corresponding final surgical pathology diagnoses. The clinical-radiologic findings (i.e. size of nodule, solid vs. cystic nature and vascularity) were obtained from the electronic medical records. All FNAB slides reviewed were blinded to the cytologic and histologic diagnosis. Cytomorphologic characteristics including overall cellularity, percentage of HCs, monotony, naked nuclei, nucleoli, percentage of single cells, percent of follicular cells forming sheets, microfollicles, transgressing vessels, small-cell dysplasia, large-cell dysplasia, background colloid and lymphocytes were noted. The description of small-cell dysplasia and large-cell dysplasia by Renshaw [4] was applied, as was that by Elliott et al. [5] of transgressing vessels being capillaries coursing through sheets or clusters of HCs. We tabulated the cytologic features and assigned a scoring system (table 1).


Seventy surgically resected HC-rich nodules from 68 patients were included in this study. Two patients had bilateral nodules. The patients ranged in age from 25 to 78 years and included 22 males and 46 females. The median patient age was 58 years for males and 52 years for females. The cytologic diagnoses are summarized in table 2. The comparison of the histologic and cytologic results is summarized in table 3. Thirty-six of the 70 nodules were classified as ‘negative for neoplasm’ (table 2). These included benign colloid nodules or cysts which were considered nonneoplas146

Acta Cytologica 2014;58:145–152 DOI: 10.1159/000358264

Table 1. Cytologic features evaluated

Cytologic feature

Assigned scores

Cellularity Percentage of HCs Monotony Naked nuclei Nucleolus Percentage of single cells

high, low, intermediate 4: >90%, 3: 50–90%, 2: 90% HCs, scant colloid, prominent nucleoli

Table 5. Cytologic features in the 19 false-negative cases, all of which had a cytologic diagnosis of ‘negative for neoplasm’


Histologic diagnosis

Cytologic features

Discrepant cause

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

HCC HCC PTC classic PTC with Hashimoto’s thyroiditis PTCFV, oncocytic PTCFV, oncocytic HCA with Hashimoto’s thyroiditis HCA HCA HCA HCA HCA HCA HCA HCA FA with HCM FA with HCM FA with HCM trabecular adenoma

LC LC LC, no nuclear features LC, no nuclear features, abundant colloid LC, no nuclear features, cystic, abundant colloid LC, abundant colloid, rare grooves LC, >90% HC, some colloid, sheets >50% LC, >90% HC, scant colloid, single cells >50% LC, 50% IC, >90% HC, abundant colloid, sheets >50% Hi C, >50% HC, some colloid, sheets >50% Hi C, 50% HC, abundant colloid, sheets >90% IC, 90%). Taking the scant colloid into consideration, this case may have been better classified as FLUS. Two cases classified as MNG with low cellularity would have been better classified as FLUS as the smears showed >90% HCs and 1 of them had scant colloid. Low cellularity does not necessarily exclude HCNs. Less-cellular samples have a greater likelihood of being nonneoplastic. As an indication of this, 81% of our cases with >90% HCs were neoplastic lesions. On the other hand, we found 8 cases of HCN which showed 90% HCs on FNAB are consistently seen in a neoplastic HC process. In instances when a high cellularity and a high percentage of HCs are associated with the presence of abundant colloid and or a background of Hashimoto’s thyroiditis, these lesions are better classified as follicular lesions or HCs of uncertain significance rather than as suspicious or positive for HCN. A finding of prominent nucleoli is more commonly seen in a neoplastic process. However, the presence of prominent nucleoli on a background of Hashimoto’s thyroiditis is to be interpreted with caution in order to avoid overdiagnosing these nodules as neoplastic. A finding of transgressing vessels is noted in a neoplastic process as opposed to nonneoplastic nodules that are benign. The follicular and oncocytic variants of PTC remain diagnostic challenges. Acta Cytologica 2014;58:145–152 DOI: 10.1159/000358264


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rounding thyroid gland observed on ultrasound could help in avoiding this pitfall.



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Acta Cytologica 2014;58:145–152 DOI: 10.1159/000358264

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Fine-needle aspiration cytology of thyroid nodules with Hürthle cells: cytomorphologic predictors for neoplasms, improving diagnostic accuracy and overcoming pitfalls.

Hürthle cells (HCs) are follicular-derived oncocytic cells seen in a variety of neoplastic and nonneoplastic pathologic entities of the thyroid gland...
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