Anatomic Pathology / FEATURES OF THYROID PAPILLARY CARCINOMA IN FINE-NEEDLE ASPIRATION AND AT RESECTION

Focal Features of Papillary Carcinoma of the Thyroid in Fine-Needle Aspiration Material Are Strongly Associated With Papillary Carcinoma at Resection
Andrew A. Renshaw, MD
Key Words: Thyroid; Papillary carcinoma; Cytology; Cytopathology; Fine-needle aspiration; Diagnosis; Criteria

Abstract
The cytologic features of papillary carcinoma of the thyroid in fine-needle aspiration material have been well described. The significance of finding these features in only a small population of cells is not well characterized. I reviewed the results of 28 thyroid fineneedle aspirates processed as direct smears and cell blocks in which only a small population (<20 cells) showed features of papillary carcinoma. Papillary carcinoma was considered in 142 (8.98%) of 1,581 aspirates, and in 28 cases (1.77%), 20 cells or fewer showed features of papillary carcinoma and follow-up was available. Papillary carcinomas greater than 1 cm were identified in 11 cases (39%; 3 follicular variants), papillary carcinomas less than 1 cm were identified in 4 cases (14%), and benign lesions in the remaining 13 cases (46%). The background material (either scant or abundant benign epithelium) did not correlate significantly with the result of resection. Identifying features of papillary carcinoma in a small population of cells in either a scant or an abundant thyroid aspirate are associated with a high rate of papillary carcinomas at resection, only a minority of which represent either the follicular variant or incidental tumors.

The classic cytologic criteria for papillary carcinoma of the thyroid have been studied and delineated by numerous authors1-11 and consist primarily of enlarged, often overlapping nuclei with fine, dusty or powdery chromatin; intranuclear cytoplasmic inclusions; and linear chromatin ridges (grooves) with irregular nuclear outlines. When these features are present in numerous cells, there is little diagnostic difficulty. When these features are present in only a few cells, either in a scanty specimen or in a specimen with abundant benign material in the background, the diagnosis is less certain. Whether these patients are best served by clinical follow-up, repeated aspiration, or resection is not clear. Recent studies suggest that cases with only focal features of papillary carcinoma often are associated with the follicular variant of papillary carcinoma at resection.12 To further characterize aspirates with these features, I correlated a large group of patients with these findings on fine-needle aspiration with the results of subsequent surgical resection.

Materials and Methods

All fine-needle aspirates interpreted at the Baptist Hospital of Miami, Miami, FL, from August 1996 through August 2001, were studied. All aspirates were performed by clinicians. In approximately one third of cases, this was performed in the radiology department with ultrasound guidance and cytologic assessment of adequacy at the time of aspiration; the remaining two thirds of cases were performed in clinicians offices. All slides were prepared as alcohol-fixed direct smears, and, if adequate material was available, a cell block was made. Material was stained with either Papanicolaou or H&E staining.
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The adequacy criteria used during the time of the study were those of Goellner et al,13 which required 6 groups of 10 benign follicular cells for a specimen to be adequate. The total number of slides in cases included in the study varied from 2 to 42 (mean, 14 slides). For the purposes of the study, only cases that contained 20 or fewer cells with features of papillary carcinoma were considered. This cutoff was arbitrary and was determined after review of the available material. The nuclear features identified were enlarged, often overlapping nuclei with pale chromatin, irregular nuclear outlines, and nuclear grooves. Intranuclear inclusions were sought but almost never identified. Statistical comparisons were performed by using the Fisher exact test and a level of .05 for significance.

the follicular variant. While the incidence of benign findings, including follicular adenoma and multinodular hyperplasia, was greater when the background was abundant rather than scant (ie, there was abundant benign-appearing follicular epithelium in a predominantly macrofollicular pattern), this difference was not statistically significant.

Discussion
I was motivated to write this article by a lack of agreement about the significance of minimal findings for papillary carcinoma in thyroid aspirates within our own group. Several of my colleagues were uncomfortable recommending resection on the basis of such minimal findings and preferred to recommend reaspiration. The literature is not very helpful in this regard. Only a few relatively recent reports even include atypical12,15,16 as a diagnostic category for papillary carcinoma. Interestingly, one of these reports12 suggested that these minimal findings were strongly associated with the follicular variant of papillary carcinoma. The maximum number of cells with features of papillary carcinoma necessary to qualify for this report is admittedly arbitrary and is based purely on a review of the cases involved. By using the number 20, I do not in any way mean to imply that aspirates with more than this number of cells are necessarily different from those with fewer than 20, but rather to give the reader a quantitative assessment of the degree of focality of the findings. This quantitative assessment may not be applicable to other preparations. For instance, in my experience, it may be more common to routinely identify cases of papillary carcinoma on Thinprep processing (Cytyc, Boxborough MA) on the basis of relatively few cells, in much the same way as cases of highgrade squamous intraepithelial lesion may be identified more routinely on the basis of relatively few cells by this same processing technique compared with conventional smears. My results suggest that while minimal findings are associated with papillary carcinoma at resection in more than

Results
A total of 1,581 aspirates were performed during this period, and papillary carcinoma was considered in the diagnosis in 142 cases (8.98%). Of these, 53 were interpreted as positive, 28 as suspicious, and 61 as atypical. Of the 61 atypical cases, 6 had features of the histiocytoid variant of papillary carcinoma, which is described elsewhere.14 Of the remaining 55 cases, a total of 28 cases (51%) qualified as having fewer than 20 cells with features of papillary carcinoma and had subsequent resection. These 28 cases form the basis of the present study. These 28 cases came from 6 men and 22 women aged 29 to 66 years (median, 42 years). The cytologic features and results of subsequent resection are summarized in Table 1. All cases with scant cellularity were diagnosed as nondiagnostic, while all cases with abundant benign epithelium in the background were diagnosed as adequate but atypical. The nondiagnostic cases accounted for approximately 5% of all nondiagnostic specimens received during the aforementioned time period. There were no cases of papillary carcinoma at resection that measured between 0.5 and 1 cm. Overall, 15 (54%) of 28 cases had papillary carcinoma at resection, and 11 of these tumors measured greater than 1 cm. Only 3 were

Table 1 Cytologic Features and Results of Subsequent Resection in Patients With Thyroid Fine-Needle Aspirates With Focal Features of Papillary Carcinoma*
Follow-up Background Scant (n = 10) Abundant normal epithelium (n = 18) Total cases (n = 28)
*

Benign Multinodular hyperplasia (1); cyst (1) Follicular adenoma (4); multinodular hyperplasia (5); cyst (2) 13

Papillary Carcinoma Routine variant, >1 cm (5); follicular variant, >1 cm (2) and <0.5 cm (1) Routine variant, >1 cm (3); follicular variant, >1 cm (1) and <0.5 cm (3) 15

See the Materials and Methods section for definition. Numbers in parentheses are the number of cases. Epithelium on the slide other than the atypical epithelium was identified.

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50% of cases and that the majority of such tumors are more than 1 cm in dimension, only a minority of these tumors are the follicular variant. This is different from findings given in a previous report that emphasized that focal features of papillary carcinoma were strongly associated with the follicular variant.12 There are several possible explanations for this. First, my definition is strictly quantitative. The previous report was not so strict about the number of cells involved and included cases with poorly developed features as well. It may be that aspirates in which the findings of papillary carcinoma are diffuse but poorly developed may be associated more strongly with the follicular variant than with cases in which the features are well developed but very focal. In addition, this other study included air-dried material as well as alcohol-fixed material, and it is possible that this affected the results. Also, it is well known that there are substantial differences in the diagnostic threshold for the follicular variant of papillary carcinoma on resection material,17 and it is possible that some of the cases I classified as follicular adenomas may be classified differently by others. Finally, an important distinction between the present study and previous studies may be sampling. A previous study12 examined aspirates that were almost entirely performed under radiologic guidance with cytologic assessment of adequacy. The majority of cases in the present study were performed in clinicians offices. This setting may be more likely to focally sample only the nodule of interest. Indeed, my results imply that many of these aspirates result simply from poor sampling. The frequent association of focal findings of papillary carcinoma with very small incidental papillary carcinomas at resection, as well as the frequent finding of abundant benign tissue in many of these aspirates, suggests the clinician may simply be sampling the surrounding thyroid tissue. However, these results cannot be entirely explained by poor sampling, since a high rate of significant disease was found with focal findings in another study12 that used almost exclusively radiologic guidance and immediate cytologic evaluation and had a very high adequacy rate. I have shown that in a setting in which the majority of aspirates are performed without radiologic guidance and processed with alcohol-fixed direct smears, the identification of fewer than 20 cells with features of papillary carcinoma on thyroid fine-needle aspirations, regardless of the background in which it is identified, is strongly associated with a high incidence of papillary carcinoma at resection and that these tumors are typically large and have a papillary rather than a follicular architecture. High rates of significant disease also have been found with focal features of papillary carcinoma in settings in which the aspiration was performed under radiologic guidance and with immediate cytologic evaluation. Taken together, these results suggest that resection in patients with such minimal findings is justified.
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From the Department of Pathology, Baptist Hospital of Miami, Miami, FL. Address reprint requests to Dr Renshaw: Dept of Pathology, Baptist Hospital of Miami, 8900 N Kendall Dr, Miami, FL 33176.

References
1. Kini SR. In: Kline TS, ed. Guides to Clinical Aspiration Biopsy: Thyroid. 2nd ed. New York, NY: Igaku-Shoin; 1996. 2. Kini SR, Miller JM, Hamburger JI, et al. Cytopathology of papillary carcinoma of the thyroid by fine needle aspiration. Acta Cytol. 1980;24:511-521. 3. Gould E, Watzak L, Chamizo W, et al. Nuclear grooves in cytologic preparations: a study of the utility of this feature in the diagnosis of papillary carcinoma. Acta Cytol. 1989;33:16-20. 4. Miller TR, Bottles K, Holly EA, et al. A step-wise logistic regression analysis of papillary carcinoma of the thyroid. Acta Cytol. 1986;30:285-293. 5. Rupp M, Ehya H. Nuclear grooves in the aspiration cytology of papillary carcinoma of the thyroid. Acta Cytol. 1989;33:2126. 6. Bhambhani S, Kashyap V, Das DK. Nuclear grooves: valuable diagnostic feature in May-Grnwald-Giemsa stained fine needle aspirates of papillary carcinoma of the thyroid. Acta Cytol. 1990;34:809-812. 7. Kaur A, Jayaram G. Thyroid tumors: cytomorphology of papillary carcinoma. Diagn Cytopathol. 1991;7:462-468. 8. Deligeorgi-Politi H. Nuclear crease as a cytodiagnostic feature of papillary thyroid carcinoma in fine-needle aspiration biopsies. Diagn Cytopathol. 1987;3:307-310. 9. Basu D, Jayaram G. A logistic model for thyroid lesions. Diagn Cytopathol. 1992;8:23-27. 10. Chan JKC, Saw D. The grooved nucleus: a useful diagnostic criterion of papillary carcinoma of the thyroid. Am J Surg Pathol. 1986;10:672-679. 11. Scopa CD, Melachrinou M, Saradopoulou C, et al. The significance of the grooved nucleus in thyroid lesions. Mod Pathol. 1993;6:691-694. 12. Logani S, Gupta PK, LiVolsi VA, et al. Thyroid nodules with FNA cytology suspicious for follicular variant of papillary thyroid carcinoma: follow-up and management. Diagn Cytopathol. 2000;23:380-385. 13. Goellner JR, Gharib H, Grant CS, et al. Fine needle aspiration cytology of the thyroid, 1980-1986. Acta Cytol. 1987;31:587-590. 14. Renshaw AA. Histiocytoid cells in fine needle aspirates of papillary carcinoma of the thyroid: frequency and significance of an under-recognized cytologic pattern. Cancer. In press. 15. Chen H, Zeiger M, Clark DP, et al. Papillary carcinoma of the thyroid: can operative management be based solely on fineneedle aspiration? J Am Coll Surg. 1997;184:605-610. 16. Renshaw AA. Accuracy of thyroid fine-needle aspiration using receiver operator characteristic curves. Am J Clin Pathol. 2001;116:477-482. 17. Renshaw AA, Gould EW. Why there is the tendency to overdiagnose the follicular variant of papillary thyroid carcinoma [editorial]. Am J Clin Pathol. 2002;117:19-21.

Am J Clin Pathol 2002;118:208-210

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