To date several published series have documented the difficulty in diagnosing follicular patterned lesions of the thyroid in cytology preparations [5
]. The histologic follow-up of cases diagnosed as follicular lesions of neoplasm includes hyperplastic/adenomatoid nodules, follicular adenoma, follicular carcinoma and follicular variant of papillary carcinoma [6
]. An earlier study published by Schlinkert et al from Mayo clinic showed that only 12% cases diagnosed as "suspicious for follicular neoplasm" on FNA were malignant on histologic follow-up. Interestingly, 27% were papillary carcinomas (majority were follicular variant) [4
]. Tuttle et al reported malignancy rate of 21% in their series of 149 patients diagnosed as follicular neoplasm on cytology [8
]. In our previous study the malignancy rate was 31% in 122 patients diagnosed as follicular neoplasm and almost half of these cases were follicular variant of papillary carcinoma.
In view of these above-mentioned studies we retrospectively reviewed the cases of FVPTC and found that some cases are under-diagnosed as follicular neoplasm due to the paucity of nuclear features of papillary carcinoma, an exact reflection of what is seen in surgical pathology of some cases of FVPTC [3
]. Similar findings have been reported by other authors [17
]. In view of these studies at our institution the thyroid FNA specimens are classified as benign, neoplastic, FDN/suspicious for papillary carcinoma, definitely malignant and non-diagnostic.
In the present study, 339 cases were diagnosed as follicular neoplasm; the malignancy rate in this group was 22% and half of the cases were FVPTC. These findings are similar to previously published studies. Of the 120 cases diagnosed as FDN 72% (86 cases) were malignant and papillary carcinoma was present in 92% (79/86) of cases.
It has been shown that thyroid nodules can be divided into high and low risk of malignancy on the basis of clinical characteristics. Schlinkert et al reported that findings of larger diameter, fixation of mass and younger age of patients were associated with high risk of malignancy [4
]. According to study by Tyler et al patients greater than 50 years of age with a diagnosis of follicular neoplasm had a higher risk of malignancy as compared to patients younger than 50 years [9
]. In a previous study of 122 patients diagnosed as FON we showed that patients aged 40 years or more had higher risk of malignancy than those younger than 40 years [6
]. Interestingly, the current study which consists of a much larger group of patients and combines cases diagnosed as FON and FDN the malignancy rate was higher in patients younger than 40 years than those aged 40 years or higher (53% vs. 30%). No significant difference in malignancy rates was noted between thyroid nodules measuring less than 3 cm or equal to and greater than 3 cm. (Fig ). These differences from the previous studies could be due to a higher number of cases diagnosed as papillary carcinomas (>70%) in the present study. Since, papillary carcinoma is common at younger age and can occur in any size as compared to follicular or Hurthle cell carcinoma.
Figure 1 Monotonous population of follicular cells arranged in cohesive follicular groups with nuclear overlapping and crowding, case diagnosed as follicular neoplasm (1A). Histologic follow-up showing follicular adenoma (thickly encapsulated follicular patterned (more ...)
The other significant predictor of malignancy in our study was sex of patient; malignant tumors were more common in males as compared to female patients (41% vs. 33%). In addition, though not statistically significant FCA was more common in males as compared to females (30% vs. 21%).
Frozen section is usually not recommended for the diagnosis of thyroid lesions [20
]. Studies have shown that intraoperative consultation is of no value in the diagnosis of follicular carcinoma since its diagnosis is dependent upon invasion of tumor capsule and/or capsular vessels, which can be missed by limited sampling of tumor capsule on frozen section [20
]. However, frozen section combined with intraoperative cytology has been shown to be of value in cases diagnosed as suspicious of papillary carcinoma in preventing two-step surgical excision (lobectomy followed by total thyroidectomy)[21
]. At our institution, we recommend intraoperative consultation in cases diagnosed as FDN on cytology[5
]. In the present study 36(30%) cases were diagnosed as papillary carcinoma on frozen section and intraoperative cytology.
It has been shown that molecular markers can be of value in the cytologic diagnosis of malignant lesions of thyroid. Ret-oncogene rearrangements are believed to be specific to papillary carcinoma of the thyroid, and this marker can be of value in identifying cases of FVPTC in thyroid FNA [22
]. Recently, BRAF rearrangements have been reported in papillary carcinoma and shown to be specific to this tumor. Similar studies regarding detection of BRAF rearrangements in thyroid FNA specimens have shown promise as a diagnostic aid to morphology [22
]. However, BRAF expression is less common in FVPTC as compared to classic papillary carcinoma; therefore, its use in the diagnosis of FVPTC in FNA specimens may be of limited value.
In conclusion, until a specific markers or panel of markers is devised which can effectively distinguishes between benign and malignant follicular lesions of the thyroid in FNA specimens morphology remains the gold standard. The category of follicular lesion/neoplasm can further modified by dividing these cases into two: lesions with and without subtle nuclear features of papillary carcinoma because of marked difference in malignancy rates (22% vs. 72%).