The Correlation of Age with Prognosis of Atypia of Undetermined Significance and Follicular Lesion of Undetermined Significance in Thyroid Nodules

Figures & data

Figure 1 Cytological specimens of TNs assigned to the AUS/FLUS category of TBSRTC. Hematoxylin and eosin staining, 400× magnification. (A) Cytological atypia. Some cells have mild nuclear enlargement and slight nuclear pleomorphism. (B) Predominant population of microfollicles in an aspirate. (C) Cellular sample composed almost entirely of Hürthle-like cells in a sparse cellular aspirate. Atypia of undetermined significance presenting focal crowded follicular cell clusters with abundant colloid. AUS/FLUS: atypia of undetermined significance/follicular lesion of undetermined significance; TBSRTC: The Bethesda System for Reporting Thyroid Cytopathology.

Figure 2 Suspicious ultrasound imaging features of TNs assigned to the AUS/FLUS category in UG-FNAB examination. (A) Transverse US imaging of a TN with microcalcifications (white arrows) without posterior acoustic shadowing. Histopathology revealed PTC. (B) Transverse US imaging of a TN with irregular margins (yellow arrows), microcalcifications (white arrows) and marked hypoechogenicity (blue arrows). Histopathology revealed fvPTC. (C) Transverse US imaging of a TN demonstrating a taller-than-wide shape (brackets). Hypoechogenicity is also presented. Histology revealed PTC. (D) Sagittal US imaging of TN with irregular margins (yellow arrows), microcalcifications (white arrows), cystic components (blue arrows) and hypoechogenicity. Histopathology revealed PTC. AUS/FLUS: atypia of undetermined significance/follicular lesion of undetermined significance; UG-FNAB: ultrasound guided fine needle aspiration biopsy; US: ultrasonography; TN: thyroid nodule; PTC: papillary thyroid cancer; fvPTC: follicular variant of papillary thyroid cancer.

Figure 3 Flowchart of patient selection with individuals finally included in the study. AUS/FLUS: atypia of undetermined significance/follicular lesion of undetermined significance.

Table 1 Demographic and Clinical Parameters and Ultrasound Features of the 161 Patients with Bethesda Category III (AUS/FLUS)

Variables	Number of Observations (n)	Percent (%)
Age (years)	50.60 ± 16.12*
Age:
<55 years	91	56.5
55–75 years	58	36.0
>75 years	12	7.5
Sex
Male	31	19.3
Female	130	80.7
Final diagnosis
Adenoma	48	29.8
Goiter	66	41.0
Thyroiditis	26	16.1
NIFTP	2	1.2
PTC	16	9.9
fvPTC	2	1.2
FTC	1	0.6
Thyroid nodules
Benign	142	88.2
Malignant	19	11.8
Ultrasound features
Composition
Solid	123	76.4
Cystic	17	10.6
Spongiform	21	13.0
Microcalcifications
Yes	38	23.6
No	123	76.4
Echogenicity
Hypoechoic	63	39.1
Hyperechoic	98	60.9
Irregular margin
Yes	61	37.9
No	100	62.1
Taller than wide
Yes	50	31.1
No	111	68.9
High vascularity
Yes	78	48.4
No	83	51.6
Fast growth
Yes	49	30.4
No	112	69.6
Macrocalcifications
Yes	69	42.9
No	92	57.1

Note: *Mean ± SD.

Abbreviations: AUS/FLUS, atypia of undetermined significance/follicular lesion of undetermined significance; NIFTP, noninvasive follicular neoplasm with papillary-like features; PTC, papillary thyroid cancer; fvPTC, follicular variant of papillary thyroid cancer; FTC, follicular thyroid cancer.

Table 2 Demographic, Clinical and Ultrasound Characteristics of Three Subgroups of Patients with Bethesda III Category According to Age Parameter. Data are Presented as the Number of Observations (Percent)

Variables	Age: <55 Years (n=91)	Age: 55–75 Years (n=58)	Age: >75 Years (n=12)	P-value
Sex				0.122
Male	16 (17.6)	10 (17.2)	5 (41.7)
Female	75 (82.4)	48 (82.8)	7 (58.3)
Thyroid nodules				0.021*
Benign	76 (82.6)	55 (96.5)	11 (91.7)
Cancer	16 (17.4)	2 (3.5)	1 (8.3)
Composition				0.188
Solid	70 (76.9)	44 (75.8)	9 (75.0)
Cystic	7 (7.7)	7 (12.1)	3 (25.0)
Spongiform	14 (15.4)	7 (12.1)	0 (0.0)
Microcalcifications				0.072
Yes	26 (28.6)	8 (13.8)	4 (33.3)
No	65 (71.4)	50 (86.2)	8 (66.7)
Echogenicity				0.345
Hypoechoic  Hyperechoic	33 (36.3) 58 (63.7)	23 (39.7) 35 (60.3)	7 (58.3) 5 (41.7)
Irregular margin				0.329
Yes	33 (36.3)	21 (36.2)	7 (58.3)
No	58 (63.7)	37 (63.8)	5 (41.7)

Note: *Statistically significant.

Table 3 Logistic Regression Analysis of Ultrasound Variables as Risk Factors of Cancer Presence in Total Group of Patients with Bethesda III Category. Results Were Calculated by Chi-Square Wald Test

Independent Variables	OR (± 95% CI)	p-value
For: hypoechogenicity	38.80 (4.94–304.48)	<0.001*
For: microcalcifications	13.77 (4.49–42.19)	<0.0001*
For: high vascularity	1.94 (0.73–5.34)	0.177
For: fast growth	11.91 (3.67–38.66)	<0.0001*
For: irregular margins	41.44 (5.27–325.47)	<0.001*
For: taller than wide	16.94 (4.60–62.27)	<0.0001*
For: macrocalcifications	0.75 (0.27–2.04)	0.573

Note: *Statistically significant.

Abbreviations: OR, odds ratio; ±95% CI, ± 95% confidence interval.

Table 4 Logistic Regression Analysis of Age Variable as Risk Factors of Malignancy Presence, High Vascularity and Fast Growth of Thyroid Nodules in Patients with Bethesda III Category. Results Were Calculated by Chi-Square Wald Test

Age as Independent Variable	Cancer Presence		High Vascularity		Fast Growth
	OR (± 95% CI)	p-value	OR (± 95% CI)	p-value	OR (± 95% CI)	p-value
For <55 years	3.72 (1.17–11.78)	0.024*	1.89 (1.00–3.54)	0.045*	3.19 (1.52–6.70)	0.002*
For 55–75 years	0.18 (0.04–0.84)	0.040*	0.93 (0.48–1.79)	0.839	0.30 (0.13–0.68)	0.004*
For >75 years	0.66 (0.08–5.52)	0.700	0.09 (0.01–0.68)	0.019*	0.43 (0.09–2.08)	0.293

Note: *Statistically significant.

Abbreviations: OR, odds ratio; ±95% CI, ± 95% confidence interval.