Research Article
Annals Thyroid Res. 2019; 5(1): 188-195.
New Score for Risk Stratification and Sub-classification of Bethesda III Thyroid Nodule for Optimum Management; CUC Score (Cytological, Radiological, and Clinical Scoring System)
Elsaady A1*, Abdelgawad W2
1Department of General Surgery, Kafr Elshikh General Hospital, Egypt
2Facuty of Medicine, Suez University, Egypt
*Corresponding author: Ahmed Elsaady, Department of General Surgery, Kafr Elshikh General Hospital, Egypt
Received: March 05, 2019; Accepted: April 12, 2019; Published: April 19, 2019
Abstract
Background: Thyroid swelling is a common clinical problem. The Bethesda classification of FNAC of the thyroid swelling is very helpful in decision making and choosing the optimum management policy. However, Bethesda III is still a problem with a wide recommendation in the management. Histologically, Bethesda III is a heterogeneous group with considerable cytological variations that proved to be of variable malignant risk. Accordingly, there is a need to subcategorize the Bethesda III into subgroups of variable malignant risk and clear recommendation in the management in order to avoid unnecessary surgery or omit necessary one.
Materials and Methods: The study assumed a score system that includes the cytological and ultrasongraphic features in addition to the clinical risk factors in the assessment and getting subcategories for Bethesda III. The study is a retrospective one that was delivered from May 2016 to January 2019. The cytological features were further subdivided into follicular lesion of undetermined significance or atypia of undetermined significance, while the ultrasound features were standardized by TIRABS. The patients were also assessed for the age, gender, and family history of thyroid cancer, in addition to the red flag sings in the clinical data The latter includes hard consistency, fixed nodule, and or rapid growth or recent onset of the swelling within four to six months. The patients were classified according to the CUC (cytological, ultrasongraphic & clinical) score into three groups; group CUC I; which includes patients with score three or less. Group CUC (2) includes patients with score four or five, and group CUC (3) which includes patients with score six or more. The study assessed the malignant risk in each group. Results: Five hundred and sixty-nine (569) patients were presented in the study and with Bethesda III constituted 23% (131/569). (9/131) Patients (7%) with Bethesda III were sent for repetition of FNAC and 18% (24/131) were observed. While 106 (81%) patients sent for surgery. The total cases with reported malignancy after thyroidectomy were 14 patients (13%). The malignant cases were two (5.5%) in CUC (1) group and four cases (9.5%) in CUC (2) and eight cases (28%) in group CUC (3). On comparisons the three groups, a significant difference was present in the rate of malignancy. Group CUC (3) has the highest risk for malignancy with five folds more than group CUC (I) and three folds more than group CUC (2).
Conclusion: CUC score is a scoring system that utilizes the cytologic and ultrasongraphic features in addition to the demographic & clinical characteristics in determining the malignant risk and sub-categorized Bethesda III. The score provides three groups with variable malignant risk and management policy. CUC (1) group (low risk group) had the lowest malignant risk (5.5%) where ultrasound follow up is recommended as management policy. The CUC (2) groups (intermediate risk group) had an intermediate risk (9.5%) where cytological follow up by repletion of FNAC is recommended. While CUC (3) (high risk group) carries the highest risk (28%) and surgical treatment is recommend.
Keywords: Thyroid nodule; Bethesda classification; Bethesda III subgroups; Thyroid swelling; Cancer thyroid; CUC score for Bethesda III
Introduction
Most thyroid diseases occur in a nodular form and can reach a prevalence of up to 68% in adult women [1]. Bethesda classification of FNAC is very helpful in decision making of the optimum management [2]. However, Bethesda III is still a hazy area, with unclear recommendations for the management. It is very variable from just follow up to surgical treatment (lobectomy or total thyroidectomy). It represents a heterogonous group in the cytological features with wide range in the malignant risk. The limitations of FNA cytology imply that other diagnostic options may be valuable to delineate risk further and assist clinicians in choosing the best management. Accordingly the study assumed a score (CUC Score) involving cytological & ultrasound features as well as the risk factors in the demographic and clinical data to subcategorize Bethesda III into three sub-groups according to the degree of risk and malignant potentiality. The study is a retrospective one that aims at assessment of the significance of the CUC score (cytological, ultrasound & clinical score) in determining the degree of the malignancy risk among patients with Bethesda III and accordingly the optimum management.
Materials & Methods
The study is a retrospective one that was delivered from May 2016 to January 2019). All patients presented with thyroid diseases and sent for fine needle aspiration cytology were involved in the study, to assess the prevalence of Bethesda III among them. Patient with Bethesda III were re-assessed by cytological, ultrasound & clinical score system (CUC score) shown in (Table 1). This score sub-classifies the Bethesda III category into three groups according to the cyto-pathologic, radiologic and clinical risk characteristic in order to determine the approximate risk for malignancy more precisely than the mere use of Bethesda classification. The cytological features were further subdivided into Bethesda III A (follicular lesion of undetermined significance) that given one point in the score, and Bethesda IIIB (atypia of undetermined significance) that given three points in the score. The ultrasound features (standardized by TIRABS) were assessed with increasing the score according to the TIRABS category (as in Table 1). The patients were assessed for age, gender, family history of thyroid cancer, or syndromes associated with thyroid cancer as in (Table 2), in addition to the red flag sings in the clinical data which entail hard consistency, fixed nodule, rapid growth or recent onset of the swelling within four to six months. For each clinical risk factor present 0.5 was given in the score assessment as in (Table 1). According to the patient data, every patient was given a score according to assumed risk mention in (Table 3). The patients were classified according to the CUC score into three groups; CUC (1) group; which includes patients with score three or less, that assumed to have low risk for malignancy. CUC (2) group; which includes patients with score four or five, and assumed to have intermediate risk for malignancy, and CUC (3) group which includes patients with score six or more, and assumed to have high malignant risk. Every group was assessed for the rate of malignancies reported after operative interference.
Risk Factor
Definition
Details
Score; point
Bethesda III
Bethesda III A
follicular lesion of undetermined significance (FLUS)
1
Bethesda III B
atypia of undetermined significance (AUS)
3
TIRADS
TIRADS 0
Normal thyroid gland
0
TIRADS 1
Purely cystic nodule, no solid component.
1
TIRADS 2
Spongiform or partially cystic nodule without any of the sonographic features described in TIRADS 3,4 or 5
2
TIRADS 3
Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid areas, without micro-calcification, irregular margin or ETEc (extra-thyroid extension),
or taller than wider.3
TIRADS 4
Hypoechoic solid nodule with smooth margins without micro-calcification, ETEc, or taller than wider.
4
TIRADS 5
Solid hypoechoic nodule, or solid hypoechoic component of a partially cystic nodule with one or more of the following features;
- irregular margin (infiltrative, micro-lobulated)
- micro-calcification,
- taller than wider shape,
- rim calcifications with small extrusive soft tissue component,
- evidence of ETE (extra-thyroid extension),5
Clinical Data
Age
Less than 14 years, or more than 65 years
Gender
Male
Family History
family history of thyroid carcinoma in a first –degree relative,
Duration
Recent onset or rapid growth within four month in a previously diseased thyroid gland
Clinical signs
Hardness & or fixation of the nodule.
The presence of one or two of these factors
1
The presence of three or more of these factors
2
Total 10
Table 1: CUC score (Cytological, radiological and clinical scoring system) for sub-classification of Bethesda III patients.
• Familial adenomatous polyposis
• Gardner's syndrome
• PTEN hamartoma tumor syndrome
• Carney complex
• Multiple endocrine neoplasia (MEN 2A and 2B)
Familial medullary thyroid cancer
• Cowden's syndrome
• Werner's syndrome
Table 2: Thyroid cancer syndrome; inherited syndromes associated with thyroid cancer.
Items
BTC (1)
BTC (2)
BTC (3)
Prevalence (from 131)
36 (34%)
42 (40%)
28 (26%)
Age (in years)
46
45
48
Gender
Females 36 (100%)
Females 40/42 (95%)
Females 26/28 ( 93%)
Reported Malignancy
2 (5.5%)
4 (9.5)
8 (28.5%)
Table 3: Comparisons between the assumed three CUC subgroups of Bethesda III.
Results
Five hundred and sixty nine (569) patients were presented in the study and with Bethesda III constituted 23% (131/569), while Bethesda II 57% (327/569), Bethesda I 0.9% (5/569), Bethesda IV 12% (69/569), Bethesda V 4% (23/569) & Bethesda VI 3% (17/569). Patients with Bethesda III were prepared for surgery in 75% (98/131), while 7% (9/131) sent for repetition of FNAC and 18% (24/131) were observed. Two patients from the group of repetition of FNAC were sent for surgery while six patients in the observed group were sent for surgery after follow up. Thus the total number of patients sent for surgery was 106 (81%). Eight patients in the observation group were lost in follow up. (Figures 1,2,&3) show cases presented with Bethesda III on FNAC and different pathology after excision biopsy.
Figure 1: Female patient with huge goiter, Bethesda III in FNAC and colloid nodular hyperplasia after thyroidectomy.
Figure 2: Male Patient with right thyroid nodule (STN) & Bethesda III on FNAC. Total thyroidectomy was done and papillary thyroid carcinoma was reported in
biopsy.
Figure 3: Female patient with thyroid swelling, TIRADS 2, Bethesda III with follicular lesion of undetermined significance. Right hemi-thyroidectomy was done and
adenomatous colloid multi-nodular goiter reported in biopsy.
The total cases with reported malignancy after thyroidectomy were 14 patients (13%).
On assessment of CUC (1) group (assumed low risk group), which included patients with score three or less; 36 patients (34%) were presented, the mean age was 46 years and all patients were female (100%). The malignant cases were two (5.5%).
While CUC (2) group (assumed intermediate risk group)m that included patients with score 4 or 5, contained 42 patients (40%), the mean age was forty five years, forty patients were females (95%). The malignancy was reported in four cases (9.5%).
The CUC (3) group (assumed high risk group),which included patients with score 6 or more, has 28 patients (26%), with the mean age was forty eight, and twenty six patients were females (95%). The malignancy was reported in eight cases (28%).
On comparisons the three groups (Table 4); there is no significant difference in the mean age or gender. But a significant difference was present in the rate of malignancy. CUC (3) group has the highest risk for malignancy with five folds more than CUC (1) group and three folds more than CUC (2) group.
Bethesda category
Cytopathologic
category
Approximate
expected frequency
Malignancy rate
Suggested treatment (Prior to availability of molecular testing)
I
Non-diagnostic/Inadequate
5-11%
1-4%
Repeat FNA
II
Benign
55-74%
0-3%
US follow-up
I I I
Atypia/fdlioular lesion of undetermined significance
5-15%
5-15%
Repeat FNA or US follow-up or Lobectomy
I V
Follicular neoplasm/ St-ISPiCiOLJS for FN
2-25%
15-30%
Lobectomy
V
Suspicious for malignancy
1-6%
60-75%
Lobectorny or Thyroidectomy
VI
Malignant
2-5%
97.99%
Near-total thyroidectomy
FNA: Fine-needle aspiration; FN: Follicular neoplasm; US: Ultrasonographic
Table 4: Bethesda System for Reporting Thyroid Cytopathology.
Discussion
Thyroid disease is a common clinical problem. Most of thyroid diseases occur in a nodular form. The prevalence of thyroid nodules in adults is reported between 4 to 8% [1], and up to 67% by ultrasound, while in autopsies up to 49–57% [3]. Although most of these nodules are benign, the possibility of malignancy is a major concern [4]. In fact, the differential diagnosis of a thyroid nodule is the most common endocrine problem [3]. Fine Needle Aspiration Cytology (FNAC) is the corner stone in decision making in the management of thyroid nodules especially after the FNAC reports had been standardized by the Bethesda System for Reporting Thyroid Cytopathology according to the suspected rate of malignancy [5]. Bethesda system consists of six categories that usually provide clear decision in the management of the patients as shown in (Table 4).
However, the category of Bethesda III is still a major problem with no clear recommendation or cut off for surgical interference. They represent a considerable ratio of cases, that is variable in different studies as shown in (Table 5) [6]. However, a recent large study reported a prevalence of more than 35% of the all Bethesda categories [7].
Study
Year Country
Total
FNAC
casesPercentage of cases in each
Bethesda categoryFNAC
withfollow-ups
Risk of malignancy in each
Bethesda category (X)
IV
v
VI
►
it
in
iv
v
VI
TEtSPTC[14]
2010
2-20
60-70 3-7
•
2-8
3-7
1.4
0-3
5.15
15.30
60-75
97-99
Middle East
Present study
2017 Bahrain
681
10.1
68.8 12.4
2.9
2.6
4.1
126
6.67
Is
28
22.2
72.7
100
Mufti and Mola[3]
2012 KSA
250
11.6
77.6 0.8
4
2.4
3.6
84
20
3.1
SO
20
80
100
Al Dawish et al. [14]
2017 KSA
1433
3.2
75.3 9.1
5
2.2
5.1
124
25
8.9
14.3
47.2
69.7
96.7
Kapita et al. [17]
2015 Kuwait
374
4.8
30.5 15.8
4.5
21.4
23
374
33.3
11.4
18.6
35.3
61.3
96.5
Sinna and Exaatl[18]
2012 Egypt
296
7.1
33.1 13
16.5
10.1
19.5
220
2
32.7
96.7
96.0
Other countries
Bongiovanni et al. [13]
2012 Meta-analysis 2.5.445
12.9
59.3 9.6
10.1
2.7
5.4
6.362
16.8
3.7
15.9
26.1
75.2
98.6
Wu et al. [3]
2012 USA 1382
20.1
39 27.2
8.4
2.6
2.7
221
3
6
22
56
100
Kiernan et al. [11]
2014 USA
777
3
36 26
9
8
18
777
4
4.3
IS
26
65
97
Jo et al. [9]
2010 USA
3080
18.6
59 3.4
9.7
2.3
7
892
8.9
1.1
17
25.4
70
98.1
Sarkis et al. [1]
2014 Australia
2076
12.8
74.7 4.7
4.7
0.8
2.3
425
4.2
0.26
9.3
15.3
79
100
Melo-Uribe et al. [2]
2015 Colombia
196
4.1
23.5 2
16.8
37.2
16.3
196
75
13
75
39
90
100
Mondal et al. [4]
2013 India
1020
1.2
87.5
4.2
1.4
4.7
323
0
4.5
20
30.6
75
97.8
*FNAC with follow-up: Cases of FNAC underwent surgical treatment and correlation was done between cytology and histology result. KSA: Kingdom of Saudi Arabia; USA: United States of America; FNAC: Fine needle aspiration cytology.
Table 5: Comparison of percentages of cases in each Bethesda Category and risk of malignancy between different studies.
The expected malignancy rates for the Bethesda III category range from 5 to 15% according to relevant published studies [7]. Some recent papers have shown higher malignancy rates in lesions associated with nuclear atypia [8] and even the risk may exceed category Bethesda IV [9], suggesting that the heterogeneity of lesions within Bethesda III may have relevant impacts on the diagnosis and management of patients [10]. The current recommendation for the management of Bethesda III includes repetition of FNAC, ultrasound follow up or surgical interference (lobectomy) [11].
Some modifications of the Bethesda III have been developed to be subcategorized according to cytopathological characteristics to get more precise malignant risk.
Leticia et al subcategorized Bethesda III into; Bethesda IIIA which entails Follicular Lesion of Undetermined Significance (FLUS), and Bethesda IIIB that consists of lesion with Atypia of Undetermined Significance (AUS) [7]. They reported significantly higher malignancy rates for Bethesda Class IIIB than those for Bethesda Class IIIA and even Bethesda Class IV [7]. Other study has divided Bethesda III into; cases presenting common characteristics of papillary carcinomas and cases without features of papillary carcinoma. This study showed increased malignancy rates associated with the papillary features [5]. On the other hand Renshaw subdivided Bethesda III into four groups, and reported a difference in the malignancy risks that reached to 38% higher risk in lesions with papillary carcinoma characteristics [12]. Others have divided Bethesda III nodules into those with low cellularity with a micro-follicular pattern and those showing nuclear atypia with significant increase in the malignant risk in atypia group [13]. Some studies have suggested that nuclear atypia is an independent risk factor [14]. Kelman et al. found that up to 60% of thyroid nodules with nuclear atypia were related to malignant disease, while only 7% of those without atypia had the same diagnosis [14].
Similarly, other authors re-evaluated the sub classification of Bethesda III and considered two categories: architectural atypia and nuclear atypia and concluded that; patients with nuclear atypia had a malignancy rate of 35% compared to a rate of 10% for other Bethesda III cases [15]. Again, Bethesda III is re-classified in another study into four groups; nonspecific, favor benign , papillary cancer cannot be excluded, Hurthle cell neoplasm can`t be excluded, & follicular neoplasm can`t be excluded as in (Table 6) with variable malignancy risk among these groups [16]. Other published cohorts of smaller size have suggested wide-ranging malignancy risk for Bethesda III [16]. Parengi et al. observed an incidence of 16% [17], while Vander Laan et al. reported a prevalence of 46% [18]. These and other outcomes have been confounded by study periods predating the Bethesda System for Reporting Thyroid Cytopathology, an incidence of AUS/ FLUS diagnoses that is higher than the 7% expected, and, in some cases, inflation of the malignancy rate with incidental cancers [19].
AUS/FLUS cases with surgery
Benigna
Malignant
AUSIFLUS—NOS (n=218)
41.3% [CI 36.0-46.6]
36.2% [CI 29.4-42.5]
AUS/FLUS—favor benign (n=13)
76.9% [CI 69.2-84.6]
7.7% [CI 1.9-36.0]
AUS/FLUS—cannot exclude FTC (n=28)
28.6% ICI 9.4-47.8)
53.6% [CI 33.9-72.1]
AUSiFLUS—cannot exclude Hiinhle cell neoplasm (n=44)
341% [CI 20.5-47.7]
29.5% [CI 16.8-45.2]
AUS/FLUS—cannot exclude follicular neoplasm (n=78)
24.4% [CI 11.9-36.9]
56.4% [Cl 443-67.6]
aExcludes nonmalignant neoplasms.
CI: Confidence Interval; PTC: Papillary Thyroid Carcinoma; NOS: Not Otherwise Specified.
Table 6: Cytologic substratification of Bethesda III nodules.
A large study was done at Memorial Sloan–Kettering Cancer Center to determine the risk of malignancy in Bethesda iii and concluded that; the risk of malignancy in Bethesda III group is higher than estimated, with an estimated prevalence of 26.6-37.8%. Repetition of FNAC may not have clear utility in clinical decisionmaking and the guidelines recommending repeat FNA or observation merit reconsideration [16]. In addition the study added The limitations of FNA cytology imply that other diagnostic options may be valuable to delineate risk further and assist clinicians in identifying low-risk patients who may not require surgery [16].
Accordingly this Bethesda III category represents a heterogeneous group in terms of lesion characteristics, and wide range in both the malignancy rates, and the assumed management policy [15]. Consequently, Bethesda III need to be further reassessed in order to reach a clear guideline in the management.
On the other hand many sonographic characteristics of a thyroid nodule associated with a higher likelihood of malignancy include hypo echogenicity, increased intra-nodular vascularity, irregular margins, micro calcifications, absent halo, and a taller-than-wide shape measured in the transverse dimension [20]. Accordingly, ultrasound assessment and participation in decision making in the management of thyroid nodules is progressively increasing and well established. Similarly, the sonographic data and reports are recently standardized by Thyroid Imaging Reporting and Data Systems (TIRADS), that have been proposed for risk stratification of thyroid nodules (demonstrated in figure 4) [15]. The terminology of TIRADS was first used by Horvath et al. [21]. The initial purpose of TIRADS was to improve patient management and cost-effectiveness by avoiding unnecessary FNA Biopsies in patients with thyroid nodules (Table 7), with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 88, 49, 49, 88, and 94%, respectively [22]. However, its clinical use is still very limited and its practical application in clinical practice is questioned [22]. Some modifications of TIRAB were developed to improve the accuracy, such as Kwack that further subcategorized TIRAB categories [23]. However, large study has reported that TIRADS described by Horvath is not practicable due to numerous unclassifiable nodules, while the revised TIRADS published by Kwak is feasible and suitable to assess the prevalence of malignancy, but it cannot replace scintigraphic imaging and still of limited value compared to Bethesda in recommendation for the best management [24]. Moreover, till now FNAC is the most accurate method for determining malignancy, and is a fundamental part of current thyroid nodule evaluation [22].
Sonographic Pattern
Ultrasound Features
Estimated Risk of Malignancy
High Suspicion (TIRAB V)
Solid hypoechoic nodule or solid hypoechoic component of a partially cystic nodule with one or more of the following features:
Irregular margins (infiltrative, microlobulatecl), microcalcifications, taller than wide shape, rim calcifications with small extrusive soft tissue component, evidence of ETE
>70% to 90%°
Intermediate
(TIRAB IV)
Hypoechoic solid nodule with smooth mar- gins without microcalcifications, ETE, or tatter than wide shape
10% to 20%
Low Suspicion
(TIRAB III)
Isoechoic or hyperechoic solid nodule, or partially cystic nodule with eccentric solid areas, without microcalcification, irregular margin or ETEc, or taller than wide shape.
5%-10%
Very Low Suspicion
(TIRAB II)
Spongiform or partially cystic nodules without any of the sonographic features described in low, Intermediate, or high suspicion patterns
Benign (TIRAB I)
Purely cystic nodules (no solid component)
<1%
Normal (TIRAB O)
Norm thyroid gland
Table 7: Thyroid Imaging Reporting and Data Systems (TIRADS).
Figure 4: TIRADS for sonographic assessment of thyroid nodule and risk of malignancy. (ATA (American thyroid association) guidelines in the management of
thyroid nodule, 2015).
In addition some demographics of the patients are important and should not be ignored in assessment of the malignant potentiality. The risk of cancer is higher with extremes of age (< 14 or >65) and male gender [3]. Also, family history of thyroid carcinoma in a first ¬degree relative, and positive family history of syndromes that are associated with differentiated thyroid cancer (Figure 4) constitute considerable risk factors that should be considered [3]. Clinical data such as hardness or fixation of the nodule as well as recent onset or rapid growth within four month in a previously diseased thyroid gland are considered one of the red flag signs for malignancy [25]. Subsequently, this study assumed a scoring system (CUC scoring system) for risk scarification of Bethesda III category considering the cytopathologic, ultrasound, and clinical characteristics (Table 8), to get a clear surgical decision in these cases. Cytologicaly, the study re-classified Bethesda III into Bethesda III A which entails Follicular lesion of Undetermined Significance (FUS) giving it a point in the score and Bethesda III B which consists of lesion of an Atypia of Undetermined Significance (AUS), giving it three points in the score. This based on the data from different studies that reported risk of malignancy three fold or more in cases presented with nuclear atypia than those with undetermined follicular lesions. Shrestha et al. showed a 36.8% malignancy rate for patients with nuclear atypia compared to rate of 10.8% in those without nuclear atypia [8]. Similary, Rosario PW et al, reported a malignancy rate of 41.5% in patients with nuclear atypia, while those with architectural atypia or others had a malignancy rate of 15.5% [26]. The CUC scoring system incorporate the ultrasonographic features that were standardized by TIRADS in the assessment giving the lesion scoring from zero to five according to the ultrasound findings. The CUC scor also consider the red flag signs in the clinical data in its assessment of the malignant potentiality of the lesion. For each clinical risk factor present, 0.5 was given in the score assessment as in (Table 1). The Cytological, ultrasound & clinical score system (CUC score) sub-classifies the Bethesda III into three groups according to the degree of malignant risk.
BTC Scoring System
Score
Risk for malignancy
recommendation for management
BTC (1)
1,2,3
5.5%
Follow up after 4 months (clinical & ultrasound)
and reassessment and Re-scoring.
BTC (2)
4,5
9.5%
Repetition of FNAC after 4 -6 months
With re assessment clinical & ultrasound,
and re-scoring
BTC (3)
6 or more
28.5%
Lobectomy or total thyroidectomy.
Table 8: CUC Scoring System for Bethesda III and selection of the management policy.
Bethesda III low risk group (CUC 1): Which has score three point or less, this has a low risk for malignancy (5.5%), and the study suggested follow up management poly for these patient with clinical and ultrasound re assessment after four months and re scoring again.
Bethesda III Intermediate risk group (CUC 2): Which has score of four or five points, this has a intermediate risk for malignancy (9.5%), and the study suggested cytological follow up by repetition of FNAC re-assessment.
Bethesda III High risk group (CUC 3): Which has score six points or more, this has a high risk for malignancy (~28.5%), and the study suggested surgical management for this patients with lobectomy or total thyroidectomy.
Although further studies may be needed for more evaluation of the significance of CUC score, but there no doubt in the necessity of sub categorizing the Bethesda III category for better risk assessment and precise choice of the optimum management.
Conclusion
The differential diagnosis of a thyroid nodule is the most common endocrine problem with the Fine Needle Aspiration Cytology (FNAC) standardized by Bethesda system is the corner stone in decision making & management. However, Bethesda III is still a problem that needs to be subcategorized for better risk assessment and consequently the optimum management. The Cytological, ultrasound & clinical score (CUC score) is a scoring system that utilizes the cytologic and ultrasongraphic features in addition to the risk factors in the clinical data in determining the malignant risk. The score provides three groups with variable malignant risk and management policy. The study subcategorized the Bethesda III category into three groups. Low risk group (CUC 1) that has a low malignant risk (5.5%) where ultrasound follow up is recommended as management policy. Intermediate risk group (CUC 2) group; that has an intermediate risk (9.5%) where cytological follow up by repetition of FNAC is recommended. And High risk group (CUC 3) that carries a high malignant risk (28%) and surgical treatment is recommend in this group.
References
- Rosário PW, Ward LS, Carvalho GA, Graf H, Maciel RM, Maciel LM, et al. Thyroid nodules and differentiated thyroid cancer: update on the Brazilian consensus. Arq Bras Endocrinol Metabol. 2013;57: 240–264.
- Heller MT, Gilbert C, Ohori NP, Tublin ME. Correlation of Ultrasound Findings With the Bethesda Cytopathology Classification for Thyroid Nodule Fine-Needle Aspiration: A Primer for Radiologists. American Journal of Roentgenology. 2013; 201: 487-494.
- Maher Ghanem, Matthew T Olson, Martha A Zeiger. Approach to Thyroid Nodules. In Textbook of Endocrine Surgery. Orlo H Clark, Quan-Yang Duh, Electron Kebebew et al., The Health Sciences Publisher Third Edition 2016; 10; 122-132.
- Hong MJ, Na DG, Baek JH, Sung JY, Kim JH. Cytology-Ultrasonography Risk-Stratification Scoring System Based on Fine-Needle Aspiration Cytology and the Korean-Thyroid Imaging Reporting and Data System. Thyroid. 2017; 27: 953-959.
- Cibas ES, Ali SZ. NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009; 132: 658–665.
- Alshaikh S, Harb Z, Aljufairi E, Almahari SA. Classification of thyroid fineneedle aspiration cytology into Bethesda categories: An institutional experience and review of the literature. Cytojournal. 2018; 15: 4.
- Mosca L, Ferraz da Silva ILF, Carneiro PC, Chacon DA, Furtado de Araujo- Neto VJ, Furtado de Araujo-Filho IVJ, et al. Malignancy rates for Bethesda III subcategories in thyroid fine needle aspiration biopsy (FNAB). Clinics (Sao Paulo). 2018; 73: e370.
- Shrestha RT, Hennessey JV. Cytologic subclassification of atypia of undetermined significance may predict thyroid nodules more likely to be malignant at surgery. Diagn Cytopathol. 2016; 44: 492–498.
- Lee YB, Kim JY, Cho H, Hahn SY, Shin JH, Lee SE, et al. Modified Bethesda system informing cytopathologic adequacy improves malignancy risk stratification in nodules considered benign or atypia (follicular lesion) of undetermined significance. Scientific Reports. 2018; 8: 13503.
- Gao LY, Wang Y, Jiang YX, Yang X, Liu RY, Xi XH, et al, Ultrasound is helpful to differentiate Bethesda class III thyroid nodules: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2017; 96: 6564.
- Ho AS, Sarti EE, Jain KS, Wang H, Nixon IJ, Shaha AR, et al. Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS). Thyroid: official journal of the American Thyroid Association. 2014; 24: 832–839.
- Renshaw AA. Should “atypical follicular cells” in thyroid fine-needle aspirates be subclassified. Cancer Cytopathol. 2010;118: 186–189.
- Ustün H, Astarci HM, Altunkaya C, Yilmaz S, Barin A, Ekici S, et al. Fineneedle aspiration of follicular patterned lesions of the thyroid: diagnosis, management, and follow-up according to thyroid Bethesda system. Acta Cytol. 2012; 56: 361–369.
- Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Thyroid. 2009; 19: 1215–1223.
- Gan TR, Nga ME, Lum JH, Wong WM, Tan WB, Parameswaran R, et al. Thyroid cytology-nuclear versus architectural atypia within the “Atypia of undetermined significance/follicular lesion of undetermined significance” Bethesda category have significantly different rates of malignancy. Cancer Cytopathol. 2017; 125: 245–256.
- Ho AS, Sarti EE, Jain KS, Wang H, Nixon IJ, Shaha AR, et al. Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III (AUS/FLUS). THYROID. 2014; 24: 832-839.
- Nagarkatti SS, Faquin WC, Lubitz CC, Garcia DM, Barbesino G, Ross DS, et al. Management of thyroid nodules with atypical cytology on fine-needle aspiration biopsy. Ann Surg Oncol. 2013; 20: 60–65.
- VanderLaan PA, Marqusee E, Krane JF. Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: should repeated FNA be the preferred initial approach? Am J Clin Pathol. 2011; 135: 770-775.
- Jo VY, Stelow EB, Dustin SM, Hanley KZ. Malignancy risk for fine-needle aspiration of thyroid lesions according to the Bethesda System for Reporting Thyroid Cytopathology. Am J Clin Pathol. 2010; 134: 450–456.
- Yoon JH, Lee HS, Kim EK, Moon HJ, Kwak JY. Malignancy risk stratification of thyroid nodules: comparison between the thyroid imaging reporting and data system and the 2014 American thyroid association management guidelines. Radiology. 2016; 278: 917–924.
- Horvath E, Majlis S, Rossi R, Franco C, Niedmann JP, Castro A, et al. An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management. J Clin Endocrinol Metab. 2009; 94: 1748–1751.
- Hernando Vargas-Uricoechea, Ivonne Meza-Cabrera, Jorge Herrera- Chaparro. Concordance between the TIRADS ultrasound criteria and the BETHESDA cytology criteria on the nontoxic thyroid nodule. Thyroid Res. 2017; 10: 1.
- Kwak JY, Han KH, Yoon JH, Moon HJ, Son EJ, Park SH, et al. Thyroid imaging reporting and data system for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 2011; 260: 892–899.
- Schenke S1, Rink T, Zimny M. TIRADS for sonographic assessment of hypofunctioning and indifferent thyroid nodules. Nuklearmedizin. 2015; 54: 144-1450.
- Paul R. Maddox, Malcolm H Wheeler. Approach to Thyroid Nodules. Textbook of Endocrine Surgery Orlo H Clark, Quan-Yang Duh, Electron Kebebew et al. The ELSEVIER SAUNDERS. 2nd Edition. 2005; 9; 85-92.
- Rosario PW, Calsolari MR. Importance of cytological subclassification of thyroid nodules with Bethesda category III cytology (AUS/FLUS) into architectural atypia only and nuclear atypia: A prospective study. Diagn Cytopathol. 2017; 45: 604–607.
Download PDF