|Year : 2019 | Volume
| Issue : 3 | Page : 1142-1148
Relationship between thyroid nodule size and incidence of thyroid cancer
Ahmed S El-Gammal, Mohammed A E-Balshy, Kareem M Zahran
Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||06-May-2018|
|Date of Acceptance||28-Jul-2018|
|Date of Web Publication||17-Oct-2019|
Kareem M Zahran
Source of Support: None, Conflict of Interest: None
The aim of this study was to study the size of thyroid nodule as a risk factor of thyroid malignancy.
The nodular thyroid lesions are of interest to surgeons and patients since the major differential diagnosis is cancer. These thyroid lesions are present as solitary or multiple nodules.
Patients and methods
This study was carried out on 330 patients aged from 13 to 65 years, every patient included in the study were subjected to history taking, physical examination, preoperative investigations (thyroid function test and routine investigations and ultrasonography on thyroid gland to detect the size of lobes and size of nodules and their dimensions). According to the cases we performed they were classified as total, subtotal, or hemithyroidectomy. The specimens were sent for routine histopathology after the operation to detect the percentage of thyroid cancer related to the thyroid nodule size
Our results showed that most of the studied patients with thyroid nodules were aged less than 45 years and most of them were women. About 81% of the patients had nodular sizes greater than or equal to 2 cm. The prevalence of cancer was 15.5% among the studied cases. The prevalence of cancer among female patients aged greater than or equal to 45 years, had bilateral nodules with normal function. The cases with a nodular size of 1.0–1.9 cm were more prevalent among cancer patients than in benign cases. After adjustment of confounding factors, the size of nodules (1.0–1.9 cm) and age were still predictors of cancer in the studied cases. Nodular size had 2.5 times prediction of cancer while age had about 0.5 times.
A larger nodule size increases malignancy risk by up to 2 cm but further growth beyond 2 cm no longer influences malignant risk.
Keywords: cancer, incidence, nodule, thyroid, ultrasound
|How to cite this article:|
El-Gammal AS, E-Balshy MA, Zahran KM. Relationship between thyroid nodule size and incidence of thyroid cancer. Menoufia Med J 2019;32:1142-8
|How to cite this URL:|
El-Gammal AS, E-Balshy MA, Zahran KM. Relationship between thyroid nodule size and incidence of thyroid cancer. Menoufia Med J [serial online] 2019 [cited 2020 Apr 4];32:1142-8. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/1142/268812
| Introduction|| |
Palpable thyroid nodules occur in about 6% of women and 2% of men with higher prevelance in the elderly and iodine-deficient areas. However, the great majority of thyroid nodules are impalpable and asymptomatic with an estimated prevalence of 20–76% in the general population .
These small nodules are increasingly detected by neck ultrasound and parallel the rising incidence of small differentiated thyroid cancer over the last two decades .
The most common causes of thyroid nodules are colloid nodules, Hashimoto's, subacute thyroditis, cysts, follicular adenomas, and thyroid cancer . The presenting clinical problems include hyperthyroidism, pain (often due to hemorrhage into a cyst) and compressive symptoms (due to multinodular goiter). However, the clinical priority in the initial management of a thyroid nodule is to evaluate its thyroid cancer risk to guide decision regarding thyroidectomy .
Thyroid cancer occurs in 0.5–2% of multinodular goiter and 5–10% in solitary thyroid nodule. Approximatly 90% of all thyroid cancers are of differentiated type and 85% of which are papillary cancer.
Evaluation of thyroid cancer risk includes the clinical picture, thyroid function, ultrasound characteristics of the nodule and fine needle and also there is a method that is safe, cost effective and without morbidity  which is aspiration biopsy .
The goal of thyroid nodule evaluation is to assess accurately the risk of such a nodule being cancerous via methods that are accurate and precise.
A number of clinical findings indicate an increased risk of thyroid cancer. These include hard nodule, evidence of local invasion such as fixation to adjacent structures or vocal cord palsy, cervical lymphadenopathy, or rapid nodule growth. Other important clinical risk factors include a prior hemithyroidectomy with discovery of thyroid cancer, history of thyroid cancer, and history of head and neck irradiation ,.
In the evaluation of thyroid nodules for malignancy, the size of the nodule has been a cause of concern, mainly because the size – if it is a carcinoma – directly influences the staging, the data on the size of thyroid nodule as a determinant of carcinoma are conflicting. The current study assesses the impact of nodule size on the risk of cancer by analyzing the clinical database ,.
| Patients and Methods|| |
This study was carried out on 330 patients admitted to the Department of Surgery, Faculty of Medicine, Menofiya University and Tala Central Hospital from September 2015 to December 2017. Their age ranged from 13 to 65 years (243 women, 87 men). All patients with thyroid nodule(s) of both sexes and age between 13 and 65 years old were include in our study. Patients with previous thyroid surgery for thyroid cancer and patients with previous cervical nodal biopsy were excluded.
The study was approved by the Ethics Committee of Menoufia, Faculty of Medicine. Written informed consent was obtained from the patients of each participant after explaining the aim of the study.
Every patient was subjected to history taking (including history of present illness and analysis of it, onest, course and duration of the nodule, history of loss of weight and history of change of voice), physical examination, where the clinical data of all patients were recorded in proforma including, general examination: to detect any signs of thyrotoxicity and local examination of thyroid gland, its size and vascularity, consistency of the gland and of the nodule.
Preoperative investigations included, laboratory (thyroid function test and routine investigations such as liver function tests, complete blood picture using Celltac made in Japan), and imaging (ultrasonography on thyroid gland to detect the size of lobes and size of nodules and their dimensions). All patients had undergone thyroid ultrasonography preoperatively to measure three dimensions of the thyroid nodule over than 1 cm (length, width, anteroposterior) using logic P made in USA; also FNAC was done for every patient. According to the case we performed (total thyroidectomy, subtotal thyroidectomy, or hemithyroidectomy. The specimen was sent for routine histopathology after the operation for histopathology examination to detect the percentage of thyroid cancer related to thyroid nodule size. The patients received antibiotics after operation with close observation for 24 h to detect any complication.
Results were collected, tabulated, and statistically analyzed by IBM personal computer and statistical package SPSS version 22 (, 2013; IBM Corp., Armonk, New York, USA). Two types of statistics were done: descriptive statistics, for example, percentage and analytic statistics, for example, χ2-test was used to study the association between two qualitative variables.
Z test was used to test the difference between two population proportions.
Binary logistic regression as a predictive analysis was performed to examine the independent effects of age, numbers of nodules, and nodular sizes on cancer.
A P value of less than 0.05 was considered statistically significant.
| Results|| |
Our results showed that most of the studied patients with thyroid nodules were aged less than 45 years and most of them were women. More than half of the patients had solitary nodules with normal function. About 81% of the patients had nodular sizes greater than or equal to 2 cm. The prevalence of cancer was 15.5% among the studied cases. Total thyroidectomy was the most common surgical operation performed on the cases, followed by hemithyroidectomy [Table 1].
Regarding the ultrasonographic criteria of benign and malignant nodules. there were statistically significant ultrasound data predicting malignancy in thyroid nodules such as microcalcification (P = 0.002), ill-defined edges (P = 0.0003), increased intranodular vascularity (P = 0.0008), size below 2 cm (P = 0.0063), solid consistency (P = 0.002), and hypoechogenicity (P = 0.004) [Table 2].
The results of FNAC which was done preoperatively showed that the incidence of malignancy increases from B(II) to B(VI) with the greatest incidence in B(VI), which is a good predictor of malignancy (χ2 = 99.97, P < 0.0001) [Figure 1].
The result of histopathology done postoperatively show that papillary carcinoma was the commonest type of malignant nodules. On the other hand, follicular adenomas followed by nodular hyperplasia were the most common pathological diagnosis among benign nodules [Table 3]. The prevalence of cancer among female patients aged greater than or equal to 45 years, had bilateral nodules with normal function. As regards nodular sizes, the cases with a nodular size of 1.0–1.9 cm was more prevalent among cancer patients than in benign cases. All cancer cases had euthyroid after adjusting for confounding factors; the size of the nodules (1.0–1.9 cm) and age were still predictors of cancer in the studied cases. Nodular size had 2.5 times prediction of cancer while age had about 0.5 times [Table 4]. There were no significant relationships between nodular size with age, sex, or numbers of nodules. On the other hand, there were significant relationship between nodular size and types of cancers, where all cancer cases having a nodular size of 1.0–1.9 cm were diagnosed as papillary carcinoma while papillary carcinoma constituted about 58.3% of cancer cases having larger sizes (≥2 cm) [Table 5].
|Table 3: Pathological diagnosis of the studied patients with thyroid nodules|
Click here to view
|Table 4: Comparison between cancer and benign patients with thyroid nodules regarding personal and clinical characteristics|
Click here to view
|Table 5: Size of thyroid nodules of cancer patients in relation to personal and clinical characteristics|
Click here to view
| Discussion|| |
Thyroid nodules are common, and prevalence increases with age. Although most are benign, ~10–15% prove malignant, and more than 2000 patients will die from this disease .
The goal of thyroid nodule evaluation is to assess accurately the risk such as whether the nodule is cancerous via methods that are accurate and precise, yet also safe, cost effective, and without morbidity .
Thyroid nodules are a common clinical problem. Epidemiological studies have shown the prevalence of palpable thyroid nodules to be ~5% in women and 1% in men living in iodine sufficient parts of the world. In addition, high-resolution ultrasound can detect thyroid nodules in 19–67% of randomly selected individuals with higher frequency in women and the elderly .
Ultrasound imaging has replaced nuclear medicine as the most frequently used imaging test of the thyroid . The increase in the use of thyroid ultrasound imaging by radiologists, endocrinologists, and head and neck surgeons has led to the discovery of large numbers of asymptomatic thyroid nodules, which may occur in 50% or more of adults , as well as a rapid increase in the diagnosis of thyroid cancer. In contrast, clinically apparent thyroid cancer is rare, affecting one in 10 000 people annually and less than 1% of individuals throughout their lives .
Owing to the high prevalence of nodules and the rarity of symptomatic cancer, only a small percentage of thyroid nodules are malignant. Uncertainty about which nodules may harbor cancer and lack of evidence-based management guidelines have resulted in a myriad of conflicting recommendations regarding which nodules warrant biopsy , frequent thyroid biopsies, and the overdiagnosis of thyroid cancers that would otherwise likely have remained asymptomatic in the absence of detection .
Beyond the diagnostic test characteristics, the size of the nodule may also influence the accuracy of thyroid fine needle aspiration (FNA). Some data suggest that the diagnostic accuracy of FNA in large nodules may be limited due to both sampling inaccuracy in larger nodules and altered pretest probabilities, but no overarching consensus has emerged. Some authors claim the false negative rate and prevalence of malignancy are high in large thyroid nodules such that lobectomy is indicated regardless of the FNA results. Others, however, support the utility of FNA regardless of the lesion size, reporting no associated difference in the diagnostic accuracy or prevalence of malignancy. These issues represent substantial clinical problems in the management of common thyroid nodule disease .
Thyroid-related mortality has remained constant despite the increasing incidence of thyroid carcinoma. Most thyroid nodules are benign; therefore, ultrasound and FNA are integral in cancer screening. We hypothesize that increased nodule size at ultrasound does not predict malignancy and correlation between nodule size at ultrasound and pathologic examination is good .
In our study we aim to study the relation between thyroid nodule size and prevelance of thyroid cancer. This study was carried out on 330 patients aged from 13 to 65 years (243 women and 87 men) complaining of thyroid nodule who were admitted to the Department of Surgery, Faculty of Medicine, Menoufiya University and Tala Central Hospital.
In our study, the mean age of the patients included was 40.32 ± 10.51 and we found that the prevalence of cancer thyroid among patients aged greater than or equal to 45 years was statistically significant than those aged less than 45 years. In aggrement with our result Hughes et al.  reported the same result in their study of the incidence rate of thyroid cancer on American patients from 1973 to 2006. Also Reynolds et al.  reported that thyroid cancer was more common in older age groups than in younger age groups. In contrast to our study Chen et al.  reported that thyroid cancer was common among the age group of less than 45 years, while Witczak et al.  reported that there was no statistically significant difference between patients with benign diseases than those with malignant diseases regarding different age groups.
Regarding our study, women had a higher incidence of malignancy than men. A recent study reported similar data with a high incidence of malignancy in women . On the other hand, Paul P, et al.  reported that the incidence of malignancy is higher in men. In a recent study published by Jaheen and Sakr  that has been no significant difference between both sexes regarding the incidence of malignancy. Moreover, Jang et al.  found no statistically significant difference in the incidence of thyroid malignancy between men and women. This difference between studies may be due to the geographic differences and the number of population studied.
In our study the size of the nodule up to 2 cm was statistically significant in predicting cancer and beyond 2 cm there is no significant increase in the percentage of malignancy. Also, thyroid nodules 1.0–1.9 cm in diameter provided baseline cancer risk for comparison (29.4% risk of cancer). The overall prevalence of cancer in nodules 2.0–2.9 cm was 23.5%; in nodules 3.0–3.9 cm, 23.5%; and in nodules 4.0 cm, 23.5%. This was statistically significant (P = 0.032). However, the primary influence of this association was the high malignancy rate in nodules 1.0–1.9 cm. When comparing nodules 2.0–2.9 cm, 3.0–3.9 cm, or 4.0 cm, no difference in malignancy rate was demonstrated. This suggests a possible threshold effect. Indeed (larger nodule size increases malignancy risk ≥2 cm but further growth beyond 2 cm no longer influences malignant risk).
In agreement with our result, Kamran et al.  reported that greater nodule size influences cancer risk, although the increase in absolute risk between small (1.0–1.9 cm) and large (4.0 cm) nodules is modest. Notably, a threshold effect is detected at ∼2.0 cm in nodule diameter. Thereafter, larger nodule size imparts no further malignant risk, even if 4.0 cm or larger .
On the contrary, Kuru et al.  reported that nodule size greater than or equal to 4 cm was an independent factor associated with malignancy. Carrillo et al.  reported that nodules greater than or equal to 4 cm were significantly more likely to contain malignancy. Kamran et al.  reported that nodules greater than or equal to 4 cm had a higher prevalence of malignancy than nodules less than 4 cm; nodules greater than or equal to 2 cm had a higher prevalence of malignancy than nodules less than 2 cm. On the other hand, Albuja-Cruz et al.  reported that a nodule size greater than or equal to 4 cm is not associated with a higher prevalence of malignancy overall. Shin et al.  reported that large nodules have a higher probability of malignancy. Cavallo et al. , reported that the risk of malignancy is inversely related to the nodule size. McHenry et al.  reported that the likelihood of malignancy significantly decreased nonlinearly with increasing size. Smith-Bindman et al.  reported that malignancy is more common in thyroid nodule with a diameter of more than 2 cm. Cappelli et al.  reported that malignancy incidence is more common in lesions of more than 1 cm. This may be due to the difference in the number of cases in these studies.
Bohacek et al.  reported that there is no trend towards a higher prevalence of malignancy with larger nodule size overall, but when nodules categorized by size in centimeters, there was a statistically significant difference in the rate of malignancy among nodules of 2–3 cm (36.7%) category compared with the rest, as well as in the 3–4 cm.
Shrestha et al.  reported no suggested difference in malignancy prevalence according to size.
Regarding the number of nodules, in our study, out of 330 patients with thyroid nodules there were 141 patients with multinodular goiter (MNG) and 189 patients with solitary thyroid nodules. Out of the 141 patients with MNG, there were 111 patients with benign nodules and 30 patients with malignant nodules. On the other hand, out of 189 patients with solitary thyroid nodules there were only 21 patients with malignant nodules, with high statistically significant difference between solitary nodules and MNG (P = 0.011), which denote that MNG is a predictor of malignancy in thyroid nodules.
Contrary to our result, Frates et al.  reported that the incidence of malignancy in solitary thyroid nodules is higher than that of MNG (P = 0.01).
Historically, MNG was considered a benign condition with low risk of malignancy, but recent studies reported that the incidence of malignancy is equal in both solitary thyroid nodules and MNG . The difference in the reported rates of malignancy among patients with solitary thyroid nodules and MNG in the above studies undoubtedly reflects the difference in the selection criteria used for analysis, as well as geographic difference in the population studied .
Also in our study we found that all cancer patients had normal thyroid function, which denotes that the thyroid function tests are not indicators of thyroid cancer and most people with thyroid cancer have normal thyroid function .
In the current study, there were no significant relationships between nodular size with age, sex, or size of nodules. On the other hand, there were significant relationship between nodular size and types of cancers where papillary adenocarcinoma was the predominant type in cancer cases having a nodular size of 1.0–1.9 cm, while papillary carcinoma was predominant in larger sizes (≥2 cm). Contrary to our result, Kamran et al.  reported that increasing nodule size was associated with a lower proportion of papillary carcinomas (P < 0.01) [Table 6].
|Table 6: Frequency distributions of cancer types in relation to nodular size of cancer patients|
Click here to view
| Conclusion|| |
Increasing thyroid nodule size impacts cancer risk in a nonlinear manner. A threshold is detected at 2.0 cm, beyond which cancer risk is unchanged (a larger nodule size increases malignancy risk up to 2 cm but further growth beyond 2 cm no longer influences malignant risk).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
American Association of Clinical Endocrinologists and Association. Medici Endocrinologi medical guidelines for clinical practice for diagnosis and management of thyroid nodules. Endocr Pract 2006: 63–102.
Moon WJ, Jung SL, Lee JH, Na DG, Baek JH, Lee YH, et al
. Benign and malignant thyroid nodules; us differentiation-multicenter retrospective study. Radiology 2008; 247
Hegedus L. The thyroid nodule. N Engl J Med 2004; 351
Mazzaferri EL. Managment of a solitary thyroid. N Engl J Med 1993; 328
Cooper DS, Doherty GM, Haugen BR Revised American Thyroid Association management guidelines for patient with thyroid nodules and differentiated thyroid cancer. Throid 2009; 19
Kang KW, Kim SK, Kang HS, Lee ES, Sim JS, Lee IG, et al
. Prevvelance and risk of cancer of focal thyroid incidentaloma identified by F- fluorodexyglucose positron emission tomography for metastasis evaluation and cancer screening in healthy subject. J Clin Endocrinol Metab 2003; 88
D'Avanzo A, Treseler P, Philip H Ituarte G, Mariwil W, Streja L, et al
. Follicularthyroid carcinoma: Histology and prognosis. Cancer J 2004; 100
Reparia K, Min SK, Mody DR, Anton R, Amrikachi M, Chen k, et al
. clinical outcomes for 'suspicious' category in thyroid fine-needle aspiration biopsy: patient sex and nodule size are possible predictors of mal-ignancy. Arch Pathol Lab Med 2009; 133
McHenry CR, Huh ES, Machekano RN. Is nodule size an independent predictor of thyroid malignancy? Surgery 2008; 144
Smith-bindman R, Lebda P, Feldstein VA, Sellami D, Goldstein RB, Brasic N et al
. Risk of thyroid cancer based onthyroid ultrasound imaging characteristics: results of a populationbased study. JAMA Intern Med August 2013; 25
Ezzat, S, Sarti, DA, Cain, DR, Braunstein, GD. Thyroid incidentalomas. Prevalence by palpation and ultrasonography. Arch Intern Med 1994; 154
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 2006; 295
Alexander EK, Marqusee E, Orcutt J, Carol B, BensonMary C, Frates M et al
. Thyroid nodule shape and prediction of malignancy. Thyroid 2004; 14
Shin J, Caragacianu D, Randolph G, Han W, Moon HG, Rauch SD. Impact of nodule size onprevalence and post test probability of malignancy: a systemic review. Laryngoscope 2015; 125
Hughes DT, Haymart MR, Miller BS, Gauger PG, Doherty GM. The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years. Thyroid 2011; 21
Reynolds RM, Jennifer W, Stockton DL, David H. Changing trends in incidence and mortality of thyroid cancer in Scotland. Clin Endocrinol (Oxf) 2004; 62
Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer 2009; 115
Witczak J, Taylor P, Chai J, Amphlett B, Soukias J, Das G, et al
. Predicting malignancy in thyroid nodules: feasibility of a predictivemodel integrating clinical, biochemical, and ultrasound characteristics. Thyroid Res 2016; 9
Paul P, Ali KA, Jasir M. Predictors of malignancy in solitary nodulethyroid. Int Surg J 2017; 4
Jaheen H, Sakr M. Predictors of malignancy in patients with solitary and multiple thyroid nodules. J Surg 2016; 12
Jang J, Keon H, Seo M, Kang J, Cho J, Kim H et al
. The effects of patients' sex, age and thyroid-stimulating hormone on malignancy rate of thyroid nodules. Korean J Fam Pract 2017; 7
Kamran SC, Marqusee E, Kim MI, Mary C Frates MC, Ritner J et al
. Thyroid nodule size and prediction of cancer. J Clin Endocrinol Metab 2013; 98
Kuru B, Gulcelik NE, Gulcelik MA, Dincer H. The false-negative rate of fine-needle aspiration cytology for diagnosing thyroid carcinoma in thyroid nodules. Langenbecks Arch Surg 2010; 395
Carrillo JF, Frias-Mendivil M, Ochoa-Carrillo FJ. Accuracy of fine-needle aspiration biopsy of the thyroid combined with an evaluation of clinical and radiologic factors. Otolaryngol Head Neck Surg 2000; 122
Albuja-Cruz MB, Goldfarb M, Gondek S Reliability of fine-needle aspiration for thyroid nodules greater than or equal to 4 cm. J Surg Res 2013; 181
Cavallo A, Johnson DN, White MG, Siddiqui S, Antic T, Mathew M et al
. Throid nodule size at ultrasound as a predictor of malignancy and final pathologic size. Thyroid 2017; 3
Cappelli C, Castellano M, Pirola I, Cumetti D, Agosti B, Gandossi E et al
. The predictive value of ultrasound findings in the management of thyroid nodules. QJM 2007; 100
Bohacek L, Milasjamie M, Allan M, Eren S, Berbe A. Diagnostic accuracy of surgeon-performed ultrasound-guided fine-needle aspiration of thyroid nodules. Ann Surg Oncol 2012; 19:45–51.
Shrestha M, Crothers BA, Burch HB, Magister MJ, Chaikhoutdinov I, Schaefer E et al
. The impact of thyroid nodule size on the risk of malignancy and accuracy of fine-needle aspiration: a 10-year study from a single institution. Thyroid 2012; 22
Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES, et al
. Prevalence and distribution of carcinomainpatients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab 2006; 91
Lue J, McManus C, Chen H, Sippel RS. Are there predictors of malignancy in patients with multinodular goiter? J Surg Res 2012; 174
Tollin SR, Mery GM, Jelveh N, Fallon EF, Mikhail M, Blumenfeld W, et al
. The use of fine-needle aspiration biopsy under ultrasoundguidance to assess the risk of malignancy in patients with a multinodular goiter. Thyroid 2000; 10
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]