Thyroid nodules refer to localized lesions within the thyroid gland that are palpably or radiologically distinct from the surrounding thyroid parenchyma. [22].
Because of the high risk for malignancy , surgeons tend to treat them with a high degree of suspicion and plan treatment in a systematic manner. Clinically, STNs are common and are present in up to 50% of the elderly population. The majority of STNs are malignant. [ 2, 10 , 11] .
Therefore, it is recommended that all thyroid nodules >1 cm in size should undergo evaluation. This includes both palpable and nonpalpable nodules or nodules detected by imaging. [ 22].
Benign causes of thyroid nodules include colloid nodules, hyperplastic nodules, and adenomatous nodules . Occasionally, nodularity is noticed in patients with Hashimoto's thyroiditis and toxic adenoma . Malignant causes of nodules include thyroid cancer, lymphoma and metastasis to the thyroid gland. [ 22].
In our country, a different study was performed on thyroid cancer Al-Hureibi, Abdulmughni, Y. Thyroid FNAC . (2003)[66], Abdulmughni, Yasser A., et al. thyroid cancer (2004)[67]. Al-Jaradi, Mansour, et al. Prevalence of thyroid cancer(2005)[34],. Al-Sharafi, Butheinah A., et al.thyroid cancer (2020)[68].
During our study period, 135 patients had solitary thyroid nodules; there were 126 (93%) females with STNs and 9 (7%) male patients with solitary thyroid nodules.
Thyroid nodules are more common in females similar as noted in the previous study.[ 2, 6].
Solitary thyroid nodules were 10–11times more common in females as compared to males,[ 2, 10], Our study showed that solitary thyroid nodules were 14 times more common in female than male.
In our study 135 Patients with Solitary Thyroid Nodule b/n age 14-65 years, median age 41 years, mode 45 years , average mean age 39.76 years, range 51 years and Stander deviation 13.98 . The age range and mean slightly wide, and higher compared with previous study by (Gupta ).[ 10].
In our study Solitary thyroid nodule more Common in age group between 21-30 years old are about 50 patients and the next age group between 41-50 years old are about 29 patients. That mean second decade involved by majority of the patients (37%) this is lower than previous study by Gupta[[10] and Dorairajan and Jayashree in that third decade of life majority of the patients involved (44%).
Evaluation of solitary thyroid nodules requires the collaboration of the primary care physician, endocrinologist, pathologist, radiologist, and head and neck surgeon to provide comprehensive and appropriate management of this clinical entity.[ 42].
Preliminary investigation should include careful history and thorough clinical examination and thyroid function tests.combination with thyroid ultrasound and FNAC becoming relevant in the management of thyroid nodules.[ 22] [ 23].
Further investigation should be considered if the following factors are present in addition to the thyroid nodule like male gender, extremes of age (<20 or >70 years), history of neck irradiation, nodule >4 cm in size or the presence of any pressure symptoms.[ 22] None of our patients in the study group had history of radiation exposure.
Patients under the age of 20 or over 70 years with thyroid nodules have an increased risk of malignancy, as do men. A history of persistent hoarseness, dysphagia, or dyspnea also increases the risk, although these symptoms may also occur with benign nodules. Rapid painless growth of a solid nodule is concerning and raises the suspicion for thyroid cancer. [25].
Numerous studies have documented that the risk of malignancy in patients with thyroid nodules is 5%–17%, whether detected by palpation or ultrasonography.
There were 135 cases of clinically detected STNs with available ultrasound findings in the study group. Thirty-five (26%) (3:1) clinically detected STNs were reported as malignant in the final HPE. This high incidence of malignancy reported in our study is similar to that of Tai et al.[ 2]. A total of 36.6% (97) of the 265 patients also reported a 20% and 42.27% incidence in the papers. [ 10, 11] were proven to be malignant, which was higher than the general incidence of malignancy of 5%. It seems that STN has a higher risk of malignancy, so in this condition, we should focus on the potential danger to all these patients.
A retrospective study by Keh et al of 61 patients found that 75.4% of solitary thyroid nodules had a neoplastic pathology and 34.4% were malignant. [ 51] .
The rise in incidence seems to be attributable both to the growing use of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical nodules [52] and early diagnosis of low‐risk lesions [53].
The fact that the malignant percentages obtained in this study were higher is partly due to the pattern we used for selecting patients. In other words, we selected the cases from surgery wards, whereas other studies included in their experiments all the cases that were subjected to FNAC. As noted above, the risk of malignancy in this group has been reported to be 26%; however, a higher rate has also been reported. [ 38, 39, 40].
In our study, 35 patients were diagnosed with malignant solitary thyroid nodules; 31 patients were female, and 4 patients were male.
Among female patients, 31/126 (25%) were reported as malignant in histopathology results . Additionally, malignancy was found in 4 (44%) out of 9 male patients with solitary thyroid nodules . Hence, thyroid nodules predominate in females . [ 2, 6] and the increased incidence of malignant thyroid nodules in males noted in our study are similar to those of Tai et al (36%). [ 2,] [ 26].
The age of patients with malignant tumors ranged from b/n 15_62 years, median age 35 years, mode 23 years, average mean age 35.97 years and standard deviation 11.91.
In our study, malignant solitary thyroid nodules were more common in the age group between 21-30 years old, with approximately 12 patients (34%).
Different studies have shown different results regarding the role of age as a risk factor for thyroid malignancy. Pinchot et al (54) and Muratli et al.,[ 38] reported that thyroid carcinoma prevalence was higher in the elderly than in others, while Rosario et al. did not observe a significant difference between the ages of the patients (55). Nevertheless, some studies, including ours, revealed that the prevalence of thyroid carcinoma is higher in younger patients[ 56, 57].
In our study, most solitary thyroid nodules, even benign or malignant nodules, were between 2.1_4 Cm. The size of the nodule had no relation with malignancy in our study, which was also reported by Tai et al.[ 2] A study by Kamran et al. opined that the risk of follicular carcinomas and other rare thyroid malignancies increases as nodules enlarge. [ 27] However, no such association with size was seen in our cases.
Usually, the size of the thyroid nodule does not predict the likelihood of thyroid cancer. Only 8% of incidentally found thyroid nodules measuring <5 mm, 15% of nodules measuring 5–10 mm, and 13% of nodules measuring 10–15 mm are malignant [24].
The results of this study revealed that the size of thyroid nodules is not reliable at predicting malignancy and should not be applied in medical decision making. [58 ][59] was similar to the our study .
A study by Valderrabano et al indicated that regardless of size, most solitary cytologically indeterminate thyroid nodules can be successfully treated with thyroid lobectomy. Comparing indeterminate tumors of less than 4 cm with those 4 cm or greater, size was not seen as a categorical or continuous variable in relation to cancer rate. Moreover, the prevalence of extrathyroidal extension, positive margins, lymphovascular invasion, lymph node metastasis, and distant metastasis did not differ by size. The investigators also found the majority of malignant tumors in both size groups to be low-risk lesions. [45].
In our study (72%, 63%), the Rt-side thyroid was more affected by either benign or malignant solitary thyroid nodules. A similar study by Liechty et al 9 noticed that there was a predilection for benign and malignant nodules to occur in the right lobe, and Robinson et al 1 also found that in 40% of cases, the nodules were located in the right lobe. [60].
In our study Most common results of histopathology was Benign solitary thyroid nodule in 100 (74%), of that Benign non neoplastic 60(44%)including colloid nodule 20(15%) patients, adenomatous nodule 13(10%)patients, hyperplastic nodule 12(9%),cystic nodule 5(4%)patients, chronic thyroiditis 7(5%) patients (hashimotos and lymphocytes thyroiditis )and toxic adenoma 3(2%)patients. The benign neoplastic nodule 40(30%)patients including follicular adenoma 28(21%),hurthle cell adenoma 6(4.4%) patients, and 6(4.4%) non invasive follicular neoplasia with papillary features (NIFTP).
Malignant solitary thyroid nodules appeared in 35 (26%) patients, and papillary thyroid cancer (74%) was the most common, followed by follicular thyroid cancer (14%), followed by equal frequency (3%), hurthle, medullary, lymphoma and anaplastic thyroid cancer.
Malignant solitary thyroid nodules appeared in 3/6 (50%) patients with hypothyroidism before the operation. The histopathology results showed malignant nodules such as papillary thyroid cancer on a background of Hashimotos thyroiditis, one of whom had lymph node metastasis. This means a higher risk for malignant transformation, especially papillary thyroid cancer, than lymphoma[ 50].
Ultrasonography is the most cost-effective imaging procedure and is highly sensitive in assessing nodule size and number. There are ultrasound patterns that suggest malignancy such as irregular shape, ill-defined borders, hypoechogenicity, solid texture, heterogeneous internal echoes, microcalcification, absence of a halo, an anteroposterior to transverse diameter ratio (A/T) >1, infiltration into regional structures, and suspicious regional lymph nodes. [ 22].
Thyroid ultrasonography can be helpful in certain cases when it is used to guide FNAB. Data have suggested that ultrasonography-guided FNAB may be preferable to palpation-guided FNAB. [61]
Ultrasound may aid in the localization and examination of nodules, but FNA or excisional biopsy is necessary to definitively determine the presence of malignancy[62].
addition, high-resolution ultrasound and ancillary testing in the form of molecular genetics and immunocytochemistry can improve diagnostic accuracy. [ 41][63].
The likelihood that the increased incidence of thyroid cancer is largely related to early detection by high-resolution ultrasound and discovery of subclinical thyroid nodules. [63 ][64] is supported by evidence suggesting that survival rates for thyroid cancer have remained fairly stable. [65].
In our study, 28 patients out of a total 35 (80%) malignant cases had microcalcifications by thyroid ultrasound, in contrast to 10 of 100 (10%) benign nodules. This finding suggests that in the presence of microcalcifications, the incidence of malignancy is more similar to that in a study by Kuo et al, which indicated that on ultrasonographic examination, the presence of calcifications within a thyroid lesion and nodule-like solid masses are independent factors for thyroid cancer, especially follicular thyroid carcinoma instead of follicular adenoma. [47]. Additionally, an article by Rago et al. suggested that atypia at cytology and spot microcalcification at ultrasound were predictive of malignancy[29].
The presence of solid echogenicity contributes to an increased incidence of malignancy in comparison to either cystic or mixed echogenicity of the nodule. [ 2] Our study showed that similar results were solid in 30/35 (86%) patients with malignant nodules. The findings of our study also suggest that the presence of cervical lymphadenopathy is high in the presence of malignant thyroid nodules. Twenty-four of 35 (69%) malignant nodules had lymph node enlargement compared with only 2 of 100 (2%) benign nodules.
Noted male gander, solid nodule, hypoechoic, irregular borders, microcalcification, increased vascularity, and cervical lymphadenopathy are malignancy risk factors for solitary thyroid nodules study by Uyar et al( [44] ) and ( 2)( 47)( 29)( 30)( 62).
In our study, ultrasound revealed hypoechoic nodules in 33/35 (94%) patients with malignant nodules and 15 (15%) with benign nodules. The presence of hypoechoic nodules was high in the presence of malignant thyroid nodules, similar to the study by DS Cooper - Thyroid, 2009 – Malignant lesions were found to be hypoechogenicity on ultrasound in almost 80% of cases. When the finding of hypoechogenicity lesion is combined with microcalcifications, irregular borders, and taller than wide shape, the sensitivity for malignancy increases. Simple cysts, hyperechogenic solid nodules, and spongiform architecture are all associated with benign lesions. [ 62].
Papini et al. opined that ultrasound-guided FNAC should be performed on all 8–15 mm hypoechoic nodules with irregular margins, intranodular vascular spots or microcalcifications. [ 30]
According to the literature, STNs have a higher risk of malignancy than multiple nodules. [ 2] .
In our study group, (26%)(35/135) STNs were malignant(3:1) compared to that of multinodular goiter(24/72) (22.5%). In a study from Nigeria, the authors described malignancy in 1 out of the 13 cases of STN (7.6%) and twenty-four out of 160 cases of MNG (15%). [28] Hence, multinodularity does not necessarily exclude malignancy, as seen by our study group.
Male sex, normal thyroid volume, single nodularity, nodule hypoechogenicity, and blurred margins were also associated with malignancy, but size was not significantly associated with malignancy [29].
We noted that male sex, microcalcification, solid echogenicity of the nodule, and the presence of cervical lymphadenopathy were significantly associated with malignancy, as noted by Tai et al.[ 2].
study by Yuan et al, however, indicated that the patterns of enhancement differ significantly between benign and malignant solitary thyroid nodules examined with real-time, contrast-enhanced ultrasonography, with most malignant lesions in the report demonstrating an irregular shape, an unclear boundary, and inhomogeneous and incomplete enhancement. The study involved 78 patients, including 41 with benign lesions and 37 with malignant nodules. [46]
Desjardins et al found that half of their patients with thyroid carcinoma had a cystic component in the tumor. [49].
fine-needle aspiration biopsy (FNAB) has become the most important tool in the assessment of solitary thyroid nodules. [43].
Fine-needle aspiration cytology is recommended to be a cost-effective procedure in the initial assessment and management of thyroid nodules. [2,11] It is recommended that every patient with a palpable thyroid nodule should undergo FNAC. USG-guided FNAC can lower the occurrence of nondiagnostic smears. Whenever we had problems in preoperative diagnosis by FNAC due to inadequate material or difficulty in aspiration by conventional methods, we repeated FNAC by USG guidance. In our study and previous study experience, noted a better yield of diagnostic cytological material with the help of USG-guided aspirations compared to blind FNAC. [ 31, 32].
All our patients underwent FNAC by ultrasound guidance before surgery, as it helped us to decide the type of surgery to be undertaken. When the FNAC report was malignant or suspicious, total thyroidectomy was performed. In all other cases, hemithyroidectomy was performed, and a subsequent plan was decided based on a conclusive paraffin section report.
In a recent article, the authors emphasized the role of USG by suggesting that nodules with a nondiagnostic FNAC result in the setting of low-risk demographics and benign appearance at ultrasound can be followed with serial ultrasound examinations, thereby avoiding repeat FNAC. [ 33] These findings are in contrast to the recommended current guidelines to repeat FNAC after a nondiagnostic result. [ 62].
Determining the nature of STNs is very important, as aggressive surgery may be regarded as an excessive mode of treatment. [ 2] We opted for surgery in all patients, as there is a high incidence of malignancy in STN patients, as reported in the literature. [ 2] The postoperative histopathology reports corroborated our findings, as ~1/3 of STNs were reported to be malignant.
study by Arul and Masilamani indicated that in cases of solitary thyroid nodules, fine-needle aspiration cytology reports using the Bethesda System for Reporting Thyroid Cytopathology correlate well with histopathologic diagnosis of these nodules, having a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 94.4%, 97.6%, 95.8%, 98.1%, and 93.2%, respectively. [48].
Al_ hureibi et al study 2003 on 196 patients with nodular goiter fine needle aspiration
having a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 38%, 89.9%, 72%, 66.7%, and 79.2%, respectively. [66].
In our study, thyroid fine needle aspiration had a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 61.33%, 71.66%, 64.44%, 73.1%, and 59.72%, respectively.
The sensitivity of FNA cytology in this study is low compared to published studies from outside countries where the sensitivity, specificity and accuracy of FNA cytology are more than 94%. which adversely affected the surgical decision making and the outcome. We should realise that negative FNA cytology does not exclude malignancy, and we have to seriously evaluate the situation and to rethink on how to raise the scale of sensitivity in FNA cytology in the diagnosis of thyroid nodules and to improve the level of expertise in cytology.
Yemen, as any developing country, lacks an accepted level of expertise in this field, something that makes it mandatory to continuously monitor and evaluate how valid this procedure is.
whose study reported . However, this high rate of malignancy is not surprising if we know that FNAC is currently routinely performed for most cases of thyroid nodules. This has led to a reduction in the number of unnecessary surgeries and consequently to a rise in the percentage reported for malignancy. [ 39].
The respective risk of malignancy associated with each diagnostic category is as follows:
Non diagnosed ,Benign - < 1%, Atypia (AUS) - 5-10%, Follicular neoplasm - 20-30%, Suspicious for malignancy - 50-75%, Malignant - 100% [39].
In our study, the risk of malignancy for each Bethesda category was as follows:
Non diagnosed _17%, Benign - 21%, Atypia (AUS) - 50%, Follicular neoplasm - 33%, Suspicious for malignancy – 45%, Malignant - 100%.
The correlation between FNAC and histopathological diagnoses in our study shows the accuracy with which FNAC diagnosed follicular neoplasia. There were 14 cases of false negatives that had been reported as benign nodules by FNAC examination, and histopathological analysis showed follicular adenoma in 12 cases and hurthel adenoma in 2 cases and 8 cases of false positives (FPs), diagnosed as follicular neoplasms by FNAC examination. Histopathological analysis showed that two of them were colloid nodular goiters, one adenomatous nodule, one hyperplastic nodule, one toxic adenoma and three Hashimoto's thyroiditis (chronic lymphocytic thyroiditis). There were 31 cases True positive (TP) cases, all case were follicular neoplasm by FNAC examination, by histopathological analysis, 15 cases were follicular adenoma ,3 cases were hurthel adenoma , non invasive follicular thyroid neoplasia with Papillary features and 5 papillary carcinoma,4 cases follicular carcinoma, hurthel cell carcinoma one case and one case lymphoma
The risk of malignancy for each Bethesda category ranged from 6.9% (the “benign and nonneoplastic” category) to 100% (the “malignant” category). This wide range shows the power of the Bethesda system to differentiate and determine the probability of malignancy. The percentages obtained in our research were rather close to the figures reported in other studies: 6.9% versus 0-3% (the “benign and non-neoplastic” category), 50% versus 5-15% (AUS/FLUS), 37% versus 15-30% (FN/SFN), 81.2% versus 60-75% (the “suspicious for malignancy” category), and 100% versus 97-99% (the “malignant” category). [ 39].
Surgical management
154 thyroid operation for 135 patients with solitary thyroid nodule, 100 thyroid operation for 100 patients with benign solitary thyroid nodule and 54 thyroid operation for 35 patients with malignant solitary thyroid nodule, 102/154 (66%) hemithyroidectomy either Rt or Lt side thyroid for benign or malignant solitary thyroid nodules but 19 patients of hemithyroidectomy followed by completion thyroidectomy when results of histopathology was malignant thyroid nodules.
Wagana and colleagues agreed that hemithyroidectomy is the most common operation performed in solitary thyroid nodules (81 operations were performed for solitary thyroid nodules, and the most common operations were lobectomy and isthmectomy). They performed a retrospective review of all solitary thyroid nodules excised over a 3-year period from 1st January 1999 to 31st December 2001. A simple protocol was used to manage this condition involving history, clinical examination, fine-needle aspiration of the lesion, and excision. Clinical diagnosis and operation were performed for patients who had solitary thyroid nodules over a 3-year period at Kijabe Hospital[35].
We performed hemithyroidectomy in benign nodules as reported by FNAC. In those cases where postoperative HPE was reported as malignant by paraffin section, completion thyroidectomy of the remaining lobe was performed. Total thyroidectomy was performed in those cases where FNAC was reported to be suspicious of malignancy or malignancy.
Total thyroidectomy for 22 patients, 14 patients with benign nodule and 8 patients with malignant solitary thyroid nodule (2 patients Lt Solitary thyroid nodule and 6 patients Rt Solitary thyroid nodule ) treat by total thyroidectomy and results of histopathology was 3 patients papillary thyroid cancer,4 patients follicular cancer, one anaplastic cancer . Here, papillary thyroid cancer was not followed by any type of neck dissection because total thyroidectomy depending on the FNAC result was false negative for malignancy.
Near total or subtotal thyroidectomy for 2 patients Rt Solitary thyroid nodule Toxic adenoma.
Neck dissection was performed in 26 patients, 24 of whom had malignant nodules, 6 of whom showed metastatic deposits in the lymph nodes. Five patients had papillary thyroid cancer, one patient had non-Hodgkin lymphoma in the background of hashimatous thyroiditis, and two patients had benign thyroid nodules and underwent selective lymph node dissection because FNAC gave us false positive results. This patient underwent total thyroidectomy with Rt selective lymph node dissection level 3, but the result of histopathology was a hyperplastic nodule with marked fibrosis and calcification. Another case result of histopathology was Hashimotos thyroiditis.
Central node dissection was performed in 19 (1 positive) patients, right side modified neck dissection (MND) in 3 (3 positive) patients, Lt side modified neck dissection in one patient (1 positive) and Rt selective neck lymph node dissection in 1 patient (1 positive).
Decision of neck dissection was made in those cases with either palpable lymph nodes in the neck or USG findings suggestive of lymphadenopathy. In some cases, the decision of lymph node dissection was made intraoperatively mainly for central nodes (level VI). Central node dissection was performed in all malignant cases with USG showing lymph node enlargement and in cases with enlarged intraoperative nodes.
Prophylactic central neck dissection in clinically node-negative patients remains controversial.
Calò, Pietro Giorgio, et al. found no statistically significant difference in the rates of locoregional recurrence between the three modalities of treatment. Total thyroidectomy appears to be an adequate treatment for clinically node-negative differentiated thyroid cancer. Prophylactic central neck dissection might be considered for differentiated thyroid cancer patients with large tumor sizes or extrathyroidal extension. [36].
In a study by Chen, Lawrence, et al., compared with no prophylactic central neck dissection, prophylactic central neck dissection significantly reduced locoregnal recurrence but was accompanied by numerous adverse effects.
Patients who underwent prophylactic central neck dissection had significantly lower locoregnal recurrence and locoregnal recurrence (odds ratio [OR] 0.65; 95% confidence interval [CI] 0.48–0.88) but significantly higher incidence rates of transient recurrent laryngeal nerve injury (OR 2.03; 95% CI 1.32–3.13), transient hypocalcemia (OR 2.23; 95% CI 1.84–2.70), and permanent hypocalcemia (OR 2.22; 95% CI 1.58–3.13) than those in the no prophylactic central neck dissection group. [37].
intraoperative assessment
During my study, we noted that intraoperative assessment for solitary thyroid nodules was FNAC before surgery was benign, or follicular neoplasia should be assessed for hardness and fixation of nodules if hard and fixed nodules are best intraoperatively to make decisions to perform total thyroidectomy instead of hemithyroidectomy. We found hard and fixed nodules intraoperatively in 32/35 (91%) patients diagnosed after the operation as thyroid cancer.
This means that intraoperative assessment of the hardness and fixation of the nodule and total thyroidectomy at that time are reduced require a second operation, completion thyroidectomy and complications.
Complication of surgery in solitary thyroid nodules
Complications postoperatively were temporary hypocalcaemia and hoarseness of voice in 12 patients12/135 patients 9%,all female patients,; out of them 9 (7%) patient, with temporary hypocalcaemia and 3(2.2%) patient with temporary unilateral recurrent laryngeal nerve injury
7 cases post Lt Solitary thyroid nodule and 5 cases post Rt Solitary thyroid nodule .6/135(4%) and 6 /100(6%)patients with benign nodule and 6/135(4%) and 6/35 (17%)patients with malignant nodule .
Temporary hypocalcemia 9/135 patients (7%),5/135(4%) and 5/100 (5%)patients with benign solitary thyroid nodule ,4/135(3%) and 4/35(11%)patients with malignant thyroid nodule.
Three patients (2.22%) had temporary unilateral recurrent laryngeal nerve injury and laryngeal edema, 2/35 (6%) patients had malignant nodules, and one/100 (1%) patient had benign nodules.