Malignancy in a Solitary Thyroid Nodule: A Retrospective Histopathological Evaluation

Background

Thyroid nodules are distinct lesions in the thyroid gland that are radiologically different from the surrounding thyroid parenchyma and are a common clinical presentation.¹ Palpable nodules are found in roughly 5% of the population and are discovered coincidentally on ultrasonography in up to 70% of people, with a higher prevalence in older patients.^2,3 The vast majority of nodular lesions are benign follicular nodules, which can be solitary or part of a multinodular goiter. Overall, 7–15% of thyroid nodules are cancerous.^1,4–6 The pathological origins of benign thyroid nodules are colloid nodules, Hashimoto’s thyroiditis, simple or hemorrhagic cysts, follicular adenoma, and subacute thyroiditis. Malignant thyroid nodules are papillary cancer, follicular cancer, Hurthle (oncocytic) cell cancer, anaplastic cancer, medullary cancer, thyroid lymphoma, and metastatic deposits.^1,2,7 The World Health Organization’s (WHO) histologic categorization of thyroid neoplasms, which was published in its fifth edition in 2022, incorporates a grading system along with newly identified tumor types and subtypes. Benign tumors, low-risk neoplasms, and malignant neoplasms are the three groups (classes) of follicular cell-derived neoplasms. In this revised WHO classification, “Oncocytic cell” has taken the position of “Hürthle cell”.⁸

A solitary thyroid nodule (STN) is defined as a localized thyroid enlargement accompanied by an apparently normal neighboring gland.^9–11 In the assessment of thyroid nodules, ultrasound has become an important diagnostic tool. It is extremely sensitive for detecting nodules, and the sonographic characteristics of the nodules can be used to determine whether further investigation is required.¹²

To enhance malignancy prediction in thyroid nodules and avoid unnecessary fine needle aspiration cytology (FNAC) from the benign nodules, various ultrasonographic systems have been described. American Thyroid Association (ATA) system categorized thyroid nodules based on echostructure, echogenicity, margins, presence or absence of microcalcifications, and shape. It offers a 5-class scoring system with the following anticipated rates of malignancy for each class: 1% for benign class, 3% for very-low suspicion, 5–10% for low suspicion, 10–20% for intermediate suspicion, and >70–90% for high suspicion.¹ The British Thyroid Association (BTA) ultrasonographic classification of thyroid nodules consists of five categories: normal (U1), benign (U2), equivocal/indeterminate (U3), suspicious (U4), and malignant (U5). The following ultrasonographic features are considered predictors of malignancy: eccentric location of the solid portion in partially cystic nodules, non-smooth margins, hypoechogenicity of the solid portion, microcalcification, and taller-than-wide shape.¹³ However, the most widely accepted ultrasonographic classification system to evaluate thyroid nodules is Thyroid Imaging Reporting and Data System (TI-RADS). TIRADS 1 to TIRADS 5 are the categories. TIRADS 1 corresponds to a normal thyroid gland, TIRADS 2 to benign nodules, TIRADS 3 to possibly benign nodules, TIRADS 4 to nodules with ultrasound features suggestive of malignancy, and TIRADS 5 to nodules with ultrasound features strongly suggestive of malignancy.^14–18

The main objective of this study was to assess the presence and type of malignancy in patients who underwent thyroid surgery with clinically detected STNs.

Methods

A retrospective cohort study was conducted of all patients who underwent thyroid surgery for STNs identified clinically and confirmed by ultrasonography between 1 January 2019 and 31 October 2022 in Abha Private Hospital, southwestern Saudi Arabia. The electronic records of our pathology department were used to determine the pathological diagnosis.

This research followed the declaration of Helsinki’s ethical principles. The institutional review board of King Khalid University approved the research (ECM #2022-112).

All cases that underwent thyroid surgery for STNs and histopathological evaluation were reviewed. The following parameters were determined for all patients: age, sex, nodule size, type of surgery, and histopathological diagnosis.

The data were entered into a Microsoft Excel spreadsheet. Statistical analysis was performed using Statistical Packages for Social Sciences (SPSS), version 20.0 software (SPSS Inc, Chicago, IL, USA). Proportions were compared between groups using the χ2 test. p <0.05 was considered significant.

Results

During the study period, 42 patients underwent surgery for STNs. Most patients were female (n = 32, 76.2%), 13 cases of STNs (31%) were reported to be malignant, and thyroid lobectomy was the most commonly performed procedure (30, 71.4%) (Table 1).

Table 1 Bio-Demographic Data

The mean age was 39.1 ± 12.6 years, and there was a wide range (min–max: 15–67 years). Echogenicity of STNs and their internal contents were variable (Figures 1 and 2). The mean nodule size was 3.8 ± 1.9 cm, and there was a wide range (min–max: 0.6–9.5 cm). Further analysis found that 18 (48.9%) STNs were equal or larger than 4 cm. However, there was no significant correlation between nodule size and the risk of malignancy (p = 0.70). In terms of postoperative histopathology, ten out of the thirteen malignant cases (76.9%) were female, and three (23.1%) were male (male: female ratio of 1:3.3). The remaining 29 STNs were reported to be benign (7 males and 22 females). There was no significant correlation between sex and tumor type (p = 0.999) (Table 2).

Table 2 Distribution of Nodule Pathology Type by Different Bio-Demographic Data

Figure 1 An isoechoic nodule at the postero-medial aspect of the right lobe showing cystic degeneration.

Figure 2 An ill-defined irregular hypoechoic non capsulated nodule of the right lobe with multiple foci of pathological heavy calcification.

Further histopathological analysis found that malignant STNs were papillary carcinoma in nine cases (21.4%), follicular carcinoma in three cases (7.1%), and oncocytic cell carcinoma in one case (2.4%). Benign STNs were mostly colloid nodules (31%), followed by follicular adenoma (19%), Hashimoto’s thyroiditis (11.9%), and oncocytic cell adenoma (2.4%) (Table 3).

Table 3 Pathology Results

Discussion

Our study revealed that the malignancy rate of STNs was 31%. This indicated that nearly one-third of patients who undergo surgery for STNs have thyroid cancer, which is a significant number. This finding is consistent with most published international data, which indicate that STNs have a higher chance of being malignant than multiple nodules.^9–11,19,20 Our study was similar to that reported by Tai et al, who reported that the malignancy rate of STNs was 33.6%.⁹ Additionally, Iqbal et al reported high cancer frequency for STNs (42.27%).¹¹ Moreover, more recent studies by Keh et al and Nasr et al reported that the prevalence of malignancy in STNs was 34.4% and 26%, respectively.^19,20

On the contrary, these findings contradict published data from other parts of the world, which indicate that STNs have a low and the same risk of malignancy as multiple nodules.^21–23 Papini et al found that only 9.2% of STNs were malignant.²² Frates et al found that the prevalence of cancer was similar between patients with STNs and patients with multiple nodules, whereas it was estimated to be 14.8 and 14.9, respectively.²³ However, a recent meta-analysis by Brito et al refuted these published data by demonstrating that patients with multiple nodules are less likely to have thyroid cancer than patients with a solitary nodule.²⁴ Consequently, surgeons frequently view STNs with a high level of suspicion and tend to favor surgical excision.

Our study revealed that the most common malignancy type was papillary (69.2%), followed by follicular (23.1%). This result is consistent with data published about the pattern of thyroid cancers in Saudi Arabia.^25,26 Our results are also consistent with international data indicating that papillary and follicular thyroid cancers are the most common types and account for 90% of all thyroid cancers.^1,27,28 Additionally, our results demonstrated that the nodule size in ultrasonography is not predictive of malignancy, consistent with most international published data.^22,29–32

Although the current study has limitations related to its design and the low number of studied subjects, it shows that STNs should be managed with a high index of suspicion because the chance of malignancy is high.

This study retrospectively focused solely on the postoperative histopathological malignancy rate of STNs in a single institute. We anticipate that future multicenter studies will further explore STNs in sonographic findings and FNAC analysis and compare them with multinodular goiters.

Conclusions

The study offers insightful information on the characteristics of patients undergoing thyroid surgery for STNs. It indicates that 31% of STNs were malignant, with papillary carcinoma being the most frequent kind of malignancy. Nodule size and malignancy risk did not significantly correlate, according to the study. This study demonstrates that STNs have a high probability of becoming malignant (31%); therefore, they should be extensively investigated and treated with a high index of suspicion.